Dosing and uses of Zinplava (bezlotoxumab)
Adult dosage forms and strengths
solution for injection
- 1000mg/40mL vial (25mg/mL)
Clostridium difficile Infection
Indicated to reduce recurrence of Clostridium difficile infection (CDI) in adults who are receiving antibacterial drug treatment for CDI and are at a high risk of recurrence
10 mg/kg IV infused over 1 hr as a single dose
See Administration for information on preparing IV dilution and use of filter during IV infusion
Dosage modifications
Renal or hepatic impairment
- No dosage adjustment required
- No clinically meaningful differences in the exposure of bezlotoxumab were found between patients with renal or hepatic impairment and patients with normal renal or normal hepatic function
Dosing Considerations
Safety and efficacy of repeat administration in patients with CDI have not been studied
Limitations of use
- Not indicated for the treatment of CDI
- Bezlotoxumab is not an antibacterial drug
- Should only be used in conjunction with antibacterial drug treatment of CDI
Pediatric dosage forms and strengths
<18 years: Safety and efficacy not established
Zinplava (bezlotoxumab) adverse (side) effects
>10%
Heart failure, history of CHF (12.7%)
1-10%
Infusion-related reactions (10%)
Nausea 7%
Pyrexia 5%
Headache 4%
Heart failure, no history of CHF (2.3%)
Warnings
Contraindications
None
Cautions
Heart failure was reported more commonly in clinical trials in bezlotoxumab-treated patients compared with placebo; these adverse reactions occurred primarily in patients with underlying congestive heart failure
In patients with a history of CHF, bezlotoxumab should be reserved for use when benefits outweigh risks
Pregnancy
Pregnancy
Adequate and well-controlled studies of bezlotoxumab have not been conducted in pregnant women
No animal reproductive and developmental studies have been conducted
Lactation
Unknown if distributed in human breast milk
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.
Pharmacology of Zinplava (bezlotoxumab)
Mechanism of action
Human monoclonal antibody that binds to C difficile toxin B and neutralizes its effects; does not bind to C difficile toxin A
Absorption
Peak plasma concentration: 185 mcg/mL
AUC: 53 mg·h/mL
Distribution
Vd: 7.33 L
Metabolism
Eliminated by catabolism; no metabolic drug-drug interactions are expected
Elimination
Half-life: ~19 days
Clearance: 0.317 L/day; increases with increasing body weight
Administration
IV Compatibilities
0.9% NaCL
D5W
IV Preparation
Must be diluted before IV infusion
Prepare the diluted solution immediately after removal of the vial(s) from refrigerated storage, or the vial(s) may be stored at room temperature protected from light for up to 24 hr before preparation of the diluted solution
Inspect vial contents for discoloration and particulate matter prior to dilution; should appear as a clear-to-moderately opalescent, colorless-to-pale yellow solution
Do not use the vial if the solution is discolored or contains visible particles
Do not shake the viaL
Withdraw the required volume from the vial(s) based on the patient’s weight (in kg) and transfer into an IV bag containing either 0.9% NaCl or D5W to prepare a diluted solution with a final concentration ranging from 1-10 mg/mL
Mix diluted solution by gentle inversion; do not shake
Discard vial(s) and all unused contents
IV Administration
Infuse diluted solution IV over 1 hr as a one-time single dose using a sterile, nonpyrogenic, low-protein binding 0.2-5 micron inline or add-on filter
Can be infused via a central line or peripheral catheter
Do not administer as an IV push or bolus
Do not coadminister other drugs simultaneously through the same infusion line
Administer during antibacterial drug treatment for CDI
Storage
Does not contain preservatives
Unopened vials
- Refrigerate at 2-8ºC (36-46ºF) in original carton to protect from light
- Do not freeze
- Do not shake
Diluted solution
- May be stored either at room temperature for up to 16 hr or under refrigeration at 2-8°C (36-46°F) for up to 24 hr
- If refrigerated, allow the IV bag to come to room temperature prior to use
- These time limits include storage of the infusion solution in the IV bag through the duration of infusion
- Do not freeze the diluted solution
