V

COVID-19 vaccine (Nuvaxovid)

Ability to drive, COVID-19 vaccine [2] ---> SmPC of [2] of EMA

Nuvaxovid has no or negligible influence on the ability to drive and use machines. However, some of the effects mentioned under section 4.8 may temporarily affect the ability to drive or use machines.

Breast-feeding, COVID-19 vaccine [2] ---> SmPC of [2] of EMA

No effects on the breast-fed newborn/infant are anticipated since the systemic exposure of the breast- feeding woman to Nuvaxovid is negligible.

COVID-19 vaccine [1], fertility ---> SmPC of [1] of EMA

Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity

COVID-19 vaccine [1], influenza vaccine ---> SmPC of [1] of EMA

The binding antibody response to SARS-CoV-2 was lower when Nuvaxovid was given concomitantly with inactivated influenza vaccine.

COVID-19 vaccine [1], pregnancy ---> SmPC of [1] of EMA

Administration of Nuvaxovid in pregnancy should only be considered when the potential benefits outweigh any potential risks for the mother and foetus.

COVID-19 vaccine [1], vaccinations ---> SmPC of [1] of EMA

Concomitant administration of Nuvaxovid with other vaccines has not been studied.

CONTRAINDICATIONS of COVID-19 vaccine (Nuvaxovid)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/nuvaxovid-epar-product-information_en.pdf 16/10/2024

Other trade names: Bimervax,

Hepatitis A (inactivated) and hepatitis B (rDNA) (HAB) vaccine (adsorbed) (Ambirix)

Breast-feeding, hepatitis A (inactivated) and hepatitis B (rDNA) (HAB) vaccine (adsorbed) [2] ---> SmPC of [2] of

Ambirix should only be used during breast-feeding when the possible advantages outweigh the potential risks.

Fertility, hepatitis A (inactivated) and hepatitis B (rDNA) (HAB) vaccine (adsorbed) [2] ---> SmPC of [2] of EMA

No fertility data are available.

Hepatitis A (inactivated) and hepatitis B (rDNA) (HAB) vaccine (adsorbed) [1], immunoglobulins ---> SmPC of [1] of

Concomitant immunoglobulin administration may result in lower antibody titres.

Hepatitis A (inactivated) and hepatitis B (rDNA) (HAB) vaccine (adsorbed) [1], immunosuppressives ---> SmPC of [1]

It may be expected that in patients receiving immunosuppressive treatment or patients with immunodeficiency, an adequate response may not be achieved.

Hepatitis A (inactivated) and hepatitis B (rDNA) (HAB) vaccine (adsorbed) [1], pregnancy ---> SmPC of [1] of EMA

Ambirix can be used during pregnancy only when clearly needed, and the possible advantages outweigh the potential risks for the foetus.

Hepatitis A (inactivated) and hepatitis B (rDNA) (HAB) vaccine (adsorbed) [1], vaccinations ---> SmPC of [1] of EM

It is advised that Ambirix should not be administered at the same time as other vaccines unless absolutely necessary. Concomitant vaccines should always be administered at separate injection sites and preferably into different limbs.

CONTRAINDICATIONS of Hepatitis A (inactivated) and hepatitis B (rDNA) (HAB) vaccine (adsorbed) (Ambirix)

- Hypersensitivity to the active substances or to any of the excipients listed in section 6.1, or neomycin.

- Hypersensitivity after previous administration of hepatitis A and/or hepatitis B vaccines.

- As with other vaccines, the administration of Ambirix should be postponed in subjects suffering from acute severe febrile illness.

https://www.ema.europa.eu/en/documents/product-information/ambirix-epar-product-information_en.pdf 08/02/2024

Hepatitis B vaccine (Fendrix)

Ability to drive, hepatitis B vaccine [2] ---> SmPC of [2] of EMA

Fendrix has moderate influence on the ability to drive and use machine. Some of the undesirable effects mentioned under section 4.8 may affect the ability to drive or use machines.

Breast-feeding, hepatitis B vaccine [2] ---> SmPC of [2] of EMA

Vaccination should only be performed if the risk-benefit ratio at individual level outweighs possible risks for the infant.

Fertility, hepatitis B vaccine [2] ---> SmPC of [2] of EMA

No fertility data are available.

Hepatitis B vaccine [1], immunosuppressives ---> SmPC of [1] of EMA

It may be expected that in patients receiving immunosuppressive treatment or patients with immunodeficiency, an adequate immune response may not be elicited.

Hepatitis B vaccine [1], pregnancy ---> SmPC of [1] of EMA

Vaccination during pregnancy should only be performed if the risk-benefit ratio at individual level outweighs possible risks for the foetus.

Hepatitis B vaccine [1], vaccinations ---> SmPC of [1] of EMA

As no data are available for the concomitant administration of this particular vaccine with other vaccines, an interval of 2 to 3 weeks should be respected.

CONTRAINDICATIONS of Hepatitis B vaccine (Fendrix)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Hypersensitivity after previous administration of other hepatitis B vaccines.

- The administration of Fendrix should be postponed in subjects suffering from acute severe febrile illness. The presence of a minor infection such as a cold, is not a contraindication for immunisation.

https://www.ema.europa.eu/en/documents/product-information/fendrix-epar-product-information_en.pdf 24/05/2023

Other trade names: HBVaxPro,

Human papillomavirus 9-valent vaccine (recombinant, adsorbed) (Gardasil 9)

Ability to drive, human papillomavirus 9-valent vaccine (recombinant, adsorbed) [2] ---> SmPC of [2] of EMA

There were no serious adverse experiences reported in infants who were breast-feeding during the vaccination period.

Breast-feeding, human papillomavirus 9-valent vaccine (recombinant, adsorbed) [2] ---> SmPC of [2] of EMA

There were no serious adverse experiences reported in infants who were breast-feeding during the vaccination period. Gardasil 9 can be used during breast-feeding.

Fertility, human papillomavirus 9-valent vaccine (recombinant, adsorbed) [2] ---> SmPC of [2] of EMA

No human data on the effect of Gardasil 9 on fertility are available. Animal studies do not indicate harmful effects on fertility (see section 5.3).

Hormonal contraceptives, human papillomavirus 9-valent vaccine (recombinant, adsorbed) [2] ---> SmPC of [2] of EMA

Use of hormonal contraceptives did not appear to affect the type specific immune responses to Gardasil 9

Human papillomavirus 9-valent vaccine (recombinant [1], adsorbed), immunogenicity ---> SmPC of [1] of EMA

Safety and immunogenicity in individuals who have received immunoglobulin or blood-derived products during the 3 months prior to vaccination have not been studied in clinical trials.

Human papillomavirus 9-valent vaccine (recombinant [1], adsorbed), pregnancy ---> SmPC of [1] of EMA

Vaccination should be postponed until completion of pregnancy

CONTRAINDICATIONS of Human papillomavirus 9-valent vaccine (recombinant, adsorbed) (Gardasil 9)

- Hypersensitivity to the active substances or to any of the excipients listed in section 6.1.

- Individuals with hypersensitivity after previous administration of Gardasil 9 or Gardasil/Silgard should not receive Gardasil 9.

https://www.ema.europa.eu/en/documents/product-information/gardasil-9-epar-product-information_en.pdf 09/10/2025

Other trade names: Cervarix, Silgard,

Smallpox vaccine (Live Modified Vaccinia Virus Ankara) (Imvanex)

Ability to drive, smallpox vaccine (Live Modified Vaccinia Virus Ankara) [2] ---> SmPC of [2] of EMA

Some of the undesirable effects may affect the ability to drive or operate machinery (e.g. dizziness).

Breast-feeding, smallpox vaccine (Live Modified Vaccinia Virus Ankara) [2] ---> SmPC of [2] of EMA

IMVANEX should be avoided during breastfeeding unless it is considered that the possible benefit in terms of preventing smallpox would outweigh the potential risk

Fertility, smallpox vaccine (Live Modified Vaccinia Virus Ankara) [2] ---> SmPC of [2] of EMA

Animal studies did not reveal any evidence of impaired female and male fertility.

Immunoglobulins, smallpox vaccine (Live Modified Vaccinia Virus Ankara) [2] ---> SmPC of [2] of EMA

The concomitant administration of the vaccine with any immunoglobulin including Vaccinia Immune Globulin (VIG) has not been studied and should be avoided

Pregnancy, smallpox vaccine (Live Modified Vaccinia Virus Ankara) [2] ---> SmPC of [2] of EMA

As a precautionary measure the use of IMVANEX should be avoided during pregnancy unless it is considered that the possible benefit in terms of preventing smallpox would outweigh the potential risk.

Smallpox vaccine (Live Modified Vaccinia Virus Ankara) [1], vaccinations ---> SmPC of [1] of EMA

No interaction studies with other vaccines or medicinal products have been performed. Therefore, concomitant administration of the smallpox vaccine with other vaccines should be avoided.

CONTRAINDICATIONS of Smallpox vaccine (Live Modified Vaccinia Virus Ankara) (Imvanex)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 or trace residues (chicken protein, benzonase, gentamicin and ciprofloxacin).

https://www.ema.europa.eu/en/documents/product-information/imvanex-epar-product-information_en.pdf 20/10/2025

Influenza vaccine (live attenuated; nasal) (Fluenz Tetra)

Breast-feeding, influenza vaccine (live attenuated; nasal) [2] ---> SmPC of [2] of EMA

Fluenz Tetra should not be used during breastfeeding.

Fertility, influenza vaccine (live attenuated; nasal) [2] ---> SmPC of [2] of EMA

No data exist regarding the possible effects of Fluenz Tetra on male and female fertility.

Inactivated vaccines, influenza vaccine (live attenuated; nasal) [2] ---> SmPC of [2] of EMA

The co-administration of Fluenz Tetra with inactivated vaccines has not been studied.

Influenza vaccine (live attenuated; nasal) [1], measles ---> SmPC of [1] of EMA

No clinically meaningful changes in immune responses to measles, mumps, varicella, orally-administered poliovirus or Fluenz have been observed.

Influenza vaccine (live attenuated; nasal) [1], pregnancy ---> SmPC of [1] of EMA

Fluenz Tetra is not recommended during pregnancy.

Influenza vaccine (live attenuated; nasal) [1], rubella vaccine ---> SmPC of [1] of EMA

The immune response to rubella vaccine was significantly altered. However, this alteration might not be of clinical relevance with the two dose immunisation schedule of the rubella vaccine.

Influenza vaccine (live attenuated; nasal) [1], salicylates ---> SmPC of [1] of EMA

Do not use salicylates in children and adolescents for 4 weeks after vaccination unless medically indicated as Reye's syndrome has been reported following the use of salicylates during wild-type influenza infection.

Influenza vaccine, influenza vaccine (live attenuated; nasal) [2] ---> SmPC of [2] of EMA

It is recommended not to administer the vaccine until 48 hours after the cessation of influenza antiviral therapy.

CONTRAINDICATIONS of Influenza vaccine (live attenuated; nasal) (Fluenz Tetra)

- Hypersensitivity to the active substances or to any of the excipients (e.g. gelatin), or to gentamicin (a possible trace residue),

- Severe allergic reaction (e.g. anaphylaxis) to eggs or to egg proteins (e.g. ovalbumin).

- Children and adolescents with clinical immunodeficiency due to conditions or immunosuppressive therapy such as: acute and chronic leukaemias; lymphoma; symptomatic HIV infection; cellular immune deficiencies; and high-dose corticosteroids. Fluenz Tetra is not contraindicated for use in individuals with asymptomatic HIV infection; or individuals who are receiving topical/inhaled corticosteroids or low-dose systemic corticosteroids or those receiving corticosteroids as replacement therapy, e.g. for adrenal insufficiency.

- Children and adolescents younger than 18 years of age receiving salicylate therapy because of the association of Reye's syndrome with salicylates and wild-type influenza infection.

https://www.ema.europa.eu/en/documents/product-information/fluenz-tetra-epar-product-information_en.pdf 14/07/2025

Influenza vaccine (split virion, inactivated) (Intanza)

Breast-feeding, influenza vaccine (split virion, inactivated) [2] ---> SmPC of [2] of EMA

This vaccine is intended for individuals 60 years of age and over. Therefore, this information is not applicable.

False positive, influenza vaccine (split virion, inactivated) [2] ---> SmPC of [2] of EMA

The Western Blot technique disproves the false-positive ELISA test results. The transient false positive reactions could be due to the IgM response by the vaccine.

Immunosuppressives, influenza vaccine (split virion, inactivated) [2] ---> SmPC of [2] of EMA

The immunological response may be diminished if the patient is undergoing immunosuppressant treatment.

Influenza vaccine (split virion [1], inactivated), pregnancy ---> SmPC of [1] of EMA

This vaccine is intended for individuals 60 years of age and over. Therefore, this information is not applicable.

CONTRAINDICATIONS of Influenza vaccine (split virion, inactivated) (Intanza)

- Hypersensitivity to the active substances, to any of the excipients listed in section 6.1, or to any residues such as eggs (ovalbumin, chicken proteins), neomycin, formaldehyde and octoxinol 9.

- Immunisation shall be postponed in subjects with febrile illness or acute infection.

https://www.ema.europa.eu/en/documents/product-information/intanza-epar-product-information_en.pdf 04/09/2018 (withdrawn)

Other trade names: IDflu,

Influenza vaccine (surface antigen, inactivated, adjuvanted) (Fluad)

Influenza vaccine (surface antigen [1], inactivated, adjuvanted), pregnancy ---> SmPC of [1] of EMA

There are no data from the use of Fluad in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity.

Influenza vaccine (surface antigen [1], inactivated, adjuvanted), women of childbearing potential ---> SmPC of [1]

This medicine is not indicated in women of childbearing potential (see section 4.1). It is not to be used in women who are, or may be, pregnant or breast-feeding.

CONTRAINDICATIONS of Influenza vaccine (surface antigen, inactivated, adjuvanted) (Fluad)

- Hypersensitivity to the active substances, to any of the components of the adjuvant, to any of the excipients listed in section 6.1, or to possible trace residues such as ovalbumin, kanamycin and neomycin sulphate, formaldehyde, cetyltrimethylammonium bromide (CTAB) and hydrocortisone.

- A severe allergic reaction (e.g. anaphylaxis) to previous influenza vaccination.

https://www.ema.europa.eu/en/documents/product-information/fluad-epar-product-information_en.pdf 03/12/2024

Influenza vaccine (surface antigen, inactivated, prepared in cell cultures) (Flucelvax)

Breast-feeding, influenza vaccine (surface antigen, inactivated, prepared in cell cultures) [2] ---> SmPC of [2] of EMA

It is unknown whether Flucelvax is excreted in human milk. No effects on breastfed newborn/infant are anticipated. Flucelvax may be given during lactation.

Fertility, influenza vaccine (surface antigen, inactivated, prepared in cell cultures) [2] ---> SmPC of [2] of EMA

No human fertility data are available. Animal data have not shown effects on female fertility. Male fertility has not been assessed in animals.

Influenza vaccine (surface antigen [1], inactivated, prepared in cell cultures), pregnancy ---> SmPC of [1] of EMA

Based on pregnancy outcomes and predefined infant safety outcomes, there was no evidence of adverse foetal, newborn or pregnancy outcomes attributable to the vaccine during any stage of pregnancy.

Influenza vaccine (surface antigen [1], inactivated, prepared in cell cultures), vaccinations ---> SmPC of [1] of EMA

Based on clinical experience Flucelvax can be given at the same time as other vaccines.

CONTRAINDICATIONS of Influenza vaccine (surface antigen, inactivated, prepared in cell cultures) (Flucelvax)

- Hypersensitivity to the active substance, to any of the excipients listed in section 6.1, or to possible trace residues such as beta-propiolactone, cetyltrimethylammonium bromide, and polysorbate 80.

https://www.ema.europa.eu/en/documents/product-information/flucelvax-epar-product-information_en.pdf 28/11/2024

Respiratory syncytial virus mRNA vaccine (mResvia)

Ability to drive, respiratory syncytial virus mRNA vaccine [2] ---> SmPC of [2] of EMA

However, some of the effects mentioned under section 4.8 (e.g., fatigue, dizziness) may temporarily affect the ability to drive or use machines.

Breast-feeding, respiratory syncytial virus mRNA vaccine [2] ---> SmPC of [2] of EMA

It is unknown whether mRESVIA is excreted in human milk.

Fertility, respiratory syncytial virus mRNA vaccine [2] ---> SmPC of [2] of EMA

Animal studies are insufficient to assess male reproductive toxicity (see section 5.3).

Pregnancy, respiratory syncytial virus mRNA vaccine [2] ---> SmPC of [2] of EMA

There are no or limited amount of data from the use of mRESVIA in pregnant women. Animal studies with mRESVIA do not indicate direct or indirect harmful effects with respect to pregnancy (see section 5.3).

Respiratory syncytial virus mRNA vaccine [1], women of childbearing potential ---> SmPC of [1] of EMA

This vaccine is not indicated in women of childbearing potential (see section 4.1). It is not to be used in women who are or may be pregnant or breast-feeding.

CONTRAINDICATIONS of Respiratory syncytial virus mRNA vaccine (mResvia)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/mresvia-epar-product-information_en.pdf 06/09/2024

Measles, mumps, and rubella vaccine (live) (M-M-RVAXPRO)

Ability to drive, measles, mumps, and rubella vaccine (live) [2] ---> SmPC of [2] of EMA

No studies on the effects on the ability to drive and use machines have been performed. M-M-RvaxPro is expected to have no or negligible influence on the ability to drive and use machines.

Blood transfusion, measles, mumps, and rubella vaccine (live) [2] ---> SmPC of [2] of EMA

Vaccination should be deferred for at least 3 months following blood or plasma transfusions, or administration of human immune serum globulin.

Breast-feeding, measles, mumps, and rubella vaccine (live) [2] ---> SmPC of [2] of EMA

Studies have shown that breast-feeding postpartum women vaccinated with live attenuated rubella vaccines may secrete the virus in breast milk and transmit it to breast-fed infants.

Childhood vaccinations, measles, mumps, and rubella vaccine (live) [2] ---> SmPC of [2] of EMA

However, since M-M-RvaxPro has been shown to have safety and immunogenicity profiles similar to the previous formulation of the combined measles, mumps and rubella vaccine manufactured, experience with this vaccine can be considered.

Containing blood products, measles, mumps, and rubella vaccine (live) [2] ---> SmPC of [2] of EMA

Administration of measles, mumps, or rubella antibody-containing blood products, including immune globulin preparations, should be avoided within 1 month after a dose of M-M-RvaxPro unless considered to be essential.

Fertility, measles, mumps, and rubella vaccine (live) [2] ---> SmPC of [2] of EMA

M-M-RvaxPro has not been evaluated in fertility studies.

Immunoglobulins, measles, mumps, and rubella vaccine (live) [2] ---> SmPC of [2] of EMA

Immune globulin (IG) is not to be given concomitantly with M-M-RVAXPRO. Administration of immune globulins concomitantly with M-M-RVAXPRO may interfere with the expected immune response.

Measles [1], mumps, and rubella vaccine (live), pregnancy ---> SmPC of [1] of EMA

Inadvertent vaccination of unknowingly pregnant women with measles-, mumps-, or rubella-containing vaccines should not be a reason for termination of pregnancy.

Measles [1], mumps, and rubella vaccine (live), pregnancy ---> SmPC of [1] of EMA

Pregnancy should be avoided for 1 month following vaccination. Women who intend to become pregnant should be advised to delay.

Measles [1], mumps, and rubella vaccine (live), tuberculin test ---> SmPC of [1] of EMA

Therefore, if a tuberculin test is to be done, it should be administered either any time before, simultaneously with, or 4 to 6 weeks after vaccination with M-M-RvaxPro.

CONTRAINDICATIONS of Measles, mumps, and rubella vaccine (live) (M-M-RVAXPRO)

- History of hypersensitivity to any measles, mumps, or rubella vaccine, or to any of the excipients, including neomycin (see sections 2, 4.4, and 6.1).

- Pregnancy. Furthermore, pregnancy should be avoided for 1 month following vaccination

- Vaccination should be postponed during any illness with fever > 38.5°C.

- Active untreated tuberculosis. Children under treatment for tuberculosis have not experienced exacerbation of the disease when immunized with live measles virus vaccine. No studies have been reported to date on the effect of measles virus vaccines on children with untreated tuberculosis.

- Blood dyscrasias, leukaemia, lymphomas of any type, or other malignant neoplasms affecting the haematopoietic and lymphatic systems.

- Current immunosuppressive therapy (including high doses of corticosteroids). M-M-RVAXPRO is not contraindicated in individuals who are receiving topical or low-dose parenteral corticosteroids (e.g. for asthma prophylaxis or replacement therapy).

- Severe humoral or cellular (primary or acquired) immunodeficiency, e.g. severe combined immunodeficiency, agammaglobulinemia and AIDS or symptomatic HIV infection or an age-specific CD4+ T-lymphocyte percentage in children below 12 months: CD4+ < 25% %; children between 12-35 months: CD4+ < 20%; children between 36-59 months: CD4+ < 15% (see section 4.4).

- In severely immunocompromised individuals inadvertently vaccinated with measles-containing vaccine, measles inclusion body encephalitis, pneumonitis, and fatal outcome as a direct consequence of disseminated measles vaccine virus infection have been reported.

- Family history of congenital or hereditary immunodeficiency, unless the immune competence of the potential vaccine recipient is demonstrated.

https://www.ema.europa.eu/en/documents/product-information/m-m-rvaxpro-epar-product-information_en.pdf 25/07/2024

Measles, mumps, rubella and varicella vaccine (live) (ProQuad)

Ability to drive, measles, mumps, rubella and varicella vaccine (live) [2] ---> SmPC of [2] of EMA

No studies on the effects on the ability to drive or use machinery have been performed. ProQuad is expected to have no or negligible influence on the ability to drive and use machines.

Blood, measles, mumps, rubella and varicella vaccine (live) [2] ---> SmPC of [2] of EMA

Therefore, administration of any of these products should be avoided within 1 month after a dose of ProQuad unless considered to be essential.

Breast-feeding, measles, mumps, rubella and varicella vaccine (live) [2] ---> SmPC of [2] of EMA

Caution should be exercised when considering whether to administer ProQuad to a breast-feeding woman.

Fertility, measles, mumps, rubella and varicella vaccine (live) [2] ---> SmPC of [2] of EMA

Animal reproduction studies have not been conducted with ProQuad. ProQuad has not been evaluated for potential to impair fertility.

Immunoglobulins, measles, mumps, rubella and varicella vaccine (live) [2] ---> SmPC of [2] of EMA

Do not give immunoglobulin (IG) or Varicella Zoster Immune Globulin (VZIG) concomitantly with this vaccination

Measles [1], mumps, rubella and varicella vaccine (live), pregnancy ---> SmPC of [1] of EMA

Pregnant women should not be vaccinated with ProQuad. Pregnancy should be avoided for 1 month following vaccination. Women who intend to become pregnant should be advised to delay.

Measles [1], mumps, rubella and varicella vaccine (live), salicylates ---> SmPC of [1] of EMA

Vaccine recipients should avoid use of salicylates for 6 weeks after vaccination

Measles [1], mumps, rubella and varicella vaccine (live), tuberculin test ---> SmPC of [1] of EMA

Therefore, if a tuberculin test is to be done, it should be administered either any time before, simultaneously with, or at least 4 to 6 weeks after immunisation with ProQuad.

Measles [1], mumps, rubella and varicella vaccine (live), vaccinations ---> SmPC of [1] of EMA

The safety profiles of the administered vaccines were comparable (see section 4.8). There are insufficient data to support the use of ProQuad with any other vaccines.

CONTRAINDICATIONS of Measles, mumps, rubella and varicella vaccine (live) (ProQuad)

- Hypersensitivity to any varicella vaccine or measles, mumps, or rubella vaccine or to any of the excipients listed in section 6.1, including neomycin (see sections 2 and 4.4).

- Blood dyscrasias, leukaemia, lymphomas of any type, or other malignant neoplasms affecting the haematopoietic and lymphatic system.

- Current immunosuppressive therapy (including high doses of corticosteroids) (see section 4.8). ProQuad is not contraindicated in individuals who are receiving topical or low-dose parenteral corticosteroids (e.g. for asthma prophylaxis or replacement therapy).

- Severe humoral or cellular (primary or acquired) immunodeficiency, e.g., severe combined immunodeficiency, agammaglobulinemia and AIDS or symptomatic HIV infection or an age-specific CD4+ T-lymphocyte percentage in children below 12 months: CD4+ <25%, children between 12-35 months: CD4+ < 20%; children between 36-59 months: CD4+ < 15%

- Family history of congenital or hereditary immunodeficiency, unless the immune competence of the potential vaccine recipient is demonstrated.

- Vaccination should be postponed during any illness with fever >38.5°C.

- Pregnancy. Furthermore, pregnancy should be avoided for 1 month following vaccination

https://www.ema.europa.eu/en/documents/product-information/proquad-epar-product-information_en.pdf 25/07/2024

Pandemic influenza vaccine (H5N1) (surface antigen, inactivated, adjuvanted) (Foclivia)

Ability to drive, pandemic influenza vaccine (H5N1) (surface antigen, inactivated, adjuvanted) [2] ---> SmPC of [2

Foclivia has no or negligible influence on the ability to drive and use machines. However, some of the effects mentioned under section 4.8 may temporarily affect the ability to drive or use machines.

Breast-feeding, pandemic influenza vaccine (H5N1) (surface antigen, inactivated, adjuvanted) [2] ---> SmPC of [2]

There are no data regarding the use of Foclivia during breast-feeding. The potential benefits and risks to the mother and infant should be considered before administering Foclivia.

Fertility, pandemic influenza vaccine (H5N1) (surface antigen, inactivated, adjuvanted) [2] ---> SmPC of [2] of EM

There are no data concerning human fertility. A study in female rabbits did not indicate reproductive or developmental toxicity of Foclivia (see section 5.3). Male fertility has not been assessed in animals.

Immunosuppressives, pandemic influenza vaccine (H5N1) (surface antigen, inactivated, adjuvanted) [2] ---> SmPC of

The immunological response may be diminished if the patient is undergoing immunosuppressant treatment.

Pandemic influenza vaccine (H5N1) (surface antigen [1], inactivated, adjuvanted), pregnancy ---> SmPC of [1] of EM

Health care providers need to assess the benefits and potential risks of administering Foclivia vaccine to pregnant women, taking into consideration official recommendations.

Pandemic influenza vaccine (H5N1) (surface antigen [1], inactivated, adjuvanted), vaccinations ---> SmPC of [1] of

There are no data on co-administration of Foclivia with vaccines other than non-adjuvanted seasonal influenza vaccines. If co-administration with another vaccine is considered, immunisation should be carried out on separate limbs.

CONTRAINDICATIONS of Pandemic influenza vaccine (H5N1) (surface antigen, inactivated, adjuvanted) (Foclivia)

- History of an anaphylactic (i.e. life-threatening) reaction to any of the constituents or trace residues (eggs, chicken proteins, ovalbumin, kanamycin sulphate, neomycin sulphate, formaldehyde, hydrocortisone and cetyltrimethylammonium bromide) of this vaccine.

- However, in a pandemic situation, it may be appropriate to give this vaccine to individuals with a history of anaphylaxis as defined above, provided that facilities for resuscitation are immediately available in case of need. See section 4.4.

https://www.ema.europa.eu/en/documents/product-information/foclivia-epar-product-information_en.pdf. 03/10/2023

Zoonotic influenza vaccine (Aflunov)

Ability to drive, zoonotic influenza vaccine [2] ---> SmPC of [2] of EMA

Some of the undesirable effects mentioned under section 4.8 may affect the ability to drive or operate machinery.

Breast-feeding, zoonotic influenza vaccine [2] ---> SmPC of [2] of EMA

The potential benefits to the mother and risks to the infant should be considered before administering AFLUNOV during breast-feeding.

Fertility, zoonotic influenza vaccine [2] ---> SmPC of [2] of EMA

There are no data concerning human fertility. A study in rabbits did not indicate reproductive or developmental toxicity of AFLUNOV (see section 5.3).

Immunosuppressives, zoonotic influenza vaccine [2] ---> SmPC of [2] of EMA

The immunological response may be diminished if the patient is undergoing immunosuppressant treatment.

Pregnancy, zoonotic influenza vaccine [2] ---> SmPC of [2] of EMA

Since AFLUNOV is expected not to be used in an emergency situation, its administration during pregnancy might be deferred as a precautionary approach.

Seasonal influenza, zoonotic influenza vaccine [2] ---> SmPC of [2] of EMA

AFLUNOV may be co-administered with non-adjuvanted seasonal influenza vaccines, and immunisation should be carried out on separate limbs.

Vaccinations, zoonotic influenza vaccine [2] ---> SmPC of [2] of EMA

If co-administration with another vaccine is considered, immunisation should be carried out on separate limbs. It should be noted that the adverse reactions may be intensified.

CONTRAINDICATIONS of Zoonotic influenza vaccine (Aflunov)

- History of an anaphylactic (i.e. life-threatening) reaction to any of the constituents or trace residues (egg and chicken proteins, ovalbumin, kanamycin and neomycin sulphate, formaldehyde, hydrocortisone and cetyltrimethylammonium bromide) of this vaccine.

- However, in a pandemic situation caused by the strain included in this vaccine, it may be appropriate to give this vaccine to individuals with a history of anaphylaxis as defined above, provided that facilities for resuscitation are immediately available in case of need.

https://www.ema.europa.eu/en/documents/product-information/aflunov-epar-product-information_en.pdf 04/11/2024

Other trade names: Seqirus,

Zoonotic influenza vaccine (H5N8) (Zoonotic Influenza Vaccine Seqirus)

Ability to drive, zoonotic influenza vaccine (H5N8) [2] ---> SmPC of [2] of EMA

Some of the undesirable effects mentioned under section 4.8 may affect the ability to drive or operate machinery.

Breast-feeding, zoonotic influenza vaccine (H5N8) [2] ---> SmPC of [2] of EMA

The potential benefits to the mother and risks to the infant should be considered before administering Zoonotic Influenza Vaccine Seqirus H5N8 during breast-feeding.

Fertility, zoonotic influenza vaccine (H5N8) [2] ---> SmPC of [2] of EMA

A study in rabbits did not indicate reproductive or developmental toxicity of Zoonotic Influenza Vaccine H5N1 (see section 5.3).

Pregnancy, zoonotic influenza vaccine (H5N8) [2] ---> SmPC of [2] of EMA

Since Zoonotic Influenza Vaccine Seqirus H5N8 is expected not to be used in an emergency situation, its administration during pregnancy might be deferred as a precautionary approach.

CONTRAINDICATIONS of Zoonotic influenza vaccine (H5N8) (Zoonotic Influenza Vaccine Seqirus)

- History of an anaphylactic (i.e. life-threatening) reaction to the active substance, to any excipients or to trace residues (egg and chicken proteins, ovalbumin, kanamycin and neomycin sulphate, formaldehyde, hydrocortisone and cetyltrimethylammonium bromide) of this vaccine (see section6.1).

https://www.ema.europa.eu/en/documents/product-information/zoonotic-influenza-vaccine-seqirus-epar-product-information_en.pdf 25/09/2024

Quadrivalent influenza vaccine (Supemtek Tetra) (previously Supemtek)

Breast-feeding, quadrivalent influenza vaccine [2] ---> SmPC of [2] of EMA

It is not known whether Supemtek vaccine is excreted in human milk. An assessment of the risks and benefits should be performed by a health care professional before administering Supemtek to a breast-feeding woman.

Fertility, quadrivalent influenza vaccine [2] ---> SmPC of [2] of EMA

No human fertility data are available. The animal study with trivalent recombinant influenza vaccine did not indicate harmful effects on female fertility.

Pregnancy, quadrivalent influenza vaccine [2] ---> SmPC of [2] of EMA

Supemtek Tetra can be used during pregnancy in accordance with official recommendations.

Quadrivalent influenza vaccine [1], vaccinations ---> SmPC of [1] of EMA

If Supemtek is to be given at the same time as another injectable vaccine, the vaccines should always be administered at different injection sites.

CONTRAINDICATIONS of Quadrivalent influenza vaccine (Supemtek Tetra) (previously Supemtek)

- Hypersensitivity to the active substances, to any of the excipients listed in section 6.1 or to any trace residuals such as octylphenol ethoxylate.

https://www.ema.europa.eu/en/documents/product-information/supemtek-epar-product-information_en.pdf 22/05/2025

Vadadustat (Vafseo)

Aluminium [1], vadadustat ---> SmPC of [1] of EMA

As vadadustat may form a chelate with multivalent cations, Vafseo should be administered at least 1 hour before or 2 hours after medicinal products whose primary component consists of multivalent cations such as calcium, magnesium or aluminium.

BCRP substrates, vadadustat [2] ---> SmPC of [2] of EMA

Vadadustat may increase the AUC of BCRP substrates, and some statins when co-administered. Dose adjustment of co-prescribed BCRP substrates may be needed.

Benzylpenicillin, vadadustat [2] ---> SmPC of [2] of EMA

If co-administration with strong or moderate OAT1 or OAT3 inhibitors (e.g. benzylpenicillin, teriflunomide or p-aminohippuric acid) occurs, patients should be managed cautiously and evaluated for excessive effects of vadadustat.

Breast-feeding, vadadustat [2] ---> SmPC of [2] of EMA

A risk to infants cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue vadadustat therapy, taking into account the benefit of breast feeding for the child and benefit of therapy for the woman.

Bupropion, vadadustat [2] ---> SmPC of [2] of EMA

Vadadustat is an in vitro inducer of CYP2B6. Co-administration of vadadustat with sensitive substrates of CYP2B6 (e.g. efavirenz, bupropion) may alter their pharmacokinetics

Celecoxib, vadadustat [2] ---> SmPC of [2] of EMA

Patients receiving warfarin or other narrow therapeutic CYP2C9 substrates (e.g., phenytoin) must therefore be managed cautiously and evaluated for excessive effects when treated with vadadustat.

CYP2C9 substrates with narrow therapeutic index, vadadustat [2] ---> SmPC of [2] of EMA

Patients receiving warfarin or other narrow therapeutic CYP2C9 substrates (e.g., phenytoin) must therefore be managed cautiously and evaluated for excessive effects when treated with vadadustat.

Cytochrome P450, vadadustat [2] ---> SmPC of [2] of EMA

Vadadustat was metabolically stable in vitro and metabolism via cytochrome P450s (CYPs) was minimal. The metabolic pathways involved were oxidation and mainly glucuronidation.

Down-regulation of CYP3A4, vadadustat [2] ---> SmPC of [2] of EMA

Vadadustat induced CYP2B6, inhibited CYP2C8 and caused down-regulation of CYP3A4 in in vitro experiments. However, these interactions have not been examined in vivo.

Drugs primarily metabolised by CYP2B6, vadadustat [2] ---> SmPC of [2] of EMA

Vadadustat is an in vitro inducer of CYP2B6. Co-administration of vadadustat with sensitive substrates of CYP2B6 (e.g. efavirenz, bupropion) may alter their pharmacokinetics

Drugs primarily metabolised by CYP2C8, vadadustat [2] ---> SmPC of [2] of EMA

Based on in vitro data, vadadustat may inhibit CYP2C8 and therefore may increase exposure to CYP2C8 substrates and therefore caution should be exercised when vadadustat is co-administered with CYP2C8 substrates.

Drugs primarily metabolised by CYP3A4, vadadustat [2] ---> SmPC of [2] of EMA

Based on in vitro data, vadadustat may have a potential for CYP3A4 downregulation. Coadministration of vadadustat with CYP3A4 substrates may alter their pharmacokinetics

Efavirenz, vadadustat [2] ---> SmPC of [2] of EMA

Vadadustat is an in vitro inducer of CYP2B6. Co-administration of vadadustat with sensitive substrates of CYP2B6 (e.g. efavirenz, bupropion) may alter their pharmacokinetics

Famotidine, vadadustat [2] ---> SmPC of [2] of EMA

Vadadustat may increase the AUC of OAT3 substrates when co-administered. Monitor for signs of excessive effects of the co-administered OAT3 substrates such as famotidine, furosemide, methotrexate, olmesartan, sitagliptin, and zidovudine.

Fertility, vadadustat [2] ---> SmPC of [2] of EMA

Studies in animals showed no effects of vadadustat on fertility (see section 5.3). The potential risk for humans is unknown.

Fluvastatin, vadadustat [2] ---> SmPC of [2] of EMA

In addition to sulfasalazine, simvastatin, and rosuvastatin, monitor for signs of excessive effects of coadministered BCRP substrates such as fluvastatin, nelfinavir, pitavastatin, and topotecan, and for the need of their dose reduction.

Furosemide, vadadustat [2] ---> SmPC of [2] of EMA

Iron, vadadustat [2] ---> SmPC of [2] of EMA

The co-administration of oral iron-based medicinal products reduced the bioavailability of vadadustat up to 90% and 92% in terms of the AUCinf and Cmax.

Methotrexate, vadadustat [2] ---> SmPC of [2] of EMA

Nelfinavir, vadadustat [2] ---> SmPC of [2] of EMA

OAT1 inhibitors, vadadustat [2] ---> SmPC of [2] of EMA

OAT3 inhibitors, vadadustat [2] ---> SmPC of [2] of EMA

OAT3 substrates, vadadustat [2] ---> SmPC of [2] of EMA

Olmesartan, vadadustat [2] ---> SmPC of [2] of EMA

Para-aminohippuric acid, vadadustat [2] ---> SmPC of [2] of EMA

Phenytoin, vadadustat [2] ---> SmPC of [2] of EMA

Patients receiving warfarin or other narrow therapeutic CYP2C9 substrates (e.g., phenytoin) must therefore be managed cautiously and evaluated for excessive effects when treated with vadadustat.

Phosphate binders, vadadustat [2] ---> SmPC of [2] of EMA

The co-administration of non-iron-containing phosphate binders reduced the bioavailability of vadadustat up to 55% and 52% for AUCinf and Cmax.

Pitavastatin, vadadustat [2] ---> SmPC of [2] of EMA

Polyvalent cations, vadadustat [2] ---> SmPC of [2] of EMA

Pregnancy, vadadustat [2] ---> SmPC of [2] of EMA

Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3). As a precautionary measure, it is preferable to avoid the use of vadadustat during pregnancy.

Probenecide, vadadustat [2] ---> SmPC of [2] of EMA

Co-administration with probenecid, an OAT1/OAT3 inhibitor, increased vadadustat AUC values almost 2-fold.

Rosuvastatin, vadadustat [2] ---> SmPC of [2] of EMA

Limit the top dose of rosuvastatin in patients with CKD on Vafseo to 10 mg daily. Monitor for signs of adverse events of rosuvastatin.

Simvastatine, vadadustat [2] ---> SmPC of [2] of EMA

Limit the top dose of simvastatin in patients with CKD on Vafseo to 20 mg daily. Monitor for signs of adverse events of simvastatin.

Sitagliptin, vadadustat [2] ---> SmPC of [2] of EMA

Statins, vadadustat [2] ---> SmPC of [2] of EMA

Vadadustat may increase the AUC of BCRP substrates, and some statins when co-administered. Dose adjustment of co-prescribed BCRP substrates may be needed.

Sulfasalazine, vadadustat [2] ---> SmPC of [2] of EMA

Monitor for signs of adverse events of sulfasalazine.

Teriflunomide, vadadustat [2] ---> SmPC of [2] of EMA

Topotecan, vadadustat [2] ---> SmPC of [2] of EMA

Vadadustat [1], zidovudine ---> SmPC of [1] of EMA

CONTRAINDICATIONS of Vadadustat (Vafseo)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/vafseo-epar-product-information_en.pdf 24/03/2026

Valaciclovir

Ability to drive, valaciclovir [2] ---> SmPC of [2] of eMC

The clinical status of the patient and the adverse reaction profile should be borne in mind when considering the patient`s ability to drive or operate machinery.

Aminoglycoside antibiotics, valaciclovir [2] ---> SmPC of [2] of eMC

The combination of valaciclovir with nephrotoxic medicinal products should be made with caution, especially in subjects with impaired renal function, and warrants regular monitoring of renal function.

Breast-feeding, valaciclovir [2] ---> SmPC of [2] of eMC

Valaciclovir should be used with caution during breast feeding and only when clinically indicated.

Cimetidine, valaciclovir [2] ---> SmPC of [2] of eMC

The medicinal products eliminated by active tubular secretion can increase the plasma concentrations of aciclovir. Valaciclovir administration may increase plasma concentrations of the concurrently administered substance.

Cyclosporine, valaciclovir [2] ---> SmPC of [2] of eMC

Foscarnet, valaciclovir [2] ---> SmPC of [2] of eMC

Iodinated contrast media, valaciclovir [2] ---> SmPC of [2] of eMC

Letermovir [1], valaciclovir ---> SmPC of [1] of EMA

No dose adjustment required.

Meglumine and sodium ioxitalamate, valaciclovir

The co-administration with other medicinal products with nephrotoxic potential may decrease the renal function and cause a permanent damage

Methotrexate, valaciclovir [2] ---> SmPC of [2] of eMC

Mycophenolate mofetil [1], valaciclovir ---> SmPC of [1] of EMA

Possible increase of plasma concentrations of valaciclovir and mycophenolate mofetil due to competition for the renal tubular secretion.

Mycophenolate, valaciclovir ---> SmPC of [mycophenolate mofetil] of EMA

Possible increase of plasma concentrations of aciclovir and also due to competition for the renal tubular secretion.

Nephrotoxic substances, valaciclovir [2] ---> SmPC of [2] of eMC

Pentamidine, valaciclovir [2] ---> SmPC of [2] of eMC

Platinum compounds, valaciclovir [2] ---> SmPC of [2] of eMC

Pregnancy, valaciclovir [2] ---> SmPC of [2] of eMC

Valaciclovir should only be used in pregnancy if the potential benefits of treatment outweigh the potential risk.

Probenecide, valaciclovir [2] ---> SmPC of [2] of eMC

Tacrolimus, valaciclovir [2] ---> SmPC of [2] of eMC

The co-administration of aciclovir with nephrotoxic drugs should only done with caution, particularly in patients with renal failure

Tenofovir, valaciclovir [2] ---> SmPC of [2] of eMC

Tipranavir/ritonavir, valaciclovir ---> SmPC of [tipranavir] of EMA

Valaciclovir and tipranavir with low dose ritonavir, may be co-administered without dose adjustment

Tubular secretion, valaciclovir [2] ---> SmPC of [2] of eMC

CONTRAINDICATIONS of Valaciclovir

- Hypersensitivity to valaciclovir or aciclovir or any of the excipients

http://www.medicines.org.uk/emc/

Valganciclovir

Ability to drive, valganciclovir [2] ---> SmPC of [2] of eMC

Convulsions, sedation, dizziness, ataxia, and/or confusion have been reported with the use of valganciclovir and/or ganciclovir.

Adefovir, ganciclovir ---> SmPC of [valganciclovir] of eMC

The renal clearance of ganciclovir may be inhibited due to nephrotoxicity caused by drugs. Concomitant use of valganciclovir with these drugs should be considered only if the potential benefits outweigh the potential risks

Adefovir, valganciclovir [2] ---> SmPC of [2] of eMC

Amphotericin B, valganciclovir [2] ---> SmPC of [2] of eMC

Toxicity may be enhanced when valganciclovir is co-administered with, or is given immediately before or after, other drugs that inhibit replication of rapidly dividing cell populations

Amphotericin, valganciclovir [2] ---> SmPC of [2] of eMC

Toxicity may be enhanced when valganciclovir is co-administered with, or is given immediately before or after, other drugs that inhibit replication of rapidly dividing cell populations

Antiretrovirals, valganciclovir [2] ---> SmPC of [2] of eMC

At clinically relevant concentrations, there is unlikely to be either a synergistic or antagonistic effect on the inhibition of either HIV in the presence of ganciclovir or CMV in the presence of a variety of antiretroviral drugs.

Boceprevir, ganciclovir ---> SmPC of [valganciclovir] of eMC

Metabolic and drug transport interactions of valganciclovir or ganciclovir with the antiviral are considered unlikely

Boceprevir, valganciclovir [2] ---> SmPC of [2] of eMC

Metabolic and drug transport interactions of valganciclovir or ganciclovir with the antiviral are considered unlikely

Breast-feeding, valganciclovir [2] ---> SmPC of [2] of eMC

The possibility of ganciclovir being excreted in the breast milk and causing serious adverse reactions in the nursing infant cannot be discounted. Therefore, breast-feeding must be discontinued

Cidofovir, valganciclovir [2] ---> SmPC of [2] of eMC

Clofarabine [1], valganciclovir ---> SmPC of [1] of EMA

The concomitant use of medicinal products eliminated by tubular secretion should be avoided

Dapsone, valganciclovir [2] ---> SmPC of [2] of eMC

Toxicity may be enhanced when valganciclovir is co-administered with, or is given immediately before or after, other drugs that inhibit replication of rapidly dividing cell populations

Darunavir, ganciclovir ---> SmPC of [valganciclovir] of eMC

Metabolic and drug transport interactions of valganciclovir or ganciclovir with the antiviral are considered unlikely

Darunavir, valganciclovir [2] ---> SmPC of [2] of eMC

Metabolic and drug transport interactions of valganciclovir or ganciclovir with the antiviral are considered unlikely

Didanosine [1], valganciclovir ---> SmPC of [1] of eMC

Los pacientes que tomen didanosina en combinación con ganciclovir y valganciclovir deben ser cuidadosamente monitorizados por las toxicidades asociadas a didanosina.

Doxorubicine, valganciclovir [2] ---> SmPC of [2] of eMC

Toxicity may be enhanced when valganciclovir is co-administered with, or is given immediately before or after, other drugs that inhibit replication of rapidly dividing cell populations

Efavirenz, ganciclovir ---> SmPC of [valganciclovir] of eMC

Metabolic and drug transport interactions of valganciclovir or ganciclovir with the antiviral are considered unlikely

Efavirenz, valganciclovir [2] ---> SmPC of [2] of eMC

Metabolic and drug transport interactions of valganciclovir or ganciclovir with the antiviral are considered unlikely

Emtricitabine, valganciclovir [2] ---> SmPC of [2] of eMC

Coadministration of valganciclovir with antiviral drugs that share the tubular secretion pathway may change the plasma concentrations of valganciclovir and/or the coadministered drug.

Emtricitabine/rilpivirine/tenofovir disoproxil [1], valganciclovir ---> SmPC of [1] of EMA

Co-administration of medicinal products that reduce renal function or compete for active tubular secretion (e.g. cidofovir) may increase serum concentrations of emtricitabine, tenofovir and/or the co-administered medicinal products.

Emtricitabine/tenofovir disoproxil [1], valganciclovir ---> SmPC of [1] of EMA

Use of Truvada should be avoided with concurrent or recent use of a nephrotoxic medicinal product

Enfuvirtide, ganciclovir ---> SmPC of [valganciclovir] of eMC

Metabolic and drug transport interactions of valganciclovir or ganciclovir with the antiviral are considered unlikely

Enfuvirtide, valganciclovir [2] ---> SmPC of [2] of eMC

Metabolic and drug transport interactions of valganciclovir or ganciclovir with the antiviral are considered unlikely

Entecavir, valganciclovir [2] ---> SmPC of [2] of eMC

Coadministration of valganciclovir with antiviral drugs that share the tubular secretion pathway may change the plasma concentrations of valganciclovir and/or the coadministered drug.

Etravirine, ganciclovir ---> SmPC of [valganciclovir] of eMC

Metabolic and drug transport interactions of valganciclovir or ganciclovir with the antiviral are considered unlikely

Etravirine, valganciclovir [2] ---> SmPC of [2] of eMC

Metabolic and drug transport interactions of valganciclovir or ganciclovir with the antiviral are considered unlikely

Flucytosine, valganciclovir [2] ---> SmPC of [2] of eMC

Toxicity may be enhanced when valganciclovir is co-administered with, or is given immediately before or after, other drugs that inhibit replication of rapidly dividing cell populations

Foscarnet, valganciclovir [2] ---> SmPC of [2] of eMC

Ganciclovir, maraviroc ---> SmPC of [valganciclovir] of eMC

Metabolic and drug transport interactions of valganciclovir or ganciclovir with the antiviral are considered unlikely

Ganciclovir, non-nucleoside reverse transcriptase inhibitors ---> SmPC of [valganciclovir] of eMC

Ganciclovir, protease inhibitors ---> SmPC of [valganciclovir] of eMC

Metabolic and drug transport interactions of valganciclovir or ganciclovir with the antiviral are considered unlikely

Ganciclovir, raltegravir ---> SmPC of [valganciclovir] of eMC

Metabolic and drug transport interactions of valganciclovir or ganciclovir with the antiviral are considered unlikely

Ganciclovir, rilpivirine ---> SmPC of [valganciclovir] of eMC

Metabolic and drug transport interactions of valganciclovir or ganciclovir with the antiviral are considered unlikely

Ganciclovir, stavudine ---> SmPC of [valganciclovir] of eMC

No clinically significant interactions were observed when stavudine and oral ganciclovir were given in combination.

