Varicella Vaccine

Pharmacologic Category

Vaccine; Vaccine, Live (Viral)

Dosing: Adult

Varicella immunization: SubQ:

US labeling: Two doses of 0.5 mL separated by ≥4 weeks (4 to 8 weeks apart per ACIP). Note: The ACIP recommends that all children and adults without evidence of immunity receive 2 doses of the vaccine; those who received only 1 dose of a varicella-containing vaccine receive a second dose (CDC/ACIP [Marin 2007]).

Canadian labeling: Two single doses 0.5 mL separated by 4 to 8 weeks (Varivax III) or ≥6 weeks (Varilrix); Note: The NACI recommends that adolescents (≥13 years of age) and adults (<50 years of age) who received only 1 dose of vaccine receive a second dose (NACI 2016).

Postexposure prophylaxis (healthy, previously unvaccinated individuals) (off-label use): SubQ: 0.5 mL administered ideally within 72 hours postexposure but may be used up to 120 hours (5 days) postexposure (CDC/ACIP [Marin 2007])

* See Dosage and Administration in AHFS Essentials for additional information.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling

Dosing: Pediatric

Note: Consult CDC/ACIP annual immunization schedules for additional information including specific detailed recommendations for catch-up scenarios and/or care of patients with high-risk conditions. According to ACIP, doses administered ≤4 days before minimum interval or age are considered valid; however, local or state mandates may supersede this timeframe (ACIP [Ezeanolue 2020]).

Primary immunization:

CDC/ACIP recommendations: Children ≥12 months: SubQ: 0.5 mL per dose for a total of 2 doses administered as follows: 12 to 15 months of age and 4 to 6 years of age. The second dose may be administered earlier provided ≥3 months have elapsed after the first dose. If the second dose was administered ≥4 weeks after the first dose, it may be considered as valid (CDC/ACIP [Marin 2007]).

Canadian labeling: National Advisory Committee on Immunization (NACI) recommends 2 doses of 0.5 mL with first dose administered at 12 to 15 months of age. Separate doses by ≥3 months; however, if rapid protection is necessary, may administer second dose after ≥4 weeks (NACI 2016).

Children:

Varilrix: SubQ: 2 doses of 0.5 mL separated by ≥6 weeks.

Varivax III: SubQ: 0.5 mL as a single dose.

Adolescents: SubQ: 2 doses of 0.5 mL separated by 4 to 8 weeks (Varivax III) or ≥6 weeks (Varilrix); Note: The NACI recommends that adolescents who received only 1 dose of vaccine receive a second dose (NACI 2016).

Catch-up immunization: Children and Adolescents: ACIP recommendations (CDC/ACIP [Marin 2007]): Note: Do not restart the series. If doses have been given, begin the below schedule at the applicable dose number. SubQ: 0.5 mL per dose for a total of 2 doses administered as follows:

First dose given on the elected date.

Second dose given at least 3 months after the first dose (if age <13 years) or at least 4 weeks after the first dose (if age ≥13 years).

Postexposure prophylaxis (healthy, previously unvaccinated individuals): Children (≥12 months) and Adolescents: SubQ: 0.5 mL administered ideally within 72 hours postexposure but may be used up to 120 hours (5 days) postexposure (CDC/ACIP [Marin 2007]).

Dosing: Renal Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling.

Use: Labeled Indications

Varicella prevention: For the prevention of varicella in persons 12 months and older

The Advisory Committee on Immunization Practices (ACIP) recommends vaccination for all children, adolescents, and adults who do not have evidence of immunity (CDC/ACIP [Marin, 2007]). Vaccination is especially important for:

• Health care personnel

• Household contacts of immunocompromised persons

• Persons living or working in environments where transmission is likely (teachers, child-care workers, residents and staff of institutional settings)

• Persons in environments where transmission has been reported

• Nonpregnant women of childbearing age

• Adolescents and adults in households with children

• International travelers

Varilrix (Canadian product): Also approved for use in high-risk patients (eg, acute leukemia [complete remission and lymphocyte count ≥1,200/mm3 or that no other evidence of lack of cellular immune competence exists], planned organ transplantation [6 to 8 weeks prior to], receiving immunosuppressive treatment [with lymphocyte count ≥1,200/mm3], or other chronic diseases); approved for use in susceptible healthy contacts of high-risk patients.

* See Uses in AHFS Essentials for additional information.

Use: Off-Label: Adult

Varicella postexposure prophylaxisLevel of Evidence [G]

Based on the Centers for Disease Control and Prevention "Prevention of Varicella: Recommendations of the Advisory Committee on Immunization Practices (ACIP)", varicella virus vaccine given within 3 days (possibly 5 days) after exposure to varicella rash is effective in preventing illness or modifying severity of disease in persons without other evidence of immunity.

