Polivy

POLIVY is a CD79b-directed antibody and microtubule inhibitor conjugate indicated:

• in combination with a rituximab product, cyclophosphamide, doxorubicin, and prednisone (R-CHP) for the treatment of adult patients who have previously untreated diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS) or high-grade B-cell lymphoma (HGBL) and who have an International Prognostic Index score of 2 or greater. (
  1.1 Previously Untreated DLBCL, NOS or HGBL

  POLIVY in combination with a rituximab product, cyclophosphamide, doxorubicin, and prednisone (R-CHP) is indicated for the treatment of adult patients who have previously untreated diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS) or high-grade B-cell lymphoma (HGBL) and who have an International Prognostic Index score of 2 or greater.
  )
• in combination with bendamustine and a rituximab product for the treatment of adult patients with relapsed or refractory DLBCL, NOS, after at least two prior therapies. (
  1.2 Relapsed or Refractory DLBCL, NOS

  POLIVY in combination with bendamustine and a rituximab product is indicated for the treatment of adult patients with relapsed or refractory DLBCL, NOS, after at least two prior therapies.
  )

• The recommended dose of POLIVY is 1.8 mg/kg as an intravenous infusion every 21 days for 6 cycles. (
  2 DOSAGE AND ADMINISTRATION

  • The recommended dose of POLIVY is 1.8 mg/kg as an intravenous infusion every 21 days for 6 cycles.
  • Administer the initial POLIVY dose over 90 minutes. Subsequent infusions may be administered over 30 minutes if the previous infusion is tolerated.
  • Premedicate with an antihistamine and antipyretic before POLIVY.
  • See Full Prescribing Information for instructions on preparation and administration.

  2.1 Recommended Dosage

  Patients with Previously Untreated DLBCL, NOS or HGBL

  The recommended dosage of POLIVY is 1.8 mg/kg administered as an intravenous infusion every 21 days for 6 cycles in combination with a rituximab product, cyclophosphamide, doxorubicin, and prednisone

  [see Clinical Studies (14.1)]

  . Administer POLIVY, cyclophosphamide, doxorubicin, and a rituximab product in any order on Day 1 after the administration of prednisone. Prednisone is administered on Days 1–5 of each cycle.

  Patients with Relapsed or Refractory DLBCL, NOS

  The recommended dosage 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/m²intravenously on Day 1 of each cycle.

  For All Indicated Patients

  If not already premedicated, administer an antihistamine and antipyretic at least 30 minutes prior to POLIVY.

  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

  Previously Untreated DLBCL, NOS or HGBL

  Table 1provides management guidelines for peripheral neuropathy in patients receiving POLIVY plus R-CHP

  [see Warnings and Precautions (5.1)]

  .

  Table 1 Management of Peripheral Neuropathy in Patients Receiving POLIVY Plus R-CHP

  Adverse reaction	Grade	Dose modification Starting dose for POLIVY is 1.8 mg/kg. First dose reduction level is 1.4 mg/kg. Second dose reduction level is 1 mg/kg. No further dose reduction is recommended beyond 1 mg/kg. If further reduction needed discontinue POLIVY.
  R-CHP should be continued if POLIVY is withheld. If there is concurrent sensory and motor neuropathy, follow the guidance for the most severe neuropathy. If the grade of sensory and motor neuropathy are the same, follow the guidance for motor neuropathy.
  Peripheral sensory neuropathy	Grade 1	None
  	Grade 2	If resolves to Grade 1 or lower before the next scheduled dose, resume at the same dose level. If Gr 2 persists at the next scheduled dose, reduce one dose level.
  	Grade 3	Withhold until Grade 2 or lower and reduce one dose level.
  	Grade 4	Permanently discontinue.
  Peripheral motor neuropathy	Grade 1	None
  	Grade 2 or 3	Withhold until Grade 1 or lower and reduce one dose level.
  	Grade 4	Permanently discontinue.

  Table 2provides management guidelines for infusion-related reaction and myelosuppression

  [see Warnings and Precautions (5.2and 5.3)]

  .

