obiltoxaximab (Rx)

>10%

Hypersensitivity (10.6%)

1-10%

Headache (8%)

Upper respiratory tract infections (5%)

Pruritus (4%)

Cough (3%)

Vessel puncture site bruise (3%)

Infusion site swelling (3%)

Nasal congestion (2%)

Infusion site pain (2%)

Urticaria (2%)

Pain in extremity (2%)

<1%

Anaphylaxis (0.9%)

Contraindications

None

Cautions

Hypersensitivity reactions were the most common adverse reactions in the safety trials (see Black Box Warnings)

Premedication with diphenhydramine is recommended prior to administration; diphenhydramine does not prevent anaphylaxis and may mask or delay onset of symptoms of hypersensitivity

Pregnancy

Data are not available on use in pregnant women to inform on drug-associated 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

Animal studies

• No evidence of harm to the pregnant New Zealand White (NZW) rabbit dam or the fetuses was observed at ~2-fold the human dose

Lactation

Unknown if distributed in human breast milk

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

Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the 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

Monoclonal antibody that binds to the protective antigen of B anthracis and prevents the formation of the anthrax toxin that directly damages cells; disrupts cell defense mechanisms that lead to organ injury, uncontrolled bacterial growth, and death

Absorption

Peak plasma concentration: 400 mcg/mL

AUC: 5170 mcg·day/mL

Distribution

Vd: Greater than plasma volume, suggesting some tissue distribution

Elimination

Clearance: Much less than GFR, indicating there is virtually no renal clearance

IV Preparation

Solution should appear clear to opalescent, colorless to pale yellow to pale brownish-yellow that may contain few translucent-to-white proteinaceous particulates

Discard vial if the solution is discolored or contains extraneous particles other than a few translucent-to-white, proteinaceous particles

Do not shake the vial

Total weight-based infusion volume and infusion rate

• >40 kg: 250 mL total volume; infuse at 167 mL/hr
• 31-40 kg: 250 mL total volume; infuse at 167 mL/hr
• 16-30 kg: 100 mL total volume; infuse at 67 mL/hr
• 11-15 kg: 100 mL total volume; infuse at 67 mL/hr
• 5-10 kg: 50 mL total volume; infuse at 33.3 mL/hr
• 3.1-4.9 kg: 25 mL total volume; infuse at 17 mL/hr
• 2.1-3 kg: 20 mL total volume; infuse at 13.3 mL/hr
• 1.1-2 kg: 15 mL total volume; infuse at 10 mL/hr
• <1 kg: 7 mL total volume; infuse at 4.7 mL/hr

Dilution in bag for infusion

• Calculate dose needed by multiplying the recommended mg/kg dose by the patient weight in kg (eg, patient wt is 60 kg: 60 kg x 16 mg/kg = 960 mg dose)
• Calculate the required dosage volume in mL and number of vials needed for the dose by dividing the calculated dose in mg by the concentration, 100 mg/mL; each single vial allows delivery of 6 mL (eg, 960 mg ÷ 100 mg/mL = 9.6 mL)
• Select an appropriate size infusion bag of 0.9% NaCl for the total volume of infusion to be administered (eg, for this example, 250 mL); withdraw a volume of solution from the bag equal to the calculated volume in mL of dose (eg, for this example 9.6 mL) and discard the solution withdrawn from the bag
• Withdraw the required dosage volume calculated from vials (eg, for this example 9.6 mL from 2 vials); discard any unused portion remaining vials
• Transfer the required dose to the selected infusion bag (eg, for this example 960 mg/9.6 mL)
• Gently invert the bag to mix the solution; do not shake
• The prepared solution is stable for 4 hr stored at room temperature or refrigerated

Dilution in syringe for infusion

• Calculate dose needed by multiplying the recommended mg/kg dose by the patient weight in kg (eg, patient wt is 10 kg: 10 kg x 32 mg/kg = 320 mg dose)
• Calculate the required dosage volume in mL and number of vials needed for the dose by dividing the calculated dose in mg by the concentration, 100 mg/mL; each single vial allows delivery of 6 mL (eg, 320 mg ÷ 100 mg/mL = 3.2 mL)
• Select an appropriate size syringe for the total volume of infusion to be administered
• Using the selected syringe, withdraw the required volume of obiltoxaximab; discard any unused portion remaining in the vial(s)
• Withdraw an appropriate amount of 0.9% NaCl to prepare the total infusion volume specified (see above); (eg, 50 mL total volume - 3.2 mL obiltoxaximab solution = 46.8 mL 0.9% NaCl)
• Gently mix the solution by inverting/rolling syringe; do not shake
• Once a diluted is solution prepared, administer immediately
• Do not store solution in syringe; discard unused product

IV Administration

Premedicate with diphenhydramine before administering obiltoxaximab

Administer obiltoxaximab in appropriately monitored settings equipped to manage anaphylaxis

Dilute injection before administering IV using the bag or syringe for infusion

After preparation of the bag or syringe for infusion, administer the infusion solution using a 0.22-micron inline filter with the infusion rate described (see IV preparation)

Administer diluted IV infusion over 90 minutes

Monitor patients closely for signs and symptoms of hypersensitivity throughout the infusion and for a period of time after administration

Stop infusion immediately and treat appropriately, if hypersensitivity or anaphylaxis occurs

Flush IV line with 0.9% NaCl at the end of infusion

Storage

Do not freeze

Do not shake

Contains no preservatives

Unopened vials: Refrigerate at 2-8°C (36-46°F) in original carton to protect from light

Prepared diluted solution in infusion bag

• Stable for 4 hr at room temperature or refrigerated at 2-8°C (36-46°F)