SIDE EFFECTS

The most common ( ≥ 10%) local (injection-site) adverse reactions observed in clinical studies were tenderness, pain, erythema and arm motion limitation. The most common ( ≥ 5%) systemic adverse reactions were muscle aches, headache, and fatigue.

Serious allergic reactions, including anaphylactic shock, have been observed during post-marketing surveillance in individuals receiving BioThrax (anthrax vaccine adsorbed emergent biosolutions) .

Clinical Trial 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.

Local and systemic reactions were monitored in an open-label safety study of 15,907 doses of BioThrax (anthrax vaccine adsorbed emergent biosolutions) administered by the subcutaneous route to approximately 7,000 textile employees, laboratory workers and other at risk individuals. Over the course of the 5-year study the following local reactions were reported: 24 (0.15% of doses administered) severe local 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 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 reactions (erythema only or induration measuring less than 30 mm in diameter). Four cases of systemic 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.

The CDC sponsored a randomized, double-blind, placebo-controlled, multi-center clinical study [NCT00119067] in which 1,564 healthy volunteers were enrolled [See Clinical Studies section]. The objective of this study was to evaluate the effect of (1) changing the route of vaccine administration from subcutaneous (SQ) to intramuscular (IM), and (2) of reducing the number of doses on the safety and immunogenicity of BioThrax (anthrax vaccine adsorbed emergent biosolutions) . A planned analysis of the first 1,005 subjects compared four treatment groups over a period of seven months in which subjects received a total of either three (3) or four (4) doses of BioThrax (anthrax vaccine adsorbed emergent biosolutions) . 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 events. Adverse reaction data were also collected from in-clinic exams, which were performed prior to, and 15 to 60 minutes post each injection, at 1 to 3 days after each injection, and at 28 days after injections 3 and 4. Demographic characteristics for each respective treatment group in the analysis are provided in Table 1.

Table 1: Demographic characteristics: CDC Study

Shown in Table 2 and Table 3, respectively, are the rates (percentage) of prospectively defined local and systemic solicited adverse reactions observed in the in-clinic exams.

The analysis of injection site (local) reactions demonstrated that administration of the vaccine by the IM route, as compared to the SQ route, resulted in a statistically significant reduction in reactogenicity (i.e. cutaneous adverse reactions). Injection site adverse reactions, including warmth, tenderness, itching, erythema, induration, edema, and nodule, consistently occurred at lower frequencies and for shorter duration in participants given BioThrax (anthrax vaccine adsorbed emergent biosolutions) by the IM route. Route of administration did not statistically significantly influence the occurrence or duration of systemic adverse reactions, with the exception of muscle ache (increased occurrence only). Most local and systemic adverse reactions were mild or moderate in severity; the proportion of participants with severe adverse reactions reported was very low ( < 1%). It was observed in this study that women receiving BioThrax (anthrax vaccine adsorbed emergent biosolutions) reported significantly more injection-site adverse reactions than did men. This gender-related difference was seen regardless of the route of administration, but was more pronounced in those receiving the vaccine by the SQ route. Women also reported more systemic adverse reactions than men (in particular fatigue, muscle ache and headache), but these gender differences were not influenced by route of administration. A brief pain or burning sensation, felt immediately after vaccine injection, was reported by most study participants. The pain was rated on a visual analog scale as 0-10. It was described as significant ( > 3) more often following SQ administration (41%) than IM administration (26%). Female participants generally experienced a higher pain scale rating than male participants.

Serious adverse reactions were infrequently reported during this study but two (2) important serious adverse reactions that were noted to be possibly related to BioThrax (anthrax vaccine adsorbed emergent biosolutions) administration include: a case of anaphylaxis and a case of an ANA positive autoimmune disorder manifesting as a moderate bilateral arthralgia of the metacarpophalangeal (MCP) joints. The majority of serious adverse reactions reported were unrelated to vaccination. Out of a total of 44 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 approximately within the first trimester (n = 15), 2 reports of spontaneous abortion were reported, along with one report of a healthy term infant with mild right clubbed foot abnormality.

Table 2: Local Adverse Reactions: In-Clinic Solicited by Dose Number*

Table 3: Systemic Adverse Reactions: In-Clinic Solicited by Dose Number*

Table 4 shows adverse events (excluding injection site reactions) that occurred in ≥ 2% of participants through Study Month 7, and excluding those that occurred at a lower rate than those observed in the placebo group.

Table 4: Solicited and Unsolicited Adverse Events Occurring in > 2% of Subjects*

Postmarketing Experience

The following adverse events have been identified during postapproval use of BioThrax (anthrax vaccine adsorbed emergent biosolutions) . 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

Lymphadenopathy

• Immune system disorders

Allergic reactions (including anaphylaxis, angioedema, rash, urticaria, pruritus, erythema multiforme, anaphylactoid reaction and Stevens Johnson syndrome)

• Nervous system disorders

Headache, paresthesia syncope, tremor, ulnar nerve neuropathy

• Musculoskeletal, connective tissue and bone disorders

Arthralgia, arthropathy, myalgia, rhabdomyolysis, alopecia

• General disorders and administration site conditions

Injection site reactions (including pain, nodule, edema, induration, erythema, warmth, pruritus, cellulitis), fatigue, pyrexia, flu-like symptoms

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.

No fatalities have been determined to have been causally related to the administration of BioThrax (anthrax vaccine adsorbed emergent biosolutions) .

Read the entire FDA prescribing information for BioThrax (Anthrax Vaccine Adsorbed Emergent BioSolutions) »