6 ML obiltoxaximab 100 MG/ML Injection

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 , 5.1 ) The effectiveness of ANTHIM is based solely on efficacy studies in animal models of inhalational anthrax. ( 1.2 , 14 ) There have been no studies of the safety or pharmacokinetics (PK) of ANTHIM in the pediatric population. Dosing in pediatric patients was derived using a population PK approach. ( 1.2 , 8.4 ) ANTHIM does not have direct antibacterial activity. ANTHIM should be used in combination with appropriate antibacterial drugs. ( 1.2 ) ANTHIM is not expected to cross the blood-brain barrier and does not prevent or treat meningitis. ( 1.2 ) 1.1 Inhalational Anthrax ANTHIM 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 not appropriate [see Indications and Usage ( 1.2 )] . 1.2 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 [see Warnings and Precautions ( 5.1 )] . The effectiveness of ANTHIM is based solely on efficacy studies in animal models of inhalational anthrax. It is not ethical or feasible to conduct controlled clinical trials with intentional exposure of humans to anthrax [see Clinical Studies ( 14 )] . Safety and PK of ANTHIM have been studied in adult healthy volunteers. There have been no studies of safety or PK of ANTHIM in the pediatric population. A population PK approach was used to derive intravenous infusion dosing regimens that are predicted to provide pediatric patients with exposure comparable to the observed exposure in adults [see Use in Specific Populations ( 8.4 )] . ANTHIM binds to the protective antigen (PA) component of B. anthracis toxin; it does not have direct antibacterial activity. ANTHIM is not expected to cross the blood-brain barrier and does not prevent or treat meningitis. ANTHIM should be used in combination with appropriate antibacterial drugs.

