Zinplava
Generic
Name: bezlotoxumab
Dosage Form: injection, solution
Medically reviewed by
Drugs.com. Last updated on Nov 1, 2019.
Indications
and Usage for Zinplava
Zinplava™ is 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. [See Dosage and Administration (2.1).]
Zinplava
Dosage and AdministrationImportant Administration Instructions
Administer Zinplava during
antibacterial drug treatment for CDI.
Dosing Recommendations in Adults
The recommended dose of
Zinplava is a single dose of 10 mg/kg administered as an intravenous infusion
over 60 minutes. The safety and efficacy of repeat administration of Zinplava
in patients with CDI have not been studied.
Preparation and Administration
Preparation of Diluted Solution
Zinplava must be diluted prior
to intravenous 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 hours prior to preparation of the diluted solution.Inspect vial contents for
discoloration and particulate matter prior to dilution. Zinplava is 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 intravenous bag containing either 0.9% Sodium Chloride Injection, USP
or 5% Dextrose Injection, USP to prepare a diluted solution with a final
concentration ranging from 1 mg/mL to 10 mg/mL. Mix diluted solution by
gentle inversion. Do not shake.Discard vial(s) and all unused
contents.
Storage of Diluted Solution
The product does not contain
preservative. The diluted solution of Zinplava may be stored either at
room temperature for up to 16 hours or under refrigeration at 2°C to 8°C
(36°F to 46°F) for up to 24 hours. If refrigerated, allow the intravenous
bag to come to room temperature prior to use.These time limits include
storage of the infusion solution in the intravenous bag through the
duration of infusion.Do not freeze the diluted
solution.
Administration
Administer the diluted
solution as an intravenous infusion over 60 minutes using a sterile,
non-pyrogenic, low-protein binding 0.2 micron to 5 micron in-line or
add-on filter.The diluted solution can be
infused via a central line or peripheral catheter. Do not administer
Zinplava as an intravenous push or bolus.Do not co-administer other
drugs simultaneously through the same infusion line.Dosage
Forms and Strengths
Injection: 1,000 mg/40 mL
(25 mg/mL) clear to moderately opalescent, colorless to pale yellow solution in
a single-dose vial.
Contraindications
None.
Warnings
and PrecautionsHeart Failure
Heart failure was reported
more commonly in the two Phase 3 clinical trials in Zinplava-treated patients
compared to placebo-treated patients. These adverse reactions occurred
primarily in patients with underlying congestive heart failure (CHF). In
patients with a history of CHF, 12.7% (15/118) of Zinplava-treated patients and
4.8% (5/104) of placebo-treated patients had the serious adverse reaction of
heart failure during the 12-week study period [see Adverse Reactions (6.1)]. Additionally,
in patients with a history of CHF, there were more deaths in Zinplava-treated
patients, 19.5% (23/118) than in placebo-treated patients, 12.5% (13/104)
during the 12-week study period. The causes of death varied and included
cardiac failure, infections, and respiratory failure.
In patients with a history
of CHF, Zinplava should be reserved for use when the benefit outweighs the
risk.
Adverse
ReactionsClinical Trials Experience
Because clinical trials are
conducted under widely varying conditions, adverse reaction rates observed in
the clinical trials of a drug cannot be directly compared to rates in the
clinical trials of another drug and may not reflect the rates observed in
practice.
The safety of Zinplava was
evaluated in two placebo-controlled, Phase 3 trials (Trial 1 n= 390 and Trial 2
n= 396). Patients received a single 10 mg/kg intravenous infusion of Zinplava
and concomitant standard of care antibacterial drugs (metronidazole, vancomycin
or fidaxomicin) for CDI (SoC). Adverse reactions reported within the first 4
weeks after Zinplava was administered are described for the pooled Phase 3
trial population of 786 patients. The median age of patients receiving Zinplava
was 65 years (range 18 to 100), 50% were age 65 years or older, 56% were
female, and 83% were white.
The most common adverse
reactions following treatment with Zinplava (reported in ≥4% of patients within
the first 4 weeks of infusion and with a frequency greater than placebo) were
nausea, pyrexia, and headache (see Table 1).
