Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, suspension:
BioThrax: Bacillus anthracis proteins (5 mL) [contains formaldehyde; contains aluminum, natural rubber/natural latex in packaging]
Pharmacology
Mechanism of Action
Active immunization against Bacillus anthracis. The vaccine is prepared from a cell-free filtrate of B. anthracis, but no dead or live bacteria. Completion of the entire vaccination series is required for full protection; annual boosters are required to maintain immunity.
Use: Labeled Indications
Anthrax prevention: Active immunization against Bacillus anthracis in persons 18 to 65 years of age.
Pre-exposure: For pre-exposure prophylaxis of disease in persons whose occupation or other activities place them at high risk of exposure.
Post-exposure: For post-exposure prophylaxis of disease following suspected or confirmed Bacillus anthracis exposure, when administered in conjunction with recommended antibacterial drugs.
The Advisory Committee on Immunization Practices (ACIP) recommends routine vaccination (pre-exposure vaccination) for the following (CDC [Wright 2010]):
- Persons who work directly with the organism in the laboratory
- Persons who handle animals or animal products only when
- potentially infected in research settings;
- in areas of high incidence of enzootic anthrax; or
- where standards and restrictions are not sufficient to prevent exposure
- Military personnel deployed to areas with high risk of exposure as recommended by the Department of Defense (DoD)
- Persons engaged in environmental investigations or remediation efforts
Routine immunization for the general population is not recommended. Routine vaccination may be offered to emergency and other responders (police and fire departments, the National Guard, etc.) on a voluntary basis under the direction of a comprehensive occupational health and safety program (CDC [Wright 2010]).
The ACIP recommends postexposure prophylaxis after inhalation exposure to aerosolized Bacillus anthracis spores for the following (in the absence of completing a preexposure, routine vaccination schedule) (CDC [Wright 2010]):
- The general public, including pregnant and breast-feeding women
- Medical professionals
- Children ages 0 to 18 years as determined on an event-by-event basis
- Persons engaged in handling certain animals or animal products
- Persons who work directly with the organism in the laboratory (postexposure vaccination dependent upon pre-event vaccination status)
- Military personnel as recommended by the DoD
- Persons engaged in environmental investigations or remediation efforts (postexposure vaccination dependent upon pre-event vaccination status)
- Emergency and other responders (police and fire departments, the National Guard, etc.)
- Persons working in postal facilities
Contraindications
Anaphylactic or anaphylactic-like reaction following a previous dose of anthrax vaccine or any component of the formulation including aluminum, benzethonium chloride, and formaldehyde.
Dosage and Administration
Dosing: Adult
Preexposure prophylaxis: Adults ≤65 years:
IM (preferred):
Primary immunization: Three injections of 0.5 mL each given at day 0, 1 month, and 6 months.
Booster injections: 0.5 mL each should be given 6 and 12 months after completion of the primary series and at 1-year intervals thereafter for persons who remain at risk
SubQ:
Primary immunization: Four injections of 0.5 mL each given at day 0, 2 weeks, 4 weeks, and 6 months.
Booster injections: 0.5 mL each should be given 6 and 12 months after completion of the primary series and at 1-year intervals thereafter for persons who remain at risk.
Note: SubQ administration is only to be used for primary immunization in persons who are at risk for hematoma formation following IM injection.
Postexposure prophylaxis (inhalation exposure): SubQ: Three injections of 0.5 mL each given at day 0, 2 weeks, and 4 weeks post-exposure.
ACIP recommendations (CDC [Wright 2010]): Administer with a 60-day course of antibiotics. (Vaccination should begin within 10 days of exposure. Refer to guidelines provided as part of emergency use authorization [EUA] or investigational new drug [IND] application at the time of the event). Note: Additional considerations for postexposure prophylaxis following occupational exposures:
Fully vaccinated: Personnel who have completed the primary vaccination series and booster injections do not require postexposure prophylaxis if wearing protective equipment. If respiratory protection is disrupted, a 30-day course of antimicrobial therapy is recommended.
Previously unvaccinated: Workers should receive the vaccine as directed per postexposure prophylaxis along with the 60-day course of antimicrobial therapy (antimicrobial therapy should continue for 14 days after the third dose of PEP vaccine), then switch to the licensed regimen at the 6-month dose.
Partially vaccinated: Any person who started but did not complete the primary vaccination series should receive a 30-day course of antimicrobial therapy and continue with the primary vaccination schedule.
Dosing: Geriatric
Safety and efficacy have not been established in persons >65 years of age.
Dosing: Pediatric
Note: Routine preexposure immunization with anthrax vaccine in pediatric patients is not recommended; use in pediatric patients is determined on an event-by-event basis (AAP [Bradley 2014]; CDC [Wright 2010]). Due to increased risk of adverse effects postvaccination and unknown effects on immunogenicity, anthrax vaccine should not be administered at the same time as routine childhood immunizations. Postexposure immunization with anthrax vaccine should take priority over routine childhood immunizations; any routine childhood immunization should be postponed until 4 weeks after completion of the anthrax series (AAP [Bradley 2014]).
Postexposure prophylaxis: Use should be in conjunction with public health official guidance and recommendations on an event-by-event basis; refer to guidelines provided as part of emergency use authorization (EUA) or investigational new drug (IND) application at the time of the event. Use in combination with a 60-day systemic antimicrobial course; vaccination should begin within 10 days of exposure (AAP [Bradley 2014]).