  Table 2 Management of Infusion-Related Reaction and Myelosuppression in Patients Receiving POLIVY Plus R-CHP

  Adverse Reaction	Dosage Modification Starting dose for POLIVY is 1.8 mg/kg. First dose reduction level is 1.4 mg/kg. Second dose reduction level is 1 mg/kg. No further dose reduction is recommended beyond 1 mg/kg. If further reduction needed discontinue POLIVY.
  Toxicity graded per National Cancer Institute (NCI) Common Terminology for Adverse Events (CTCAE) version 4.0.
  Infusion-Related Reaction Grade 1–3	Interrupt POLIVY infusion and give supportive treatment. For the first instance of Grade 3 wheezing, bronchospasm, or generalized urticaria, permanently discontinue POLIVY. For recurrent Grade 2 wheezing or urticaria, or for recurrence of any Grade 3 symptoms, permanently discontinue POLIVY. Otherwise, upon complete resolution of symptoms, infusion may be resumed at 50% of the rate achieved prior to interruption. In the absence of infusion related symptoms, the rate of infusion may be escalated in increments of 50 mg/hour every 30 minutes. For the next cycle, infuse POLIVY over 90 minutes. If no infusion-related reaction occurs, subsequent infusions may be administered over 30 minutes. Administer premedication for all cycles.
  Infusion-Related Reaction Grade 4	Stop POLIVY infusion immediately. Give supportive treatment. Discontinue POLIVY.
  Neutropenia Severity on Day 1 of any cycle. , If primary cause is lymphoma, dosage delay or reduction may not be needed. Grade 3–4	Hold all treatment until ANC recovers to greater than or equal to 1,000/microliter. Consider therapeutic G-CSF if neutropenia occurs after prophylactic G-CSF. If ANC recovers to greater than or equal to 1,000/microliter on or before Day 7, resume all treatment without any dose reductions. If ANC recovers to greater than or equal to 1,000/microliter after Day 7: resume all treatment administer prophylactic G-CSF in next cycle. If G-CSF was already given, consider a dose reduction of POLIVY.
  Thrombocytopenia , Grade 3–4	Hold all treatment until platelets recover to greater than or equal to 75,000/microliter. If platelets recover to greater than or equal to 75,000/microliter on or before Day 7, resume all treatment without any dose reductions. If platelets recover to greater than or equal to 75,000/microliter after Day 7: resume all treatment and consider a dose reduction of POLIVY.

  Relapsed or Refractory DLBCL, NOS

  Table 3provides management guidelines for peripheral neuropathy, infusion-related reaction, and myelosuppression in patients receiving POLIVY in combination with bendamustine and a rituximab product

  [see Warnings and Precautions (5.1, 5.2, 5.3)]

  .

  Table 3 Management of Peripheral Neuropathy, Infusion-Related Reaction, and Myelosuppression in Patients Receiving POLIVY Plus Bendamustine and a Rituximab Product

  Adverse Reaction	Dosage Modification Starting dose for POLIVY is 1.8 mg/kg. First dose reduction level is 1.4 mg/kg. Second dose reduction level is 1 mg/kg. No further dose reduction is recommended beyond 1 mg/kg. If further reduction needed discontinue POLIVY.
  Toxicity graded per NCI CTCAE version 4.0.
  Peripheral Neuropathy Grade 2–3	Hold POLIVY dosing until improvement to Grade 1 or lower. If recovered to Grade 1 or lower on or before Day 14, restart POLIVY with the next cycle at a permanently reduced dose of 1.4 mg/kg. If a prior dose reduction to 1.4 mg/kg has occurred, discontinue POLIVY. If not recovered to Grade 1 or lower on or before Day 14, discontinue POLIVY.
  Peripheral Neuropathy Grade 4	Discontinue POLIVY.
  Infusion-Related Reaction Grade 1–3	Interrupt POLIVY infusion and give supportive treatment. For the first instance of Grade 3 wheezing, bronchospasm, or generalized urticaria, permanently discontinue POLIVY. For recurrent Grade 2 wheezing or urticaria, or for recurrence of any Grade 3 symptoms, permanently discontinue POLIVY. Otherwise, upon complete resolution of symptoms, infusion may be resumed at 50% of the rate achieved prior to interruption. In the absence of infusion related symptoms, the rate of infusion may be escalated in increments of 50 mg/hour every 30 minutes. For the next cycle, infuse POLIVY over 90 minutes. If no infusion-related reaction occurs, subsequent infusions may be administered over 30 minutes. Administer premedication for all cycles.
  Infusion-Related Reaction Grade 4	Stop POLIVY infusion immediately. Give supportive treatment. Permanently discontinue POLIVY.
  NeutropeniaSeverity on Day 1 of any cycle.,If primary cause is lymphoma, dosage delay or reduction may not be needed. Grade 3–4	Hold all treatment until ANC recovers to greater than 1,000/microliter. If ANC recovers to greater than 1,000/microliter on or before Day 7, resume all treatment without any additional dose reductions. Consider granulocyte colony-stimulating factor prophylaxis for subsequent cycles, if not previously given. If ANC recovers to greater than 1,000/microliter after Day 7: restart all treatment. Consider granulocyte colony-stimulating factor prophylaxis for subsequent cycles, if not previously given. If prophylaxis was given, consider dose reduction of bendamustine. if dose reduction of bendamustine has already occurred, consider dose reduction of POLIVY to 1.4 mg/kg.
  Thrombocytopenia , Grade 3–4	Hold all treatment until platelets recover to greater than 75,000/microliter. If platelets recover to greater than 75,000/microliter on or before Day 7, resume all treatment without any additional dose reductions. If platelets recover to greater than 75,000/microliter after Day 7: restart all treatment, with dose reduction of bendamustine. if dose reduction of bendamustine has already occurred, consider dose reduction of POLIVY to 1.4 mg/kg.