Ganciclovir, telaprevir ---> SmPC of [valganciclovir] of eMC

Metabolic and drug transport interactions of valganciclovir or ganciclovir with the antiviral are considered unlikely

Hydroxyurea, valganciclovir [2] ---> SmPC of [2] of eMC

Toxicity may be enhanced when valganciclovir is co-administered with, or is given immediately before or after, other drugs that inhibit replication of rapidly dividing cell populations

Imipenem/cilastatin, valganciclovir [2] ---> SmPC of [2] of eMC

Convulsions have been reported in patients taking imipenem-cilastatin and ganciclovir. Valganciclovir should not be used concomitantly with imipenem-cilastatin unless the potential benefits outweigh the potential risks

Lamivudine, valganciclovir [2] ---> SmPC of [2] of eMC

Coadministration of valganciclovir with antiviral drugs that share the tubular secretion pathway may change the plasma concentrations of valganciclovir and/or the coadministered drug.

Maraviroc, valganciclovir [2] ---> SmPC of [2] of eMC

Metabolic and drug transport interactions of valganciclovir or ganciclovir with the antiviral are considered unlikely

Mycophenolate mofetil [1], valganciclovir ---> SmPC of [1] of EMA

Possible increase of plasma concentrations of ganciclovir and mycophenolate mofetil due to competition for the renal tubular secretion.

Mycophenolate, valganciclovir ---> SmPC of [mycophenolate mofetil] of EMA

Possible increase of plasma concentrations of ganciclovir and also due to competition for the renal tubular secretion.

Nephrotoxic substances, valganciclovir [2] ---> SmPC of [2] of eMC

Non-nucleoside reverse transcriptase inhibitors, valganciclovir

Metabolic and drug transport interactions of valganciclovir or ganciclovir with the antiviral are considered unlikely

Non-nucleoside reverse transcriptase inhibitors, valganciclovir [2] ---> SmPC of [2] of eMC

Nucleoside analogues, valganciclovir [2] ---> SmPC of [2] of eMC

Toxicity may be enhanced when valganciclovir is co-administered with, or is given immediately before or after, other drugs that inhibit replication of rapidly dividing cell populations such as occur in the bone marrow

Peginterferon/ribavirin, valganciclovir [2] ---> SmPC of [2] of eMC

Pentamidine, valganciclovir [2] ---> SmPC of [2] of eMC

Toxicity may be enhanced when valganciclovir is co-administered with, or is given immediately before or after, other drugs that inhibit replication of rapidly dividing cell populations

Peripheral neuropathy, valganciclovir ---> SmPC of [ganciclovir] of eMC

Both active principles have the potential to cause peripheral neuropathy and patients should be monitored for such events

Pregnancy, valganciclovir [2] ---> SmPC of [2] of eMC

Valganciclovir should not be used in pregnancy unless the therapeutic benefit for the mother outweighs the potential risk of teratogenic damage to the child.

Probenecide, valganciclovir [2] ---> SmPC of [2] of eMC

Probenecid given with oral ganciclovir resulted in statistically significantly decreased renal clearance of ganciclovir (20 %) leading to statistically significantly increased exposure (40 %).

Protease inhibitors, valganciclovir [2] ---> SmPC of [2] of eMC

Metabolic and drug transport interactions of valganciclovir or ganciclovir with the antiviral are considered unlikely

Raltegravir, valganciclovir [2] ---> SmPC of [2] of eMC

Metabolic and drug transport interactions of valganciclovir or ganciclovir with the antiviral are considered unlikely

Rilpivirine, valganciclovir [2] ---> SmPC of [2] of eMC

Metabolic and drug transport interactions of valganciclovir or ganciclovir with the antiviral are considered unlikely

Stavudine, valganciclovir [2] ---> SmPC of [2] of eMC

No clinically significant interactions were observed when stavudine and oral ganciclovir were given in combination.

Telaprevir, valganciclovir [2] ---> SmPC of [2] of eMC

Metabolic and drug transport interactions of valganciclovir or ganciclovir with the antiviral are considered unlikely

Tenofovir, valganciclovir [2] ---> SmPC of [2] of eMC

Trimethoprim, valganciclovir [2] ---> SmPC of [2] of eMC

There is a potential for toxicity to be enhanced since trimethoprim and ganciclovir are known to be myelosuppressive and therefore both drugs should be used concomitantly only if the potential benefits outweigh the risks.

Trimethoprim/sulfamethoxazol, valganciclovir [2] ---> SmPC of [2] of eMC

Toxicity may be enhanced when valganciclovir is co-administered with, or is given immediately before or after, other drugs that inhibit replication of rapidly dividing cell populations

Tubular secretion, valganciclovir

Coadministration of valganciclovir with antiviral drugs that share the tubular secretion pathway may change the plasma concentrations of valganciclovir and/or the coadministered drug.

Valganciclovir [1], vinblastine ---> SmPC of [1] of eMC

Toxicity may be enhanced when valganciclovir is co-administered with, or is given immediately before or after, other drugs that inhibit replication of rapidly dividing cell populations

Valganciclovir [1], vincristine ---> SmPC of [1] of eMC

Toxicity may be enhanced when valganciclovir is co-administered with, or is given immediately before or after, other drugs that inhibit replication of rapidly dividing cell populations

Valganciclovir [1], zidovudine ---> SmPC of [1] of eMC

When zidovudine was given in the presence of oral ganciclovir there was a small (17 %), but statistically significant increase in the AUC of zidovudine. Zidovudine and ganciclovir have the potential to cause neutropenia and anaemia

CONTRAINDICATIONS of Valganciclovir

- Valcyte is contra-indicated in patients with hypersensitivity to valganciclovir, ganciclovir or to any of the excipients

- Due to the similarity of the chemical structure of Valcyte and that of aciclovir and valaciclovir, a cross-hypersensitivity reaction between these drugs is possible. Therefore, Valcyte is contra-indicated in patients with hypersensitivity to aciclovir and valaciclovir.

- Valcyte is contra-indicated during breast-feeding

http://www.medicines.org.uk/emc/

Valoctocogene roxaparvovec (Roctavian)

Ability to drive, valoctocogene roxaparvovec [2] ---> SmPC of [2] of EMA

Patients should be advised to use caution when driving and operating machinery until they are certain that this medicinal product does not adversely affect them (see section 4.8).

Breast-feeding, valoctocogene roxaparvovec [2] ---> SmPC of [2] of EMA

It is unknown whether valoctocogene roxaparvovec is excreted in human milk. A risk to the new-borns/infants cannot be excluded. ROCTAVIAN should not be used during breast-feeding.

Corticosteroids, valoctocogene roxaparvovec [2] ---> SmPC of [2] of EMA

Agents that may reduce or increase the plasma concentration of corticosteroids (e.g., agents that induce or inhibit cytochrome P450 3A4) can decrease the efficacy of the corticosteroid regimen or increase their side effects (see section 4.4).

Efavirenz, valoctocogene roxaparvovec [2] ---> SmPC of [2] of EMA

Efavirenz is not recommended in patients who are benefiting from valoctocogene roxaparvovec. The use of non-efavirenz treatments should be considered.

Factor VIII, valoctocogene roxaparvovec [2] ---> SmPC of [2] of EMA

When a new medication is started, close monitoring of ALT and factor VIII activity levels (e.g., weekly to every 2 weeks for the first month) is recommended to assess potential effects on both levels.

Fertility, valoctocogene roxaparvovec [2] ---> SmPC of [2] of EMA

No non-clinical or clinical studies were performed to evaluate the effect of valoctocogene roxaparvovec on fertility (see Contraception after administration to males).

Hepatotoxic drugs, valoctocogene roxaparvovec [2] ---> SmPC of [2] of EMA

Caution of use with hepatotoxic medications or hepatotoxic substances should be applied due to limited experience. The safety and efficacy of valoctocogene roxaparvovec in these circumstances have not been established (see section 4.4).

Isotretinoin, valoctocogene roxaparvovec [2] ---> SmPC of [2] of EMA

Isotretinoin is not recommended in patients who are benefiting from valoctocogene roxaparvovec.

Medicinal products, valoctocogene roxaparvovec [2] ---> SmPC of [2] of EMA

Prior to valoctocogene roxaparvovec administration, the patient's existing medicinal products should be reviewed to determine if they should be modified to prevent anticipated interactions described in this section.

Men, valoctocogene roxaparvovec [2] ---> SmPC of [2] of EMA

Treated patients of reproductive potential and their female partners of childbearing potential must prevent or postpone pregnancy using double barrier contraception, and men must not donate semen.

Pregnancy, valoctocogene roxaparvovec [2] ---> SmPC of [2] of EMA

ROCTAVIAN should not be used during pregnancy.

Valoctocogene roxaparvovec [1], women of childbearing potential ---> SmPC of [1] of EMA

Moreover, no data are available to recommend a specific duration of contraceptive measures in women of childbearing potential. Therefore, ROCTAVIAN is not recommended in women of childbearing potential.

CONTRAINDICATIONS of Valoctocogene roxaparvovec (Roctavian)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Active infections, either acute or uncontrolled chronic; or patients with known significant hepatic fibrosis, or cirrhosis (see section 4.4).

https://www.ema.europa.eu/en/documents/product-information/roctavian-epar-product-information_en.pdf 17/09/2024

Valsartan

Ability to drive, valsartan [2] ---> SmPC of [2] of eMC

When driving vehicles or operating machines it should be taken into account that occasionally dizziness or weariness may occur.

ACE inhibitors, valsartan [2] ---> SmPC of [2] of eMC

There is evidence that the concomitant use of ACE-inhibitors, AIIRAs or aliskiren increases the risk of hypotension, hyperkalaemia and decreased renal function (including acute renal failure). Dual blockade of RAAS is not recommended

Acetylsalicylic acid, valsartan [2] ---> SmPC of [2] of eMC

When AIIRAs are administered simultaneously with NSAIDs, attenuation of the antihypertensive effect may occur. Furthermore, the concomitant use may lead to an increased risk of worsening of renal function and an increase in serum potassium.

AIIRA, valsartan

The dual blockade of the RAA-system through the combined use of ACE-inhibitors, AIIRA or aliskiren is associated with a higher frequency of adverse events such as hypotension, hyperkalaemia and decreased renal function (including acute renal failure)

Alfa-adrenergic receptor blockers, valsartan

The combination may increase the antihypertensive effect

Aliskiren, valsartan ---> SmPC of [amlodipine/valsartan] of EMA

The concomitant use of ARBs with aliskiren is contraindicated in patients with diabetes mellitus or renal impairment (GFR < 60 ml/min/1.73 m²)

Amiloride, valsartan [2] ---> SmPC of [2] of eMC

Concomitant use with of valsartan with potassium supplements, potassium-sparing diuretics, salt substitutes containing potassium, or other agents that may increase potassium levels (heparin, etc.) is not recommended.

Amlodipine, valsartan [2] ---> SmPC of [2] of eMC

In drug interaction studies with valsartan, no interactions of clinical significance have been found with valsartan and amlodipine

Antihypertensives, valsartan

The blood pressure lowering effect can be increased

Ataluren [1], valsartan ---> SmPC of [1] of EMA

Caution should be exercised when ataluren is co-administered with medicinal products that are substrates of UGT1A9, OAT1, OAT3, or OATP1B3 because of the risk of increase concentration of these medicinal products

Atenolol, valsartan [2] ---> SmPC of [2] of eMC

In drug interaction studies with valsartan, no interactions of clinical significance have been found with valsartan and atenolol

Breast-feeding, valsartan [2] ---> SmPC of [2] of eMC

Valsartan is not recommended during breastfeeding

Cabazitaxel [1], valsartan ---> SmPC of [1] of EMA

The risk of interaction with OATP1B1 substrates is possible, notably during the infusion duration (1 hour) and up to 20 minutes after the end of the infusion.

Cimetidine, valsartan [2] ---> SmPC of [2] of eMC

In drug interaction studies with valsartan, no interactions of clinical significance have been found with valsartan and cimetidine

Coxibs, valsartan [2] ---> SmPC of [2] of eMC

Cyclosporine, valsartan ---> SmPC of [amlodipine/valsartan/hydrochlorothiazide] of EMA

The results of an in vitro study with human liver tissue indicate that valsartan is a substrate of the hepatic uptake transporter OATP1B1. Co-administration of inhibitors of OATP1B1 may increase the systemic exposure to valsartan.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, valsartan ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of EM

CYP3A4 and/or OATP1B inhibition by paritaprevir. Clinical monitoring and dose reduction is recommended for angiotensin receptor blockers when co-administered with Viekirax with or without dasabuvir.

Digoxin, valsartan [2] ---> SmPC of [2] of eMC

In drug interaction studies with valsartan, no interactions of clinical significance have been found with valsartan and digoxine

Glecaprevir/pibrentasvir [1], valsartan ---> SmPC of [1] of EMA

No dose adjustment is required.

Glibenclamide, valsartan [2] ---> SmPC of [2] of eMC

In drug interaction studies with valsartan, no interactions of clinical significance have been found with valsartan and glibenclamide

Heparin, valsartan [2] ---> SmPC of [2] of eMC

Hydrochlorothiazide, valsartan [2] ---> SmPC of [2] of eMC

In drug interaction studies with valsartan, no interactions of clinical significance have been found with valsartan and hydrochlorothiazide

Hyperkalemia, valsartan ---> SmPC of [amlodipine/valsartan/hydrochlorothiazide] of EMA

If a medicinal product that affects potassium levels is considered necessary in combination with valsartan, frequent monitoring of potassium plasma levels is advised.

Indometacin, valsartan [2] ---> SmPC of [2] of eMC

In drug interaction studies with valsartan, no interactions of clinical significance have been found with valsartan and indometacin

Lithium, valsartan [2] ---> SmPC of [2] of eMC

Reversible increases in serum lithium concentrations and toxicity have been reported during concurrent use of ACE inhibitors. Due to the lack of experience with concomitant use of valsartan and lithium, this combination is not recommended.

MRP2 inhibitors, valsartan [2] ---> SmPC of [2] of eMC

Co-administration of inhibitors of the uptake transporter OATP1B1/OATP1B3 (eg. rifampin, ciclosporin) or efflux transporter (eg. ritonavir) may increase the systemic exposure to valsartan.

NSAID, valsartan [2] ---> SmPC of [2] of eMC

OATP1B1 inhibitors, valsartan [2] ---> SmPC of [2] of eMC

Co-administration of inhibitors of the uptake transporter OATP1B1/OATP1B3 (eg. rifampin, ciclosporin) or efflux transporter (eg. ritonavir) may increase the systemic exposure to valsartan.

OATP1B3 inhibitors, valsartan [2] ---> SmPC of [2] of eMC

Co-administration of inhibitors of the uptake transporter OATP1B1/OATP1B3 (eg. rifampin, ciclosporin) or efflux transporter (eg. ritonavir) may increase the systemic exposure to valsartan.

Olaparib [1], valsartan ---> SmPC of [1] of EMA

Olaparib is an inhibitor of OATP1B1. It cannot be excluded that olaparib may increase the exposure to substrates of OATP1B1

Ombitasvir/paritaprevir/ritonavir [1], valsartan ---> SmPC of [1] of EMA

CYP3A4 and/or OATP1B inhibition by paritaprevir. Clinical monitoring and dose reduction is recommended for angiotensin receptor blockers when co-administered with Viekirax with or without dasabuvir.

Potassium, valsartan [2] ---> SmPC of [2] of eMC

Potassium-sparing diuretics, valsartan [2] ---> SmPC of [2] of eMC

Pregnancy, valsartan [2] ---> SmPC of [2] of eMC

The use of AIIRAs is not recommended during the first trimester of pregnancy. The use of AIIRAs is contraindicated during the second and third trimesters of pregnancy

Primary hyperaldosteronism, valsartan ---> SmPC of [amlodipine/valsartan/hydrochlorothiazide] of EMA

Patients with primary hyperaldosteronism should not be treated with the angiotensin II antagonist valsartan as their renin-angiotensin system is not activated. Therefore, Dafiro HCT is not recommended in this population.

Rifampicin, valsartan ---> SmPC of [amlodipine/valsartan/hydrochlorothiazide] of EMA

Ritonavir, valsartan [2] ---> SmPC of [2] of eMC

Co-administration of inhibitors of the uptake transporter OATP1B1/OATP1B3 (eg. rifampin, ciclosporin) or efflux transporter (eg. ritonavir) may increase the systemic exposure to valsartan.

Tobramycin, valsartan

Increased risk of nephrotoxicity

Tricyclic antidepressant, valsartan

The combination may increase the antihypertensive effect

Valsartan [1], warfarin ---> SmPC of [1] of eMC

In drug interaction studies with valsartan, no interactions of clinical significance have been found with valsartan and warfarin

Valsartan, vildagliptin ---> SmPC of [vildagliptin/metformin] of EMA

Drug-drug interaction studies in healthy subjects were conducted with amlodipine, ramipril, valsartan and simvastatin. No clinically relevant pharmacokinetic interactions were observed after co-administration with vildagliptin.

Valsartan, vildagliptin/metformin [2] ---> SmPC of [2] of EMA

Valsartan, vismodegib [2] ---> SmPC of [2] of EMA

In vitro, vismodegib is an inhibitor of OATP1B1. It cannot be excluded that vismodegib may increase the exposure to substrates of OATP1B1. In particular, caution should be exercised if vismodegib is administered in combination with any statin.

CONTRAINDICATIONS of Valsartan

- Hypersensitivity to the active substance or to any of the excipients

- Severe hepatic impairment, biliary cirrhosis and cholestasis.

- Second and third trimester of pregnancy

http://www.medicines.org.uk/emc/

Vamorolone (Agamree)

Antagonist at the mineralocorticoid receptor, vamorolone [2] ---> SmPC of [2] of EMA

Vamorolone acts as an antagonist at the mineralocorticoid receptor. The use of vamorolone in combination with mineralocorticoid receptor antagonist may increase the risk of hyperkalaemia.

Breast-feeding, vamorolone [2] ---> SmPC of [2] of EMA

There are no data on the excretion of vamorolone or its metabolites in human milk. A risk to the newborns / infants cannot be excluded. Breast-feeding should be discontinued during treatment with AGAMREE.

Carbamazepine, vamorolone [2] ---> SmPC of [2] of EMA

Strong CYP3A4 inducers or strong PXR inducers (e.g. carbamazepine, phenytoin, rifampicin, St. John's wort) may decrease plasma concentrations of vamorolone and lead to lack of efficacy

Clarithromycin, vamorolone [2] ---> SmPC of [2] of EMA

The recommended dose of vamorolone when administered with strong CYP3A4 inhibitors (e.g telithromycin, clarithromycin, voriconazole, grapefruit juice) is 4 mg/kg/day.

Endocrine function, vamorolone [2] ---> SmPC of [2] of EMA

Vamorolone causes alterations in endocrine function, especially with chronic use. In addition, patients with altered thyroid function, or pheochromocytoma may be at increased risk for endocrine effects.

Eplerenone, vamorolone [2] ---> SmPC of [2] of EMA

No cases of hyperkalaemia have been observed in patients using vamorolone alone or in combination with eplerenone or spironolactone.

Fertility, vamorolone [2] ---> SmPC of [2] of EMA

There are no clinical data on the effects of vamorolone on fertility. Long-term vamorolone treatment inhibited male and female fertility in dogs (see section 5.3).

Glucuronidation inhibitors, vamorolone [2] ---> SmPC of [2] of EMA

The potential for drug-drug-interactions involving UGTs has not been fully evaluated, therefore all inhibitors of UGTs should be avoided as concomitant medication and should be used with caution if medically required.

Grapefruit juice, vamorolone [2] ---> SmPC of [2] of EMA

The recommended dose of vamorolone when administered with strong CYP3A4 inhibitors (e.g telithromycin, clarithromycin, voriconazole, grapefruit juice) is 4 mg/kg/day.

Hydrocortisone, vamorolone [2] ---> SmPC of [2] of EMA

Regular treatment with AGAMREE should be temporarily supplemented with systemic hydrocortisone to prevent the risk of adrenal crisis.

Itraconazol, vamorolone [2] ---> SmPC of [2] of EMA

The recommended dose of vamorolone when administered with strong CYP3A4 inhibitors (e.g telithromycin, clarithromycin, voriconazole, grapefruit juice) is 4 mg/kg/day.

Live attenuated vaccines, vamorolone [2] ---> SmPC of [2] of EMA

Live attenuated or live vaccines should be administered at least 6 weeks prior to starting AGAMREE treatment.

Phenytoin, vamorolone [2] ---> SmPC of [2] of EMA

Strong CYP3A4 inducers or strong PXR inducers (e.g. carbamazepine, phenytoin, rifampicin, St. John's wort) may decrease plasma concentrations of vamorolone and lead to lack of efficacy

Pregnancy, vamorolone [2] ---> SmPC of [2] of EMA

AGAMREE should not be used during pregnancy unless the clinical condition of the woman requires treatment with vamorolone.

Rifampicin, vamorolone [2] ---> SmPC of [2] of EMA

Strong CYP3A4 inducers or strong PXR inducers (e.g. carbamazepine, phenytoin, rifampicin, St. John's wort) may decrease plasma concentrations of vamorolone and lead to lack of efficacy

Spironolactone, vamorolone [2] ---> SmPC of [2] of EMA

No cases of hyperkalaemia have been observed in patients using vamorolone alone or in combination with eplerenone or spironolactone.

St. John's wort, vamorolone [2] ---> SmPC of [2] of EMA

Strong CYP3A4 inducers or strong PXR inducers (e.g. carbamazepine, phenytoin, rifampicin, St. John's wort) may decrease plasma concentrations of vamorolone and lead to lack of efficacy

Strong CYP3A4 inductors, vamorolone [2] ---> SmPC of [2] of EMA

Strong CYP3A4 inducers or strong PXR inducers (e.g. carbamazepine, phenytoin, rifampicin, St. John's wort) may decrease plasma concentrations of vamorolone and lead to lack of efficacy

Telithromycin, vamorolone [2] ---> SmPC of [2] of EMA

The recommended dose of vamorolone when administered with strong CYP3A4 inhibitors (e.g telithromycin, clarithromycin, voriconazole, grapefruit juice) is 4 mg/kg/day.

Vaccination against varicella zoster virus, vamorolone [2] ---> SmPC of [2] of EMA

For patients without a history of chicken pox or vaccination, vaccination against varicella zoster virus should be initiated before treatment with AGAMREE.

Vaccinations with live organism vaccines, vamorolone [2] ---> SmPC of [2] of EMA

Live attenuated or live vaccines should be administered at least 6 weeks prior to starting AGAMREE treatment.

Vaccinations, vamorolone [2] ---> SmPC of [2] of EMA

Response to live or live attenuated vaccines can be altered in patients treated with glucocorticoids. The risk with AGAMREE is unknown.

Vamorolone [1], voriconazole ---> SmPC of [1] of EMA

The recommended dose of vamorolone when administered with strong CYP3A4 inhibitors (e.g telithromycin, clarithromycin, voriconazole, grapefruit juice) is 4 mg/kg/day.

Vamorolone [1], women of childbearing potential ---> SmPC of [1] of EMA

Women of childbearing potential have to use effective contraception during treatment with AGAMREE.

CONTRAINDICATIONS of Vamorolone (Agamree)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Severe liver impairment (Child-Pugh class C).

- Use of live or live-attenuated vaccines in the 6 weeks prior to starting treatment and during the treatment (see section 4.4).

https://www.ema.europa.eu/en/documents/product-information/agamree-epar-product-information_en.pdf. 04/01/2024

Vancomycin

Acetylsalicylic acid [1], vancomycin ---> SmPC of [1] of eMC

The acetylsalicylic acid increases the ototoxicity risk of vancomycin.

Adefovir dipivoxil [1], vancomycin ---> SmPC of [1] of EMA

Co-administration of adefovir dipivoxil with other medicinal products that are eliminated by tubular secretion or alter tubular function may increase serum concentrations of either adefovir or the co-administered medicinal product

Amikacine, vancomycin [2] ---> SmPC of [2] of eMC

Concurrent or sequential systemic or topical use of other potentially neurotoxic or nephrotoxic drugs may potentiate the nephrotoxicity and/or ototoxicity of vancomycin and consequently requires careful monitoring.

Aminoglycoside antibiotics, vancomycin [2] ---> SmPC of [2] of eMC

If vancomycin is co-administrated with an aminoglycoside (e.a. gentamycin) patients should be monitored carefully for signs of neurotoxicity and ototoxicity. The dosage should be adjusted when renal disturbance occurs

Amphotericin, vancomycin [2] ---> SmPC of [2] of eMC

Anaesthetics, vancomycin [2] ---> SmPC of [2] of eMC

The combination may increase the frequency of adverse effects. These may be minimized by the vancomycin administration as a 60-minute infusion prior to anaesthetic induction

Atracurium [1], vancomycin ---> SmPC of [1] of eMC

As with all non-depolarising neuromuscular blocking agents the magnitude and/or duration of a non-depolarising neuromuscular block may be increased as a result of interaction with antibiotics

Bacitracin, vancomycin [2] ---> SmPC of [2] of eMC

Benzylpenicillin, vancomycin

Incompatible with benzylpenicillin in solution

Breast-feeding, vancomycin [2] ---> SmPC of [2] of eMC

Vancomycin is excreted in human milk. Considering the importance of this medicine for nursing mother, the decision to stop breastfeeding should be considered.

Carboplatin, vancomycin [2] ---> SmPC of [2] of eMC

Ceftriaxone, vancomycin [2] ---> SmPC of [2] of eMC

Based on literature reports ceftriaxone is incompatible with vancomycin

Cephalosporins, vancomycin ---> SmPC of [cephalexin] of

Cephalosporins may have an increased risk of nephrotoxicity in the presence of vancomycin

Chlorprothixene, vancomycin

Chlorprothixene may enhance the respiratory depression caused by the polypeptide antibiotic

Cisplatin, vancomycin [2] ---> SmPC of [2] of eMC

Colistin, vancomycin [2] ---> SmPC of [2] of eMC

Cyclizine, vancomycin

The co-administration may mask ototoxicity symptoms

Cyclosporine [1], vancomycin ---> SmPC of [1] of eMC

Care should be taken when using ciclosporin together with other active substances that exhibit nephrotoxic synergy

Efavirenz/emtricitabine/tenofovir disoproxil [1], vancomycin ---> SmPC of [1] of EMA

Use of Atripla should be avoided with concurrent or recent use of a nephrotoxic medicinal product.

Elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil [1], vancomycin ---> SmPC of [1] of EMA

Use of emtricitabine/rilpivirine/tenofovir should be avoided with concurrent or recent use of a nephrotoxic medicinal product

Emtricitabine/rilpivirine/tenofovir disoproxil [1], vancomycin ---> SmPC of [1] of EMA

Use of emtricitabine/rilpivirine/tenofovir should be avoided with concurrent or recent use of a nephrotoxic medicinal product

Emtricitabine/tenofovir disoproxil [1], vancomycin ---> SmPC of [1] of EMA

Use of Truvada should be avoided with concurrent or recent use of a nephrotoxic medicinal product

Fosfomycin, vancomycin

The combination of fosfomycin with vancomycin may have an additive to synergistic effect.

Gentamicin, vancomycin [2] ---> SmPC of [2] of eMC

Kanamycin, vancomycin [2] ---> SmPC of [2] of eMC

Meglumine and sodium ioxitalamate, vancomycin

The co-administration with other medicinal products with nephrotoxic potential may decrease the renal function and cause a permanent damage

Muscle relaxants (non-depolarizing), vancomycin ---> SmPC of [atracurium] of eMC

As with all non-depolarising neuromuscular blocking agents the magnitude and/or duration of a non-depolarising neuromuscular block may be increased as a result of interaction with antibiotics

Muscle relaxants, vancomycin [2] ---> SmPC of [2] of eMC

There is an increased potential of neuromuscular blockade with concomitant administration of vancomycin and neuromuscular blocking agents.

Neomycin, vancomycin [2] ---> SmPC of [2] of eMC

Nephrotoxic substances, vancomycin [2] ---> SmPC of [2] of eMC

Netilmicin, vancomycin [2] ---> SmPC of [2] of eMC

Ototoxic agents, vancomycin [2] ---> SmPC of [2] of eMC

Polymyxin, vancomycin [2] ---> SmPC of [2] of eMC

Polypeptide antibiotics, vancomycin [2] ---> SmPC of [2] of eMC

Pregnancy, vancomycin [2] ---> SmPC of [2] of eMC

Vancomycin penetrates the placenta. Therefore vancomycin should be given in pregnancy only if clearly needed and after a careful risk/benefit evaluation.

Streptomycin, vancomycin [2] ---> SmPC of [2] of eMC

Tacrolimus [1], vancomycin ---> SmPC of [1] of EMA

Concurrent use of tacrolimus with medicinal products known to have nephrotoxic or neurotoxic effects may increase these effects

Taurolidine, vancomycin

The systemic use of vancomycin may decrease the effect of taurolidine

Telbivudine [1], vancomycin ---> SmPC of [1] of EMA

Since telbivudine is eliminated primarily by renal excretion, co-administration with substances that affect renal function may affect plasma concentrations of telbivudine and/or the co-administered substance. The combination should be used with caution.

Tenofovir disoproxil [1], vancomycin ---> SmPC of [1] of EMA

Use of tenofovir should be avoided with recent or concurrent use of a nephrotoxic medicinal product

Tenofovir, vancomycin ---> SmPC of [tenofovir disoproxil] of EMA

Use of tenofovir should be avoided with recent or concurrent use of a nephrotoxic medicinal product

Tobramycin, vancomycin [2] ---> SmPC of [2] of eMC

The administration concurrent or sequential of vancomycin with other potentially nephrotoxic or ototoxic drugs may increase the nephrotoxicity and/or ototoxicity

Vancomycin [1], viomycin ---> SmPC of [1] of eMC

CONTRAINDICATIONS of Vancomycin

- Hypersensitivity to the active substance or to any of the excipients.

http://www.medicines.org.uk/emc/

Vandetanib (Caprelsa)

Ability to drive, vandetanib [2] ---> SmPC of [2] of EMA

However, fatigue and blurred vision have been reported and those patients who experience these symptoms should observe caution when driving or using machines.

Amisulpride, vandetanib [2] ---> SmPC of [2] of EMA

The concomitant use of vandetanib with medicinal products known to also prolong the QTc interval and/or induce Torsades de pointes is either contraindicated or not recommended

Arsenic, vandetanib [2] ---> SmPC of [2] of EMA

The concomitant use of vandetanib with medicinal products known to also prolong the QTc interval and/or induce Torsades de pointes is either contraindicated or not recommended

Artesunate [1], vandetanib ---> SmPC of [1] of EMA

Co-administration of intravenous artesunate with strong inhibitors of UGT enzymes (e.g. axitinib, vandetanib, imatinib, diclofenac) may increase plasma exposures to DHA. Co-administration should be avoided if possible.

Bortezomib, vandetanib

Vandetanib, CYP3A4 inductor, may decrease the plasma levels of bortezomib. Caution should be exercised

Breast-feeding, vandetanib [2] ---> SmPC of [2] of EMA

Breast-feeding is contraindicated while receiving vandetanib therapy

Carbamazepine, vandetanib [2] ---> SmPC of [2] of EMA

The concomitant use of vandetanib with strong CYP3A4 inducers (such as rifampicin, St John's Wort, carbamazepine, phenobarbital) should be avoided (see section 4.5).

Chlorpromazine, vandetanib [2] ---> SmPC of [2] of EMA

The concomitant use of vandetanib with medicinal products known to also prolong the QTc interval and/or induce Torsades de pointes is either contraindicated or not recommended

Cisapride, vandetanib [2] ---> SmPC of [2] of EMA

The concomitant use of vandetanib with medicinal products known to also prolong the QTc interval and/or induce Torsades de pointes is either contraindicated or not recommended

Clarithromycin, vandetanib [2] ---> SmPC of [2] of EMA

In healthy subjects, no clinically significant interaction was shown between vandetanib (a single dose of 300 mg) and the potent CYP3A4 inhibitor, itraconazole

Class IA antiarrhythmic agents, vandetanib [2] ---> SmPC of [2] of EMA

The concomitant use of vandetanib with medicinal products known to also prolong the QTc interval and/or induce Torsades de pointes is either contraindicated or not recommended

Class III antiarrhythmic agents, vandetanib [2] ---> SmPC of [2] of EMA

The concomitant use of vandetanib with medicinal products known to also prolong the QTc interval and/or induce Torsades de pointes is either contraindicated or not recommended

Cyclosporine, vandetanib

Vandetanib, CYP3A4 inductor, may decrease the plasma levels of cyclosporine. Caution should be exercised

Dabigatran, vandetanib [2] ---> SmPC of [2] of EMA

As regards other P-gp substrates such as dabigatran, a clinical monitoring is recommended in case of combination with vandetanib.

Digoxin, vandetanib [2] ---> SmPC of [2] of EMA

Vandetanib, P-glycoprotein inhibitor, may increase the plasma levels of digoxin. The bradycardiac effect of digoxin may increase the risk of vandetanib QTc interval prolongation and Torsade de Pointes. Increased clinical and biological surveillance

Docetaxel, vandetanib

Vandetanib, CYP3A4 inductor, may decrease the plasma levels of docetaxel. Caution should be exercised

Drugs metabolised by CYP3A4, vandetanib

Vandetanib, CYP3A4 inductor, may decrease the plasma levels of the medicinal products metabolized by CYP3A4. Caution should be exercised

Empagliflozin/metformin [1], vandetanib ---> SmPC of [1] of EMA

Co-administration of metformin with Inhibitors of OCT2 may decrease the renal elimination of metformin and thus lead to an increase in metformin plasma concentration.

Ertugliflozin/metformin [1], vandetanib ---> SmPC of [1] of EMA

Inhibitors of OCT2 may decrease the renal elimination of metformin and thus lead to an increase in metformin plasma concentration.

Erythromycin, vandetanib [2] ---> SmPC of [2] of EMA

The concomitant use of vandetanib with medicinal products known to also prolong the QTc interval and/or induce Torsades de pointes is either contraindicated or not recommended (erythromycin intravenous)

Fertility, vandetanib [2] ---> SmPC of [2] of EMA

In rats, vandetanib had no effect on male fertility but impaired female fertility (see section 5.3). Effects on reproduction in paediatric patients treated with vandetanib are not known.

Halofantrine, vandetanib [2] ---> SmPC of [2] of EMA

The concomitant use of vandetanib with medicinal products known to also prolong the QTc interval and/or induce Torsades de pointes is either contraindicated or not recommended

Haloperidol, vandetanib [2] ---> SmPC of [2] of EMA

The concomitant use of vandetanib with medicinal products known to also prolong the QTc interval and/or induce Torsades de pointes is either contraindicated or not recommended

Hydroxyzine [1], vandetanib ---> SmPC of [1] of eMC

Co-administration of hydroxyzine with drugs known to prolong the QT interval and/or induce Torsade de Pointes increase the risk of cardiac arrhythmia. Therefore, the combination is contra-indicated

Itraconazol, vandetanib [2] ---> SmPC of [2] of EMA

In healthy subjects, no clinically significant interaction was shown between vandetanib (a single dose of 300 mg) and the potent CYP3A4 inhibitor, itraconazole

Lumefantrine, vandetanib [2] ---> SmPC of [2] of EMA

The concomitant use of vandetanib with medicinal products known to also prolong the QTc interval and/or induce Torsades de pointes is either contraindicated or not recommended

Metformin, vandetanib [2] ---> SmPC of [2] of EMA

In healthy subjects with wild type for OCT2, the AUC(0-t) and Cmax for metformin (OCT2 substrate) were increased by 74% and 50%, respectively and CLR of metformin was decreased by 52% when given together with vandetanib.

Metformin/saxagliptin/dapagliflozin [1], vandetanib ---> SmPC of [1] of EMA

Co-administration of metformin with inhibitors of OCT2 may decrease the renal elimination of metformin and thus lead to an increase in metformin plasma concentration;

Methadone, vandetanib [2] ---> SmPC of [2] of EMA

The concomitant use of vandetanib with medicinal products known to also prolong the QTc interval and/or induce Torsades de pointes is either contraindicated or not recommended

Midazolam, vandetanib [2] ---> SmPC of [2] of EMA

In healthy subjects, the exposure for midazolam (CYP3A4 substrate) was not affected when given together with a single dose of vandetanib at 800 mg.

Mizolastine, vandetanib [2] ---> SmPC of [2] of EMA

The concomitant use of vandetanib with medicinal products known to also prolong the QTc interval and/or induce Torsades de pointes is either contraindicated or not recommended

Moxifloxacin, vandetanib [2] ---> SmPC of [2] of EMA

The concomitant use of vandetanib with medicinal products known to also prolong the QTc interval and/or induce Torsades de pointes is either contraindicated or not recommended

OCT2 substrates, vandetanib [2] ---> SmPC of [2] of EMA

Vandetanib, inhibitor of organic cation transporter 2, may increase the exposition of organic cation transporter 2 substrate. Careful monitoring

Omeprazole, vandetanib [2] ---> SmPC of [2] of EMA

No change in dose of vandetanib is required when vandetanib is given with either omeprazole

Ondansetron, vandetanib [2] ---> SmPC of [2] of EMA

Therefore, the concomitant use of ondansetron with vandetanib is not recommended. If ondansetron is administered with vandetanib, closer monitoring of serum electrolytes and ECGs and aggressive management of any abnormalities is required.

P-glycoprotein substrates, vandetanib [2] ---> SmPC of [2] of EMA

Vandetanib, P-glycoprotein inhibitor, may increase the plasma levels of the substrate of P-glycoprotein. Increased clinical and biological surveillance

Pentamidine, vandetanib [2] ---> SmPC of [2] of EMA

The concomitant use of vandetanib with medicinal products known to also prolong the QTc interval and/or induce Torsades de pointes is either contraindicated or not recommended

Phenobarbital, vandetanib [2] ---> SmPC of [2] of EMA

The concomitant use of vandetanib with strong CYP3A4 inducers (such as rifampicin, St John's Wort, carbamazepine, phenobarbital) should be avoided (see section 4.5).

Phenytoin, vandetanib [2] ---> SmPC of [2] of EMA

The concomitant use of vandetanib with strong CYP3A4 inducers (such as rifampicin, St John's Wort, carbamazepine, phenobarbital) should be avoided (see section 4.5).

Pregnancy, vandetanib [2] ---> SmPC of [2] of EMA

If vandetanib is used during pregnancy or if the patient becomes pregnant while receiving vandetanib, she should be apprised of the potential for foetal abnormalities or loss of the pregnancy

Pregnancy, vandetanib [2] ---> SmPC of [2] of EMA

Treatment should only be continued in pregnant women if the potential benefit to the mother outweighs the risk to the foetus.

Pregnancy, vandetanib [2] ---> SmPC of [2] of EMA

As expected from its pharmacological actions, vandetanib has shown significant effects on all stages of female reproduction in rats (see section 5.3).

Proton pump inhibitors, vandetanib [2] ---> SmPC of [2] of EMA

The co-administration of vandetanib with proton pump inhibitors may reduce a patient's exposure to vandetanib. Co-administration is not recommended

QT interval prolonging drugs, vandetanib [2] ---> SmPC of [2] of EMA

The concomitant use of vandetanib with medicinal products known to also prolong the QTc interval and/or induce Torsades de pointes is either contraindicated or not recommended

Ranitidine, vandetanib [2] ---> SmPC of [2] of EMA

No change in dose of vandetanib is required when vandetanib is given with either ranitidine.

Rifampicin, vandetanib [2] ---> SmPC of [2] of EMA

The concomitant use of vandetanib with strong CYP3A4 inducers (such as rifampicin, St John's Wort, carbamazepine, phenobarbital) should be avoided (see section 4.5).

Ritonavir, vandetanib [2] ---> SmPC of [2] of EMA

In healthy subjects, no clinically significant interaction was shown between vandetanib (a single dose of 300 mg) and the potent CYP3A4 inhibitor, itraconazole

St. John's wort, vandetanib [2] ---> SmPC of [2] of EMA

The concomitant use of vandetanib with strong CYP3A4 inducers (such as rifampicin, St Johns' Wort, carbamazepine, phenobarbital) should be avoided

Strong CYP3A4 inductors, vandetanib [2] ---> SmPC of [2] of EMA

The concomitant use of vandetanib with strong CYP3A4 inducers (such as rifampicin, St John's Wort, carbamazepine, phenobarbital) should be avoided (see section 4.5).

Strong CYP3A4 inhibitors, vandetanib [2] ---> SmPC of [2] of EMA

In healthy subjects, no clinically significant interaction was shown between vandetanib (a single dose of 300 mg) and the potent CYP3A4 inhibitor, itraconazole

Sulpiride, vandetanib [2] ---> SmPC of [2] of EMA

Combination of sulpiride with drugs which could induce torsades de pointes or prolong the QT interval is not recommended

Sun, vandetanib [2] ---> SmPC of [2] of EMA

Care should be taken with sun exposure by wearing protective clothing and /or sunscreen due to the potential risk of phototoxicity reactions associated with vandetanib treatment.

Tacrolimus, vandetanib

Vandetanib, CYP3A4 inductor, may decrease the plasma levels of tacrolimus. Caution should be exercised

Toremifene, vandetanib [2] ---> SmPC of [2] of EMA

The concomitant use of vandetanib with medicinal products known to also prolong the QTc interval and/or induce Torsades de pointes is either contraindicated or not recommended

Torsades de pointes inducing drugs, vandetanib [2] ---> SmPC of [2] of EMA

The concomitant use of vandetanib with medicinal products known to also prolong the QTc interval and/or induce Torsades de pointes is either contraindicated or not recommended

Vandetanib [1], vitamin K antagonists ---> SmPC of [1] of EMA

In consideration of the high intra-individual variability of the response to anticoagulation, and the possibility of interaction between vitamin K antagonists and chemotherapy, an increased frequency of the INR monitoring is recommended

Vandetanib [1], women of childbearing potential ---> SmPC of [1] of EMA

Women of childbearing potential must use effective contraception during therapy and for at least four months following the last dose.

Vandetanib [1], zuclopenthixol ---> SmPC of [1] of EMA

The concomitant use of vandetanib with medicinal products known to also prolong the QTc interval and/or induce Torsades de pointes is either contraindicated or not recommended

Vandetanib, vildagliptin/metformin [2] ---> SmPC of [2] of EMA

Concomitant use of medicinal products that interfere with common renal tubular transport systems involved in the renal elimination of metformin could increase systemic exposure to metformin.

CONTRAINDICATIONS of Vandetanib (Caprelsa)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Congenital long QTc syndrome

- Patients with a QTc interval over 480 msec

- Concomitant use of vandetanib with the following medicinal products known to also prolong the QTc interval and / or induce Torsades de pointes: Arsenic, cisapride, erythromycin intravenous (IV), toremifene, mizolastine, moxifloxacine, Class IA and III antiarrhythmics

- Breast-feeding

https://www.ema.europa.eu/en/documents/product-information/caprelsa-epar-product-information_en.pdf 25/06/2025

Vardenafil (Levitra)

Ability to drive, vardenafil [2] ---> SmPC of [2] of EMA

As dizziness and abnormal vision have been reported in clinical trials with vardenafil, patients should be aware of how they react to Levitra, before driving or operating machines.

ACE inhibitors, vardenafil [2] ---> SmPC of [2] of EMA

Population pharmacokinetic analysis showed no effect on vardenafil pharmacokinetics of both medicinal products concomitant administered

Acetylsalicylic acid, vardenafil [2] ---> SmPC of [2] of EMA

Vardenafil (10 mg) did not potentiate the increase in bleeding time caused by acetylsalicylic acid (2 x 81 mg).

Alcohol, vardenafil [2] ---> SmPC of [2] of EMA

When vardenafil and alcohol were taken together, vardenafil did not potentiate the effects of alcohol on blood pressure and heart rate and the pharmacokinetics of vardenafil were not altered.

Alfa1-adrenergic receptor blockers, vardenafil [2] ---> SmPC of [2] of EMA

Vardenafil may be administered at any time with tamsulosin or alfuzosin. With other alpha-blockers a time separation of dosing should be considered when vardenafil is prescribed concomitantly (see section 4.4).

Alfuzosin, vardenafil [2] ---> SmPC of [2] of EMA

When vardenafil (film-coated tablets) was given at doses of 5 or 10 mg on a background of stable therapy with alfuzosin, compared to placebo, there was no symptomatic reduction in blood pressure.

Alpha-blockers, vardenafil [2] ---> SmPC of [2] of EMA

The concomitant use of alpha-blockers and vardenafil may lead to symptomatic hypotension in some patients because both are vasodilators. Concomitant treatment with vardenafil should only be initiated if the patient has been stabilised

Amiodarone, vardenafil [2] ---> SmPC of [2] of EMA

Medicinal products that may prolong QTc interval, including vardenafil, are best avoided in patients with relevant risk factors, for example concomitant administration of antiarrhythmic medicinal products in Class III

Amyl nitrite, vardenafil [2] ---> SmPC of [2] of EMA

However, there is no information on the possible potentiation of the hypotensive effects of nitrates by vardenafil in patients, and concomitant use is therefore contraindicated (see section 4.3).

Antacids, vardenafil [2] ---> SmPC of [2] of EMA

The pharmacokinetics of vardenafil (20 mg) was not affected by single doses of antacid (magnesium hydroxide/aluminium hydroxide).

Antiaggregatory effect, vardenafil [2] ---> SmPC of [2] of EMA

In vitro studies with human platelets indicate that vardenafil has no antiaggregatory effect on its own, but at high (super-therapeutic) concentrations vardenafil potentiates the antiaggregatory effect of the nitric oxide donor sodium nitroprusside.

Atazanavir [1], vardenafil ---> SmPC of [1] of EMA

Vardenafil is metabolised by CYP3A4. Co-administration with Atazanavir may result in increased concentrations of the PDE5 inhibitor and an increase in PDE5-associated adverse events, including hypotension, visual changes, and priapism.

Atazanavir/cobicistat [1], vardenafil ---> SmPC of [1] of EMA

Vardenafil is metabolised by CYP3A4. Co-administration with EVOTAZ may result in increased concentrations of the PDE5 inhibitor. The mechanism of this interaction is CYP3A4 inhibition by atazanavir and cobicistat.

Betablockers, vardenafil [2] ---> SmPC of [2] of EMA

Population pharmacokinetic analysis showed no effect on vardenafil pharmacokinetics of both medicinal products concomitant administered

Breast-feeding, vardenafil [2] ---> SmPC of [2] of EMA

Levitra is not indicated for use by women.

Bunazosin, vardenafil

The co-administration may cause hypotension or syncopes

Cardiovascular status, vardenafil [2] ---> SmPC of [2] of EMA

Prior to initiating any treatment for erectile dysfunction, physicians should consider the cardiovascular status of their patients, since there is a degree of cardiac risk associated with sexual activity (see section 4.3).

Cimetidine, vardenafil [2] ---> SmPC of [2] of EMA

Cimetidine (400 mg twice daily), a non-specific cytochrome P450 inhibitor, had no effect on vardenafil AUC and Cmax when co-administered with vardenafil (20 mg) to healthy volunteers.

Clarithromycin, vardenafil [2] ---> SmPC of [2] of EMA

Although a specific interaction study has not been conducted, the co-administration of clarithromycin can be expected to result in similar effects on vardenafil AUC and Cmax

Class IA antiarrhythmic agents, vardenafil [2] ---> SmPC of [2] of EMA

Class III antiarrhythmic agents, vardenafil [2] ---> SmPC of [2] of EMA

Cobicistat [1], vardenafil ---> SmPC of [1] of EMA

Co-administration with cobicistat may result in increased vardenafil plasma concentrations, which may result in PDE-5 inhibitor-associated adverse reactions.

CYP3A4 inhibitors, vardenafil [2] ---> SmPC of [2] of EMA

Vardenafil is metabolised predominantly by hepatic enzymes via cytochrome P450 (CYP) isoform 3A4, with some contribution from CYP3A5 and CYP2C isoforms. Therefore, inhibitors of these isoenzymes may reduce vardenafil clearance.

Darunavir/cobicistat [1], vardenafil ---> SmPC of [1] of EMA

Based on theoretical considerations darunavir/cobicistat (CYP3A inhibition) is expected to increase the PDE-5 inhibitor plasma concentrations.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], vardenafil ---> SmPC of [1] of EMA

Concomitant use of PDE-5 inhibitors for the treatment of erectile dysfunction with Symtuza should be done with caution.

