Medical Editor: John P. Cunha, DO, FACOEP
BioThrax (anthrax) Vaccine Adsorbed is an immunization used to help prevent anthrax disease in people exposed to the bacteria through the skin or lungs. BioThrax vaccine works by exposing you to an antigen protein that causes your body to develop immunity to the disease. BioThrax does not contain live or killed forms of the bacteria that cause anthrax. BioThrax vaccine will not treat an active infection. Common side effects of BioThrax include injection site reactions (pain, redness, swelling, warmth, itching, or tenderness), limited arm movement or stiffness in the injected arm, joint or muscle ache or pain, headache, dizziness, tiredness, weakness, low fever, swelling in your hands or feet, or skin rash.
Immunization with BioThrax consists of a series of 5 intramuscular doses administered at 0 and 4 weeks and 6, 12 and 18 months. Select a different injection site for each sequential injection of this vaccine. Individuals should not be considered protected until they have received the full series of vaccinations. BioThrax may interact with other vaccines, steroids, medicines to treat or prevent organ transplant rejection, or medications to treat psoriasis, rheumatoid arthritis, or other autoimmune disorders. Tell your doctor all medications and supplements you use and all vaccines you recently received. BioThrax is not recommended for use during pregnancy. It may harm a fetus. It is unknown if this medication passes into breast milk. Consult your doctor before breastfeeding.
Our BioThrax (anthrax) Vaccine Adsorbed Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.
This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
You should not receive a booster vaccine if you had a life-threatening allergic reaction after the first shot.
Keep track of any and all side effects you have after receiving this vaccine. When you receive a booster dose, you will need to tell the doctor if the previous shots caused any side effects.
Becoming infected with anthrax is much more dangerous to your health than receiving the vaccine to protect against it. Like any medicine, this vaccine can cause side effects, but the risk of serious side effects is extremely low.
Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.
Call your doctor at once if you have a serious side effect (some are rare but serious) such as:
- severe swelling or a hard lump where the shot was given;
- severe swelling spreading to other parts of your arm;
- fever, chills, body aches, nausea, flu symptoms;
- pale skin, easy bruising or bleeding;
- confusion, changes in mood or behavior;
- seizure (convulsions);
- blistering, redness, and swelling or warmth of the skin;
- weakness, numbness or tingly feeling in your feet spreading upward;
- problems with vision, hearing, speech, swallowing, or bladder and bowel functions;
- severe lower back pain; or
- slow heart rate, trouble breathing, weak pulse, or feeling like you might pass out.
Less serious side effects include:
- mild redness, warmth, itching, or tenderness where the shot was given;
- low fever;
- feeling tired or weak;
- headache, dizziness;
- mild pain or stiffness in the injected arm;
- joint or muscle pain;
- swelling in your hands or feet; or
- mild skin rash.
This is not a complete list of side effects and others may occur. Tell your doctor about any unusual or bothersome side effect. You may report side effects to FDA at 1-800-FDA-1088.
Read the entire detailed patient monograph for BioThrax (Anthrax Vaccine Adsorbed Emergent BioSolutions)
The most common ( ≥ 10%) local (injection-site) adverse reactions observed in clinical studies were tenderness, pain, erythema, edema, and arm motion limitation. The most common ( ≥ 5%) systemic adverse reactions were muscle aches, headache, and fatigue.
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a product cannot be directly compared to rates in the clinical trials of another product and may not reflect the rates observed in clinical practice.
In an open-label safety study of 15,907 doses of BioThrax administered by the subcutaneous route to approximately 7,000 textile employees, laboratory workers and other at risk individuals, local and systemic reactions were monitored. Over the course of the 5-year study the following local adverse reactions were reported: 24 (0.15% of doses administered) severe local adverse reactions (defined as edema or induration measuring greater than 120 mm in diameter or accompanied by marked limitation of arm motion or marked axillary node tenderness), 150 (0.94% of doses administered) moderate local adverse reactions (edema or induration greater than 30 mm but less than 120 mm in diameter), and 1,373 (8.63% of doses administered) mild local adverse reactions (erythema only or induration measuring less than 30 mm in diameter). Four cases of systemic adverse reactions were reported during the 5-year reporting period ( < 0.06% of doses administered). These reactions, which were reported to have been transient, included fever, chills, nausea, and general body aches.
In a randomized, double-blinded, placebo-controlled, and active-controlled multi-center clinical study, [NCT00119067] 1,564 healthy subjects were enrolled. The objective of this study was to evaluate the effect of (1) changing the route of vaccine administration from subcutaneous (SC) to intramuscular (IM), and (2) of reducing the number of doses on the safety and immunogenicity of BioThrax. The dosing schedules and routes studied are provided in Table 1. [See Clinical Studies]
Group A (8SC) (N=259) received BioThrax via the SC route of administration at Weeks 0, 2, 4, and Months 6, 12, 18 followed by 2 annual boosters (original U.S. licensed route/schedule). Group A served as the active control in this study.
