IV Dilution &
Medication Reference

bezlotoxumab- ZINPLAVA™ injection

Usual Diluents Return to article top

Standard Dilutions [Amount of drug] [Infusion volume] [Infusion rate] Return to article top

Example 70 kg patient:
[700 mg ] [100 - 500 mL] [60 minutes]

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.

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.

WARNINGS Return to article top

DESCRIPTION Return to article top

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.

CLINICAL PHARMACOLOGY: Return to article top

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.

INDICATIONS AND USAGE Return to article top

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.

CONTRAINDICATIONS Return to article top

PRECAUTIONS Return to article top

Heart 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 REACTIONS Return to article top

Most common adverse reactions (reported in >/=4% of patients) included nausea, pyrexia, and headache. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., at 1-877-888-4231 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.

Revised: 10/2016

See PACKAGE INSERT for PATIENT COUNSELING INFORMATION and Medication Guide.

DOSAGE AND ADMINISTRATION Return to article top

DOSAGE AND ADMINISTRATION:

2.1 Important Administration Instructions
Administer ZINPLAVA during antibacterial drug treatment for CDI.

2.2 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.

2.3 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.

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.

HOW SUPPLIED Return to article top

Storage and Stability Return to article top

Carton (NDC 0006-3025-00) containing one (1) single-dose vial of ZINPLAVA 1,000 mg/40 mL (25 mg/mL).

SStore in a refrigerator, 2ºC to 8ºC (36ºF to 46ºF) in original carton to protect from light. Do Not Freeze. Do Not Shake.

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.