Level of Evidence Definitions

Level of Evidence Scale

Clinical Practice Guidelines

ACIP, "General Best Practice Guidelines for Immunization," April 2017

CDC, Epidemiology and Prevention of Vaccine-Preventable Diseases (Pink Book), 2015

CDC, Health Information for International Travel (Yellow Book) 2018

CDC, "Immunization of Health-Care Personnel," November 2011

CDC, “Prevention of Varicella: Recommendations of the Advisory Committee on Immunization Practices (ACIP),” June 22, 2007

CDC, Recommended Immunization Schedules (Adults)

IDSA, "Vaccination of the Immunocompromised Host," 2013

NACI/CATMAT, Canadian Immunization Guide, 2017

Administration: IM

SubQ administration is recommended; however, doses inadvertently given IM have resulted in similar seroconversion (ACIP [Kroger 2017]). Do not mix with other vaccines or injections; separate needles and syringes should be used for each injection (ACIP [Kroger 2017]). To prevent syncope related injuries, patients should be vaccinated while seated or lying down (ACIP [Kroger 2017]). US law requires that the date of administration, the vaccine manufacturer, lot number of vaccine, and the administering person's name, title, and address be entered into the patient's permanent medical record.

Administration: Subcutaneous

For SubQ injection only; inject in the outer aspect of upper arm or the anterolateral thigh. Varilrix (Canadian product) is to be administered in the deltoid region only. Do not administer IV or IM. Administer immediately following reconstitution. To prevent syncope related injuries, patients should be vaccinated while seated or lying down (ACIP [Kroger 2017]). US law requires that the date of administration, the vaccine manufacturer, lot number of vaccine, and the administering person's name, title, and address be entered into the patient's permanent medical record.

Administration: Pediatric

Parenteral:

SubQ: Inject subcutaneously into the outer aspect of the upper arm or anterolateral aspect of the thigh; not for IV or IM administration. Do not mix with other vaccines or injections; separate needles and syringes should be used for each injection (ACIP [Ezeanolue 2020]). To prevent syncope-related injuries, adolescents should be vaccinated while seated or lying down (ACIP [Ezeanolue 2020]). US law requires that the date of administration, the vaccine manufacturer, lot number of vaccine, vaccine information statement (VIS) edition date and date it was provided, and the administering person's name, title, and address be recorded.

Storage/Stability

Prior to reconstitution and during shipping, store vaccine in freezer at -50°C to -15°C (-58°F to 5°F). Use of dry ice may subject vaccine to temperatures colder than -58°F (-50°C). Vaccine may be stored under refrigeration at 2°C to 8°C (36°F to 46°F) for up to 72 hours. Protect from light. Store diluent at room temperature of 20°C to 25°C (68°F to 77°F) or in refrigerator. Gently agitate to mix thoroughly. (Total volume of reconstituted vaccine will be ~0.5 mL.) Administer immediately following reconstitution, discard reconstituted vaccine if not used within 30 minutes.

Varilrix (Canadian product): Prior to reconstitution, store vaccine under refrigeration at 2°C to 8°C (36°F to 46°F). Vaccine not affected by freezing. Store diluent at 25°C (77°F) or under refrigeration. Following reconstitution, vaccine may be stored for 90 minutes at 25°C (77°F) or up to 8 hours under refrigeration. Discard if not used within recommended times.

Preparation for Administration: Adult

Use the total volume of the provided diluent to reconstitute vaccine. Gently agitate to mix thoroughly. (Total volume of reconstituted vaccine will be ~0.5 mL.) Administer vaccine within 30 minutes of preparation (90 minutes for Varilrix [Canadian product]).

Preparation for Administration: Pediatric

SubQ: Reconstitute vaccine with total volume of the provided diluent. Gently agitate to mix thoroughly. Total volume of reconstituted vaccine will be ~0.5 mL. Administer vaccine within 30 minutes of preparation.

Medication Patient Education with HCAHPS Considerations

What is this drug used for?

• It is used to prevent chickenpox infection.

Frequently reported side effects of this drug

• Irritability

• Injection site pain, swelling, or irritation

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Chickenpox-like rash

• Shingles

• Wheezing

• Bruising

• Flat spots under skin

• Abnormal gait

• Severe skin irritation

• Skin infection

• Headache

• Chills

• Nausea

• Vomiting

• Neck rigidity

• Seizures

• Fatigue

• Confusion

• Sensitivity to light

• Shortness of breath

• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Medication Safety Issues

Sound-alike/look-alike issues:

Other safety concerns:

Medication Guide and/or Vaccine Information Statement (VIS)

In the U.S, the appropriate CDC-approved Vaccine Information Statement (VIS) must be provided to the patient prior to administering each dose of this vaccine; VIS is available at http://www.cdc.gov/vaccines/hcp/vis/vis-statements/varicella.html.

