The safety of ANTHIM has been studied only in healthy volunteers. It has not been studied in patients with inhalational anthrax.
The safety of ANTHIM was evaluated in 320 healthy subjects treated with one or more 16 mg/kg IV doses in three clinical studies. Study 1 was a placebo-controlled study evaluating a single dose of ANTHIM vs. placebo (210 subjects received ANTHIM, 70 received placebo). Study 2 was a repeat-dose study in which 70 subjects received the first dose, then 34 and 31 subjects received a second dose of ANTHIM in sequences A (2 weeks apart) and B (≥ 4 months apart), respectively. Study 3 was a drug interaction study of a single dose of ANTHIM with ciprofloxacin in 40 subjects (20 subjects received ANTHIM alone and 20 subjects received ANTHIM plus ciprofloxacin for 9 days). Subjects were 18 to 79 years of age, 54% were male, 70% Caucasian, 26% Black/African American, 2% American Indian/Alaska Native, 1% Asian and 10% Hispanic.
N = 70 (%)
|Single Dose ANTHIM
N = 300* (%)
|Headache||4 (6%)||24 (8%)|
|Pruritus||1 (1%)||11 (4%)|
|Infections of the upper respiratory tract||2 (3%)||14 (5%)|
|Vessel puncture site bruise||1 (1%)||8 (3%)|
|Infusion site swelling||1 (1%)||8 (3%)|
|Nasal congestion||1 (1%)||5 (2%)|
|Infusion site pain||0||7 (2%)|
|Pain in extremity||1 (1%)||5 (2%)|
*Single-dose population: 210 subjects in study 1 plus 70 subjects in the first treatment period of study 2 plus 20 subjects in the ANTHIM alone treatment arm of study 3.
Overall in the single-dose population, subjects who received pre-medication with diphenhydramine were less likely to experience adverse reactions with administration of ANTHIM compared to those who did not (42% vs. 58% respectively). Specifically, the incidence of the following adverse reactions was lower in the subjects who received diphenhydramine prior to ANTHIM infusion compared to those who did not: headache (5% vs. 16%), cough (1% vs. 8%), rash (2% vs. 7%), pruritus (3% vs. 4%) throat irritation (0 vs. 3%), rhinorrhea (0 vs. 3%), and infusion site erythema (0% vs. 4%). Somnolence was only reported in subjects who were pretreated with diphenhydramine.
ANTHIM® (obiltoxaximab) is indicated in adult and pediatric patients for the treatment of inhalational anthrax due to Bacillus anthracis in combination with appropriate antibacterial drugs. ANTHIM is indicated for prophylaxis of inhalational anthrax due to B. anthracis when alternative therapies are not available or are not appropriate.
WARNING: HYPERSENSITIVITY and ANAPHYLAXIS
Hypersensitivity and anaphylaxis have been reported during the intravenous infusion of ANTHIM. Due to the risk of hypersensitivity and anaphylaxis, ANTHIM should be administered in monitored settings by personnel trained and equipped to manage anaphylaxis. Monitor individuals who receive ANTHIM closely for signs and symptoms of hypersensitivity reactions throughout the infusion and for a period of time after administration. Stop ANTHIM infusion immediately and treat appropriately if hypersensitivity or anaphylaxis occurs.
Hypersensitivity reactions were the most common adverse reactions in the safety trials of ANTHIM, occurring in 34/320 healthy subjects (10.6%). Three (0.9%) cases of anaphylaxis occurred during or immediately after the infusion. In clinical trials, manifestations of anaphylaxis were rash/urticaria, cough, dyspnea, cyanosis, postural dizziness and chest discomfort. ANTHIM infusion was discontinued in 8 (2.5%) subjects due to hypersensitivity or anaphylaxis. The adverse reactions reported in these 8 subjects included urticaria, rash, cough, pruritus, dizziness, throat irritation, dysphonia, dyspnea and chest discomfort. The remaining subjects with hypersensitivity had predominantly skin-related symptoms such as pruritus and rash, and 6 subjects reported cough.
Premedication with diphenhydramine is recommended prior to administration of ANTHIM. Diphenhydramine premedication does not prevent anaphylaxis, and may mask or delay onset of symptoms of hypersensitivity.
The safety of ANTHIM has been studied only in healthy volunteers. It has not been studied in patients with inhalational anthrax. The most frequently reported adverse reactions (occurred in >1.5% of healthy subjects) were headache, pruritus, infections of the upper respiratory tract, cough, vessel puncture site bruise, infusion site swelling, urticaria, nasal congestion, infusion site pain, and pain in extremity.
No adequate and well-controlled studies in pregnant women were conducted. Because animal reproduction studies are not always predictive of human response, ANTHIM should be used during pregnancy only if clearly needed.
There have been no studies of the safety or PK of ANTHIM in the pediatric population.