  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.

  Administer prophylactic granulocyte colony-stimulating factor (G-CSF) for neutropenia in patients receiving POLIVY plus R-CHP. Consider prophylactic G-CSF administration for neutropenia in patients receiving POLIVY plus bendamustine and a rituximab product

  [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 hazardous 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 4, 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 4 Reconstitution Volumes

  Strength	Volume of Sterile Water for Injection, USP required for reconstitution
  30 mg vial	1.8 mL
  140 mg vial	7.2 mL

  • 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 5. Discard if storage time exceeds these limits.
    Do not freeze or expose to direct sunlight
    .

  Table 5 Diluted POLIVY Solution Storage Conditions

  Diluent Used to Prepare Solution for Infusion	Diluted POLIVY Solution Storage ConditionsTo ensure product stability, do not exceed specified storage durations.
  0.9% Sodium Chloride Injection, USP	Up to 36 hours at 2°C to 8°C (36°F to 46°F) or up to 4 hours at room temperature (9 to 25°C, 47 to 77°F)
  0.45% Sodium Chloride Injection, USP	Up to 18 hours at 2°C to 8°C (36°F to 46°F) or up to 4 hours at room temperature (9 to 25°C, 47 to 77°F)
  5% Dextrose Injection, USP	Up to 36 hours at 2°C to 8°C (36°F to 46°F) or up to 6 hours at room temperature (9 to 25°C, 47 to 77°F)

  • 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 5.
  • 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.
  • 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.
  • 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.
  )
• Administer the initial POLIVY dose over 90 minutes. Subsequent infusions may be administered over 30 minutes if the previous infusion is tolerated. (
  2 DOSAGE AND ADMINISTRATION

  • The recommended dose of POLIVY is 1.8 mg/kg as an intravenous infusion every 21 days for 6 cycles.
  • Administer the initial POLIVY dose over 90 minutes. Subsequent infusions may be administered over 30 minutes if the previous infusion is tolerated.
  • Premedicate with an antihistamine and antipyretic before POLIVY.
  • See Full Prescribing Information for instructions on preparation and administration.

  2.1 Recommended Dosage

  Patients with Previously Untreated DLBCL, NOS or HGBL

  The recommended dosage of POLIVY is 1.8 mg/kg administered as an intravenous infusion every 21 days for 6 cycles in combination with a rituximab product, cyclophosphamide, doxorubicin, and prednisone

  [see Clinical Studies (14.1)]

  . Administer POLIVY, cyclophosphamide, doxorubicin, and a rituximab product in any order on Day 1 after the administration of prednisone. Prednisone is administered on Days 1–5 of each cycle.

  Patients with Relapsed or Refractory DLBCL, NOS

  The recommended dosage 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/m²intravenously on Day 1 of each cycle.

  For All Indicated Patients

  If not already premedicated, administer an antihistamine and antipyretic at least 30 minutes prior to POLIVY.

  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

  Previously Untreated DLBCL, NOS or HGBL

  Table 1provides management guidelines for peripheral neuropathy in patients receiving POLIVY plus R-CHP

  [see Warnings and Precautions (5.1)]

  .