Contraindications

Severe allergic or anaphylactic reaction to the vaccine, neomycin, gelatin, or any component of the formulation; immunosuppressed or immunodeficient individuals including individuals with leukemia, lymphomas, or other malignant neoplasms affecting the bone marrow or lymphatic systems; persons with AIDs or other clinical manifestations of HIV; those receiving immunosuppressive therapy (including immunosuppressive doses of corticosteroids); history of primary and acquired immunodeficiency states; active, untreated tuberculosis; current febrile illness (per manufacturer labeling); pregnancy

Canadian labeling: Additional contraindications (not in US labeling): Varivax III: Family history of congenital or hereditary immunodeficiency (unless immune competence of vaccine recipient is demonstrated); Varilrix: Primary or acquired immunodeficiency with a total lymphocyte count <1,200/mm3

Warnings/Precautions

Concerns related to adverse effects:

• Anaphylactoid/hypersensitivity reactions: Immediate treatment (including epinephrine 1 mg/mL) for anaphylactoid and/or hypersensitivity reactions should be available during vaccine use (ACIP [Ezeanolue 2020]).

• CNS infection: Cases of encephalitis or meningitis caused by vaccine strain varicella virus have been reported in immunocompetent individuals previously vaccinated with varicella virus vaccine months to years after vaccination. Cases are often associated with preceding or concurrent herpes zoster rash.

• Syncope: Syncope has been reported with use of injectable vaccines and may result in serious secondary injury (eg, skull fracture, cerebral hemorrhage); typically reported in adolescents and young adults and within 15 minutes after vaccination. Procedures should be in place to avoid injuries from falling and to restore cerebral perfusion if syncope occurs (ACIP [Ezeanolue 2020]).

Disease-related concerns:

• Acute illness: Although fever is a contraindication per the manufacturer, current guidelines allow for administration to patients with mild acute illness with or without low grade fever (CDC/ACIP [Marin 2007]). Defer administration in patients with moderate or severe acute illness (with or without fever) (ACIP [Ezeanolue 2020]).

• Altered immunocompetence: Use of this vaccine is contraindicated in persons who are immunosuppressed or immunodeficient. Household and close contacts of persons with altered immunocompetence may receive most age appropriate vaccines (ACIP [Ezeanolue 2020]). Live vaccines should be administered ≥4 weeks prior to planned immunosuppression and avoided within 2 weeks of immunosuppression when feasible; live vaccines should not be administered for at least 3 months after immunosuppressive therapy (ACIP [Ezeanolue 2020]; IDSA [Rubin 2014]).

• HIV: Although the manufacturer contraindicates administration to persons with HIV, guidelines for use are available. Children ≤8 years with HIV infection with age-specific CD4+ T-lymphocyte percentages ≥15% may receive live attenuated varicella vaccine. Vaccination may also be considered for children >8 years, adolescents, and adults with CD4+ T-lymphocyte counts ≥200 cells/microliter; refer to guidelines for specific information (CDC/ACIP [Marin 2007]).

Concurrent drug therapy issues:

• Antibody-containing products: Varicella vaccine and antibody-containing products (eg, immune globulin, blood products) should not be administered simultaneously. Guidelines with suggested administration intervals are available (ACIP [Ezeanolue 2020]).

• Antiviral drugs: Medications active against the herpesvirus family (eg, acyclovir, famciclovir, valacyclovir) may interfere with the varicella vaccine; avoid varicella vaccination to a patient who has received these antivirals 24 hours before vaccination; avoid use of these antiviral agents for 14 days after varicella vaccination (ACIP [Ezeanolue 2020]).

• Salicylates: Avoid salicylates in children and adolescents 12 months through 17 years of age for 6 weeks after vaccination; varicella may increase the risk of Reye syndrome.

• Vaccines: In order to maximize vaccination rates, the ACIP recommends simultaneous administration (ie, >1 vaccine on the same day at different anatomic sites) of all age-appropriate vaccines (live or inactivated) for which a person is eligible at a single clinic visit, unless contraindications exist. The use of combination vaccines is generally preferred over separate injections, taking into consideration provider assessment, patient preference, and adverse events. When using combination vaccines, the minimum age for administration is the oldest minimum age for any individual component; the minimum interval between dosing is the greatest minimum interval between any individual components (ACIP [Ezeanolue 2020]).

Dosage form specific issues:

• Albumin: Products may contain albumin.

• Gelatin: Products may contain gelatin. Use is contraindicated in patients with a history of anaphylactic/anaphylactoid reaction to gelatin.

• Neomycin: Products may contain neomycin. Use is contraindicated in patients with history of anaphylactic/anaphylactoid reactions to neomycin. Contact dermatitis due to neomycin is not a contraindication to the vaccine (CDC/ACIP [Marin 2007]).

