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Raxibacumab

Class: Anti-infectives, Miscellaneous

Introduction

Raxibacumab is a human IgG1λ monoclonal antibody that binds the protective antigen (PA) component of Bacillus anthracis toxin.1

Uses for Raxibacumab

Raxibacumab has the following uses:

Raxibacumab is indicated for the treatment of adult and pediatric patients with 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

Raxibacumab has the following limitations of use:

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

There have been no studies of raxibacumab in the pediatric population. Dosing in pediatric patients was derived using a population pharmacokinetic (PK) approach.1

Raxibacumab does not cross the blood-brain barrier and does not prevent or treat meningitis. Raxibacumab should be used in combination with appropriate antibacterial drugs.1

Raxibacumab Dosage and Administration

General

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

Injection: 1,700 mg/34 mL (50 mg/mL) solution in a single-use vial.1

Raxibacumab 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

  • Dilute and administer as an intravenous infusion over 2 hours and 15 minutes.1

  • Adults: 40 mg/kg raxibacumab.1

  • Pediatrics greater than 50 kg: 40 mg/kg raxibacumab.1

  • Pediatrics greater than 15 kg to 50 kg: 60 mg/kg raxibacumab.1

  • Pediatrics 15 kg or less: 80 mg/kg raxibacumab.1

Cautions for Raxibacumab

Contraindications

None.1

Warnings/Precautions

Infusion Reactions

Infusion-related reactions were reported during administration of raxibacumab in clinical trials, including reports of rash, urticaria, and pruritus. If these reactions occur, slow or interrupt raxibacumab infusion and administer appropriate treatment based on severity of the reaction.1

Premedicate with diphenhydramine within 1 hour prior to administering raxibacumab to reduce the risk of infusion reactions.1

Specific Populations

Pregnancy

Pregnancy category B.1

A single embryonic-fetal development study was conducted in pregnant, healthy New Zealand White rabbits administered 2 intravenous doses of raxibacumab up to 120 mg/kg (3 times the human dose on a mg/kg basis) on gestation days 7 and 14. No evidence of harm to the pregnant dam or the fetuses due to raxibacumab was observed. Cmaxvalues in rabbits after dosing with 120 mg/kg were 3,629 mcg/mL and 4,337 mcg/mL after the first and second doses of raxibacumab, respectively; these are more than 3 and 4 times the mean Cmax values in humans. Estimates of exposure (AUC) were not generated in the embryo-fetal rabbit study. No adequate and well-controlled studies in pregnant women were conducted. Because animal reproduction studies are not always predictive of human response, raxibacumab should be used during pregnancy only if clearly needed.1

Nursing Mothers

Raxibacumab 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 raxibacumab on a nursing infant are unknown.1

Pediatric Use

As in adults, the effectiveness of raxibacumab in pediatric patients is based solely on efficacy studies in animal models of inhalational anthrax. As exposure of healthy children to raxibacumab is not ethical, a population PK approach was used to derive dosing regimens that are predicted to provide pediatric patients with exposure comparable to the observed exposure in adults receiving 40 mg/kg. The dose for pediatric patients is based on weight.1

Safety or PK of raxibacumab have not been studied in the pediatric population.1

Geriatric Use

Clinical trials of raxibacumab did not include sufficient numbers of subjects aged 65 years and older to determine whether they respond differently from younger subjects. Of the total number of subjects in clinical trials of raxibacumab, 6.4% (21/326) were 65 years and older, while 1.5% (5/326) were 75 years and older. However, no alteration of dosing is needed for patients ≥65 years of age.1

Common Adverse Effects

Common adverse reactions in healthy adult subjects (≥1.5%) were rash, pain in extremity, pruritus, and somnolence.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

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

Microbiology

Raxibacumab is a monoclonal antibody that binds free PA with an affinity equilibrium dissociation constant (Kd) of 2.78 ± 0.9 nM. Raxibacumab 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

Raxibacumab binds in vitro to PA from the Ames, Vollum, and Sterne strains of B. anthracis. Raxibacumab binds to an epitope on PA that is conserved across reported strains of B. anthracis. 1 In vivo studies in rats suggest that raxibacumab neutralizes the toxicity due to lethal toxin, as animals slowly infused with lethal toxin (a combination of PA and lethal factor) survived 7 days following administration. The median time to death in control rats was 16 hours. Similar observations were noted in animal efficacy studies in rabbits and monkeys challenged with B. anthracis spores by the inhalational route. PA was detected in animals following exposure to B. anthracis spores. PA levels rose and then fell to undetectable levels in animals that responded to treatment and survived, whereas levels continued to rise in animals that failed treatment and died or were euthanized because of poor clinical condition.1

Advice to Patients

See FDA-approved patient labeling (Patient Information).

Efficacy Based on Animal Models

Inform patients that the efficacy of raxibacumab is based solely on efficacy studies demonstrating a survival benefit in animals and that the effectiveness of raxibacumab has not been tested in humans with anthrax. The safety of raxibacumab has been tested in healthy adults, but no safety data are available in children or pregnant women. Limited data are available in geriatric patients.1

Pregnancy and Nursing Mothers

Inform patients that raxibacumab has not been studied in pregnant women or nursing mothers so the effects of raxibacumab on pregnant women or nursing infants are not known. Instruct patients to tell their healthcare professional if they are pregnant, become pregnant, or are thinking about becoming pregnant. Instruct patients to tell their healthcare professional if they plan to breastfeed their infant.1

Infusion Reactions

Infusion-related reactions were reported during administration of raxibacumab in clinical trials, including reports of rash, urticaria, and pruritus.1

Prophylactic administration of diphenhydramine is recommended within 1 hour prior to administering raxibacumab. Diphenhydramine route of administration (oral or IV) should be based on the temporal proximity to the start of raxibacumab infusion.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.

Raxibacumab 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

Raxibacumab

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection

50 mg /1 mL

Raxibacumab

Human Genome Sciences Inc.

50 mg /1 mL

Raxibacumab

Human Genome Sciences Inc.

AHFS DI Essentials. © Copyright, 2016, American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

Date published: September 08, 2016
Last reviewed: September 08, 2016
Date modified: November 09, 2016

References

1. Human Genome Sciences, Inc. Raxibacumab (raxibacumab) INTRAVENOUS prescribing information. 2016 Mar.

2. Food and Drug Administration. Center for Drug Evaluation and Research: Application number 125349Orig1s000. Other review(s). 2012 Dec 10. From FDA website

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