  Table 1 Management of Peripheral Neuropathy in Patients Receiving POLIVY Plus R-CHP

  Adverse reaction	Grade	Dose modification Starting dose for POLIVY is 1.8 mg/kg. First dose reduction level is 1.4 mg/kg. Second dose reduction level is 1 mg/kg. No further dose reduction is recommended beyond 1 mg/kg. If further reduction needed discontinue POLIVY.
  R-CHP should be continued if POLIVY is withheld. If there is concurrent sensory and motor neuropathy, follow the guidance for the most severe neuropathy. If the grade of sensory and motor neuropathy are the same, follow the guidance for motor neuropathy.
  Peripheral sensory neuropathy	Grade 1	None
  	Grade 2	If resolves to Grade 1 or lower before the next scheduled dose, resume at the same dose level. If Gr 2 persists at the next scheduled dose, reduce one dose level.
  	Grade 3	Withhold until Grade 2 or lower and reduce one dose level.
  	Grade 4	Permanently discontinue.
  Peripheral motor neuropathy	Grade 1	None
  	Grade 2 or 3	Withhold until Grade 1 or lower and reduce one dose level.
  	Grade 4	Permanently discontinue.

  Table 2provides management guidelines for infusion-related reaction and myelosuppression

  [see Warnings and Precautions (5.2and 5.3)]

  .

  Table 2 Management of Infusion-Related Reaction and Myelosuppression in Patients Receiving POLIVY Plus R-CHP

  Adverse Reaction	Dosage Modification Starting dose for POLIVY is 1.8 mg/kg. First dose reduction level is 1.4 mg/kg. Second dose reduction level is 1 mg/kg. No further dose reduction is recommended beyond 1 mg/kg. If further reduction needed discontinue POLIVY.
  Toxicity graded per National Cancer Institute (NCI) Common Terminology for Adverse Events (CTCAE) version 4.0.
  Infusion-Related Reaction Grade 1–3	Interrupt POLIVY infusion and give supportive treatment. For the first instance of Grade 3 wheezing, bronchospasm, or generalized urticaria, permanently discontinue POLIVY. For recurrent Grade 2 wheezing or urticaria, or for recurrence of any Grade 3 symptoms, permanently discontinue POLIVY. Otherwise, upon complete resolution of symptoms, infusion may be resumed at 50% of the rate achieved prior to interruption. In the absence of infusion related symptoms, the rate of infusion may be escalated in increments of 50 mg/hour every 30 minutes. For the next cycle, infuse POLIVY over 90 minutes. If no infusion-related reaction occurs, subsequent infusions may be administered over 30 minutes. Administer premedication for all cycles.
  Infusion-Related Reaction Grade 4	Stop POLIVY infusion immediately. Give supportive treatment. Discontinue POLIVY.
  Neutropenia Severity on Day 1 of any cycle. , If primary cause is lymphoma, dosage delay or reduction may not be needed. Grade 3–4	Hold all treatment until ANC recovers to greater than or equal to 1,000/microliter. Consider therapeutic G-CSF if neutropenia occurs after prophylactic G-CSF. If ANC recovers to greater than or equal to 1,000/microliter on or before Day 7, resume all treatment without any dose reductions. If ANC recovers to greater than or equal to 1,000/microliter after Day 7: resume all treatment administer prophylactic G-CSF in next cycle. If G-CSF was already given, consider a dose reduction of POLIVY.
  Thrombocytopenia , Grade 3–4	Hold all treatment until platelets recover to greater than or equal to 75,000/microliter. If platelets recover to greater than or equal to 75,000/microliter on or before Day 7, resume all treatment without any dose reductions. If platelets recover to greater than or equal to 75,000/microliter after Day 7: resume all treatment and consider a dose reduction of POLIVY.

  Relapsed or Refractory DLBCL, NOS

  Table 3provides management guidelines for peripheral neuropathy, infusion-related reaction, and myelosuppression in patients receiving POLIVY in combination with bendamustine and a rituximab product

  [see Warnings and Precautions (5.1, 5.2, 5.3)]

  .