Other warnings/precautions:

• Appropriate use:

- Use of this vaccine for specific medical and/or other indications (eg, immunocompromising conditions, hepatic or kidney disease, diabetes) is also addressed in the annual ACIP Recommended Immunization Schedules (refer to the Centers for Disease Control and Prevention [CDC] schedule for detailed information). Specific recommendations for use of this vaccine in immunocompromised patients with asplenia, cancer, HIV infection, cerebrospinal fluid leaks, cochlear implants, hematopoietic stem cell transplant (prior to or after), sickle cell disease, solid organ transplant (prior to or after), or those receiving immunosuppressive therapy for chronic conditions as well as contacts of immunocompromised patients are available from the IDSA (Rubin 2014).

- Varilrix and Varivax III [Canadian products]: Canadian National Advisory Committee on Immunization (NACI) suggests that Varivax III and Varilrix may also be used for select groups (NACI 2017). Consult product labeling and/or NACI for specific recommendations regarding appropriate use in high risk patients.

• Antipyretics: Antipyretics have not been shown to prevent febrile seizures; antipyretics may be used to treat fever or discomfort following vaccination (ACIP [Ezeanolue 2020]). One study reported that routine prophylactic administration of acetaminophen prior to vaccination to prevent fever decreased the immune response of some vaccines; the clinical significance of this reduction in immune response has not been established (Prymula 2009).

• Congenital or hereditary immunodeficiency: Defer use in patients with a family history of congenital or hereditary immunodeficiency until immune competence in the vaccine recipient is demonstrated (CDC/ACIP [Marin 2007]).

• Effective immunity: Vaccination may not result in effective immunity in all patients. Response depends upon multiple factors (eg, type of vaccine, age of patient) and may be improved by administering the vaccine at the recommended dose, route, and interval. Vaccines may not be effective if administered during periods of altered immune competence (ACIP [Ezeanolue 2020]).

• Transmission of virus: Transmission of varicella vaccine virus resulting in varicella infection may occur (rare) between vaccine recipients (with or without varicella-like rash) and contacts susceptible to varicella (including healthy and high-risk individuals). The manufacturer notes that vaccinated individuals should not have close association with susceptible high-risk individuals for up to 6 weeks following vaccination. High-risk individuals include immunocompromised persons, pregnant women without evidence of immunity, newborns of mothers without evidence of immunity, and all infants born <28 weeks' gestation (regardless of maternal immunity). However, the CDC recommends that vaccine recipients who develop a vaccine-related rash avoid contact with susceptible individuals at high risk for complications until the lesions are resolved (crusted over or fade away) or until no new lesions appear for 24 hours. According to the CDC guidelines, having a pregnant household member is not a contraindication to vaccination (CDC/ACIP [Marin 2007]).

* See Cautions in AHFS Essentials for additional information.

Warnings: Additional Pediatric Considerations

Herpes zoster caused by vaccine-strain varicella zoster virus (VZV) has been reported rarely in children postvaccination with varicella virus vaccine; in patients with herpes zoster caused by vaccine-strain VZV, the rash was more likely to correspond to site of vaccine injection than in patients with herpes zoster caused by wild-type VZV (Guffey 2017; Weinmann 2013). Onset of rash at previous injection site occurred between 6 and 61 months postvaccination in a case series describing 7 patients (age range: 1 to 6 years) with herpes zoster; precipitating factors and symptoms varied (Song 2018).

Reproductive Considerations

Pregnancy should be avoided for 3 months (per manufacturer labeling; 1 month per ACIP) following vaccination (CDC/ACIP [Marin 2007]).

Pregnancy Considerations

Varicella virus vaccine is contraindicated for use in pregnant females.

Information was collected from 1995-2013 using the manufacturer’s pregnancy registry, and included 905 women who received a varicella containing vaccine (30% within 3 months prior to conception) and who had known pregnancy outcomes. Among these women, the rates of miscarriage and birth defects was not increased above background rates, and there were no infants born with abnormalities consistent with congenital varicella syndrome.

Varicella disease during the first or second trimesters may result in congenital varicella syndrome. The onset of maternal varicella infection from 5 days prior to 2 days after delivery may cause varicella infection in the newborn. All women should be assessed for immunity during a prenatal visit; those without evidence of immunity should be vaccinated upon completion or termination of pregnancy (CDC/ACIP [Marin 2007]).

Any exposures to the vaccine during pregnancy or within 3 months prior to pregnancy should be reported to the manufacturer (Merck & Co, 877-888-4231) or to VAERS (800-822-7967) as suspected adverse reactions.

Breast-Feeding Considerations

It is not known if varicella virus vaccine is present in breast milk.

Following immunization, varicella virus was not detected in the milk samples of 12 breastfeeding women and none of the breastfed infants seroconverted (Bohlke 2003; CDC/ACIP [Marin 2007]). According to the manufacturer, the decision to breastfeed following immunization should take into account the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother. Guidelines note that immunization should not be delayed due to breastfeeding and vaccinated women may continue to breastfeed (CDC/ACIP [Marin 2007]). Breastfed infants should be vaccinated according to the recommended schedules (ACIP [Kroger 2017]).

