ANTHIM Solution for injection Ref.[10346] Active ingredients: Obiltoxaximab

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):

• 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:

Preparation and Dilution in Bag for Infusion:

1. Calculate the milligrams of ANTHIM injection needed by multiplying the recommended mg/kg dose in Table 2 by the patient weight in kilograms.
2. 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.
3. 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.
4. 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).
5. Transfer the required volume of ANTHIM injection to the selected infusion bag.
6. Gently invert the bag to mix the solution. Do not shake.
7. 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:

1. Calculate the milligrams of ANTHIM injection needed by multiplying the recommended mg/kg dose in Table 2 by the patient weight in kilograms.
2. 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.
3. Select an appropriate size syringe for the total volume of infusion to be administered.
4. Using the selected syringe, withdraw the required volume of ANTHIM injection (calculated from step 2). Discard any unused portion remaining in the ANTHIM vial(s).
5. Withdraw an appropriate amount of 0.9% Sodium Chloride Injection, USP to prepare the total infusion volume specified in Table 2.
6. Gently mix the solution. Do not shake.
7. Once a diluted solution of ANTHIM has been prepared, administer immediately. Do not store solution in syringe. Discard unused 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.

There is no clinical experience with overdosage of ANTHIM. In case of overdosage, monitor patients for any signs or symptoms of adverse effects.

Store in refrigerator at 2°C to 8°C (36°F to 46°F) in original carton to protect from light. Do Not Freeze. Do Not Shake.