  Table 3 Management of Peripheral Neuropathy, Infusion-Related Reaction, and Myelosuppression in Patients Receiving POLIVY Plus Bendamustine and a Rituximab Product

  Adverse Reaction	Dosage Modification Starting dose for POLIVY is 1.8 mg/kg. First dose reduction level is 1.4 mg/kg. Second dose reduction level is 1 mg/kg. No further dose reduction is recommended beyond 1 mg/kg. If further reduction needed discontinue POLIVY.
  Toxicity graded per NCI CTCAE version 4.0.
  Peripheral Neuropathy Grade 2–3	Hold POLIVY dosing until improvement to Grade 1 or lower. If recovered to Grade 1 or lower on or before Day 14, restart POLIVY with the next cycle at a permanently reduced dose of 1.4 mg/kg. If a prior dose reduction to 1.4 mg/kg has occurred, discontinue POLIVY. If not recovered to Grade 1 or lower on or before Day 14, discontinue POLIVY.
  Peripheral Neuropathy Grade 4	Discontinue POLIVY.
  Infusion-Related Reaction Grade 1–3	Interrupt POLIVY infusion and give supportive treatment. For the first instance of Grade 3 wheezing, bronchospasm, or generalized urticaria, permanently discontinue POLIVY. For recurrent Grade 2 wheezing or urticaria, or for recurrence of any Grade 3 symptoms, permanently discontinue POLIVY. Otherwise, upon complete resolution of symptoms, infusion may be resumed at 50% of the rate achieved prior to interruption. In the absence of infusion related symptoms, the rate of infusion may be escalated in increments of 50 mg/hour every 30 minutes. For the next cycle, infuse POLIVY over 90 minutes. If no infusion-related reaction occurs, subsequent infusions may be administered over 30 minutes. Administer premedication for all cycles.
  Infusion-Related Reaction Grade 4	Stop POLIVY infusion immediately. Give supportive treatment. Permanently discontinue POLIVY.
  NeutropeniaSeverity on Day 1 of any cycle.,If primary cause is lymphoma, dosage delay or reduction may not be needed. Grade 3–4	Hold all treatment until ANC recovers to greater than 1,000/microliter. If ANC recovers to greater than 1,000/microliter on or before Day 7, resume all treatment without any additional dose reductions. Consider granulocyte colony-stimulating factor prophylaxis for subsequent cycles, if not previously given. If ANC recovers to greater than 1,000/microliter after Day 7: restart all treatment. Consider granulocyte colony-stimulating factor prophylaxis for subsequent cycles, if not previously given. If prophylaxis was given, consider dose reduction of bendamustine. if dose reduction of bendamustine has already occurred, consider dose reduction of POLIVY to 1.4 mg/kg.
  Thrombocytopenia , Grade 3–4	Hold all treatment until platelets recover to greater than 75,000/microliter. If platelets recover to greater than 75,000/microliter on or before Day 7, resume all treatment without any additional dose reductions. If platelets recover to greater than 75,000/microliter after Day 7: restart all treatment, with dose reduction of bendamustine. if dose reduction of bendamustine has already occurred, consider dose reduction of POLIVY to 1.4 mg/kg.

  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.

  Administer prophylactic granulocyte colony-stimulating factor (G-CSF) for neutropenia in patients receiving POLIVY plus R-CHP. Consider prophylactic G-CSF administration for neutropenia in patients receiving POLIVY plus bendamustine and a rituximab product

  [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 hazardous 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 4, 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 4 Reconstitution Volumes

  Strength	Volume of Sterile Water for Injection, USP required for reconstitution
  30 mg vial	1.8 mL
  140 mg vial	7.2 mL

  • 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 5. Discard if storage time exceeds these limits.
    Do not freeze or expose to direct sunlight
    .

  Table 5 Diluted POLIVY Solution Storage Conditions

  Diluent Used to Prepare Solution for Infusion	Diluted POLIVY Solution Storage ConditionsTo ensure product stability, do not exceed specified storage durations.
  0.9% Sodium Chloride Injection, USP	Up to 36 hours at 2°C to 8°C (36°F to 46°F) or up to 4 hours at room temperature (9 to 25°C, 47 to 77°F)
  0.45% Sodium Chloride Injection, USP	Up to 18 hours at 2°C to 8°C (36°F to 46°F) or up to 4 hours at room temperature (9 to 25°C, 47 to 77°F)
  5% Dextrose Injection, USP	Up to 36 hours at 2°C to 8°C (36°F to 46°F) or up to 6 hours at room temperature (9 to 25°C, 47 to 77°F)

  • 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 5.
  • 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.
  • 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.
  • 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.
  )
• Premedicate with an antihistamine and antipyretic before POLIVY. (
  2 DOSAGE AND ADMINISTRATION

  • The recommended dose of POLIVY is 1.8 mg/kg as an intravenous infusion every 21 days for 6 cycles.
  • Administer the initial POLIVY dose over 90 minutes. Subsequent infusions may be administered over 30 minutes if the previous infusion is tolerated.
  • Premedicate with an antihistamine and antipyretic before POLIVY.
  • See Full Prescribing Information for instructions on preparation and administration.