Darunavir/ritonavir, vardenafil ---> SmPC of [darunavir] of EMA

The co-administration may increase the plasma levels of vardenafil

Digoxin, vardenafil [2] ---> SmPC of [2] of EMA

The pharmacokinetics of vardenafil (20 mg) was not affected by co-administration with digoxine

Dipyridamole, vardenafil [2] ---> SmPC of [2] of EMA

There are no data on the interaction of vardenafil and non-specific phosphodiesterase inhibitors such as theophylline or dipyridamole.

Diuretics, vardenafil [2] ---> SmPC of [2] of EMA

Population pharmacokinetic analysis showed no effect on vardenafil pharmacokinetics of both medicinal products concomitant administered

Dolutegravir/rilpivirine [1], vardenafil ---> SmPC of [1] of EMA

No dose adjustment is required.

Doxazosin [1], vardenafil ---> SmPC of [1] of eMC

Concomitant administration of doxazosin with a PDE-5 inhibitor may lead to symptomatic hypotension in some patients

Duvelisib [1], vardenafil ---> SmPC of [1] of EMA

Dose reduction of CYP3A4 substrate should be considered when co-administered with duvelisib, especially for medicinal products with narrow therapeutic index.

Elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil [1], vardenafil ---> SmPC of [1] of EMA

Cobicistat, strong CYP3A4 inhibitor, may increase the plasma levels of vardenafil

Emtricitabine/rilpivirine/tenofovir alafenamide [1], vardenafil ---> SmPC of [1] of EMA

No dose adjustment is required.

Emtricitabine/rilpivirine/tenofovir disoproxil [1], vardenafil ---> SmPC of [1] of EMA

No dosage adjustment necessary.

Erythromycin, vardenafil [2] ---> SmPC of [2] of EMA

Co-administration of erythromycin (500 mg three times a day), a CYP3A4 inhibitor, with vardenafil (5 mg) resulted in a 4-fold increase in vardenafil AUC and a 3-fold increase in Cmax.

Etravirine [1], vardenafil ---> SmPC of [1] of EMA

Concomitant use of PDE-5 inhibitors with etravirine may require dose adjustment of the PDE-5 inhibitor to attain the desired clinical effect.

Fertility, vardenafil [2] ---> SmPC of [2] of EMA

There are no fertility data available.

Fosamprenavir/ritonavir, vardenafil ---> SmPC of [fosamprenavir] of EMA

Fosamprenavir, CYP3A4 inhibitor, may increase the vardenafil plasma levels and cause hypotension, visual changes and priapism. The combination is not recommended

Glibenclamide, vardenafil [2] ---> SmPC of [2] of EMA

The pharmacokinetics of vardenafil (20 mg) was not affected by co-administration with glibenclamide

Glycerol trinitrate, vardenafil [2] ---> SmPC of [2] of EMA

However, there is no information on the possible potentiation of the hypotensive effects of nitrates by vardenafil in patients, and concomitant use is therefore contraindicated (see section 4.3).

Grapefruit juice, vardenafil [2] ---> SmPC of [2] of EMA

Concomitant intake of grapefruit or grapefruit juice is expected to increase the plasma concentrations of vardenafil. The combination should be avoided (see section 4.5).

Grapefruit, vardenafil [2] ---> SmPC of [2] of EMA

Concomitant intake of grapefruit or grapefruit juice is expected to increase the plasma concentrations of vardenafil. The combination should be avoided (see section 4.5).

Hypokalemia, vardenafil [2] ---> SmPC of [2] of EMA

Medicinal products that may prolong QTc interval, including vardenafil, are best avoided in patients with relevant risk factors, for example, hypokalaemia

Indinavir, vardenafil [2] ---> SmPC of [2] of EMA

Co-administration of the HIV protease inhibitor indinavir (800 mg three times a day), a potent CYP3A4 inhibitor, with vardenafil (10 mg film-coated tablets) resulted in a 16-fold increase in vardenafil AUC and a 7-fold increase in vardenafil Cmax.

Indinavir/ritonavir, vardenafil ---> SmPC of [indinavir] of EMA

Vardenafil dose should not exceed a maximum of 2.5 mg in a 72-hour period when given with a boosted protease inhibitor.

Ischaemic optic neuropathy, PDE5 inhibitors ---> SmPC of [vardenafil] of EMA

Visual defects, including Central Serous Chorioretinopathy (CSCR), and cases of non-arteritic ischemic optic neuropathy (NAION) have been reported in connection with the intake of Levitra and other PDE5 inhibitors.

Ischaemic optic neuropathy, vardenafil [2] ---> SmPC of [2] of EMA

Isosorbide dinitrate [1], vardenafil ---> SmPC of [1] of eMC

The hypotensive effect of nitrates is potentiated by concurrent administration of phosphodiesterase inhibitors

Isosorbide mononitrate [1], vardenafil ---> SmPC of [1] of eMC

Phosphodiesterase type-5 inhibitors have been shown to potentiate the hypotensive effects of nitrates, and its co-administration with nitrates or nitric oxide donors is therefore contra-indicated.

Itraconazol, vardenafil [2] ---> SmPC of [2] of EMA

The concomitant use of other potent CYP3A4 inhibitors (such as itraconazole) can be expected to produce vardenafil plasma levels comparable to those produced by ketoconazole.

Ketoconazole [1], vardenafil ---> SmPC of [1] of EMA

The coadministration of ketoconazole with vardenafil is contraindicated in men older than 75-years due to increased risk of adverse reactions;

Ketoconazole, vardenafil [2] ---> SmPC of [2] of EMA

Co-administration of ketoconazole (200 mg), a potent CYP3A4 inhibitor, with vardenafil (5 mg) resulted in a 10-fold increase in vardenafil AUC and a 4-fold increase in vardenafil Cmax (see section 4.4).

Lefamulin [1], vardenafil ---> SmPC of [1] of EMA

Lefamulin is a moderate CYP3A inhibitor but has no induction potential. Co-administration of oral lefamulin with agents metabolised by CYP3A may result in increased plasma concentrations of these medicinal products.

Lenacapavir [1], vardenafil ---> SmPC of [1] of EMA

Use of PDE-5 inhibitors for erectile dysfunction: Vardenafil: No more than 5 mg in a 24-hour period.

Lopinavir/ritonavir [1], vardenafil ---> SmPC of [1] of EMA

Due to CYP3A inhibition by lopinavir/ritonavir. The use of vardenafil with Kaletra is contraindicated

Men, vardenafil [2] ---> SmPC of [2] of EMA

In men older than 75 years the concomitant use of vardenafil with itraconazole or ketoconazole is contraindicated (see section 4.3).

Metformin, vardenafil [2] ---> SmPC of [2] of EMA

Population pharmacokinetic analysis showed no effect on vardenafil pharmacokinetics of both medicinal products concomitant administered

Miconazole, vardenafil

Oral miconazole is contraindicated with medicinal products that are metabolised by CYP3A4 and may prolong also the QT interval

Moderate CYP3A4 inhibitors, vardenafil [2] ---> SmPC of [2] of EMA

Vardenafil dose adjustment might be necessary if moderate CYP3A4 inhibitors such as erythromycin and clarithromycin, are given concomitantly (see sections 4.5 and 4.2).

Molsidomine, vardenafil

The co-administration is contraindicated due to the risk of pronounced potentiation of hypotensive effects that can cause syncopes and myocardial infarctation

Nelfinavir [1], vardenafil ---> SmPC of [1] of EMA

Concomitant use of vardenafil and nelfinavir may increase plasma levels of vardenafil. Use with increased monitoring for adverse events associated with increased exposure to vardenafil.

Nicorandil, vardenafil [2] ---> SmPC of [2] of EMA

Nicorandil is a hybrid of potassium channel opener and nitrate. Due to the nitrate component it has the potential to have serious interaction with vardenafil.

Nifedipine, vardenafil [2] ---> SmPC of [2] of EMA

In a specific study, where vardenafil (20 mg) was co-administered with slow release nifedipine (30 mg or 60 mg) in hypertensive patients, there was an additional reduction on blood pressure

Nirmatrelvir/ritonavir [1], vardenafil ---> SmPC of [1] of EMA

Concomitant use of avanafil, sildenafil, tadalafil and vardenafil with Paxlovid is contraindicated (see section 4.3).

Nitric oxide donors, vardenafil [2] ---> SmPC of [2] of EMA

However, there is no information on the possible potentiation of the hypotensive effects of nitrates by vardenafil in patients, and concomitant use is therefore contraindicated (see section 4.3).

Nitroglycerine, vardenafil [2] ---> SmPC of [2] of EMA

However, there is no information on the possible potentiation of the hypotensive effects of nitrates by vardenafil in patients, and concomitant use is therefore contraindicated (see section 4.3).

Organic nitrates, vardenafil [2] ---> SmPC of [2] of EMA

However, there is no information on the possible potentiation of the hypotensive effects of nitrates by vardenafil in patients, and concomitant use is therefore contraindicated (see section 4.3).

PDE5 inhibitors, riociguat ---> SmPC of [vardenafil] of EMA

Preclinical studies showed additive systemic blood pressure lowering effect when PDE5 inhibitors were combined with riociguat. Concomitant use of riociguat with PDE5 inhibitors, including vardenafil, is contraindicated

Pregnancy, vardenafil [2] ---> SmPC of [2] of EMA

Levitra is not indicated for use by women. There are no studies of vardenafil in pregnant women.

Procainamide, vardenafil [2] ---> SmPC of [2] of EMA

Protease inhibitors, vardenafil [2] ---> SmPC of [2] of EMA

Concomitant use of vardenafil with HIV protease inhibitors is contraindicated, as they are very potent inhibitors of CYP3A4

QT interval prolonging drugs, vardenafil [2] ---> SmPC of [2] of EMA

Medicinal products that may prolong QTc interval, including vardenafil, are best avoided in patients with relevant risk factors

Quinidine, vardenafil [2] ---> SmPC of [2] of EMA

Ranitidine, vardenafil [2] ---> SmPC of [2] of EMA

The pharmacokinetics of vardenafil (20 mg) was not affected by co-administration with the H2-antagonist ranitidine

Rilpivirine [1], vardenafil ---> SmPC of [1] of EMA

No dose adjustment is required.

Riociguat, vardenafil [2] ---> SmPC of [2] of EMA

Ritonavir [1], vardenafil ---> SmPC of [1] of EMA

Increased plasma concentrations of vardenafil. Concomitant use of vardenafil with ritonavir is contraindicated

Ritonavir, vardenafil [2] ---> SmPC of [2] of EMA

Co-administration of vardenafil with ritonavir (600 mg twice daily) resulted in a 13-fold increase in vardenafil Cmax. Ritonavir significantly prolonged the half-life of vardenafil to 25.7 hours.

Saquinavir, vardenafil [2] ---> SmPC of [2] of EMA

Concomitant use of vardenafil with HIV protease inhibitors is contraindicated, as they are very potent inhibitors of CYP3A4

Saquinavir/ritonavir, vardenafil ---> SmPC of [saquinavir] of EMA

Saquinavir may increase the plasma concentrations of vardenafil. Contraindicated due to the potential for life threatening cardiac arrhythmia

Selpercatinib [1], vardenafil ---> SmPC of [1] of EMA

Selpercatinib increased Cmax and AUC of midazolam (a CYP3A4 substrate) by approximately 39% and 54%, respectively. Therefore, concomitant use with sensitive CYP3A4 substrates should be avoided.

Simeprevir [1], vardenafil ---> SmPC of [1] of EMA

The intestinal CYP3A4 enzyme inhibition may increase the concentrations of PDE-5 inhibitors.

Sotalol, vardenafil [2] ---> SmPC of [2] of EMA

Strong CYP3A4 inhibitors, vardenafil [2] ---> SmPC of [2] of EMA

Concomitant use of vardenafil with potent CYP3A4 inhibitors such as itraconazole and ketoconazole (oral form) should be avoided as very high plasma concentrations of vardenafil are reached if the medicinal products are combined

Sulfonylureas, vardenafil [2] ---> SmPC of [2] of EMA

Population pharmacokinetic analysis showed no effect on vardenafil pharmacokinetics of both medicinal products concomitant administered

Tamsulosin, vardenafil [2] ---> SmPC of [2] of EMA

there was no symptomatic reduction in blood pressure, although 3/21 tamsulosin treated subjects exhibited transient standing systolic blood pressures of less than 85 mmHg.

Tecovirimat, vardenafil [2] ---> SmPC of [2] of EMA

A risk for decreases in PDE-5 inhibitor plasma concentrations cannot be excluded (CYP3A4 substrate). The combination of tecovirimat and PDE-5 inhibitors should be used with caution.

Telaprevir [1], vardenafil ---> SmPC of [1] of EMA

Increased plasma levels of vardenafil. Association not recommended in the treatment of erectile dysfunction

Terazosine, vardenafil [2] ---> SmPC of [2] of EMA

One of 21 patients experienced symptomatic postural hypotension. Hypotension was not observed when vardenafil 5 mg and terazosin administration was separated by 6 hours.

Theophylline, vardenafil [2] ---> SmPC of [2] of EMA

There are no data on the interaction of vardenafil and non-specific phosphodiesterase inhibitors such as theophylline or dipyridamole.

Tipranavir/ritonavir, vardenafil ---> SmPC of [tipranavir] of EMA

Tipranavir/ritonavir, CYP3A4 inhibitors, may increase vardenafil plasma levels. There is increased potential for PDE5 inhibitor-associated adverse events (which include visual disturbances, hypotension, prolonged erection, and syncope).

Toxic epidermal necrolysis, vardenafil [2] ---> SmPC of [2] of EMA

Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN), which can be life-threatening or fatal, have been reported in association with vardenafil treatment (see section 4.8).

Tucatinib [1], vardenafil ---> SmPC of [1] of EMA

Co-administration of tucatinib with sensitive CYP3A substrates may increase their systemic exposures which may increase the toxicity associated with a CYP3A substrate.

Vardenafil [1], warfarin ---> SmPC of [1] of EMA

No significant interactions were shown when warfarin (25 mg), which is metabolised by CYP2C9, or digoxin (0.375 mg) was co-administered with vardenafil (20 mg film-coated tablets).

Vardenafil [1], weak CYP3A4 inhibitors ---> SmPC of [1] of EMA

Population pharmacokinetic analysis showed no effect on vardenafil pharmacokinetics of both medicinal products concomitant administered

CONTRAINDICATIONS of Vardenafil (Levitra)

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

The co-administration of vardenafil with nitrates or nitric oxide donors (such as amyl nitrite) in any form is contraindicated (see sections 4.5 and 5.1).

Levitra is contraindicated in patients who have loss of vision in one eye because of non-arteritic anterior ischemic optic neuropathy (NAION), regardless of whether this episode was in connection or not with previous phosphodiesterase 5 (PDE5) inhibitor exposure (see section 4.4).

Medicinal products for the treatment of erectile dysfunction should generally not be used in men for whom sexual activity is inadvisable (e.g. patients with severe cardiovascular disorders such as unstable angina or severe cardiac failure [New York Heart Association III or IV]).

The safety of vardenafil has not been studied in the following sub-groups of patients and its use is therefore contraindicated until further information is available:

- severe hepatic impairment (Child-Pugh C),

- end stage renal disease requiring dialysis,

- hypotension (blood pressure <90/50 mmHg),

- recent history of stroke or myocardial infarction (within the last 6 months),

- unstable angina and known hereditary retinal degenerative disorders such as retinitis pigmentosa.

Concomitant use of vardenafil with the potent CYP3A4 inhibitors ketoconazole and itraconazole (oral form) is contraindicated in men older than 75 years.

Concomitant use of vardenafil with HIV protease inhibitors such as ritonavir and indinavir is contraindicated, as they are very potent inhibitors of CYP3A4 (see section 4.5).

The co-administration of PDE5 inhibitors, including vardenafil, with guanylate cyclase stimulators, such as riociguat, is contraindicated as it may potentially lead to symptomatic hypotension

https://www.ema.europa.eu/en/documents/product-information/levitra-epar-product-information_en.pdf 20/01/2025

Other trade names: Vivanza (withdrawn),

Varenicline (Champix)

Ability to drive, varenicline [2] ---> SmPC of [2] of EMA

CHAMPIX may cause dizziness, somnolence and transient loss of consciousness, and therefore may influence the ability to drive and use machines.

Alcohol, varenicline [2] ---> SmPC of [2] of EMA

There is limited clinical data on any potential interaction between alcohol and varenicline. There have been post marketing reports of increased intoxicating effects of alcohol in patients treated with varenicline.

Breast-feeding, varenicline [2] ---> SmPC of [2] of EMA

A decision on whether to continue/discontinue breast-feeding or to continue/discontinue therapy with CHAMPIX should be made taking into account the benefit of breast-feeding to the child and the benefit of CHAMPIX therapy to the woman.

Bupropion, varenicline [2] ---> SmPC of [2] of EMA

Varenicline did not alter the steady-state pharmacokinetics of bupropion.

Cimetidine, varenicline [2] ---> SmPC of [2] of EMA

Co-administration of cimetidine with varenicline increased the systemic exposure of varenicline due to a reduction in varenicline renal clearance. In patients with severe renal impairment, the concomitant use should be avoided.

Cytochrome P450, varenicline [2] ---> SmPC of [2] of EMA

Since metabolism of varenicline represents less than 10% of its clearance, active substances known to affect the cytochrome P450 system are unlikely to alter the pharmacokinetics of varenicline

Digoxin, varenicline [2] ---> SmPC of [2] of EMA

Varenicline did not alter the steady-state pharmacokinetics of digoxin.

Drugs primarily metabolised by CYP1A2, varenicline [2] ---> SmPC of [2] of EMA

As smoking induces CYP1A2, smoking cessation may result in an increase of plasma levels of CYP1A2 substrates.

Fertility, varenicline [2] ---> SmPC of [2] of EMA

There are no clinical data on the effects of varenicline on fertility. Non-clinical data revealed no hazard for humans based on standard male and female fertility studies in the rat (see section 5.3).

Insulin, varenicline [2] ---> SmPC of [2] of EMA

Physiological changes resulting from smoking cessation, with or without treatment with varenicline, may alter the pharmacokinetics or pharmacodynamics of some medicinal products, for which dosage adjustment may be necessary

Lamotrigine [1], varenicline ---> SmPC of [1] of eMC

Co-administration of lamotrigine (OCT2 inhibitor) with renally excreted medicinal products which are substrates of OCT2 may result in increased plasma levels of these drugs.

Metformin, varenicline [2] ---> SmPC of [2] of EMA

Varenicline did not affect the pharmacokinetics of metformin. Metformin had no effect on varenicline pharmacokinetics.

Nicotine replacement therapy, varenicline [2] ---> SmPC of [2] of EMA

When varenicline and transdermal NRT were co-administered to smokers for 12 days, there was a statistically significant decrease in average systolic blood pressure (mean 2.6 mmHg) measured on the final day of the study.

OCT2 inhibitors, varenicline [2] ---> SmPC of [2] of EMA

In vitro studies demonstrate that varenicline does not inhibit human renal transport proteins at therapeutic concentrations. Therefore, active substances that are cleared by renal secretion are unlikely to be affected by varenicline.

Pregnancy, varenicline [2] ---> SmPC of [2] of EMA

Animal studies have shown reproductive toxicity (see section 5.3). As a precautionary measure, it is preferable to avoid the use of varenicline during pregnancy (see section 5.1).

Ranolazine [1], varenicline ---> SmPC of [1] of EMA

Plasma exposure of metformin (1000 mg twice daily) increased 1.4- and 1.8-fold in subjects with type 2 diabetes mellitus when coadministered with RANEXA 500 mg and 1000 mg twice daily respectively.

Theophylline, varenicline [2] ---> SmPC of [2] of EMA

Varenicline [1], warfarin ---> SmPC of [1] of EMA

Varenicline did not alter the pharmacokinetics of warfarin. Smoking cessation itself may result in changes to warfarin pharmacokinetics

CONTRAINDICATIONS of Varenicline (Champix)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/champix-epar-product-information_en.pdf 11/09/2025

Vecuronium

Ability to drive, vecuronium [2] ---> SmPC of [2] of eMC

Since vecuronium bromide is used as an adjunct to general anaesthesia, the usual precautionary measures after a general anaesthesia should be taken for ambulatory patients.

Acylamino-penicillins, vecuronium [2] ---> SmPC of [2] of eMC

Recurarisation has been reported after post-operative administration of acylamino-penicillins

Aminoglycoside antibiotics, vecuronium [2] ---> SmPC of [2] of eMC

Recurarisation has been reported after post-operative administration of aminoglycoside antibiotics

Breast-feeding, vecuronium [2] ---> SmPC of [2] of eMC

A decision on whether to continue/discontinue breast-feeding or to continue/discontinue therapy with vecuronium bromide should be made

Carbamazepine, vecuronium [2] ---> SmPC of [2] of eMC

The prior chronic administration of carbamazepine decreases vecuronium effects

Corticosteroids, vecuronium [2] ---> SmPC of [2] of eMC

Long-term concomitant use of corticosteroids and vecuronium in the ICU may result in prolonged duration of neuromuscular block or myopathy

Halogenated anaesthetics, vecuronium [2] ---> SmPC of [2] of eMC

Halogenated volatile anaesthetics potentiate the neuromuscular block of vecuronium. The effect only becomes apparent with maintenance dosing

Lidocaine, vecuronium [2] ---> SmPC of [2] of eMC

Vecuronium combined with lidocaine may result in a quicker onset of action of lidocaine.

Lincosamides, vecuronium [2] ---> SmPC of [2] of eMC

Recurarisation has been reported after post-operative administration of lincosamide

Magnesium, vecuronium [2] ---> SmPC of [2] of eMC

Recurarisation has been reported after post-operative administration of magnesium salts

Mercaptopurine, vecuronium

Decreased effect of the muscle relaxant

Metronidazole, vecuronium

Metronidazole may increase the vecuronium effects

Muscle relaxants (non-depolarizing), vecuronium [2] ---> SmPC of [2] of eMC

Administration of other non-depolarising neuromuscular blocking agents in combination with vecuronium may produce attenuation or potentiation of the neuromuscular

Nitrendipine, vecuronium

The duration and intensity of action of muscle relaxants may be enhanced.

Ornidazole, vecuronium

Ornidazole prolongs the muscle relaxant effect of vecuronium

Phenytoin, vecuronium [2] ---> SmPC of [2] of eMC

The prior chronic administration of phenytoin decreases vecuronium effects

Piperacillin, vecuronium ---> SmPC of [piperacillin/tazobactam] of eMC

Piperacillin when used concomitantly with vecuronium has been implicated in the prolongation of the neuromuscular blockade of vecuronium.

Piperacillin/tazobactam [1], vecuronium ---> SmPC of [1] of eMC

Piperacillin when used concomitantly with vecuronium has been implicated in the prolongation of the neuromuscular blockade of vecuronium.

Piritramide, vecuronium

Piritramide may enhance the effect of vecuronium

Polypeptide antibiotics, vecuronium [2] ---> SmPC of [2] of eMC

Recurarisation has been reported after post-operative administration of polypeptide antibiotics

Pregnancy, vecuronium [2] ---> SmPC of [2] of eMC

Vecuronium bromide should be given to a pregnant woman only when the attending physician decides that the benefits outweigh the risks.

Primidone [1], vecuronium ---> SmPC of [1] of eMC

Primidone therapy may lead to altered pharmacokinetics in concomitantly administered drugs, whose metabolism may be increased and lead to lowered plasma levels and/or a shorter half-life.

Pyridostigmine [1], vecuronium ---> SmPC of [1] of eMC

Pyridostigmine antagonises the effect of non-depolarising muscle relaxants (e.g. pancuronium and vecuronium).

Quinidine, vecuronium [2] ---> SmPC of [2] of eMC

Recurarisation has been reported after post-operative administration of quinidine

Sevoflurane [1], vecuronium ---> SmPC of [1] of eMC

When used to supplement alfentanil-N2O anaesthesia, sevoflurane potentiates neuromuscular block induced with vecuronium.

Succinylcholine, vecuronium [2] ---> SmPC of [2] of eMC

Suxamethonium given after the administration of vecuronium may produce potentiation or attenuation of the neuromuscular blocking effect of vecuronium.

Sufentanil, vecuronium

The co-administration may cause bradycardia

Suxamethonium, vecuronium [2] ---> SmPC of [2] of eMC

Suxamethonium given after the administration of vecuronium may produce potentiation or attenuation of the neuromuscular blocking effect of vecuronium.

CONTRAINDICATIONS of Vecuronium

- Hypersensitivity to vecuronium or the bromide ion or to any of the excipients

http://www.medicines.org.uk/emc/

Vedolizumab (Entyvio)

Ability to drive, vedolizumab [2] ---> SmPC of [2] of EMA

Vedolizumab has minor influence on the ability to drive and use machines, as dizziness has been reported in a small number of patients.

Biologic immunosuppressant, vedolizumab [2] ---> SmPC of [2] of EMA

No clinical trial data for concomitant use of vedolizumab with biologic immunosuppressants are available. Therefore, the use of Entyvio in such patients is not recommended.

Breast-feeding, vedolizumab [2] ---> SmPC of [2] of EMA

The use of vedolizumab in lactating women should take into account the benefit of therapy to the mother and potential risks to the infant.

Corticosteroids, vedolizumab [2] ---> SmPC of [2] of EMA

Vedolizumab administered in patients without concomitant corticosteroid treatment may be less effective for induction of remission in Crohn's disease than in those patients already receiving concomitant corticosteroids

Fertility, vedolizumab [2] ---> SmPC of [2] of EMA

There are no data on the effects of vedolizumab on human fertility. Effects on male and female fertility have not been formally evaluated in animal studies (see section 5.3).

Natalizumab, vedolizumab [2] ---> SmPC of [2] of EMA

No vedolizumab clinical trial data are available for patients previously treated with natalizumab or rituximab. Caution should be exercised when considering the use of Entyvio in these patients.

Pharmacokinetics, vedolizumab [2] ---> SmPC of [2] of EMA

Population pharmacokinetic analyses suggest that co-administration of such agents did not have a clinically meaningful effect on vedolizumab pharmacokinetics.

Pharmacokinetics, vedolizumab [2] ---> SmPC of [2] of EMA

Vedolizumab has been studied in adult ulcerative colitis and Crohn's disease patients with concomitant administration of corticosteroids, immunomodulators (azathioprine, 6-mercaptopurine, and methotrexate), and aminosalicylates.

Pregnancy, vedolizumab [2] ---> SmPC of [2] of EMA

As a precautionary measure, it is preferable to avoid the use of vedolizumab during pregnancy unless the benefits clearly outweigh any potential risk to both the mother and foetus.

Rituximab, vedolizumab [2] ---> SmPC of [2] of EMA

No vedolizumab clinical trial data are available for patients previously treated with natalizumab or rituximab. Caution should be exercised when considering the use of Entyvio in these patients.

Vaccinations with live organism vaccines, vedolizumab [2] ---> SmPC of [2] of EMA

Live vaccines, in particular live oral vaccines, should be used with caution concurrently with vedolizumab (see section 4.4).

Vedolizumab [1], women of childbearing potential ---> SmPC of [1] of EMA

Women of childbearing potential should use adequate contraception to prevent pregnancy and to continue its use for at least 18 weeks after the last treatment.

CONTRAINDICATIONS of Vedolizumab (Entyvio)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Active severe infections such as tuberculosis, sepsis, cytomegalovirus, listeriosis, and opportunistic infections such as Progressive Multifocal Leukoencephalopathy (PML)

https://www.ema.europa.eu/en/documents/product-information/entyvio-epar-product-information_en.pdf. 14/09/2023

Velaglucerase alfa (Vpriv)

Breast-feeding, velaglucerase alfa [2] ---> SmPC of [2] of EMA

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from VPRIV taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Fertility, velaglucerase alfa [2] ---> SmPC of [2] of EMA

Animal studies show no evidence of impaired fertility (see section 5.3).

Pregnancy, velaglucerase alfa [2] ---> SmPC of [2] of EMA

Close monitoring of the pregnancy and clinical manifestations of Gaucher disease is necessary for the individualisation of therapy. Caution should be exercised when prescribing to pregnant women.

Velaglucerase alfa [1], women of childbearing potential ---> SmPC of [1] of EMA

Patients who have Gaucher disease and become pregnant may experience a period of increased disease activity during pregnancy and the puerperium.

Velaglucerase alfa [1], women of childbearing potential ---> SmPC of [1] of EMA

A risk-benefit assessment is required for women with Gaucher disease who are considering pregnancy.

CONTRAINDICATIONS of Velaglucerase alfa (Vpriv)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/vpriv-epar-product-information_en.pdf 08/08/2023

Velmanase alfa (Lamzede)

Breast-feeding, velmanase alfa [2] ---> SmPC of [2] of EMA

The absorption of any ingested milk-containing velmanase alfa in the breastfed child is considered to be minimal and no untoward effects are therefore anticipated. Lamzede can be used during breastfeeding.

Fertility, velmanase alfa [2] ---> SmPC of [2] of EMA

There are no clinical data on the effects of velmanase alfa on fertility. Animal studies do not show evidence of impaired fertility.

Pregnancy, velmanase alfa [2] ---> SmPC of [2] of EMA

As velmanase alfa aims at normalizing alpha-mannosidase in alpha-mannosidosis patients, Lamzede is not recommended to be used during pregnancy unless the clinical condition of the woman requires treatment with velmanase alfa.

CONTRAINDICATIONS of Velmanase alfa (Lamzede)

- Severe allergic reaction to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/lamzede-epar-product-information_en.pdf 22/02/2023

Vemurafenib (Zelboraf)

Ability to drive, vemurafenib [2] ---> SmPC of [2] of EMA

Vemurafenib has minor influence on the ability to drive and use machines. Patients should be made aware of the potential fatigue or eye problems that could be a reason for not driving.

Agomelatine, vemurafenib [2] ---> SmPC of [2] of EMA

Concomitant use of vemurafenib with agents metabolized by CYP1A2 with narrow therapeutic windows (e.g. agomelatine, alosetron, duloxetine, melatonin, ramelteon, tacrine, tizanidine, theophylline) is not recommended.

Aliskiren, vemurafenib [2] ---> SmPC of [2] of EMA

Consider additional drug level monitoring for P-gp substrate medicinal products with a narrow therapeutic index (NTI) (e.g. digoxin, dabigatran etexilate, aliskiren) (see section 4.4).

Alosetron, vemurafenib [2] ---> SmPC of [2] of EMA

Ambrisentan, vemurafenib [2] ---> SmPC of [2] of EMA

Caution should be exercised when dosing vemurafenib concurrently with P-gp substrates and dose reduction of the concomitant medicinal product may be considered, if clinically indicated.

Atazanavir, vemurafenib [2] ---> SmPC of [2] of EMA

Vemurafenib should be used with caution in combination with potent inhibitors of CYP3A4, glucuronidation and/or transport proteins

BCRP inductors, vemurafenib [2] ---> SmPC of [2] of EMA

Vemurafenib is a substrate of the efflux transporters P-gp and BCRP. It cannot be excluded that vemurafenib pharmacokinetics could be affected by medicines that influence P-gp or BCRP

BCRP inhibitors, vemurafenib [2] ---> SmPC of [2] of EMA

Vemurafenib is a substrate of the efflux transporters P-gp and BCRP. It cannot be excluded that vemurafenib pharmacokinetics could be affected by medicines that influence P-gp or BCRP

BCRP substrates, vemurafenib [2] ---> SmPC of [2] of EMA

The effects of vemurafenib on drugs that are substrates of BCRP are unknown. It cannot be excluded that vemurafenib may increase the exposure of medicines transported by BCRP (e.g. methotrexate, mitoxantrone, rosuvastatin).

Breast-feeding, vemurafenib [2] ---> SmPC of [2] of EMA

A decision must be made whether to discontinue breast-feeding or to discontinue vemurafenib therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Bupropion, vemurafenib [2] ---> SmPC of [2] of EMA

It is currently unknown whether vemurafenib at a plasma level of 100 然 observed in patients at steady state (approximately 50 痢/ml) may decrease plasma concentrations of concomitantly administered CYP2B6 substrates, such as bupropion.

Caffeine, vemurafenib [2] ---> SmPC of [2] of EMA

Co-administration of vemurafenib increased the plasma exposure (AUC) of caffeine (CYP1A2 substrate) 2.6-fold.

Carbamazepine, vemurafenib [2] ---> SmPC of [2] of EMA

Concomitant administration of vemurafenib and potent inducers of CYP3A4 may lead to suboptimal exposure to vemurafenib and should be avoided.

Cobimetinib [1], vemurafenib ---> SmPC of [1] of EMA

There is no evidence of any clinically significant drug-drug interaction between cobimetinib and vemurafenib in unresectable or metastatic melanoma patients and therefore no dose adjustments is recommended.

Colchicine, vemurafenib [2] ---> SmPC of [2] of EMA

Caution should be exercised when dosing vemurafenib concurrently with P-gp substrates and dose reduction of the concomitant medicinal product may be considered, if clinically indicated.

Cyclosporine, vemurafenib [2] ---> SmPC of [2] of EMA

In vitro studies have demonstrated that vemurafenib is a substrate of the efflux transporters P-gp and BCRP. It cannot be excluded that vemurafenib pharmacokinetics could be affected by medicines that influence P-gp or BCRP

CYP1A2 substrates with narrow therapeutic index, vemurafenib [2] ---> SmPC of [2] of EMA

CYP3A4 and P-glycoprotein-inhibitors, vemurafenib [2] ---> SmPC of [2] of EMA

Vemurafenib should be used with caution in combination with potent inhibitors of CYP3A4, glucuronidation and/or transport proteins

CYP3A4 substrates with narrow therapeutic index, vemurafenib [2] ---> SmPC of [2] of EMA

Concomitant use of vemurafenib with agents metabolized by CYP3A4 with narrow therapeutic windows is not recommended.

Dabigatran etexilate, vemurafenib [2] ---> SmPC of [2] of EMA

Consider additional drug level monitoring for P-gp substrate medicinal products with a narrow therapeutic index (NTI) (e.g. digoxin, dabigatran etexilate, aliskiren) (see section 4.4).

Digoxin, vemurafenib [2] ---> SmPC of [2] of EMA

Consider additional drug level monitoring for P-gp substrate medicinal products with a narrow therapeutic index (NTI) (e.g. digoxin, dabigatran etexilate, aliskiren) (see section 4.4).

Drugs primarily metabolised by CYP1A2, vemurafenib [2] ---> SmPC of [2] of EMA

Vemurafenib may increase the plasma exposure of substances predominantly metabolised by CYP1A2 and dose adjustments may be considered, if clinically indicated.

Drugs primarily metabolised by CYP3A4, vemurafenib [2] ---> SmPC of [2] of EMA

Vemurafenib may decrease the plasma exposure of substances predominantly metabolised by CYP3A4.

Duloxetine, vemurafenib [2] ---> SmPC of [2] of EMA

Electrolyte imbalance, vemurafenib [2] ---> SmPC of [2] of EMA

Treatment with vemurafenib is not recommended in patients with uncorrectable electrolyte abnormalities (including magnesium), long QT syndrome or who are taking medicinal products known to prolong the QT interval.

Everolimus, vemurafenib [2] ---> SmPC of [2] of EMA

Caution should be exercised when dosing vemurafenib concurrently with P-gp substrates and dose reduction of the concomitant medicinal product may be considered, if clinically indicated.

Fertility, vemurafenib [2] ---> SmPC of [2] of EMA

However, in repeat-dose toxicity studies in rats and dogs, no histopathological findings were noted in reproductive organs in males and females (see section 5.3).

Fexofenadine, vemurafenib [2] ---> SmPC of [2] of EMA

Caution should be exercised when dosing vemurafenib concurrently with P-gp substrates and dose reduction of the concomitant medicinal product may be considered, if clinically indicated.

Gefitinib, vemurafenib [2] ---> SmPC of [2] of EMA

Half-life, vemurafenib [2] ---> SmPC of [2] of EMA

Due to the long half-life of vemurafenib, the full inhibitory effect of vemurafenib on a concomitant medicinal product might not be observed before 8 days of vemurafenib treatment.

Ipilimumab, vemurafenib [2] ---> SmPC of [2] of EMA

In a Phase I trial, asymptomatic grade 3 increases in transaminases (ALT/AST >5 x ULN) and bilirubin (total bilirubin >3x ULN) were reported with concurrent administration of ipilimumab and vemurafenib. Concurrent administration is not recommended.

Itraconazol, vemurafenib [2] ---> SmPC of [2] of EMA

Vemurafenib should be used with caution in combination with potent inhibitors of CYP3A4, glucuronidation and/or transport proteins

Ketoconazole, vemurafenib [2] ---> SmPC of [2] of EMA

Vemurafenib should be used with caution in combination with potent inhibitors of CYP3A4, glucuronidation and/or transport proteins

Lapatinib, vemurafenib [2] ---> SmPC of [2] of EMA

Caution should be exercised when dosing vemurafenib concurrently with P-gp substrates and dose reduction of the concomitant medicinal product may be considered, if clinically indicated.

Maraviroc, vemurafenib [2] ---> SmPC of [2] of EMA

Caution should be exercised when dosing vemurafenib concurrently with P-gp substrates and dose reduction of the concomitant medicinal product may be considered, if clinically indicated.

Melatonin, vemurafenib [2] ---> SmPC of [2] of EMA

Metabolized by CYP2C8 with narrow therapeutic index, vemurafenib [2] ---> SmPC of [2] of EMA

Concomitant administration of CYP2C8 substrates with a narrow therapeutic window should be made with caution since vemurafenib may increase their concentrations.

Methotrexate, vemurafenib [2] ---> SmPC of [2] of EMA

Midazolam, vemurafenib [2] ---> SmPC of [2] of EMA

CYP3A4 induction was observed in a clinical trial when a single dose of midazolam was co-administered after repeat dosing with vemurafenib for 15 days.

Mitoxantrone, vemurafenib [2] ---> SmPC of [2] of EMA

Nefazodone, vemurafenib [2] ---> SmPC of [2] of EMA

Vemurafenib should be used with caution in combination with potent inhibitors of CYP3A4, glucuronidation and/or transport proteins

Nilotinib, vemurafenib [2] ---> SmPC of [2] of EMA

Caution should be exercised when dosing vemurafenib concurrently with P-gp substrates and dose reduction of the concomitant medicinal product may be considered, if clinically indicated.

Oral contraceptives, vemurafenib [2] ---> SmPC of [2] of EMA

The efficacy of contraceptive pills metabolised by CYP3A4 used concomitantly with vemurafenib might be decreased.

P-glycoprotein substrates with small therapeutic index, vemurafenib [2] ---> SmPC of [2] of EMA

Consider additional drug level monitoring for P-gp substrate medicinal products with a narrow therapeutic index (NTI) (e.g. digoxin, dabigatran etexilate, aliskiren) (see section 4.4).

P-glycoprotein substrates, vemurafenib [2] ---> SmPC of [2] of EMA

Caution should be exercised when dosing vemurafenib concurrently with P-gp substrates and dose reduction of the concomitant medicinal product may be considered, if clinically indicated.

Phenytoin, vemurafenib [2] ---> SmPC of [2] of EMA

Concomitant administration of vemurafenib and potent inducers of CYP3A4 may lead to suboptimal exposure to vemurafenib and should be avoided.

Photosensitizing agents, vemurafenib [2] ---> SmPC of [2] of EMA

Mild to severe photosensitivity was reported in patients who received vemurafenib in clinical studies. All patients should be advised to avoid sun exposure while taking vemurafenib.

Posaconazole, vemurafenib [2] ---> SmPC of [2] of EMA

Caution should be exercised when dosing vemurafenib concurrently with P-gp substrates and dose reduction of the concomitant medicinal product may be considered, if clinically indicated.

Pregnancy, vemurafenib [2] ---> SmPC of [2] of EMA

Vemurafenib should not be administered to pregnant women unless the possible benefit to the mother outweighs the possible risk to the foetus

QT interval prolonging drugs, vemurafenib [2] ---> SmPC of [2] of EMA

Radiation, vemurafenib [2] ---> SmPC of [2] of EMA

Potentiation of radiation treatment toxicity has been reported in patients receiving vemurafenib (see sections 4.4 and 4.8).

Ramelteon, vemurafenib [2] ---> SmPC of [2] of EMA

Ranolazine, vemurafenib [2] ---> SmPC of [2] of EMA

Caution should be exercised when dosing vemurafenib concurrently with P-gp substrates and dose reduction of the concomitant medicinal product may be considered, if clinically indicated.

Rifabutin, vemurafenib [2] ---> SmPC of [2] of EMA

Concomitant administration of vemurafenib and potent inducers of CYP3A4 may lead to suboptimal exposure to vemurafenib and should be avoided.

Rifampicin, vemurafenib [2] ---> SmPC of [2] of EMA

Concomitant administration of vemurafenib and potent inducers of CYP3A4 may lead to suboptimal exposure to vemurafenib and should be avoided.

Ritonavir, vemurafenib [2] ---> SmPC of [2] of EMA

Vemurafenib should be used with caution in combination with potent inhibitors of CYP3A4, glucuronidation and/or transport proteins

Rosuvastatin, vemurafenib [2] ---> SmPC of [2] of EMA

Saquinavir, vemurafenib [2] ---> SmPC of [2] of EMA

Vemurafenib should be used with caution in combination with potent inhibitors of CYP3A4, glucuronidation and/or transport proteins

Sirolimus, vemurafenib [2] ---> SmPC of [2] of EMA

Caution should be exercised when dosing vemurafenib concurrently with P-gp substrates and dose reduction of the concomitant medicinal product may be considered, if clinically indicated.

Sitagliptin, vemurafenib [2] ---> SmPC of [2] of EMA

Caution should be exercised when dosing vemurafenib concurrently with P-gp substrates and dose reduction of the concomitant medicinal product may be considered, if clinically indicated.

St. John's wort, vemurafenib [2] ---> SmPC of [2] of EMA

Concomitant administration of vemurafenib and potent inducers of CYP3A4 may lead to suboptimal exposure to vemurafenib and should be avoided.

Strong CYP3A4 inductors, vemurafenib [2] ---> SmPC of [2] of EMA

Concomitant administration of vemurafenib and potent inducers of CYP3A4 may lead to suboptimal exposure to vemurafenib and should be avoided.

Strong CYP3A4 inhibitors, vemurafenib [2] ---> SmPC of [2] of EMA

Vemurafenib should be used with caution in combination with potent inhibitors of CYP3A4, glucuronidation and/or transport proteins

Strong glucuronidation inductors, vemurafenib [2] ---> SmPC of [2] of EMA

Concomitant administration of vemurafenib and potent inducers of glucuronidation may lead to suboptimal exposure to vemurafenib and should be avoided.

Strong glucuronidation inhibitors, vemurafenib [2] ---> SmPC of [2] of EMA

Vemurafenib should be used with caution in combination with potent inhibitors of CYP3A4, glucuronidation and/or transport proteins

Strong P-gp inductors, vemurafenib [2] ---> SmPC of [2] of EMA

Concomitant administration of vemurafenib and potent inducers of P-gp may lead to suboptimal exposure to vemurafenib and should be avoided.

Strong P-gp inhibitors, vemurafenib [2] ---> SmPC of [2] of EMA

Vemurafenib should be used with caution in combination with potent inhibitors of CYP3A4, glucuronidation and/or transport proteins

Sun, vemurafenib [2] ---> SmPC of [2] of EMA

Mild to severe photosensitivity was reported in patients who received vemurafenib in clinical studies. All patients should be advised to avoid sun exposure while taking vemurafenib.

Tacrine, vemurafenib [2] ---> SmPC of [2] of EMA

Talinolol, vemurafenib [2] ---> SmPC of [2] of EMA

Caution should be exercised when dosing vemurafenib concurrently with P-gp substrates and dose reduction of the concomitant medicinal product may be considered, if clinically indicated.

Telithromycin, vemurafenib [2] ---> SmPC of [2] of EMA

Vemurafenib should be used with caution in combination with potent inhibitors of CYP3A4, glucuronidation and/or transport proteins

Theophylline, vemurafenib [2] ---> SmPC of [2] of EMA

Tizanidine, vemurafenib [2] ---> SmPC of [2] of EMA

Topotecan, vemurafenib [2] ---> SmPC of [2] of EMA

Caution should be exercised when dosing vemurafenib concurrently with P-gp substrates and dose reduction of the concomitant medicinal product may be considered, if clinically indicated.

Vemurafenib [1], verapamil ---> SmPC of [1] of EMA

Vemurafenib [1], voriconazole ---> SmPC of [1] of EMA

Vemurafenib should be used with caution in combination with potent inhibitors of CYP3A4, glucuronidation and/or transport proteins

Vemurafenib [1], warfarin ---> SmPC of [1] of EMA

Exercise caution and consider additional INR (international normalized ratio) monitoring when vemurafenib is used concomitantly with warfarin (see section 4.4).

Vemurafenib [1], women of childbearing potential ---> SmPC of [1] of EMA

Women of childbearing potential have to use effective contraception during treatment and for at least 6 months after treatment. Vemurafenib might decrease the efficacy of hormonal contraceptives (see section 4.5).

CONTRAINDICATIONS of Vemurafenib (Zelboraf)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/zelboraf-epar-product-information_en.pdf 27/03/2024

Venetoclax (Venclyxto)

Ability to drive, venetoclax [2] ---> SmPC of [2] of EMA

Fatigue and dizziness have been reported in some patients taking venetoclax and should be considered when assessing a patient's ability to drive or operate machines.

Antacids, venetoclax [2] ---> SmPC of [2] of EMA

Based on population pharmacokinetic analysis, gastric acid reducing agents (e.g., proton pump inhibitors, H2-receptor antagonists, antacids) do not affect venetoclax bioavailability.

Azithromycin, venetoclax [2] ---> SmPC of [2] of EMA

No dose adjustment is needed during short-term use of azithromycin when administered concomitantly with venetoclax.

BCRP and P-gp substrates, venetoclax [2] ---> SmPC of [2] of EMA

Concomitant use of venetoclax with P-gp and BCRP inhibitors at initiation and during the dose-titration phase should be avoided; if a P-gp and BCRP inhibitor must be used, patients should be monitored closely for signs of toxicities

BCRP substrates with narrow therapeutic range, venetoclax [2] ---> SmPC of [2] of EMA

Venetoclax is a P-gp, BCRP and OATP1B1 inhibitor in vitro. Co-administration of narrow therapeutic index P-gp, or BCRP substrates (e.g., digoxin, dabigatran, everolimus, sirolimus) with Venclyxto should be avoided.

BCRP substrates, venetoclax [2] ---> SmPC of [2] of EMA

Bile-acid sequestrants, venetoclax [2] ---> SmPC of [2] of EMA

Co-administration of bile acid sequestrants with venetoclax is not recommended as this may reduce the absorption of venetoclax. If a bile acid sequestrant is to be co-administered, venetoclax should be administered at least 4-6 hours after the sequestran

Bosentan, venetoclax [2] ---> SmPC of [2] of EMA

Concomitant use of venetoclax with strong CYP3A inducers (e.g., carbamazepine, phenytoin, rifampicin) or moderate CYP3A inducers (e.g., bosentan, efavirenz, etravirine, modafinil, nafcillin) should be avoided.

Breast-feeding, venetoclax [2] ---> SmPC of [2] of EMA

Breast-feeding should be discontinued during treatment with Venclyxto.

Carbamazepine, venetoclax [2] ---> SmPC of [2] of EMA

Ciprofloxacin, venetoclax [2] ---> SmPC of [2] of EMA

For patients requiring concomitant use of venetoclax with strong CYP3A inhibitors or moderate CYP3A inhibitors, venetoclax dosing should be administered according to Table 7

Clarithromycin, venetoclax [2] ---> SmPC of [2] of EMA

For patients requiring concomitant use of venetoclax with strong CYP3A inhibitors or moderate CYP3A inhibitors, venetoclax dosing should be administered according to Table 7

Contraceptives, venetoclax [2] ---> SmPC of [2] of EMA

It is currently unknown whether venetoclax may reduce the effectiveness of hormonal contraceptives, and therefore women using hormonal contraceptives should add a barrier method.

Dabigatran etexilate, venetoclax [2] ---> SmPC of [2] of EMA

Digoxin, venetoclax [2] ---> SmPC of [2] of EMA

Diltiazem, venetoclax [2] ---> SmPC of [2] of EMA

For patients requiring concomitant use of venetoclax with strong CYP3A inhibitors or moderate CYP3A inhibitors, venetoclax dosing should be administered according to Table 7

Efavirenz, venetoclax [2] ---> SmPC of [2] of EMA

Erythromycin, venetoclax [2] ---> SmPC of [2] of EMA

For patients requiring concomitant use of venetoclax with strong CYP3A inhibitors or moderate CYP3A inhibitors, venetoclax dosing should be administered according to Table 7

Etravirine, venetoclax [2] ---> SmPC of [2] of EMA

Everolimus, venetoclax [2] ---> SmPC of [2] of EMA

Fertility, venetoclax [2] ---> SmPC of [2] of EMA

Before starting treatment, counselling on sperm storage may be considered in some male patients.

Fluconazole, venetoclax [2] ---> SmPC of [2] of EMA

For patients requiring concomitant use of venetoclax with strong CYP3A inhibitors or moderate CYP3A inhibitors, venetoclax dosing should be administered according to Table 7

Foods, venetoclax [2] ---> SmPC of [2] of EMA

The tablets should be taken with a meal in order to avoid a risk for lack of efficacy. The tablets should not be chewed, crushed, or broken before swallowing.

Grapefruit juice, venetoclax [2] ---> SmPC of [2] of EMA

Grapefruit products, Seville oranges, and starfruit (carambola) should be avoided during treatment with venetoclax as they contain inhibitors of CYP3A.

Grapefruit, venetoclax [2] ---> SmPC of [2] of EMA

Grapefruit products, Seville oranges, and starfruit (carambola) should be avoided during treatment with venetoclax as they contain inhibitors of CYP3A.

H2 antagonists, venetoclax [2] ---> SmPC of [2] of EMA

Based on population pharmacokinetic analysis, gastric acid reducing agents (e.g., proton pump inhibitors, H2-receptor antagonists, antacids) do not affect venetoclax bioavailability.

Itraconazol, venetoclax [2] ---> SmPC of [2] of EMA

For patients requiring concomitant use of venetoclax with strong CYP3A inhibitors or moderate CYP3A inhibitors, venetoclax dosing should be administered according to Table 7

Ketoconazole, venetoclax [2] ---> SmPC of [2] of EMA

For patients requiring concomitant use of venetoclax with strong CYP3A inhibitors or moderate CYP3A inhibitors, venetoclax dosing should be administered according to Table 7

Lopinavir/ritonavir [1], venetoclax ---> SmPC of [1] of EMA

Serum concentrations may be increased due to CYP3A inhibition by lopinavir/ritonavir, resulting in increased risk of tumor lysis syndrome at the dose initiation and during the ramp-up phase

Modafinil, venetoclax [2] ---> SmPC of [2] of EMA

Moderate CYP3A4 inhibitors, venetoclax [2] ---> SmPC of [2] of EMA

For patients requiring concomitant use of venetoclax with strong CYP3A inhibitors or moderate CYP3A inhibitors, venetoclax dosing should be administered according to Table 7

Nafcillin, venetoclax [2] ---> SmPC of [2] of EMA

Nirmatrelvir/ritonavir [1], venetoclax ---> SmPC of [1] of EMA

Serum concentrations may be increased due to CYP3A inhibition by ritonavir, resulting in increased risk of tumour lysis syndrome at the dose initiation and during the ramp-up phase and is therefore contraindicated

OATP1B1 substrates, venetoclax [2] ---> SmPC of [2] of EMA

If a statin (OATP substrate) is used concomitantly with venetoclax, close monitoring of statin-related toxicity is recommended.

P-glycoprotein substrates with small therapeutic index, venetoclax [2] ---> SmPC of [2] of EMA

P-glycoprotein substrates, venetoclax [2] ---> SmPC of [2] of EMA

Phenytoin, venetoclax [2] ---> SmPC of [2] of EMA

Posaconazole, venetoclax [2] ---> SmPC of [2] of EMA

For patients requiring concomitant use of venetoclax with strong CYP3A inhibitors or moderate CYP3A inhibitors, venetoclax dosing should be administered according to Table 7

Pregnancy, venetoclax [2] ---> SmPC of [2] of EMA

Venetoclax is not recommended during pregnancy and in women of childbearing potential not using highly effective contraception.

Proton pump inhibitors, venetoclax [2] ---> SmPC of [2] of EMA

Based on population pharmacokinetic analysis, gastric acid reducing agents (e.g., proton pump inhibitors, H2-receptor antagonists, antacids) do not affect venetoclax bioavailability.

Rifampicin, venetoclax [2] ---> SmPC of [2] of EMA

Ritonavir, venetoclax [2] ---> SmPC of [2] of EMA

For patients requiring concomitant use of venetoclax with strong CYP3A inhibitors or moderate CYP3A inhibitors, venetoclax dosing should be administered according to Table 7

Seville orange, venetoclax [2] ---> SmPC of [2] of EMA

Grapefruit products, Seville oranges, and starfruit (carambola) should be avoided during treatment with venetoclax as they contain inhibitors of CYP3A.

Sirolimus, venetoclax [2] ---> SmPC of [2] of EMA

St. John's wort, venetoclax [2] ---> SmPC of [2] of EMA

Preparations containing St. John's wort are contraindicated during treatment with venetoclax, as efficacy may be reduced

Star fruit, venetoclax [2] ---> SmPC of [2] of EMA

Grapefruit products, Seville oranges, and starfruit (carambola) should be avoided during treatment with venetoclax as they contain inhibitors of CYP3A.

Statins, venetoclax [2] ---> SmPC of [2] of EMA

If a statin (OATP substrate) is used concomitantly with venetoclax, close monitoring of statin-related toxicity is recommended.

Strong CYP3A4 inductors, venetoclax [2] ---> SmPC of [2] of EMA

Strong CYP3A4 inhibitors, venetoclax [2] ---> SmPC of [2] of EMA

For patients requiring concomitant use of venetoclax with strong CYP3A inhibitors or moderate CYP3A inhibitors, venetoclax dosing should be administered according to Table 7

Vaccinations with live organism vaccines, venetoclax [2] ---> SmPC of [2] of EMA

Live vaccines should not be administered during treatment and thereafter until B-cell recovery.

Venetoclax [1], verapamil ---> SmPC of [1] of EMA

For patients requiring concomitant use of venetoclax with strong CYP3A inhibitors or moderate CYP3A inhibitors, venetoclax dosing should be administered according to Table 7

Venetoclax [1], warfarin ---> SmPC of [1] of EMA

Because venetoclax was not dosed to steady state, it is recommended that the international normalized ratio (INR) be monitored closely in patients receiving warfarin.

Venetoclax [1], women of childbearing potential ---> SmPC of [1] of EMA

Women should avoid becoming pregnant while taking Venclyxto and for at least 30 days after ending treatment.

Venetoclax, voriconazole [2] ---> SmPC of [2] of EMA

Voriconazole is likely to significantly increase the plasma concentrations of venetoclax. Concomitant administration of voriconazole is contraindicated at initiation and during venetoclax dose titration phase

CONTRAINDICATIONS of Venetoclax (Venclyxto)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- In patients with CLL, concomitant use of strong CYP3A inhibitors at initiation and during the dose-titration phase (see sections 4.2 and 4.5).

- Concomitant use of preparations containing St. John’s wort

https://www.ema.europa.eu/en/documents/product-information/venclyxto-epar-product-information_en.pdf 14/01/2025

Venlafaxine

Ability to drive, venlafaxine [2] ---> SmPC of [2] of eMC

Any psychoactive medicinal product may impair judgment, thinking, and motor skills.

Abiraterone [1], venlafaxine ---> SmPC of [1] of EMA

Caution is advised when administering abiraterone with medicinal products activated by or metabolised by CYP2D6, particularly with medicinal products that have a narrow therapeutic index.

Acetylsalicylic acid, venlafaxine

Possible prolongation of bleeding time. Caution is recommended

Adrenaline, venlafaxine

The effects of adrenaline may be potentiated by noradrenergic-serotoninergic antidepressants.

Alcohol, venlafaxine [2] ---> SmPC of [2] of eMC

As with all CNS-active substances, patients should be advised to avoid alcohol consumption.

Alfa and beta-adrenergic agonists, venlafaxine

The combination of venlafaxine with the alfa- and beta-adrenergic agonist administered intravenously can cause paroxysmal hypertension with possible heart rhythm disorders

Anticoagulants, venlafaxine

Possible prolongation of bleeding time. Caution is recommended

Aripiprazole [1], venlafaxine ---> SmPC of [1] of EMA

When aripiprazole was administered concomitantly with venlafaxine, there was no clinically important change in concentrations of venlafaxine. Thus, no dosage adjustment is required

Atazanavir, venlafaxine [2] ---> SmPC of [2] of eMC

Concomitant use of CYP3A4 inhibitors and venlafaxine may increase levels of venlafaxine and O-desmethylvenlafaxine. Therefore, caution is advised if a patient's therapy includes a CYP3A4 inhibitor and venlafaxine concomitantly.

Atomoxetine, venlafaxine

Drugs that affect noradrenaline should be used cautiously when co-administered with atomoxetine because of the potential for additive or synergistic pharmacological effects.

Azithromycin, venlafaxine

The concomitant use may increase the risk of cardiac arrhythmia.

Benzodiazepines, venlafaxine [2] ---> SmPC of [2] of eMC

Venlafaxine has no effects on the pharmacokinetics and pharmacodynamics of diazepam and its active metabolite, desmethyldiazepam. It is unknown whether a pharmacokinetic and/or pharmacodynamic interaction with other benzodiazepines exists.

Breast-feeding, venlafaxine [2] ---> SmPC of [2] of eMC

Venlafaxine and its active metabolite, O-desmethylvenlafaxine, are excreted in breast milk. A decision to continue/discontinue breast-feeding or to continue/discontinue therapy with venlafaxine should be made

Cabergoline, venlafaxine

Increased risk of serotonin syndrome.

Chlorpromazine, venlafaxine

Chlorpromazine, strong CYP2D6 inhibitor, may increase the plasma levels of venlafaxine

Cimetidine, venlafaxine

Cimetidine inhibits the first-pass metabolism of venlafaxine

Clarithromycin, venlafaxine [2] ---> SmPC of [2] of eMC

Clozapine, venlafaxine

Increased plasma levels of clozapine

CNS depressants, venlafaxine [2] ---> SmPC of [2] of eMC

Caution is advised when venlafaxine is taken in combination with other CNS-active substances

Diazepam, venlafaxine [2] ---> SmPC of [2] of eMC

Dopamine, venlafaxine

The combination of venlafaxine with the alfa- and beta-adrenergic agonist administered intravenously can cause paroxysmal hypertension with possible heart rhythm disorders

Entacapone [1], venlafaxine ---> SmPC of [1] of EMA

The combination should be done with care, because there is currently not enough experience

Epinephrine, venlafaxine

The effects of adrenaline may be potentiated by noradrenergic-serotoninergic antidepressants.

Haloperidol [1], venlafaxine ---> SmPC of [1] of eMC

Inhibition of the CYP2D6 by another drug may result in increased haloperidol concentrations and an increased risk of adverse events, including QT-prolongation.

IMAOs, venlafaxine

Combination (contraindicated) may cause serious and sometimes fatal reactions. After discontinuing MAOI, wait (depending on IMAO) 5/2 weeks or 1 day before administering SSRI

Imipramine, venlafaxine [2] ---> SmPC of [2] of eMC

Caution should be exercised with co-administration of venlafaxine and imipramine.

Indinavir, venlafaxine [2] ---> SmPC of [2] of eMC

Irreversible MAO-inhibitors, venlafaxine [2] ---> SmPC of [2] of eMC

Combination contraindicated. Venlafaxine should not be administrated within at least 7 days BEFORE initiating nor 14 days AFTER discontinuing a therapy with irreversible MAOI

Irreversible non-selective MAO-inhibitors, venlafaxine [2] ---> SmPC of [2] of eMC

Combination contraindicated. Venlafaxine should not be administrated within at least 7 days BEFORE initiating nor 14 days AFTER discontinuing a therapy with irreversible MAOI

Irreversible selective MAO-A inhibitors, venlafaxine [2] ---> SmPC of [2] of eMC

Combination contraindicated. Venlafaxine should not be administrated within at least 7 days BEFORE initiating nor 14 days AFTER discontinuing a therapy with irreversible MAOI

Irreversible selective MAO-B inhibitors, venlafaxine [2] ---> SmPC of [2] of eMC

Combination contraindicated. Venlafaxine should not be administrated within at least 7 days BEFORE initiating nor 14 days AFTER discontinuing a therapy with irreversible MAOI

Itraconazol, venlafaxine [2] ---> SmPC of [2] of eMC

Ketoconazole, venlafaxine [2] ---> SmPC of [2] of eMC

Linezolid, venlafaxine [2] ---> SmPC of [2] of eMC

The antibiotic linezolid is a weak reversible and non-selective MAOI and should not be given to patients treated with venlafaxine

Lithium, venlafaxine [2] ---> SmPC of [2] of eMC

Serotonin syndrome may occur with the concomitant use of venlafaxine and lithium

Methylthioninium [1], venlafaxine ---> SmPC of [1] of EMA

Methylthioninium should be avoided with medicinal products that enhance serotonergic transmission

Metoprolol, venlafaxine [2] ---> SmPC of [2] of eMC

Concomitant administration of venlafaxine and metoprolol resulted in an increase of plasma concentrations of metoprolol by approximately 30-40% without altering the plasma concentrations of its active metabolite

Miconazole, venlafaxine

Oral miconazole is contraindicated with medicinal products that are metabolised by CYP3A4 and may prolong also the QT interval

Mirtazapine [1], venlafaxine ---> SmPC of [1] of eMC

Co-administration of mirtazapine with other serotonergic active substances may lead to an incidence of serotonin associated effects (serotonin syndrome). Caution should be advised

Moclobemide, venlafaxine [2] ---> SmPC of [2] of eMC

Combination contraindicated. Venlafaxine should not be administrated within at least 7 days BEFORE initiating nor 14 days AFTER discontinuing a therapy with reversible MAOI

Nelfinavir, venlafaxine [2] ---> SmPC of [2] of eMC

Noradrenaline, venlafaxine

The combination of venlafaxine with the alfa- and beta-adrenergic agonist administered intravenously can cause paroxysmal hypertension with possible heart rhythm disorders

NSAID, venlafaxine

Possible prolongation of bleeding time. Caution is recommended

Opicapone [1], venlafaxine ---> SmPC of [1] of EMA

There is limited experience with opicapone when used concomitantly with tricyclic antidepressants and noradrenaline re-uptake inhibitors. Thus, their concomitant use should be considered with appropriate caution.

Pitolisant [1], venlafaxine ---> SmPC of [1] of EMA

Given the 2-fold increase of pitolisant exposure, its coadministration with CYP2D6 inhibitors should be done with caution. A dosage adjustment during the combination could eventually be considered.

Posaconazole, venlafaxine [2] ---> SmPC of [2] of eMC

Pregnancy, venlafaxine [2] ---> SmPC of [2] of eMC

Venlafaxine must only be administered to pregnant women if the expected benefits outweigh any possible risk.

Propafenone [1], venlafaxine ---> SmPC of [1] of eMC

Coadministration of propafenone hydrochloride with drugs metabolised by CYP2D6 might lead to increased levels of these drugs.

Reversible non-selective MAO-inhibitors, venlafaxine

Co-administration is not recommended. Possible severe adverse reactions resembling neuroleptic malignant syndrome

Reversible selective MAO-A inhibitors, venlafaxine [2] ---> SmPC of [2] of eMC

Combination contraindicated. Venlafaxine should not be administrated within at least 7 days BEFORE initiating nor 14 days AFTER discontinuing a therapy with reversible MAOI

Reversible selective MAO-B inhibitors, venlafaxine [2] ---> SmPC of [2] of eMC

Combination contraindicated. Venlafaxine should not be administrated within at least 7 days BEFORE initiating nor 14 days AFTER discontinuing a therapy with reversible MAOI

Risperidone, venlafaxine [2] ---> SmPC of [2] of eMC

Venlafaxine increased the risperidone AUC by 50%, but did not significantly alter the pharmacokinetic profile of the total active moiety (risperidone plus 9-hydroxyrisperidone). The clinical significance of this interaction is unknown.

Ritonavir, venlafaxine [2] ---> SmPC of [2] of eMC

Saquinavir, venlafaxine [2] ---> SmPC of [2] of eMC

Serotonergic medicines, venlafaxine [2] ---> SmPC of [2] of eMC

Serotonin syndrome may occur with venlafaxine treatment, particularly with concomitant use of other agents that may affect the serotonergic neurotransmitter system

Sibutramine, venlafaxine [2] ---> SmPC of [2] of eMC

Serotonin syndrome may occur with venlafaxine treatment, particularly with concomitant use of other agents that may affect the serotonergic neurotransmitter system

SSNRI, venlafaxine [2] ---> SmPC of [2] of eMC

Serotonin syndrome may occur with venlafaxine treatment, particularly with concomitant use of other agents that may affect the serotonergic neurotransmitter system

SSRI, venlafaxine [2] ---> SmPC of [2] of eMC

Serotonin syndrome may occur with venlafaxine treatment, particularly with concomitant use of other agents that may affect the serotonergic neurotransmitter system

St. John's wort, venlafaxine [2] ---> SmPC of [2] of eMC

Serotonin syndrome may occur with venlafaxine treatment, particularly with concomitant use of other agents that may affect the serotonergic neurotransmitter system

Strong CYP3A4 inhibitors, venlafaxine [2] ---> SmPC of [2] of eMC

Telithromycin, venlafaxine [2] ---> SmPC of [2] of eMC

Ticlopidine, venlafaxine

Possible prolongation of bleeding time. Caution is recommended

Tolcapone [1], venlafaxine ---> SmPC of [1] of EMA

Caution should be exercised when potent noradrenaline uptake inhibitors are administered to Parkinson's disease patients being treated with tolcapone and levodopa preparations.

Tramadol, venlafaxine [2] ---> SmPC of [2] of eMC

Serotonin syndrome may occur with venlafaxine treatment, particularly with concomitant use of other agents that may affect the serotonergic neurotransmitter system

Tranylcypromine, venlafaxine

Tranylcypromine should not be used concomitantly with drugs with marked serotonin-reuptake inhibition. Risk of serotonin syndrome with symptoms like hypertension, irritability, hyperthermia with possible fatal outcome

Triptans, venlafaxine [2] ---> SmPC of [2] of eMC

Serotonin syndrome may occur with venlafaxine treatment, particularly with concomitant use of other agents that may affect the serotonergic neurotransmitter system

Tryptophan, venlafaxine [2] ---> SmPC of [2] of eMC

Serotonin syndrome may occur with venlafaxine treatment, particularly with concomitant use of other agents that may affect the serotonergic neurotransmitter system

Venlafaxine, warfarin

Possible prolongation of bleeding time. Caution is recommended

CONTRAINDICATIONS of Venlafaxine

- Hypersensitivity to the active substance or to any of the excipients.

- Concomitant treatment with irreversible monoamine oxidase inhibitors (MAOIs) is contraindicated due to the risk of serotonin syndrome with symptoms such as agitation, tremor and hyperthermia. Venlafaxine must not be initiated for at least 14 days after discontinuation of treatment with an irreversible MAOI.

- Venlafaxine must be discontinued for at least 7 days before starting treatment with an irreversible MAOI

http://www.medicines.org.uk/emc/

Verapamil

Ability to drive, verapamil [2] ---> SmPC of [2] of eMC

Depending on individual susceptibility, the patient's ability to drive a vehicle or operate machinery or work under hazardous conditions may be impaired.

Acebutolol, verapamil

Bradycardic rhythm disorders until AV block (contraindication)

Acetylsalicylic acid, verapamil [2] ---> SmPC of [2] of eMC

Concomitant use of verapamil and acetylsalicylic acid may increase the risk of bleeding.

Afatinib [1], verapamil ---> SmPC of [1] of EMA

Increased exposure to afatinib. It is recommended to administer strong P-gp inhibitors using staggered dosing, preferably 6 hours or 12 hours apart from afatinib

Alcohol, verapamil [2] ---> SmPC of [2] of eMC

Plasma concentration of alcohol may be increased

Aliskiren [1], verapamil ---> SmPC of [1] of EMA

The moderate inhibition of P-glycoprotein may increase aliskiren gastrointestinal absorption and decrease its biliary excretion. Caution is recommended

Aliskiren/amlodipine [1], verapamil ---> SmPC of [1] of EMA

Concomitant use of amlodipine with strong or moderate CYP3A4 inhibitors may give rise to significant increase in amlodipine exposure. Clinical monitoring and dose adjustment may thus be required.

Aliskiren/amlodipine/hydrochlorothiazide [1], verapamil ---> SmPC of [1] of EMA

The moderate inhibition of P-glycoprotein may increase aliskiren gastrointestinal absorption and decrease its biliary excretion. Caution is recommended

Aliskiren/hydrochlorothiazide [1], verapamil ---> SmPC of [1] of EMA

The moderate inhibition of P-glycoprotein may increase aliskiren gastrointestinal absorption and decrease its biliary excretion. Caution is recommended

Almotriptan [1], verapamil ---> SmPC of [1] of eMC

Multiple dosing with the calcium channel blocker verapamil, a substrate of CYP3A4, resulted in a 20% increase in Cmax and AUC of almotriptan. The increase is not considered clinically relevant.

Aminophylline [1], verapamil ---> SmPC of [1] of eMC

Calcium channel blockers may decrease aminophylline clearance resulting in increased plasma theophylline concentrations and the potential for increased toxicity

Amiodarone [1], verapamil ---> SmPC of [1] of eMC

Certain calcium channel inhibitors (diltiazem, verapamil); potentiation of negative chronotropic properties and conduction slowing effects may occur. Combined therapy is not recommended

Amisulpride, verapamil

Concomitant use of amisulpride with drugs inducing bradycardia is not recommended

Amitriptyline [1], verapamil ---> SmPC of [1] of eMC

Verapamil may possibly increase the plasma concentration of amitriptyline.

Amlodipine, verapamil ---> SmPC of [amlodipine/valsartan] of EMA

Concomitant use of amlodipine with strong or moderate CYP3A4 inhibitors may give rise to significant increase in amlodipine exposure. Clinical monitoring and dose adjustment may thus be required.

Amlodipine/valsartan [1], verapamil ---> SmPC of [1] of EMA

Concomitant use of amlodipine with strong or moderate CYP3A4 inhibitors may give rise to significant increase in amlodipine exposure. Clinical monitoring and dose adjustment may thus be required.

Amlodipine/valsartan/hydrochlorothiazide [1], verapamil ---> SmPC of [1] of EMA

Concomitant use of amlodipine with strong or moderate CYP3A4 inhibitors may give rise to significant increase in amlodipine exposure.

Antiarrhythmics, verapamil [2] ---> SmPC of [2] of eMC

The combination of anti-arrhythmic agents with verapamil may lead to additive cardiovascular effects (e.g. AV block, bradycardia, hypotension, heart failure).

Antidiabetics, verapamil

Increased plasma levels of antidiabetic agent

Antihypertensives, verapamil [2] ---> SmPC of [2] of eMC

Potentiation of the hypotensive effect

Apixaban [1], verapamil ---> SmPC of [1] of EMA

Active substances which are not considered strong inhibitors of both CYP3A4 and P-gp are expected to increase apixaban plasma concentration to a lesser extent. No dose adjustment for apixaban is required

Atazanavir [1], verapamil ---> SmPC of [1] of EMA

The co-administration of atazanavir (CYP3A4 inhibitor) may increase the plasma concentrations of verapamil. Caution is warranted

Atazanavir/cobicistat [1], verapamil ---> SmPC of [1] of EMA

Concentrations of the calcium channel blocker may be increased when co-administered with EVOTAZ. The mechanism of interaction is inhibition of CYP3A4 by atazanavir and cobicistat. Caution is warranted.

Atenolol [1], verapamil ---> SmPC of [1] of eMC

Combination should be used with caution in patients with impaired ventricular function, and not at all in patients with conduction abnormalities. May result in severe hypotension, bradycardia and cardiac failure.

Atenolol/chlortalidone [1], verapamil ---> SmPC of [1] of eMC

Combined use of beta-blockers and calcium channel blockers with negative inotropic effects can lead to an exaggeration of these effects. This may result in severe hypotension, bradycardia and cardiac failure.

Atenolol/nifedipine, verapamil ---> SmPC of [atenolol] of eMC

Atenolol/nifedipine must not be used in conjunction with calcium channel blockers with negative inotropic effects since this can lead to an exaggeration of these effects. It may result in severe hypotension, bradycardia and cardiac failure

Atorvastatin [1], verapamil ---> SmPC of [1] of eMC

Moderate CYP3A4 inhibitors may increase plasma concentrations of atorvastatin. Appropriate clinical monitoring of the patient is recommended when concomitantly used of atorvastatin with moderate CYP3A4 inhibitors.

Atropine, verapamil

Possible enhancement of induced tachycardia by atropine, as anticholinergics increase the effect of verapamil on the cardiac rhythm

Avanafil [1], verapamil ---> SmPC of [1] of EMA

Avanafil is predominantly metabolised by CYP3A4. The moderate CYP3A4 inhibitors may increase the exposition of avanafil. The maximum recommended dose of avanafil is 100 mg, not to exceed once every 48 hours

Azole antifungals, verapamil [2] ---> SmPC of [2] of eMC

Clinically significant interactions have been reported with inhibitors of CYP3A4 causing elevation of plasma levels of verapamil hydrochloride, therefore, patients should be monitored for drug interactions.

Betablockers, verapamil [2] ---> SmPC of [2] of eMC

The combination of beta-blockers with verapamil may lead to additive cardiovascular effects (e.g. AV block, bradycardia, hypotension, heart failure).

Betaxolol, verapamil

Betaxolol should not be administered concomitantly (or after some day's treatment with) calcium antagonists of verapamil type.

Bictegravir/emtricitabine/tenofovir alafenamide [1], verapamil ---> SmPC of [1] of EMA

Caution is recommended when bictegravir is combined with medicinal products known to inhibit P-gp and/or BCRP

Bisoprolol [1], verapamil ---> SmPC of [1] of eMC

Intravenous administration of verapamil in patients on beta-blocker treatment may lead to profound hypotension and atrioventricular block.

Boceprevir [1], verapamil ---> SmPC of [1] of EMA

Boceprevir, CYP3A4 inhibitor, may increase the plasma concentrations of calcium channel blocker. Caution is warranted and clinical monitoring of patients is recommended.

Bosutinib [1], verapamil ---> SmPC of [1] of EMA

The concomitant use of bosutinib with moderate CYP3A inhibitors should be avoided, as an increase in bosutinib plasma levels will occur. Selection of an alternate concomitant medicine with no or minimal CYP3A enzyme inhibition potential is recommended.

Breast-feeding, verapamil [2] ---> SmPC of [2] of eMC

Verapamil is excreted into the breast milk in small amounts and is unlikely to be harmful. However, it should only be used during lactation if, in the clinician's judgement, it is essential for the welfare of the patient.

Brigatinib [1], verapamil ---> SmPC of [1] of EMA

No dose adjustment is required for Alunbrig in combination with moderate CYP3A inhibitors.

Buflomedil, verapamil

The co-administration may increase the hypotensive effect

Buspirone, verapamil [2] ---> SmPC of [2] of eMC

Concomitant administration of buspirone and a CYP3A4 inhibitor increased the plasma concentrations of buspirone. A low dose of buspirone is recommended.

Calcifediol, verapamil

There are studies which describe an inhibition of antianginal effect due to antagonism of actions

Calcium antagonists, halogenated anaesthetics ---> SmPC of [verapamil] of eMC

Caution should be exercised when calcium antagonists are used concomitantly with inhalation anaesthetics due to the risk of additive negative inotropic effect.

Calcium, verapamil

The co-administration may weaken the effect of verapamil, particularly in heart rhythm disorders

Carbamazepine, verapamil [2] ---> SmPC of [2] of eMC

Verapamil may increase the plasma concentrations of carbamazepine. This may produce side effects such as diplopia, headache, ataxia or dizziness.

Cardiodepressants, verapamil ---> SmPC of [trandolapril/verapamil] of eMC

The concurrent use of verapamil and cardiodepressives, i.e., medicinal products that inhibit cardiac impulse generation and conduction, may produce undesirable additive effects

Cariprazine [1], verapamil ---> SmPC of [1] of EMA

Metabolism of cariprazine and its major active metabolites is mediated mainly by CYP3A4. The co-administration of cariprazine with strong or moderate inhibitors of CYP3A4 is contraindicated

Carteolol [1], verapamil ---> SmPC of [1] of eMC

There is a potential for additive effects resulting in hypotension and/or marked bradycardia when ophthalmic beta-blockers solution is administered concomitantly with oral calcium channel blockers

Carvedilol [1], verapamil ---> SmPC of [1] of eMC

Isolated cases of conduction disturbance (rarely compromised haemodynamics) have been reported, if oral carvedilol and verapamil are given concomitantly. The intravenous co-administration is contraindicated

Celiprolol [1], verapamil ---> SmPC of [1] of eMC

Calcium channel antagonists such as verapamil (and to a lesser extent diltiazem) and beta blockers both slow A-V conduction and depress myocardial contractility through different mechanisms.

Cimetidine, verapamil ---> SmPC of [trandolapril/verapamil] of eMC

Verapamil concentrations may be increased by cimetidine

Clarithromycin, verapamil [2] ---> SmPC of [2] of eMC

Clarithromycin may increase the plasma concentrations of verapamil.

Clotrimazole, verapamil [2] ---> SmPC of [2] of eMC

Cobicistat [1], verapamil ---> SmPC of [1] of EMA

Concentrations of calcium channel blockers may be increased when co-administered with cobicistat. Clinical monitoring of therapeutic effect and adverse events is recommended when these medicinal products are co-administered with Tybost.

Cobimetinib [1], verapamil ---> SmPC of [1] of EMA

Caution should be exercised if cobimetinib is coadministered with moderate CYP3A inhibitors. When cobimetinib is co-administered with a moderate CYP3A inhibitor, patients should be carefully monitored for safety.

Colchicine, verapamil [2] ---> SmPC of [2] of eMC

When verapamil and colchicine are administered together, inhibition of P-gp and/or CYP3A by verapamil may lead to increased exposure to colchicine. Combined use is not recommended.

Colesevelam [1], verapamil ---> SmPC of [1] of EMA

The bile-acid sequestrant may decrease the bioavailability of verapamil

Crizotinib [1], verapamil ---> SmPC of [1] of EMA

Bradycardia has been reported during clinical studies; therefore, use crizotinib with caution due to the risk of excessive bradycardia when used in combination with other bradycardic agents

Cyclophosphamide, verapamil

Decreased absorption of verapamil

Cyclosporine [1], verapamil ---> SmPC of [1] of eMC

Inhibitors of CYP3A4 may lead to increased levels of cyclosporine.

CYP3A4 inhibitors, verapamil [2] ---> SmPC of [2] of eMC

Dabigatran etexilate [1], verapamil ---> SmPC of [1] of EMA

Dabigatran etexilate is a substrate for the efflux transporter P-gp. Caution should be exercised with mild to moderate P-gp inhibitors

Dabigatran [1], verapamil ---> SmPC of [1] of EMA

Dabigatran etexilate is a substrate for the efflux transporter P-gp. Caution should be exercised with mild to moderate P-gp inhibitors

Dabrafenib [1], verapamil ---> SmPC of [1] of EMA

Interactions with many medicinal products eliminated through metabolism or active transport is expected. These medicinal products are to be avoided or used with caution.

Daclatasvir [1], verapamil ---> SmPC of [1] of EMA

Administration of daclatasvir with verapamil (CYP3A4 and P-gp inhibitor) may result in increased concentrations of daclatasvir. Caution is advised.

Dalbavancin [1], verapamil ---> SmPC of [1] of EMA

It is not known if dalbavancin is a substrate for hepatic uptake and efflux transporters. Co-administration with inhibitors of these transporters may increase the exposure to dalbavancin.

Dantrolene, verapamil ---> SmPC of [trandolapril/verapamil] of eMC

The simultaneous use of verapamil with dantrolene is not recommended.

Dapoxetine [1], verapamil ---> SmPC of [1] of eMC

Concomitant treatment of dapoxetine with moderate CYP3A4 inhibitors may give rise to significantly increased exposure of dapoxetine and desmethyldapoxetine, especially in CYP2D6 poor metabolizers.

Darifenacin [1], verapamil ---> SmPC of [1] of EMA

Concomitant treatment of darifenacin with potent P-glycoprotein inhibitors should be avoided.

Darunavir/cobicistat [1], verapamil ---> SmPC of [1] of EMA

Darunavir/cobicistat is expected to increase the calcium channel blocker plasma concentrations. (CYP3A and/or CYP2D6 inhibition)

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], verapamil ---> SmPC of [1] of EMA

Based on theoretical considerations DRV/COBI is expected to increase this calcium channel blocker plasma concentrations. CYP3A inhibition

Darunavir/ritonavir, verapamil ---> SmPC of [darunavir] of EMA

Boosted darunavir can be expected to increase the plasma concentrations of calcium channel blocker. (CYP3A and/or CYP2D6 inhibition)

Dasabuvir with ombitasvir/paritaprevir/ritonavir, verapamil ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of EM

CYP3A4/P-gp inhibition. Caution is advised due to the expected increase in paritaprevir exposures. Dose decrease and clinical monitoring of calcium channel blockers is recommended when coadministered with Viekirax with and without dasabuvir.

Dextromethorphan/quinidine [1], verapamil ---> SmPC of [1] of EMA

Concomitant administration of medicines that inhibit CYP3A4 can be expected to increase plasma levels of quinidine, which could increase risk relating to QTc prolongation. Strong and moderate CYP3A4 inhibitors should be avoided during treatment.

Digitoxin, verapamil ---> SmPC of [trandolapril/verapamil] of eMC

Verapamil may increase the plasma concentrations of digitoxin thus increasing risk of toxicity

Digoxin, verapamil [2] ---> SmPC of [2] of eMC

Verapamil has been shown to increase the serum concentration of digoxin and caution should be exercised with regard to digitalis toxicity.

Disopyramide [1], verapamil ---> SmPC of [1] of eMC

Antiarrhythmic combination should be avoided except under certain circumstances

Diuretics, verapamil [2] ---> SmPC of [2] of eMC

Potentiation of the hypotensive effect

Dofetilide [1], verapamil ---> SmPC of [1] of EMA

The co-administration may increase the plasma levels of dofetilide. The combination is contraindicated

Doxorubicine, verapamil ---> SmPC of [trandolapril/verapamil] of eMC

Verapamil may increase the plasma concentrations of doxorubicine thus increasing risk of toxicity

Dronedarone [1], verapamil ---> SmPC of [1] of EMA

Calcium antagonists with depressant effects on sinus and atrio-ventricular node such as verapamil and diltiazem should be used with caution when associated with dronedarone.

Droperidol [1], verapamil ---> SmPC of [1] of eMC

Substances inhibiting the activity of cytochrome P450 iso-enzyme CYP3A4 could decrease the rate at which droperidol is metabolised and prolong its pharmacological action.

Drugs primarily metabolised by CYP3A4, verapamil

Verapamil, CYP3A4 inhibitor, may increase the plasma concentrations of the medicinal product mainly metabolized by CYP3A4

Drugs with high protein binding, verapamil

Verapamil is extensively bound to plasma proteins. Possible interactions with other active substances known to have high affinity for plasma proteins should be considered

Dutasteride [1], verapamil ---> SmPC of [1] of eMC

Dutasteride serum levels were on average 1.6 to 1.8 times greater, respectively, in a small number of patients treated concurrently with verapamil or diltiazem (moderate inhibitors of CYP3A4 and inhibitors of P-glycoprotein) than in other patients

Edoxaban [1], verapamil ---> SmPC of [1] of EMA

Edoxaban is a substrate for the efflux transporter P-gp. In pharmacokinetic (PK) studies, concomitant administration of edoxaban with the P-gp inhibitor resulted in increased plasma concentrations of edoxaban. Concomitant use does not require dose reduction

Efavirenz [1], verapamil ---> SmPC of [1] of EMA

Efavirenz, CYP3A4 inductor, may decrease the plasma concentrations of calcium antagonist

Efavirenz/emtricitabine/tenofovir disoproxil [1], verapamil ---> SmPC of [1] of EMA

Efavirenz, CYP3A4 inductor, may decrease the plasma concentrations of calcium antagonist

Eliglustat [1], verapamil ---> SmPC of [1] of EMA

It is predicted that concomitant use of moderate CYP3A inhibitors would increase eliglustat exposure approximately up to 3-fold. Caution should be used with moderate CYP3A inhibitors in intermediate and extensive metabolisers.

Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide [1], verapamil ---> SmPC of [1] of EMA

Concentrations of calcium channel blocker may be increased when co-administered with cobicistat.

Elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil [1], verapamil ---> SmPC of [1] of EMA

Concentrations of calcium channel blockers may be increased when co-administered with cobicistat.

Empagliflozin [1], verapamil ---> SmPC of [1] of EMA

Empagliflozin exposure was similar with and without co-administration with verapamil, a P-gp inhibitor, indicating that inhibition of P-gp does not have any clinically relevant effect on empagliflozin.

Empagliflozin/metformin [1], verapamil ---> SmPC of [1] of EMA

Enzalutamide [1], verapamil ---> SmPC of [1] of EMA

Enzalutamide, enzymatic inductor, may increase the metabolism of verapamil and decrease its plasma levels and effect

Eplerenone [1], verapamil ---> SmPC of [1] of eMC

Moderate CYP3A4 inhibitors may increase the AUC of eplerenone. Eplerenone dosing should not exceed 25 mg when moderate inhibitors of CYP3A4 are co-administered with eplerenone

Erlotinib [1], verapamil ---> SmPC of [1] of EMA

Erlotinib is a substrate for the P-glycoprotein active substance transporter. Concomitant administration of inhibitors of Pgp may lead to altered distribution and/or altered elimination of erlotinib.

Ertugliflozin/metformin [1], verapamil ---> SmPC of [1] of EMA

Metformin is a substrate of both transporters OCT1 and OCT2. Coadministration of metformin with inhibitors of OCT1 (such as verapamil) may reduce efficacy of metformin.

Erythromycin, verapamil [2] ---> SmPC of [2] of eMC

Erythromycin may increase the plasma concentrations of verapamil.

Esmolol [1], verapamil ---> SmPC of [1] of eMC

Calcium antagonists such as verapamil and to a lesser extent diltiazem have a negative influence on contractility and AV-conduction. This combination should be used with caution with verapamil in patients with impaired ventricular function

Everolimus [1], verapamil ---> SmPC of [1] of EMA

The moderate CYP3A4 inhibition may increase the plasma concentrations of everolimus. Caution should be exercised

Ezetimibe/atorvastatin [1], verapamil ---> SmPC of [1] of eMC

Moderate CYP3A4 inhibitors may increase plasma concentrations of atorvastatin. Appropriate clinical monitoring of the patient is recommended when concomitantly used with moderate CYP3A4 inhibitors.

Ezetimibe/simvastatine [1], verapamil ---> SmPC of [1] of eMC

The risk of myopathy and rhabdomyolysis is increased by concomitant administration of verapamil with simvastatin 40 mg or 80 mg

Felodipine/metoprolol, verapamil

Metoprolol should not be given in combination with calcium channel blockers of verapamil type since this may cause bradycardia, hypotension, heart failure and asystole and may increase auriculo-ventricular conduction time.

Fenofibrate/simvastatin [1], verapamil ---> SmPC of [1] of EMA

Caution should be exercised when combining fenofibrate/simvastatine with certain other less potent CYP 3A4 inhibitors. The risk of myopathy and rhabdomyolysis is increased by concomitant use of verapamil with simvastatin 40 mg per day.

Fentanyl [1], verapamil ---> SmPC of [1] of EMA

The concomitant use of fentanyl with moderate CYP3A4 inhibitors may result in increased fentanyl plasma concentrations, potentially causing serious adverse drug reactions including fatal respiratory depression.

Fesoterodine [1], verapamil ---> SmPC of [1] of EMA

Caution should be exercised when prescribing fesoterodine to patients in whom an increased exposure to the active metabolite is expected, e. g. coadministration of moderate CYP3A4 inhibitors. No dosing adjustments are recommended

Fidaxomicin [1], verapamil ---> SmPC of [1] of EMA

Fidaxomicin is a substrate of P-gp. Co-administration of potent inhibitors of P-gp increases fidaxomicin exposure. Co-administration of potent inhibitors of P-gp is not recommended.

Fingolimod [1], verapamil ---> SmPC of [1] of EMA

Treatment with Gilenya should not be initiated in patients receiving beta blockers, or other substances which may decrease heart rate because of the potential additive effects on heart rate

Flecainide [1], verapamil ---> SmPC of [1] of eMC

The use of flecainide with calcium channel blockers, e.g. verapamil, should be considered with caution.

Fluconazole [1], verapamil ---> SmPC of [1] of eMC

Verapamil is metabolized by CYP3A4. Fluconazole has the potential to increase the systemic exposure of verapamil. Frequent monitoring for adverse events is recommended.

Flunitrazepam, verapamil

Substances that inhibit hepatic enzymes may enhance the effect of benzodiazepines. Interactions with strong CYP3A4 inhibitors cannot be excluded

Fluticasone furoate/vilanterol [1], verapamil ---> SmPC of [1] of EMA

A clinical pharmacology study in healthy subjects with co-administered vilanterol and the potent P-gp and moderate CYP3A4 inhibitor verapamil did not show any significant effect on the pharmacokinetics of vilanterol.

Fosphenytoin [1], verapamil ---> SmPC of [1] of eMC

Blood levels and/or effects of verapamil may be altered by phenytoin (CYP3A4 induction)

Gadofosveset [1], verapamil ---> SmPC of [1] of EMA

Gadofosveset demonstrated no adverse interaction at clinically relevant concentrations.

Glibenclamide, verapamil ---> SmPC of [trandolapril/verapamil] of eMC

Verapamil may increase the plasma concentrations of glibenclamide thus increasing risk of toxicity

Grapefruit juice, verapamil [2] ---> SmPC of [2] of eMC

Grapefruit juice may increase the plasma concentrations of verapamil.

Guanfacin [1], verapamil ---> SmPC of [1] of EMA

Co-administration of Intuniv with moderate and strong CYP3A4/5 inhibitors elevates plasma guanfacine concentrations and increases the risk of adverse reactions such as hypotension, bradycardia, and sedation.

Halogenated anaesthetics, verapamil [2] ---> SmPC of [2] of eMC

The combination of inhaled anaesthetics with verapamil may lead to additive cardiovascular effects (e.g. AV block, bradycardia, hypotension, heart failure).

Hydantoins, verapamil

The hydantoin may weaken the effect of verapamil

Hydroquinidine, verapamil

Concomitant use of hydroquinidine and bradycardiac agents increases the risk of heart rhythm disorders (torsades de pointes)

Ibrutinib [1], verapamil ---> SmPC of [1] of EMA

Ibrutinib is primarily metabolised by cytochrome P450 enzyme 3A4. Concomitant use of ibrutinib and medicinal products that moderately inhibit CYP3A4 can increase ibrutinib exposure and should be avoided.

Imipramine [1], verapamil ---> SmPC of [1] of eMC

Blood levels of imipramine may be increased by calcium channel blockers

Indinavir, verapamil [2] ---> SmPC of [2] of eMC

Itraconazol [1], verapamil ---> SmPC of [1] of eMC

Calcium channel blockers can have negative inotropic effects which may be additive to those of itraconazole. In addition, itraconazole can inhibit the metabolism of calcium channel blockers.

Ivabradine [1], verapamil ---> SmPC of [1] of EMA

The combination of ivabradine with the heart rate reducing agent verapamil (moderate CYP3A4 inhibitor) resulted in an increase in ivabradine exposure. The concomitant use of ivabradine with verapamil is contraindicated

Ixabepilone, verapamil

The moderate CYP3A4 inhibition may increase the plasma concentrations of ixabepilone. Caution is recommended

Ketoconazole [1], verapamil ---> SmPC of [1] of EMA

Potential increased in plasma concentrations of verapamil. Careful monitoring. Dose adjustment of verapamil may be required.

Lapatinib [1], verapamil ---> SmPC of [1] of EMA

The CYP3A4 and P-glycoprotein inhibition may increase the systemic exposure of lapatinib. Concomitant use should be avoided

Letermovir [1], verapamil ---> SmPC of [1] of EMA

Caution is advised if P-gp/BCRP inhibitors are added to letermovir combined with cyclosporine.

Levobupivacaine, verapamil

In vitro studies indicate that the CYP3A4 isoform and CYP1A2 isoform mediate the metabolism of levobupivacaine. Metabolism of levobupivacaine may be affected by CYP3A4 inhibitors and CYP1A2 inhibitors

Liposome-encapsulated doxorubicin-citrate complex [1], verapamil ---> SmPC of [1] of EMA

Plasma levels of doxorubicin and its metabolite, doxorubicinol, may be increased when doxorubicin is administered with cyclosporine, verapamil, paclitaxel or other agents that inhibit P-glycoprotein (P-Gp).

Lithium, verapamil [2] ---> SmPC of [2] of eMC

Serum levels of lithium may be reduced (pharmacokinetic effect); there may be increased sensitivity to lithium causing enhanced neurotoxicity (pharmacodynamic effect)

Lofepramine, verapamil

Verapamil may increase the plasma levels of lofepramine

Lomitapide [1], verapamil ---> SmPC of [1] of EMA

The strong CYP3A4 inhibition may increase lomitapide AUC. The combination of lomitapide with strong CYP3A4 inhibitors is contra-indicated

Loperamide, verapamil

The inhibition of P-glycoprotein may increase the plasma levels of loperamide

Lovastatine, verapamil

Verapamil, CYP3A4 inhibitor, may increase the plasma levels of lovastatin and the risk of muscular toxicity (myopathy/rhabdomyolysis)

Lurasidone [1], verapamil ---> SmPC of [1] of EMA

Coadministration of lurasidone with medicinal products that moderately inhibit CYP3A4 may increase exposure to lurasidone.

Macrolide antibiotics, verapamil [2] ---> SmPC of [2] of eMC

Methadone, verapamil

Methadone is substrate of P-glycoprotein. Medicinal products that the substrate inhibit (quinidine, verapamil) may increase plasma concentrations of methadone

Metildigoxin, verapamil

Increased plasma levels of metildigoxin

Metoprolol [1], verapamil ---> SmPC of [1] of eMC

Midazolam [1], verapamil ---> SmPC of [1] of EMA

Verapamil has been shown to reduce the clearance of midazolam and other benzodiazepines and may potentiate their actions.

Muscle relaxants, verapamil [2] ---> SmPC of [2] of eMC

The effects of neuromuscular blocking agents employed in anaesthesia may be potentiated.

Nadolol [1], verapamil ---> SmPC of [1] of eMC

Beta-adrenoceptor stimulants such as isoprenaline and verapamil, or alpha-adrenoceptor stimulants such as noradrenaline and adrenaline, will reverse the hypotensive effects and increase vasoconstrictor activity.

Naloxegol [1], verapamil ---> SmPC of [1] of EMA

Concomitant use of naloxegol with CYP3A4 inhibitors increases naloxegol exposition. A dose adjustment of naloxegol is recommended when co-administered with moderate CYP3A4 inhibitors

Nebivolol [1], verapamil ---> SmPC of [1] of eMC

Negative influence on contractility and atrio-ventricular conduction. Intravenous administration of verapamil in patients with ß-blocker treatment may lead to profound hypotension and atrio-ventricular block

Neratinib [1], verapamil ---> SmPC of [1] of EMA

Co-administration of neratinib with moderate CYP3A4/P-gp inhibitors is contraindicated

Neuroleptics, verapamil

The co-administration may enhance the hypotensive effect of verapamil

Nicergoline, verapamil

Nicergoline may enhance the hypotensive effect of the coadministered hypotensive agents

Olaparib [1], verapamil ---> SmPC of [1] of EMA

Known strong or moderate CYP3A inhibitors are not recommended with olaparib

Olmesartan medoxomil/amlodipine [1], verapamil ---> SmPC of [1] of eMC

Concomitant use of amlodipine with strong or moderate CYP3A4 inhibitors may give rise to significant increase in amlodipine exposure.

Ombitasvir/paritaprevir/ritonavir [1], verapamil ---> SmPC of [1] of EMA

Oxprenolol [1], verapamil ---> SmPC of [1] of eMC

Calcium antagonists may enhance bradycardia, myocardial depression and hypotension; particularly after i.v. use of verapamil in patients taking oral betablockers, the possibility of hypotension and cardiac arrhythmias cannot be excluded

Pasireotide [1], verapamil ---> SmPC of [1] of EMA

Clinical monitoring of heart rate, notably at the beginning of treatment, is recommended in patients receiving pasireotide concomitantly with bradycardic medicinal products

Penbutolol, verapamil

The co-administration of calcium antagonists of verapamil- and diltiazem type with penbutolol may increase the tendency to cardiac conduction and rhythm disorders and cause strong hypotension

Phenazone, verapamil

Concomitant use of phenazone and calcium antagonists delays the elimination of phenazone. There is the possibility of an accumulation

Phenobarbital, verapamil [2] ---> SmPC of [2] of eMC

Phenobarbital may reduce the plasma concentrations of verapamil.

Phenytoin, verapamil [2] ---> SmPC of [2] of eMC

Levels of verapamil may be reduced when taken with phenytoin.

