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Bezlotoxumab

Pronunciation

(bez loe TOX ue mab)

Index Terms

  • MK-6072
  • Zinplava

Pharmacologic Category

  • Monoclonal Antibody

Pharmacology

Bezlotoxumab is a human IgG1 monoclonal antibody which binds to C. difficile toxin B and neutralizes it to prevent its toxic effects; bezlotoxumab does not bind to C. difficile toxin A.

Distribution

7.33 L

Metabolism

Metabolized via catabolism

Excretion

Eliminated primarily through catabolism

Half-Life Elimination

~19 days

Use: Labeled Indications

Clostridium difficile infection, adjunctive therapy: To reduce recurrence of Clostridium difficile infection (CDI) in patients ≥18 years of age who are receiving antibacterial drug treatment of CDI and are at a high risk for CDI recurrence

Limitations of use: Bezlotoxumab is not indicated for the treatment of CDI. Bezlotoxumab is not an antibacterial drug and should only be used in conjunction with antibacterial drug treatment of CDI.

Contraindications

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

Dosing: Adult

Clostridium difficile infection, adjunctive therapy: IV: 10 mg/kg as a single dose during antibacterial treatment for Clostridium difficile infection. Repeat doses have not been studied.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment

There are no dosage adjustments provided in the manufacturer’s labeling, although in a pharmacokinetic study, no clinically meaningful differences in exposure between patients with renal impairment and normal renal function were noted.

Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer’s labeling, although in a pharmacokinetic study, no clinically meaningful differences in exposure between patients with hepatic impairment and normal hepatic function were noted.

Reconstitution

Must be diluted prior to infusion. Immediately after removing vial from refrigerator, withdraw appropriate volume from vial and transfer to infusion bag of either normal saline or D5W to a final concentration between 1 to 10 mg/mL. Do not use vials if solution is discolored or if particulates are visible. Gently invert to mix; do not shake.

Administration

Infuse IV over 60 minutes through a sterile, nonpyrogenic, low-protein binding 0.2 to 5 micron in-line or add-on filter. Do not administer as an IV push or bolus. May be infused via a central line or peripheral catheter. Do not coadminister other drugs simultaneously through the same infusion line. If infusion solution was refrigerated, allow to come to room temperature prior to administration. Infusion should be completed within 16 hours of preparation (if stored at room temperature) or within 24 hour (if refrigerated).

Compatibility

Compatible in NS, D5W.

Storage

Store intact vials at 2°C to 8°C (36°F to 46°F). Do not freeze. Protect from light. Do not shake vials. Solutions diluted for infusion may be stored either at room temperature for up to 16 hours or refrigerated at 2°C to 8°C (36°F to 46°F) for up to 24 hours. Infusion must be completed within these time frames. If refrigerated, allow the intravenous bag to come to room temperature prior to use. Do not freeze diluted solution.

Drug Interactions

Belimumab: Monoclonal Antibodies may enhance the adverse/toxic effect of Belimumab. Avoid combination

Adverse Reactions

>10%: Cardiovascular: Exacerbation of congestive heart failure (13%)

1% to 10%:

Cardiovascular: Congestive heart failure (2%)

Central nervous system: Headache (4%)

Gastrointestinal: Nausea (7%)

Miscellaneous: Infusion related reaction (10%; including nausea, fatigue, fever, dizziness, headache, dyspnea, and hypertension), fever (5%)

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

Warnings/Precautions

Concerns related to adverse effects:

• Heart failure: Heart failure has been reported at a higher rate in patients treated with bezlotoxumab (compared to placebo), primarily occurring in patients with underlying heart failure. Additionally, a higher mortality rate due to cardiac failure, infection, and respiratory failure was observed in patients with a history of heart failure who received bezlotoxumab (compared to those who received placebo). In patients with a history of heart failure, bezlotoxumab use should be reserved for situations when the benefits outweigh risks.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Pregnancy Considerations

Animal reproduction studies have not been conducted. Bezlotoxumab is monoclonal antibody; monoclonal antibodies are known to cross the placenta, with increasing amounts during the second and third trimesters (Simister 2003).

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