Download Zinplava

New Drug Introduction: Zinplava / bezlotoxumab
Pharmacology
Manufacturer
Approval Date
Indication
Contraindications
Black Box Warnings
Warnings/
Precautions
Pregnancy/Lactation
Pharmacokinetics
Drug Interactions –
Object/Precipitant
Drug
Adverse Effects
(Zinplava™) [placebo]
Monitoring Efficacy
Monitoring Toxicity
Dosing
Dosing – Maximum
Renal Adjustment
Hepatic Adjustment
Administration

Zinplava™, bezlotoxumab, is a human monoclonal antibody that binds
to Clostridium difficile toxin B and neutralizes its effects
Merck & Co., Inc.
October 21st, 2016
To reduce the recurrence of Clostridium difficile infection (CDI) in patients
18 years of age or older who are receiving antibacterial drug treatment of
CDI and who are at high risk for CDI recurrence.
 Limitation – not indicated for treatment of CDI as this agent is not an
antibacterial drug. Bezlotoxumab should only be used in conjunction
with antibacterial therapy
None
None
Heart Failure: Heart failure was reported more commonly in patients with a
history of congestive heart failure (CHF) in the two Phase 3 clinical trials
with this agent compared to placebo-treated patients.
 In patients with a history of CHF, bezlotoxumab should be reserved for
use when the benefit outweighs the risk
Category: C
Lactation Recommendation: No information available
A – AUC 53000 mcg · h/mL; Cmax 185 mcg/mL
 After a single dose of 10 mg/kg bezlotoxumab
D – Vd 7.33 L (16%)
M – Cl 0.317 L/day (41%)
 Clearance of bezlotoxumab increased with increasing body weight
(rationale for using weight-based dosing)
E – Elimination half-life (t1/2) approx. 19 days (28%)
 Eliminated by catabolism
Because bezlotoxumab is eliminated by catabolism, no metabolic
drug-drug interactions are expected
(With standard of care: antibiotics, etc.)
Nausea (7%) [5%]
Pyrexia (5%) [3%]
Headache (4%) [3%]
CDI recurrence
No findings of toxicity observed in studies
Single dose of 10 mg/kg administered as an IV infusion over 60 minutes
No well-established max dose per the prescribing information
 The safety and efficacy of repeat administration of Zinplava in patients
with CDI have not been studied
No adjustment necessary
No adjustment necessary
 Administer the diluted solution as an IV infusion over 60 minutes using
a sterile, non-pyrogenic, low-protein binding 0.2 micron to 5 micron inline or add-on filter
 Can be infused via a central line or peripheral line
 Avoid simultaneous co-administration with other drugs through the
same infusion line
Cost: Merck Sharp & Dohme Corp: Accessed 12/16/2016
Dose(s)
Brandor – Generic
Zinplava™ Single dose vial – 1000 mg/40 mL
(25mg/mL) injection solution
bezlotoxumab
$ (full treatment/single dose)
Expected to be available
first quarter 2017
Summary
 Zinplava™, bezlotoxumab, is a monoclonal antibody that binds Clostridium difficile toxin B
 Bezlotoxumab is used in conjunction with antibacterial drug treatment for CDI to
reduce the recurrence of CDI in patients who are at high risk for CDI recurrence
 It is dosed as a single weight-based dose of 10 mg/kg, administered by IV infusion
over 60 minutes.
 There is no well-established maximum dose per the prescribing information
 Adverse effects of bezlotoxumab include: nausea, pyrexia, and headache
 Cautious risk/benefit use is suggested in patients with a history of CHF
References:
1. www.zinplava.com
2. Zinplava (bezlotoxumab) [prescribing information]. Whitehouse Station, NJ: Merck &
Co., Inc.; October 2016.
3. Zar FA, Bakkanagari SR, Moorthi KM, Davis MB. A comparison of vancomycin and
metronidazole for the treatment of Clostridium difficile-associated diarrhea, stratified by
disease severity. Clin Infect Dis 2007;45(3):302-7.
Date Prepared: 12/16/2016
Editor: Peter G. Koval, Pharm.D., BCPS
Author: Amanda D’Ostroph, Pharm.D. Candidate, UNC Eshelman School of Pharmacy