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Anthim

Generic Name: Obiltoxaximab
Class: Antitoxins and Immune Globulins

Warning(s)

Warning: Hypersensitivity and Anaphylaxis

See full prescribing information for complete boxed warning. 1

  • Hypersensitivity reactions, including anaphylaxis, have been reported during obiltoxaximab infusion.1

  • Obiltoxaximab should be administered in monitored settings by personnel trained and equipped to manage anaphylaxis.1

  • Stop obiltoxaximab infusion immediately and treat appropriately if hypersensitivity or anaphylaxis occurs.1

Introduction

Obiltoxaximab is a chimeric IgG1 kappa monoclonal antibody that binds the protective antigen (PA) component of Bacillus anthracis toxin.1

Uses for Anthim

Obiltoxaximab has the following uses:

Obiltoxaximab 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

Obiltoxaximab has the following limitations of use:

Obiltoxaximab should be used for prophylaxis only when its benefit for prevention of inhalational anthrax outweighs the risk of hypersensitivity and anaphylaxis.1

The effectiveness of obiltoxaximab is based solely on efficacy studies in animal models of inhalational anthrax.1

There have been no studies of the safety or pharmacokinetics (PK) of obiltoxaximab in the pediatric population. Dosing in pediatric patients was derived using a population PK approach.1

Obiltoxaximab does not have direct antibacterial activity and should be used in combination with appropriate antibacterial drugs.1

Obiltoxaximab is not expected to cross the blood-brain barrier and does not prevent or treat meningitis.1

Anthim Dosage and Administration

General

Obiltoxaximab is available in the following dosage form(s) and strength(s):

Injection: 600 mg/6 mL (100 mg/mL) solution in single-dose vial.1

Obiltoxaximab is stored in the US Strategic National Stockpile (SNS). FDA-approved vial and carton labeling and separate NDC numbers distinguish stockpile units of the drug from any units intended for commercial use.1 2

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

  • Premedicate with diphenhydramine.1

  • Administer in a monitored setting equipped to manage anaphylaxis.1

  • Dilute in 0.9% Sodium Chloride Injection, USP, as directed by the manufacturer and administer as an intravenous (IV) infusion over 1 hour and 30 minutes.1

  • Adults: 16 mg/kg.1

  • Pediatric Patients Greater than 40 kg: 16 mg/kg.1

  • Pediatric Patients Greater than 15 kg to 40 kg: 24 mg/kg.1

  • Pediatric Patients Less than or equal to 15 kg: 32 mg/kg.1

Cautions for Anthim

Contraindications

None.1

Warnings/Precautions

Hypersensitivity and Anaphylaxis

Hypersensitivity reactions were the most common adverse reactions in the safety trials of obiltoxaximab, 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. Obiltoxaximab 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.1

Due to the risk of anaphylaxis, obiltoxaximab 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.1

Premedication with diphenhydramine is recommended prior to administration of obiltoxaximab. Diphenhydramine premedication does not prevent anaphylaxis, and may mask or delay onset of symptoms of hypersensitivity.1

Specific Populations

Pregnancy

Pregnancy Category B.

No adequate and well-controlled studies in pregnant women were conducted. Because animal reproduction studies are not always predictive of human response, obiltoxaximab should be used during pregnancy only if clearly needed.1

A single embryonic-fetal development study was conducted in pregnant, healthy New Zealand White (NZW) rabbits administered 4 intravenous doses of obiltoxaximab up to 32 mg/kg (2 times the human dose on a mg/kg basis) on gestation days 6, 10, 13, and 17. No evidence of harm to the pregnant dam or the fetuses due to obiltoxaximab was observed. Cumulative exposures in NZW rabbits (10,000 mcg•day/mL) at the NOAEL of 32 mg/kg/dose (n=4 doses) based on AUC0-15 days were approximately two-fold the human male and female combined mean AUC at the clinical intravenous dose of 16 mg/kg. Cmax values following a 32 mg/kg/dose were 1180 mcg•day/mL.1