Pindolol [1], verapamil ---> SmPC of [1] of eMC

This medicine should not be used with calcium-channel blockers with negative inotropic effects e.g. verapamil and to a lesser extent diltiazem.

Pindolol/clopamide [1], verapamil ---> SmPC of [1] of eMC

This medicine should not be used with calcium-channel blockers with negative inotropic effects e.g. verapamil and to a lesser extent diltiazem.

Piperaquine/artenimol [1], verapamil ---> SmPC of [1] of EMA

Concomitant treatment with medicinal products which inhibit CYP3A4 may lead to a marked increase of piperaquine plasma concentration resulting in an exacerbation of the effect on QTc

Posaconazole [1], verapamil ---> SmPC of [1] of EMA

Concomitant use of posaconazole with calcium channel blockers metabolised through CYP3A4 increases plasma concentrations of the calcium channel blocker.

Prajmalium, verapamil

Prajmalium increases verapamil plasma levels

Pramipexole, verapamil

Decreased pramipexole clearance. Reduction of the pramipexole dose should be considered

Prasugrel [1], verapamil ---> SmPC of [1] of EMA

CYP3A inhibitors are not anticipated to have a significant effect on the pharmacokinetics of the prasugrel active metabolite.

Prazosin, verapamil ---> SmPC of [trandolapril/verapamil] of eMC

Verapamil may increase the plasma concentrations of prazosin thus increasing risk of toxicity

Pregnancy, verapamil [2] ---> SmPC of [2] of eMC

Verapamil should not be given during the first trimester of pregnancy unless, in the clinician's judgement, it is essential for the welfare of the patient.

Propranolol [1], verapamil ---> SmPC of [1] of EMA

Co-administration of verapamil bepridil with propranolol can cause altered automaticity (excessive bradycardia, sinus arrest), sino-atrial and AV conduction disorders, and increased risk of ventricular arrhythmias along with heart failure.

Protease inhibitors, verapamil

Prucalopride [1], verapamil ---> SmPC of [1] of EMA

The inhibition of P-glycoprotein may increase the systemic exposure to prucalopride. This effect is too small to be clinically relevant.

Quinidine, verapamil ---> SmPC of [trandolapril/verapamil] of eMC

Verapamil may increase the plasma concentrations of quinidine thus increasing risk of toxicity

Radiologic contrasts, verapamil

The co-administration of verapamil with a radiologic contract for coronary angiography may enhance die cardiodepressant effect

Ranolazine [1], verapamil ---> SmPC of [1] of EMA

Ranolazine is a substrate for P-gp. Inhibitors of P-gp (e.g. ciclosporin, verapamil) increase plasma levels of ranolazine. Careful dose titration of Ranexa is recommended in patients treated with P-gp inhibitors. Down-titration of Ranexa may be required

Ribociclib [1], verapamil ---> SmPC of [1] of EMA

Concomitant use of strong CYP3A4 inhibitors should be avoided and an alternative concomitant medicinal product with less potential to inhibit CYP3A4 inhibition should be considered.

Rifabutin, verapamil

Rifabutin has a similar structure as rifampicin. Concomitant use of rifabutin and verapamil may decrease verapamil effects

Rifampicin, verapamil [2] ---> SmPC of [2] of eMC

Clinically significant interactions have been reported with inducers of CYP3A4 that have caused a lowering of plasma levels of verapamil, therefore, patients should be monitored for drug interactions.

Risperidone [1], verapamil ---> SmPC of [1] of eMC

The CYP3A4 and P-glycoprotein inhibition may increase the plasma levels of risperidone

Ritonavir, verapamil [2] ---> SmPC of [2] of eMC

Saquinavir/ritonavir, verapamil ---> SmPC of [saquinavir] of EMA

Possible increase in the plasma concentrations of calcium channel antagonist. Careful monitoring of therapeutic and adverse effects is recommended.

Sertindole, verapamil

The concomitant administration of CYP3A inhibitors and sertindole is contraindicated, as this may lead to significant increases in sertindole levels

Sevoflurane [1], verapamil ---> SmPC of [1] of eMC

Impairment of atrioventricular conduction was observed when verapamil and sevoflurane were administered at the same time.

Simeprevir [1], verapamil ---> SmPC of [1] of EMA

The intestinal CYP3A4 enzyme and P-gp transporter inhibition by simeprevir may increase the plasma concentrations of orally administered calcium channel blocker. Verapamil, CYP3A4 inhibitor, may increase the plasma levels of simeprevir

Simvastatine [1], verapamil ---> SmPC of [1] of eMC

The risk of myopathy and rhabdomyolysis is increased by concomitant administration of verapamil with simvastatin 40 mg or 80 mg. The dose of simvastatin should not exceed 20 mg daily in patients receiving concomitant medication with verapamil.

Sirolimus [1], verapamil ---> SmPC of [1] of EMA

Multiple-dose administration of erythromycin and sirolimus oral solution significantly increased the rate and extent of absorption of both medicinal products.

Solifenacin [1], verapamil ---> SmPC of [1] of eMC

Since solifenacin is metabolised by CYP3A4, pharmacokinetic interactions are possible with other CYP3A4 substrates with higher affinity (e.g. verapamil, diltiazem)

Sotalol [1], verapamil ---> SmPC of [1] of eMC

Beta-blockers should be avoided in combination with cardiodepressant calcium-channel blockers such as verapamil and diltiazem because of the additive effects on atrioventricular conduction, and ventricular function.

St. John's wort, verapamil ---> SmPC of [trandolapril/verapamil] of eMC

Verapamil concentrations may be reduced by St. John's wort

Statins metabolised by CYP3A4, verapamil ---> SmPC of [trandolapril/verapamil] of eMC

Increase in serum exposure (and the myopathy and rhabdomyolysis risk) has been reported for simvastatin when concomitantly administered with verapamil. The dose of simvastatin (and other statins also metabolised by CYP3A4) should be adapted accordingly.

Strong CYP3A4 inductors, verapamil [2] ---> SmPC of [2] of eMC

Strong CYP3A4 inhibitors, verapamil [2] ---> SmPC of [2] of eMC

Succinylcholine, verapamil ---> SmPC of [suxamethonium] of eMC

Enhancement or prolongation of the neuromuscular effects of suxamethonium by mechanisms unrelated to plasma cholinesterase activity.

Sulfinpyrazone, verapamil [2] ---> SmPC of [2] of eMC

Sulfinpyrazone may reduce the plasma concentrations of verapamil which may produce a reduced blood pressure lowering effect.

Sulfonylureas, verapamil

Increased plasma levels of antidiabetic agent

Sulpiride [1], verapamil ---> SmPC of [1] of eMC

The combination of sulpiride with bradycardia-inducing medications is not recommended

Suxamethonium [1], verapamil ---> SmPC of [1] of eMC

Enhancement or prolongation of the neuromuscular effects of suxamethonium by mechanisms unrelated to plasma cholinesterase activity.

Tacrolimus [1], verapamil ---> SmPC of [1] of EMA

Concomitant use of substances known to inhibit CYP3A4 may affect the metabolism of tacrolimus and thereby increase tacrolimus blood levels.

Talinolol, verapamil

Combined use of beta-adrenoceptor blocking drugs and calcium channel blockers with negative inotropic effects can lead to prolongation of SA and AV conduction. This may result in severe hypotension, bradycardia and cardiac failure.

Telaprevir [1], verapamil ---> SmPC of [1] of EMA

Inhibition of CYP3A and/or effect on P-gp transport in the gut increases plasma concentration of calcium channel blocker. Caution is warranted and clinical monitoring of patients is recommended.

Telithromycin [1], verapamil ---> SmPC of [1] of EMA

The strong CYP3A4 inhibition by telithromycin may increase the plasma concentrations of verapamil and may result in hypotension, bradycardia or loss of consciousness, and should therefore be avoided.

Temsirolimus [1], verapamil ---> SmPC of [1] of EMA

Concomitant treatment with moderate CYP3A4 inhibitors should only be administered with caution in patients receiving 25 mg and should be avoided in patients receiving temsirolimus doses higher than 25 mg

Terazosine, verapamil ---> SmPC of [trandolapril/verapamil] of eMC

Verapamil may increase the plasma concentrations of terazosin thus increasing risk of toxicity

Tetracyclic antidepressant, verapamil

The co-administration may enhance the hypotensive effect of verapamil

Theophylline [1], verapamil ---> SmPC of [1] of eMC

Calcium antagonists reduce clearance of theophylline and a reduced dosage may therefore be necessary to avoid side-effects

Tiapride, verapamil

Tiapride should not be combined with drugs that prolong the QT interval. These drugs (with the exception of anti-infectious) should be discontinued, if possible, if they induce torsades de pointes

Ticagrelor [1], verapamil ---> SmPC of [1] of EMA

Concomitant use of ticagrelor with drugs that are potent P-glycoprotein inhibitors and moderate CYP3A4 inhibitors may increase ticagrelor exposure. If the association cannot be avoided, their concomitant use should be made with caution

Tolterodine, verapamil

The co-administration may increase the plasma concentrations of tolterodine

Trabectedin [1], verapamil ---> SmPC of [1] of EMA

Preclinical data have demonstrated that trabectedin is a substrate to P-gp. Concomitant administration of inhibitors of P-gp may alter trabectedin distribution and/or elimination.

Trametinib [1], verapamil ---> SmPC of [1] of EMA

As it cannot be excluded that strong inhibition of hepatic P-gp may result in increased levels of trametinib, caution is advised when coadministering trametinib with medicinal products that are strong inhibitors of P-gp

Triazolam, verapamil

Caution is advised when combining triazolam with verapamil

Tricyclic antidepressant, verapamil

The co-administration may enhance the hypotensive effect of verapamil

Triptorelin [1], verapamil ---> SmPC of [1] of eMC

Drugs which raise prolactin levels should not be prescribed concomitantly as they reduce the level of GnRH receptors in the pituitary.

Umeclidinium [1], verapamil ---> SmPC of [1] of EMA

No effect of verapamil was observed on umeclidinium bromide Cmax.

Vasodilators, verapamil [2] ---> SmPC of [2] of eMC

Potentiation of the hypotensive effect

Vemurafenib [1], verapamil ---> SmPC of [1] of EMA

Venetoclax [1], verapamil ---> SmPC of [1] of EMA

At initiation and during the dose-titration phase, concomitant use of venetoclax with moderate CYP3A inhibitors should be avoided. Alternative treatments should be considered.

Verapamil, vitamin D

The co-administration may weaken the effect of verapamil, particularly in heart rhythm disorders

Verapamil, ziprasidone

The co-administration of ziprasidone with P glycoprotein inhibitors may increase the plasma concentrations of ziprasidone

CONTRAINDICATIONS of Verapamil

- Hypersensitivity to verapamil or any of the excipients

- Cardiogenic shock

- Acute myocardial infarction complicated by bradycardia, hypotension or left ventricular failure

- Second or third degree atrioventricular block

- Sino-atrial block

- Sick sinus syndrome

- Uncompensated heart failure

- Bradycardia of less than 50 beats/minute (Except in patients with functioning artificial ventricular pacemaker)

- Intravenous dantrolene

- Hypotension of less than 90 mm Hg systolic

- Atrial flutter or fibrillation associated with an accessory pathway (e.g. Wolff-Parkinson-White syndrome, Lown-Ganong-Levine syndrome)

- Porphyria

- Concomitant ingestion of grapefruit juice.

http://www.medicines.org.uk/emc/

Vericiguat (Verquvo)

Ability to drive, vericiguat [2] ---> SmPC of [2] of EMA

When driving vehicles or operating machines it should be taken into account that dizziness may occur occasionally.

Acetylsalicylic acid, vericiguat [2] ---> SmPC of [2] of EMA

Co-administration of acetylsalicylic acid was not associated with a clinically relevant effect on the exposure (AUC and Cmax) of vericiguat.

Aluminium hydroxide, vericiguat [2] ---> SmPC of [2] of EMA

Co-treatment with medicinal products that increase gastric pH, did not affect vericiguat exposure when vericiguat was taken as directed with food in heart failure patients (see section 4.2).

Antacids, vericiguat [2] ---> SmPC of [2] of EMA

Co-treatment with medicinal products that increase gastric pH, did not affect vericiguat exposure when vericiguat was taken as directed with food in heart failure patients (see section 4.2).

Breast-feeding, vericiguat [2] ---> SmPC of [2] of EMA

A decision must be made whether to discontinue breast-feeding or to discontinue or abstain from vericiguat therapy, taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Digoxin, vericiguat [2] ---> SmPC of [2] of EMA

No clinically meaningful effect on midazolam (CYP3A substrate) or digoxin (P-gp substrate) exposure was observed when vericiguat was co-administered with these medicinal products.

Fertility, vericiguat [2] ---> SmPC of [2] of EMA

In a study with male and female rats, vericiguat showed no impairment of fertility (see section 5.3).

Foods, vericiguat [2] ---> SmPC of [2] of EMA

Verquvo should be taken with food (see section 5.2). For patients who are unable to swallow whole tablets, Verquvo may be crushed and mixed with water immediately before administration (see section 5.2).

Gastric pH increasing medication, vericiguat [2] ---> SmPC of [2] of EMA

Co-treatment with medicinal products that increase gastric pH, did not affect vericiguat exposure when vericiguat was taken as directed with food in heart failure patients (see section 4.2).

H2 antagonists, vericiguat [2] ---> SmPC of [2] of EMA

Co-treatment with medicinal products that increase gastric pH, did not affect vericiguat exposure when vericiguat was taken as directed with food in heart failure patients (see section 4.2).

Isosorbide mononitrate, vericiguat [2] ---> SmPC of [2] of EMA

In patients with heart failure, concomitant use of short-acting nitrates was well tolerated. There is limited experience with concomitant use of vericiguat and long-acting nitrates in patients with heart failure (see section 4.4).

Ketoconazole, vericiguat [2] ---> SmPC of [2] of EMA

No clinically meaningful effect on vericiguat exposure was observed when vericiguat was co-administered with ketoconazole (multi-pathway CYP and transporter inhibitor),

Magnesium hydroxide, vericiguat [2] ---> SmPC of [2] of EMA

Co-treatment with medicinal products that increase gastric pH, did not affect vericiguat exposure when vericiguat was taken as directed with food in heart failure patients (see section 4.2).

Mefenamic acid, vericiguat [2] ---> SmPC of [2] of EMA

No clinically meaningful effect on vericiguat exposure was observed when vericiguat was co- administered with mefenamic acid (weak to moderate UGT1A9 inhibitor).

Midazolam, vericiguat [2] ---> SmPC of [2] of EMA

No clinically meaningful effect on midazolam (CYP3A substrate) or digoxin (P-gp substrate) exposure was observed when vericiguat was co-administered with these medicinal products.

Nitroglycerine, vericiguat [2] ---> SmPC of [2] of EMA

Omeprazole, vericiguat [2] ---> SmPC of [2] of EMA

Co-treatment with medicinal products that increase gastric pH, did not affect vericiguat exposure when vericiguat was taken as directed with food in heart failure patients (see section 4.2).

Organic nitrates, vericiguat [2] ---> SmPC of [2] of EMA

PDE5 inhibitors, vericiguat [2] ---> SmPC of [2] of EMA

Co-administration not recommended due to the potential increased risk for symptomatic hypotension (see section 4.4).

Pregnancy, vericiguat [2] ---> SmPC of [2] of EMA

As a precautionary measure, vericiguat should not be used during pregnancy and in women of childbearing potential not using contraception.

Proton pump inhibitors, vericiguat [2] ---> SmPC of [2] of EMA

Co-treatment with medicinal products that increase gastric pH, did not affect vericiguat exposure when vericiguat was taken as directed with food in heart failure patients (see section 4.2).

Rifampicin, vericiguat [2] ---> SmPC of [2] of EMA

No clinically meaningful effect on vericiguat exposure was observed when vericiguat was co-administered with rifampicin (multi-pathway UGT, CYP and transporter inducer).

Sacubitril/valsartan, vericiguat [2] ---> SmPC of [2] of EMA

Co-administration was not associated with a clinically relevant effect on the exposure (AUC and Cmax) of either medicinal product.

Sildenafil, vericiguat [2] ---> SmPC of [2] of EMA

No dose-dependent trend was observed with the different sildenafil doses.

Soluble guanylate cyclase stimulators, vericiguat [2] ---> SmPC of [2] of EMA

Verquvo is contraindicated in patients with concomitant use of other soluble guanylate cyclase (sGC) stimulators, such as riociguat (see section 4.3).

Strong UGT1A1 inhibitors, vericiguat [2] ---> SmPC of [2] of EMA

As strong inhibition of UGT1A9 or combined UGT1A9/1A1 has not been tested in clinical drug interaction studies due to the lack of available inhibitors, the clinical consequences of co- administration with these medicinal products are currently unknown.

Strong UGT1A9 inhibitors, vericiguat [2] ---> SmPC of [2] of EMA

UGT1A1 inhibitors, vericiguat [2] ---> SmPC of [2] of EMA

Vericiguat is metabolised by UGT1A9 and UGT1A1. Inhibitors of these UGTs may result in increased exposure of vericiguat.

UGT1A9 inhibitors, vericiguat [2] ---> SmPC of [2] of EMA

Vericiguat is metabolised by UGT1A9 and UGT1A1. Inhibitors of these UGTs may result in increased exposure of vericiguat.

Vericiguat [1], warfarin ---> SmPC of [1] of EMA

Co-administration was not associated with a clinically relevant effect on the exposure (AUC and Cmax) of either medicinal product.

CONTRAINDICATIONS of Vericiguat (Verquvo)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Concomitant use of other soluble guanylate cyclase (sGC) stimulators, such as riociguat (see section 4.5).

https://www.ema.europa.eu/en/documents/product-information/verquvo-epar-product-information_en.pdf. 27/07/2021

Vernakalant (Brinavess)

Ability to drive, vernakalant [2] ---> SmPC of [2] of EMA

Vernakalant has minor to moderate influence on the ability to drive and use machines. Dizziness has been reported within the first 2 hours after receiving it (see section 4.8).

Antiarrhythmic agents, vernakalant [2] ---> SmPC of [2] of EMA

Vernakalant must not be administered in patients who received intravenous AADs (class I and III) within 4 hours prior to vernakalant (see section 4.3).

Breast-feeding, vernakalant [2] ---> SmPC of [2] of EMA

A risk to the suckling child cannot be excluded. Caution should be exercised when used in breastfeeding women.

CYP2D6 inhibitors, vernakalant [2] ---> SmPC of [2] of EMA

No dose adjustment of vernakalant is required on the basis of CYP2D6 metaboliser status, or when vernakalant is administered concurrently with 2D6 inhibitors.

Fertility, vernakalant [2] ---> SmPC of [2] of EMA

Vernakalant was not shown to alter fertility in animal studies.

Interactions, vernakalant [2] ---> SmPC of [2] of EMA

Vernakalant given by infusion is not expected to perpetrate meaningful drug interactions

Mexiletine [1], vernakalant ---> SmPC of [1] of EMA

The concomitant use of mexiletine and antiarrhythmic medicines inducing torsades de pointes is contraindicated

Pregnancy, vernakalant [2] ---> SmPC of [2] of EMA

As a precautionary measure, it is preferable to avoid the use of vernakalant during pregnancy.

QT interval prolonging drugs, vernakalant [2] ---> SmPC of [2] of EMA

Vernakalant has been administered to patients with an uncorrected QT less than 440 msec without an increased risk of torsade de pointes.

Strong CYP2D6 inhibitors, vernakalant [2] ---> SmPC of [2] of EMA

No dose adjustment of vernakalant is required on the basis of CYP2D6 metaboliser status, or when vernakalant is administered concurrently with 2D6 inhibitors.

CONTRAINDICATIONS of Vernakalant (Brinavess)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Patients with severe aortic stenosis, patients with systolic blood pressure < 100 mm Hg, and patients with heart failure class NYHA III and NYHA IV.

- Patients with prolonged QT at baseline (uncorrected > 440 msec), or severe bradycardia, sinus node dysfunction or second degree and third degree heart block in the absence of a pacemaker.

- Use of intravenous rhythm control antiarrhythmics (class I and class III) within 4 hours prior to, as well as in the first 4 hours after, BRINAVESS administration.

- Acute coronary syndrome (including myocardial infarction) within the last 30 days.

https://www.ema.europa.eu/en/documents/product-information/brinavess-epar-product-information_en.pdf 19/02/2024

Verteporfin (Visudyne)

Ability to drive, verteporfin [2] ---> SmPC of [2] of EMA

Following Visudyne treatment, patients may develop transient visual disturbances such as abnormal vision, vision decrease, or visual field defects that may interfere with their ability to drive or use machines.

Aflibercept [1], verteporfin ---> SmPC of [1] of EMA

Adjunctive use of verteporfin photodynamic therapy (PDT) and aflibercept has not been studied, therefore, a safety profile is not established.

Alcohol, verteporfin [2] ---> SmPC of [2] of EMA

Possible quenching of the activated oxygen species generated by verteporfin, resulting in decreased verteporfin activity.

Antidiabetics, verteporfin [2] ---> SmPC of [2] of EMA

It is possible that concomitant use of other photosensitizing medicinal products could increase the potential for photosensitivity reactions. Caution should be exercised

Betacarotene, verteporfin [2] ---> SmPC of [2] of EMA

Possible quenching of the activated oxygen species generated by verteporfin, resulting in decreased verteporfin activity.

Breast-feeding, verteporfin [2] ---> SmPC of [2] of EMA

It should not be administered to nursing mothers, or breastfeeding should be interrupted for 48 hours after administration.

Calcium antagonists, verteporfin [2] ---> SmPC of [2] of EMA

The co-administration may enhance the verteporfin tissue-uptake

Dimethylsulfoxide, verteporfin [2] ---> SmPC of [2] of EMA

Possible quenching of the activated oxygen species generated by verteporfin, resulting in decreased verteporfin activity.

Fertility, verteporfin [2] ---> SmPC of [2] of EMA

Patients of reproductive age should be made aware of the lack of fertility data, and Visudyne should only be given after consideration of individual risks and benefits.

Formiate, verteporfin [2] ---> SmPC of [2] of EMA

Possible quenching of the activated oxygen species generated by verteporfin, resulting in decreased verteporfin activity.

Griseofulvin, verteporfin [2] ---> SmPC of [2] of EMA

It is possible that concomitant use of other photosensitizing medicinal products could increase the potential for photosensitivity reactions. Caution should be exercised

Hypoglycemic drugs, verteporfin [2] ---> SmPC of [2] of EMA

It is possible that concomitant use of other photosensitizing medicinal products could increase the potential for photosensitivity reactions. Caution should be exercised

Mannitol, verteporfin [2] ---> SmPC of [2] of EMA

Possible quenching of the activated oxygen species generated by verteporfin, resulting in decreased verteporfin activity.

Phenothiazines, verteporfin [2] ---> SmPC of [2] of EMA

It is possible that concomitant use of other photosensitizing medicinal products could increase the potential for photosensitivity reactions. Caution should be exercised

Photosensitizing agents, verteporfin [2] ---> SmPC of [2] of EMA

It is possible that concomitant use of other photosensitizing medicinal products could increase the potential for photosensitivity reactions. Caution should be exercised

Platelet aggregation inhibitors, verteporfin [2] ---> SmPC of [2] of EMA

There is a theoretical possibility that agents such as vasodilators and those which diminish clotting and platelet aggregation (e.g. thromboxane A2 inhibitors) can antagonise the action of verteporfin.

Polymyxin, verteporfin [2] ---> SmPC of [2] of EMA

The co-administration may enhance the verteporfin tissue-uptake

Pregnancy, verteporfin [2] ---> SmPC of [2] of EMA

Visudyne should not be used during pregnancy unless clearly needed (only if the benefit justifies the potential risk to the foetus).

Radiotherapy, verteporfin [2] ---> SmPC of [2] of EMA

The co-administration may enhance the verteporfin tissue-uptake

Sulfonylureas, verteporfin [2] ---> SmPC of [2] of EMA

It is possible that concomitant use of other photosensitizing medicinal products could increase the potential for photosensitivity reactions. Caution should be exercised

Sulphamides, verteporfin [2] ---> SmPC of [2] of EMA

It is possible that concomitant use of other photosensitizing medicinal products could increase the potential for photosensitivity reactions. Caution should be exercised

Tetracyclines, verteporfin [2] ---> SmPC of [2] of EMA

It is possible that concomitant use of other photosensitizing medicinal products could increase the potential for photosensitivity reactions. Caution should be exercised

Thiazides, verteporfin [2] ---> SmPC of [2] of EMA

It is possible that concomitant use of other photosensitizing medicinal products could increase the potential for photosensitivity reactions. Caution should be exercised

Vasodilators, verteporfin [2] ---> SmPC of [2] of EMA

CONTRAINDICATIONS of Verteporfin (Visudyne)

- Hypersensitivity to the active substance or to any of the excipients

- Visudyne is also contraindicated in patients with porphyria and in patients with severe hepatic impairment

https://www.ema.europa.eu/en/documents/product-information/visudyne-epar-product-information_en.pdf 16/09/2020 (withdrawn)

Vestronidase alfa (Mepsevii)

Breast-feeding, vestronidase alfa [2] ---> SmPC of [2] of EMA

Vestronidase alfa should only be administered to a breast-feeding woman if the potential benefit of vestronidase alfa to the mother and the benefit of breast-feeding to the infant outweighs the potential theoretical risks to the infant

Fertility, vestronidase alfa [2] ---> SmPC of [2] of EMA

No human data are available on the effect of vestronidase alfa on fertility. Animal studies with vestronidase alfa do not indicate any impact on male or female fertility (see section 5.3).

Interactions, vestronidase alfa [2] ---> SmPC of [2] of EMA

Because it is a recombinant human protein and its enzyme action is within the lysosome, vestronidase alfa is not expected to interact with other medicinal products.

Pregnancy, vestronidase alfa [2] ---> SmPC of [2] of EMA

As a precautionary measure, it is preferable to avoid the use of vestronidase alfa during pregnancy, unless the potential benefit to the mother outweighs the potential theoretical risks to the foetus.

CONTRAINDICATIONS of Vestronidase alfa (Mepsevii)

- Life-threatening hypersensitivity (anaphylactic reaction) to the active substance or to any of the excipients listed in section 6.1

https://www.ema.europa.eu/en/documents/product-information/mepsevii-epar-product-information_en.pdf 28/06/2024

Vibegron (Obgemsa)

Amlodipine, vibegron [2] ---> SmPC of [2] of EMA

Co-administration of vibegron with metoprolol, a representative beta-blocker, or amlodipine, a representative vasodilator, did not result in a clinically meaningful decrease or increase in systolic blood pressure (SBP)

Apixaban, vibegron [2] ---> SmPC of [2] of EMA

The potential for interaction with P-gp by vibegron should be considered when combined with sensitive P-gp substrates with narrow therapeutic index e.g. dabigatran etexilate, apixaban or rivaroxaban.

Breast-feeding, vibegron [2] ---> SmPC of [2] of EMA

A risk to the newborns/infants cannot be excluded. Vibegron should not be used during breast-feeding.

Dabigatran etexilate, vibegron [2] ---> SmPC of [2] of EMA

The potential for interaction with P-gp by vibegron should be considered when combined with sensitive P-gp substrates with narrow therapeutic index e.g. dabigatran etexilate, apixaban or rivaroxaban.

Digoxin, vibegron [2] ---> SmPC of [2] of EMA

Serum digoxin concentrations should be monitored and used for titration of the digoxin dose to obtain the desired clinical effect.

Diltiazem, vibegron [2] ---> SmPC of [2] of EMA

Vibegron exposure (AUC) was increased 2.1-and 1.6-fold in the presence of the strong and moderate inhibitor of CYP3A/P-gp ketoconazole and diltiazem, respectively, in healthy volunteers. No dose-adjustment is needed when vibegron is combined

Fertility, vibegron [2] ---> SmPC of [2] of EMA

The effect of vibegron on human fertility has not been established. Studies in animals have not shown effects on female or male rat fertility (see section 5.3).

Ketoconazole, vibegron [2] ---> SmPC of [2] of EMA

Metoprolol, vibegron [2] ---> SmPC of [2] of EMA

Moderate CYP3A4 inhibitors, vibegron [2] ---> SmPC of [2] of EMA

P-glycoprotein substrates with small therapeutic index, vibegron [2] ---> SmPC of [2] of EMA

The potential for interaction with P-gp by vibegron should be considered when combined with sensitive P-gp substrates with narrow therapeutic index e.g. dabigatran etexilate, apixaban or rivaroxaban.

P-gp inductors, vibegron [2] ---> SmPC of [2] of EMA

Vibegron AUC was not affected by repeat-dose administration of rifampicin, a strong inducer of CYP3A/P-gp, in healthy volunteers, while vibegron Cmax was 86% higher. No dose adjustment is needed for vibegron when administered

P-gp inhibitors, vibegron [2] ---> SmPC of [2] of EMA

Pregnancy, vibegron [2] ---> SmPC of [2] of EMA

Vibegron is not recommended during pregnancy. When pregnancy is planned or diagnosed, treatment with vibegron should be stopped and, if appropriate, alternative therapy should be started.

Rifampicin, vibegron [2] ---> SmPC of [2] of EMA

Rivaroxaban, vibegron [2] ---> SmPC of [2] of EMA

The potential for interaction with P-gp by vibegron should be considered when combined with sensitive P-gp substrates with narrow therapeutic index e.g. dabigatran etexilate, apixaban or rivaroxaban.

Strong CYP3A4 inductors, vibegron [2] ---> SmPC of [2] of EMA

Strong CYP3A4 inhibitors, vibegron [2] ---> SmPC of [2] of EMA

Vibegron [1], women of childbearing potential ---> SmPC of [1] of EMA

Vibegron is not recommended in women of childbearing potential not using contraception.

CONTRAINDICATIONS of Vibegron (Obgemsa)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/obgemsa-epar-product-information_en.pdf 08/07/2025

Vigabatrin

Ability to drive, vigabatrin [2] ---> SmPC of [2] of eMC

Visual field defects which can significantly affect the ability to drive and use machines have been frequently reported

Betaine anhydrous [1], vigabatrin ---> SmPC of [1] of EMA

To minimise the risk of potential drug interactions, it is advisable to leave 30 minutes between the intake of betaine anhydrous and amino acids mixtures and/or medicinal products containing vigabatrin and GABA analogues

Breast-feeding, vigabatrin [2] ---> SmPC of [2] of eMC

Vigabatrin is excreted into breast milk. Breast feeding is not recommended during vigabatrin treatment.

Carbamazepine [1], vigabatrin ---> SmPC of [1] of eMC

The plasma concentrations of carbamazepine may be increased

Efavirenz [1], vigabatrin ---> SmPC of [1] of EMA

Clinically significant interactions are not expected since vigabatrin is exclusively eliminated unchanged in the urine

Efavirenz/emtricitabine/tenofovir disoproxil [1], vigabatrin ---> SmPC of [1] of EMA

Clinically significant interactions are not expected since vigabatrin is exclusively eliminated unchanged in the urine

Fosphenytoin, vigabatrin [2] ---> SmPC of [2] of eMC

During controlled clinical studies, a gradual reduction of 16-33% in the plasma concentration of phenytoin has been observed.

Phenytoin, vigabatrin [2] ---> SmPC of [2] of eMC

During controlled clinical studies, a gradual reduction of 16-33% in the plasma concentration of phenytoin has been observed.

Pregnancy, vigabatrin [2] ---> SmPC of [2] of eMC

Vigabatrin should only be used during pregnancy if clearly necessary.

Retinotoxic drugs, vigabatrin [2] ---> SmPC of [2] of eMC

Vigabatrin should not be used concomitantly with other retinotoxic drugs.

Rufinamide, vigabatrin

Possible decreased rufinamide plasma concentrations

CONTRAINDICATIONS of Vigabatrin

- Hypersensitivity to vigabatrin or to any excipient in the medicinal product.

http://www.medicines.org.uk/emc/

Vildagliptin (Galvus)

Ability to drive, vildagliptin [2] ---> SmPC of [2] of EMA

Patients who experience dizziness as an adverse reaction should avoid driving vehicles or using machines.

ACE inhibitors, vildagliptin [2] ---> SmPC of [2] of EMA

There may be an increased risk of angioedema in patients concomitantly taking ACE-inhibitors.

Amlodipine, vildagliptin [2] ---> SmPC of [2] of EMA

In these studies, no clinically relevant pharmacokinetic interactions were observed after co-administration with vildagliptin.

Breast-feeding, vildagliptin [2] ---> SmPC of [2] of EMA

It is unknown whether vildagliptin is excreted in human milk. Animal studies have shown excretion of vildagliptin in milk. Galvus should not be used during breast-feeding.

Corticosteroids, vildagliptin [2] ---> SmPC of [2] of EMA

As with other oral antidiabetic medicinal products the hypoglycaemic effect of vildagliptin may be reduced by certain active substances, including thiazides, corticosteroids, thyroid products and sympathomimetics.

Cytochrome P450, vildagliptin [2] ---> SmPC of [2] of EMA

Since vildagliptin is not a cytochrome P (CYP) 450 enzyme substrate and does not inhibit or induce CYP 450 enzymes, it is not likely to interact with active substances that are substrates, inhibitors or inducers of these enzymes.

Digoxin, vildagliptin [2] ---> SmPC of [2] of EMA

Clinical studies performed with healthy subjects have shown no clinically relevant pharmacokinetic interactions. However, this has not been established in the target population.

Fertility, vildagliptin [2] ---> SmPC of [2] of EMA

No studies on the effect on human fertility have been conducted for Galvus (see section 5.3).

Glyburide, vildagliptin [2] ---> SmPC of [2] of EMA

Results from studies conducted with this oral antidiabetic have shown no clinically relevant pharmacokinetic interactions.

Metformin, vildagliptin [2] ---> SmPC of [2] of EMA

Results from studies conducted with this oral antidiabetic have shown no clinically relevant pharmacokinetic interactions.

Pasireotide [1], vildagliptin ---> SmPC of [1] of EMA

Dose adjustments (decrease or increase) of insulin and antidiabetic medicinal products may be required when administered concomitantly with pasireotide

Perindopril [1], vildagliptin ---> SmPC of [1] of eMC

Increased risk of angio-oedema, due to dipeptidyl peptidase IV (DPP-IV) decreased activity by the gliptin, in patients co-treated with an ACE inhibitor.

Pioglitazone, vildagliptin [2] ---> SmPC of [2] of EMA

Results from studies conducted with this oral antidiabetic have shown no clinically relevant pharmacokinetic interactions.

Pregnancy, vildagliptin [2] ---> SmPC of [2] of EMA

Due to lack of human data, Galvus should not be used during pregnancy.

Quinapril, vildagliptin

The co-administration of ACE inhibitors and dipeptidyl peptidase-4 inhibitors may increase the risk of angioedema

Ramipril, vildagliptin [2] ---> SmPC of [2] of EMA

In these studies, no clinically relevant pharmacokinetic interactions were observed after co-administration with vildagliptin.

Simvastatine, vildagliptin [2] ---> SmPC of [2] of EMA

In these studies, no clinically relevant pharmacokinetic interactions were observed after co-administration with vildagliptin.

Sympathomimetics, vildagliptin [2] ---> SmPC of [2] of EMA

Thiazides, vildagliptin [2] ---> SmPC of [2] of EMA

Thyroid hormones, vildagliptin [2] ---> SmPC of [2] of EMA

Valsartan, vildagliptin [2] ---> SmPC of [2] of EMA

In these studies, no clinically relevant pharmacokinetic interactions were observed after co-administration with vildagliptin.

Vildagliptin [1], warfarin ---> SmPC of [1] of EMA

Clinical studies performed with healthy subjects have shown no clinically relevant pharmacokinetic interactions. However, this has not been established in the target population.

CONTRAINDICATIONS of Vildagliptin (Galvus)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/galvus-epar-product-information_en.pdf 29/01/2025

Other trade names: Jalra, Xiliarx,

Vildagliptin/metformin (Icandra)

Ability to drive, vildagliptin/metformin [2] ---> SmPC of [2] of EMA

Patients who may experience dizziness as an adverse reaction should avoid driving vehicles or using machines.

ACE inhibitors, metformin ---> SmPC of [vildagliptin/metformin] of EMA

ACE-inhibitors may decrease the blood glucose levels.

ACE inhibitors, vildagliptin/metformin [2] ---> SmPC of [2] of EMA

ACE-inhibitors may decrease the blood glucose levels. There may be an increased risk of angioedema in patients concomitantly taking ACE-inhibitors.

Alcohol, vildagliptin/metformin [2] ---> SmPC of [2] of EMA

There is increased risk of lactic acidosis in acute alcohol intoxication due to the metformin active substance. Consumption of alcohol and medicinal products containing alcohol should be avoided.

Amlodipine, vildagliptin ---> SmPC of [vildagliptin/metformin] of EMA

Amlodipine, vildagliptin/metformin [2] ---> SmPC of [2] of EMA

Beta2-adrenergic agonists, vildagliptin/metformin [2] ---> SmPC of [2] of EMA

Beta-2 agonists have intrinsic hyperglycaemic activity. Should be more frequent blood glucose monitoring performed

Breast-feeding, vildagliptin/metformin [2] ---> SmPC of [2] of EMA

Icandra should not be used during breast-feeding

Cationic substances eliminated by renal tubular secretion, vildagliptin/metformin [2] ---> SmPC of [2] of EMA

Cationic active substances that are eliminated by renal tubular secretion may interact with metformin by competing for common renal tubular transport systems and hence delay the elimination of metformin

Cimetidine, metformin ---> SmPC of [vildagliptin/metformin] of EMA

Cimetidine, vildagliptin/metformin [2] ---> SmPC of [2] of EMA

Corticosteroids, vildagliptin/metformin [2] ---> SmPC of [2] of EMA

Coxibs, vildagliptin/metformin [2] ---> SmPC of [2] of EMA

Some medicinal products can adversely affect renal function which may increase the risk of lactic acidosis. Close monitoring of renal function is necessary.

CYP450, vildagliptin ---> SmPC of [vildagliptin/metformin] of EMA

CYP450, vildagliptin/metformin [2] ---> SmPC of [2] of EMA

Digoxin, vildagliptin ---> SmPC of [vildagliptin/metformin] of EMA

Drug-drug interaction studies with digoxin (P-glycoprotein substrate) and warfarin (CYP2C9 substrate) in healthy subjects have shown no clinically relevant pharmacokinetic interactions after coadministration with vildagliptin.

Digoxin, vildagliptin/metformin [2] ---> SmPC of [2] of EMA

Diuretics, vildagliptin/metformin [2] ---> SmPC of [2] of EMA

Diuretics may increase the risk of lactic acidosis due to their potential to decrease renal function. Diuretics have also hyperglycemic effect.

Dolutegravir, vildagliptin/metformin [2] ---> SmPC of [2] of EMA

Concomitant use of medicinal products that interfere with common renal tubular transport systems involved in the renal elimination of metformin could increase systemic exposure to metformin.

Fertility, vildagliptin/metformin [2] ---> SmPC of [2] of EMA

No studies on the effect on human fertility have been conducted for Icandra (see section 5.3).

Foods, vildagliptin/metformin [2] ---> SmPC of [2] of EMA

Administration of vildagliptin with food resulted in a decreased Cmax (19%) compared to dosing in the fasting state.

Glucocorticoids, vildagliptin/metformin [2] ---> SmPC of [2] of EMA

Glucocorticoids have intrinsic hyperglycaemic activity. Should be more frequent blood glucose monitoring performed

Glyburide, vildagliptin/metformin [2] ---> SmPC of [2] of EMA

Results from clinical trials conducted with the oral antidiabetics pioglitazone, metformin and glyburide in combination with vildagliptin have shown no clinically relevant pharmacokinetic interactions in the target population.

Iodinated contrast media, vildagliptin/metformin [2] ---> SmPC of [2] of EMA

Metformin must be discontinued prior to or at the time of the imaging procedure and not restarted until at least 48 hours after, provided that renal function has been re-evaluated and found to be stable (see sections 4.2 and 4.4).

Metformin, vildagliptin/metformin [2] ---> SmPC of [2] of EMA

NSAID, vildagliptin/metformin [2] ---> SmPC of [2] of EMA

Some medicinal products can adversely affect renal function which may increase the risk of lactic acidosis. Close monitoring of renal function is necessary.

Pioglitazone, vildagliptin/metformin [2] ---> SmPC of [2] of EMA

Pregnancy, vildagliptin/metformin [2] ---> SmPC of [2] of EMA

Icandra should not be used during pregnancy.

Ramipril, vildagliptin ---> SmPC of [vildagliptin/metformin] of EMA

Ramipril, vildagliptin/metformin [2] ---> SmPC of [2] of EMA

Ranolazine, vildagliptin/metformin [2] ---> SmPC of [2] of EMA

Concomitant use of medicinal products that interfere with common renal tubular transport systems involved in the renal elimination of metformin could increase systemic exposure to metformin.

Simvastatine, vildagliptin ---> SmPC of [vildagliptin/metformin] of EMA

Simvastatine, vildagliptin/metformin [2] ---> SmPC of [2] of EMA

Sympathomimetics, vildagliptin/metformin [2] ---> SmPC of [2] of EMA

Thiazides, vildagliptin/metformin [2] ---> SmPC of [2] of EMA

Thyroid hormones, vildagliptin/metformin [2] ---> SmPC of [2] of EMA

Tubular secretion, vildagliptin/metformin [2] ---> SmPC of [2] of EMA

The co-administration may increase the serum levels of either one and/or both principle actives due to competition for the active tubular secretion.

Valsartan, vildagliptin ---> SmPC of [vildagliptin/metformin] of EMA

Valsartan, vildagliptin/metformin [2] ---> SmPC of [2] of EMA

Vandetanib, vildagliptin/metformin [2] ---> SmPC of [2] of EMA

Concomitant use of medicinal products that interfere with common renal tubular transport systems involved in the renal elimination of metformin could increase systemic exposure to metformin.

Vildagliptin, warfarin ---> SmPC of [vildagliptin/metformin] of EMA

Vildagliptin/metformin [1], warfarin ---> SmPC of [1] of EMA

CONTRAINDICATIONS of Vildagliptin/metformin (Icandra)

- Hypersensitivity to the active substances or to any of the excipients listed in section 6.1.

- Any type of acute metabolic acidosis (such as lactic acidosis, diabetic ketoacidosis)

- Diabetic pre-coma

- Severe renal failure (GFR < 30 ml/min) (see section 4.4)

- Acute conditions with the potential to alter renal function, such as:

-dehydration,

-severe infection,

-shock,

-intravascular administration of iodinated contrast agents (see section 4.4).

- Acute or chronic disease which may cause tissue hypoxia, such as:

-cardiac or respiratory failure,

-recent myocardial infarction,

-shock.

- Hepatic impairment (see sections 4.2, 4.4 and 4.8)

- Acute alcohol intoxication, alcoholism

- Breast-feeding (see section 4.6)

https://www.ema.europa.eu/en/documents/product-information/icandra-epar-product-information_en.pdf. 08/01/2024

Other trade names: Eucreas, Icandra (previously Vildagliptin / metformin hydrochloride Novartis), Zomarist,

Vilobelimab (Gohibic)

Breast-feeding, vilobelimab [2] ---> SmPC of [2] of EMA

Consequently, a risk to the breast-fed infant cannot be excluded during this short period. Afterwards, vilobelimab could be used during breast-feeding if clinically needed.

Cytochrome P450, vilobelimab [2] ---> SmPC of [2] of EMA

Therefore, interactions with concomitant medicinal products that are renally excreted or that are substrates, inducers, or inhibitors of cytochrome P450 enzymes are unlikely.

Fertility, vilobelimab [2] ---> SmPC of [2] of EMA

Non-clinical data do not suggest any effect on male or female fertility under treatment with vilobelimab (see section 5.3).

Infection, vilobelimab [2] ---> SmPC of [2] of EMA

A patient who develops a new infection during treatment with vilobelimab should undergo diagnostic investigations. Appropriate treatment should be initiated and the patient should be closely monitored.

Pregnancy, vilobelimab [2] ---> SmPC of [2] of EMA

CONTRAINDICATIONS of Vilobelimab (Gohibic)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/gohibic-epar-product-information_en.pdf 17/03/2026

Vimseltinib (Romvimza)

Ability to drive, vimseltinib [2] ---> SmPC of [2] of EMA

ROMVIMZA has minor influence on the ability to drive and use machines. Fatigue or blurred vision may occur following administration of ROMVIMZA (see section 4.8).

BCRP inhibitors, vimseltinib [2] ---> SmPC of [2] of EMA

Concomitant use of vimseltinib with BCRP substrates (e.g. rosuvastatin) may increase the levels of BCRP substrates and increase the risk of adverse reactions related to these substrates. Clinical studies with BCRP substrates have not been conducted.

Bilirubin, vimseltinib [2] ---> SmPC of [2] of EMA

Thus, ROMVIMZA treatment should be avoided in patients with pre-existing serum transaminase elevations, total bilirubin or direct bilirubin elevations, or active liver or biliary tract disease.

Breast-feeding, vimseltinib [2] ---> SmPC of [2] of EMA

It is unknown whether vimseltinib is excreted in human milk. A risk to the breast-fed child cannot be excluded. Women should not breast-feed during treatment with vimseltinib.

Creatinine, vimseltinib [2] ---> SmPC of [2] of EMA

Treatment with ROMVIMZA in clinical studies was frequently associated with an increase in creatinine. The underlying reason is currently unknown.

Dabigatran, vimseltinib [2] ---> SmPC of [2] of EMA

Vimseltinib is an inhibitor of P-gp in vitro. Concomitant use of vimseltinib with P-gp substrates (e.g. digoxin, dabigatran) may increase the concentrations of P-gp substrates and increase the risk of adverse reactions related to these substrates.

Digoxin, vimseltinib [2] ---> SmPC of [2] of EMA

Fertility, vimseltinib [2] ---> SmPC of [2] of EMA

Based on findings from animal studies, ROMVIMZA may impair fertility in males (see section 5.3).

Hepatic function, vimseltinib [2] ---> SmPC of [2] of EMA

Patients should be monitored for liver function prior to the start of ROMVIMZA, once a month for the first two months and once every 3 months for the first year of therapy and as clinically indicated thereafter.

Hormonal contraceptives, vimseltinib [2] ---> SmPC of [2] of EMA

It is unknown whether vimseltinib may reduce the effectiveness of systemically acting hormonal contraceptives, and therefore women using systemically acting hormonal contraceptives should add a barrier method.

Hypertensive drugs, vimseltinib [2] ---> SmPC of [2] of EMA

Treatment with ROMVIMZA in clinical studies was frequently associated with an increase in blood pressure.

Itraconazol, vimseltinib [2] ---> SmPC of [2] of EMA

Dose adjustment is not required.

Metformin, vimseltinib [2] ---> SmPC of [2] of EMA

Concomitant use of vimseltinib with OCT2 substrates (e.g. metformin) may increase the concentrations of OCT2 substrates and increase the risk of adverse reactions related to these substrates. Clinical studies with OCT2 substrates have not been conducted.

OCT2 substrates, vimseltinib [2] ---> SmPC of [2] of EMA

P-glycoprotein substrates, vimseltinib [2] ---> SmPC of [2] of EMA

P-gp inhibitors, vimseltinib [2] ---> SmPC of [2] of EMA

Dose adjustment is not required.

Pregnancy, vimseltinib [2] ---> SmPC of [2] of EMA

Studies in animals have shown reproductive toxicity (foetal structural abnormalities and cardiac malformations, see section 5.3). Vimseltinib is contraindicated in pregnant women (see section 4.3).

Pregnant women, vimseltinib [2] ---> SmPC of [2] of EMA

Women should be advised to avoid pregnancy while taking vimseltinib. Pregnant women should be informed of the potential risk to the foetus.

Proton pump inhibitors, vimseltinib [2] ---> SmPC of [2] of EMA

Dose adjustment is not required.

Pruritus, vimseltinib [2] ---> SmPC of [2] of EMA

Pruritus has been reported in patients receiving vimseltinib. In the pooled safety population, pruritus was reported in 27% of patients (see section 4.8). Pruritus has also been reported after single doses of vimseltinib in healthy participants.

Rabeprazole, vimseltinib [2] ---> SmPC of [2] of EMA

Dose adjustment is not required.

Rosuvastatin, vimseltinib [2] ---> SmPC of [2] of EMA

Vimseltinib [1], women of childbearing potential ---> SmPC of [1] of EMA

Women of childbearing potential must use effective contraception during treatment with vimseltinib and for 30 days after the final dose.

