ZYNYZ Solution for injection Ref.[107364] Active ingredients: Retifanlimab

2.1 Recommended Dosage

The recommended dosage of ZYNYZ is 500 mg administered as an intravenous infusion over 30 minutes every 4 weeks until disease progression, unacceptable toxicity, or up to 24 months.

Administer ZYNYZ as an intravenous infusion after dilution [see Dosage and Administration (2.3)].

2.2 Dosage Modifications for Adverse Reactions

No dose reduction of ZYNYZ is recommended. In general, withhold ZYNYZ for severe (Grade 3) immune-mediated adverse reactions. Permanently discontinue ZYNYZ for life‑threatening (Grade 4) immune-mediated adverse reactions, recurrent severe (Grade 3) immune-mediated reactions that require systemic immunosuppressive treatment, or an inability to reduce corticosteroid dose to 10 mg or less of prednisone equivalent per day within 12 weeks of initiating steroids.

Dosage modifications for ZYNYZ for adverse reactions that require management different from these general guidelines are summarized in Table 1.

Table 1. Recommended Dosage Modifications for Adverse Reactions:

AST = aspartate aminotransferase; ALT = alanine aminotransferase; DRESS = drug rash with eosinophilia and systemic symptoms; SJS = Stevens-Johnson syndrome; TEN = toxic epidermal necrolysis; ULN = upper limit of normal.
^* Toxicity graded per National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.
^† Resume in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper. Permanently discontinue if no resolution within 12 weeks of initiating steroids or inability to reduce prednisone to less than 10 mg/day (or equivalent) within 12 weeks of initiating steroids.
^‡ If AST and ALT are less than or equal to ULN at baseline in patients with liver involvement, withhold or permanently discontinue ZYNYZ based on recommendations for hepatitis with no liver involvement.
^§ Depending on clinical severity, consider withholding for Grade 2 endocrinopathy until symptom improvement with hormone replacement. Resume once acute symptoms have resolved.

2.3 Preparation and Administration

Do not administer ZYNYZ using a polyurethane infusion set.

Visually inspect the vial for particulate matter and discoloration prior to administration. ZYNYZ is a clear to slightly opalescent, colorless to pale yellow solution and is free of particles. Discard the vial if the solution is cloudy, discolored, or contains particulate matter.

Do not shake the vial.

Preparation:

• Withdraw 20 mL (500 mg) of ZYNYZ from one vial and discard vial with any unused portion.
• Dilute ZYNYZ with either 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP to a final concentration between 1.4 mg/mL to 10 mg/mL. Use polyvinylchloride (PVC) and di-2-ethylhexyl phthalate (DEHP), polyolefin copolymer, polyolefin with polyamide, or ethylene vinyl acetate infusion bags.
• Mix diluted solution by gentle inversion. Do not shake.
• Visually inspect the infusion bag for particulate matter and discoloration prior to administration. Discard if the solution is discolored or contains particulate matter.

Storage of diluted ZYNYZ solution:

Protect the diluted ZYNYZ solution from light during storage.

Store diluted ZYNYZ solution:

• At room temperature [up to 25°C (77°F)] for no more than 8 hours from the time of preparation to the end of the infusion.

OR

• Under refrigeration at 2°C to 8°C (36°F to 46°F) for no more than 24 hours from the time of preparation to the end of the infusion. If refrigerated, allow the diluted solution to come to room temperature prior to administration. The diluted solution must be administered within 4 hours (including infusion time) once it is removed from the refrigerator.

Do not freeze or shake diluted solution.

Administration:

• Administer diluted ZYNYZ solution by intravenous infusion over 30 minutes through a polyethylene or PVC with DEHP intravenous line containing a sterile, non-pyrogenic, low-protein binding polyethersulfone, polyvinylidene fluoride, or cellulose acetate 0.2 micron to 5 micron in-line or add-on filter or 15 micron mesh in-line or add-on filter. DO NOT administer ZYNYZ as an intravenous push or bolus injection.
• Do not co‑administer other drugs through the same infusion line.

Store refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light. Do not freeze or shake.