Zinplava (Concentrate) Instructions for Use

Marketing Authorization Holder

MSD Pharmaceuticals, LLC (Russia)

Manufactured By

MSD Ireland (Carlow) (Ireland)

Packaging and Quality Control Release

SCHERING-PLOUGH LABO, N.V. (Belgium)

ATC Code

J06BC03 (Bezlotoxumab)

Active Substance

Bezlotoxumab (Rec.INN registered by WHO)

Dosage Form

Zinplava

Concentrate for solution for infusion 25 mg/1 ml: fl. 1 pc.

Dosage Form, Packaging, and Composition

Concentrate for solution for infusion is a clear or moderately opalescent, colorless to light yellow liquid.

Excipients: sodium chloride – 351 mg, sodium citrate dihydrate – 190 mg, citric acid monohydrate – 32 mg, polysorbate 80 – 10 mg, diethylenetriaminepentaacetic acid – 0.31 mg, water for injections – up to 40 ml.

40 ml – colorless glass vials (1) – cardboard boxes.

Clinical-Pharmacological Group

Antimicrobial drug. Monoclonal antibodies

Pharmacotherapeutic Group

Systemic antimicrobial agent, specific immunoglobulin, monoclonal antibodies

Pharmacological Action

Bezlotoxumab is a human monoclonal antibody that binds with high affinity to Clostridium difficile toxin B and neutralizes its activity.

Bezlotoxumab prevents the recurrence of Clostridium difficile infection by providing passive immunity against the toxin produced during the germination of persistent Clostridium difficile spores or upon reinfection.

Pharmacokinetics

Following intravenous administration of bezlotoxumab at a dose of 10 mg/kg in patients with Clostridium difficile infection, the mean AUC_0-∞ and C_max values were 53000 µg×h/ml and 185 µg/ml, respectively.

Bezlotoxumab exposure in healthy volunteers increased approximately proportionally with increasing dose over the dose range from 0.3 to 20 mg/kg. The extravascular distribution of bezlotoxumab is limited. The mean V_d of bezlotoxumab was 7.33 L (CV: 16%).

Bezlotoxumab is catabolized via protein degradation processes; metabolic processes do not play a role in the clearance of the drug. Elimination of bezlotoxumab from the body occurs primarily through protein degradation. The mean clearance of bezlotoxumab was 0.317 L/day (CV: 41%), and the T_1/2 in the terminal phase was approximately 19 days (28%).

Bezlotoxumab clearance increased with increasing body weight; the resulting differences in exposure are effectively corrected by using a body weight-based dose.

Indications

For the prevention of recurrence of Clostridium difficile infection in adults at high risk of recurrence of Clostridium difficile infection.

ICD codes

Dosage Regimen

Administer Zinplava as a single intravenous infusion at a dose of 10 mg/kg body weight.

Calculate the exact dose based on the patient’s body weight immediately prior to the infusion.

Initiate the infusion during the course of standard oral antibacterial therapy for Clostridium difficile infection.

Do not administer bezlotoxumab as a treatment for the current, active episode of Clostridium difficile infection.

Do not use bezlotoxumab as a standalone therapy; it is only for the prevention of recurrence.

Prepare the solution for infusion by diluting the concentrate in 0.9% sodium chloride intravenous infusion bag.

Use the prepared diluted solution immediately; if storage is necessary, hold at 2°C to 8°C for no more than 16 hours.

Infuse the total volume of the diluted solution intravenously over 60 minutes using a sterile, low-protein binding 0.2-5 micron in-line or add-on filter.

Do not administer Zinplava as an intravenous push or bolus.

Monitor the patient for infusion-related reactions during and for at least one hour after completion of the infusion.

Adverse Reactions

Nervous system disorders common – headache.

Gastrointestinal disorders common – nausea, diarrhea.

General disorders and administration site conditions common – pyrexia, infusion-related reactions.

Contraindications

Hypersensitivity to bezlotoxumab; pregnancy, breastfeeding period; age under 18 years.

Use in Pregnancy and Lactation

The use of bezlotoxumab during pregnancy and lactation is contraindicated.

Use in Hepatic Impairment

No dose adjustment is required in patients with hepatic impairment.

Use in Renal Impairment

No dose adjustment is required in patients with renal impairment.

Pediatric Use

Contraindicated for use under 18 years of age.

Geriatric Use

No dose adjustment is required in patients aged 65 years and older.

Special Precautions

Bezlotoxumab is not a treatment for Clostridium difficile infection and has no effect on the current episode of Clostridium difficile infection.

Bezlotoxumab should be used during the course of antibacterial therapy for Clostridium difficile infection.

Drug Interactions

Drug interaction mediated by bezlotoxumab is unlikely because the target for bezlotoxumab is an exogenous toxin.

Bezlotoxumab is used concomitantly with standard oral antibacterial therapy for Clostridium difficile infection.

Storage Conditions

Store at 2°C (36°F) to 8°C (46°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.