  2.1 Recommended Dosage

  Patients with Previously Untreated DLBCL, NOS or HGBL

  The recommended dosage of POLIVY is 1.8 mg/kg administered as an intravenous infusion every 21 days for 6 cycles in combination with a rituximab product, cyclophosphamide, doxorubicin, and prednisone

  [see Clinical Studies (14.1)]

  . Administer POLIVY, cyclophosphamide, doxorubicin, and a rituximab product in any order on Day 1 after the administration of prednisone. Prednisone is administered on Days 1–5 of each cycle.

  Patients with Relapsed or Refractory DLBCL, NOS

  The recommended dosage 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/m²intravenously on Day 1 of each cycle.

  For All Indicated Patients

  If not already premedicated, administer an antihistamine and antipyretic at least 30 minutes prior to POLIVY.

  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

  Previously Untreated DLBCL, NOS or HGBL

  Table 1provides management guidelines for peripheral neuropathy in patients receiving POLIVY plus R-CHP

  [see Warnings and Precautions (5.1)]

  .

  Table 1 Management of Peripheral Neuropathy in Patients Receiving POLIVY Plus R-CHP

  Adverse reaction	Grade	Dose modification Starting dose for POLIVY is 1.8 mg/kg. First dose reduction level is 1.4 mg/kg. Second dose reduction level is 1 mg/kg. No further dose reduction is recommended beyond 1 mg/kg. If further reduction needed discontinue POLIVY.
  R-CHP should be continued if POLIVY is withheld. If there is concurrent sensory and motor neuropathy, follow the guidance for the most severe neuropathy. If the grade of sensory and motor neuropathy are the same, follow the guidance for motor neuropathy.
  Peripheral sensory neuropathy	Grade 1	None
  	Grade 2	If resolves to Grade 1 or lower before the next scheduled dose, resume at the same dose level. If Gr 2 persists at the next scheduled dose, reduce one dose level.
  	Grade 3	Withhold until Grade 2 or lower and reduce one dose level.
  	Grade 4	Permanently discontinue.
  Peripheral motor neuropathy	Grade 1	None
  	Grade 2 or 3	Withhold until Grade 1 or lower and reduce one dose level.
  	Grade 4	Permanently discontinue.

  Table 2provides management guidelines for infusion-related reaction and myelosuppression

  [see Warnings and Precautions (5.2and 5.3)]

  .

  Table 2 Management of Infusion-Related Reaction and Myelosuppression in Patients Receiving POLIVY Plus R-CHP

  Adverse Reaction	Dosage Modification Starting dose for POLIVY is 1.8 mg/kg. First dose reduction level is 1.4 mg/kg. Second dose reduction level is 1 mg/kg. No further dose reduction is recommended beyond 1 mg/kg. If further reduction needed discontinue POLIVY.
  Toxicity graded per National Cancer Institute (NCI) Common Terminology for Adverse Events (CTCAE) version 4.0.
  Infusion-Related Reaction Grade 1–3	Interrupt POLIVY infusion and give supportive treatment. For the first instance of Grade 3 wheezing, bronchospasm, or generalized urticaria, permanently discontinue POLIVY. For recurrent Grade 2 wheezing or urticaria, or for recurrence of any Grade 3 symptoms, permanently discontinue POLIVY. Otherwise, upon complete resolution of symptoms, infusion may be resumed at 50% of the rate achieved prior to interruption. In the absence of infusion related symptoms, the rate of infusion may be escalated in increments of 50 mg/hour every 30 minutes. For the next cycle, infuse POLIVY over 90 minutes. If no infusion-related reaction occurs, subsequent infusions may be administered over 30 minutes. Administer premedication for all cycles.
  Infusion-Related Reaction Grade 4	Stop POLIVY infusion immediately. Give supportive treatment. Discontinue POLIVY.
  Neutropenia Severity on Day 1 of any cycle. , If primary cause is lymphoma, dosage delay or reduction may not be needed. Grade 3–4	Hold all treatment until ANC recovers to greater than or equal to 1,000/microliter. Consider therapeutic G-CSF if neutropenia occurs after prophylactic G-CSF. If ANC recovers to greater than or equal to 1,000/microliter on or before Day 7, resume all treatment without any dose reductions. If ANC recovers to greater than or equal to 1,000/microliter after Day 7: resume all treatment administer prophylactic G-CSF in next cycle. If G-CSF was already given, consider a dose reduction of POLIVY.
  Thrombocytopenia , Grade 3–4	Hold all treatment until platelets recover to greater than or equal to 75,000/microliter. If platelets recover to greater than or equal to 75,000/microliter on or before Day 7, resume all treatment without any dose reductions. If platelets recover to greater than or equal to 75,000/microliter after Day 7: resume all treatment and consider a dose reduction of POLIVY.

