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Raxibacumab (United States: Availability limited to Strategic National Stockpile distribution): Drug information

Raxibacumab (United States: Availability limited to Strategic National Stockpile distribution): Drug information
(For additional information see "Raxibacumab (United States: Availability limited to Strategic National Stockpile distribution): Patient drug information" and see "Raxibacumab (United States: Availability limited to Strategic National Stockpile distribution): Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
ALERT: US Boxed Warning
Hypersensitivity and anaphylaxis:

Hypersensitivity reactions, including anaphylaxis, have been reported during or after administration of raxibacumab by IV infusion. Administer raxibacumab by IV infusion in monitored settings where appropriate equipment, medication (including epinephrine), and personnel trained in the management of hypersensitivity, anaphylaxis, and shock are available.

Pharmacologic Category
  • Antidote;
  • Monoclonal Antibody
Dosing: Adult
Anthrax, prophylaxis or treatment

Anthrax, prophylaxis or treatment:

IV: 40 mg/kg as a single dose.

Note: Administer diphenhydramine 25 to 50 mg (may administer oral or IV depending on the proximity to start of raxibacumab infusion) ≤1 hour prior to administration of raxibacumab to reduce the risk and/or severity of infusion reactions. When used for treatment, must be administered in combination with appropriate antimicrobial therapy.

Dosing: Kidney Impairment: Adult

There are no dosage adjustments provided in manufacturer's labeling; however, dosage adjustment unlikely as clearance is nonrenal.

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in manufacturer's labeling (has not been studied).

Dosing: Pediatric

(For additional information see "Raxibacumab (United States: Availability limited to Strategic National Stockpile distribution): Pediatric drug information")

Note: Experts recommend anthrax antitoxin (raxibacumab or anthrax immune globulin) for all patients with highly suspect or confirmed systemic anthrax in combination with antimicrobial therapy. If number of patient exposures exceeds drug availability, use should be reserved for patients who would most likely benefit from antitoxin therapy: Noncritically ill, nonmoribund patients in stable condition with confirmed systemic anthrax or critically ill, nonmoribund patients who may have progressive disease with 1 or more organ system dysfunction (AAP [Bradley 2014]). Due to ethical considerations, pediatric approval based on efficacy demonstrated in animal models, safety data from adult humans, and extrapolation of safety data to pediatric patients; monitor patients closely.

Anthrax, prophylaxis or treatment

Anthrax, prophylaxis or treatment: Note: Administer in a monitored setting appropriately equipped to manage anaphylaxis, hypersensitivity, and shock. Administer diphenhydramine (oral or IV depending on the proximity to start of raxibacumab infusion) ≤1 hour prior to administration of raxibacumab to reduce the risk and/or severity of infusion reactions.

Infants, Children, and Adolescents:

≤10 kg: IV: 80 mg/kg as a single dose.

>10 to 40 kg: IV: 60 mg/kg as a single dose.

>40 kg: IV: 40 mg/kg as a single dose.

Dosing: Kidney Impairment: Pediatric

There are no dosage adjustments provided in manufacturer's labeling; however, dosage adjustment unlikely as clearance is nonrenal.

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustment provided in manufacturer's labeling (has not been studied).

Dosing: Older Adult

Refer to adult dosing.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Injection, solution: 50 mg/mL (34 mL) [contains polysorbate 80, sucrose 10 mg/mL]

Generic Equivalent Available: US

No

Prescribing and Access Restrictions

Raxibacumab is not available for general public use. All supplies are currently owned by the federal government for inclusion in the Strategic National Stockpile and for use by the US military.

Administration: Adult

IV: Administer in a monitored setting appropriately equipped to manage anaphylaxis, hypersensitivity, and shock. Premedicate with diphenhydramine ≤1 hour prior to raxibacumab infusion. Infuse at 15 mL/hour for 20 minutes, then increase rate to 125 mL/hour for the remaining infusion (total administration time of 2 hours and 15 minutes). Administration rate may be slowed or interrupted for adverse reactions (including infusion-related reactions).

Administration: Pediatric

Note: Administer in a monitored setting appropriately equipped to manage anaphylaxis, hypersensitivity, and shock. Premedicate with diphenhydramine ≤1 hour prior to raxibacumab infusion.

IV: Must be diluted prior to administration. Start at slower administration rate for the first 20 minutes to monitor for adverse reactions; then increase rate if tolerated for remainder of infusion. Slow or interrupt infusion if adverse reactions (including infusion-related reactions) occur. Administer as follows:

Neonates, Infants, Children, and Adolescents <18 years:

Body Weight

(kg)

Initial Infusion Rate

(mL/hour)

for 20 minutes

Final Infusion Rate

(mL/hour)

<1 kg

0.5

3.5

1 to <2 kg

1

7

2 to <3 kg

1.2

10

3 to <5 kg

1.5

12

5 to 10 kg

3

20

10 to <15 kg

6

25

15 to <30 kg

6

50

30 to 40 kg

15

62.5

>40 kg

15

75

Adolescents ≥18 years: Infuse at 15 mL/hour for 20 minutes; increase rate to 125 mL/hour for the remaining infusion.