Table 1: Adverse Reactions Reported in
≥4% of Zinplava-Treated Patients with CDI and at a Frequency Greater than
Placebo in Trial 1 and Trial 2*,†
|
|
Adverse Reaction
|
Zinplava with SoC‡
N=786
%
|
Placebo with SoC‡
N=781
%
|
|
*
All patients as treated population, defined as all
randomized patients who received a dose of study medication, by treatment
received
†
Adverse reactions reported within 4 weeks of
administration of Zinplava or placebo
‡
SoC = Standard of Care antibacterial drugs
(metronidazole or vancomycin or fidaxomicin) for CDI
|
|
Gastrointestinal disorders
|
|
Nausea
|
7%
|
5%
|
|
General disorders and administration site conditions
|
|
Pyrexia
|
5%
|
3%
|
|
Nervous system disorders
|
|
Headache
|
4%
|
3%
|
Serious adverse reactions
occurring within 12 weeks following infusion were reported in 29% of
Zinplava-treated patients and 33% of placebo-treated patients. Heart failure
was reported as a serious adverse reaction in 2.3% of the Zinplava-treated
patients and 1.0% of the placebo-treated patients [see Warnings and Precautions (5.1)].
One patient discontinued the
Zinplava infusion due to ventricular tachyarrhythmia that occurred 30 minutes
after the start of the infusion.
Mortality rates were 7.1%
and 7.6% in Zinplava-treated patients and placebo-treated patients,
respectively, during the 12-week follow-up period.
Infusion Related Reactions
Overall, 10% of
Zinplava-treated patients experienced one or more infusion specific adverse
reactions on the day of, or the day after, the infusion compared to 8% of
placebo-treated patients. Infusion specific adverse reactions reported in ≥0.5%
of patients receiving Zinplava and at a frequency greater than placebo were
nausea (3%), fatigue (1%), pyrexia (1%), dizziness (1%), headache (2%), dyspnea
(1%) and hypertension (1%). Of these patients, 78% and 20% of patients
experienced mild and moderate adverse reactions, respectively. These reactions
resolved within 24 hours following onset.
Immunogenicity
As with all therapeutic
proteins, there is a potential for immunogenicity following administration of
Zinplava. The detection of antibody formation is highly dependent on the
sensitivity and specificity of the assay. Additionally, the observed incidence
of antibody (including neutralizing antibody) positivity in an assay may be
influenced by several factors including assay methodology, sample handling,
timing of sample collection, concomitant medications, and underlying disease.
For these reasons, comparison of the incidence of antibodies to bezlotoxumab in
the studies described below with the incidence of antibodies in other studies
or to other products may be misleading.
Following treatment with
Zinplava in Trial 1 and Trial 2, none of the 710 evaluable patients tested
positive for treatment-emergent anti-bezlotoxumab antibodies.
Drug
Interactions
Since Zinplava is eliminated
by catabolism, no metabolic drug-drug interactions are expected [see Clinical Pharmacology (12.3)].
USE IN
SPECIFIC POPULATIONSPregnancy
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 theU.S.general population of major birth defects is 2-4% and of miscarriage is 15-20%
of clinically recognized pregnancies.
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 mother's clinical
need for Zinplava and any potential adverse effects on the breastfed child from
Zinplava or from the underlying maternal condition.
Pediatric Use
Safety and efficacy of
Zinplava in patients below 18 years of age have not been established.
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 [see Clinical Studies (14)]. No dose adjustment is
necessary for patients ≥65 years of age [see Clinical Pharmacology (12.3)].
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.
Zinplava
Description
Bezlotoxumab is a human
monoclonal antibody that binds to C. difficile toxin
B and neutralizes its effects. Bezlotoxumab is an IgG1 immunoglobulin with an
approximate molecular weight of 148.2 kDa.