  Relapsed or Refractory DLBCL, NOS

  Table 3provides management guidelines for peripheral neuropathy, infusion-related reaction, and myelosuppression in patients receiving POLIVY in combination with bendamustine and a rituximab product

  [see Warnings and Precautions (5.1, 5.2, 5.3)]

  .

  Table 3 Management of Peripheral Neuropathy, Infusion-Related Reaction, and Myelosuppression in Patients Receiving POLIVY Plus Bendamustine and a Rituximab Product

  Adverse Reaction	Dosage Modification Starting dose for POLIVY is 1.8 mg/kg. First dose reduction level is 1.4 mg/kg. Second dose reduction level is 1 mg/kg. No further dose reduction is recommended beyond 1 mg/kg. If further reduction needed discontinue POLIVY.
  Toxicity graded per NCI CTCAE version 4.0.
  Peripheral Neuropathy Grade 2–3	Hold POLIVY dosing until improvement to Grade 1 or lower. If recovered to Grade 1 or lower on or before Day 14, restart POLIVY with the next cycle at a permanently reduced dose of 1.4 mg/kg. If a prior dose reduction to 1.4 mg/kg has occurred, discontinue POLIVY. If not recovered to Grade 1 or lower on or before Day 14, discontinue POLIVY.
  Peripheral Neuropathy Grade 4	Discontinue POLIVY.
  Infusion-Related Reaction Grade 1–3	Interrupt POLIVY infusion and give supportive treatment. For the first instance of Grade 3 wheezing, bronchospasm, or generalized urticaria, permanently discontinue POLIVY. For recurrent Grade 2 wheezing or urticaria, or for recurrence of any Grade 3 symptoms, permanently discontinue POLIVY. Otherwise, upon complete resolution of symptoms, infusion may be resumed at 50% of the rate achieved prior to interruption. In the absence of infusion related symptoms, the rate of infusion may be escalated in increments of 50 mg/hour every 30 minutes. For the next cycle, infuse POLIVY over 90 minutes. If no infusion-related reaction occurs, subsequent infusions may be administered over 30 minutes. Administer premedication for all cycles.
  Infusion-Related Reaction Grade 4	Stop POLIVY infusion immediately. Give supportive treatment. Permanently discontinue POLIVY.
  NeutropeniaSeverity on Day 1 of any cycle.,If primary cause is lymphoma, dosage delay or reduction may not be needed. Grade 3–4	Hold all treatment until ANC recovers to greater than 1,000/microliter. If ANC recovers to greater than 1,000/microliter on or before Day 7, resume all treatment without any additional dose reductions. Consider granulocyte colony-stimulating factor prophylaxis for subsequent cycles, if not previously given. If ANC recovers to greater than 1,000/microliter after Day 7: restart all treatment. Consider granulocyte colony-stimulating factor prophylaxis for subsequent cycles, if not previously given. If prophylaxis was given, consider dose reduction of bendamustine. if dose reduction of bendamustine has already occurred, consider dose reduction of POLIVY to 1.4 mg/kg.
  Thrombocytopenia , Grade 3–4	Hold all treatment until platelets recover to greater than 75,000/microliter. If platelets recover to greater than 75,000/microliter on or before Day 7, resume all treatment without any additional dose reductions. If platelets recover to greater than 75,000/microliter after Day 7: restart all treatment, with dose reduction of bendamustine. if dose reduction of bendamustine has already occurred, consider dose reduction of POLIVY to 1.4 mg/kg.

