Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, emulsion [monovalent]: GlaxoSmithKline product: Adjuvanted Hemagglutinin [A/Indonesia/05/2005 (H5N1)] 3.75 mcg/0.5 mL (5 mL) [contains egg protein, polysorbate 80, and thimerosal]
Injection, suspension [monovalent]: Sanofi Pasteur product: Hemagglutinin [A/Vietnam/1203/2004 (H5N1)] 90 mcg/mL (5 mL) [contains chicken and egg protein, porcine gelatin, and thimerosal]
Pharmacology
Mechanism of Action
The GlaxoSmithKline product is an adjuvanted monovalent split virus (inactivated) preparation of the type A, subtype H5N1 avian strain of influenza virus (A/Indonesia/05/2005)
The Sanofi Pasteur product is a monovalent, split virus (inactivated) preparation of the type A, subtype H5N1 avian strain of influenza virus (A/Vietnam/1203/2004)
Both promote active immunity to influenza A H5N1 (avian).
Pharmacokinetics/Pharmacodynamics
Onset of Action
GlaxoSmithKline product (adjuvanted): Fourfold increase in antibody titers (measured by hemagglutination inhibition [HI]) occurred in up to 90% of patients 18-64 years of age and 74% of patients ≥65 years of age 21 days after the second dose
Sanofi Pasteur product: Fourfold increase in antibody titers (measured by HI) occurred in up to 58% of patients 28 days after the second dose (Treanor, 2006).
Use: Labeled Indications
Influenza A (H5N1) prevention:
GlaxoSmithKline product (adjuvanted): For active immunization of persons ≥6 months of age at increased risk of exposure to the influenza A (H5N1) virus subtype contained in the vaccine
Sanofi Pasteur product: For active immunization of persons 18-64 years of age at increased risk of exposure to the influenza A (H5N1) virus subtype contained in the vaccine
Contraindications
GlaxoSmithKline product (adjuvanted): Known severe allergic reactions (eg, anaphylaxis) to any component of the vaccine, including egg protein, or after a previous dose of an influenza vaccine.
Sanofi Pasteur product: There are no contraindications listed in the manufacturer's labeling.
Dosage and Administration
Dosing: Adult
Primary immunization:
GlaxoSmithKline product (adjuvanted): Adults ≥18 years: IM: 0.5 mL, followed by a second 0.5 mL dose administered 21 days later
Sanofi Pasteur product: Adults 18 to 64 years: IM: 1 mL, followed by second 1 mL dose administered approximately 28 days later (acceptable range: 21 to 35 days)
Dosing: Pediatric
Primary immunization: GlaxoSmithKline product (adjuvanted): Children ≥6 months and Adolescents: IM: 0.25 mL, followed by a second 0.25 mL dose administered 21 days later.
Reconstitution
GlaxoSmithKline product (adjuvanted): Prior to mixing, bring one vial of H5N1 antigen and one vial of AS03 adjuvant to room temperature (minimum of 15 minutes). Invert each vial to mix; do not use if particulate matter or discoloration are present. Withdraw contents of adjuvant vial and add to the H5N1 antigen vial. Mix thoroughly by inversion and label with the time and date of mixing on vial. Use within 24 hours of mixing.
Administration
For IM administration only. Shake well prior to use. Inspect for particulate matter and discoloration prior to administration. Administer into the deltoid muscle. 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.
GlaxoSmithKline product (adjuvanted): If vaccine is stored under refrigeration after mixing, bring to room temperature prior to administration (minimum 15 minutes).
For patients at risk of hemorrhage following intramuscular injection, the vaccine should be administered intramuscularly if, in the opinion of the physician familiar with the patient's bleeding risk, the vaccine can be administered by this route with reasonable safety. If the patient receives antihemophilia or other similar therapy, intramuscular vaccination can be scheduled shortly after such therapy is administered. A fine needle (23 gauge or smaller) can be used for the vaccination and firm pressure applied to the site (without rubbing) for at least 2 minutes. The patient should be instructed concerning the risk of hematoma from the injection. Patients on anticoagulant therapy should be considered to have the same bleeding risks and treated as those with clotting factor disorders (ACIP [Kroger 2017]).
Storage
Sanofi Pasteur product: Store in a refrigerator at 2°C to 8°C (35°F to 46°F). Do not freeze. Discard if frozen. Protect from light.
