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Raxibacumab

FDA Drug Information • Also known as: Raxibacumab

Brand Names
Raxibacumab
Dosage Form
LIQUID
Product Type
BULK INGREDIENT

⚠ Boxed Warning (Black Box)

WARNING: HYPERSENSITIVITY and ANAPHYLAXIS Hypersensitivity reactions, including anaphylaxis, have been reported during or after the administration of raxibacumab by intravenous infusion [see Warnings and Precautions ( 5.1 )] . Administer raxibacumab by intravenous infusion in monitored settings where appropriate equipment, medication (including epinephrine) and personnel trained in the management of hypersensitivity, anaphylaxis, and shock are available [see Warnings and Precautions ( 2.3 , 5.1 )] . WARNING: HYPERSENSITIVITY and ANAPHYLAXIS See full prescribing information for complete boxed warning Hypersensitivity reactions, including anaphylaxis, have been reported during or after the administration of raxibacumab by intravenous infusion ( 5.1 ). Administer raxibacumab by intravenous infusion in monitored settings where appropriate equipment, medication (including epinephrine) and personnel trained in the management of hypersensitivity, anaphylaxis, and shock are available ( 2.3 , 5.1 ).

Description

11 DESCRIPTION Raxibacumab is a human IgG1λ monoclonal antibody that binds the PA component of B. anthracis toxin. Raxibacumab has a molecular weight of approximately 146 kilodaltons. Raxibacumab is produced by recombinant DNA technology in a murine cell expression system. Raxibacumab is supplied as a sterile, preservative-free, clear to opalescent, colorless to pale yellow liquid formulation in single-use vials for intravenous infusion. Each vial contains 1,700 mg/34 mL (50 mg/mL) raxibacumab in citric acid (0.13 mg/mL), glycine (18 mg/mL), polysorbate 80 [0.2 mg/mL (w/v)], sodium citrate (2.8 mg/mL), sucrose (10 mg/mL), and Water for Injection, with a pH of 6.5.

What Is Raxibacumab Used For?

1 INDICATIONS AND USAGE Raxibacumab is indicated for the treatment of adult and pediatric patients with inhalational anthrax due to Bacillus anthracis in combination with appropriate antibacterial drugs, and for prophylaxis of inhalational anthrax when alternative therapies are not available or are not appropriate. ( 1.1 ) Limitations of Use: The effectiveness of raxibacumab is based solely on efficacy studies in animal models of inhalational anthrax. ( 1.2 , 14.1 ) There have been no studies of raxibacumab in the pediatric population. Dosing in pediatric patients was derived using an extrapolation approach. ( 1.2 , 8.4 ) 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. ( 1.2 ) 1.1 Inhalational Anthrax Raxibacumab is indicated for the treatment of adult and pediatric patients with inhalational anthrax due to Bacillus anthracis in combination with appropriate antibacterial drugs. Raxibacumab is also indicated for prophylaxis of inhalational anthrax when alternative therapies are not available or are not appropriate. 1.2 Limitations of Use The effectiveness of raxibacumab is based solely on efficacy studies in animal models of inhalational anthrax. It is not ethical or feasible to conduct controlled clinical trials with intentional exposure of humans to anthrax [see Clinical Studies ( 14.1 )]. Safety and pharmacokinetics (PK) of raxibacumab have been studied in adult healthy volunteers. There have been no trials of safety or PK of raxibacumab in the pediatric population. 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 [see Use in Specific Populations ( 8.4 )]. Raxibacumab binds to the protective antigen (PA) of B. anthracis ; it does not have direct antibacterial activity. 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.

