Obiltoxaximab

Pharmacology

Mechanism of Action

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.

Pharmacokinetics/Pharmacodynamics

Distribution

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

Excretion

Minimal renal elimination

Use: Labeled Indications

Anthrax, inhalational:

Treatment of inhalational anthrax due to Bacillus anthracis in combination with appropriate antibacterial drugs

Prophylaxis of inhalational anthrax due to B. anthracis when alternative therapies are not available or not appropriate

Limitations of use: Should only be used for prophylaxis when the benefit for prevention of inhalational anthrax outweighs the risk of hypersensitivity and anaphylaxis.

Contraindications

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

Dosage and Administration

Dosing: Adult

Anthrax, inhalational (treatment and prophylaxis): IV: Note: Premedicate with diphenhydramine prior to infusion.

<40 kg: 24 mg/kg/dose as a single dose

>40 kg: 16 mg/kg/dose as a single dose

Dosing: Geriatric

Refer to adult dosing

Dosing: Pediatric

Note: Premedicate with diphenhydramine prior to infusion.

Anthrax, inhalational; treatment and prophylaxis: Infants, Children, and Adolescents: IV:

≤15 kg: 32 mg/kg as a single dose

>15 kg to 40 kg: 24 mg/kg as a single dose

>40 kg: 16 mg/kg as a single dose

Reconstitution

IV bag for infusion: Volume of prepared solution for infusion is based upon patient weight. Select an appropriate size bag of NS (outlined below) and withdraw a volume of solution from the bag equal to the calculated volume of obiltoxaximab needed for the patient dose. Discard the solution that was withdrawn from the bag. Inject obiltoxaximab dose into the bag and gently invert to mix; do not shake.

IV syringe for infusion: Volume of prepared solution for infusion is based upon patient weight. Select an appropriate size syringe for the total volume of infusion (outlined below). Withdraw obiltoxaximab dose into syringe, then withdraw an appropriate volume of NS into syringe to equal the total infusion volume needed. Gently mix the solution; do not shake.

Total obiltoxaximab infusion volume by body weight:

≥31 kg or adult: 250 mL

11 to 30 kg: 100 mL

5 to 10 kg: 50 mL

3.1 to 4.9 kg: 25 mL

2.1 to 3 kg: 20 mL

1.1 to 2 kg: 15 mL

≤1 kg or less: 7 mL

Administration

IV: Premedication with diphenhydramine is recommended. Administer prepared solution (IV infusion bag or syringe) using a 0.22 micron inline filter over 1 hour and 30 minutes. Flush the line with NS at the end of the infusion.

Storage

Store in refrigerator at 2°C to 8°C (36°F to 46°F); protect from light. Do not freeze or shake. Prepared solution in NS in an IV bag for infusion is stable at room temperature or refrigerated for up to 8 hours after admixture. Prepared solution in a syringe for infusion should be administered immediately; do not store.

Drug Interactions

There are no known significant interactions.

Adverse Reactions

>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%, postmarketing, and/or case reports: Anaphylaxis

Warnings/Precautions

Concerns related to adverse effects:

• Hypersensitivity: [US Boxed Warning]: Hypersensitivity or anaphylactic reactions (eg, rash/urticaria, cough, dyspnea, cyanosis, postural dizziness, chest discomfort) may occur. Administer in a monitored setting; monitor patients closely for signs and symptoms of hypersensitivity during and after the infusion. If hypersensitivity or anaphylaxis occurs, discontinue the infusion immediately and treat 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). Refer to manufacturer's labeling.

Monitoring Parameters

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

Pregnancy

Pregnancy Considerations

Obiltoxaximab is a chimeric monoclonal antibody (IgG₁). Placental transfer of human IgG is dependent upon the IgG subclass, maternal serum concentrations, birth weight, and gestational age, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis (Palmeira 2012; Pentsuk 2009).

Untreated maternal anthrax infection has a high risk of maternal, fetal, and neonatal death. 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).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience headache. Have patient report immediately to prescriber cough, shortness of breath, blue/gray skin discoloration, dizziness, passing out, chest pain, sore throat, or difficulty speaking (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.