CONTRAINDICATIONS of Vimseltinib (Romvimza)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Pregnancy (see sections 4.4 and 4.6).

https://www.ema.europa.eu/en/documents/product-information/romvimza-epar-product-information_en.pdf 22/09/2025

Vinblastine

Abacavir/lamivudine/zidovudine [1], vinblastine ---> SmPC of [1] of EMA

Concomitant treatment, especially acute therapy, with potentially nephrotoxic or myelosuppressive medicinal products may increase the risk of adverse reactions to zidovudine

Ability to drive, vinblastine [2] ---> SmPC of [2] of eMC

None known.

Aldesleukin [1], vinblastine ---> SmPC of [1] of eMC

Fatal tumour lysis syndrome has been reported in combination of aldesleukin with treatment with cis-platinum, vinblastine and dacarbazine. Concomitant use of the mentioned active substances is therefore not recommended.

Anticoagulants, vinblastine

Patients treated with anticoagulant and antineoplastic agents should be monitored more frequently

Antiepileptics, vinblastine

Vinblastine may decrease the plasma levels of anticonvulsant

Atazanavir/cobicistat [1], vinblastine ---> SmPC of [1] of EMA

Concentrations of the antineoplastic may be increased when coadministered with EVOTAZ resulting in the potential for increased adverse events. The mechanism of interaction is CYP3A4 inhibition by cobicistat.

Bexarotene [1], vinblastine ---> SmPC of [1] of EMA

Caution is advised in case of combination of bexarotene with CYP3A4-metabolised cytotoxics

Breast-feeding, vinblastine [2] ---> SmPC of [2] of eMC

A decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the mother.

Carmustine, vinblastine

The co-administration of carmustine with other myelosuppressive agents may increase the myelotoxicity (thrombopenia and leucopenia)

Cisplatin, vinblastine

The co-administration may increase the plasma levels of vinblastine and the neurotoxicity of cisplatin

Cobicistat [1], vinblastine ---> SmPC of [1] of EMA

Concentrations of vinblastine may be increased when co-administered with cobicistat resulting in the potential for increased adverse events usually associated with this anticancer medicinal product.

Cyclosporine, vinblastine

The co-administration may cause an excessive immunosuppression with risk of lymphoproliferation

Cytostatics, vinblastine

Enhancement of therapeutic and toxic effects

Darunavir/cobicistat [1], vinblastine ---> SmPC of [1] of EMA

Based on theoretical considerations darunavir/cobicistat (CYP3A inhibition) is expected to increase the anti-neoplastic plasma concentrations.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], vinblastine ---> SmPC of [1] of EMA

Based on theoretical considerations DRV/COBI is expected to increase these anti-neoplastic plasma concentrations. CYP3A inhibition

Darunavir/ritonavir, vinblastine ---> SmPC of [darunavir] of EMA

Boosted darunavir is expected to increase the antineoplastic plasma concentrations. (CYP3A inhibition)

Digitoxin, vinblastine

The co-administration may decrease the plasma levels and effect of digitoxin

Erythromycin [1], vinblastine ---> SmPC of [1] of eMC

The co-administration of drugs metabolised by the cytochrome P450 system may be associated with elevated serum levels if administered concomitantly with erythromycin.

Fluconazole [1], vinblastine ---> SmPC of [1] of eMC

Fluconazole may increase the plasma levels of the vinca alkaloids and lead to neurotoxicity, which is possibly due to an inhibitory effect on CYP3A4.

Ganciclovir [1], vinblastine ---> SmPC of [1] of eMC

Toxicity may be enhanced when valganciclovir is co-administered with, or is given immediately before or after, other drugs that inhibit replication of rapidly dividing cell populations

Idelalisib [1], vinblastine ---> SmPC of [1] of EMA

The co-administration of idelalisib with vinblastine may increase the serum concentrations of vinblastine. Careful monitoring of the tolerance to these anti-cancer agents is recommended.

Immunosuppressives, vinblastine

Enhancement of therapeutic and toxic effects

Interferon, vinblastine

Vinblastine may increase the neurotoxicity and cardiotoxicity of interferon

Isavuconazole [1], vinblastine ---> SmPC of [1] of EMA

No CRESEMBA dose adjustment necessary. Vinca alkaloids: careful monitoring for any occurrence of drug toxicity, and dose reduction if required.

Ketoconazole [1], vinblastine ---> SmPC of [1] of EMA

Potential increase in plasma concentrations of vinca alkaloid. Careful monitoring as it may cause an earlier onset and/or an increased severity of side-effects.

Lamivudine/zidovudine [1], vinblastine ---> SmPC of [1] of EMA

Concomitant treatment, especially acute therapy, with potentially nephrotoxic or myelosuppressive medicinal products may increase the risk of adverse reactions to zidovudine.

Lopinavir/ritonavir [1], vinblastine ---> SmPC of [1] of EMA

Most tyrosine kinase inhibitors such as dasatinib and nilotinib, also vincristine and vinblastine: Risk of increased adverse events due to higher serum concentrations because of CYP3A4 inhibition by Kaletra.

Medicines with myelotoxic effects, vinblastine

The co-administration may increase the risk of toxicity

Mytomicin [1], vinblastine ---> SmPC of [1] of eMC

Acute shortness of breath and severe bronchospasm have been reported following the administration of the vinca alkaloids in combination with mitomycin-C

Neurotoxic substances, vinblastine

The co-administration may increase the risk of toxicity

Phenytoin, vinblastine [2] ---> SmPC of [2] of eMC

The simultaneous oral or i.v. administration of phenytoin and anti-neoplastic chemotherapy combinations, that included vinblastine sulphate, have been reported to reduce blood levels of the anticonvulsant and to increase seizure activity.

Posaconazole [1], vinblastine ---> SmPC of [1] of EMA

Posaconazole may increase the plasma concentration of vinca, which may lead to neurotoxicity. The co-administration should be avoided

Pregnancy, vinblastine [2] ---> SmPC of [2] of eMC

Information on the use of vinblastine during human pregnancy is very limited but vinblastine can cause foetal harm when administered to a pregnant woman.

Primidone, vinblastine

The co-administration may decrease the plasma levels of primidone

Radiotherapy, vinblastine

Radiotherapy may increase the risk of toxicity

Ritonavir [1], vinblastine ---> SmPC of [1] of EMA

Serum concentrations of vinblastine may be increased when co-administered with ritonavir resulting in the potential for increased incidence of adverse events.

Strong CYP3A4 inhibitors, vinblastine [2] ---> SmPC of [2] of eMC

Concurrent administration of vinblastine sulphate with an inhibitor of CYP 3A subfamily may cause an earlier onset and/or an increased severity of side-effects.

Strong P-gp inhibitors, vinblastine

The strong inhibition of P-glycoprotein may increase the exposure to vinblastine

Tacrolimus, vinblastine

The co-administration may cause an excessive immunosuppression with risk of lymphoproliferation

Tolterodine, vinblastine

The co-administration may increase the plasma concentrations of tolterodine

Vaccinations with live organism vaccines, vinblastine

The co-administration may decrease the antibody production and increase the risk of systemic vaccinal disease. The combination is not recommended

Valganciclovir [1], vinblastine ---> SmPC of [1] of eMC

Toxicity may be enhanced when valganciclovir is co-administered with, or is given immediately before or after, other drugs that inhibit replication of rapidly dividing cell populations

Vinblastine, voriconazole [2] ---> SmPC of [2] of EMA

Voriconazole is likely to increase the plasma concentrations of vinca alkaloids and lead to neurotoxicity.

Vinblastine, zidovudine ---> SmPC of [lamivudine/zidovudine] of EMA

Concomitant treatment, especially acute therapy, with potentially nephrotoxic or myelosuppressive medicinal products may increase the risk of adverse reactions to zidovudine.

CONTRAINDICATIONS of Vinblastine

FATAL IF GIVEN BY OTHER ROUTES. FOR INTRAVENOUS USE ONLY.

In case of mistaken administration by intrathecal route, see section 4.4.

- Vinblastine is contra-indicated in patients who are leucopenic, unless this is the result of the disease being treated. It should not be used in the presence of bacterial infection. Such infections must be brought under control with antiseptics or antibiotics before using vinblastine.

http://www.medicines.org.uk/emc/

Vimseltinib (Romvimza)

Ability to drive, vimseltinib [2] ---> SmPC of [2] of EMA

ROMVIMZA has minor influence on the ability to drive and use machines. Fatigue or blurred vision may occur following administration of ROMVIMZA (see section 4.8).

BCRP inhibitors, vimseltinib [2] ---> SmPC of [2] of EMA

Bilirubin, vimseltinib [2] ---> SmPC of [2] of EMA

Thus, ROMVIMZA treatment should be avoided in patients with pre-existing serum transaminase elevations, total bilirubin or direct bilirubin elevations, or active liver or biliary tract disease.

Breast-feeding, vimseltinib [2] ---> SmPC of [2] of EMA

It is unknown whether vimseltinib is excreted in human milk. A risk to the breast-fed child cannot be excluded. Women should not breast-feed during treatment with vimseltinib.

Creatinine, vimseltinib [2] ---> SmPC of [2] of EMA

Treatment with ROMVIMZA in clinical studies was frequently associated with an increase in creatinine. The underlying reason is currently unknown.

Dabigatran, vimseltinib [2] ---> SmPC of [2] of EMA

Digoxin, vimseltinib [2] ---> SmPC of [2] of EMA

Fertility, vimseltinib [2] ---> SmPC of [2] of EMA

Based on findings from animal studies, ROMVIMZA may impair fertility in males (see section 5.3).

Hepatic function, vimseltinib [2] ---> SmPC of [2] of EMA

Hormonal contraceptives, vimseltinib [2] ---> SmPC of [2] of EMA

Hypertensive drugs, vimseltinib [2] ---> SmPC of [2] of EMA

Treatment with ROMVIMZA in clinical studies was frequently associated with an increase in blood pressure.

Itraconazol, vimseltinib [2] ---> SmPC of [2] of EMA

Dose adjustment is not required.

Metformin, vimseltinib [2] ---> SmPC of [2] of EMA

OCT2 substrates, vimseltinib [2] ---> SmPC of [2] of EMA

P-glycoprotein substrates, vimseltinib [2] ---> SmPC of [2] of EMA

P-gp inhibitors, vimseltinib [2] ---> SmPC of [2] of EMA

Dose adjustment is not required.

Pregnancy, vimseltinib [2] ---> SmPC of [2] of EMA

Studies in animals have shown reproductive toxicity (foetal structural abnormalities and cardiac malformations, see section 5.3). Vimseltinib is contraindicated in pregnant women (see section 4.3).

Pregnant women, vimseltinib [2] ---> SmPC of [2] of EMA

Women should be advised to avoid pregnancy while taking vimseltinib. Pregnant women should be informed of the potential risk to the foetus.

Proton pump inhibitors, vimseltinib [2] ---> SmPC of [2] of EMA

Dose adjustment is not required.

Pruritus, vimseltinib [2] ---> SmPC of [2] of EMA

Rabeprazole, vimseltinib [2] ---> SmPC of [2] of EMA

Dose adjustment is not required.

Rosuvastatin, vimseltinib [2] ---> SmPC of [2] of EMA

Vimseltinib [1], women of childbearing potential ---> SmPC of [1] of EMA

Women of childbearing potential must use effective contraception during treatment with vimseltinib and for 30 days after the final dose.

CONTRAINDICATIONS of Vimseltinib (Romvimza)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Pregnancy (see sections 4.4 and 4.6).

https://www.ema.europa.eu/en/documents/product-information/romvimza-epar-product-information_en.pdf 22/09/2025

Vincristine

Abacavir/lamivudine/zidovudine [1], vincristine ---> SmPC of [1] of EMA

Concomitant treatment, especially acute therapy, with potentially nephrotoxic or myelosuppressive medicinal products may increase the risk of adverse reactions to zidovudine

Ability to drive, vincristine [2] ---> SmPC of [2] of eMC

Not known.

Anticoagulants, vincristine

Patients treated with anticoagulant and antineoplastic agents should be monitored more frequently

Asparaginase [1], vincristine ---> SmPC of [1] of EMA

The toxicity of vincristine may be additive with that of asparaginase if both agents are administered concomitantly. Therefore, vincristine should be given 3 to 24 hours before administration of asparaginase in order to minimise toxicity.

Atazanavir/cobicistat [1], vincristine ---> SmPC of [1] of EMA

Atenolol/nifedipine, vincristine

The co-administration may decrease the plasma clearance of vincristine and increase the toxicity risk

Bexarotene [1], vincristine ---> SmPC of [1] of EMA

Caution is advised in case of combination of bexarotene with CYP3A4-metabolised cytotoxics

Bleomycin, vincristine

In the combination with bleomycin, vincristine may cause dose-dependent a Raynaud syndrome

Breast-feeding, vincristine [2] ---> SmPC of [2] of eMC

Because of the potential for serious adverse reactions due to vincristine in nursing infants, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the mother.

Bromelain, vincristine

Bromelain may enhance the actions of vincristine

Calcium antagonists, vincristine

The co-administration may decrease the plasma clearance of vincristine and increase the toxicity risk

Cobicistat [1], vincristine ---> SmPC of [1] of EMA

Concentrations of vincristine may be increased when co-administered with cobicistat resulting in the potential for increased adverse events usually associated with this anticancer medicinal product.

Colaspase, vincristine

The just before or concomitant treatment with vincristine increases the risk of anaphylactic reactions

Colony stimulating factors, vincristine

The co-administration may cause atypical neuropathies

Cyclosporine, vincristine

The co-administration of vincristine and ciclosporin A may cause neurotoxicity

CYP3A4 and P-glycoprotein-inhibitors, vincristine [2] ---> SmPC of [2] of eMC

The metabolism of vinca alkaloids has been shown to be mediated by hepatic cytochrome P450 isoenzymes in the CYP3A subfamily. This metabolic pathway may be impaired in patients who are taking concomitant potent inhibitors of these isoenzymes

Cytostatics, vincristine

Pharmacodynamic interactions may occur with other cytostatic drugs: Potentiation of therapeutic and toxic effect

Dactinomycin, vincristine

The co-administration may cause severe liver toxicity

Darunavir/cobicistat [1], vincristine ---> SmPC of [1] of EMA

Based on theoretical considerations darunavir/cobicistat (CYP3A inhibition) is expected to increase the anti-neoplastic plasma concentrations.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], vincristine ---> SmPC of [1] of EMA

Based on theoretical considerations DRV/COBI is expected to increase these anti-neoplastic plasma concentrations. CYP3A inhibition

Darunavir/ritonavir, vincristine ---> SmPC of [darunavir] of EMA

Boosted darunavir is expected to increase the antineoplastic plasma concentrations. (CYP3A inhibition)

Digoxin, vincristine

The co-administration may decrease the absorption of digoxin

Doxorubicine, vincristine

Concomitant use of vincristine and other myelosuppressive drugs (e. g. doxorubicine, particularly in combination with prednisone) may enhance the suppressive effects on bone marrow

Erythromycin, vincristine [2] ---> SmPC of [2] of eMC

Fluconazole [1], vincristine ---> SmPC of [1] of eMC

Fluconazole may increase the plasma levels of the vinca alkaloids and lead to neurotoxicity, which is possibly due to an inhibitory effect on CYP3A4.

Fluorouracil, vincristine

The co-administration may increase the efficacy and toxicity of fluorouracil

Ganciclovir [1], vincristine ---> SmPC of [1] of eMC

Toxicity may be enhanced when valganciclovir is co-administered with, or is given immediately before or after, other drugs that inhibit replication of rapidly dividing cell populations

Idelalisib [1], vincristine ---> SmPC of [1] of EMA

The co-administration of idelalisib with vincristine may increase the serum concentrations of vincristine. Careful monitoring of the tolerance to these anti-cancer agents is recommended.

Isavuconazole [1], vincristine ---> SmPC of [1] of EMA

No CRESEMBA dose adjustment necessary. Vinca alkaloids: careful monitoring for any occurrence of drug toxicity, and dose reduction if required.

Isoniazid, vincristine

The co-administration of vincristine and neurotoxic drugs may cause severe and long-lasting peripheral neuropathy

Itraconazol, vincristine [2] ---> SmPC of [2] of eMC

Co-administration of vincristine and itraconazole has been reported to cause an earlier onset and/or an increased severity of neuromuscular side-effects. It is presumed to be related to inhibition of the metabolism of vincristine.

Ketoconazole [1], vincristine ---> SmPC of [1] of EMA

Potential increase in plasma concentrations of vinca alkaloid. Careful monitoring as it may cause an earlier onset and/or an increased severity of side-effects.

Ketoconazole, vinca alkaloids ---> SmPC of [vincristine] of eMC

Lamivudine/zidovudine [1], vincristine ---> SmPC of [1] of EMA

Concomitant treatment, especially acute therapy, with potentially nephrotoxic or myelosuppressive medicinal products may increase the risk of adverse reactions to zidovudine.

Lopinavir/ritonavir [1], vincristine ---> SmPC of [1] of EMA

Myelosuppressive agents, vincristine

Concomitant use of vincristine and other myelosuppressive drugs (e. g. doxorubicine, particularly in combination with prednisone) may enhance the suppressive effects on bone marrow

Mytomicin, vincristine [2] ---> SmPC of [2] of eMC

Acute shortness of breath and severe bronchospasm have been reported following the administration of vinca alkaloids.

Nefazodone, vincristine [2] ---> SmPC of [2] of eMC

Nelfinavir, vincristine [2] ---> SmPC of [2] of eMC

Neurotoxic substances, vincristine

The co-administration of vincristine and neurotoxic drugs may cause severe and long-lasting peripheral neuropathy

Nifedipine, vincristine [2] ---> SmPC of [2] of eMC

Caution should be exercised in patients concurrently taking drugs known to inhibit drug metabolism by hepatic cytochrome P450 isoenzymes in the CYP 3A subfamily

Pegaspargase [1], vincristine ---> SmPC of [1] of EMA

Immediately preceding or simultaneous treatment with vincristine can increase the toxicity of Oncaspar and increases the risk of anaphylactic reactions.

Phenytoin, vincristine [2] ---> SmPC of [2] of eMC

The simultaneous oral or intravenous administration of phenytoin and anti-neoplastic chemotherapy combinations, that included vincristine, have been reported to reduce anticonvulsant blood levels and to increase seizure activity.

Posaconazole [1], vincristine ---> SmPC of [1] of EMA

Posaconazole may increase the plasma concentration of vinca, which may lead to neurotoxicity. The co-administration should be avoided

Pregnancy, vincristine [2] ---> SmPC of [2] of eMC

Caution is necessary with the use of all oncolytic drugs during pregnancy.

Proteolytic enzymes enriched in bromelain [1], vincristine ---> SmPC of [1] of EMA

Bromelain may enhance the actions of vincristine

Radiotherapy, vincristine [2] ---> SmPC of [2] of eMC

When chemotherapy is being given in conjunction with radiation therapy through portals which include the liver, the use of vincristine should be delayed until radiation therapy has been completed.

Ritonavir [1], vincristine ---> SmPC of [1] of EMA

Serum concentrations of vincristine may be increased when co-administered with ritonavir resulting in the potential for increased incidence of adverse events.

Strong CYP3A4 inductors, vincristine

The CYP3A4 induction may decrease plasma concentrations of vincristine

Strong CYP3A4 inhibitors, vincristine [2] ---> SmPC of [2] of eMC

Strong P-gp inhibitors, vincristine [2] ---> SmPC of [2] of eMC

Tacrolimus, vincristine

The co-administration may cause an excessive immunosuppression with risk of lymphoproliferation

Temsirolimus [1], vincristine ---> SmPC of [1] of EMA

When temsirolimus is co-administered with medicinal products which are P-gp substrates close monitoring for adverse events related to the co-administered medicinal products should be observed.

Thalidomide [1], vincristine ---> SmPC of [1] of EMA

Medicinal products known to be associated with peripheral neuropathy should be used with caution in patients receiving thalidomide

Vaccinations with live organism vaccines, vincristine

The co-administration may decrease the antibody production and increase the risk of systemic vaccinal disease. The combination is not recommended

Vaccinations, vincristine

Treatment with vincristine may cause immune system suppression. The antibody formation may be reduced as vaccine reaction

Valganciclovir [1], vincristine ---> SmPC of [1] of eMC

Toxicity may be enhanced when valganciclovir is co-administered with, or is given immediately before or after, other drugs that inhibit replication of rapidly dividing cell populations

Vincristine, voriconazole [2] ---> SmPC of [2] of EMA

Voriconazole is likely to increase the plasma concentrations of vinca alkaloids and lead to neurotoxicity.

Vincristine, zidovudine ---> SmPC of [lamivudine/zidovudine] of EMA

Concomitant treatment, especially acute therapy, with potentially nephrotoxic or myelosuppressive medicinal products may increase the risk of adverse reactions to zidovudine.

CONTRAINDICATIONS of Vincristine

FOR INTRAVENOUS USE ONLY. FATAL IF GIVEN BY OTHER ROUTES.

See 'Special warnings and precautions for use' section for the treatment of patients given intrathecal Vincristine

Patients with the demyelinating form of Charcot-Marie-Tooth syndrome should not be given vincristine.

http://www.medicines.org.uk/emc/

Vindesine

Ability to drive, vindesine

CNS-related adverse events.

Anticoagulants, vindesine

Increased bleeding risk. More frequent controls of INR are recommended

Asparaginase, vindesine

The co-administration may decrease the hepatic clearance of vindesine and cause accumulative toxicity

Bexarotene [1], vindesine ---> SmPC of [1] of EMA

Caution is advised in case of combination of bexarotene with CYP3A4-metabolised cytotoxics

Breast-feeding, vindesine

Vindesine is contraindicated during breast-feeding

CYP3A4 inhibitors, vindesine

Concurrent administration of vindesine with an inhibitor of CYP 3A subfamily may cause an earlier onset and/or an increased severity of side-effects.

Interferon alfa, vindesine

The co-administration may cause severe myelosuppression

Mytomicin [1], vindesine ---> SmPC of [1] of eMC

Acute shortness of breath and severe bronchospasm have been reported following the administration of the vinca alkaloids in combination with mitomycin-C

Neurotoxic substances, vindesine

It is recommended caution when administering vindesine und medicinal products with potential neurotoxic

Ototoxic agents, vindesine

The co-administration may cause damage of the eighth cranial nerve, equilibrium organ and organ of hearing. Special caution is recommended

Phenytoin, vindesine

The simultaneous oral or i.v. administration of phenytoin and anti-neoplastic chemotherapy combinations, that included vindesine, have been reported to reduce blood levels of the anticonvulsant and to increase seizure activity.

Platinum compounds, vindesine

The co-administration may cause damage of the eighth cranial nerve, equilibrium organ and organ of hearing. Special caution is recommended

Pregnancy, vindesine

Vindesine is contraindicated during pregnancy

Radiotherapy, vindesine

Radiotherapy may increase the adverse effects on the bone marrow function and nervous system

Strong CYP3A4 inhibitors, vindesine

Concurrent administration of vindesine with an inhibitor of CYP 3A subfamily may cause an earlier onset and/or an increased severity of side-effects.

Thioguanine, vindesine

The co-administration may enhance the haematopoietic disorders y neutropenia. Special caution is recommended

Tiopronin, vindesine

Blood count alterations

Vaccinations with live organism vaccines, vindesine

The co-administration may decrease the antibody production and increase the risk of systemic vaccinal disease. The combination is not recommended

Vaccinations, vindesine

The immunization during the treatment with vindesine can be ineffective

Vinflunine (Javlor)

Ability to drive, vinflunine [2] ---> SmPC of [2] of EMA

Javlor may cause adverse reactions such as fatigue (very common) and dizziness (common) which may lead to a minor or moderate influence on the ability to drive and use machines.

Bexarotene [1], vinflunine ---> SmPC of [1] of EMA

Caution is advised in case of combination of bexarotene with CYP3A4-metabolised cytotoxics

Breast-feeding, vinflunine [2] ---> SmPC of [2] of EMA

It is unknown whether vinflunine or its metabolites are excreted in human milk. Due to the possible very harmful effects on the infants, breast-feeding during treatment with vinflunine is contraindicated (see section 4.3).

Capecitabine, vinflunine [2] ---> SmPC of [2] of EMA

No pharmacokinetic interaction was observed in patients when vinflunine was combined with either cisplatin, carboplatin, capecitabine or gemcitabine.

Carboplatin, vinflunine [2] ---> SmPC of [2] of EMA

No pharmacokinetic interaction was observed in patients when vinflunine was combined with either cisplatin, carboplatin, capecitabine or gemcitabine.

Cisplatin, vinflunine [2] ---> SmPC of [2] of EMA

No pharmacokinetic interaction was observed in patients when vinflunine was combined with either cisplatin, carboplatin, capecitabine or gemcitabine.

Contraceptives, vinflunine [2] ---> SmPC of [2] of EMA

Both male and female patients should take adequate contraceptive measures up to three months after the discontinuation of the therapy.

Cyclosporine, vinflunine

The co-administration may cause an excessive immunosuppression with risk of lymphoproliferation

Docetaxel, vinflunine [2] ---> SmPC of [2] of EMA

A possible interaction with paclitaxel and docetaxel (CYP3 substrates) has been suggested from an in vitro study (slight inhibition of vinflunine metabolism).

Doxorubicin pegylated liposomal, vinflunine [2] ---> SmPC of [2] of EMA

A pharmacokinetic interaction between vinflunine and pegylated/liposomal doxorubicin was observed, resulting in a 15% to 30% apparent increase in vinflunine exposure and a 2 to 3-fold apparent decrease of doxorubicin AUC

Doxorubicine, vinflunine [2] ---> SmPC of [2] of EMA

No pharmacokinetic interaction was observed in patients when vinflunine was combined with doxorubicin. However, this combination was associated with a particularly high risk of haematological toxicity.

Fertility, vinflunine [2] ---> SmPC of [2] of EMA

Advice on conservation of sperm should be sought prior to treatment because of the possibility of irreversible infertility due to therapy with vinflunine.

Gemcitabine, vinflunine [2] ---> SmPC of [2] of EMA

No pharmacokinetic interaction was observed in patients when vinflunine was combined with either cisplatin, carboplatin, capecitabine or gemcitabine.

Grapefruit juice, vinflunine [2] ---> SmPC of [2] of EMA

The concomitant use of vinflunine and potent CYP3A4 inhibitors should be avoided since they may increase vinflunine and DVFL concentrations

Itraconazol, vinflunine [2] ---> SmPC of [2] of EMA

The concomitant use of vinflunine and potent CYP3A4 inhibitors should be avoided since they may increase vinflunine and DVFL concentrations

Ketoconazole, vinflunine [2] ---> SmPC of [2] of EMA

The concomitant use of vinflunine and potent CYP3A4 inhibitors should be avoided since they may increase vinflunine and DVFL concentrations

Males and females, vinflunine [2] ---> SmPC of [2] of EMA

Due to the genotoxic potential of vinflunine, both male and female patients should take adequate and effective contraceptive measures during treatment and up to 4 months after the discontinuation of the therapy for men and 7 months for women.

Opiates, vinflunine [2] ---> SmPC of [2] of EMA

The concomitant use of opioids could enhance the risk of constipation.

P-glycoprotein substrates, vinflunine [2] ---> SmPC of [2] of EMA

In vitro studies showed that vinflunine is a Pgp-substrate like other vinca alkaloids, but with a lower affinity. Therefore, risks of clinically significant interactions should be unlikely.

Paclitaxel, vinflunine [2] ---> SmPC of [2] of EMA

A possible interaction with paclitaxel and docetaxel (CYP3 substrates) has been suggested from an in vitro study (slight inhibition of vinflunine metabolism).

Phenytoin, vinflunine

The combination may increase the metabolism of both principles and decrease the effects: Increased seizure risk and decreased cytostatic effect. Combination not recommended

Pregnancy, vinflunine [2] ---> SmPC of [2] of EMA

If pregnancy occurs during treatment, the patient should be informed about the risk for the unborn child and be monitored carefully. The possibility of genetic counselling should be considered.

Pregnancy, vinflunine [2] ---> SmPC of [2] of EMA

Vinflunine should not be used during pregnancy, unless it is strictly necessary.

QT interval prolonging drugs, vinflunine [2] ---> SmPC of [2] of EMA

The concomitant use of vinflunine with others QT/QTc interval prolonging medicinal products should be avoided (see section 4.4).

Rifampicin, vinflunine [2] ---> SmPC of [2] of EMA

The concomitant use of vinflunine and potent CYP3A4 inducers should be avoided since they may decrease vinflunine and DVFL concentrations

Ritonavir, vinflunine [2] ---> SmPC of [2] of EMA

The concomitant use of vinflunine and potent CYP3A4 inhibitors should be avoided since they may increase vinflunine and DVFL concentrations

St. John's wort, vinflunine [2] ---> SmPC of [2] of EMA

The concomitant use of vinflunine and potent CYP3A4 inducers should be avoided since they may decrease vinflunine and DVFL concentrations

Strong CYP3A4 inductors, vinflunine [2] ---> SmPC of [2] of EMA

The concomitant use of vinflunine and potent CYP3A4 inducers should be avoided since they may decrease vinflunine and DVFL concentrations

Strong CYP3A4 inhibitors, vinflunine [2] ---> SmPC of [2] of EMA

The concomitant use of vinflunine and potent CYP3A4 inhibitors should be avoided since they may increase vinflunine and DVFL concentrations

Tacrolimus, vinflunine

The co-administration may cause an excessive immunosuppression with risk of lymphoproliferation

Vaccinations with live organism vaccines, vinflunine

The co-administration may decrease the antibody production and increase the risk of systemic vaccinal disease. The combination is not recommended

Vinflunine [1], women of childbearing potential ---> SmPC of [1] of EMA

Women of child-bearing potential must use effective contraception during treatment and for 7 months after treatment.

CONTRAINDICATIONS of Vinflunine (Javlor)

- Hypersensitivity to the active substance or other vinca alkaloids

- Recent (within 2 weeks) or current severe infection

- Baseline ANC < 1,500/mmł for the first administration, baseline ANC < 1,000/mmł for subsequent administrations

- Platelets < 100,000/ mmł

- Lactation

https://www.ema.europa.eu/en/documents/product-information/javlor-epar-product-information_en.pdf 18/04/2024

Vinorelbine

Ability to drive, vinorelbine [2] ---> SmPC of [2] of eMC

Caution is necessary in patient treated with vinorelbine considering some adverse effects of the drug.

Anticoagulants, vinorelbine [2] ---> SmPC of [2] of eMC

The eventuality of interaction between oral anticoagulants and anticancer chemotherapy require, if it is decided to treat the patient with oral anticoagulants, to increase frequency of the INR (International Normalised Ratio) monitoring.

Aprepitant [1], vinorelbine ---> SmPC of [1] of EMA

An interaction of aprepitant with orally administered chemotherapeutic medicinal products metabolised primarily or in part by CYP3A4 cannot be excluded. Caution is advised

Bexarotene [1], vinorelbine ---> SmPC of [1] of EMA

Caution is advised in case of combination of bexarotene with CYP3A4-metabolised cytotoxics

Breast-feeding, vinorelbine [2] ---> SmPC of [2] of eMC

A risk to the suckling cannot be excluded therefore breastfeeding must be discontinued before starting treatment with vinorelbine

Carbamazepine, vinorelbine [2] ---> SmPC of [2] of eMC

CYP3A4 is the main enzyme involved in the metabolism of vinorelbine, and the combination with a drug that induces this iso-enzyme can affect the concentration of vinorelbine

Cisplatin, vinorelbine [2] ---> SmPC of [2] of eMC

A higher incidence of granulocytopenia has been reported in patients receiving combination therapy with vinorelbine and cisplatin than in those receiving vinorelbine alone.

Clarithromycin, vinorelbine [2] ---> SmPC of [2] of eMC

CYP3A4 is the main enzyme involved in the metabolism of vinorelbine, and the combination with a drug that inhibits this iso-enzyme can affect the concentration of vinorelbine

Cyclosporine, vinorelbine [2] ---> SmPC of [2] of eMC

The co-administration may cause an excessive immunosuppression with risk of lymphoproliferation

CYP3A4 and P-glycoprotein-inhibitors, vinorelbine

The strong CYP3A4 and P-glycoprotein inhibition may increase the plasma levels of the vinca alkaloid and increases its neurotoxicity. The combination is not recommended

Erythromycin, vinorelbine [2] ---> SmPC of [2] of eMC

CYP3A4 is the main enzyme involved in the metabolism of vinorelbine, and the combination with a drug that inhibits this iso-enzyme can affect the concentration of vinorelbine

Fluorouracil [1], vinorelbine ---> SmPC of [1] of eMC

Serious, potentially life-threatening mucositis may occur following co-administration of vinorelbine and 5-fluorouracil/folinic acid.

Fosaprepitant [1], vinorelbine ---> SmPC of [1] of EMA

Based on studies with oral aprepitant and docetaxel and vinorelbine, IVEMEND 150 mg is not expected to have a clinically relevant interaction with intravenously administered docetaxel and vinorelbine.

Fosaprepitant [1], vinorelbine ---> SmPC of [1] of EMA

An interaction with orally administered chemotherapeutic medicinal products metabolised primarily or partly by CYP3A4 (e.g. etoposide, vinorelbine) cannot be excluded.

Gefitinib [1], vinorelbine ---> SmPC of [1] of EMA

Data from phase II clinical trials, where gefitinib and vinorelbine have been used concomitantly, indicate that gefitinib may exacerbate the neutropenic effect of vinorelbine.

Itraconazol, vinorelbine [2] ---> SmPC of [2] of eMC

The strong CYP3A4 and P-glycoprotein inhibition may increase the plasma levels of the vinca alkaloid and increases its neurotoxicity. The combination is not recommended

Ketoconazole, vinorelbine [2] ---> SmPC of [2] of eMC

CYP3A4 is the main enzyme involved in the metabolism of vinorelbine, and the combination with a drug that inhibits this iso-enzyme can affect the concentration of vinorelbine

Medicines with myelotoxic effects, vinorelbine [2] ---> SmPC of [2] of eMC

The combination of vinorelbine and other drugs with known bone marrow toxicity is likely to increase the myelosuppressive adverse reactions.

Miconazole, vinorelbine

Oral miconazole is contraindicated with medicinal products that are metabolised by CYP3A4 and may prolong also the QT interval

Mytomicin, vinorelbine [2] ---> SmPC of [2] of eMC

The co-administration of mitomycin C and vinorelbine may increase the risk of bronchospasm and dyspnoea, in rare case in interstitial pneumonitis was observed.

Nefazodone, vinorelbine [2] ---> SmPC of [2] of eMC

CYP3A4 is the main enzyme involved in the metabolism of vinorelbine, and the combination with a drug that inhibits this iso-enzyme can affect the concentration of vinorelbine

P-glycoprotein and CYP3A4 inhibitors, vinorelbine

The P-glycoprotein and CYP3A4 inhibition may increase the plasma concentrations of vinorelbine

Phenobarbital, vinorelbine [2] ---> SmPC of [2] of eMC

CYP3A4 is the main enzyme involved in the metabolism of vinorelbine, and the combination with a drug that induces this iso-enzyme can affect the concentration of vinorelbine

Phenytoin, vinorelbine [2] ---> SmPC of [2] of eMC

Risk of exacerbation of convulsions resulting from the decrease of phenytoin digestive absorption by cytotoxic drug or risk of toxicity enhancement or loss of efficacy of the cytotoxic drug due to increased hepatic metabolism by phenytoin.

Pregnancy, vinorelbine [2] ---> SmPC of [2] of eMC

Vinorelbine is contraindicated in pregnancy

Protease inhibitors, vinorelbine [2] ---> SmPC of [2] of eMC

CYP3A4 is the main enzyme involved in the metabolism of vinorelbine, and the combination with a drug that inhibits this iso-enzyme can affect the concentration of vinorelbine

Quinidine, vinorelbine [2] ---> SmPC of [2] of eMC

As vinca-alkaloids are known as substrates for P-glycoprotein, caution should be exercised when combining vinorelbine with strong modulators of this membrane transporter.

Radiotherapy, vinorelbine [2] ---> SmPC of [2] of eMC

Vinorelbine 10 mg/ml concentrate for solution for infusion should not be given concomitantly with radiotherapy if the treatment field includes the liver.

Rifampicin, vinorelbine [2] ---> SmPC of [2] of eMC

CYP3A4 is the main enzyme involved in the metabolism of vinorelbine, and the combination with a drug that induces this iso-enzyme can affect the concentration of vinorelbine

Ritonavir, vinorelbine [2] ---> SmPC of [2] of eMC

As vinca-alkaloids are known as substrates for P-glycoprotein, caution should be exercised when combining vinorelbine with strong modulators of this membrane transporter.

St. John's wort, vinorelbine [2] ---> SmPC of [2] of eMC

CYP3A4 is the main enzyme involved in the metabolism of vinorelbine, and the combination with a drug that induces this iso-enzyme can affect the concentration of vinorelbine

Strong CYP3A4 inductors, vinorelbine [2] ---> SmPC of [2] of eMC

CYP3A4 is the main enzyme involved in the metabolism of vinorelbine, and the combination with a drug that induces this iso-enzyme can affect the concentration of vinorelbine

Strong CYP3A4 inhibitors, vinorelbine [2] ---> SmPC of [2] of eMC

CYP3A4 is the main enzyme involved in the metabolism of vinorelbine, and the combination with a drug that inhibits this iso-enzyme can affect the concentration of vinorelbine

Strong P-gp inhibitors, vinorelbine [2] ---> SmPC of [2] of eMC

As vinca-alkaloids are known as substrates for P-glycoprotein, caution should be exercised when combining vinorelbine with strong modulators of this membrane transporter.

Tacrolimus, vinorelbine [2] ---> SmPC of [2] of eMC

The co-administration may cause an excessive immunosuppression with risk of lymphoproliferation

Telithromycin, vinorelbine [2] ---> SmPC of [2] of eMC

CYP3A4 is the main enzyme involved in the metabolism of vinorelbine, and the combination with a drug that inhibits this iso-enzyme can affect the concentration of vinorelbine

Vaccinations with live organism vaccines, vinorelbine [2] ---> SmPC of [2] of eMC

Risk of generalised vaccine disease, possibly fatal. Concomitant use not recommended

Vinorelbine [1], yellow fever vaccine ---> SmPC of [1] of eMC

Risk of fatal generalised vaccine disease. Concomitant use is contraindicated

CONTRAINDICATIONS of Vinorelbine

- The use of intrathecal route is contra-indicated

- Hypersensitivity to vinorelbine or other Vinca alkaloids or to any of the excipients.

- Neutrophil granulocytes count < 1,500/mm³ or serious, current or recent infection (within 2 weeks).

- Platelet count below 100,000/mm³

- Pregnancy

- Breast-feeding should be discontinued during treatment with vinorelbine

- Severe hepatic impairment not related to the tumoral process

- Women of childbearing potential not using effective contraception

- In combination with yellow fever vaccine

http://www.medicines.org.uk/emc/

Vismodegib (Erivedge)

BCRP substrates, vismodegib [2] ---> SmPC of [2] of EMA

Vismodegib, BCRP inhibitor, may increase exposure of medicinal products transported by this protein. The co-administration should be undertaken with caution

Bosentan, vismodegib [2] ---> SmPC of [2] of EMA

Breast-feeding, vismodegib [2] ---> SmPC of [2] of EMA

Due to its potential to cause serious developmental defects women must not breast-feed while taking Erivedge and for 24 months after the final dose

Carbamazepine, vismodegib [2] ---> SmPC of [2] of EMA

When vismodegib is administered with CYP inducers (rifampicin, carbamazepine, phenytoin, St. John´s wort), exposure to vismodegib may be decreased (see sections 4.3 and 4.4).

Contraceptive steroids, vismodegib [2] ---> SmPC of [2] of EMA

Enzym induction by vismodegib could lead to decreases in systemic exposure of the contraceptive steroids and thereby reduced contraceptive efficacy.

CYP450 inductors, vismodegib [2] ---> SmPC of [2] of EMA

When vismodegib is administered with CYP inducers, exposure to vismodegib may be decreased.

CYP450 inhibitors, vismodegib [2] ---> SmPC of [2] of EMA

Clinically significant PK interactions between vismodegib and CYP450 inhibitors are not expected

CYP450 substrates, vismodegib [2] ---> SmPC of [2] of EMA

Clinically significant PK interactions between vismodegib and CYP450 substrates are not expected

Ethinyl estradiol, vismodegib [2] ---> SmPC of [2] of EMA

However, the interaction study was of only 7 days duration and it cannot be excluded that vismodegib upon longer treatment is an inducer of enzymes which metabolise contraceptive steroids.

Ezetimibe, vismodegib [2] ---> SmPC of [2] of EMA

Fertility, vismodegib [2] ---> SmPC of [2] of EMA

Fertility preservation strategies should be discussed with WCBP prior to starting treatment with Erivedge. Fertility impairment in human males is not expected (see section 5.3).

Fertility, vismodegib [2] ---> SmPC of [2] of EMA

Human female fertility may be compromised by treatment with Erivedge (see section 5.3). Reversibility of fertility impairment is unknown.

Fluconazole, vismodegib [2] ---> SmPC of [2] of EMA

But this interaction is not expected to be clinically significant.

Gastric pH increasing medication, vismodegib [2] ---> SmPC of [2] of EMA

Clinically significant pharmacokinetic (PK) interactions between vismodegib and pH elevating agents are not expected.

Glibenclamide, vismodegib [2] ---> SmPC of [2] of EMA

Itraconazol, vismodegib [2] ---> SmPC of [2] of EMA

Itraconazole (a strong CYP3A4 inhibitor) 200 mg daily did not influence vismodegib AUC0-24h after 7 days co-treatment in healthy volunteers.

Itraconazol, vismodegib [2] ---> SmPC of [2] of EMA

Itraconazole (a strong CYP3A4 inhibitor) 200 mg daily did not influence vismodegib AUC0-24 h after 7 days co-treatment in healthy volunteers.

Men, vismodegib [2] ---> SmPC of [2] of EMA

Vismodegib is present in semen. To avoid potential foetal exposure during pregnancy, male patients must always use a condom (with spermicide, if available), even after a vasectomy, when having sex with a female partner while taking Erivedge and for 2 months after the final dose.

Missed menstrual period, vismodegib [2] ---> SmPC of [2] of EMA

If the patient does become pregnant, misses a menstrual period, or suspects for any reason that she may be pregnant, she must notify her treating physician immediately.

Norethindrone, vismodegib [2] ---> SmPC of [2] of EMA

However, the interaction study was of only 7 days duration and it cannot be excluded that vismodegib upon longer treatment is an inducer of enzymes which metabolise contraceptive steroids.

OATP1B1 substrates, vismodegib [2] ---> SmPC of [2] of EMA

Phenytoin, vismodegib [2] ---> SmPC of [2] of EMA

When vismodegib is administered with CYP inducers (rifampicin, carbamazepine, phenytoin, St. John´s wort), exposure to vismodegib may be decreased (see sections 4.3 and 4.4).

Pregnancy, vismodegib [2] ---> SmPC of [2] of EMA

In case of pregnancy in a woman treated with Erivedge, treatment must be stopped immediately.

Pregnancy, vismodegib [2] ---> SmPC of [2] of EMA

Contraindicated. Vismodegib may cause embryo-foetal death or severe birth defects when administered to a pregnant woman

Repaglinide, vismodegib [2] ---> SmPC of [2] of EMA

Rifampicin, vismodegib [2] ---> SmPC of [2] of EMA

When vismodegib is administered with CYP inducers (rifampicin, carbamazepine, phenytoin, St. John´s wort), exposure to vismodegib may be decreased (see sections 4.3 and 4.4).

Rosiglitazone, vismodegib [2] ---> SmPC of [2] of EMA

The systemic exposure of rosiglitazone (a CYP2C8 substrate) is not altered when co-administered with vismodegib. Thus inhibition of CYP enzymes by vismodegib in vivo may be excluded.

Rosuvastatin, vismodegib [2] ---> SmPC of [2] of EMA

Vismodegib, BCRP inhibitor, may increase exposure of medicinal products transported by this protein. The co-administration should be undertaken with caution

St. John's wort, vismodegib [2] ---> SmPC of [2] of EMA

When vismodegib is administered with CYP inducers, exposure to vismodegib may be decreased. St. John's wort is contraindicated

Statins, vismodegib [2] ---> SmPC of [2] of EMA

Strong CYP inducers, vismodegib [2] ---> SmPC of [2] of EMA

When vismodegib is administered with CYP inducers (rifampicin, carbamazepine, phenytoin, St. John´s wort), exposure to vismodegib may be decreased (see sections 4.3 and 4.4).

Strong P-gp inhibitors, vismodegib [2] ---> SmPC of [2] of EMA

Clinically significant PK interactions between vismodegib and P-gp inhibitors are not expected.

Sulfasalazine, vismodegib [2] ---> SmPC of [2] of EMA

Vismodegib, BCRP inhibitor, may increase exposure of medicinal products transported by this protein. The co-administration should be undertaken with caution

Topotecan, vismodegib [2] ---> SmPC of [2] of EMA

Vismodegib, BCRP inhibitor, may increase exposure of medicinal products transported by this protein. The co-administration should be undertaken with caution

Valsartan, vismodegib [2] ---> SmPC of [2] of EMA

Vismodegib [1], women of childbearing potential ---> SmPC of [1] of EMA

Erivedge is contraindicated in WCBP who do not comply with the Erivedge Pregnancy Prevention Programme.

Vismodegib [1], women of childbearing potential ---> SmPC of [1] of EMA

Due to the risk of embryo-foetal death or severe birth defects caused by vismodegib, women taking Erivedge must not be pregnant or become pregnant during treatment and for 24 months after the final dose (see sections 4.3 and 4.4).

Vismodegib [1], women of childbearing potential ---> SmPC of [1] of EMA

WCBP must use two methods of recommended contraception including one highly effective method and a barrier method during Erivedge therapy and for 24 months after the final dose.

CONTRAINDICATIONS of Vismodegib (Erivedge)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Women who are pregnant or breast-feeding

- Women of childbearing potential who do not comply with the Erivedge Pregnancy Prevention Programme

- Coadministration of St John's wort (Hypericum perforatum)

https://www.ema.europa.eu/en/documents/product-information/erivedge-epar-product-information_en.pdf 20/03/2023

Vitamin A

Abciximab, vitamin A

Concomitant use of parenteral anticoagulants with vitamin A may increase the anticoagulant effect and the risk of bleeding

Acenocoumarol, vitamin A

Possibly increased anticoagulant effect and risk of bleeding

Acitretin [1], vitamin A ---> SmPC of [1] of eMC

Risk of hypervitaminosis A. The combination is contraindicated

Alitretinoin [1], vitamin A ---> SmPC of [1] of eMC

Patients should not take vitamin A or other retinoids as concurrent medication due to the risk of hypervitaminosis A.

Antithrombin III, vitamin A

Concomitant use of parenteral anticoagulants with vitamin A may increase the anticoagulant effect and the risk of bleeding

Bexarotene [1], vitamin A ---> SmPC of [1] of EMA

Because of the relationship of bexarotene to vitamin A, patients should be advised to limit vitamin A supplements to ≤15,000 IU/day to avoid potential additive toxic effects.

Breast-feeding, vitamin A

Vitamin A is excreted in breast milk. A risk cannot be precluded

Calcium, vitamin A

The co-administration may increase the absorption of calcium salt

Cholestyramine, vitamin A

Cholestyramine may delay/decrease the absorption of the fat-soluble vitamin. The vitamin should be administered 1 hour before or 4-6 hours after colestyramine

Clopidogrel, vitamin A

Concomitant use of antiplatelet drugs with vitamin A may increase the anticoagulant effect and the risk of bleeding

Colestipol, vitamin A

The bile-acid sequestrant may decrease the absortion of the fat-soluble vitamins. It is recommended to separate the times of administration by at least 2 hours

Dicoumarol, vitamin A

Possibly increased anticoagulant effect and risk of bleeding

Eptifibatide, vitamin A

Concomitant use of antiplatelet drugs with vitamin A may increase the anticoagulant effect and the risk of bleeding

Fluconazole [1], vitamin A ---> SmPC of [1] of eMC

Based on a case-report in one patient receiving combination therapy with all trans-retinoid acid (an acid form of vitamin A) and fluconazole, CNS related undesirable effects have developed in the form of pseudotumour cerebri

Fondaparinux, vitamin A

Concomitant use of parenteral anticoagulants with vitamin A may increase the anticoagulant effect and the risk of bleeding

Heparin, vitamin A

Concomitant use of parenteral anticoagulants with vitamin A may increase the anticoagulant effect and the risk of bleeding

Isotretinoin [1], vitamin A ---> SmPC of [1] of eMC

Patients should not take vitamin A as concurrent medication due to the risk of developing hypervitaminosis A.