Use: Labeled Indications

Anthrax, prophylaxis or treatment: Treatment of inhalational anthrax following exposure to Bacillus anthracis in combination with appropriate antimicrobial therapy; prophylaxis of inhalational anthrax when alternative therapies are unavailable or not appropriate.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%: Dermatologic: Skin rash (infusion-related; without diphenhydramine premedication: 22%; with diphenhydramine premedication: ≤3%, including erythematous rash and papular rash)

1% to 10%:

Cardiovascular: Flushing (<2%), hypertension (<2%), palpitations (<2%), peripheral edema (<2%), syncope (<2%)

Dermatologic: Pruritus (3%)

Gastrointestinal: Increased serum amylase (<2%)

Hematologic & oncologic: Anemia (<2%), leukopenia (<2%), lymphadenopathy (<2%), prolonged prothrombin time (<2%)

Hypersensitivity: Hypersensitivity reaction (5%; including chest tightness and hypotension)

Local: Infusion-site pain (<2%)

Nervous system: Drowsiness (1% to 4%), fatigue (<2%), insomnia (<2%), vertigo (<2%)

Neuromuscular & skeletal: Back pain (<2%), increased creatinine phosphokinase in blood specimen (<2%), limb pain (3%), muscle spasm (<2%)

<1%: Hypersensitivity: Anaphylaxis

Frequency not defined:

Dermatologic: Urticaria

Nervous system: Clonus

Respiratory: Dyspnea

Contraindications

There are no contraindications listed in the manufacturer’s labeling.

Warnings/Precautions

Concerns related to adverse effects:

• Hypersensitivity reactions: Hypersensitivity reactions (eg, rash, urticaria, pruritus, chills, chest and throat tightness, lip and throat swelling, hypotension, anaphylaxis) have been reported during or after the infusion. Premedication with diphenhydramine is recommended to reduce the risk and/or severity; however, this may mask or delay onset of hypersensitivity symptoms. The administration rate is slowed over the first 20 minutes to monitor for adverse reactions; decrease the infusion rate or stop the infusion if adverse reactions (including infusion-related reactions) occur and treat immediately and appropriately.

Dosage form specific issues:

• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson, 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer’s labeling.

Other warnings/precautions:

• Appropriate use: Inhalational anthrax prophylaxis and treatment: Raxibacumab is not an antimicrobial agent; use during treatment of anthrax should always be in combination with appropriate antimicrobial therapy. Raxibacumab does not cross the blood brain barrier and is not appropriate for the prevention or treatment of meningitis due to anthrax infection. Antitoxin therapy with raxibacumab may improve survival in addition to the known increased survival from antimicrobial therapy alone; use may be beneficial in patients in whom toxin accumulation is likely and those who have failed antimicrobial therapy (Huang 2015). The use of raxibacumab in addition to antimicrobials may provide prophylactic protection against infection up to 7 days post-spore exposure (Rubinson 2017).

• Efficacy: The efficacy of raxibacumab in humans is presumptive and based solely on efficacy studies in animals.

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Efgartigimod Alfa: May diminish the therapeutic effect of Fc Receptor-Binding Agents. Risk C: Monitor therapy

Pregnancy Considerations

Adverse events were not observed in animal reproduction studies.

Raxibacumab is a humanized monoclonal antibody (IgG1). Human IgG is known to cross the placenta; exposure is dependent upon the IgG subclass, maternal serum concentrations, newborn birth weight, and GA, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis (Palmeira 2012; Pentsuk 2009).

In general, guidelines for the prophylaxis and treatment of inhalational anthrax following exposure to Bacillus anthracis in pregnant and postpartum patients are the same as nonpregnant adults (Meaney-Delman 2014).

Breastfeeding Considerations

It is not known if raxibacumab is present in breast milk.

In general, guidelines for the prophylaxis and treatment of inhalational anthrax following exposure to Bacillus anthracis in lactating patients are the same as nonpregnant adults (Meaney-Delman 2014).

Monitoring Parameters

Signs or symptoms of hypersensitivity reactions during and for a period of time after infusion.

Mechanism of Action

Raxibacumab is a recombinant human IgG1 lambda monoclonal antibody which binds and neutralizes free protective antigen (PA) component of Bacillus anthracis toxin; as a result, PA-mediated delivery of lethal toxin and edema toxin via the anthrax toxin receptor (ATR) into host cells of anthrax-infected individuals is inhibited (Huang 2015; Singh 2016).

Pharmacokinetics

Distribution: Vd: 0.07 L/kg (Migone 2009)

Half-life elimination: Terminal: 20.44 ± 6.46 days (Migone 2009)

Excretion: Nonrenal (Migone 2009)

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