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 , 5.1 ) See Full Prescribing Information for instructions on preparation, dilution and administration of ANTHIM injection. ( 2.3 , 2.4 ) 2.1 Dosage for Adult Patients Pre-medicate with diphenhydramine prior to administering ANTHIM [see Warnings and Precautions ( 5.1 )] . Dilute the injection in 0.9% Sodium Chloride Injection, USP, before administering as an intravenous infusion [see Dosage and Administration ( 2.3 )] . The recommended dosage of ANTHIM in adult patients is a single dose of 16 mg/kg administered intravenously over 90 minutes (1 hour and 30 minutes) [see Dosage and Administration ( 2.4 )] . For adult patients weighing less than 40 kg, see Table 1 below. 2.2 Dosage for Pediatric Patients Pre-medicate with diphenhydramine prior to administering ANTHIM [see Warnings and Precautions ( 5.1 )]. Dilute the injection in 0.9% Sodium Chloride Injection, USP, before administering as an intravenous infusion [see Dosage and Administration ( 2.3 )]. The recommended dose for pediatric patients is based on weight as shown in Table 1 below. Table 1. Recommended Pediatric Dose of ANTHIM (weight-based dosing) Body Weight Dose 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 Administer the recommended dose of ANTHIM intravenously over 90 minutes (1 hour and 30 minutes) [see Dosage and Administration ( 2.4 )] . There have been no studies of the safety or PK of ANTHIM conducted in the pediatric population. The dosing recommendations in Table 1 are derived from simulations using a population PK approach designed to match the observed adult exposure to ANTHIM at a 16 mg/kg dose [see Use in Specific Populations ( 8.4 )] . 2.3 Preparation and Dilution for Administration Important Preparation Instructions Keep vials in their cartons prior to preparation of an infusion solution to protect ANTHIM from light. ANTHIM vials contain no preservative. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Discard the vial if the solution is discolored or contains extraneous particles other than a few translucent-to- white, proteinaceous particles [see Description ( 11 )] . Do not shake the vial. Table 2. ANTHIM Dose, Total Infusion Volume and Infusion Rate by Body Weight Body Weight (weight-based dosing) Total Infusion Volume Infusion Rate Greater than 40 kg or adult (16 mg/kg) Greater than 40 kg 250 mL 167 mL/hr Greater than 15 kg to 40 kg (24 mg/kg) 31 kg to 40 kg 250 mL 167 mL/hr 16 kg to 30 kg 100 mL 67 mL/hr 15 kg or less (32 mg/kg) 11 kg to 15 kg 100 mL 67 mL/hr 5 kg to 10 kg 50 mL 33.3 mL/hr 3.1 kg to 4.9 kg 25 mL 17 mL/hr 2.1 kg to 3 kg 20 mL 13.3 mL/hr 1.1 kg to 2 kg 15 mL 10 mL/hr 1 kg or less 7 mL 4.7 mL/hr Preparation and Dilution in Bag for Infusion Calculate the milligrams of ANTHIM injection needed by multiplying the recommended mg/kg dose in Table 2 by the patient weight in kilograms. Calculate the required volume in milliliters of ANTHIM injection and number of vials needed for the dose by dividing the calculated dose in milligrams (step 1) by the concentration, 100 mg/mL. Each single vial allows delivery of 6 mL of ANTHIM. Select an appropriate size bag of 0.9% Sodium Chloride Injection, USP. Withdraw a volume of solution from the bag equal to the calculated volume in milliliters of ANTHIM in step 2 above. Discard the solution that was withdrawn from the bag. Withdraw the required volume of ANTHIM injection (calculated from step 2) from the ANTHIM vial(s). Discard any unused portion remaining in the ANTHIM vial(s). Transfer the required volume of ANTHIM injection to the selected infusion bag. Gently invert the bag to mix the solution. Do not shake. The prepared solution is stable for 8 hours stored at room temperature 20°C to 25°C (68°F to 77°F) or 8 hours stored in the refrigerator at 2°C to 8°C (36°F to 46°F). Preparation and Dilution in Syringe for Infusion Calculate lunused product. 2.4 Administration Administer ANTHIM in appropriately monitored settings which are equipped to manage anaphylaxis [see Warnings and Precautions ( 5.1 )] . Dilute ANTHIM injection [see Dosage and Administration ( 2.3 )] before administering ANTHIM intravenously using the bag or syringe for infusion. After preparation of the bag or syringe for infusion administer the infusion solution using a 0.22 micron inline filter with the infusion rate described in Table 2 [see Dosage and Administration ( 2.3 )] . Administer diluted ANTHIM intravenous infusion over 1 hour and 30 minutes. Monitor patients closely for signs and symptoms of hypersensitivity throughout the infusion and for a period of time after administration [see Warnings and Precautions ( 5.1 )] . Stop the infusion immediately and treat appropriately, if hypersensitivity or anaphylaxis occurs [see Warnings and Precautions ( 5.1 )] . Flush the line with 0.9% Sodium Chloride Injection, USP at the end of the intravenous infusion.

WARNINGS AND PRECAUTIONS Hypersensitivity reactions, including anaphylaxis ( Boxed Warning , 1.2 , 2.1 , 12.4 , 5.1 ) 5.1 Hypersensitivity and Anaphylaxis 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 [see Adverse Reactions 6.1 ]. Due to the risk of anaphylaxis, ANTHIM should be administered in monitored settings by personnel trained and equipped to manage anaphylaxis. Patients should be monitored closely throughout the infusion period and for a period of time after administration [see Patient Counseling Information ( 17 )]. If anaphylaxis or hypersensitivity reactions occur, stop the infusion immediately and treat appropriately. Premedication with diphenhydramine is recommended prior to administration of ANTHIM [see Dosage and Administration ( 2.1 ) and Adverse Reactions ( 6.1 )] . Diphenhydramine premedication does not prevent anaphylaxis, and may mask or delay onset of symptoms of hypersensitivity.

CONTRAINDICATIONS None. None ( 4 )

Mechanism of Action Obiltoxaximab is a monoclonal antibody that binds the PA of B. anthracis [see Microbiology ( 12.4 )] .