Summary Of Exposure |
A) USES: Raxibacumab is approved for the treatment of inhalational anthrax in adult and pediatric patients and is given in combination with appropriate antibacterial therapy. It is also approved for the prophylaxis of inhalational anthrax, when alternative therapies are unavailable or not appropriate.
B) PHARMACOLOGY: Raxibacumab is a human IgG (lambda) monoclonal antibody, with no direct antibacterial activity, that binds to the protective antigen (PA) of Bacillus (B) anthracis. The binding of raxibacumab to the PA of B anthracis prevents intracellular entry of anthrax lethal factor and edema factor, the enzymatic toxin components responsible for the pathogenic effects of anthrax toxin.
C) EPIDEMIOLOGY: Overdose has not been reported.
D) WITH THERAPEUTIC USE
1) COMMON: The most common adverse effects reported in at least 1.5% of patients during clinical trials were rash, pruritus, pain in the extremity, and somnolence.
2) INFREQUENT: Other adverse effects that occurred in less than 1.5% of patients, but at a higher rate than in patients receiving a placebo, include palpitations, vertigo, anemia, leukopenia, prolonged prothrombin time, lymphadenopathy, fatigue, peripheral edema, increased blood amylase and creatine phosphokinase concentrations, back pain, muscle spasms, vasovagal syncope, insomnia, flushing, and hypertension.
E) WITH POISONING/EXPOSURE
1) There have been no reports of overdose. Signs and symptoms of an acute overdose are anticipated to be similar to excessive pharmacologic adverse events.
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Cardiovascular |
3.5.2) CLINICAL EFFECTS
A) PALPITATIONS 1) WITH THERAPEUTIC USE a) In clinical trials, palpitations were reported in less than 1.5% of patients who received raxibacumab, and at a higher rate than in patients who received placebo (Prod Info RAXIBACUMAB intravenous injection liquid, 2012).
B) PERIPHERAL EDEMA 1) WITH THERAPEUTIC USE a) In clinical trials, peripheral edema was reported in less than 1.5% of patients who received raxibacumab, and at a higher rate than in patients who received placebo (Prod Info RAXIBACUMAB intravenous injection liquid, 2012).
C) VASOVAGAL SYNCOPE 1) WITH THERAPEUTIC USE a) In clinical trials, vasovagal syncope was reported in less than 1.5% of patients who received raxibacumab, and at a higher rate than in patients who received placebo (Prod Info RAXIBACUMAB intravenous injection liquid, 2012).
D) HYPERTENSIVE DISORDER 1) WITH THERAPEUTIC USE a) In clinical trials, hypertension was reported in less than 1.5% of patients who received raxibacumab, and at a higher rate than in patients who received placebo (Prod Info RAXIBACUMAB intravenous injection liquid, 2012).
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Neurologic |
3.7.2) CLINICAL EFFECTS
A) DROWSY 1) WITH THERAPEUTIC USE a) In 3 clinical trials with raxibacumab, somnolence was reported in 1.4% of patients who received a single dose of raxibacumab (n=283) compared with 0% who received placebo (n=80). Somnolence was reported in 4.3% of patients who received 2 raxibacumab doses (n=23) in 1 of the trials, but in 0% of patients who received 2 raxibacumab doses in another trial (n=20) (Prod Info RAXIBACUMAB intravenous injection liquid, 2012).
B) VERTIGO 1) WITH THERAPEUTIC USE a) In clinical trials, vertigo was reported in less than 1.5% of patients who received raxibacumab, and at a higher rate than in patients who received placebo (Prod Info RAXIBACUMAB intravenous injection liquid, 2012).
C) INSOMNIA 1) WITH THERAPEUTIC USE a) In clinical trials, insomnia was reported in less than 1.5% of patients who received raxibacumab, and at a higher rate than in patients who received placebo (Prod Info RAXIBACUMAB intravenous injection liquid, 2012).
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Gastrointestinal |
3.8.2) CLINICAL EFFECTS
A) SERUM AMYLASE RAISED 1) WITH THERAPEUTIC USE a) In clinical trials, increased serum amylase was reported in less than 1.5% of patients who received raxibacumab, and at a higher rate than in patients who received placebo (Prod Info RAXIBACUMAB intravenous injection liquid, 2012).
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Hematologic |
3.13.2) CLINICAL EFFECTS
A) ANEMIA 1) WITH THERAPEUTIC USE a) In clinical trials, anemia was reported in less than 1.5% of patients who received raxibacumab, and at a higher rate than in patients who received placebo (Prod Info RAXIBACUMAB intravenous injection liquid, 2012).
B) LEUKOPENIA 1) WITH THERAPEUTIC USE a) In clinical trials, leukopenia was reported in less than 1.5% of patients who received raxibacumab, and at a higher rate than in patients who received placebo (Prod Info RAXIBACUMAB intravenous injection liquid, 2012).
C) PROTHROMBIN TIME INCREASED 1) WITH THERAPEUTIC USE a) In clinical trials, prolonged prothrombin time was reported in less than 1.5% of patients who received raxibacumab, and at a higher rate than in patients who received placebo (Prod Info RAXIBACUMAB intravenous injection liquid, 2012).