Briggs' Drugs in Pregnancy & Lactation

• Vaccine, Varicella Virus

Adverse Reactions

>10%:

Local: Injection site reaction (19% to 33%; includes erythema, hematoma, induration, numbness, pain, swelling, stiffness)

Miscellaneous: Fever (10% to 15%)

1% to 10%:

Central nervous system: Chills, fatigue, headache, irritability, malaise, nervousness, sleep disturbance

Dermatologic: Varicella-like rash (≤6%; at injection site and generalized), contact dermatitis, dermatitis (children), diaper rash (children), eczema (children), miliaria (children), pruritus, skin rash, urticaria, xeroderma (children)

Gastrointestinal: Abdominal pain, anorexia, aphthous stomatitis (adolescents & adults), constipation, dental discomfort (teething; children), diarrhea, nausea, vomiting

Genitourinary: Herpes labialis (adolescents & adults)

Hematologic & oncologic: Lymphadenopathy

Hypersensitivity: Hypersensitivity reaction

Neuromuscular & skeletal: Arthralgia, myalgia, neck stiffness

Ophthalmic: Eye discomfort

Otic: Otitis

Respiratory: Cough, respiratory tract disease (lower/upper)

<1%, postmarketing, and/or case reports: Anaphylactic shock, anaphylaxis, angioedema, anterior uveitis (children; Krall 2014), aplastic anemia, aseptic meningitis, ataxia, Bell palsy, cellulitis, cerebrovascular accident, dizziness, encephalitis, erythema multiforme, facial edema, febrile seizures, Guillain-Barré syndrome, Henoch-Schonlein purpura, herpes zoster, immune thrombocytopenia, impetigo, keratitis (children; Krall 2014), meningitis, necrotizing retinitis (immunocompromised patients), paresthesia, peripheral edema, pharyngitis, pneumonia, pneumonitis, secondary skin infection, seizure (nonfebrile), Stevens-Johnson syndrome, thrombocytopenia, transverse myelitis, varicella infection - chickenpox (including virus transmission to susceptible contacts)

* See Cautions in AHFS Essentials for additional information.

Allergy and Idiosyncratic Reactions

• Aminoglycoside Allergy

Metabolism/Transport Effects

None known.

Drug Interactions Open Interactions

5-Aminosalicylic Acid Derivatives: May enhance the adverse/toxic effect of Varicella Virus-Containing Vaccines. The primary concern is the potential development of Reye's Syndrome, a condition that has been associated with the use of salicylates in children with varicella infections. Management: Avoid administration of salicylates for at least 6 weeks after adminstration of a varicella virus-containing vaccine. Risk D: Consider therapy modification

Acyclovir-Valacyclovir: May diminish the therapeutic effect of Varicella Virus Vaccine. Management: When possible, avoid use of acyclovir or valacyclovir within the 24 hours prior to administration of the varicella vaccine, and avoid use of these antiviral agents for 14 days after vaccination. Risk X: Avoid combination

Axicabtagene Ciloleucel: May enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of infection may be increased. Axicabtagene Ciloleucel may diminish the therapeutic effect of Vaccines (Live). Management: Avoid live virus vaccines for at least 6 weeks prior to initiation of lymphodepleting therapy, during axicabtagene ciloleucel infusion, and after treatment until full immune recovery is achieved. Risk D: Consider therapy modification

AzaTHIOprine: May enhance the adverse/toxic effect of Vaccines (Live). AzaTHIOprine may diminish the therapeutic effect of Vaccines (Live). Management: Low-dose azathioprine (3 mg/kg/day or less) is not considered sufficiently immunosuppressive to create vaccine safety concerns and is not a contraindication for administration of zoster vaccine. Higher doses of azathioprine should be avoided. Risk D: Consider therapy modification

Belimumab: May enhance the adverse/toxic effect of Vaccines (Live). Risk X: Avoid combination

Corticosteroids (Systemic): May enhance the adverse/toxic effect of Vaccines (Live). Corticosteroids (Systemic) may diminish the therapeutic effect of Vaccines (Live). Management: Doses equivalent to less than 2 mg/kg or 20 mg per day of prednisone administered for less than 2 weeks are not considered sufficiently immunosuppressive to create vaccine safety concerns. Higher doses and longer durations should be avoided. Exceptions: Deflazacort. Risk D: Consider therapy modification

Daclizumab: May enhance the adverse/toxic effect of Vaccines (Live). Daclizumab may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination

Deflazacort: May enhance the adverse/toxic effect of Vaccines (Live). Deflazacort may diminish the therapeutic effect of Vaccines (Live). Management: Administer all vaccines according to immunization guidelines prior to initiating deflazacort. Live vaccines should be administered at least 4 to 6 weeks prior to initiating deflazacort. Risk D: Consider therapy modification