  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.

  Administer prophylactic granulocyte colony-stimulating factor (G-CSF) for neutropenia in patients receiving POLIVY plus R-CHP. Consider prophylactic G-CSF administration for neutropenia in patients receiving POLIVY plus bendamustine and a rituximab product

  [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 hazardous 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 4, 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 4 Reconstitution Volumes

  Strength	Volume of Sterile Water for Injection, USP required for reconstitution
  30 mg vial	1.8 mL
  140 mg vial	7.2 mL

  • 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 5. Discard if storage time exceeds these limits.
    Do not freeze or expose to direct sunlight
    .

  Table 5 Diluted POLIVY Solution Storage Conditions

  Diluent Used to Prepare Solution for Infusion	Diluted POLIVY Solution Storage ConditionsTo ensure product stability, do not exceed specified storage durations.
  0.9% Sodium Chloride Injection, USP	Up to 36 hours at 2°C to 8°C (36°F to 46°F) or up to 4 hours at room temperature (9 to 25°C, 47 to 77°F)
  0.45% Sodium Chloride Injection, USP	Up to 18 hours at 2°C to 8°C (36°F to 46°F) or up to 4 hours at room temperature (9 to 25°C, 47 to 77°F)
  5% Dextrose Injection, USP	Up to 36 hours at 2°C to 8°C (36°F to 46°F) or up to 6 hours at room temperature (9 to 25°C, 47 to 77°F)

  • 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 5.
  • 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.
  • 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.
  • 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.
  )
• See Full Prescribing Information for instructions on preparation and administration. (
  2.4 Instructions for Preparation and Administration

  Reconstitute and further dilute POLIVY prior to intravenous infusion.

  POLIVY is a hazardous 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 4, 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 4 Reconstitution Volumes

  Strength	Volume of Sterile Water for Injection, USP required for reconstitution
  30 mg vial	1.8 mL
  140 mg vial	7.2 mL

  • 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 5. Discard if storage time exceeds these limits.
    Do not freeze or expose to direct sunlight
    .

  Table 5 Diluted POLIVY Solution Storage Conditions

  Diluent Used to Prepare Solution for Infusion	Diluted POLIVY Solution Storage ConditionsTo ensure product stability, do not exceed specified storage durations.
  0.9% Sodium Chloride Injection, USP	Up to 36 hours at 2°C to 8°C (36°F to 46°F) or up to 4 hours at room temperature (9 to 25°C, 47 to 77°F)
  0.45% Sodium Chloride Injection, USP	Up to 18 hours at 2°C to 8°C (36°F to 46°F) or up to 4 hours at room temperature (9 to 25°C, 47 to 77°F)
  5% Dextrose Injection, USP	Up to 36 hours at 2°C to 8°C (36°F to 46°F) or up to 6 hours at room temperature (9 to 25°C, 47 to 77°F)

  • 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 5.
  • 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.
  • 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.
  • 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.
  )

For injection: 30 mg/vial or 140 mg/vial of polatuzumab vedotin-piiq as a white to grayish-white lyophilized powder in a single-dose vial for reconstitution and further dilution.

• Hepatic impairment has the potential to increase exposure to MMAE. Monitor patients for adverse reactions. (
  8.6 Hepatic Impairment

  Avoid the administration of POLIVY in patients with moderate or severe hepatic impairment (total bilirubin greater than 1.5 × ULN and any AST). Patients with moderate or severe hepatic impairment are likely to have increased exposure to MMAE, which may increase the risk of adverse reactions. POLIVY has not been studied in patients with moderate or severe hepatic impairment

  [see Clinical Pharmacology (12.3)and Warnings and Precautions (5.7)].

  No adjustment in the starting dose is required when administering POLIVY to patients with mild hepatic impairment (total bilirubin 1 to 1.5 × ULN or AST greater than ULN).
  )
• Lactation: Advise not to breastfeed. (
  8.2 Lactation

  Risk Summary

  There is no information regarding the presence of polatuzumab vedotin-piiq in human milk, the effects on the breastfed child, or milk production. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with POLIVY and for 2 months after the last dose.
  )