Class: Antitoxins and Immune Globulins
ATC Class: J06BB18
Chemical Name: Immunoglobulin G1, anti-(anthrax protective antigen) (human monoclonal PA heavy chain), disulfide with human monoclonal PAλ-chain, dimer.
Molecular Formula: C6320H9794N1702O1998S42
CAS Number: 565451-13-0
Raxibacumab is a human IgG1λ monoclonal antibody that binds the protective antigen (PA) component of Bacillus anthracis toxin.
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.
Raxibacumab has the following limitations of use:
The effectiveness of raxibacumab is based solely on efficacy studies in animal models of inhalational anthrax.
There have been no studies of raxibacumab in the pediatric population. Dosing in pediatric patients was derived using a population pharmacokinetic (PK) approach.
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.
Raxibacumab Dosage and Administration
Raxibacumab is available in the following dosage form(s) and strength(s):
Injection: 1,700 mg/34 mL (50 mg/mL) solution in single-use vial.
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.
Dilute and administer as an intravenous infusion over 2 hours and 15 minutes.
Adults: 40 mg/kg.
Pediatric Patients Weighing Greater than 40 kg: 40 mg/kg.
Pediatric Patients Weighing Greater than 10 kg to 40 kg: 60 mg/kg.
Pediatric Patients Weighing 10 kg or Less: 80 mg/kg.
Cautions for Raxibacumab
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.
Premedicate with diphenhydramine within 1 hour prior to administering raxibacumab to reduce the risk of infusion reactions.
Risk Summary: There are no data on the use of raxibacumab in pregnant women to inform on drug-associated risk. In pregnant rabbits, intravenous administration of raxibacumab was not associated with teratogenicity or other adverse developmental outcomes at 3 times the human maximum plasma concentrations at the maximum recommended adult dose.
All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background rate of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies.
Disease-Associated Maternal and/or Embryo/Fetal Risk: Limited data in the form of case reports of anthrax infection in pregnant women indicate that maternal infection is associated with a high risk of maternal, fetal, and neonatal deaths, particularly in the absence of treatment.
Animal Data: A study was conducted in pregnant, healthy New Zealand White rabbits administered intravenous raxibacumab at dose levels of 40 or 120 mg/kg on gestation days 7 and 14. No teratogenicity or other adverse developmental outcomes were observed in pregnant rabbits at 3 times the human maximum plasma concentrations at the maximum recommended adult dose of 40 mg/kg. Maternal toxicity was observed at both doses (reduced body weight gain late in gestation, but no difference in mean total weight gain).
There is no information available on the presence of raxibacumab in human milk, the effects on the breastfed child, or the effects on milk production. Maternal IgG is known to be present in human milk. Therefore, the developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for raxibacumab and any potential adverse effects on the breastfed child from raxibacumab or from the underlying maternal condition.
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, an extrapolation 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.
Safety or PK of raxibacumab have not been studied in the pediatric population.
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.
Common Adverse Effects
Common adverse reactions in healthy adult subjects (≥1.5%) were rash, pain in extremity, pruritus, and somnolence.
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.
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.
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. 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.
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.
Infusion-related reactions were reported during administration of raxibacumab in clinical trials, including reports of rash, urticaria, and pruritus.
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.
AHFSfirstReleasetm. 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.
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) and is not commercially available in the US. The SNS ensures that certain drugs and medical supplies are readily available to prevent or treat specific diseases, including during public health emergencies, and is managed by the US Department of Health and Human Services (HHS) Office of the Assistant Secretary for Preparedness and Response (ASPR). To request a drug from the SNS, state health departments can contact the US Centers for Disease Control and Prevention (CDC) Emergency Operations Center at 770-488-7100 or the HHS Secretary's Operations Center at 202-619-7800.
AHFS Drug Information. © Copyright 2021, Selected Revisions April 8, 2019. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.