Infants ≥6 weeks, Children, and Adolescents <18 years of age: Very limited data available; use in pediatric patients extrapolated from adult experience (AAP [Bradley 2014]). SubQ: 0.5 mL as a 3-dose series administered at 0, 2, and 4 weeks after exposure (AAP [Bradley 2014]; CDC [Wright 2010]).
Adolescents ≥18 years: SubQ: 0.5 mL as a 3-dose series administered at 0, 2, and 4 weeks after exposure (CDC [Wright 2010]).
Administration
Shake well before use. Do not use if discolored or contains particulate matter. Do not use the same site for more than one injection. Do not mix with other vaccines or injections; separate needles and syringes should be used for each injection. 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.
Preexposure (routine vaccination): For IM administration into the deltoid muscle; do not inject IV or intradermally. For patients at risk of bleeding/hematoma following IM injection, the vaccine can be administered SubQ over the deltoid muscle.
Postexposure prophylaxis: Administer SubQ over the deltoid muscle.
Storage
Store at 2°C to 8°C (36°F to 46°F); do not freeze.
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
>10%:
Central nervous system: Burning sensation (45% to 97%), fatigue (6% to 13%), headache (2% to 11%)
Endocrine & metabolic: Edema at insertion site (subcutaneous: 17% to 46%; intramuscular: 5% to 30%)
Local: Tenderness at injection site (subcutaneous: 48% to 72%; intramuscular: 41% to 51%), erythema at injection site (subcutaneous: 53% to 71%; intramuscular: 15% to 48%), warm sensation at injection site (subcutaneous: 29% to 51%; intramuscular: 4% to 19%), injection site nodule (subcutaneous: 21% to 42%; intramuscular: 3% to 9%), induration at injection site (subcutaneous: 26% to 40%; intramuscular: 7% to 23%), itching at injection site (subcutaneous: 3% to 26%; intramuscular: 1% to 10%), pain at injection site (12% to 22%)
Neuromuscular & skeletal: Decreased range of motion (5% to 15%; arm), myalgia (3% to 13%)
1% to 10%:
Hematologic & oncologic: Lymphadenopathy (≤2%; painful axillary nodes)
Local: Bruising at injection site (2% to 7%)
<1%, postmarketing, and/or case reports: Alopecia, anaphylactoid reaction, anaphylaxis, angioedema, arthralgia, arthropathy, cellulitis, dizziness, erythema multiforme, flu-like symptoms, flushing, hypersensitivity reaction, insomnia, lymphadenopathy, malaise, nausea, pain, paresthesia, pruritus, rhabdomyolysis, skin rash, Stevens-Johnson syndrome, syncope, tremor, ulnar nerve neuropathy, urticaria
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 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 [Kroger 2017]).
Disease-related concerns:
- Acute illness: May consider deferring administration in patients with moderate or severe acute illness (with or without fever) in preexposure vaccination programs; may administer to patients with mild acute illness (with or without fever). When used for postexposure prophylaxis, consider the benefits versus risks in patients with moderate or severe acute illness (CDC [Wright 2010]).
- Anthrax disease: Persons with a history of anthrax disease may have an increased risk for severe local adverse reactions from the vaccine.
- Bleeding disorders: Use with caution in patients with a history of 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]). For patients at risk of hemorrhage following IM injection, the vaccine can be administered SubQ.
- Cutaneous or gastrointestinal anthrax exposure: Vaccination is not recommended after cutaneous or gastrointestinal exposures that pose no risk of inhalational exposure to Bacillus anthracis spores; antimicrobial postexposure prophylaxis may be considered in these patients (CDC [Wright 2010]).
Concurrent drug therapy issues:
- Anticoagulant therapy: Use with caution in patients receiving anticoagulant therapy; bleeding/hematoma may occur from IM administration (ACIP [Kroger 2017]). For patients at risk of hemorrhage following IM injection, the vaccine can be administered SubQ.
- Vaccines: Anthrax vaccine should not be administered with routine childhood immunization doses due to increased potential for adverse reactions and unknown effects on immunogenicity; routine childhood immunizations should be postponed until 4 weeks after completion of anthrax series (AAP [Bradley 2014]).
Special populations:
- Altered immunocompetence: Consider deferring preexposure 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: Safety and efficacy have not been established in adults ≥65 years of age.
Dosage form specific issues:
- Latex: Packaging may contain natural latex rubber.
Other warnings/precautions:
- 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 local reactions, chills, fever, anaphylaxis. Monitor for 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 Considerations
Data from the Department of Defense suggest the vaccine may be linked with a slightly increased number of atrial septal defects when given during the first trimester of pregnancy; however, when premature infants are excluded from analysis, the association is not statistically significant. Current ACIP guidelines recommend deferring preexposure vaccination when possible; however, postexposure prophylaxis is recommended in pregnant women.
Male fertility is not affected by vaccine administration (CDC [Wright 2010]).
Health care providers are encouraged to enroll pregnant women exposed to this vaccine in Emergent’s vaccination pregnancy registry (1-619-553-9255).
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 injection site irritation, redness, or edema; difficulty moving arm where shot was given; muscle pain; headache; or loss of strength and energy. Have patient report immediately to prescriber severe dizziness or passing out (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 health care 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.