Dimethyl Fumarate: May enhance the adverse/toxic effect of Vaccines (Live). Specifically, Dimethyl Fumarate may increase the risk of vaccinal infection. Dimethyl Fumarate may diminish the therapeutic effect of Vaccines (Live). Management: Non-US labeling for dimethyl fumarate states that live attenuated vaccine administration is not recommended during treatment. US labeling states that safety and effectiveness of live vaccines administered with dimethyl fumarate has not been assessed. Risk C: Monitor therapy

Dupilumab: May enhance the adverse/toxic effect of Vaccines (Live). Risk X: Avoid combination

Famciclovir: May diminish the therapeutic effect of Varicella Virus Vaccine. Management: When possible, avoid use of famciclovir within the 24 hours prior to administration of the varicella vaccine, and avoid use of famciclovir for 14 days after vaccination. Risk X: Avoid combination

Fingolimod: May enhance the adverse/toxic effect of Vaccines (Live). Vaccinal infections may develop. Fingolimod may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination

Guselkumab: May enhance the adverse/toxic effect of Vaccines (Live). Risk X: Avoid combination

Immune Globulins: May diminish the therapeutic effect of Vaccines (Live). Management: Consult full interaction monograph for dose interval recommendations. This interaction does not apply to oral Ty21a typhoid vaccine or others listed as exceptions. Risk D: Consider therapy modification

Immunosuppressants: May enhance the adverse/toxic effect of Vaccines (Live). Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Exceptions: AzaTHIOprine; Beclomethasone (Oral Inhalation); Betamethasone (Systemic); Budesonide (Systemic); Corticotropin; Cortisone; Cytarabine (Liposomal); Deflazacort; DexAMETHasone (Systemic); Fludrocortisone; Fluticasone (Oral Inhalation); Hydrocortisone (Systemic); Leflunomide; Mercaptopurine; Methotrexate; MethylPREDNISolone; PrednisoLONE (Systemic); PredniSONE; Triamcinolone (Systemic). Risk X: Avoid combination

Leflunomide: May enhance the adverse/toxic effect of Vaccines (Live). Leflunomide may diminish the therapeutic effect of Vaccines (Live). Management: The ACIP guidelines state that live-attenuated vaccines should generally be avoided for at least 3 months after cessation of immunosuppressant therapy. However, the ACR does not recommend avoiding live vaccines in patients being treated with leflunomide. Risk D: Consider therapy modification

Mercaptopurine: May enhance the adverse/toxic effect of Vaccines (Live). Mercaptopurine may diminish the therapeutic effect of Vaccines (Live). Management: Low-dose 6-mercaptopurine (1.5 mg/kg/day or less) is not considered sufficiently immunosuppressive to create vaccine safety concerns and is not a contraindication for administration of zoster vaccine. Higher doses of mercaptopurine should be avoided. Risk D: Consider therapy modification

Methotrexate: May enhance the adverse/toxic effect of Vaccines (Live). Methotrexate may diminish the therapeutic effect of Vaccines (Live). Management: Low-dose methotrexate (0.4 mg/kg/week or less) is not considered sufficiently immunosuppressive to create vaccine safety concerns. Higher doses of methotrexate should be avoided. Risk D: Consider therapy modification

Ocrelizumab: May enhance the adverse/toxic effect of Vaccines (Live). Ocrelizumab may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination

Ozanimod: May enhance the adverse/toxic effect of Varicella Virus-Containing Vaccines. The risk of developing a clinical infection from the live vaccine may be increased. Ozanimod may diminish the therapeutic effect of Varicella Virus-Containing Vaccines. Risk X: Avoid combination

Rabies Immune Globulin (Human): May diminish the therapeutic effect of Vaccines (Live). Management: Avoid administering the measles vaccine within 4 months after administration of rabies immune globulin. Avoid administering other live vaccines within 3 months after administration of rabies immune globulin. Risk D: Consider therapy modification

Rho(D) Immune Globulin: May diminish the therapeutic effect of Varicella Virus Vaccine. Management: Do not delay administration of the varicella virus vaccine in women who have recently received Rho (D) immune globulin. If possible, women should be tested 3 or more months after vaccine administration to ensure immunity. Risk D: Consider therapy modification

Risankizumab: May enhance the adverse/toxic effect of Vaccines (Live). Risk X: Avoid combination

Salicylates: May enhance the adverse/toxic effect of Varicella Virus-Containing Vaccines. Specifically, the risk for Reye's syndrome may increase. Risk X: Avoid combination

Smallpox Vaccine Live: May enhance the adverse/toxic effect of Varicella Virus Vaccine. It may be difficult to determine which vaccine caused skin lesions or other adverse effects. Management: Separate the administration of smallpox and varicella vaccines by at least 4 weeks. Risk D: Consider therapy modification