Oral anticoagulants, vitamin A

Possibly increased anticoagulant effect and risk of bleeding

Oral contraceptives, vitamin A

Concomitant use of oral contraceptives with vitamin A may increase the plasma levels of vitamin

Platelet aggregation inhibitors, vitamin A

Concomitant use of antiplatelet drugs with vitamin A may increase the anticoagulant effect and the risk of bleeding

Pregnancy, vitamin A

Dose over the recommended daily dose (2.500 IU/day, in the USA) should be avoided in pregnant women

Retinoids, vitamin A

Vitamin A analogs may increase the risk of hypervitaminosis A. Concomitant use should be avoided

Tetracyclines, vitamin A ---> SmPC of [alitretinoin] of eMC

Cases of benign intracranial hypertension (pseudotumor cerebri) have been reported with concomitant use of retinoids and tetracyclines. Therefore, concomitant treatment with tetracyclines must be avoided

Tirofiban, vitamin A

Concomitant use of antiplatelet drugs with vitamin A may increase the anticoagulant effect and the risk of bleeding

Tocofersolan [1], vitamin A ---> SmPC of [1] of EMA

Due to inhibition of P-Glycoprotein transporter, tocofersolan may also enhance intestinal absorption of other concomitant fat-soluble vitamins (A, D, E, K)

Vitamin A, vitamin A

Risk of A hypervitaminosis. The co-administration should be avoided.

Vitamin A, warfarin

Possibly increased anticoagulant effect and risk of bleeding

Voclosporine (Lupkynis)

Atorvastatin, voclosporine [2] ---> SmPC of [2] of EMA

Patients should be monitored for adverse events such as myopathy and rhabdomyolysis when OATP1B1/OATP1B3 substrates are used concomitantly with voclosporin.

BCRP substrates with narrow therapeutic range, voclosporine [2] ---> SmPC of [2] of EMA

Monitor use of BCRP substrates where small concentration changes may lead to serious toxicity (e.g., rosuvastatin) when used concomitantly with voclosporin.

BCRP substrates, voclosporine [2] ---> SmPC of [2] of EMA

A relevant inhibition of intestinal BCRP cannot be excluded and voclosporin may increase the concentration of these substrates.

Breast-feeding, voclosporine [2] ---> SmPC of [2] of EMA

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Lupkynis therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Carbamazepine, voclosporine [2] ---> SmPC of [2] of EMA

Strong and moderate CYP3A4 inducers (e.g., carbamazepine, phenobarbital, rifampicin, St John's Wort, efavirenz) are not recommended to be dosed concomitantly with voclosporin (see section 4.4).

Clarithromycin, voclosporine [2] ---> SmPC of [2] of EMA

Co-administration of voclosporin with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin) is contraindicated (see section 4.3).

Cyclophosphamide, voclosporine [2] ---> SmPC of [2] of EMA

The safety and efficacy of voclosporin have not been established in combination with cyclophosphamide.

CYP3A4 inductors, voclosporine [2] ---> SmPC of [2] of EMA

Mild inducers of CYP3A4 may also result in decreased exposure and possibly a decreased effect, but the clinical relevance is unknown.

CYP3A4 inhibitors, voclosporine [2] ---> SmPC of [2] of EMA

No dose adjustment is required when voclosporin is co-administered with mild CYP3A4 inhibitors but additional monitoring of eGFR is recommended when initiating treatment with a mild CYP3A4 inhibitor.

Dabigatran etexilate, voclosporine [2] ---> SmPC of [2] of EMA

Caution must be exercised in case of co-administration of voclosporin with sensitive P-gp substrates, especially those with narrow therapeutic index where patients should be appropriately monitored as outlined in respective product labelling.

Digoxin, voclosporine [2] ---> SmPC of [2] of EMA

Concomitant administration of voclosporin with multiple doses of digoxin increased digoxin Cmax and area under the curve (AUC) by 1.51-fold and 1.25-fold, respectively.

Diltiazem, voclosporine [2] ---> SmPC of [2] of EMA

Reduce the dose to 15.8 mg in the morning and 7.9 mg in the evening when voclosporin is co-administered with moderate CYP3A4 inhibitors (e.g., verapamil, fluconazole, erythromycin, diltiazem, grapefruit and grapefruit juice, see section 4.2).

Drugs primarily metabolised by CYP3A4, voclosporine [2] ---> SmPC of [2] of EMA

Concomitant use of medicinal products or herbal remedies known to inhibit or induce CYP3A4 may affect the metabolism of voclosporin and thereby increase or decrease voclosporin blood levels.

Efavirenz, voclosporine [2] ---> SmPC of [2] of EMA

Strong and moderate CYP3A4 inducers (e.g., carbamazepine, phenobarbital, rifampicin, St John's Wort, efavirenz) are not recommended to be dosed concomitantly with voclosporin (see section 4.4).

Erythromycin, voclosporine [2] ---> SmPC of [2] of EMA

Fertility, voclosporine [2] ---> SmPC of [2] of EMA

There are no data on the effect of voclosporin on human fertility. In animal studies, voclosporin- related changes in the male reproductive tract were observed (see section 5.3).

Fexofenadine, voclosporine [2] ---> SmPC of [2] of EMA

Fluconazole, voclosporine [2] ---> SmPC of [2] of EMA

Grapefruit juice [1], voclosporine ---> SmPC of [1] of EMA

Grapefruit, voclosporine [2] ---> SmPC of [2] of EMA

Itraconazol, voclosporine [2] ---> SmPC of [2] of EMA

Co-administration of voclosporin with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin) is contraindicated (see section 4.3).

Ketoconazole, voclosporine [2] ---> SmPC of [2] of EMA

Voclosporin exposure was 18.6-fold higher in the presence of the strong CYP3A4 inhibitor ketoconazole compared to voclosporin administered alone.

Midazolam, voclosporine [2] ---> SmPC of [2] of EMA

Multiple administrations of voclosporin orally (0.4 mg/kg twice daily) had no clinically relevant effect on the pharmacokinetics of the sensitive CYP3A4 substrate midazolam.

Moderate CYP3A4 inductors, voclosporine [2] ---> SmPC of [2] of EMA

Co-administration of multiple doses of moderate CYP3A4 inducers are also expected to result in clinically relevant decreases of voclosporin exposure.

Moderate CYP3A4 inhibitors, voclosporine [2] ---> SmPC of [2] of EMA

Mycophenolate mofetil, voclosporine [2] ---> SmPC of [2] of EMA

Co-administration of voclosporin with mycophenolate mofetil (MMF) had no clinically significant impact on mycophenolic acid (MPA) blood concentrations.

OATP1B1 substrates, voclosporine [2] ---> SmPC of [2] of EMA

Patients should be monitored for adverse events such as myopathy and rhabdomyolysis when OATP1B1/OATP1B3 substrates are used concomitantly with voclosporin.

OATP1B3 substrates, voclosporine [2] ---> SmPC of [2] of EMA

Patients should be monitored for adverse events such as myopathy and rhabdomyolysis when OATP1B1/OATP1B3 substrates are used concomitantly with voclosporin.

Oral sorbitol, voclosporine [2] ---> SmPC of [2] of EMA

The content of sorbitol in medicinal products for oral use may affect the bioavailability of other medicinal products for oral use administered concomitantly.

P-glycoprotein substrates with small therapeutic index, voclosporine [2] ---> SmPC of [2] of EMA

P-glycoprotein substrates, voclosporine [2] ---> SmPC of [2] of EMA

Phenobarbital, voclosporine [2] ---> SmPC of [2] of EMA

Strong and moderate CYP3A4 inducers (e.g., carbamazepine, phenobarbital, rifampicin, St John's Wort, efavirenz) are not recommended to be dosed concomitantly with voclosporin (see section 4.4).

Pravastatine, voclosporine [2] ---> SmPC of [2] of EMA

Patients should be monitored for adverse events such as myopathy and rhabdomyolysis when OATP1B1/OATP1B3 substrates are used concomitantly with voclosporin.

Pregnancy, voclosporine [2] ---> SmPC of [2] of EMA

Lupkynis is not recommended during pregnancy and in women of childbearing potential not using contraception.

QT interval prolonging drugs, voclosporine [2] ---> SmPC of [2] of EMA

The use of voclosporin in combination with other medicinal products that are known to prolong QTc may result in clinically significant QT prolongation.

Rifampicin, voclosporine [2] ---> SmPC of [2] of EMA

Voclosporin exposure was 87 % lower and maximum concentration (Cmax) was 68 % lower in the presence of the strong CYP3A4 inducer rifampicin (600 mg once daily for 10 consecutive days) compared to voclosporin administration alone.

Simvastatine, voclosporine [2] ---> SmPC of [2] of EMA

Patients should be monitored for adverse events such as myopathy and rhabdomyolysis when OATP1B1/OATP1B3 substrates are used concomitantly with voclosporin.

Sorbitol, voclosporine [2] ---> SmPC of [2] of EMA

The additive effect of concomitantly administered products containing sorbitol (or fructose) and dietary intake of sorbitol (or fructose) should be taken into account.

St. John's wort, voclosporine [2] ---> SmPC of [2] of EMA

Strong and moderate CYP3A4 inducers (e.g., carbamazepine, phenobarbital, rifampicin, St John's Wort, efavirenz) are not recommended to be dosed concomitantly with voclosporin (see section 4.4).

Strong CYP3A4 inductors, voclosporine [2] ---> SmPC of [2] of EMA

Strong and moderate CYP3A4 inducers (e.g., carbamazepine, phenobarbital, rifampicin, St John's Wort, efavirenz) are not recommended to be dosed concomitantly with voclosporin (see section 4.4).

Strong CYP3A4 inhibitors, voclosporine [2] ---> SmPC of [2] of EMA

Co-administration of voclosporin with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin) is contraindicated (see section 4.3).

Vaccinations, voclosporine [2] ---> SmPC of [2] of EMA

Immunosuppressants may affect the response to vaccination, and vaccination during treatment with voclosporin may be less effective. The use of live attenuated vaccines should be avoided.

Verapamil, voclosporine [2] ---> SmPC of [2] of EMA

Voclosporin exposure was 2.71-fold higher in the presence of the moderate CYP3A4 inhibitor verapamil compared to voclosporin administration alone.

CONTRAINDICATIONS of Voclosporine (Lupkynis)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Co-administration of voclosporin with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin) (see section 4.5).

https://www.ema.europa.eu/en/documents/product-information/lupkynis-epar-product-information_en.pdf 24/11/2025

Volanesorsen (Waylivra)

Alcohol, volanesorsen [2] ---> SmPC of [2] of EMA

The effect of coadministration of this medicine with alcohol/medicinal products known to have potential for hepatotoxicity (e.g., paracetamol) is unknown. If signs and symptoms of hepatotoxicity develop, use of medicinal product should be discontinued.

Antithrombotics, volanesorsen [2] ---> SmPC of [2] of EMA

It is not known whether the risk of bleeding is increased by concomitant use of volanesorsen and antithrombotic agents or medicinal products that may lower platelet count or affect platelet function.

Breast-feeding, volanesorsen [2] ---> SmPC of [2] of EMA

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman.

Cytochrome P450, volanesorsen [2] ---> SmPC of [2] of EMA

Clinically relevant pharmacokinetic interactions are not expected between volanesorsen and substrates, inducers or inhibitors of cytochrome P450 (CYP) enzymes, and drug transporters.

Fertility, volanesorsen [2] ---> SmPC of [2] of EMA

No clinical data on the effect of this medicinal product on human fertility are available. Volanesorsen had no effect on fertility in mice.

Fibrates, volanesorsen [2] ---> SmPC of [2] of EMA

In clinical studies, this medicinal product has been used in combination with fibrates and fish oils with no impact on the medicinal product related to drug-drug interactions reported during the clinical program

Fish oil, volanesorsen [2] ---> SmPC of [2] of EMA

Hepatotoxic drugs, volanesorsen [2] ---> SmPC of [2] of EMA

Paracetamol, volanesorsen [2] ---> SmPC of [2] of EMA

Pregnancy, volanesorsen [2] ---> SmPC of [2] of EMA

As a precautionary measure, it is preferable to avoid the use of this medicinal product during pregnancy.

CONTRAINDICATIONS of Volanesorsen (Waylivra)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Chronic or unexplained thrombocytopenia. Treatment should not be initiated in patients with thrombocytopenia (platelet count <140 x 109/L).

https://www.ema.europa.eu/en/documents/product-information/waylivra-epar-product-information_en.pdf 14/07/2025

Vonicog alfa (Veyvondi)

Breast-feeding, vonicog alfa [2] ---> SmPC of [2] of EMA

VEYVONDI should be administered to lactating von Willebrand factor deficient women only if clearly indicated.

Fertility, vonicog alfa [2] ---> SmPC of [2] of EMA

The effects of VEYVONDI on fertility have not been established.

Medicinal products, vonicog alfa [2] ---> SmPC of [2] of EMA

No interactions of human von Willebrand factor products with other medicinal products are known.

Pregnancy, vonicog alfa [2] ---> SmPC of [2] of EMA

VEYVONDI should be administered to pregnant women only if clearly indicated, taking into consideration that delivery confers an increased risk of haemorrhagic events in these patients.

CONTRAINDICATIONS of Vonicog alfa (Veyvondi)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Known allergic reaction to mouse or hamster proteins.

https://www.ema.europa.eu/en/documents/product-information/veyvondi-epar-product-information_en.pdf 20/01/2026

Vorapaxar (Zontivity)

Aluminium hydroxide, vorapaxar [2] ---> SmPC of [2] of EMA

No clinically relevant differences in vorapaxar pharmacokinetics were observed following daily co-administration of an aluminium hydroxide/magnesium carbonate antacid or pantoprazole (a proton pump inhibitor)

Boceprevir, vorapaxar [2] ---> SmPC of [2] of EMA

Co-administration of ketoconazole with vorapaxar significantly increased the vorapaxar exposition. Concomitant use of vorapaxar with strong inhibitors of CYP3A should be avoided.

Breast-feeding, vorapaxar [2] ---> SmPC of [2] of EMA

Due to the unknown potential for adverse reactions in breast-feeding infants from Zontivity, discontinue breast-feeding or discontinue Zontivity; taking into account the importance of the medicinal product to the mother.

Carbamazepine, vorapaxar [2] ---> SmPC of [2] of EMA

Co-administration of rifampin with vorapaxar substantially decreased the vorapaxar mean Cmax and AUC. Concomitant use of vorapaxar with strong (potent) inducers of CYP3A should be avoided.

Clarithromycin, vorapaxar [2] ---> SmPC of [2] of EMA

Co-administration of ketoconazole with vorapaxar significantly increased the vorapaxar exposition. Concomitant use of vorapaxar with strong inhibitors of CYP3A should be avoided.

Conivaptan, vorapaxar [2] ---> SmPC of [2] of EMA

Co-administration of ketoconazole with vorapaxar significantly increased the vorapaxar exposition. Concomitant use of vorapaxar with strong inhibitors of CYP3A should be avoided.

CYP2J2 substrates, vorapaxar [2] ---> SmPC of [2] of EMA

Vorapaxar is also a substrate of CYP2J2; therefore, there is a potential for potent inhibitors of CYP2J2 to result in increases in vorapaxar exposure.

CYP3A4 inhibitors, vorapaxar [2] ---> SmPC of [2] of EMA

Co-administration of a weak or moderate CYP3A inhibitor with vorapaxar does not increase bleeding risk or alter the efficacy of vorapaxar. No dose adjustment for vorapaxar is required in patients taking weak to moderate inhibitors of CYP3A.

Digoxin, vorapaxar [2] ---> SmPC of [2] of EMA

Vorapaxar is a weak inhibitor of the intestinal P-glycoprotein (P-gp) transporter. Co-administration of vorapaxar and digoxin increased digoxin Cmax and AUC. No dosage adjustment is recommended.

Heparin, vorapaxar [2] ---> SmPC of [2] of EMA

In patients treated with vorapaxar the concomitant use of heparin (including LMWH) might be associated with an increased risk of bleeding and caution is advised.

Indinavir, vorapaxar [2] ---> SmPC of [2] of EMA

Co-administration of ketoconazole with vorapaxar significantly increased the vorapaxar exposition. Concomitant use of vorapaxar with strong inhibitors of CYP3A should be avoided.

Itraconazol, vorapaxar [2] ---> SmPC of [2] of EMA

Co-administration of ketoconazole with vorapaxar significantly increased the vorapaxar exposition. Concomitant use of vorapaxar with strong inhibitors of CYP3A should be avoided.

Ketoconazole, vorapaxar [2] ---> SmPC of [2] of EMA

Co-administration of ketoconazole with vorapaxar significantly increased the vorapaxar exposition. Concomitant use of vorapaxar with strong inhibitors of CYP3A should be avoided.

Lopinavir/ritonavir [1], vorapaxar ---> SmPC of [1] of EMA

Serum concentrations may be increased due to CYP3A inhibition by Kaletra. The coadministration of vorapaxar with Kaletra is not recommended

Magnesium carbonate, vorapaxar [2] ---> SmPC of [2] of EMA

Moderate CYP3A4 inhibitors, vorapaxar [2] ---> SmPC of [2] of EMA

Nefazodone, vorapaxar [2] ---> SmPC of [2] of EMA

Co-administration of ketoconazole with vorapaxar significantly increased the vorapaxar exposition. Concomitant use of vorapaxar with strong inhibitors of CYP3A should be avoided.

Nelfinavir, vorapaxar [2] ---> SmPC of [2] of EMA

Co-administration of ketoconazole with vorapaxar significantly increased the vorapaxar exposition. Concomitant use of vorapaxar with strong inhibitors of CYP3A should be avoided.

NSAID, vorapaxar [2] ---> SmPC of [2] of EMA

The use of certain concomitant medicinal products (e.g., chronic nonsteroidal anti-inflammatory drugs (NSAIDS)) may increase the risk of bleeding in patients taking vorapaxar.

Oral anticoagulants, vorapaxar [2] ---> SmPC of [2] of EMA

When vorapaxar was co-administered with warfarin, there were no alterations in the pharmacokinetics/pharmacodynamics of warfarin. The coadministration of vorapaxar with anticoagulants e.g., warfarin and new oral anticoagulants (NOACs), should be avoided.

Pantoprazole, vorapaxar [2] ---> SmPC of [2] of EMA

Phenytoin, vorapaxar [2] ---> SmPC of [2] of EMA

Co-administration of rifampin with vorapaxar substantially decreased the vorapaxar mean Cmax and AUC. Concomitant use of vorapaxar with strong (potent) inducers of CYP3A should be avoided.

Posaconazole, vorapaxar [2] ---> SmPC of [2] of EMA

Co-administration of ketoconazole with vorapaxar significantly increased the vorapaxar exposition. Concomitant use of vorapaxar with strong inhibitors of CYP3A should be avoided.

Prasugrel, vorapaxar [2] ---> SmPC of [2] of EMA

When vorapaxar was co-administered with prasugrel, no clinically significant pharmacokinetic interaction was demonstrated. Vorapaxar should not be used with prasugrel or ticagrelor

Pregnancy, vorapaxar [2] ---> SmPC of [2] of EMA

Zontivity should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the foetus.

Rifampicin, vorapaxar [2] ---> SmPC of [2] of EMA

Co-administration of rifampin with vorapaxar substantially decreased the vorapaxar mean Cmax and AUC. Concomitant use of vorapaxar with strong (potent) inducers of CYP3A should be avoided.

Ritonavir [1], vorapaxar ---> SmPC of [1] of EMA

Serum concentrations may be increased due to CYP3A inhibition by ritonavir. The coadministration of vorapaxar with Norvir is not recommended

Rosiglitazone, vorapaxar [2] ---> SmPC of [2] of EMA

Co-administration with vorapaxar did not alter the single-dose pharmacokinetics of rosiglitazone (8 mg), a CYP2C8 substrate.

Saquinavir, vorapaxar [2] ---> SmPC of [2] of EMA

Co-administration of ketoconazole with vorapaxar significantly increased the vorapaxar exposition. Concomitant use of vorapaxar with strong inhibitors of CYP3A should be avoided.

SNRIs, vorapaxar [2] ---> SmPC of [2] of EMA

The use of certain concomitant medicinal products (e.g., serotonin norepinephrine reuptake inhibitors) may increase the risk of bleeding in patients taking vorapaxar.

SSRI, vorapaxar [2] ---> SmPC of [2] of EMA

The use of certain concomitant medicinal products (e.g., selective serotonin reuptake inhibitors) may increase the risk of bleeding in patients taking vorapaxar.

Strong CYP3A4 inductors, vorapaxar [2] ---> SmPC of [2] of EMA

Co-administration of rifampin with vorapaxar substantially decreased the vorapaxar mean Cmax and AUC. Concomitant use of vorapaxar with strong (potent) inducers of CYP3A should be avoided.

Strong CYP3A4 inhibitors, vorapaxar [2] ---> SmPC of [2] of EMA

Co-administration of ketoconazole with vorapaxar significantly increased the vorapaxar exposition. Concomitant use of vorapaxar with strong inhibitors of CYP3A should be avoided.

Telaprevir, vorapaxar [2] ---> SmPC of [2] of EMA

Co-administration of ketoconazole with vorapaxar significantly increased the vorapaxar exposition. Concomitant use of vorapaxar with strong inhibitors of CYP3A should be avoided.

Telithromycin, vorapaxar [2] ---> SmPC of [2] of EMA

Co-administration of ketoconazole with vorapaxar significantly increased the vorapaxar exposition. Concomitant use of vorapaxar with strong inhibitors of CYP3A should be avoided.

Thrombolytics, vorapaxar [2] ---> SmPC of [2] of EMA

The use of certain concomitant medicinal products (e.g., fibrinolytics) may increase the risk of bleeding in patients taking vorapaxar.

Ticagrelor, vorapaxar [2] ---> SmPC of [2] of EMA

When vorapaxar was co-administered with prasugrel, no clinically significant pharmacokinetic interaction was demonstrated. Vorapaxar should not be used with prasugrel or ticagrelor

Vorapaxar [1], warfarin ---> SmPC of [1] of EMA

CONTRAINDICATIONS of Vorapaxar (Zontivity)

- Patients with a history of stroke or transient ischaemic attack (TIA)

- Patients with a history of intracranial haemorrhage (ICH)

- Patients with any active pathological bleeding

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1

- Severe hepatic impairment

https://www.ema.europa.eu/en/documents/product-information/zontivity-epar-product-information_en.pdf 20/09/2017 (withdrawn) 20/09/2017 (Zontivity)

Voretigene neparvovec (Luxturna)

Ability to drive, voretigene neparvovec [2] ---> SmPC of [2] of EMA

Voretigene neparvovec has minor influence on the ability to drive and use machines. Patients may experience temporary visual disturbances after receiving subretinal injection of Luxturna.

Breast-feeding, voretigene neparvovec [2] ---> SmPC of [2] of EMA

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from voretigene neparvovec therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Fertility, voretigene neparvovec [2] ---> SmPC of [2] of EMA

No clinical data on the effect of the medicinal product on fertility are available. Effects on male and female fertility have not been evaluated in animal studies.

Pregnancy, voretigene neparvovec [2] ---> SmPC of [2] of EMA

As a precautionary measure, it is preferable to avoid the use of Luxturna during pregnancy.

CONTRAINDICATIONS of Voretigene neparvovec (Luxturna)

- Hypersensitivity to the active substance(s) or to any of the excipients listed in section 6.1.

- Ocular or periocular infection.

- Active intraocular inflammation.

https://www.ema.europa.eu/en/documents/product-information/luxturna-epar-product-information_en.pdf 21/10/2025

Voriconazole (Vfend)

Abemaciclib [1], voriconazole ---> SmPC of [1] of EMA

Use of strong CYP3A4 inhibitors together with abemaciclib should be avoided. If strong CYP3A4 inhibitors need to be co-administered, the dose of abemaciclib should be reduced, followed by careful monitoring of toxicity.

Ability to drive, voriconazole [2] ---> SmPC of [2] of EMA

VFEND has moderate influence on the ability to drive and use machines. It may cause transient and reversible changes to vision, including blurring, altered/enhanced visual perception and/or photophobia.

Acalabrutinib [1], voriconazole ---> SmPC of [1] of EMA

If the strong CYP3A/P-gp inhibitors (e.g., ketoconazole, conivaptan, clarithromycin, indinavir, itraconazole, ritonavir, telaprevir, posaconazole, voriconazole) will be used short-term, treatment with Calquence should be interrupted

Acenocoumarol, voriconazole [2] ---> SmPC of [2] of EMA

Voriconazole may increase the plasma concentrations of coumarins that may cause an increase in prothrombin time. Close monitoring of prothrombin time or other suitable anticoagulation tests is recommended

Alectinib [1], voriconazole ---> SmPC of [1] of EMA

Appropriate monitoring is recommended for patients taking concomitant strong CYP3A inhibitors

Alfentanyl, voriconazole [2] ---> SmPC of [2] of EMA

Dose reduction of short-acting opiates similar in structure to alfentanil and metabolised by CYP3A4 should be considered. Extended and frequent monitoring for respiratory depression and other opiate-associated adverse reactions is recommended.

Alprazolam, voriconazole [2] ---> SmPC of [2] of EMA

Voriconazole is likely to increase the plasma concentrations of benzodiazepines that are metabolised by CYP3A4 and lead to a prolonged sedative effect.

Amlodipine, voriconazole ---> SmPC of [amlodipine/valsartan] of EMA

Concomitant use of amlodipine with strong or moderate CYP3A4 inhibitors may give rise to significant increase in amlodipine exposure. Clinical monitoring and dose adjustment may thus be required.

Amprenavir, voriconazole [2] ---> SmPC of [2] of EMA

In vitro studies show that voriconazole may inhibit the metabolism of HIV protease inhibitors and the metabolism of voriconazole may also be inhibited by HIV protease inhibitors.

Apixaban [1], voriconazole ---> SmPC of [1] of EMA

The use of apixaban is not recommended in patients receiving concomitant systemic treatment with strong inhibitors of both CYP3A4 and P-gp

Aprepitant [1], voriconazole ---> SmPC of [1] of EMA

Concomitant administration of aprepitant with active substances that inhibit CYP3A4 activity should be approached cautiously, as the combination is expected to result several-fold in increased plasma concentrations of aprepitant

Astemizole, voriconazole [2] ---> SmPC of [2] of EMA

The combination of voriconazole, CYP3A4 inhibitor, with drugs metabolized by CYP3A4 and may prolong the QTc interval is contraindicated and rare occurrences of torsades de pointes

Atazanavir [1], voriconazole ---> SmPC of [1] of EMA

In the majority of patients, a reduction in both voriconazole and atazanavir exposures are expected. In a small number of patients without a functional CYP2C19 allele, significantly increased voriconazole exposures are expected

Atazanavir/cobicistat [1], voriconazole ---> SmPC of [1] of EMA

Voriconazole should not be coadministered with EVOTAZ unless the benefit/risk assessment justifies the use of voriconazole. Clinical monitoring may be needed upon coadministration with EVOTAZ.

Atazanavir/ritonavir, voriconazole ---> SmPC of [atazanavir] of EMA

Co-administration of voriconazole and atazanavir/ritonavir is not recommended unless an assessment of the benefit/risk to the patient justifies the use of voriconazole

Atenolol/nifedipine [1], voriconazole ---> SmPC of [1] of eMC

Drugs known to inhibit the cytochrome P450 3A4 system when administered orally with nifedipine may substantial increase the systemic bioavailability of nifedipine due to a decreased first pass metabolism and a decreased elimination

Atorvastatin, voriconazole [2] ---> SmPC of [2] of EMA

Voriconazole is likely to increase the plasma concentrations of statins that are metabolised by CYP3A4 and could lead to rhabdomyolysis.

Avacopan [1], voriconazole ---> SmPC of [1] of EMA

Strong CYP3A4 enzyme inhibitors should be used with caution in patients who are being treated with avacopan.

Avanafil [1], voriconazole ---> SmPC of [1] of EMA

Avanafil is predominantly metabolised by CYP3A4. The strong CYP3A4 inhibitors may increase the exposition of avanafil. Co-administration of avanafil with potent CYP3A4 inhibitors is contraindicated

Avapritinib [1], voriconazole ---> SmPC of [1] of EMA

Co-administration with strong or moderate CYP3A inhibitors should be avoided because it may increase the plasma concentration of avapritinib

Axitinib, voriconazole [2] ---> SmPC of [2] of EMA

Voriconazole may increase plasma concentrations of tyrosine kinase inhibitors metabolised by CYP3A4. If concomitant use cannot be avoided, dose reduction of the tyrosine kinase inhibitor is recommended (see section 4.4).

Azithromycin, voriconazole [2] ---> SmPC of [2] of EMA

No dose adjustment

Benzodiazepine primarily metabolised by CYP3A4, voriconazole [2] ---> SmPC of [2] of EMA

Voriconazole is likely to increase the plasma concentrations of benzodiazepines that are metabolised by CYP3A4 and lead to a prolonged sedative effect.

Bictegravir/emtricitabine/tenofovir alafenamide [1], voriconazole ---> SmPC of [1] of EMA

No dose adjustment is required upon co-administration.

Boceprevir [1], voriconazole ---> SmPC of [1] of EMA

The inhibition of CYP3A4 and P-glycoprotein may increase the plasma concentrations of boceprevir. Caution should be exercised when boceprevir is combined with azole antifungals

Bosentan [1], voriconazole ---> SmPC of [1] of EMA

Bosentan is metabolised by CYP2C9 and CYP3A4. Inhibition of these isoenzymes may increase the plasma concentration of bosentan. The combination should be used with caution.

Bosutinib [1], voriconazole ---> SmPC of [1] of EMA

The concomitant use of bosutinib with potent CYP3A inhibitors should be avoided, as an increase in bosutinib plasma levels will occur. Selection of an alternate concomitant medicine with no or minimal CYP3A enzyme inhibition potential is recommended.

Breast-feeding, voriconazole [2] ---> SmPC of [2] of EMA

Breast-feeding must be stopped on initiation of treatment with VFEND

Brigatinib [1], voriconazole ---> SmPC of [1] of EMA

The concomitant use of strong CYP3A inhibitors with Alunbrig should be avoided

Budesonide, voriconazole ---> SmPC of [budesonide/formoterol] of EMA

Potent inhibitors of CYP3A4 are likely to markedly increase plasma levels of budesonide and concomitant use should be avoided.

Budesonide/formoterol [1], voriconazole ---> SmPC of [1] of EMA

Potent inhibitors of CYP3A4 are likely to markedly increase plasma levels of budesonide and concomitant use should be avoided.

Budipine, voriconazole

The co-administration of budipine with drugs known to prolong QT interval is contraindicated

Cabazitaxel [1], voriconazole ---> SmPC of [1] of EMA

Repeated administration of ketoconazole, a strong CYP3A inhibitor, decreased cabazitaxel clearance. Therefore concomitant administration of strong CYP3A inhibitors should be avoided as an increase of plasma concentrations of cabazitaxel may occur

Cabozantinib, voriconazole [2] ---> SmPC of [2] of EMA

Capmatinib [1], voriconazole ---> SmPC of [1] of EMA

Patients should be closely monitored for adverse reactions during co-administration of Tabrecta with strong CYP3A inhibitors

Carbamazepine, voriconazole [2] ---> SmPC of [2] of EMA

Carbamazepine and long-acting barbiturates are likely to significantly decrease plasma voriconazole concentrations. The coadministration is Contraindicated

Cariprazine [1], voriconazole ---> SmPC of [1] of EMA

Metabolism of cariprazine and its major active metabolites is mediated mainly by CYP3A4. The co-administration of cariprazine with strong or moderate inhibitors of CYP3A4 is contraindicated

Ceritinib [1], voriconazole ---> SmPC of [1] of EMA

If it is not possible to avoid concomitant use with strong CYP3A inhibitors, reduce the ceritinib dose by approximately one third, rounded to the nearest multiple of the 150 mg dosage strength.

Cimetidine, voriconazole [2] ---> SmPC of [2] of EMA

No dose adjustment

Cinacalcet [1], voriconazole ---> SmPC of [1] of EMA

Cinacalcet is metabolised in part by the enzyme CYP3A4. Co-administration of a strong inhibitor of CYP3A4 may increase cinacalcet levels. Dose adjustment of cinacalcet may be required

Cisapride, voriconazole [2] ---> SmPC of [2] of EMA

The combination of voriconazole, CYP3A4 inhibitor, with drugs metabolized by CYP3A4 and may prolong the QTc interval is contraindicated and rare occurrences of torsades de pointes

Clopidogrel [1], voriconazole ---> SmPC of [1] of EMA

Since clopidogrel is metabolised to its active metabolite partly by CYP2C19, use of medicinal products that inhibit the activity of this enzyme would be expected to result in reduced drug levels of the active metabolite of clopidogrel.

Clopidogrel/acetylsalicylic acid [1], voriconazole ---> SmPC of [1] of EMA

Cobicistat [1], voriconazole ---> SmPC of [1] of EMA

Concentrations of voriconazole may be increased or decreased when co-administered with cobicistat.

Cobimetinib [1], voriconazole ---> SmPC of [1] of EMA

Avoid concurrent use of strong CYP3A inhibitors during treatment with cobimetinib. If concomitant use of a strong CYP3A inhibitor is unavoidable, patients should be carefully monitored for safety.

Coumarin anticoagulants, voriconazole [2] ---> SmPC of [2] of EMA

Crizotinib [1], voriconazole ---> SmPC of [1] of EMA

Coadministration of crizotinib with strong CYP3A inhibitors may increase crizotinib plasma concentrations. Therefore, the concomitant use of strong CYP3A inhibitors should be avoided.

Cyclosporine, voriconazole [2] ---> SmPC of [2] of EMA

The CYP3A4 inhibition by voriconazole may increase the plasma concentrations of ciclosporin. Dose adjustment may be required. Increased ciclosporin levels have been associated with nephrotoxicity.

Dabrafenib [1], voriconazole ---> SmPC of [1] of EMA

Dabrafenib is a substrate for the metabolising enzymes CYP3A4. Medicines that are strong inhibitors of CYP3A4 are therefore likely to increase dabrafenib concentrations. Use caution if strong inhibitors are coadministered with dabrafenib.

Daclatasvir [1], voriconazole ---> SmPC of [1] of EMA

Strong inhibitors of CYP3A4 may increase the plasma levels of daclatasvir. Dose adjustment of daclatasvir is recommended when coadministered with strong inhibitors of CYP3A4

Darunavir/cobicistat [1], voriconazole ---> SmPC of [1] of EMA

Concentrations of voriconazole may increase or decrease when co-administered with REZOLSTA. Voriconazole should not be combined with REZOLSTA unless an assessment of the benefit/risk ratio justifies the use of voriconazole.

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide [1], voriconazole ---> SmPC of [1] of EMA

Concentrations of voriconazole may increase or decrease when co-administered with DRV/COBI.

Darunavir/ritonavir, voriconazole ---> SmPC of [darunavir] of EMA

Ritonavir (induction of CYP450 enzymes) may decrease plasma concentrations of voriconazole. Voriconazole should not be combined with darunavir/ritonavir unless an assessment of the benefit/risk ratio justifies the use of voriconazole.

Dasabuvir with ombitasvir/paritaprevir/ritonavir, voriconazole ---> SmPC of [ombitasvir/paritaprevir/ritonavir] of

Co-administration of ombitasvir/paritaprevir/ritonavir with or without dasabuvir with medicinal products that are strong inhibitors of CYP3A4 is expected to increase paritaprevir plasma concentrations. The coadministration is contraindicated

Dasatinib, voriconazole [2] ---> SmPC of [2] of EMA

Delavirdine, voriconazole [2] ---> SmPC of [2] of EMA

In vitro studies show that the metabolism of voriconazole may be inhibited by NNRTIs and voriconazole may inhibit the metabolism of NNRTIs. Careful monitoring for any occurrence of drug toxicity and/or lack of efficacy

Diclofenac, voriconazole [2] ---> SmPC of [2] of EMA

Frequent monitoring for adverse reactions and toxicity related to NSAIDs is recommended. Dose reduction of NSAIDs may be needed.

Digitoxin, voriconazole

The CYP3A4 inhibition may increase the plasma levels of digitoxin

Digoxin, voriconazole [2] ---> SmPC of [2] of EMA

No dose adjustment

Dihydroergotamine, voriconazole [2] ---> SmPC of [2] of EMA

Voriconazole is likely to increase the plasma concentrations of ergot alkaloids and lead to ergotism. The co-administration is Contraindicated

Docetaxel [1], voriconazole ---> SmPC of [1] of EMA

In case of combination of docetaxel with CYP3A4 inhibitors, the occurrence of docetaxel adverse reactions may increase, as a result of reduced metabolism

Dolutegravir [1], voriconazole ---> SmPC of [1] of EMA

The inhibition of CYP3A4 may increase plasma levels of dolutegravir. No dose adjustment is necessary. Based on data from other CYP3A4 inhibitors, a marked increase is not expected.

Dolutegravir/rilpivirine [1], voriconazole ---> SmPC of [1] of EMA

May cause an increase in the plasma concentrations of rilpivirine (inhibition of CYP3A enzymes). No dose adjustment is required.

Doravirine [1], voriconazole ---> SmPC of [1] of EMA

No dose adjustment is required.

Doravirine/lamivudine/tenofovir disoproxil [1], voriconazole ---> SmPC of [1] of EMA

No dose adjustment is required.

Drugs primarily metabolised by CYP2C19, voriconazole [2] ---> SmPC of [2] of EMA

Voriconazole inhibits the activity of, cytochrome P450 isoenzymes, CYP2C19, CYP2C9, and CYP3A4. There is potential for voriconazole to increase the plasma concentrations of substances metabolised by these CYP450 isoenzymes.

Drugs primarily metabolised by CYP2C9, voriconazole [2] ---> SmPC of [2] of EMA

Drugs primarily metabolised by CYP3A4, voriconazole [2] ---> SmPC of [2] of EMA

Duvelisib [1], voriconazole ---> SmPC of [1] of EMA

Duvelisib dose should be reduced to 15 mg twice daily when co-administered with a strong CYP3A4 inhibitor

Efavirenz, voriconazole [2] ---> SmPC of [2] of EMA

Voriconazole may be coadministered with efavirenz if the voriconazole maintenance dose is increased to 400 mg BID and the efavirenz dose is decreased to 300 mg QD. When voriconazole treatment is stopped, the initial dose of efavirenz should be restored

Eliglustat [1], voriconazole ---> SmPC of [1] of EMA

Increased eliglustat exposition would be expected for strong inhibitors of CYP3A. Caution should be used with strong CYP3A inhibitors in intermediate and extensive metabolisers.

Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide [1], voriconazole ---> SmPC of [1] of EMA

Concentrations of voriconazole may increase or decrease when co-administered with Genvoya.

Elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil [1], voriconazole ---> SmPC of [1] of EMA

Concentrations of voriconazole may be increased or decreased when co-administered with elvitegravir/cobicistat/emtricitabine/tenofovir.

Emtricitabine/rilpivirine/tenofovir alafenamide [1], voriconazole ---> SmPC of [1] of EMA

Co-administration of this antifungal agent is expected to increase plasma concentrations of rilpivirine (inhibition of CYP3A) and tenofovir alafenamide (inhibition of P-gp). Co-administration is not recommended.

Emtricitabine/rilpivirine/tenofovir disoproxil [1], voriconazole ---> SmPC of [1] of EMA

Concomitant use of Eviplera with azole antifungal agents may cause an increase in the plasma concentrations of rilpivirine (inhibition of CYP3A enzymes). At a dose of 25 mg of rilpivirine, dose adjustment is required.

Enfortumab vedotin [1], voriconazole ---> SmPC of [1] of EMA

Patients receiving concomitant strong CYP3A4 inhibitors should be monitored more closely for signs of toxicities.

Entrectinib [1], voriconazole ---> SmPC of [1] of EMA

Co-administration of strong and moderate CYP3A inhibitors (including, but not limited to, ritonavir, saquinavir, ketoconazole, itraconazole, voriconazole, posaconazole, grapefruit or Seville oranges) should be avoided.

Ergot derivatives, voriconazole [2] ---> SmPC of [2] of EMA

Voriconazole is likely to increase the plasma concentrations of ergot alkaloids and lead to ergotism. The co-administration is Contraindicated

Ergotamine, voriconazole [2] ---> SmPC of [2] of EMA

Voriconazole is likely to increase the plasma concentrations of ergot alkaloids and lead to ergotism. The co-administration is Contraindicated

Erlotinib [1], voriconazole ---> SmPC of [1] of EMA

Erlotinib is metabolised in the liver by the hepatic cytochromes in humans, primarily CYP3A4 and to a lesser extent by CYP1A2. Potent inhibitors of CYP3A4 activity decrease erlotinib metabolism and increase erlotinib plasma concentrations.

Erythromycin, voriconazole [2] ---> SmPC of [2] of EMA

No dose adjustment

Esomeprazole [1], voriconazole ---> SmPC of [1] of EMA

Concomitant administration of esomeprazole and a combined inhibitor of CYP2C19 and CYP 3A4 may result in more than doubling of the esomeprazole exposure. A dose adjustment of esomeprazole is not regularly required

Ethinylestradiol/norgestimate [1], voriconazole ---> SmPC of [1] of eMC

Increase in plasma hormone levels associated with co-administered drug

Etoricoxib [1], voriconazole ---> SmPC of [1] of eMC

Co-administration of either oral voriconazole or topical miconazole oral gel, strong CYP3A4 inhibitors, with etoricoxib caused a slight increase in exposure to etoricoxib, but is not considered to be clinically meaningful based on published data.

Etravirine [1], voriconazole ---> SmPC of [1] of EMA

Concomitant use may increase plasma concentrations of both drugs. The co-administration can be used without dose adjustments.

Everolimus, voriconazole [2] ---> SmPC of [2] of EMA

The inhibition of CYP3A4 and of the P-glycoprotein increases the everolimus plasma levels significantly. The co-administration is not recommended

Ezetimibe/atorvastatin [1], voriconazole ---> SmPC of [1] of eMC

Potent CYP3A4 inhibitors have been shown to lead to markedly increased concentrations of atorvastatin. Coadministration of potent CYP3A4 inhibitors should be avoided if possible.

Fentanyl, voriconazole [2] ---> SmPC of [2] of EMA

Flucloxacillin, voriconazole [2] ---> SmPC of [2] of EMA

Flucloxacillin [CYP450 inducer]. Significantly decreased plasma voriconazole concentrations have been reported. If co-administration of voriconazole with flucloxacillin cannot be avoided, monitor for potential loss of voriconazole effectiveness

Fluconazole, voriconazole [2] ---> SmPC of [2] of EMA

The reduced dose and/or frequency of voriconazole and fluconazole that would eliminate this effect have not been established. Monitoring for voriconazole-associated adverse reactions is recommended if voriconazole is used sequentially after fluconazole.

Foods, voriconazole [2] ---> SmPC of [2] of EMA

VFEND film-coated tablets are to be taken at least one hour before, or one hour following, a meal.

Fosaprepitant [1], voriconazole ---> SmPC of [1] of EMA

Concomitant administration of fosaprepitant with active substances that inhibit CYP3A4 activity should be approached cautiously as the combination is expected to result in increased plasma concentrations of aprepitant

Fosphenytoin [1], voriconazole ---> SmPC of [1] of eMC

Phenytoin is mainly metabolized in the liver by the CYP2C9 and CYP2C19 enzymes. Inhibition of phenytoin metabolism may produce significant increases in plasma phenytoin concentrations and increase the risk of phenytoin toxicity.

Fostamatinib [1], voriconazole ---> SmPC of [1] of EMA

Concomitant use of fostamatinib with strong CYP3A4 inhibitors increases exposure to R406 (the major active metabolite), which may increase the risk of adverse reactions.

Fostemsavir [1], voriconazole ---> SmPC of [1] of EMA

Fostemsavir may be co-administered with strong CYP3A4, BCRP and/or P-gp inhibitors without dose adjustment based on the results of clinical drug interaction studies with cobicistat and ritonavir.

Gefitinib [1], voriconazole ---> SmPC of [1] of EMA

Concomitant administration with potent inhibitors of CYP3A4 activity may increase gefitinib plasma concentrations. The increase may be clinically relevant since adverse reactions are related to dose and exposure.

Gilteritinib [1], voriconazole ---> SmPC of [1] of EMA

Caution is required when prescribing gilteritinib with medicines that are strong inhibitors of CYP3A and/or P-gp because they can increase gilteritinib exposure. Alternative medicines that do not strongly inhibit CYP3A and/or P-gp should be considered.

Glasdegib [1], voriconazole ---> SmPC of [1] of EMA

Caution should be used when administering concomitantly with strong CYP3A4 inhibitors as an increase in glasdegib plasma concentration may occur.

Glipizide, voriconazole [2] ---> SmPC of [2] of EMA

Voriconazole is likely to increase the plasma concentrations of sulphonylurea and cause hypoglycaemia.

Glyburide, voriconazole [2] ---> SmPC of [2] of EMA

Voriconazole is likely to increase the plasma concentrations of sulphonylurea and cause hypoglycaemia.

Hydrocodone, voriconazole [2] ---> SmPC of [2] of EMA

Dose reduction in oxycodone and other long-acting opiates metabolised by CYP3A4 (e.g., hydrocodone) should be considered. Frequent monitoring for opiate-associated adverse reactions may be necessary.

Hydrocortisone [1], voriconazole ---> SmPC of [1] of EMA

Potent CYP 3A4 inhibitors can inhibit the metabolism of hydrocortisone, and thus increase blood levels.

Ibrutinib [1], voriconazole ---> SmPC of [1] of EMA

Ibuprofen, voriconazole [2] ---> SmPC of [2] of EMA

Frequent monitoring for adverse reactions and toxicity related to NSAIDs is recommended. Dose reduction of NSAIDs may be needed.

Idelalisib [1], voriconazole ---> SmPC of [1] of EMA

The co-administration of idelalisib with voriconazole may increase the serum concentrations of voriconazole. Clinical monitoring is recommended.

Imatinib [1], voriconazole ---> SmPC of [1] of EMA

Substances that inhibit the cytochrome P450 isoenzyme CYP3A4 activity could decrease metabolism and increase imatinib concentrations. Caution should be taken when administering imatinib with inhibitors of the CYP3A4 family.

Indinavir, voriconazole [2] ---> SmPC of [2] of EMA

No dose adjustment

Irinotecan [1], voriconazole ---> SmPC of [1] of EMA

Co-administration of ONIVYDE with other inhibitors of CYP3A4 may increase systemic exposure of ONIVYDE.

Isradipine [1], voriconazole ---> SmPC of [1] of eMC

Caution should be exercised when co-administering isradipine with strong CYP3A inhibitors

Ivabradine, voriconazole [2] ---> SmPC of [2] of EMA

The combination of voriconazole, CYP3A4 inhibitor, with drugs metabolized by CYP3A4 and may prolong the QTc interval is contraindicated and rare occurrences of torsades de pointes

Ivacaftor [1], voriconazole ---> SmPC of [1] of EMA

Ivacaftor is a sensitive CYP3A substrate. A reduction of the Kalydeco dose to 150 mg twice a week is recommended for co-administration with strong CYP3A inhibitors

Ivacaftor/tezacaftor/elexacaftor [1], voriconazole ---> SmPC of [1] of EMA

The dose of IVA/TEZ/ELX and ivacaftor should be reduced when co-administered with strong CYP3A inhibitors (see Table 1 in section 4.2 and section 4.4).

Ivosidenib [1], voriconazole ---> SmPC of [1] of EMA

Coadministration of moderate or strong CYP3A4 inhibitors increases ivosidenib plasma levels. This may increase the risk of QTc interval prolongation and suitable alternatives that are not moderate or strong CYP3A4 inhibitors should be considered

Ixabepilone, voriconazole

The strong CYP3A4 inhibition may increase the plasma concentrations of ixabepilone. The coadministration should be avoided

Lapatinib [1], voriconazole ---> SmPC of [1] of EMA

Lapatinib is predominantly metabolised by CYP3A. The strong CYP3A4 inhibition increases the exposition to lapatinib. Co-administration of lapatinib with strong inhibitors of CYP3A4 should be avoided.

Larotrectinib [1], voriconazole ---> SmPC of [1] of EMA

Larotrectinib is a substrate of cytochrome P450 (CYP) 3A, P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). Co-administration of VITRAKVI with strong CYP3A inhibitors, P-gp and BCRP inhibitors may increase larotrectinib plasma levels

Lefamulin [1], voriconazole ---> SmPC of [1] of EMA

Medicinal products that are strong CYP3A and P-gp inhibitors may alter absorption of lefamulin and therefore increase lefamulin plasma concentrations. Co- administration is contraindicated

Lenacapavir [1], voriconazole ---> SmPC of [1] of EMA

No dose adjustment of lenacapavir is required.

Letermovir [1], voriconazole ---> SmPC of [1] of EMA

Co-administration of PREVYMIS with voriconazole (a CYP2C19 substrate) results in significantly decreased voriconazole plasma concentrations, indicating that letermovir is an inducer of CYP2C19.