Dosage and Administration

2 DOSAGE AND ADMINISTRATION Premedicate with diphenhydramine. ( 2.1 , 2.2 , 5.1 ) Dilute and administer as an intravenous infusion over 2 hours and 15 minutes. ( 2.3 ) - Adults: 40 mg/kg raxibacumab. ( 2.1 ) - Pediatrics greater than 40 kg: 40 mg/kg raxibacumab. ( 2.2 ) - Pediatrics greater than 10 kg to 40 kg: 60 mg/kg raxibacumab. ( 2.2 ) - Pediatrics 10 kg or less: 80 mg/kg raxibacumab. ( 2.2 ) 2.1 Dose and Schedule for Adults Administer raxibacumab as a single dose of 40 mg/kg intravenously over 2 hours and 15 minutes after dilution in 0.9% Sodium Chloride Injection, USP (normal saline) to a final volume of 250 mL. Administer 25 to 50 mg diphenhydramine within 1 hour prior to the raxibacumab infusion to reduce the risk of occurrence and/or the severity of an infusion reaction. Diphenhydramine route of administration (oral or intravenous) should be based on the temporal proximity to the start of the raxibacumab infusion [see Warnings and Precautions ( 5.1 ) , Adverse Reactions ( 6.1 )]. 2.2 Dose and Schedule for Pediatric Patients The recommended dose for pediatric patients is based on weight as shown in Table 1 . Table 1. Recommended Pediatric Dose Pediatric Body Weight Pediatric Dose Greater than 40 kg 40 mg/kg Greater than 10 kg to 40 kg 60 mg/kg 10 kg or less 80 mg/kg Premedicate with diphenhydramine within 1 hour prior to the raxibacumab infusion to reduce the risk of occurrence and/or the severity of an infusion reaction. Diphenhydramine route of administration (oral or intravenous) should be based on the temporal proximity to the start of the raxibacumab infusion. Infuse raxibacumab over 2 hours and 15 minutes. No pediatric patients were studied during the development of raxibacumab. The dosing recommendations in Table 1 are derived from simulations designed to match the observed adult exposure to raxibacumab at a 40 mg/kg dose [see Use in Specific Populations ( 8.4 )]. 2.3 Preparation and Administration of Raxibacumab The recommended dose of raxibacumab is weight-based, given as an intravenous infusion after dilution in a compatible solution to a final volume of 250 mL in adults or to a volume indicated based on the child’s weight ( Table 2 ). Dilute raxibacumab using one of the following compatible solutions: 0.9% Sodium Chloride Injection, USP 0.45% Sodium Chloride Injection, USP Keep vials in their cartons prior to preparation of an infusion solution to protect raxibacumab from light. Raxibacumab vials contain no preservative. Table 2. Raxibacumab Dose, Diluents, Infusion Volumes, and Rates by Body Weight a For patients requiring maximal fluid restriction, dilution factors can be adjusted at the discretion of the physician to a maximal concentration of 32 mg/mL. Preparation Administration Body Weight Dose Total Infusion Volume a Type of Diluent Infusion Rate Infusion Rate First 20 Minutes Remaining Infusion Adults 40 mg/kg 250 mL 0.9% Sodium Chloride Injection 15 mL/hour 125 mL/hour Pediatric Patients (Younger than 18 Years) Less...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS Common adverse reactions in healthy adult subjects (≥1.5%) were injection site reaction, erythema and pain, headache, rash, pain in extremity, pruritus, and somnolence. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Emergent BioSolutions at 1-800-768-2304 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of raxibacumab has been studied only in healthy volunteers. It has not been studied in patients with inhalational anthrax. In the three pre-licensure clinical trials (Trials 1, 2, and 3), the safety of raxibacumab was evaluated in 326 healthy subjects treated with a dose of 40 mg/kg in 3 clinical trials: a drug interaction trial with ciprofloxacin (Trial 1), a repeat-dose trial of 20 subjects with the second raxibacumab dose administered ≥4 months after the first dose (Trial 2), and a placebo-controlled trial evaluating single doses with a subset of subjects receiving 2 raxibacumab doses 14 days apart (Trial 3). Raxibacumab was administered to 86 healthy subjects in Trial 1. In Trial 3, 240 healthy subjects received raxibacumab (217 received 1 dose and 23 received 2 doses) and 80 subjects received placebo. The overall safety of raxibacumab was evaluated as an integrated summary of these 3 clinical trials. Of 326 raxibacumab subjects, 283 received single doses, 23 received 2 doses 14 days apart, and 20 received 2 doses more than 4 months apart. The subjects were aged 18 to 88 years, 53% female, 74% white, 17% black/African American, 6% Asian, and 15% Hispanic. Trial 4 was a post-marketing trial in healthy subjects designed to evaluate the effect of a single 40 mg/kg infusion of raxibacumab on the immunogenicity of a concurrently administered 3-dose subcutaneous (SC) regimen of Anthrax Vaccine Adsorbed (AVA) [N=286] compared with an AVA-alone regimen [N=286]. In the combination arm, the first dose of AVA was administered immediately following the raxibacumab infusion (Day 1), while the second and third doses were administered on Days 15 and 29. The mean age of subjects was 36 years in both arms, 52% of subjects in the AVA arm and 50% in the AVA + raxibacumab arm were female, 75% and 77% in the two arms, respectively, were white, while 21% and 20%, respectively, were African American. Adverse Reactions Leading to Discontinuation or Interruption of Raxibacumab Infusion Four subjects (1.2%) in Trials 1, 2 and 3 had their infusion of raxibacumab discontinued for hypersensitivity and anaphylaxis: 2 subjects (neither of whom received diphenhydramine premedication) discontinued due to urticaria (mild), and 1 subject each discontinued for clonus (mild) and dyspnea (moderate). In Trial 4, six (2.1%) subjects required discontinuation of the raxibacumab infusion and 3 (1.0%) subjects required infusion interruption due to hypersensitivity or anaphylaxis [see Warnings and Precautions ( 5.1 )] . Most Frequently Reported Adverse Reactions Trials 1, 2, and -3 In Trials 1, 2, and 3, the most frequently reported adverse reactions were rash, pain in extremity, pruritus, and somnolence ( Table 3 ). Table 3. Adverse Reactions Reported in ≥1.5% of Healthy Adult Subjects Exposed to Raxibacumab 40 mg/kg Intravenously in Trials 1, 2, and 3 Adverse Reaction Placebo N = 80 (%) Single-Dose Raxibacumab N = 283 (%) Double-Dose Raxibacumab ≥4 Months Apart N = 20 (%) Double-Dose Raxibacumab 2 Weeks Apart N = 23 (%) Total Raxibacumab Subjects N = 326 (%) Rash/Rash erythematous/Rash papular 1 (1.3) 9 (3.2) 0 0 9 (2.8) Pain in extremity 1 (1.3) 7 (2.5) 0 0 7 (2.1) Pruritus 0 7 (2.5) 0 0 7 (2.1) Somnolence 0 4 (1.4) 0 1 (4.3) 5 (1.5) Rashes For all subjects exposed to raxibacumab in Trials 1, 2, and 3, the rate of rash was 2.8%...

