ZINPLAVA

Immunomodulators, Monoclonal Antibodies

Administer by intravenous infusion.
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

Dilution
Do not shake the vial(s).
Withdraw the required volume from the vial(s) based on the patient's weight and transfer into an intravenous bag containing either 0.9% Sodium Chloride Injection or 5% Dextrose Injection to prepare a diluted solution with a final concentration from 1 to 10 mg/mL.
Mix the diluted solution by gentle inversion. Do not shake.
Storage: The diluted solution may be stored at room temperature for 16 hours or under refrigeration at 2 to 8 degrees C (36 to 46 degrees F) for up to 24 hours. If refrigerated, allow the infusion solution to come to room temperature prior to use. Storage time limits include infusion duration. Do not freeze.
 
Intravenous (IV) Infusion
Infuse the diluted solution IV over 60 minutes using a sterile, non-pyrogenic, low-protein binding 0.2 to 5 micron in-line or add-on filter.
Administer via a central line or a peripheral catheter.
Do not administer as IV push or bolus.
Do not co-administer other drugs simultaneously through the same infusion line.

heart failure / Delayed / 2.3-2.3
ventricular tachycardia / Early / Incidence not known

infusion-related reactions / Rapid / 1.0-10.0
hypertension / Early / 1.0-1.0
dyspnea / Early / 1.0-1.0
antibody formation / Delayed / Incidence not known

fever / Early / 5.0-18.0
headache / Early / 4.0-14.0
nausea / Early / 7.0-7.0
dizziness / Early / 1.0-1.0
fatigue / Early / 1.0-1.0

ZINPLAVA

Rx

Human monoclonal antibody that binds to C. difficile toxin B
Used to reduce recurrence of C. difficile infection (CDI) in adults and pediatric patients 1 year and older who are receiving antibacterial treatment of CDI and are at high risk for CDI recurrence
Must be used with appropriate antibacterial agents

10 mg/kg IV as a single dose as adjunct therapy. Bezlotoxumab is not an antibacterial drug; therefore, use only in combination with antibacterial CDI treatment.

10 mg/kg IV as a single dose as adjunct therapy. Bezlotoxumab is not an antibacterial drug; therefore, use only in combination with antibacterial CDI treatment.

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

There are no drug interactions associated with Bezlotoxumab products.

ZINPLAVA Intravenous Inj Sol: 1mL, 25mg

10 mg/kg IV once.

10 mg/kg IV once.

10 mg/kg IV once.

10 mg/kg IV once.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Bezlotoxumab is a human monoclonal antibody that binds to C. difficile toxin B, thereby inhibiting the binding of toxin B and neutralizing its effects. It does not bind C. difficile toxin A. Bezlotoxumab is not an antibiotic and is used in conjunction with appropriate antibacterial agents. There are several factors associated with the virulence of C. difficile, which include toxin production. Toxin B is one of the protein toxins secreted by C. difficile. A rise in C. difficile-associated disease (CDAD) has been associated with the emergence of more virulent strains categorized as North American pulsotype 1/PCR-ribotype 027 (NAP1/027). This increased virulence is due in part to a higher production of toxin A and toxin B as well a more cytopathic form of toxin B. Toxins damage the colonic epithelium by causing cell death and disrupting cell-cell junctions, which may lead to increased epithelial permeability and lumenal fluid accumulation. These toxins also induce the secretion of cytokines, which may be involved in the recruitment and activation of neutrophils that are present in high amounts at sites of C. difficile-associated inflammation. Anti-toxin antibodies are naturally produced; however, mechanisms that control this production are not understood. Lower endogenous anti-toxin antibodies may be a risk factor for recurrent disease.

Bezlotoxumab is administered intravenously. Based on a population pharmacokinetic analysis, the geometric mean (%CV) clearance is 0.317 L/day (41%), with a mean volume of distribution of 7.33 L (16%). The clearance of bezlotoxumab is increased with increasing body weight. Bezlotoxumab is eliminated by catabolism, and the elimination half-life is approximately 19 days.
 
Affected cytochrome P450 isoenzymes: none
No drug-drug interactions are expected due to the catabolic clearance of bezlotoxumab.

After a single intravenous dose of bezlotoxumab 10 mg/kg, the geometric mean AUC was 53,000 mcg x hour/mL and the Cmax was 185 mcg/mL.

There are no adequate and well controlled studies with bezlotoxumab in human pregnancy. No animal reproductive and developmental studies have been conducted.

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. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for bezlotoxumab and any potential adverse effects on the breast-fed child from bezlotoxumab or the underlying maternal condition.