Group B (8IM) (N=262) received BioThrax via the IM route of administration at Weeks 0, 2, 4, and Months 6, 12, 18 followed by 2 annual boosters.
Group C (COM) (N=782) received BioThrax via the IM route of administration at Weeks 0, 4 (no Week 2 dose), and Month 6 with various schedules thereafter. (Group C represents data from 3 randomized groups [Groups D, E, and F] combined for the analysis through Month 7 because the schedules are identical through the Month 6 dose.)
Group D (7IM) (N=256) received BioThrax via the IM route of administration at Weeks 0, 4 (no Week 2 dose), and Months 6, 12, 18 followed by 2 annual boosters.
Group E (5IM) (N=258) received BioThrax via the IM route of administration at Weeks 0, 4 (no Week 2 dose), and Months 6, 18 followed by 1 booster dose at Month 42 (2 year interval).
Group F (4IM) (N=268) received BioThrax via the IM route of administration at Weeks 0, 4 (no Week 2 dose), and Month 6 followed by 1 booster dose at Month 42 (3 year interval).
Table 1: Vaccination
Schedules and Routes Evaluated
|Group A (8SC)*||V||V||V||V||V||V||V||V|
|Group B (8IM)||V||V||V||V||V||V||V||V|
|Group D (7IM)||V||S||V||V||V||V||V||V|
|Group E (5IM)||V||S||V||V||S||V||S||V|
|Group F (4IM)||V||S||V||V||S||S||S||V|
|SC: subcutaneous; IM: intramuscular; V: vaccine, S:
^Subjects randomized to the control group were then re-randomized (1:1) to receive saline by the IM or SC route. The IM and SC placebo groups are combined in analyses.
Subjects were instructed to complete a 14-day post-vaccination diary card after the first 2 doses and a 28-day diary card after the subsequent doses to capture solicited and unsolicited adverse reactions. Adverse reaction data were also collected from in-clinic exams, which were performed prior to, and 15 to 60 minutes after each injection, at 1 to 3 days after each injection, and at 28 days after injections 3 through 8. The mean age, gender ratio, and race distribution were not significantly different across treatment groups among the vaccinated cohort (N=1563). The mean age was 39 years (range 18 to 62 years). Fifty-one percent of participants were female and 49% were male. Seventy-four percent were white, 21% were black and 5% were categorized as “other”.
Shown in Table 2 are the rates (percentage) of prospectively defined local and systemic solicited adverse reactions observed in the in-clinic exams for doses 1-4 as well as the rates (percentage) of local and systemic solicited adverse reactions observed in the in-clinic exams for doses 5-8.
Analysis of injection site (local) adverse reactions by study group was performed after each dose. It was observed that groups receiving BioThrax by the IM route had a statistically significantly lower incidence of any (one or more) local adverse reactions compared to the BioThrax SC route, by dose in the in-clinic data set, in almost all analyses. Injection site adverse reactions, including warmth, tenderness, itching, erythema, induration, edema, and nodule occurred at lower frequencies in participants given BioThrax by the IM route after each dose, in almost all comparisons. However, by dose, the incidence of arm motion limitation was usually higher in each BioThrax IM group compared to the 8SC group (excluding doses where IM groups received a placebo). The incidence of any moderate or severe local adverse reactions was consistently lower in BioThrax IM groups, compared to the 8SC group after each dose. Route of administration did not affect the occurrence of systemic adverse reactions, with the exception of muscle ache (increased incidence in the BioThrax IM groups after most doses). There was no clear pattern for differences in the incidence of any moderate or severe systemic adverse reactions for BioThrax IM groups compared to the 8SC group after each dose. The proportion of participants with severe local or systemic adverse reactions reported by adverse reaction category after each dose was very low (generally < 1%).
Overall, women had a higher incidence of any local adverse reaction than did men, by dose, within BioThrax groups, regardless of the route of administration. Overall, women also had a higher incidence of any systemic adverse reaction than men, within BioThrax groups, regardless of the route of administration. A brief pain or burning sensation, felt immediately after vaccine injection, and distinct from injection site pain, was reported by 45 - 97% of all study participants receiving BioThrax. Reporting frequency and event intensity varied with route of administration and vaccine dose. Up to 11% of subjects rated the brief pain or burning they experienced immediately after vaccine injection as 8 out of 10 or greater. Female participants generally experienced a higher pain scale rating than male participants.