Tildrakizumab: May enhance the adverse/toxic effect of Vaccines (Live). The risk for contracting an infection from the vaccine may be increased. Tildrakizumab may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination

Tisagenlecleucel: May enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of infection may be increased. Tisagenlecleucel may diminish the therapeutic effect of Vaccines (Live). Management: Avoid live virus vaccines for two weeks prior to initiation of lymphodepleting therapy, during tisagenlecleucel infusion, and after treatment until full immune recovery is achieved. Risk D: Consider therapy modification

Tuberculin Tests: Vaccines (Live) may diminish the diagnostic effect of Tuberculin Tests. Management: If a parenteral live vaccine has been recently administered, a scheduled PPD skin test should not be administered for at least 4-6 weeks following the administration of the vaccine. Risk D: Consider therapy modification

Vaccines (Live): May diminish the therapeutic effect of other Vaccines (Live). Management: Two or more injectable or nasally administered live vaccines not administered on the same day should be separated by at least 28 days (ie, 4 weeks). If not, the vaccine administered second should be repeated at least 4 week later. Exceptions: Adenovirus (Types 4, 7) Vaccine; Cholera Vaccine; Rotavirus Vaccine. Risk C: Monitor therapy

Venetoclax: May enhance the adverse/toxic effect of Vaccines (Live). Venetoclax may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live, attenuated vaccines before, during, or after (prior to B-cell recovery) venetoclax treatment. Risk X: Avoid combination

Monitoring Parameters

Rash, fever; monitor for anaphylaxis and syncope for 15 minutes following administration (ACIP [Kroger 2017]). If seizure-like activity associated with syncope occurs, maintain patient in supine or Trendelenburg position to reestablish adequate cerebral perfusion.

Advanced Practitioners Physical Assessment/Monitoring

This vaccine is a live vaccine. Do not administer to people with weakened immune systems, regardless of the etiology, or pregnant females. Most common reactions are fever, rash, mild soreness, or redness at injection site.

Nursing Physical Assessment/Monitoring

Review allergies and immunization records prior to administration. Should not be given to pregnant females. Monitor for allergic reactions after administration.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Injectable, Subcutaneous [preservative free]:

Varivax: 1350 PFU/0.5 mL (1 ea) [contains albumin bovine, edetic acid, neomycin]

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Injectable, Subcutaneous:

Varilrix: 2000 PFU/0.5 mL (0.5 mL)

Varivax III: 1350 units/0.5 mL (0.5 mL)

Anatomic Therapeutic Chemical (ATC) Classification

• J07BK01

Generic Available (US)

No

Pricing: US

Injection (Varivax Subcutaneous)

1350 pfu/0.5 mL (per each): $162.72

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Mechanism of Action

As a live, attenuated vaccine, varicella virus vaccine offers active immunity to disease caused by the varicella-zoster virus by inducing cell mediated and humoral immune responses

Pharmacodynamics/Kinetics

Onset of action: Seroconversion occurred in 97% of healthy children ~4 to 6 weeks following a one dose regimen; using a two dose regimen, the seroconversion rate was 99.9% 6 weeks after the second dose. In adolescents≥13 years of age and adults, the seroconversion rate was ~75% 4 weeks after the first dose and 99% 4 weeks after the second dose

Duration: Antibody titers detectable at 10 years postvaccination. Actual antibody titers vary by year and age group, but are ~99% to 100% for children at 10 years and 100% for adolescents and adults at 6 years postvaccination. Exposure to wild-type varicella may boost antibody levels.

Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Effects on Dental Treatment

Key adverse event(s) related to dental treatment: Cold/canker sores.

Effects on Bleeding

No information available to require special precautions

Related Information

• Centers for Disease Control and Prevention (CDC) and Other Links
• Immunization Administration Recommendations
• Immunization Schedules

Pharmacotherapy Pearls

Evidence of immunity to varicella includes any of the following (CDC, 2007):

Documentation of age appropriate vaccination with varicella vaccine.

Laboratory evidence of immunity or laboratory confirmation of disease.

Birth in the United States prior to 1980 (except for health care personnel, pregnant women and the immunocompromised).

Diagnosis or verification of varicella disease by healthcare provider.

Diagnosis or verification of herpes zoster by healthcare provider.

Persons who lack evidence of immunity should be vaccinated.