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Dermatologic |
3.14.2) CLINICAL EFFECTS
A) ERUPTION 1) WITH THERAPEUTIC USE a) In 3 clinical trials with raxibacumab, rash was reported in 3.2% of patients who received a single dose of raxibacumab (n=283) compared with 1.3% who received placebo (n=80) (Prod Info RAXIBACUMAB intravenous injection liquid, 2012).
b) In a clinical study with combination raxibacumab and ciprofloxacin, mild to moderate infusion-related rashes were observed in 22.2% (6 of 27) of patients who were not premedicated with diphenhydramine, compared with 3.3% (2 of 61) of patients premedicated with diphenhydramine (Prod Info RAXIBACUMAB intravenous injection liquid, 2012).
B) ITCHING OF SKIN 1) WITH THERAPEUTIC USE a) In 3 clinical trials with raxibacumab, pruritus was reported in 2.5% of patients who received a single dose of raxibacumab (n=283) compared with 0% who received placebo (n=80); however, pruritus was not reported in patients who received 2 raxibacumab doses (n=46) in 2 of the trials (Prod Info RAXIBACUMAB intravenous injection liquid, 2012).
C) FLUSHING 1) WITH THERAPEUTIC USE a) In clinical trials, flushing was reported in less than 1.5% of patients who received raxibacumab, and at a higher rate than in patients who received placebo (Prod Info RAXIBACUMAB intravenous injection liquid, 2012).
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Musculoskeletal |
3.15.2) CLINICAL EFFECTS
A) PAIN IN LIMB 1) WITH THERAPEUTIC USE a) In 3 clinical trials with raxibacumab, pain in extremity was reported in 2.5% of patients who received a single dose of raxibacumab (n=283) compared with 1.3% who received placebo (n=80); however, pain in extremity was not reported in patients who received 2 raxibacumab doses (n=46) in 2 of the trials (Prod Info RAXIBACUMAB intravenous injection liquid, 2012).
B) INCREASED CREATINE KINASE LEVEL 1) WITH THERAPEUTIC USE a) In clinical trials, increased creatine phosphokinase was reported in less than 1.5% of patients who received raxibacumab, and at a higher rate than in patients who received placebo (Prod Info RAXIBACUMAB intravenous injection liquid, 2012).
C) SPASM 1) WITH THERAPEUTIC USE a) In clinical trials, muscle spasm was reported in less than 1.5% of patients who received raxibacumab, and at a higher rate than in patients who received placebo (Prod Info RAXIBACUMAB intravenous injection liquid, 2012).
D) BACKACHE 1) WITH THERAPEUTIC USE a) In clinical trials, back pain was reported in less than 1.5% of patients who received raxibacumab, and at a higher rate than in patients who received placebo (Prod Info RAXIBACUMAB intravenous injection liquid, 2012).
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Immunologic |
3.19.2) CLINICAL EFFECTS
A) LYMPHADENOPATHY 1) WITH THERAPEUTIC USE a) In clinical trials, lymphadenopathy was reported in less than 1.5% of patients who received raxibacumab, and at a higher rate than in patients who received placebo (Prod Info RAXIBACUMAB intravenous injection liquid, 2012).
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Reproductive |
3.20.1) SUMMARY
A) Raxibacumab is classified as FDA pregnancy category B. There are no adequate and well-controlled studies of raxibacumab in pregnant women. In animal studies, there was no evidence of teratogenicity following IV administration.
3.20.2) TERATOGENICITY
A) ANIMAL STUDIES 1) LACK OF EFFECT a) RABBITS: There was no evidence of teratogenicity in rabbit offspring with raxibacumab exposures up to 3 times the human dose on a mg/kg basis on gestation days 7 and 14. Dosing in this study resulted in raxibacumab Cmax values that were more than 3 and 4 times the mean Cmax values in humans after the first and second dose, respectively (Prod Info raxibacumab intravenous injection, 2014).
3.20.3) EFFECTS IN PREGNANCY
A) PREGNANCY CATEGORY 1) Raxibacumab is classified as FDA pregnancy category B (Prod Info raxibacumab intravenous injection, 2014).
2) There are no adequate and well-controlled studies of raxibacumab in pregnant women. Although teratogenicity was not evident in studies with IV administration of raxibacumab in rabbits, animal studies are not always predictive of human response. Therefore, it is recommended that raxibacumab be used during pregnancy only if clearly needed (Prod Info raxibacumab intravenous injection, 2014).
3.20.4) EFFECTS DURING BREAST-FEEDING
A) BREAST MILK 1) No reports describing the use of raxibacumab during human lactation or measuring the amount, if any, of the specific drug excreted into milk have been located. However, human immunoglobulins are excreted in human milk (Prod Info raxibacumab intravenous injection, 2014). Nonetheless, IV administration of human immunoglobulins is considered compatible with breastfeeding by the World Health Organization (Anon, 2002), as neonatal consumption of human milk does not result in substantial absorption of maternal immunoglobulins into circulation according to published data. Caution is recommended when administering raxibacumab to a lactating woman, because the effects of local gastrointestinal and systemic exposure to the drug on a nursing infant are unknown (Prod Info raxibacumab intravenous injection, 2014).
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