POLIVY Powder for solution for injection Ref.[10172] Active ingredients: Polatuzumab vedotin

2.1 Recommended Dosage

The recommended dose of POLIVY is 1.8 mg/kg administered as an intravenous infusion every 21 days for 6 cycles in combination with bendamustine and a rituximab product. Administer POLIVY, bendamustine, and a rituximab product in any order on Day 1 of each cycle. The recommended dose of bendamustine is 90 mg/m²/day on Days 1 and 2 when administered with POLIVY and a rituximab product. The recommended dose of rituximab product is 375 mg/m² intravenously on Day 1 of each cycle.

If not already premedicated, administer an antihistamine and antipyretic at least 30 minutes prior to POLIVY. Administer the initial dose of POLIVY over 90 minutes. Monitor patients for infusion-related reactions during the infusion and for a minimum of 90 minutes following completion of the initial dose. If the previous infusion was well tolerated, the subsequent dose of POLIVY may be administered as a 30-minute infusion and patients should be monitored during the infusion and for at least 30 minutes after completion of the infusion.

If a planned dose of POLIVY is missed, administer as soon as possible. Adjust the schedule of administration to maintain a 21-day interval between doses.

2.2 Management of Adverse Reactions

Table 1 provides management guidelines for peripheral neuropathy, infusion-related reaction, and myelosuppression.

Table 1. Management of Peripheral Neuropathy, Infusion-Related Reaction, and Myelosuppression:

* Severity on Day 1 of any cycle.
^† If primary cause is due to lymphoma, dose delay or reduction may not be needed

2.3 Recommended Prophylactic Medications

If not already premedicated for a rituximab product, administer an antihistamine and antipyretic at least 30 to 60 minutes prior to POLIVY for potential infusion-related reactions [see Warnings and Precautions (5.2)].

Administer prophylaxis for Pneumocystis jiroveci pneumonia and herpesvirus throughout treatment with POLIVY.

Consider prophylactic granulocyte colony stimulating factor administration for neutropenia [see Warnings and Precautions (5.3)].

Administer tumor lysis syndrome prophylaxis for patients at increased risk of tumor lysis syndrome [see Warnings and Precautions (5.6)].

2.4 Instructions for Preparation and Administration

Reconstitute and further dilute POLIVY prior to intravenous infusion.

POLIVY is a cytotoxic drug. Follow applicable special handling and disposal procedures.¹

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Reconstitution:

• Reconstitute immediately before dilution.
• More than one vial may be needed for a full dose. Calculate the dose, the total volume of reconstituted POLIVY solution required, and the number of POLIVY vials needed.
• Using a sterile syringe, slowly inject Sterile Water for Injection, USP, using the volume provided in Table 2, into the POLIVY vial, with the stream directed toward the inside wall of the vial to obtain a concentration of 20 mg/mL of polatuzumab vedotin-piiq.

Table 2. Reconstitution Volumes:

• Swirl the vial gently until completely dissolved. Do not shake.
• Inspect the reconstituted solution for discoloration and particulate matter. The reconstituted solution should appear colorless to slightly brown, clear to slightly opalescent, and free of visible particulates. Do not use if the reconstituted solution is discolored, is cloudy, or contains visible particulates. Do not freeze or expose to direct sunlight.
• If needed, store unused reconstituted POLIVY solution refrigerated at 2°C to 8°C (36°F to 46°F) for up to 48 hours or at room temperature (9°C to 25°C, 47°F to 77°F) up to a maximum of 8 hours prior to dilution. Discard vial when cumulative storage time prior to dilution exceeds 48 hours.

Dilution:

• Dilute polatuzumab vedotin-piiq to a final concentration of 0.72–2.7 mg/mL in an intravenous infusion bag with a minimum volume of 50 mL containing 0.9% Sodium Chloride Injection, USP, 0.45% Sodium Chloride Injection, USP, or 5% Dextrose Injection, USP.
• Determine the volume of 20 mg/mL reconstituted solution needed based on the required dose.
• Withdraw the required volume of reconstituted solution from the POLIVY vial using a sterile syringe and dilute into the intravenous infusion bag. Discard any unused portion left in the vial.
• Gently mix the intravenous bag by slowly inverting the bag. Do not shake.
• Inspect the intravenous bag for particulates and discard if present.
• If not used immediately, store the diluted POLIVY solution as specified in Table 3. Discard if storage time exceeds these limits. Do not freeze or expose to direct sunlight.

Table 3. Diluted POLIVY Solution Storage Conditions:

* To ensure product stability, do not exceed specified storage durations.

• Limit transportation to 30 minutes at 9°C to 25°C or 24 hours at 2°C to 8°C (refer to instructions below). The total storage plus transportation times of the diluted product should not exceed the storage duration specified in Table 3.
• Agitation stress can result in aggregation. Limit agitation of diluted product during preparation and transportation to administration site. Do not transport diluted product through an automated system (e.g., pneumatic tube or automated cart). If the prepared solution will be transported to a separate facility, remove air from the infusion bag to prevent aggregation. If air is removed, an infusion set with a vented spike is required to ensure accurate dosing during the infusion.
• No incompatibilities have been observed between POLIVY and intravenous infusion bags with product-contacting materials of polyvinyl chloride (PVC) or polyolefins (PO) such as polyethylene (PE) and polypropylene (PP). No incompatibilities have been observed with infusion sets or infusion aids with product-contacting materials of PVC, PE, polyurethane (PU), polybutadiene (PBD), acrylonitrile butadiene styrene (ABS), polycarbonate (PC), polyetherurethane (PEU), fluorinated ethylene propylene (FEP), or polytetrafluorethylene (PTFE), or with filter membranes composed of polyether sulfone (PES) or polysulfone (PSU).

Administration:

• Administer POLIVY as an intravenous infusion only.
• POLIVY must be administered using a dedicated infusion line equipped with a sterile, non-pyrogenic, low-protein-binding in-line or add-on filter (0.2- or 0.22-micron pore size) and a catheter.
• Do not mix POLIVY with or administer as an infusion with other drugs.

Store refrigerated at 2°C to 8°C (36°F to 46°F) in original carton to protect from light. Do not use beyond the expiration date shown on the carton. Do not freeze. Do not shake.

POLIVY is a cytotoxic drug. Follow applicable special handling and disposal procedures.¹