GlaxoSmithKline product (adjuvanted): Prior to mixing, the H5N1 antigen and AS03 adjuvant vials should be stored in a refrigerator between 2°C and 8°C (36°F and 46°F). Do not freeze. Discard if frozen. Protect from light. After mixing, the vaccine may be stored under refrigeration between 2°C and 8°C (36°F and 46°F) or at room temperature up to 30°C (86°F) for up to 24 hours. Do not freeze. Discard if frozen. Protect from light.
Drug 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. 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). 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. Consider therapy modification
Venetoclax: May diminish the therapeutic effect of Vaccines (Inactivated). Monitor therapy
Adverse Reactions
All serious adverse reactions must be reported to the U.S. Department of Health and Human Services (DHHS) Vaccine Adverse Event Reporting System (VAERS) 1-800-822-7967 or online at https://vaers.hhs.gov/.
>10%:
Central nervous system: Headache (3% to 35%), fatigue (34%), shivering (17%)
Dermatologic: Diaphoresis (11%)
Local: Pain at injection site (74% to 83%), tenderness at injection site (70%), erythema at injection site (9% to 20%), swelling at injection site (10% to 15%)
Neuromuscular & skeletal: Myalgia (45%), arthralgia (25%)
1% to 10%:
Gastrointestinal: Nausea (10%), diarrhea (6%)
Local: Itching at injection site (2%), burning sensation at injection site (1%)
Respiratory: Nasal congestion (1%)
Miscellaneous: Fever (5%)
<1%: Celiac disease, cerebrovascular accident, convulsions, cranial nerve palsy (IV), Crohn’s disease, erythema nodosum, facial paralysis, giant-cell arteritis, hepatitis, injection site reaction, malignant neoplasm of thyroid, organ transplant rejection (corneal), polymyalgia rheumatica, psoriasis, pulmonary embolism, radiculopathy, rheumatoid arthritis, rheumatoid lung, skin rash
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]).
- Syncope: Syncope has been reported with use of injectable vaccines and may be accompanied by transient visual disturbances, weakness, or tonic-clonic movements. 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 bleeding disorders (including thrombocytopenia); bleeding/hematoma may occur from 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]).
- Guillain-Barré syndrome: Use with caution in patients with a history of Guillain-Barré syndrome (GBS); patients with history of GBS have a greater likelihood of developing GBS than those without. Relationship to this influenza vaccine formulation is not known. As a precaution, the ACIP recommends that patients with a history of GBS and who are at low risk for severe influenza complications, and patients known to have experienced GBS within 6 weeks following previous vaccination should generally not be vaccinated (consider influenza antiviral chemoprophylaxis in these patients). The benefits of vaccination may outweigh the potential risks in persons with a history of GBS who are also at high risk for complications of influenza (CDC 2013). Recent studies of patients who received the trivalent inactivated influenza vaccine or the monovalent H1N1 influenza vaccine have shown the risk of GBS is lower with vaccination than with influenza infection (Baxter 2013; Greene 2013; Kwong 2013).
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 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 ACIP prefers each dose of a specific vaccine in a series come from the same manufacturer when possible; however vaccination should not be deferred because a specific brand name is unavailable (ACIP [Kroger 2017]).
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]).
- Elderly: Sanofi Pasteur product has not been evaluated in patients ≥65 years of age
- Pediatric: Apnea has occurred following intramuscular vaccine administration in premature infants; consider clinical status implications. In general, preterm infants should be vaccinated at the same chronological age as full-term infants (ACIP [Kroger 2017]).
Dosage form specific issues:
- Chicken egg protein: Product may be manufactured with chicken egg protein.
- Thimerosal: Product may contain thimerosal; hypersensitivity reactions may occur.
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 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).
- 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]).
Monitoring Parameters
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.
Pregnancy
Pregnancy Risk Factor
C (Sanofi Pasteur product)
Pregnancy Considerations
Adverse events were not observed in animal reproduction studies using the H5N1 vaccine GlaxoSmithKline adjuvanted product; animal reproduction studies have not been conducted with the Sanofi Pasteur product. Inactivated viral vaccines have not been shown to cause increased risks to the fetus (ACIP [Kroger 2017]).
Patient Education
- Discuss specific use of vaccine and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience headache; fatigue; shivering; sweating; injection site pain, tenderness, edema, itching, or burning; muscle pain, joint pain; nausea; or diarrhea (HCAHPS).
- Educate patient about signs of a significant reaction (eg, 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. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.