Zinplava (bezlotoxumab)
Injection is a sterile, preservative-free, clear to moderately opalescent,
colorless to pale yellow solution that requires dilution for intravenous
infusion. The product is provided in a 50 mL vial that contains 1000 mg of
bezlotoxumab in 40 mL of solution. Each mL of solution contains bezlotoxumab
(25 mg), citric acid monohydrate (0.8 mg), diethylenetriaminepentaacetic acid
(0.0078 mg), polysorbate 80 (0.25 mg), sodium chloride (8.77 mg), sodium
citrate dihydrate (4.75 mg), and Water for Injection, USP. The vial may contain
sodium hydroxide to adjust the pH to 6.0.
Zinplava -
Clinical PharmacologyMechanism of Action
Zinplava (bezlotoxumab) is a
human monoclonal antibody that binds to C. difficile toxin
B and neutralizes its effects [see Microbiology (12.4)].
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 (t½) of approximately
19 days (28%). After a single intravenous dose of 10 mg/kg bezlotoxumab,
geometric mean AUC0-INF and Cmax were 53000 mcg∙h/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 ≥2× ULN; [3] total bilirubin ≥1.3× 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.
Drug Interaction Studies
Because bezlotoxumab is
eliminated by catabolism, no metabolic drug-drug interactions are expected.
Microbiology
Mechanism of Action
Bezlotoxumab is a human
monoclonal antibody that binds C. difficile toxin
B with an equilibrium dissociation constant (Kd) of <1×10-9M. Bezlotoxumab inhibits the
binding of toxin B and prevents its effects on mammalian cells. Bezlotoxumab
does not bind to C. difficile toxin A.
Activity In Vitro
Bezlotoxumab binds to an
epitope on toxin B that is conserved across reported strains of C. difficile, although amino acid sequence variation
within the epitope does occur. In vitro studies
in cell-based assays using Vero cells or Caco-2 cells, suggest that
bezlotoxumab neutralizes the toxic effects of toxin B.
Nonclinical
ToxicologyCarcinogenesis, Mutagenesis, Impairment of Fertility
No studies have been
performed to test the potential of bezlotoxumab for carcinogenicity or
genotoxicity.
Fertility studies have not
been conducted with bezlotoxumab.
Clinical
Studies
The safety and efficacy of
Zinplava were investigated in two randomized, double-blind, placebo-controlled,
multicenter, Phase 3 trials (Trial 1 and Trial 2) in patients receiving
Standard of Care antibacterial drugs for treatment of CDI (SoC). Randomization
was stratified by SoC (metronidazole, vancomycin, or fidaxomicin) and
hospitalization status (inpatient vs. outpatient) at the time of study entry.
Enrolled patients were 18
years of age or older and had a confirmed diagnosis of CDI, which was defined
as diarrhea (passage of 3 or more loose bowel movements in 24 or fewer hours)
and a positive stool test for toxigenic C. difficile from
a stool sample collected no more than 7 days before study entry. Patients were
excluded if surgery for CDI was planned, or if they had uncontrolled chronic
diarrheal illness. Patients received a 10- to 14-day course of oral SoC and a
single infusion of Zinplava or placebo was administered during the course of
SoC. Patients on oral vancomycin or oral fidaxomicin could have also received
intravenous metronidazole. Choice of SoC was at the discretion of the health
care provider. The day of the infusion of Zinplava or placebo in relation to
the start of SoC ranged from the day prior to the start of SoC to 14 days after
the start of SoC with the median being day 3 of SoC.
In Trial 1, 403 patients
were randomized to receive Zinplava and 404 patients were randomized to receive
placebo. In Trial 2, 407 subjects were randomized to receive Zinplava and 399
patients were randomized to receive placebo. The Full Analysis Set (FAS) was a
subset of all randomized subjects with exclusions for: (i) not receiving infusion
of study medication; (ii) not having a positive local stool test for
toxigenic C. difficile; (iii) not receiving
protocol defined standard of care therapy within a 1 day window of the
infusion. The baseline characteristics of the 1554 patients randomized to
Zinplava or placebo in the FAS were similar across treatment arms and in Trial
1 and Trial 2. The median age was 65 years, 85% were white, 57% were female,
and 68% were inpatients. A similar proportion of patients received oral
metronidazole (48%) or oral vancomycin (48%) and 4% of the patients received
oral fidaxomicin as their SoC.
