Obiltoxaximab

Obiltoxaximab may be found in some form under the following brand names:

• Anthim

Obiltoxaximab is a chimeric IgG1 kappa monoclonal antibody that binds the protective antigen (PA) component of Bacillus anthracis toxin.1

Contraindications

None.1

Warnings/Precautions

Hypersensitivity and Anaphylaxis

Hypersensitivity reactions were the most common adverse reactions in the safety trials of obiltoxaximab, occurring in 34/320 healthy subjects (10.6%). Three (0.9%) cases of anaphylaxis occurred during or immediately after the infusion. In clinical trials, manifestations of anaphylaxis were rash/urticaria, cough, dyspnea, cyanosis, postural dizziness and chest discomfort. Obiltoxaximab infusion was discontinued in 8 (2.5%) subjects due to hypersensitivity or anaphylaxis. The adverse reactions reported in these 8 subjects included urticaria, rash, cough, pruritus, dizziness, throat irritation, dysphonia, dyspnea and chest discomfort. The remaining subjects with hypersensitivity had predominantly skin-related symptoms such as pruritus and rash, and 6 subjects reported cough.1

Due to the risk of anaphylaxis, obiltoxaximab should be administered in monitored settings by personnel trained and equipped to manage anaphylaxis. Patients should be monitored closely throughout the infusion period and for a period of time after administration. If anaphylaxis or hypersensitivity reactions occur, stop the infusion immediately and treat appropriately.1

Premedication with diphenhydramine is recommended prior to administration of obiltoxaximab. Diphenhydramine premedication does not prevent anaphylaxis, and may mask or delay onset of symptoms of hypersensitivity.1

Specific Populations

Pregnancy Category B.

No adequate and well-controlled studies in pregnant women were conducted. Because animal reproduction studies are not always predictive of human response, obiltoxaximab should be used during pregnancy only if clearly needed.1

A single embryonic-fetal development study was conducted in pregnant, healthy New Zealand White (NZW) rabbits administered 4 intravenous doses of obiltoxaximab up to 32 mg/kg (2 times the human dose on a mg/kg basis) on gestation days 6, 10, 13, and 17. No evidence of harm to the pregnant dam or the fetuses due to obiltoxaximab was observed. Cumulative exposures in NZW rabbits (10,000 mcg•day/mL) at the NOAEL of 32 mg/kg/dose (n=4 doses) based on AUC0-15 days were approximately two-fold the human male and female combined mean AUC at the clinical intravenous dose of 16 mg/kg. Cmax values following a 32 mg/kg/dose were 1180 mcg•day/mL.1

Obiltoxaximab 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 obiltoxaximab on nursing infant are unknown.1

As in adults, the effectiveness of obiltoxaximab in pediatric patients is based solely on efficacy studies in animal models of inhalational anthrax. As exposure of healthy children to obiltoxaximab is not ethical, a population PK approach was used to derive intravenous dosing regimens that are predicted to provide pediatric patients with exposure comparable to the observed exposure in adults receiving 16 mg/kg. The dose for pediatric patients is based on weight.1

There have been no studies of safety or PK of obiltoxaximab in the pediatric population.1

Clinical studies of obiltoxaximab did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently from younger subjects. Of the 320 subjects in clinical studies of obiltoxaximab, 9.4% (30/320) were 65 years and over, while 2% (6/320) were 75 years and over. No alteration of dosing is needed for patients ≥65 years of age.1

Common Adverse Effects

Most frequently reported adverse reactions in healthy adult subjects (≥1.5%) were headache, pruritus, infections of the upper respiratory tract, cough, vessel puncture site bruise, infusion site swelling, nasal congestion, infusion site pain, urticaria and pain in extremity.1

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.

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.

Obiltoxaximab 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

Obiltoxaximab is a monoclonal antibody that binds the free protective antigen component of B. anthracis toxin thereby preventing the intracellular entry of the anthrax lethal factor and edema factor, the enzymatic toxin components responsible for the pathogenic effects of anthrax toxin.

Distribution

Greater than plasma volume (eg, some tissue distribution).

Excretion

Minimal renal elimination

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

>10%: Central nervous system: Headache (8% to 16%)

1% to 10%:

Cardiovascular: Chest discomfort (<2%), chest pain (<2%), palpitations (<2%)

Central nervous system: Dizziness (<2%), fatigue (<2%), voice disorder (<2%)

Dermatologic: Skin rash (7%), pruritus (4%), urticaria (2%)

Gastrointestinal: Vomiting (<2%), xerostomia (<2%)

Hematologic & oncologic: Abnormal lymphocyte count (decreased: <2%), change in neutrophil count (decreased: <2%), decreased white blood cell count (<2%)

Hypersensitivity: Hypersensitivity reaction (11%)

Immunologic: Antibody development (3%; no evidence of therapeutic efficacy not altered)

Local: Infusion site reaction (erythema: 4%), bruising at injection site (3%), local discoloration (at infusion site: <2%)

Neuromuscular & skeletal: Limb pain (2%), increased creatine phosphokinase (<2%), musculoskeletal pain (<2%), myalgia (<2%)

Respiratory: Cough (3% to 8%), upper respiratory tract infection (5%), throat irritation (3%), rhinorrhea (<2% to 3%), nasal congestion (2%), cyanosis (<2%), dyspnea (<2%), oropharyngeal pain (<2%), sinus congestion (<2%)

Miscellaneous: Fever (<2%), infusion related reaction (swelling: <2%)

<1% (Limited to important or life-threatening): Anaphylaxis

Monitor patients closely for signs and symptoms of hypersensitivity during and after the infusion.

Adverse events were not observed in animal reproduction studies. In general, guidelines for the prophylaxis and treatment of inhalational anthrax following exposure to Bacillus anthracis in pregnant and postpartum women are the same as nonpregnant adults (Meaney-Delman 2014).