Index Terms

Chickenpox Vaccine; VAR; Varicella-Zoster Virus (VZV) Vaccine (Varicella); VZV Vaccine (Varicella)

FDA Approval Date

March 17, 1995

References

Bernstein HH, Rothstein EP, Watson BM, et al, “Clinical Survey of Natural Varicella Compared With Breakthrough Varicella After Immunization With Live Attenuated Oka/Merck Varicella Vaccine,” Pediatrics, 1993, 92(6):833-7.[PubMed 8233746]

Bohlke K, Galil K, Jackson LA, et al. Postpartum varicella vaccination: is the vaccine virus excreted in breast milk? Obstet Gynecol. 2003;102(5 Pt 1):970-977.[PubMed 14672472]

Chaves SS, Gargiullo P, Zhang JX, et al, “Loss of Vaccine-Induced Immunity to Varicella Over Time,” N Engl J Med, 2007, 356(11):1121-9.[PubMed 17360990]

Ezeanolue E, Harriman K, Hunter P, Kroger A, Pellegrini C. General best practice guidelines for immunization: best practices guidance of the Advisory Committee on Immunization Practices (ACIP). https://www.cdc.gov/vaccines/hcp/acip-recs/general-recs/downloads/general-recs.pdf. Accessed April 10, 2020.

Guffey DJ, Koch SB, Bomar L, Huang WW. Herpes zoster following varicella vaccination in children. Cutis. 2017;99(3):207-211.[PubMed 28398421]

Krall P, Kubal A. Herpes zoster stromal keratitis after varicella vaccine booster in a pediatric patient. Cornea. 2014;33(9):988-989.[PubMed 25062334 ]

Kroger AT, Duchin J, Vazquez M. General Best Practice Guidelines for Immunization. Best Practices Guidance of the Advisory Committee on Immunization Practices (ACIP). https://www.cdc.gov/vaccines/hcp/acip-recs/general-recs/downloads/general-recs.pdf. Accessed April 4, 2017.

Kuter BJ, Weibel RE, Guess HA, et al, “Oka/Merck Varicella Vaccine in Healthy Children: Final Report of a 2-Year Efficacy Study and 7-Year Follow-up Studies,” Vaccine, 1991, 9(9):643-7.[PubMed 1659052]

Marin M, Guris D, Chaves SS, Schmid S, Seward JF; Advisory Committee on Immunization Practices; Centers for Disease Control and Prevention (CDC). Prevention of varicella: recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep. 2007;56(RR-4):1-40. http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5604a1.htm.[PubMed 17585291]

National Advisory Committee on Immunization (NACI), "Active Vaccines: Varicella Vaccine,” from Public Health Agency of Canada, Ottawa, ONT: Minister of Public Works and Government Services Canada. https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-4-active-vaccines/page-24-varicella-chickenpox-vaccine.html. Accessed September 2017.

Prymula R, Siegrist CA, Chlibek R, et al, “Effect of Prophylactic Paracetamol Administration at Time of Vaccination on Febrile Reactions and Antibody Responses in Children: Two Open-Label, Randomised Controlled Trials,” Lancet, 2009, 374(9698):1339-50.[PubMed 19837254]

Rubin LG, Levin MJ, Ljungman P, et al. 2013 IDSA clinical practice guideline for vaccination of the immunocompromised host. Clin Infect Dis. 2014;58(3):e44-e100.[PubMed 24311479]

Song H, Morley KW, Trowbridge RM, et al. Herpes zoster at the vaccination site in immunized healthy children. Pediatr Dermatol. 2018;35(2):230-233.[PubMed 29405375]

Tomblyn M, Chiller T, Einsele H et al. Guidelines for preventing infectious complications among hematopoietic cell transplant recipients: a global perspective. Biol Blood Marrow Transplant. 2009;15(10):1143-238.[PubMed 19747629]10.1016/j.bbmt.2009.06.019

Varilrix (varicella virus vaccine) [product monograph]. Mississauga, Ontario, Canada: GlaxoSmithKline Inc; August 2019.

Varivax (varicella virus vaccine) [prescribing information]. Whitehouse Station, NJ: Merck & Co; March 2020.

Varivax (varicella virus vaccine) [product monograph]. Kirkland, Quebec, Canada: Merck Canada Inc.; February 2014.

Varivax III (varicella virus vaccine) [product monograph]. Kirkland, Quebec, Canada: Merck Canada Inc; July 2018.

Weinmann S, Chun C, Schmid DS, et al. Incidence and clinical characteristics of herpes zoster among children in the varicella vaccine era, 2005-2009. J Infect Dis. 2013;208(11):1859-1868.[PubMed 23922376]

Brand Names: International

Okavax (HK, ID, SG, TW, VN); V-Z Vax (PH); Vaccin Varilrix (FR); Varcelvax (PH); Varicela Biken (EC); Varilrix (AE, AR, AU, BB, BE, BM, BS, BZ, CH, CL, CN, CO, CR, CY, CZ, DK, DO, EE, ES, FI, GB, GT, GY, HK, HN, HU, IL, IN, IS, JM, KR, LB, LK, LT, LU, LV, MT, MX, MY, NI, NL, NO, PA, PE, PH, PY, RO, SA, SE, SG, SI, SR, SV, TT, TW, UA, UY, VN); Varipox (IN); Varivax (DE, ES, FR, GB, HK, IE, LB, LT, MT, MY, NO, PH, SI, SK, TH, TR, VN)

Last Updated 5/2/20