The following risk factors
associated with a high risk of CDI recurrence or CDI-related adverse outcomes
were present in the study population: 51% were ≥65 years of age, 39% received
one or more systemic antibacterial drugs (during the 12-week follow-up period),
28% had one or more episodes of CDI within the six months prior to the episode
under treatment (15% had two or more episodes prior to the episode under treatment),
21% were immunocompromised and 16% presented at study entry with clinically
severe CDI (as defined by a Zar score of ≥21). A hypervirulent strain
(ribotypes 027, 078 or 244) was isolated in 22% of patients who had a positive
baseline culture, of which 87% (189 of 217 strains) were ribotype 027.
Patients were assessed for
clinical cure of the presenting CDI episode, defined as no diarrhea for 2
consecutive days following the completion of a ≤14 day SoC regimen. Patients
who achieved clinical cure were then assessed for recurrence of CDI through 12
weeks following administration of the infusion of Zinplava or placebo. CDI
recurrence was defined as the development of a new episode of diarrhea
associated with a positive stool test for toxigenic C.
difficile following clinical cure of the presenting CDI episode.
Sustained clinical response was defined as clinical cure of the presenting CDI
episode and no CDI recurrence through 12 weeks after infusion. Table 2 contains
the results for Trial 1 and Trial 2.
Table 2: Efficacy Results Through 12
Weeks After Infusion (Trial 1 and Trial 2, Full Analysis Set*)
|
|
Trial
|
|
Zinplava with SoC†
|
Placebo with SoC†
|
Adjusted Difference
(95% CI)‡
|
|
|
n (%)
|
n (%)
|
|
|
n (%) = Number
(percentage) of subjects in the analysis population meeting the criteria for
endpoint
|
|
N = Number of
subjects included in the analysis population
|
|
*
Full Analysis Set = a subset of all randomized subjects
with exclusions for: (i) did not receive infusion of study medication; (ii)
did not have a positive local stool test for toxigenic C. difficile; (iii) did not receive protocol
defined standard of care therapy within a 1 day window of the infusion
†
SoC = Standard of Care antibacterial drugs
(metronidazole or vancomycin or fidaxomicin) for CDI
‡
Adjusted difference of Zinplava-placebo (95%
confidence interval) based on Miettinen and Nurminen method stratified by SoC
antibacterial drugs (metronidazole vs. vancomycin vs. fidaxomicin) and
hospitalization status (inpatient vs. outpatient).
|
|
1
|
|
N=386
|
N=395
|
|
|
|
Sustained
clinical response
|
232 (60.1)
|
218 (55.2)
|
4.8 (-2.1, 11.7)
|
|
|
Reasons for
failure to achieve sustained clinical response:
|
|
|
Clinical failure
|
87 (22.5)
|
68 (17.2)
|
|
|
|
Recurrence
|
67 (17.4)
|
109 (27.6)
|
|
|
2
|
|
N=395
|
N=378
|
|
|
|
Sustained
clinical response
|
264 (66.8)
|
197 (52.1)
|
14.6 (7.7, 21.4)
|
|
|
Reasons for
failure to achieve sustained clinical response:
|
|
|
Clinical failure
|
69 (17.5)
|
84 (22.2)
|
|
|
|
Recurrence
|
62 (15.7)
|
97 (25.7)
|
|
In Trial 1, the clinical
cure rate of the presenting CDI episode was lower in the Zinplava arm as
compared to the placebo arm and in Trial 2, the clinical cure rate was lower in
the placebo arm compared to the Zinplava arm. Patients in the Zinplava and
placebo arms who did not achieve clinical cure of the presenting CDI episode
(no diarrhea for 2 consecutive days following the completion of a ≤14 day SoC
regimen) received a mean of 18 to 19 days of SoC and had a mean of 4 additional
days of diarrhea following completion of SoC. Additional analyses showed that
by 3 weeks post study drug infusion the clinical cure rates of the presenting
CDI episode were similar between treatment arms.