Eight serious adverse events (SAEs) were reported with 6 subjects and determined to be possibly related to the administration of BioThrax: (1) a case of generalized allergic reaction, (2) a case of ANA positive autoimmune disorder manifesting as a moderate bilateral arthalgia of the metacarpophalangeal (MCP) joints, (3) a right shoulder supraspinatus tendon tear, (4) a case of bilateral pseudotumor cerebri with bilateral disc edema, (5) a case of generalized seizure and hospitalization for evaluation of hydrocephalus and endoscopic fluid ventriculostomy, (6) a case of bilateral ductal carcinoma of the breast. No SAEs were determined by the investigator to be probably or definitely related to administration of BioThrax. The percent of serious adverse events was similar between the BioThrax combined groups (193/1303 or 1.5%) and the placebo group (38/260 or 1.5%).
Out of a total of 51 pregnancies reported in this study, no distinct patterns of infant outcome were seen, with the majority of pregnancies uncomplicated and healthy term infants delivered. Of women who received vaccine within 90 days of the estimated date of conception (n = 14), 2 spontaneous abortions and a first trimester intra-utero fetal death were reported, along with one report of a healthy term infant with mild right clubbed foot abnormality.
Table 2: Adverse Reactions:
In-Clinic Day 0 - 3, Solicited by Dose Number*
|Number of Subjects (N)**||STUDY GROUP|
(BioThrax Doses 1, 3-8)
Control SC/IM (Doses 1-8)
(BioThrax Doses 1-8)
|Local Adverse Reactions|
|Presence of any local adverse reaction||60||23||68||68||69||77||76||73||22||22||19||27||25||29||25||18||81||89||80||84||81||84||84||92|
|Arm motion limitation||14||1||15||11||10||10||15||9||1||0||2||1||1||1||1||0||8||12||5||11||10||5||8||5|
|Presence of any moderate/severe local adverse reactions§||5||1||8||7||4||5||6||4||0||0||0||0||0||0||0||0||7||16||8||13||10||7||12||14|
|Presence of any large local adverse reaction|||0||0||0||2||2||4||2||2||0||0||0||0||0||0||0||0||0||1||4||2||1||2||2||4|
|Systemic Adverse Reactions|
|Presence of any systemic adverse reaction||18||12||24||19||15||19||10||9||10||10||13||11||13||8||13||4||16||20||18||21||18||14||20||17|
|Fever ≥ 100.4°F||0||0||0||0||0||0||0||0||0||0||0||0||1||0||0||0||0||0||0||0||0||0||0||0|
|Tender/painful axillary adenopathy||0||0||0||1||1||1||0||0||0||0||0||0||0||0||0||1||0||1||2||1||1||0||1||0|
|Presence of any moderate/severe systemic adverse reactions††||2||2||6||3||3||5||4||3||1||2||2||1||3||1||2||1||2||5||4||3||3||2||3||2|
|*Per-dose, statistical assessment performed on
Intent-to-Treat population data. Evaluations performed at 15-60 minutes and 1-3
days following each injection and prior to the next scheduled injection.
**N is the highest number per treatment arm (received at least one dose); denominator (N) varied with dose number due to attrition over time.
†Subjects received saline (instead of BioThrax) for the Week 2 dose. Placebo dose data for 7IM group is in italics.
‡The two saline groups (SC and IM) were combined.
§ Moderate = causes discomfort and interferes with normal daily activities; Severe = incapacitating and completely prevents performing normal daily activities. This is based on the local AE categories of warmth, tenderness, itching, pain, and arm motion limitation.
�Large = an occurrence of induration, erythema, edema, nodule, and bruise with a largest diameter greater than 120 mm.
†† Moderate = causes discomfort and interferes with normal daily activities; Severe = incapacitating and completely prevents performing normal daily activities. This is based on the systemic AE categories of fatigue, muscle ache, headache, and fever.
Solicited and unsolicited adverse reactions observed from Day 0 through month 43 at a higher frequency (by at least 5%) in the BioThrax groups (IM and SC) as compared to the placebo (P) group were: headache (70.4% IM, 78.4% SC, 68.1% P); myalgia (72% IM, 76.1% SC, 50% P); and fatigue (70.1% IM, 76.8% SC, 60.8% P).
The following adverse events, not previously listed in Section 6.1, have been identified during post-approval use of BioThrax. Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The reports included below are listed due to one or more of the following factors: (1) seriousness of the event, (2) number of reports, or (3) strength of causal relationship to the drug.
Blood and Lymphatic System Disorders
Immune System Disorders
Nervous System Disorders
Musculoskeletal, Connective Tissue, and Bone Disorders
General Disorders and Administration Site Conditions
Skin and Subcutaneous Disorders
Pruritis, rash, urticaria
Infrequent reports were also received of multisystem disorders defined as chronic symptoms involving at least two of the following three categories: fatigue, mood-cognition, and musculoskeletal system.
Read the entire FDA prescribing information for BioThrax (Anthrax Vaccine Adsorbed Emergent BioSolutions)