Bezlotoxumab-Zinplava -@- (Oct 2016)- Anti-infective
Drug Name:Bezlotoxumab-Zinplava -@- (Oct 2016)- Anti-infective
List Of Brands:
Indication Type Description:
Drug Interaction
Indication
Adverse Reaction
Contra-Indications
Dosages/ Overdosage Etc
Patient Information
Pharmacology/ Pharmacokinetics
Pregnancy and lactation
Drug Interaction:
DRUG INTERACTIONS
Since ZINPLAVA is eliminated by catabolism, no metabolic drug-drug interactions
are expected
Indication:
HIGHLIGHTS OF PRESCRIBING INFORMATION
These highlights do not include all the information needed to use ZINPLAVA safely and effectively. See full prescribing information for ZINPLAVA.
ZINPLAVA (bezlotoxumab) injection, for intravenous use
Initial U.S. Approval: 2016
INDICATIONS AND USAGE
ZINPLAVA is a human monoclonal antibody that binds to Clostridium
difficile toxin B, indicated to reduce recurrence of Clostridium difficile
infection (CDI) in patients 18 years of age or older who are receiving
antibacterial drug treatment of CDI and are at a high risk for CDI
recurrence.
Limitation of Use:
ZINPLAVA is not indicated for the treatment of CDI. ZINPLAVA is not
an antibacterial drug. ZINPLAVA should only be used in conjunction
with antibacterial drug treatment of CDI.
DRUG INNOVATION - NOVEL DRUG APPROVALS FOR 2016
No Drug Name Active Ingredient Approval Date FDA-Approved use
on Approval date
19. Zinplava Bezlotoxumab 10/21/2016
To reduce the recurrence of Clostridium infection in
patients aged 18 years or older
Press release
Approved by FDA on 10/21/2016 (Ref- FDA approved List- 2016)
Adverse Reaction:
ADVERSE REACTIONS
Most common adverse reactions (reported in .4% of patients) included nausea,
pyrexia, and headache.
Contra-Indications:
CONTRAINDICATIONS
None
WARNINGS AND PRECAUTIONS
Heart Failure: Was reported more commonly in ZINPLAVA-treated patients
with a history of congestive heart failure (CHF) in the two Phase 3 clinical trials.
In patients with a history of CHF, ZINPLAVA should be reserved for use
when the benefit outweighs the risk.
Dosages/ Overdosage Etc:
INDICATIONS AND USAGE
ZINPLAVA is a human monoclonal antibody that binds to Clostridium
difficile toxin B, indicated to reduce recurrence of Clostridium difficile
infection (CDI) in patients 18 years of age or older who are receiving
antibacterial drug treatment of CDI and are at a high risk for CDI
recurrence.
Limitation of Use:
ZINPLAVA is not indicated for the treatment of CDI. ZINPLAVA is not
an antibacterial drug. ZINPLAVA should only be used in conjunction
with antibacterial drug treatment of CDI.
DOSAGE AND ADMINISTRATION
Administer ZINPLAVA during antibacterial drug treatment for CDI.
The recommended dose is a single dose of 10 mg/kg administered as an intravenous
infusion over 60 minutes.
Dilute prior to intravenous infusion. Administer via a low-protein
binding 0.2 micron to 5 micron in-line or add-on filter. See Full
Prescribing Information for dilution and administration instructions.
DOSAGE FORMS AND STRENGTHS
Injection: 1,000 mg/40 mL (25 mg/mL) solution in a single-dose vial.
OVERDOSAGE
There is no clinical experience with overdosage of ZINPLAVA.
In case of overdose, patients should be closely monitored for signs
or symptoms of adverse reactions, and appropriate symptomatic
treatment should be instituted.
Patient Information:
HOW SUPPLIED/STORAGE AND HANDLING
ZINPLAVA Injection: is a sterile, preservative-free, clear to moderately opalescent,
colorless to pale yellow solution and is supplied in the following packaging configuration:
Carton (NDC 0006-3025-00) containing one (1) single-dose vial of ZINPLAVA
1,000 mg/40 mL (25 mg/mL).
Store in a refrigerator, 2ºC to 8ºC (36ºF to 46ºF) in original carton to protect from light.
Do Not Freeze. Do Not Shake.
PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling (Patient Information).
Concurrent Antibacterial Therapy
Inform patients that ZINPLAVA does not take the place of their antibacterial treatment for their CDI infection. They must continue their antibacterial treatment as directed
U.S. License No. 0002 At:
MSD Ireland (Carlow)
County Carlow, Ireland
For patent information: www.merck
Pharmacology/ Pharmacokinetics:
CLINICAL PHARMACOLOGY
1. Mechanism of Action
ZINPLAVA (bezlotoxumab) is a human monoclonal antibody that binds
to C. difficile toxin B and neutralizes its effects .
2.Pharmacokinetics
The pharmacokinetics of bezlotoxumab were studied in 1515 CDI patients
in two Phase 3 trials (Trial 1 and Trial 2). Based on a population PK analysis,
the geometric mean (%CV) clearance of bezlotoxumab was 0.317 L/day (41%),
with a mean volume of distribution of 7.33 L (16%), and elimination half-life (t.)
of approximately 19 days (28%).
After a single intravenous dose of 10 mg/kg bezlotoxumab, geometric mean
AUC0-INF and Cmax were 53000 mcgEh/mL and 185 mcg/mL, respectively,
in the patients with CDI.
The clearance of bezlotoxumab increased with increasing body weight;
the resulting exposure differences are adequately addressed by the
administration of a weight-based dose. Bezlotoxumab is eliminated by
catabolism.
Specific Populations
Gender, Race, Ethnicity, and Co-Morbid Conditions
The following factors had no clinically meaningful effect on the exposure
of bezlotoxumab: gender, race, ethnicity, and presence of co-morbid conditions.
Patients with Renal Impairment
The effect of renal impairment on the pharmacokinetics of bezlotoxumab
was evaluated in patients with mild (eGFR 60 to <90 mL/min/1.73 m2),
moderate (eGFR 30 to <60 mL/min/1.73 m2), or severe
(eGFR 15 to <30 mL/min/1.73 m2) renal impairment, or with end
stage renal disease (eGFR <15 mL/min/1.73 m2), as compared to patients
with normal (eGFR .90 mL/min/1.73 m2) renal function.
No clinically meaningful differences in the exposure of bezlotoxumab
were found between patients with renal impairment and patients
with normal renal function.
Patients with Hepatic Impairment
The effect of hepatic impairment on the pharmacokinetics of bezlotoxumab
was evaluated in patients with hepatic impairment (defined as having two
or more of the following: [1] albumin .3.1 g/dL; [2] ALT .2X ULN; [3]
total bilirubin .1.3X ULN; or [4] mild, moderate or severe liver disease
as reported by the Charlson Co-morbidity Index), as compared to patients
with normal hepatic function.
No clinically meaningful differences in the exposure of bezlotoxumab were
found between patients with hepatic impairment and patients
with normal hepatic function.
Geriatric Patients
The effect of age on the pharmacokinetics of bezlotoxumab was evaluated
in patients ranging from 18 to 100 years of age. No clinically meaningful differences
in the exposure of bezlotoxumab were found between patients 65 years and
older and patients under 65 years of age.
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1. Pregnancy
Risk Summary
Adequate and well controlled studies with ZINPLAVA have not been conducted
in pregnant women. No animal reproductive and developmental studies have
been conducted with bezlotoxumab.
The background risk of major birth defects and miscarriage for the indicated
population is unknown; however, the background risk in the U.S. general
population of major birth defects is 2-4% and of miscarriage is 15-20% of
clinically recognized pregnancies.
2. Lactation
Risk Summary
There is no information regarding the presence of bezlotoxumab in human milk,
the effects on the breast-fed infant, or the effects on milk production.
The developmental and health benefits of breastfeeding should be considered
along with the motherfs clinical need for ZINPLAVA and any potential adverse
effects on the breastfed child from ZINPLAVA or from the underlying maternal
condition.
3. Pediatric Use
Safety and efficacy of ZINPLAVA in patients below 18 years of age have
not been established.
4. Geriatric Use
Of the 786 patients treated with ZINPLAVA, 50% were 65 years of age and over,
and 27% were 75 years of age and over. No overall differences in safety and
efficacy were observed between these subjects and younger subjects
No dose adjustment is necessary for patients 65 years of age .