Efficacy results in patients
at high risk for CDI recurrence (i.e., patients aged 65 years and older, with a
history of CDI in the past 6 months, immunocompromised state, severe CDI at
presentation, or C. difficile ribotype
027) were consistent with the efficacy results in the overall trial population
in Trials 1 and 2.
REFERENCES
1. Zar FA, Bakkanagari SR, Moorthi KM,DavisMB. 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.
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 [see Indications and Usage (1) and Dosage and Administration (2.1)].
Manufactured by: Merck Sharp
& Dohme Corp., a subsidiary of
MERCK & CO., INC., Whitehouse Station,NJ08889,USA
U.S. License No. 0002
At:
MSDIreland(Carlow)
County Carlow,Ireland
For patent information:
www.merck.com/product/patent/home.html
Copyright
© 2016 Merck Sharp & Dohme Corp., a subsidiary of Merck
& Co., Inc.
All rights reserved.
uspi-mk6072-iv-1610r000
|
Patient Information
Zinplava™ (zin-PLAH-va)
(bezlotoxumab)
injection, for intravenous use
|
|
What you need to know about Zinplava
Before
you receive Zinplava, be sure you understand what it is for and how it
is given.Zinplava
helps decrease the risk of C-diff (Clostridium difficile infection)
from coming back by working with the antibiotic that you are taking to
treat your C-diff. Zinplava does not replace the antibiotic. Zinplava is
not an antibiotic.Keep
taking your antibiotic for your C-diff as directed by your doctor.If you
have questions about Zinplava, ask your doctor or pharmacist.Keep this Patient Information for Zinplava so
you can read it again.
|
|
What is Zinplava?
|
|
Zinplava is a
prescription medicine used to help decrease the risk of C-diff from coming
back in people 18 years of age or older who are taking an antibiotic for
C-diff and who have a high risk of C-diff coming back.
C-diff is a bacterial infection that can damage your colon and cause stomach
pain and severe diarrhea. When people get C-diff, they often take an
antibiotic to get rid of the infection. Even when treated by an antibiotic,
C-diff can come back within weeks to months. Zinplava helps to decrease the
risk of the infection from coming back. It works when given along with the
antibiotic that you are taking to treat C-diff.
|
|
How will I receive Zinplava?
|
|
· You
will receive Zinplava into your vein through an IV (intravenously).
· You
do not need to do anything to prepare for receiving Zinplava.
· You
will receive Zinplava in 1 dose and it will take about 1 hour.
· If
you miss your appointment, call your doctor right away to reschedule it.
|
|
Is Zinplava right for me?
|
|
Children
It is
not known if Zinplava is safe and effective in children under 18 years
old.
Pregnancy
If you
are pregnant or trying to get pregnant, tell your doctor before you
receive Zinplava.It is not
known if Zinplava will harm your baby while you are pregnant.You and
your doctor should decide together if you will receive Zinplava.
Breastfeeding
If you
are breastfeeding or plan to breastfeed, tell your doctor before you
receive Zinplava.It is
not known if Zinplava gets in your breast milk and will be passed to
your baby.You and
your doctor should decide together if you will receive Zinplava.
Medical
Conditions
Tell
your doctor about any medical conditions you have now or have had
before.Make
sure to tell your doctor if you have or have had congestive heart
failure (CHF).
Other
Medicines
Tell your doctor about all of the
medicines you take, including prescription and over-the-counter medicines,
vitamins, and herbal supplements.
|
|
What are the possible side effects of Zinplava?
|
|
Zinplava may cause serious side effects, including:
Heart failure. Heart failure may happen in
people who receive Zinplava and can be serious. People with a history of
congestive heart failure (CHF) who received Zinplava had a higher rate
of heart failure and death than those who did not receive Zinplava.
Common
side effects of Zinplava:
The most common side effects that may happen on the day of or the day after
receiving Zinplava:
|
|
|
· nausea
· headache
· fever
· feeling
tired
|
· shortness
of breath
· feeling
dizzy
· high
blood pressure
|
|
The most common
side effects that may happen up to four weeks after receiving Zinplava:
|
|
|
· nausea
· fever
|
· headache
|
|
If you have any side effect that bothers you or does not go away,
tell your doctor.