Drug Interactions

7 DRUG INTERACTIONS 7.1 Ciprofloxacin Co-administration of 40 mg/kg raxibacumab intravenously with intravenous or oral ciprofloxacin in human subjects did not alter the PK of either ciprofloxacin or raxibacumab [see Clinical Pharmacology ( 12.3 )] . 7.2 Anthrax Vaccine Adsorbed (AVA) Co-administration of 40 mg/kg raxibacumab intravenously (Day 1) with a SC AVA regimen (Days 1, 15, and 29) did not affect the immunogenicity of AVA [see Clinical Pharmacology ( 12.3 )].

Contraindications

4 CONTRAINDICATIONS None. None. ( 4 )

Pregnancy and Breastfeeding

8.1 Pregnancy 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 (see Data) . 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. Clinical Considerations 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. Data 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).

Overdosage

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

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING Raxibacumab is a sterile, preservative-free, clear to opalescent, colorless to pale yellow solution supplied in single-use vials containing 1,700 mg/34 mL (50 mg/mL) raxibacumab and is available in the following packaging configuration: Single Unit Carton: Contains one single-use vial of raxibacumab 1,700 mg/34 mL (NDC 71655-103-01). Raxibacumab must be refrigerated at 2°C to 8°C (36°F to 46°F). DO NOT FREEZE. Protect the vial from exposure to light, prior to use. Brief exposure to light, as with normal use, is acceptable. Store vial in original carton until time of use.

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.