Lomitapide [1], voriconazole ---> SmPC of [1] of EMA

The strong CYP3A4 inhibition may increase lomitapide AUC. The combination of lomitapide with strong CYP3A4 inhibitors is contra-indicated

Long acting barbiturate, voriconazole [2] ---> SmPC of [2] of EMA

Carbamazepine and long-acting barbiturates are likely to significantly decrease plasma voriconazole concentrations. The coadministration is Contraindicated

Loperamide, voriconazole

The CYP3A4 inhibition increases the loperamide plasma levels. Frequent monitoring for adverse events related to loperamide.

Lopinavir, voriconazole

The mutual inhibition of CYP3A4 may increase the plasma concentrations of both principle actives

Lopinavir/ritonavir [1], voriconazole ---> SmPC of [1] of EMA

Possible decreased plasma concentrations of voriconazole. Co-administration of voriconazole and low dose ritonavir should be avoided

Lorlatinib [1], voriconazole ---> SmPC of [1] of EMA

CYP3A4/5 inhibitors may increase lorlatinib plasma concentrations and should be avoided

Lovastatine, voriconazole [2] ---> SmPC of [2] of EMA

Voriconazole is likely to increase the plasma concentrations of statins that are metabolised by CYP3A4 and could lead to rhabdomyolysis.

Lumacaftor/ivacaftor [1], voriconazole ---> SmPC of [1] of EMA

Increased exposition of ivacaftor due to inhibition of CYP3A by these antifungal. Decreased exposition of the antifungal due to induction of CYP3A by lumacaftor

Lurasidone [1], voriconazole ---> SmPC of [1] of EMA

Voriconazole is likely to significantly increase the plasma concentrations of lurasidone. The co-administration is Contraindicated.

Macitentan [1], voriconazole ---> SmPC of [1] of EMA

Caution should be exercised when macitentan (by CYP3A4 metabolized) is administered concomitantly with strong CYP3A4 inhibitors

Maraviroc, voriconazole

The strong CYP3A4 inhibition may increase the plasma concentrations of maraviroc. Dose adjustment of maraviroc is recommended

Maribavir [1], voriconazole ---> SmPC of [1] of EMA

No dose adjustment is required.

Mefobarbital, voriconazole [2] ---> SmPC of [2] of EMA

Carbamazepine and long-acting barbiturates are likely to significantly decrease plasma voriconazole concentrations. The coadministration is Contraindicated

Metabolized by CYP3A4 and prolong QT, voriconazole [2] ---> SmPC of [2] of EMA

The combination of voriconazole, CYP3A4 inhibitor, with drugs metabolized by CYP3A4 and may prolong the QTc interval is contraindicated and rare occurrences of torsades de pointes

Methadone, voriconazole [2] ---> SmPC of [2] of EMA

Dose reduction in oxycodone and other long-acting opiates metabolised by CYP3A4 (e.g., hydrocodone) should be considered. Frequent monitoring for opiate-associated adverse reactions may be necessary.

Methylergometrine, voriconazole

The strong CYP3A4 inhibition may increase the plasma concentrations of methylergometrine. The concomitant use should be avoided

Midazolam [1], voriconazole ---> SmPC of [1] of EMA

Voriconazole increased the exposure of intravenous midazolam by 3-fold whereas its elimination half-life increased by about 3-fold.

Mosunetuzumab [1], voriconazole ---> SmPC of [1] of EMA

A transient clinically relevant effect on CYP450 substrates with a narrow therapeutic index cannot be excluded, since initiation of Lunsumio treatment causes a transient increase in cytokine levels which may cause inhibition of CYP450 enzymes.

Mycophenolic acid, voriconazole [2] ---> SmPC of [2] of EMA

No dose adjustment

Naloxegol, voriconazole [2] ---> SmPC of [2] of EMA

Voriconazole is likely to significantly increase the plasma concentrations of naloxegol. The co-administration is Contraindicated.

Naproxen/esomeprazole [1], voriconazole ---> SmPC of [1] of eMC

Concomitant administration of esomeprazole and a combined inhibitor of CYP2C19 and CYP3A4 may result in more than doubling of the esomeprazole exposure. Dose adjustment of esomeprazole is not required

Nelfinavir, voriconazole [2] ---> SmPC of [2] of EMA

In vitro studies show that voriconazole may inhibit the metabolism of HIV protease inhibitors and the metabolism of voriconazole may also be inhibited by HIV protease inhibitors.

Neratinib [1], voriconazole ---> SmPC of [1] of EMA

Concomitant use of strong CYP3A4/Pgp inhibitors should be avoided.

Nevirapine, voriconazole [2] ---> SmPC of [2] of EMA

Nilotinib [1], voriconazole ---> SmPC of [1] of EMA

Significant prolongation of the QT interval may occur when nilotinib is inappropriately taken with strong CYP3A4 inhibitors. Prolongation of the QT interval may expose patients to the risk of fatal outcome.

Nirmatrelvir/ritonavir [1], voriconazole ---> SmPC of [1] of EMA

Coadministration of voriconazole and ritonavir dosed as a pharmacokinetic enhancer should be avoided unless an assessment of the benefit/risk to the patient justifies the use of voriconazole.

Non-nucleoside reverse transcriptase inhibitors, voriconazole [2] ---> SmPC of [2] of EMA

Norethisterone/ethinylestradiol, voriconazole [2] ---> SmPC of [2] of EMA

Monitoring for adverse reactions related to oral contraceptives, in addition to those for voriconazole, is recommended.

Norgestimate, voriconazole

The strong CYP3A4 inhibition may increase the plasma concentrations of norgestimate

NSAIDs metabolized by CYP2C9, voriconazole [2] ---> SmPC of [2] of EMA

Frequent monitoring for adverse reactions and toxicity related to NSAIDs is recommended. Dose reduction of NSAIDs may be needed.

Ombitasvir/paritaprevir/ritonavir [1], voriconazole ---> SmPC of [1] of EMA

CYP2C19 induction and CYP3A4 inhibition by ritonavir. Concomitant use is contraindicated

Omeprazole, voriconazole [2] ---> SmPC of [2] of EMA

Proton pump inhibitors that are CYP2C19 substrates may be inhibited by voriconazole and may result in increased plasma concentrations of these medicinal products. No dose adjustment of voriconazole is recommended.

Oral contraceptives, voriconazole [2] ---> SmPC of [2] of EMA

Monitoring for adverse reactions related to oral contraceptives, in addition to those for voriconazole, is recommended.

Oxycodone, voriconazole [2] ---> SmPC of [2] of EMA

Dose reduction in oxycodone and other long-acting opiates metabolised by CYP3A4 (e.g., hydrocodone) should be considered. Frequent monitoring for opiate-associated adverse reactions may be necessary.

Palbociclib [1], voriconazole ---> SmPC of [1] of EMA

Strong inhibitors of CYP3A4 may lead to increased toxicity. Concomitant use of strong CYP3A inhibitors during treatment with palbociclib should be avoided.

Panobinostat [1], voriconazole ---> SmPC of [1] of EMA

In patients who take concomitant medicinal products which are strong CYP3A and/or Pgp inhibitors, the dose of panobinostat should be reduced

Pazopanib [1], voriconazole ---> SmPC of [1] of EMA

Concomitant treatment with strong inhibitors of CYP3A4 should be avoided due to risk of increased exposure to pazopanib

Pethidine, voriconazole

Dose reduction in oxycodone and other long-acting opiates metabolized by CYP3A4 (e.g., hydrocodone) should be considered. Frequent monitoring for opiate-associated adverse reactions may be necessary.

Phenobarbital, voriconazole [2] ---> SmPC of [2] of EMA

Carbamazepine and long-acting barbiturates are likely to significantly decrease plasma voriconazole concentrations. The coadministration is Contraindicated

Phenprocoumon, voriconazole [2] ---> SmPC of [2] of EMA

Phenytoin, voriconazole [2] ---> SmPC of [2] of EMA

Concomitant use of voriconazole and phenytoin should be avoided unless the benefit outweighs the risk. Careful monitoring of phenytoin plasma levels is recommended.

Pimozide, voriconazole [2] ---> SmPC of [2] of EMA

The combination of voriconazole, CYP3A4 inhibitor, with drugs metabolized by CYP3A4 and may prolong the QTc interval is contraindicated and rare occurrences of torsades de pointes

Polatuzumab vedotin [1], voriconazole ---> SmPC of [1] of EMA

Patients receiving concomitant strong CYP3A4 inhibitors should be monitored more closely for signs of toxicities.

Ponatinib [1], voriconazole ---> SmPC of [1] of EMA

Caution should be exercised and a reduction of the starting dose should be considered with concurrent use of ponatinib with strong CYP3A inhibitors (modest increases in ponatinib systemic exposure are possible)

Pralsetinib [1], voriconazole ---> SmPC of [1] of EMA

Therefore, co-administration of pralsetinib with strong CYP3A4 inhibitors or combined P-gp and strong CYP3A4 inhibitors should be avoided. If co-administration cannot be avoided, reduce the current dose of pralsetinib

Prednisolone, voriconazole [2] ---> SmPC of [2] of EMA

No dose adjustment

Pregnancy, voriconazole [2] ---> SmPC of [2] of EMA

VFEND must not be used during pregnancy unless the benefit to the mother clearly outweighs the potential risk to the foetus.

Protease inhibitors, voriconazole [2] ---> SmPC of [2] of EMA

In vitro studies show that voriconazole may inhibit the metabolism of HIV protease inhibitors and the metabolism of voriconazole may also be inhibited by HIV protease inhibitors.

Proton pump inhibitors, voriconazole [2] ---> SmPC of [2] of EMA

Proton pump inhibitors that are CYP2C19 substrates may be inhibited by voriconazole and may result in increased plasma concentrations of these medicinal products.

QT interval prolonging drugs, voriconazole [2] ---> SmPC of [2] of EMA

Voriconazole should be administered with caution to patients with potentially proarrhythmic conditions, such as comedication that prolongs the QTc interval

Quinidine, voriconazole [2] ---> SmPC of [2] of EMA

The combination of voriconazole, CYP3A4 inhibitor, with drugs metabolized by CYP3A4 and may prolong the QTc interval is contraindicated and rare occurrences of torsades de pointes

Ranitidine, voriconazole [2] ---> SmPC of [2] of EMA

No dose adjustment

Regorafenib [1], voriconazole ---> SmPC of [1] of EMA

It is recommended to avoid concomitant use of strong inhibitors of CYP3A4 activity, as their influence on the steady-state exposure of regorafenib and its metabolites has not been studied.

Ribociclib [1], voriconazole ---> SmPC of [1] of EMA

Concomitant use of strong CYP3A4 inhibitors should be avoided and an alternative concomitant medicinal product with less potential to inhibit CYP3A4 inhibition should be considered.

Rifabutin, voriconazole [2] ---> SmPC of [2] of EMA

Rifabutin, strong CYP3A4 inductor, may decrease the plasma levels of voriconazole. Concomitant use should be avoided

Rifampicin, voriconazole [2] ---> SmPC of [2] of EMA

Carbamazepine and long-acting barbiturates are likely to significantly decrease plasma voriconazole concentrations. The coadministration is Contraindicated

Rilpivirine [1], voriconazole ---> SmPC of [1] of EMA

Not studied. Concomitant use of rilpivirine with azole antifungal agents (inhibition of CYP3A enzymes) may cause an increase in the plasma concentrations of rilpivirine. No dose adjustment is required.

Ripretinib [1], voriconazole ---> SmPC of [1] of EMA

Strong inhibitors of CYP3A/P-gp (e.g. ketoconazole, erythromycin, clarithromycin, itraconazole, ritonavir, posaconazole, and voriconazole) are to be used with caution and patients should be monitored.

Ritonavir [1], voriconazole ---> SmPC of [1] of EMA

Concomitant use of ritonavir dosed as an antiretroviral agent and voriconazole is contraindicated due to reduction in voriconazole concentrations

Rivaroxaban [1], voriconazole ---> SmPC of [1] of EMA

Co-administration of rivaroxaban with strong inhibitors of both CYP3A4 and P-gp may lead to an increased bleeding risk. The use of rivaroxaban with inhibitors of both CYP3A4 and P-gp is not recommended

Rupatadine [1], voriconazole ---> SmPC of [1] of eMC

The concomitant administration of rupatadine with inhibitors of the isozyme CYP3A4 increases the systemic exposure to rupatadine. Rupatadine should be used with caution when it is administered concomitantly with inhibitors of CYP3A4.

Ruxolitinib [1], voriconazole ---> SmPC of [1] of EMA

The strong CYP3A4 inhibition may increase ruxolitinib exposition. When co-administering with strong CYP3A4 inhibitors the unit dose of ruxolitinib should be reduced

Saquinavir, voriconazole [2] ---> SmPC of [2] of EMA

In vitro studies show that voriconazole may inhibit the metabolism of HIV protease inhibitors and the metabolism of voriconazole may also be inhibited by HIV protease inhibitors.

Selpercatinib [1], voriconazole ---> SmPC of [1] of EMA

If strong CYP3A and/or P-gp inhibitors, e. g. ketoconazole, itraconazole, voriconazole, ritonavir, saquinavir, telithromycin, posaconazole and nefazodone, have to be coadministered, the dose of selpercatinib should be reduced

Short-acting opiates metabolised by CYP3A4, voriconazole [2] ---> SmPC of [2] of EMA

Dose reduction in oxycodone and other long-acting opiates metabolised by CYP3A4 (e.g., hydrocodone) should be considered. Frequent monitoring for opiate-associated adverse reactions may be necessary.

Simeprevir [1], voriconazole ---> SmPC of [1] of EMA

Co-administration of simeprevir with moderate or strong inhibitors of CYP3A4 may significantly increase the plasma exposure of simeprevir. Co-administration of simeprevir with these inhibitors is not recommended.

Simvastatine, voriconazole [2] ---> SmPC of [2] of EMA

Voriconazole is likely to increase the plasma concentrations of statins that are metabolised by CYP3A4 and could lead to rhabdomyolysis.

Sirolimus, voriconazole [2] ---> SmPC of [2] of EMA

Concomitant administration of voriconazole with sirolimus is contraindicated, since voriconazole is likely to increase plasma concentrations of sirolimus significantly

Sofosbuvir/velpatasvir/voxilaprevir [1], voriconazole ---> SmPC of [1] of EMA

Inhibition of CYP3A. No dose adjustment of Vosevi or voriconazole is required.

Sonidegib [1], voriconazole ---> SmPC of [1] of EMA

Sonidegib undergoes metabolism primarily by CYP3A4, and concomitant administration of strong inhibitors of CYP3A4 can increase sonidegib concentrations significantly. The sonidegib dose should be reduced to 200 mg every other day

St. John's wort, voriconazole [2] ---> SmPC of [2] of EMA

Coadministration with rifampicin, carbamazepine, phenobarbital and St John's Wort since these medicinal products are likely to decrease plasma voriconazole concentrations significantly

Statins metabolised by CYP3A4, voriconazole [2] ---> SmPC of [2] of EMA

Voriconazole is likely to increase the plasma concentrations of statins that are metabolised by CYP3A4 and could lead to rhabdomyolysis.

Strong CYP2C19 inductors, voriconazole [2] ---> SmPC of [2] of EMA

Voriconazole is metabolised by cytochrome P450 isoenzymes, CYP2C19, CYP2C9, and CYP3A4. Inducers of these isoenzymes may decrease voriconazole plasma concentrations

Strong CYP2C19 inhibitors, voriconazole [2] ---> SmPC of [2] of EMA

Voriconazole is metabolised by cytochrome P450 isoenzymes, CYP2C19, CYP2C9, and CYP3A4. Inhibitors of these isoenzymes may increase voriconazole plasma concentrations

Strong CYP2C9 inductors, voriconazole [2] ---> SmPC of [2] of EMA

Voriconazole is metabolised by cytochrome P450 isoenzymes, CYP2C19, CYP2C9, and CYP3A4. Inducers of these isoenzymes may decrease voriconazole plasma concentrations

Strong CYP2C9 inhibitors, voriconazole [2] ---> SmPC of [2] of EMA

Voriconazole is metabolised by cytochrome P450 isoenzymes, CYP2C19, CYP2C9, and CYP3A4. Inhibitors of these isoenzymes may increase voriconazole plasma concentrations

Strong CYP3A4 inductors, voriconazole [2] ---> SmPC of [2] of EMA

Voriconazole is metabolised by cytochrome P450 isoenzymes, CYP2C19, CYP2C9, and CYP3A4. Inducers of these isoenzymes may decrease voriconazole plasma concentrations

Strong CYP3A4 inhibitors, voriconazole [2] ---> SmPC of [2] of EMA

Voriconazole is metabolised by cytochrome P450 isoenzymes, CYP2C19, CYP2C9, and CYP3A4. Inhibitors of these isoenzymes may increase voriconazole plasma concentrations

Sufentanil, voriconazole [2] ---> SmPC of [2] of EMA

Sulfonylureas, voriconazole [2] ---> SmPC of [2] of EMA

Voriconazole is likely to increase the plasma concentrations of sulphonylurea and cause hypoglycaemia.

Sunitinib, voriconazole [2] ---> SmPC of [2] of EMA

Tacrolimus [1], voriconazole ---> SmPC of [1] of EMA

Concomitant use of substances known to inhibit CYP3A4 may affect the metabolism of tacrolimus and thereby increase tacrolimus blood levels.

Telaprevir [1], voriconazole ---> SmPC of [1] of EMA

CYP3A4 inhibition increases the levels of voriconazole (or decreases) and telaprevir. QT interval prolongation and Torsade de Pointes have been reported. Do not co-administer

Temsirolimus [1], voriconazole ---> SmPC of [1] of EMA

Strong CYP3A4 inhibitors may increase blood concentrations of the active moieties, temsirolimus and its metabolite, sirolimus. Therefore, concomitant treatment with agents that have strong CYP3A4 inhibition potential should be avoided.

Terfenadine, voriconazole [2] ---> SmPC of [2] of EMA

The combination of voriconazole, CYP3A4 inhibitor, with drugs metabolized by CYP3A4 and may prolong the QTc interval is contraindicated and rare occurrences of torsades de pointes

Tezacaftor/ivacaftor [1], voriconazole ---> SmPC of [1] of EMA

When co-administered with strong CYP3A inhibitors, the dose should be adjusted to one Symkevi tablet twice a week, taken approximately 3 to 4 days apart.

Tipranavir, voriconazole

The mutual inhibition of CYP3A4 may increase the plasma concentrations of both principle actives

Tipranavir/ritonavir, voriconazole ---> SmPC of [tipranavir] of EMA

Due to multiple CYP isoenzyme systems involved in voriconazole metabolism, it is difficult to predict the interaction with tipranavir, co-administered with low-dose ritonavir. The co-administration of tipranavir/r and voriconazole should be avoided

Tolbutamide, voriconazole [2] ---> SmPC of [2] of EMA

Voriconazole is likely to increase the plasma concentrations of sulphonylurea and cause hypoglycaemia.

Tolvaptan, voriconazole [2] ---> SmPC of [2] of EMA

Voriconazole is likely to significantly increase the plasma concentrations of tolvaptan. The co-administration is Contraindicated.

Toremifene [1], voriconazole ---> SmPC of [1] of EMA

Theoretically the metabolism of toremifene is inhibited by drugs known to inhibit the CYP3A enzyme system which is reported to be responsible for its main metabolic pathways. Concomitant use should be carefully considered.

Tramadol, voriconazole

Dose reduction in oxycodone and other long-acting opiates metabolized by CYP3A4 (e.g., hydrocodone) should be considered. Frequent monitoring for opiate-associated adverse reactions may be necessary.

Trastuzumab emtansine [1], voriconazole ---> SmPC of [1] of EMA

Concomitant use of strong CYP3A4 inhibitors with trastuzumab emtansine should be avoided due to the potential for an increase in DM1 exposure and toxicity.

Tretinoin, voriconazole [2] ---> SmPC of [2] of EMA

Voriconazole may increase tretinoin concentrations and increase risk of adverse reactions (pseudotumor cerebri, hypercalcaemia). Dose adjustment of tretinoin is recommended during treatment with voriconazole and after its discontinuation.

Triazolam, voriconazole [2] ---> SmPC of [2] of EMA

Voriconazole is likely to increase the plasma concentrations of benzodiazepines that are metabolised by CYP3A4 and lead to a prolonged sedative effect.

Tyrosine kinase inhibitors metabolised by CYP3A4, voriconazole [2] ---> SmPC of [2] of EMA

Upadacitinib [1], voriconazole ---> SmPC of [1] of EMA

Upadacitinib exposure is increased when co-administered with strong CYP3A4 inhibitors. Consider alternatives to strong CYP3A4 inhibitor medications when used in the long-term.

Vemurafenib [1], voriconazole ---> SmPC of [1] of EMA

Vemurafenib should be used with caution in combination with potent inhibitors of CYP3A4, glucuronidation and/or transport proteins

Venetoclax, voriconazole [2] ---> SmPC of [2] of EMA

Vinblastine, voriconazole [2] ---> SmPC of [2] of EMA

Voriconazole is likely to increase the plasma concentrations of vinca alkaloids and lead to neurotoxicity.

Vinca alkaloids, voriconazole [2] ---> SmPC of [2] of EMA

Voriconazole is likely to increase the plasma concentrations of vinca alkaloids and lead to neurotoxicity.

Vincristine, voriconazole [2] ---> SmPC of [2] of EMA

Voriconazole is likely to increase the plasma concentrations of vinca alkaloids and lead to neurotoxicity.

Voriconazole [1], warfarin ---> SmPC of [1] of EMA

Voriconazole [1], women of childbearing potential ---> SmPC of [1] of EMA

Women of child-bearing potential must always use effective contraception during treatment.

Voriconazole, vortioxetine [2] ---> SmPC of [2] of EMA

The strong CYP3A4 inhibition may increase the AUC of vortioxetine. No dosage adjustment necessary. It is caution recommended with CYP2D6 poor metabolisers

Voriconazole, zanubrutinib [2] ---> SmPC of [2] of EMA

If a strong CYP3A inhibitor must be used (e.g., posaconazole, voriconazole, ketoconazole, itraconazole, clarithromycin, indinavir, lopinavir, ritonavir, telaprevir), reduce the BRUKINSA dose to 80 mg (one capsule) for the duration of the inhibitor use.

CONTRAINDICATIONS of Voriconazole (Vfend)

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

Coadministration of voriconazole is contraindicated with medicinal products that are highly dependent on CYP3A4 for metabolism, and for which elevated plasma concentrations are associated with serious and/or life-threatening reactions (see section 4.5):

- Terfenadine, Astemizole

- Cisapride

- Pimozide, Lurasidone

- Quinidine

- Ivabradine

- Ergot alkaloids (e.g., ergotamine, dihydroergotamine)

- Sirolimus

- Naloxegol

- Tolvaptan

- Finerenone

- Venetoclax: Coadministration contraindicated at initiation and during venetoclax dose titration phase.

Coadministration of voriconazole is contraindicated with medicinal products that induce CYP3A4 and significantly reduce voriconazole plasma concentrations:

- Coadministration with rifampicin, carbamazepine, long-acting barbiturates e.g., phenobarbital, and St. John's Wort (see section 4.5).

- Efavirenz: Coadministration of standard doses of voriconazole with efavirenz doses of 400 mg once daily or higher is contraindicated (see section 4.5). For information on coadministration of voriconazole and lower doses of efavirenz see section 4.4.

- Ritonavir: Coadministration with high-dose ritonavir (400 mg and above twice daily) is contraindicated (see section 4.5). For information on coadministration with lower doses of ritonavir see section 4.4.

https://www.ema.europa.eu/en/documents/product-information/vfend-epar-product-information_en.pdf 14/07/2025

Other trade names: Voriconazole Accord, Voriconazole Hikma (previously Voriconazole Hospira),

Vortioxetina (Brintellix)

Ability to drive, vortioxetine [2] ---> SmPC of [2] of EMA

As adverse reactions such as dizziness have been reported, patients should exercise caution when driving or operating hazardous machinery, especially when starting treatment with vortioxetine or when changing the dose.

Acetylsalicylic acid, vortioxetine [2] ---> SmPC of [2] of EMA

Caution should be exercised when vortioxetine is combined with oral anticoagulants or antiplatelet medicinal products due to a potential increased risk of bleeding

Alcohol, vortioxetine [2] ---> SmPC of [2] of EMA

Alcohol intake is not advisable during antidepressant treatment

Amiodarone, vortioxetine [2] ---> SmPC of [2] of EMA

The strong CYP2C9 inhibition may increase the AUC of vortioxetine. It is caution recommended with CYP2D6 poor metabolisers

Antidepressants with serotonergic effect, butyrophenones ---> SmPC of [vortioxetine] of EMA

Caution is advised when co-administrating medicines capable of lowering the seizure threshold.

Antidepressants with serotonergic effect, lithium ---> SmPC of [vortioxetine] of EMA

There have been reports of enhanced effects when antidepressants with serotonergic effect have been given together with lithium

Antidepressants with serotonergic effect, lithium carbonate ---> SmPC of [vortioxetine] of EMA

There have been reports of enhanced effects when antidepressants with serotonergic effect have been given together with lithium

Antidepressants with serotonergic effect, mefloquine ---> SmPC of [vortioxetine] of EMA

Caution is advised when co-administrating medicines capable of lowering the seizure threshold.

Antidepressants with serotonergic effect, neuroleptics ---> SmPC of [vortioxetine] of EMA

Caution is advised when co-administrating medicines capable of lowering the seizure threshold.

Antidepressants with serotonergic effect, oral anticoagulants ---> SmPC of [vortioxetine] of EMA

Caution should be exercised when a serotonergic medicine is combined with oral anticoagulants due to a potential increased risk of bleeding

Antidepressants with serotonergic effect, phenothiazines ---> SmPC of [vortioxetine] of EMA

Caution is advised when co-administrating medicines capable of lowering the seizure threshold.

Antidepressants with serotonergic effect, platelet aggregation inhibitors ---> SmPC of [vortioxetine] of EMA

Caution should be exercised when a serotonergic medicine is combined with oral antiplatelet medicinal products due to a potential increased risk of bleeding

Antidepressants with serotonergic effect, seizure-threshold lowering drugs ---> SmPC of [vortioxetine] of EMA

Caution is advised when co-administrating medicines capable of lowering the seizure threshold.

Antidepressants with serotonergic effect, St. John's wort ---> SmPC of [vortioxetine] of EMA

Concomitant use of antidepressants with serotonergic effect and St. John's wort may result in a higher incidence of adverse reactions including serotonin syndrome

Antidepressants with serotonergic effect, thioxanthenes ---> SmPC of [vortioxetine] of EMA

Caution is advised when co-administrating medicines capable of lowering the seizure threshold.

Antidepressants with serotonergic effect, tramadol ---> SmPC of [vortioxetine] of EMA

Caution is advised when co-administrating medicines capable of lowering the seizure threshold.

Antidepressants with serotonergic effect, tricyclic antidepressant ---> SmPC of [vortioxetine] of EMA

Caution is advised when co-administrating medicines capable of lowering the seizure threshold.

Antidepressants with serotonergic effect, tryptophan ---> SmPC of [vortioxetine] of EMA

There have been reports of enhanced effects when antidepressants with serotonergic effect have been given together with tryptophan

Breast-feeding, vortioxetine [2] ---> SmPC of [2] of EMA

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Brintellix treatment taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Bupropion, vortioxetine [2] ---> SmPC of [2] of EMA

The exposure to vortioxetine increased 2.3-fold for area under the curve (AUC) when vortioxetine 10 mg/day was co-administered with bupropion (a strong CYP2D6 inhibitor 150 mg twice daily) for 14 days in healthy subjects.

Butyrophenones, vortioxetine [2] ---> SmPC of [2] of EMA

Antidepressants with serotonergic effect can lower the seizure threshold. Caution is advised when concomitantly using other medicinal products capable of lowering the seizure threshold

Carbamazepine, vortioxetine [2] ---> SmPC of [2] of EMA

Depending on individual patient response, a dose adjustment may be considered if a broad cytochrome P450 inducer (e.g., rifampicin, carbamazepine, phenytoin) is added to vortioxetine treatment (see section 4.2).

Clarithromycin, vortioxetine [2] ---> SmPC of [2] of EMA

The strong CYP3A4 inhibition may increase the AUC of vortioxetine. No dosage adjustment necessary. It is caution recommended with CYP2D6 poor metabolisers

Conivaptan, vortioxetine [2] ---> SmPC of [2] of EMA

The strong CYP3A4 inhibition may increase the AUC of vortioxetine. No dosage adjustment necessary. It is caution recommended with CYP2D6 poor metabolisers

CYP2C9 and CYP3A4 inhibitors, vortioxetine [2] ---> SmPC of [2] of EMA

Co-administration of strong inhibitors of CYP3A4 and inhibitors of CYP2C9 to CYP2D6 poor metabolisers has not been investigated specifically, but it is anticipated that it will lead to a more marked increased exposure of vortioxetine

CYP450 substrates, vortioxetine [2] ---> SmPC of [2] of EMA

In vitro, vortioxetine did not show any relevant potential for inhibition or induction of cytochrome P450 isozymes (see section 5.2).

Cytochrome P450, vortioxetine [2] ---> SmPC of [2] of EMA

In vitro, vortioxetine did not show any relevant potential for inhibition or induction of cytochrome P450 isozymes

Diazepam, vortioxetine [2] ---> SmPC of [2] of EMA

No pharmacodynamic interactions were observed. No significant impairment, relative to placebo, in cognitive function was observed for vortioxetine following co-administration with a single 10 mg dose of diazepam.

Electroconvulsive therapy, vortioxetine [2] ---> SmPC of [2] of EMA

There is no clinical experience with concurrent administration of vortioxetine and ECT, therefore caution is advisable.

Enzyme inductors, vortioxetine [2] ---> SmPC of [2] of EMA

Fertility, vortioxetine [2] ---> SmPC of [2] of EMA

Impact on human fertility has not been observed so far.

Fluconazole, vortioxetine [2] ---> SmPC of [2] of EMA

The strong CYP2C9 inhibition may increase the AUC of vortioxetine. It is caution recommended with CYP2D6 poor metabolisers

Fluoxetine, vortioxetine [2] ---> SmPC of [2] of EMA

Depending on individual patient response, a lower dose of vortioxetine may be considered if strong CYP2D6 inhibitor is added to vortioxetine treatment

Irreversible non-selective MAO-inhibitors, vortioxetine [2] ---> SmPC of [2] of EMA

Combination contraindicated. Vortioxetine should not be given within at least 14 days BEFORE initia. nor 14 days AFTER disconti. a therapy with irreversible non-selective MAOI

Irreversible selective MAO-B inhibitors, vortioxetine [2] ---> SmPC of [2] of EMA

The combination of vortioxetine with irreversible MAO-B inhibitors, such as selegiline or rasagiline should be administered with caution. Close monitoring for serotonin syndrome is necessary if used concomitantly (see section 4.4).

Itraconazol, vortioxetine [2] ---> SmPC of [2] of EMA

The strong CYP3A4 inhibition may increase the AUC of vortioxetine. No dosage adjustment necessary. It is caution recommended with CYP2D6 poor metabolisers

Ketoconazole, vortioxetine [2] ---> SmPC of [2] of EMA

The strong CYP3A4 inhibition may increase the AUC of vortioxetine. No dosage adjustment necessary. It is caution recommended with CYP2D6 poor metabolisers

Linezolid, vortioxetine [2] ---> SmPC of [2] of EMA

The combination of vortioxetine with a weak reversible and non-selective MAOI, such as the antibiotic linezolid, is contraindicated

Lithium, vortioxetine [2] ---> SmPC of [2] of EMA

There have been reports of enhanced effects when antidepressants with serotonergic effect have been given together with lithium or tryptophan; therefore, concomitant use of vortioxetine with these medicinal products should be undertaken with caution.

Mefloquine, vortioxetine [2] ---> SmPC of [2] of EMA

Antidepressants with serotonergic effect can lower the seizure threshold. Caution is advised when concomitantly using other medicinal products capable of lowering the seizure threshold

Moclobemide, vortioxetine [2] ---> SmPC of [2] of EMA

The combination of vortioxetine with a reversible and selective MAO-A inhibitor, such as moclobemide, is contraindicated

Nefazodone, vortioxetine [2] ---> SmPC of [2] of EMA

The strong CYP3A4 inhibition may increase the AUC of vortioxetine. No dosage adjustment necessary. It is caution recommended with CYP2D6 poor metabolisers

Neuroleptics, vortioxetine [2] ---> SmPC of [2] of EMA

Antidepressants with serotonergic effect can lower the seizure threshold. Caution is advised when concomitantly using other medicinal products capable of lowering the seizure threshold

NSAID, vortioxetine [2] ---> SmPC of [2] of EMA

Caution should be exercised when vortioxetine is combined with oral anticoagulants or antiplatelet medicinal products due to a potential increased risk of bleeding

Omeprazole, vortioxetine

No inhibitory effect of 40 mg single-dose omeprazole (CYP2C19 inhibitor) was observed on the multiple-dose pharmacokinetics of vortioxetine in healthy subjects.

Opiates, vortioxetine [2] ---> SmPC of [2] of EMA

Co-administration of medicinal products with serotonergic effect e.g.opioids (including tramadol) and triptans (including sumatriptan) may lead to serotonin syndrome (see section 4.4).

Oral anticoagulants, vortioxetine [2] ---> SmPC of [2] of EMA

No significant effects, relative to placebo, were observed in the levels of sex hormones following co-administration of vortioxetine with a combined oral contraceptive (ethinyl estradiol 30 痢/ levonorgestrel 150 痢).

Paroxetine, vortioxetine [2] ---> SmPC of [2] of EMA

Depending on individual patient response, a lower dose of vortioxetine may be considered if strong CYP2D6 inhibitor is added to vortioxetine treatment

Phenothiazines, vortioxetine [2] ---> SmPC of [2] of EMA

Antidepressants with serotonergic effect can lower the seizure threshold. Caution is advised when concomitantly using other medicinal products capable of lowering the seizure threshold

Phenytoin, vortioxetine [2] ---> SmPC of [2] of EMA

Platelet aggregation inhibitors, vortioxetine [2] ---> SmPC of [2] of EMA

Caution should be exercised when vortioxetine is combined with oral anticoagulants or antiplatelet medicinal products due to a potential increased risk of bleeding

Pregnancy, vortioxetine [2] ---> SmPC of [2] of EMA

Brintellix should only be administered to pregnant women if the expected benefits outweigh the potential risk to the foetus.

Quinidine, vortioxetine [2] ---> SmPC of [2] of EMA

Depending on individual patient response, a lower dose of vortioxetine may be considered if strong CYP2D6 inhibitor is added to vortioxetine treatment

Rasagiline, vortioxetine [2] ---> SmPC of [2] of EMA

Reversible non-selective MAO-inhibitors, vortioxetine [2] ---> SmPC of [2] of EMA

The combination of vortioxetine with a weak reversible and non-selective MAOI, such as the antibiotic linezolid, is contraindicated

Reversible selective MAO-A inhibitors, vortioxetine [2] ---> SmPC of [2] of EMA

The combination of vortioxetine with a reversible and selective MAO-A inhibitor, such as moclobemide, is contraindicated

Rifampicin, vortioxetine [2] ---> SmPC of [2] of EMA

Ropeginterferon alfa-2b [1], vortioxetine ---> SmPC of [1] of EMA

Caution is recommended with CYP2D6 substrates combined with ropeginterferon alfa-2b. Ropeginterferon alfa-2b may inhibit the activity of CYP1A2 and CYP2D6 and thus may increase the blood concentrations of these medicinal products.

Seizure-threshold lowering drugs, vortioxetine [2] ---> SmPC of [2] of EMA

Antidepressants with serotonergic effect can lower the seizure threshold. Caution is advised when concomitantly using other medicinal products capable of lowering the seizure threshold

Selegiline, vortioxetine [2] ---> SmPC of [2] of EMA

Serotonergic medicines, vortioxetine [2] ---> SmPC of [2] of EMA

Co-administration of medicinal products with serotonergic effect e.g.opioids (including tramadol) and triptans (including sumatriptan) may lead to serotonin syndrome (see section 4.4).

SNRIs, vortioxetine [2] ---> SmPC of [2] of EMA

Antidepressants with serotonergic effect can lower the seizure threshold. Caution is advised when concomitantly using other medicinal products capable of lowering the seizure threshold

SSRI, vortioxetine [2] ---> SmPC of [2] of EMA

Antidepressants with serotonergic effect can lower the seizure threshold. Caution is advised when concomitantly using other medicinal products capable of lowering the seizure threshold

St. John's wort, vortioxetine [2] ---> SmPC of [2] of EMA

Concomitant use of antidepressants with serotonergic effect and herbal remedies containing St. John's wort (Hypericum perforatum) may result in a higher incidence of adverse reactions including serotonin syndrome

Strong CYP2C9 inhibitors, vortioxetine [2] ---> SmPC of [2] of EMA

The strong CYP2C9 inhibition may increase the AUC of vortioxetine. It is caution recommended with CYP2D6 poor metabolisers

Strong CYP2D6 inhibitors, vortioxetine [2] ---> SmPC of [2] of EMA

Depending on individual patient response, a lower dose of vortioxetine may be considered if strong CYP2D6 inhibitor is added to vortioxetine treatment

Strong CYP3A4 inhibitors, vortioxetine [2] ---> SmPC of [2] of EMA

The strong CYP3A4 inhibition may increase the AUC of vortioxetine. No dosage adjustment necessary. It is caution recommended with CYP2D6 poor metabolisers

Sumatriptan, vortioxetine [2] ---> SmPC of [2] of EMA

Co-administration of medicinal products with serotonergic effect e.g.opioids (including tramadol) and triptans (including sumatriptan) may lead to serotonin syndrome (see section 4.4).

Telithromycin, vortioxetine [2] ---> SmPC of [2] of EMA

The strong CYP3A4 inhibition may increase the AUC of vortioxetine. No dosage adjustment necessary. It is caution recommended with CYP2D6 poor metabolisers

Thioxanthenes, vortioxetine [2] ---> SmPC of [2] of EMA

Antidepressants with serotonergic effect can lower the seizure threshold. Caution is advised when concomitantly using other medicinal products capable of lowering the seizure threshold

Tramadol, vortioxetine [2] ---> SmPC of [2] of EMA

Co-administration of medicinal products with serotonergic effect e.g.opioids (including tramadol) and triptans (including sumatriptan) may lead to serotonin syndrome (see section 4.4).

Tricyclic antidepressant, vortioxetine [2] ---> SmPC of [2] of EMA

Antidepressants with serotonergic effect can lower the seizure threshold. Caution is advised when concomitantly using other medicinal products capable of lowering the seizure threshold

Triptans, vortioxetine [2] ---> SmPC of [2] of EMA

Co-administration of medicinal products with serotonergic effect e.g.opioids (including tramadol) and triptans (including sumatriptan) may lead to serotonin syndrome (see section 4.4).

Tryptophan, vortioxetine [2] ---> SmPC of [2] of EMA

Urine drug screens, vortioxetine [2] ---> SmPC of [2] of EMA

Caution should be exercised in the interpretation of positive urine drug screen results, and confirmation by an alternative analytical technique (e.g., chromatographic methods) should be considered.

Voriconazole, vortioxetine [2] ---> SmPC of [2] of EMA

The strong CYP3A4 inhibition may increase the AUC of vortioxetine. No dosage adjustment necessary. It is caution recommended with CYP2D6 poor metabolisers

CONTRAINDICATIONS of Vortioxetine (Brintellix)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

- Concomitant use with nonselective monoamine oxidase inhibitors (MAOIs) or selective MAO-A inhibitors

https://www.ema.europa.eu/en/documents/product-information/brintellix-epar-product-information_en.pdf 19/01/2026

Vosoritide (Voxzogo)

Ability to drive, vosoritide [2] ---> SmPC of [2] of EMA

The patient's response to treatment should be considered and if appropriate, advised not to drive, cycle or use machines for at least 60 minutes after injection.

Breast-feeding, vosoritide [2] ---> SmPC of [2] of EMA

A risk to newborns/infants cannot be excluded. Vosoritide should not be used during breast-feeding.

Cytochrome P450, vosoritide [2] ---> SmPC of [2] of EMA

Results suggested that vosoritide is unlikely to cause CYP- or transporter-mediated drug-drug interactions in humans when the medicinal product is administered concomitantly with other medicinal products.

Fertility, vosoritide [2] ---> SmPC of [2] of EMA

No impairment of male or female fertility has been observed in nonclinical studies

Pregnancy, vosoritide [2] ---> SmPC of [2] of EMA

As a precautionary measure, it is preferable to avoid the use of vosoritide during pregnancy.

Recombinant human protein, vosoritide [2] ---> SmPC of [2] of EMA

Because it is a recombinant human protein, vosoritide is an unlikely candidate for drug-drug interactions.

CONTRAINDICATIONS of Vosoritide (Voxzogo)

- Hypersensitivity to the active substance(s) or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/voxzogo-epar-product-information_en.pdf 18/11/2025

Voxelotor (Oxbryta)

Ability to drive, voxelotor [2] ---> SmPC of [2] of EMA

Oxbryta has no or negligible influence on the ability to drive and use machines.

Alfentanyl, voxelotor [2] ---> SmPC of [2] of EMA

Coadministration of voxelotor with sensitive CYP3A4 substrates with a narrow therapeutic index should be avoided. If concomitant use is unavoidable, consider dose reduction of the sensitive CYP3A4 substrate(s).

BCRP substrates, voxelotor [2] ---> SmPC of [2] of EMA

It is not known if voxelotor affects the oral absorption of breast cancer resistance protein (BCRP) substrates.

Bile salt export pump, voxelotor [2] ---> SmPC of [2] of EMA

Voxelotor is not an inhibitor of bile salt export pump (BSEP).

Breast-feeding, voxelotor [2] ---> SmPC of [2] of EMA

A risk to the newborns/infants cannot be excluded. Voxelotor should not be used during breast-feeding.

Bupropion, voxelotor [2] ---> SmPC of [2] of EMA

In vitro studies indicated that voxelotor acts as an inhibitor and inducer of CYP2B6 (see section 5.2). The clinical relevance is currently unknown, and caution is recommended when co-administering voxelotor with sensitive substrates of CYP2B6.

Caffeine, voxelotor [2] ---> SmPC of [2] of EMA

Voxelotor did not change the systemic exposure of caffeine (CYP1A2 substrate) and metoprolol (CYP2D6 substrate).

Carbamazepine, voxelotor [2] ---> SmPC of [2] of EMA

Coadministration of strong CYP3A4 inducers may decrease voxelotor exposures and may lead to reduced efficacy. Coadministration of voxelotor with strong CYP3A4 inducers should be avoided.

CYP2B6 substrates, voxelotor [2] ---> SmPC of [2] of EMA

Digoxin, voxelotor [2] ---> SmPC of [2] of EMA

Concomitant use of voxelotor with digoxin (a P-gp substrate) did not alter digoxin to a clinically relevant extent.

Drugs primarily metabolised by CYP3A4 with narrow therapeutic index, voxelotor [2] ---> SmPC of [2] of EMA

Efavirenz, voxelotor [2] ---> SmPC of [2] of EMA

Exagamglogene autotemcel [1], voxelotor ---> SmPC of [1] of EMA

Discontinue the use of voxelotor and crizanlizumab at least 8 weeks prior to start of mobilisation and conditioning, as their interaction potential with mobilisation and myeloablative conditioning medicinal products is not known.

Fertility, voxelotor [2] ---> SmPC of [2] of EMA

No human data are available on the effect of voxelotor on fertility. In rats, effects on sperm motility and morphology were observed. These effects did not, however, affect the reproductive performance (see section 5.3). Relevance to human is not known.

Hydroxycarbamide, voxelotor [2] ---> SmPC of [2] of EMA

Itraconazole (a strong CYP3A4 inhibitor), omeprazole (acid reducing agent), and hydroxycarbamide had no effect on the pharmacokinetics of voxelotor.

Itraconazol, voxelotor [2] ---> SmPC of [2] of EMA

Itraconazole (a strong CYP3A4 inhibitor), omeprazole (acid reducing agent), and hydroxycarbamide had no effect on the pharmacokinetics of voxelotor.

MATE1 substrates with small therapeutic index, voxelotor [2] ---> SmPC of [2] of EMA

Voxelotor may act as an inhibitor of OATP1B1, OAT3 and MATE1 transporters. Caution is recommended when co-administering voxelotor with sensitive substrates of these transporters, especially for those substrates with a narrow therapeutic index.

Metabolized by cytochrome P450, voxelotor [2] ---> SmPC of [2] of EMA

Caution is recommended when co-administering voxelotor with sensitive substrates of CYP enzymes.

Metoprolol, voxelotor [2] ---> SmPC of [2] of EMA

Voxelotor did not change the systemic exposure of caffeine (CYP1A2 substrate) and metoprolol (CYP2D6 substrate).

Midazolam, voxelotor [2] ---> SmPC of [2] of EMA

Voxelotor increased the systemic exposure of midazolam (a sensitive CYP3A4 substrate). The observed exposure increase of the CYP3A4 substrate midazolam was 1.6-fold in healthy subjects at a voxelotor sub-therapeutic dose

OAT1 substrates with narrow therapeutic window, voxelotor [2] ---> SmPC of [2] of EMA

OAT3 substrates with narrow therapeutic window, voxelotor [2] ---> SmPC of [2] of EMA

Omeprazole, voxelotor [2] ---> SmPC of [2] of EMA

Itraconazole (a strong CYP3A4 inhibitor), omeprazole (acid reducing agent), and hydroxycarbamide had no effect on the pharmacokinetics of voxelotor.

Oral contraceptives, voxelotor [2] ---> SmPC of [2] of EMA

Based on the results of in vitro studies, a negative impact of voxelotor on contraceptive efficacy is not expected.

Phenobarbital, voxelotor [2] ---> SmPC of [2] of EMA

Coadministration of strong CYP3A4 inducers may decrease voxelotor exposures and may lead to reduced efficacy. Coadministration of voxelotor with strong CYP3A4 inducers should be avoided.

Phenytoin, voxelotor [2] ---> SmPC of [2] of EMA

Coadministration of strong CYP3A4 inducers may decrease voxelotor exposures and may lead to reduced efficacy. Coadministration of voxelotor with strong CYP3A4 inducers should be avoided.

Pregnancy, voxelotor [2] ---> SmPC of [2] of EMA

A risk to the newborns/infants cannot be excluded. Voxelotor should not be used during breast-feeding.

Rifampicin, voxelotor [2] ---> SmPC of [2] of EMA

Coadministration of strong CYP3A4 inducers may decrease voxelotor exposures and may lead to reduced efficacy. Coadministration of voxelotor with strong CYP3A4 inducers should be avoided.

Sirolimus, voxelotor [2] ---> SmPC of [2] of EMA

St. John's wort, voxelotor [2] ---> SmPC of [2] of EMA

Coadministration of strong CYP3A4 inducers may decrease voxelotor exposures and may lead to reduced efficacy. Coadministration of voxelotor with strong CYP3A4 inducers should be avoided.

Strong CYP3A4 inductors, voxelotor [2] ---> SmPC of [2] of EMA

Coadministration of strong CYP3A4 inducers may decrease voxelotor exposures and may lead to reduced efficacy. Coadministration of voxelotor with strong CYP3A4 inducers should be avoided.

Tacrolimus, voxelotor [2] ---> SmPC of [2] of EMA

CONTRAINDICATIONS of Voxelotor (Oxbryta)

- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. (see section 4.4.).

https://www.ema.europa.eu/en/documents/product-information/oxbryta-epar-product-information_en.pdf 04/06/2024 (withdrawn)

Vutrisiran (Amvuttra)

Breast-feeding, vutrisiran [2] ---> SmPC of [2] of EMA

A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Amvuttra, taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Fertility, vutrisiran [2] ---> SmPC of [2] of EMA

There are no data on the effects of Amvuttra on human fertility. No impact on male or female fertility was detected in animal studies (see section 5.3).

Pregnancy, vutrisiran [2] ---> SmPC of [2] of EMA

Due to the potential teratogenic risk arising from unbalanced vitamin A levels, Amvuttra should not be used during pregnancy.

Vutrisiran [1], women of childbearing potential ---> SmPC of [1] of EMA

Treatment with Amvuttra reduces serum levels of vitamin A. Both too high or too low vitamin A levels may be associated with an increased risk of foetal malformation.

Vutrisiran [1], women of childbearing potential1 ---> SmPC of [1] of EMA

Therefore, pregnancy should be excluded before initiation of treatment and women of childbearing potential should use effective contraception.

CONTRAINDICATIONS of Vutrisiran (Amvuttra)

- Severe hypersensitivity (e.g., anaphylaxis) to the active substance or to any of the excipients listed in section 6.1.

https://www.ema.europa.eu/en/documents/product-information/amvuttra-epar-product-information_en.pdf 13/08/2025

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