There may be other side effects to Zinplava that are not listed. Call your
doctor for medical advice about side effects. You may report side effects to
FDA at 1-800-FDA-1088.
General information about the safe and effective use of
Zinplava.
|
|
Medicines are
sometimes prescribed for purposes other than those listed in the Patient
Information. You can ask your pharmacist or doctor for information about
Zinplava that is written for doctors.
|
|
What if I have questions?
|
|
· Call
your doctor.
· Call
Merck, the company that makes Zinplava, at 1-800-444-2080.
· Go
to the website – www.Zinplava.com
You can also find the full prescribing information written for doctors at
www.Zinplava.com
|
|
What are the ingredients in Zinplava?
|
|
The active
ingredient is: bezlotoxumab
The inactive ingredients are: citric acid monohydrate,
diethylenetriaminepentaacetic acid, polysorbate 80, sodium chloride, sodium
citrate dihydrate, and water for injection, USP. Zinplava may also contain
sodium hydroxide.
|
|
This Patient Information has been approved by the U.S. Food and Drug
Administration.
|
|
Manufactured by: Merck Sharp & Dohme Corp., a subsidiary of
MERCK & CO., INC., Whitehouse Station,NJ08889,USA
|
|
U.S. License No. 0002
|
|
At:
MSDIreland(Carlow)
County Carlow,Ireland
|
|
For patent information: www.merck.com/product/patent/home.html
|
|
Copyright © 2016 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
All rights reserved.
|
|
Issued: 10/2016
usppi-mk6072-iv-1610r000
|
|
|
PRINCIPAL
DISPLAY PANEL - 1,000 mg/40 mL Vial Carton
NDC 0006-3025-00
Zinplava™
(bezlotoxumab)
Injection
1,000
mg /40 mL
(25 mg/mL)
For
Intravenous Infusion Only
Requires dilution prior to
administration.
Rx
only
Single-dose vial. Discard
unused portion.
|
Zinplava
bezlotoxumab injection, solution
|
|
Product
Information
|
|
Product
Type
|
HUMAN
PRESCRIPTION DRUG LABEL
|
Item Code
(Source)
|
NDC:0006-3025
|
|
Route of
Administration
|
INTRAVENOUS
|
DEA
Schedule
|
|
|
|
Active Ingredient/Active
Moiety
|
|
Ingredient
Name
|
Basis of
Strength
|
Strength
|
|
bezlotoxumab (bezlotoxumab)
|
bezlotoxumab
|
25 mg
in 1 mL
|
|
|
Inactive
Ingredients
|
|
Ingredient
Name
|
Strength
|
|
CITRIC
ACID MONOHYDRATE
|
0.8 mg
in 1 mL
|
|
PENTETIC
ACID
|
0.0078 mg
in 1 mL
|
|
POLYSORBATE
80
|
0.25 mg
in 1 mL
|
|
SODIUM
CHLORIDE
|
8.77 mg
in 1 mL
|
|
TRISODIUM
CITRATE DIHYDRATE
|
4.75 mg
in 1 mL
|
|
WATER
|
|
|
SODIUM
HYDROXIDE
|
|
|
|
Product
Characteristics
|
|
Color
|
YELLOW (clear
to moderately opalescent, colorless to pale yellow)
|
Score
|
|
|
Shape
|
|
Size
|
|
|
Flavor
|
|
Imprint
Code
|
|
|
Contains
|
|
|
|
|
|
Packaging
|
|
#
|
Item Code
|
Package
Description
|
|
|
1
|
NDC:0006-3025-00
|
1 VIAL,
SINGLE-DOSE in 1 CARTON
|
|
|
1
|
NDC:0006-3025-01
|
40 mL in 1
VIAL, SINGLE-DOSE
|
|
|
|
|
|
Marketing Information
|
|
Marketing
Category
|
Application
Number or Monograph Citation
|
Marketing
Start Date
|
Marketing
End Date
|
|
BLA
|
BLA761046
|
10/21/2016
|
|
|
|
Labeler - Merck Sharp & Dohme Corp. (001317601)
|
Merck Sharp &
Dohme Corp.
