Pharmacologic Category

Vaccine; Vaccine, Inactivated (Bacterial)

Dosing: Pediatric

Note: Canadian product (not available in the US). Consult National Advisory Committee on Immunization (NACI) guidelines (Canada) for additional information including specific detailed recommendations for catch-up scenarios and/or care of patients with high-risk conditions (NACI/CATMAT 2016).

Primary immunization: Canadian labeling: Note: Preterm infants should be vaccinated according to their chronological age from birth.

Healthy infants 6 weeks to 6 months:

Two-dose series: IM: 0.5 mL per dose for 2 doses, followed by a booster dose of 0.5 mL (for a total of 3 doses). The first dose may be given as young as 6 weeks of age but is typically given at 2 months of age. The second dose should be administered at 4 months of age. The booster dose may be given as young as 9 months of age but is typically administered at 11 to 12 months of age; allow a minimum interval of 2 months between doses 1 and 2, and 6 months between dose 2 and the booster dose. Note: Two-dose regimen outside of the routine infant schedule may not provide optimal protection, particularly in infants at high risk for pneumococcal disease.

Three-dose series: IM: 0.5 mL per dose for 3 doses, followed by a booster dose of 0.5 mL (for a total of 4 doses). The first dose may be given as young as 6 weeks of age but is typically given at 2 months of age. The second and third doses should be administered at 4 and 6 months of age. The booster dose may be given as young as 9 months of age but is typically administered at 12 to 15 months of age; allow a minimum interval of 1 month between each of the first 3 doses, and 6 months between dose 3 and the booster dose.

High-risk for invasive pneumococcal disease (eg, HIV, sickle cell disease): Infants 6 weeks to 6 months: IM: 0.5 mL per dose for 3 doses, followed by a booster dose of 0.5 mL (for a total of 4 doses). The first dose may be given as young as 6 weeks of age but is typically given at 2 months of age. The second and third doses should be administered at 4 and 6 months of age. The booster dose may be given as young as 9 months of age but is typically administered at 12 to 15 months of age; allow a minimum interval of 1 month between each of the first 3 doses, and 6 months between dose 3 and the booster dose.

Catch-up dosing, previously unvaccinated: Canadian labeling:

Infants 7 to 11 months: IM: 0.5 mL per dose for a total of 3 doses; 2 doses administered at least 1 month apart, followed by a third dose administered after 1 year of age and separated from the second dose by at least 2 months.

Children 12 to 23 months: IM: 0.5 mL per dose for a total of 2 doses, administered at least 2 months apart. Note: Two-dose regimen in children 12 to 23 months of age at high risk for pneumococcal disease (eg, asplenia, sickle-cell disease, immunosuppressed) may not provide optimal protection.

Children ≥24 months to <6 years: IM: 0.5 mL per dose for a total of 2 doses, administered at least 2 months apart.

Dosing: Renal Impairment: Pediatric

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

Dosing: Hepatic Impairment: Pediatric

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

Use: Labeled Indications

Note: Not approved in the US.

Pneumococcal disease prevention: Immunization of infants ≥6 weeks and children through 5 years of age against Streptococcus pneumoniae invasive diseases, pneumonia, and acute otitis media caused by serotypes included in the vaccine.

Clinical Practice Guidelines

Immunization:

NACI/CATMAT, Canadian Immunization Guide, Pneumococcal Vaccine, October 2016

Administration: Pediatric

IM: Shake well before use. Administer by IM injection only, preferably into the anterolateral aspect of the thigh in infants or into the deltoid muscle in children. Do not administer intravenously or intradermally. Subcutaneous administration has not been studied. Do not mix with other vaccines or injections; separate needles and syringes should be used for each injection.

NACI recommends that patients with bleeding disorders receive all routine recommended vaccinations according to schedule. Bleeding disorders should be corrected prior to immunization (when possible) or immunization should be scheduled shortly after antihemophilia or other similar therapy. In patients with bleeding disorder that cannot be corrected, IM gluteal injections should be avoided (if possible). When immunizing patients with bleeding disorders, a fine-gauge needle of the appropriate length can be used for the vaccination and firm pressure applied to the site (without rubbing) for at least 5 minutes. The patient should be instructed concerning the risk of hematoma from the injection. Patients on anticoagulant therapy (eg, aspirin, warfarin, heparin) may be immunized via intramuscular injection without discontinuation of their anticoagulant therapy (ACIP [Kroger 2017]; NACI 2016).

Storage/Stability

Store at 2°C to 8°C (36°F to 46°F) and in original packaging to protect from light. Do not freeze; discard if frozen. If not used immediately, may store for ≤72 hours at 8°C to 25°C (46°F to 77°F). If multidose vial is not used immediately after opening, store at 2°C to 8°C (36°F to 46°F); discard if not used within 6 hours.

Medication Safety Issues

Sound-alike/look-alike issues:

Contraindications

Hypersensitivity to any component of the vaccine

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 [Kroger 2017]).

