ANTHIM

1 Dosing Considerations  Pre-medicate with diphenhydramine prior to administering ANTHIM [see WARNINGS AND PRECAUTIONS]. 9% Sodium Chloride Injection, USP, before administering as an intravenous infusion [see Dilution].  ANTHIM should be administered in monitored settings by personnel trained and equipped to manage anaphylaxis [see WARNINGS AND PRECAUTIONS].

 Monitor individuals who receive ANTHIM closely for signs and symptoms of hypersensitivity reactions throughout the infusion and for a period of time after administration [see WARNINGS AND PRECAUTIONS]. 2 Recommended Dose and Dosage Adjustment Adults  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].

Pediatrics (< 18 yrs)  The recommended dose for pediatric patients is based on weight as shown in Table 1 below. Serious Warnings and Precautions 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 Administration]. EUND Anthim™ Product Monograph Page 6 of 24 Table 1 Recommended Pediatric Dose of ANTHIM (weight-based dosing) Body Weight Dose Greater than 40 kg 16 mg/kg Greater than 15 kg up 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].

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 ACTION AND CLINICAL PHARMACOLOGY, Pharmacokinetics, Special Populations].

3 Dilution 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.

1 Adverse Reaction Overview The safety profile presented is based on analysis in three safety studies of ANTHIM. A total of 320 healthy subjects received one or two 16 mg/kg IV doses of ANTHIM. The most frequently reported adverse reactions were pruritus, rash, cough, infusion site swelling, urticaria, and injection-site pain.

2 Clinical Trial Adverse Reactions Because clinical trials are conducted under very specific conditions, the adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.

Adverse reaction information from clinical trials is useful for identifying drug-related adverse events and for approximating rates. 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, and 34 and 31 subjects received a second dose of ANTHIM either 2 weeks apart or ≥ 4 months apart. 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).

The overall safety of ANTHIM was evaluated as an integrated summary of these three clinical trials. Of 320 subjects receiving ANTHIM, 250 received single doses, 34 received 2 doses 2 weeks apart, and 31 received 2 doses ≥ 4 months apart.

7% Hispanic. 5% of healthy subjects receiving a single dose of ANTHIM (16 mg/kg IV) and more frequently than those receiving placebo. 5% of healthy adult subjects exposed to a single dose of ANTHIM 16 mg/kg IV and more frequently than placebo.

Please see the Serious Warnings and Precautions Box at the beginning of Part 1:

Health Professional Information. 7%) heathy subjects who received placebo. One case of anaphylaxis occurred in a subject who received ANTHIIM. Hypersensitivity reactions reported in the clinical studies include rash, urticaria, pruritus, cough, dysphonia, dyspnea, cyanosis, dizziness, chest discomfort, and anaphylactic reaction.

Due to the risk of hypersensitivity and 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.

If anaphylaxis or hypersensitivity reactions occur, stop the infusion immediately and treat appropriately. [see Administration] Patients should be pre-medicated with diphenhydramine prior to administration of ANTHIM [see DOSAGE AND ADMINISTRATION and ADVERSE REACTIONS].

Diphenhydramine premedication does not prevent anaphylaxis, and may mask or delay onset of symptoms of hypersensitivity. 1 Pregnant Women 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.

2 Breast-feeding ANTHIM has not been evaluated in nursing women. It is unknown whether ANTHIM is excreted in human milk. Inform a nursing woman that the effects of local gastrointestinal and systemic exposure to ANTHIM on nursing infant are unknown.

3 Pediatrics Pediatrics (<18 years of age): As in adults, the effectiveness of ANTHIM in pediatric patients is based solely on efficacy studies in animal models of inhalational anthrax. There have been no studies of safety or PK of ANTHIM in the pediatric population.

ANTHIM is contraindicated in patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, [see DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING].