Overview
11 DESCRIPTION Obiltoxaximab is a chimeric IgG1 kappa monoclonal antibody (mAb) that binds the PA component of B. anthracis toxin. It has an approximate molecular weight of 148 kDa. ANTHIM injection is a sterile, preservative-free, clear to opalescent, colorless to pale yellow to pale brownish-yellow solution that may contain few translucent-to-white proteinaceous particulates.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Obiltoxaximab is a monoclonal antibody that binds the PA of B. anthracis [see Microbiology ( 12.4 )] . 12.3 Pharmacokinetics The PK of obiltoxaximab are linear over the dose range of 4 mg/kg (0.25 times the lowest recommended dose) to 16 mg/kg following single IV administration in healthy subjects. Following single IV administration of ANTHIM 16 mg/kg in healthy, male and female human subjects, the mean C max and AUC inf were 400 ± 91.2 mcg/mL and 5170 ± 1360 mcg•day/mL, respectively. Repeat Dosing Although ANTHIM is intended for single dose administration, the PK of obiltoxaximab following a second dose administration of 16 mg/kg IV given 2 weeks or ≥ 4 months after the first 16 mg/kg IV dose was assessed in 65 healthy subjects (study 2).
Indications
- 1 INDICATIONS AND USAGE ANTHIM ® is a monoclonal antibody directed against the protective antigen of Bacillus anthracis . It is indicated in adult and pediatric patients for treatment of inhalational anthrax due to B. anthracis in combination with appropriate antibacterial drugs and, for prophylaxis of inhalational anthrax when alternative therapies are not available or are not appropriate. ( 1.1 ) Limitations of Use ANTHIM should only be used for prophylaxis when its benefit for prevention of inhalational anthrax outweighs the risk of hypersensitivity and anaphylaxis. ( 1.2 , 5.
Common Doses
- 16 mg
- 24 mg
- 32 mg
- 250 mL
Dosage
2 DOSAGE AND ADMINISTRATION Pre-medicate with diphenhydramine. ( 2.1 , 5.1 ) Recommended Dosage of ANTHIM: Adult Patients: 16 mg/kg. ( 2.1 ) Pediatric Patients: ( 2.2 ) ➢ Greater than 40 kg: 16 mg/kg ➢ Greater than 15 kg to 40 kg: 24 mg/kg ➢ Less than or equal to 15 kg: 32 mg/kg Dilute the injection in 0.9% Sodium Chloride Injection, USP, before administering as an intravenous (IV) infusion over 1 hour and 30 minutes. ( 2.3 ) Administer ANTHIM in a monitored setting equipped to manage anaphylaxis. ( 2.4 , 5.
Black Box Warning
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 [see Indications and Usage ( 1.
Contraindications
- 4 CONTRAINDICATIONS None. None ( 4 )
Side Effects
- 6 ADVERSE REACTIONS The following clinically important adverse reactions are described elsewhere in the labeling: Hypersensitivity and Anaphylaxis [see Warnings and Precautions ( 5.1 )]. Most frequently reported adverse reactions in healthy adult subjects (≥1.5%) were headache, pruritus, infections of the upper respiratory tract, cough, vessel puncture site bruise, infusion site swelling, nasal congestion, infusion site pain, urticaria and pain in extremity. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Elusys Therapeutics, Inc. at 1-844-808-0222 or FDA at 1-800-FDA-1088 or www.fda.
Interactions
- 7 DRUG INTERACTIONS 7.1 Ciprofloxacin Co-administration of 16 mg/kg ANTHIM intravenously with intravenous or oral ciprofloxacin in human subjects did not alter the PK of either ciprofloxacin or obiltoxaximab [see Clinical Pharmacology ( 12.3 )] .