Nursing Mothers

Obiltoxaximab has not been evaluated in nursing women. Although human immunoglobulins are excreted in human milk, published data suggest that neonatal consumption of human milk does not result in substantial absorption of these maternal immunoglobulins into circulation. Inform a nursing woman that the effects of local gastrointestinal and systemic exposure to obiltoxaximab on nursing infant are unknown.1

Pediatric Use

As in adults, the effectiveness of obiltoxaximab in pediatric patients is based solely on efficacy studies in animal models of inhalational anthrax. As exposure of healthy children to obiltoxaximab is not ethical, a population PK approach was used to derive intravenous dosing regimens that are predicted to provide pediatric patients with exposure comparable to the observed exposure in adults receiving 16 mg/kg. The dose for pediatric patients is based on weight.1

There have been no studies of safety or PK of obiltoxaximab in the pediatric population.1

Geriatric Use

Clinical studies of obiltoxaximab did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently from younger subjects. Of the 320 subjects in clinical studies of obiltoxaximab, 9.4% (30/320) were 65 years and over, while 2% (6/320) were 75 years and over. No alteration of dosing is needed for patients ≥65 years of age.1

Common Adverse Effects

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.1

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

Please see product labeling for drug interaction information.

Actions and Spectrum

Mechanism of Action

Obiltoxaximab is a monoclonal antibody that binds the protective antigen (PA) of B. anthracis.1

Microbiology

Obiltoxaximab is a monoclonal antibody that binds free PA with an affinity equilibrium dissociation constant (Kd) of 0.33 nM. Obiltoxaximab inhibits the binding of PA to its cellular receptors, preventing the intracellular entry of the anthrax lethal factor and edema factor, the enzymatic toxin components responsible for the pathogenic effects of anthrax toxin.1

Obiltoxaximab binds in vitro to PA from the Ames, Vollum, and Sterne strains of B. anthracis. Obiltoxaximab binds to an epitope on PA that is conserved across reported strains of B. anthracis.1

In vitro studies in a cell-based assay, using murine macrophages, suggest that obiltoxaximab neutralizes the toxic effects of lethal toxin, a combination of PA + lethal factor.1

In vivo efficacy studies in NZW rabbits and cynomolgus macaques challenged with the spores of the Ames strain of B. anthracis by the inhalational route, showed a dose-dependent increase in survival following treatment with obiltoxaximab. Exposure to B. anthracis spores resulted in increasing concentrations of PA in the serum of NZW rabbits and cynomolgus macaques. After treatment with obiltoxaximab there was a decrease in PA concentrations in a majority of surviving animals. PA concentrations in placebo animals increased until they died.1

Advice to Patients

Patient Counseling Information

Advise the patient to read the FDA-approved patient labeling.1

Efficacy Based on Animal Models Alone

Inform patients that the effectiveness of obiltoxaximab has been studied only in animals with inhalational anthrax. Obiltoxaximab has not been tested in people who have inhalational anthrax.1

Inform patients that the safety of obiltoxaximab has been studied in healthy adults, but no safety data are available in pediatric patients or pregnant women. Limited data are available in geriatric subjects.1

Hypersensitivity Reactions and Anaphylaxis

Inform patients that hypersensitivity reactions, including anaphylaxis, have occurred with administration of obiltoxaximab.

Inform patients of the signs and symptoms of hypersensitivity reactions and anaphylaxis and instruct patients to seek immediate medical care if they experience such symptoms during or following administration of obiltoxaximab.1

Additional Information

AHFS First Release. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Obiltoxaximab is stored in the US Strategic National Stockpile (SNS). FDA-approved vial and carton labeling and separate NDC numbers distinguish stockpile units of the drug from any units intended for commercial use.1 2

Obiltoxaximab

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, for IV use

100 mg /1 mL

Anthim

Elusys Therapeutics Inc.

AHFS Drug Information. © Copyright 2016, Selected Revisions September 14, 2016. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Elusys Therapeutics, Inc.. Anthim (obiltoxaximab) INTRAVENOUS prescribing information. 2016 Mar.

2. US Food and Drug Administration. Center for Drug Evaluation and Research: Application number 1255509Orig1s000. Other review(s). 2016 Mar 18. From FDA website

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