• Shoulder injury related to vaccine administration: Vaccine administration that is too high on the upper arm may cause shoulder injury (eg, shoulder bursitis, tendinitis) resulting in shoulder pain and reduced range of motion following injection. Use proper injection technique for vaccines administered in the deltoid muscle (eg, injecting in the central, thickest part of the muscle) to reduce the risk of shoulder injury related to vaccine administration (Cross 2016; Foster 2013).

• 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 but may occur in children 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 [Kroger 2017]).

Disease-related concerns:

• Acute illness: The decision to administer or delay vaccination because of current or recent febrile illness depends on the severity of symptoms and the etiology of the disease. Defer administration in patients with moderate or severe acute illness (with or without fever); vaccination should not be delayed for patients with mild acute illness (with or without fever) (ACIP [Kroger 2017]).

• Bleeding disorders: Use with caution in patients with a history of bleeding disorders (including thrombocytopenia); bleeding/hematoma may occur from intramuscular (IM) administration; if the patient receives antihemophilia or other similar therapy, IM injection can be scheduled shortly after such therapy is administered (ACIP [Kroger 2017]).

• Pneumococcal infections: Not to be used to treat pneumococcal infections.

Concurrent drug therapy issues:

• Anticoagulant therapy: Use with caution in patients receiving anticoagulant therapy; bleeding/hematoma may occur from IM administration (ACIP [Kroger 2017]).

• Vaccines: In order to maximize vaccination rates, the Canadian National Advisory Committee on Immunization (NACI) 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 (NACI 2016).

Special populations:

• Altered immunocompetence: Consider deferring immunization during periods of severe immunosuppression (eg, patients receiving chemo/radiation therapy, or other immunosuppressive therapy including high dose corticosteroids); may have a reduced response to vaccination. In general, household and close contacts of persons with altered immunocompetence may receive all age-appropriate vaccines. Inactivated vaccines should be administered ≥2 weeks prior to planned immunosuppression when feasible; inactivated vaccines administered during chemotherapy should be readministered after immune competence is regained (ACIP [Kroger 2017]; IDSA [Rubin 2014]). Use of the 10-valent pneumococcal vaccine does not replace immunization with the 23-valent pneumococcal vaccine.

• Pediatric: Apnea has occurred following IM vaccine administration in some premature infants; consider clinical status implications. Infants born ≤28 weeks' gestation, particularly those with a prior history of respiratory immaturity, may require respiratory function monitoring for 2 to 3 days after administration. In general, preterm infants should be vaccinated at the same chronological age as full-term infants (ACIP [Kroger 2017]).

Other warnings/precautions:

• Antipyretics: Antipyretics have not been shown to prevent febrile seizures; antipyretics may be used to treat fever or discomfort following vaccination (ACIP [Kroger 2017). One study reported that routine prophylactic administration of acetaminophen to prevent fever prior to vaccination decreased the immune response of some vaccines; the clinical significance of this reduction in immune response has not been established (Prymula 2009).

• 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 [Kroger 2017)

• Routine immunization: Antibody response is provided only against pneumococcal serotypes included in the vaccine. Antibody response may also be observed to diphtheria toxoid, tetanus toxoid, and protein D (derived from nontypeable Haemophilus influenzae); however, recommended routine administration schedules for diphtheria, tetanus, or H. influenzae type b vaccines should still be followed.

Pregnancy Considerations

Animal reproduction studies have not been conducted. Inactivated vaccines have not been shown to cause increased risks to the fetus (ACIP [Kroger 2017]). This product is indicated for use in infants and children.

Breast-Feeding Considerations

Administration does not affect the safety of breastfeeding for the mother or the infant. Breastfeeding infants should be vaccinated according to the recommended schedules (ACIP [Kroger 2017]).

Adverse Reactions

>10%:

Gastrointestinal: Anorexia (17% to 31%)

Local: Pain at injection site (23% to 57%), erythema at injection site (24% to 52%) swelling at injection site (16% to 44%)

Nervous system: Irritability (32% to 66%), drowsiness (33% to 58%)

Miscellaneous: Fever (rectal; ≥38° C: 26% to 37%; >39° C: 1% to 7%)

1% to 10%: Local: Induration at injection site

<1%, postmarketing, and/or case reports: Allergic dermatitis, anaphylaxis, angioedema, apnea (in premature infants ≤28 weeks' gestation), atopic dermatitis, bleeding at injection site, crying, diarrhea, eczema, febrile seizure, headache, hematoma at injection site, hypersensitivity reaction, hypotonic/hyporesponsive episode, injection site nodule, injection site pruritus, Kawasaki syndrome, nausea, seizure, skin rash, swelling of injected limb (may involve adjacent joint), urticaria, vomiting

Allergy and Idiosyncratic Reactions

• Aluminum Allergy With Vaccines

Metabolism/Transport Effects

None known.

Drug Interactions Open Interactions

Fingolimod: May diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting fingolimod. If vaccinated during fingolimod therapy, revaccinate 2 to 3 months after fingolimod discontinuation. Risk D: Consider therapy modification

Immunosuppressants: May diminish the therapeutic effect of Vaccines (Inactivated). Management: Vaccine efficacy may be reduced. Complete all age-appropriate vaccinations at least 2 weeks prior to starting an immunosuppressant. If vaccinated during immunosuppressant therapy, revaccinate at least 3 months after immunosuppressant discontinuation. Exceptions: Cytarabine (Liposomal). Risk D: Consider therapy modification

Siponimod: May diminish the therapeutic effect of Vaccines (Inactivated). Management: Avoid administration of vaccines (inactivated) during treatment with siponimod and for 1 month after discontinuation due to potential decreased vaccine efficacy. Risk D: Consider therapy modification

Venetoclax: May diminish the therapeutic effect of Vaccines (Inactivated). Risk C: Monitor therapy

Monitoring Parameters

Consider respiratory monitoring for 48 to 72 hours in premature infants (born ≤28 weeks gestation) due to risk of apnea. Monitor for anaphylaxis and syncope for 15 minutes following administration. If seizure-like activity associated with syncope occurs, maintain patient in supine or Trendelenburg position to reestablish adequate cerebral perfusion.

Product Availability

Not available in the US

Dosage Forms: Canada

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

Injection, suspension:

Synflorix: 1 mcg of each capsular saccharide for serotypes 1, 5, 6B, 7F, 9V, 14, and 23F, and 3 mcg each of serotypes 4, 18C, and 19F (bound to protein D [from nontypeable H. Influenzae], tetanus toxoid, or diphtheria toxoid) per 0.5 mL (0.5 mL) [contains aluminum]

Anatomic Therapeutic Chemical (ATC) Classification

• J07AL02

Mechanism of Action

Promotes active immunization against invasive disease caused by S. pneumoniae capsular serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, and 23F, all which are individually conjugated to a carrier protein (protein D, tetanus toxoid, or diphtheria toxoid); the aluminum salt, a mineral adjuvant, enhances the antibody response.

Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Effects on Dental Treatment

No significant effects or complications reported

Effects on Bleeding

No information available to require special precautions

Related Information

• Immunization Administration Recommendations

Index Terms

10-Valent Pneumococcal Nontypeable Haemophilus influenzae Protein D Conjugate Vaccine; 10-Valent Pneumococcal Vaccine; PCV; PCV10; PHiD-CV; Pneumo-C-10; Pneumococcal 10-Valent Conjugate Vaccine; Pneumococcal Conjugate Vaccine (Nontypeable Haemophilus influenzae [NTHi] Protein D, Diphtheria or Tetanus Toxoid Conjugates) Adsorbed

References

Canadian Immunization Guide, Pneumococcal Vaccine. Minister of Public Works and Government Services Canada, Public Health Agency of Canada, National Advisory Committee on Immunization, October 2016. Available at https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-4-active-vaccines/page-16-pneumococcal-vaccine.html.

Canadian National Advisory Committee on Immunization (NACI) 2016. https://www.canada.ca/en/public-health/services/canadian-immunization-guide.html.

Cross GB, Moghaddas J, Buttery J, Ayoub S, Korman TM. Don't aim too high: avoiding shoulder injury related to vaccine administration. Aust Fam Physician. 2016;45(5):303‐306.[PubMed 27166466]

Croxtall JD and Keating GM, “Pneumococcal Polysaccharide Protein D-Conjugate Vaccine (Synflorix™; PHiD-CV),” Pediatr Drugs, 2009, 11(5):349-57.[PubMed 19725600]

Foster SL, Davis MV. Vaccine administration: preventing serious shoulder injuries. J Am Pharm Assoc (2003). 2013;53(1):102‐103. doi:10.1331/JAPhA.2013.13503[PubMed 23636163]

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.

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]

Synflorix pneumococcal conjugate vaccine [Non-typeable Haemophilus influenzae (NTHi) protein D, diphtheria or tetanus toxoid conjugates] adsorbed [product monograph]. Mississauga, Ontario, Canada: GlaxoSmithKline Inc; September 2017.

Synflorix pneumococcal conjugate vaccine [Non-typeable Haemophilus influenzae (NTHi) protein D, diphtheria or tetanus toxoid conjugates] adsorbed [product monograph]. Mississauga, Ontario, Canada: GlaxoSmithKline Inc; November 2019.

Brand Names: International

Synflorix (AE, AR, AT, BE, BH, CL, CR, CY, CZ, DE, DK, DO, EC, EE, ES, GB, GT, HK, HN, HR, HU, ID, IE, IL, IS, IT, JP, KR, LB, LK, LT, LV, MT, MY, NI, NL, NZ, PA, PE, PH, PL, PT, QA, RO, SA, SE, SG, SI, SK, SV, TH, TR, TW, UA, VN)

Last Updated 5/31/20