raxibacumab (Rx)

1-10%

Rash (3.2%)

Pain in extremity (2.5%)

Pruritus (2.5%)

Somnolence (1.4%)

<1%

Reported at rates higher than placebo

Blood and lymphatic system: Anemia, leukopenia, lymphadenopathy

Cardiac disorders: Palpitations

Ear and labyrinth: Vertigo

General disorders and administration site: Fatigue, infusion site pain, peripheral edema

Investigations: Blood amylase increased, blood creatine phosphokinase increased, prothrombin time prolonged

Musculoskeletal and connective tissue: Back pain, muscle spasms

Nervous system: Syncope vasovagal

Psychiatric: Insomnia

Vascular: Flushing, hypertension

Contraindications

None

Cautions

Does not cross the blood-brain barrier and, therefore, does not prevent or treat meningitis; use in combination with appropriate antibacterial drugs

Hypersensitivity and anaphylaxis

• Hypersensitivity reactions including rash, urticaria, pruritus, chills, chest and throat tightness, lip and throat swelling, and hypotension reported
• Due to risk of anaphylaxis, administer raxibacumab injection in monitored settings where appropriate equipment, medication (including epinephrine) and personnel trained to manage hypersensitivity, anaphylaxis, and shock are available
• Monitor patients closely during infusion and for a period of time after administration
• If hypersensitivity reactions or anaphylaxis occur, interrupt or stop infusion immediately and treat appropriately
• Premedicate with diphenhydramine within 1 hour prior to administering treatment to reduce risk of occurrence and/or severity of a hypersensitivity reaction
• Diphenhydramine premedication does not prevent anaphylaxis and may mask or delay the onset of symptoms of hypersensitivity

Pregnancy

There are no data on 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 human maximum plasma concentrations at maximum recommended adult dose

Limited data in the form of case reports of anthrax infection in pregnant women indicate that maternal infection is associated with high risk of maternal, fetal, and neonatal deaths, particularly in absence of treatment

Lactation

There is no information available on presence of drug in human milk, effects on breastfed child, or on milk production; maternal IgG is known to be present in human milk; therefore, developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for raxibacumab and any potential adverse effects on breastfed child from drug or from underlying maternal condition

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Recombinant human IgG1-gamma monoclonal antibody directed at the protective antigen of Bacillus anthracis

Absorption

Peak Plasma Concentration: 1020.3 mcg/mL

AUC: 15,845.8 mcg•h/mL

Distribution

Vd: 72.92 mL/kg (steady-state); suggests some tissue distribution

Elimination

Half-life: 1.76 days (alpha phase); ~22 days (beta [terminal] phase)

Renal clearance: 2.49 mL/day/kg

Excretion: Minimal in urine

IV Compatibilities

0.45% NaCl

0.9% NaCl

IV Preparation

Further dilution required before administering

• Gently invert the bag/syringe to mix the solution; do not shake
• Dilute with 0.9% or 0.45% NaCl to final volume of 250 mL for adults and children >31 kg
• For children, the final infusion volume is weight-based as described below:
• <1 kg: 7 mL
• 1.1-2 kg: 15 mL
• 2.1-3 kg: 20 mL
• 3.1-4.9 kg: 25 mL
• 5-10 kg: 50 mL
• 11-30 kg: 100 mL

IV Administration

Infusion rate

• Adults and children >31 kg: 15 mL/hr IV over initial 20 min, then increase to 125 mL/hr
• For children, the final infusion rate is weight-based as described below:
• <1 kg: 7 mL total volume; 0.5 mL/hr IV over initial 20 min, then increase to 3.5 mL/hr
• 1.1-2 kg: 15 mL total volume; 1 mL/hr IV over initial 20 min, then increase to 7 mL/hr
• 2.1-3 kg: 20 mL total volume; 1.2 mL/hr IV over initial 20 min, then increase to 10 mL/hr
• 3.1-4.9 kg: 25 mL total volume; 1.5 mL/hr IV over initial 20 min, then increase to 12 mL/hr
• 5-10 kg: 50 mL total volume; 3 mL/hr IV over initial 20 min, then increase to 25 mL/hr
• 11-30 kg: 100 mL total volume; 6 mL/hr IV over initial 20 min, then increase to 50 mL/hr
• Infusion rate may be slowed or interrupted if signs of adverse reactions, including infusion-associated symptoms occur

Storage

Unopened vials

• Refrigerate at 2-8°C (36-46°F); DO NOT FREEZE
• Contains no preservative
• Protect 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

Diluted to final volume

• Prepared solution is stable for 3 hr at room temperature