polatuzumab vedotin (Rx)

Brand and Other Names:Polivy, polatuzumab vedotin-piiq
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Dosing & Uses

AdultPediatricGeriatric

Dosage Forms & Strengths

injection, lyophilized powder for reconstitution

  • 140mg/vial (single-dose vial)

Diffuse Large B-Cell Lymphoma

Indicated in combination with bendamustine and a rituximab product for treatment of patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after ≥2 prior therapies

Administer every 21-day cycle for 6 cycles

Day 1

  • Rituximab product 375 mg/m² IV PLUS
  • Bendamustine 90 mg/m² IV PLUS
  • Polatuzumab vedotin 1.8 mg/kg IV
  • May administer drugs in any sequence on Day 1

Day 2

  • Bendamustine 90 mg/m² IV

Dosage Modifications

Peripheral neuropathy

  • Grade 2-3
    • Hold dose until improvement to grade ≤1
    • If recovered to grade ≤1 on or before Day 14, permanently reduce dose to 1.4 mg/kg and restart with next cycle
    • Discontinue treatment if dose was previously reduced to 1.4 mg/kg or if not recovered to grade ≤1 or before Day 14
  • Grade 4: Discontinue treatment

Infusion-related reactions

  • Grade 1-3
    • Interrupt infusion and provide supportive care
    • Upon complete resolution of symptoms, resume infusion at 50% of the rate achieved prior to interruption; if no infusion-related reaction occurs, infusion rate may be titrated in increments of 50 mg/hr q30min
    • For the next cycle, infuse dose over 90 minutes; if no infusion-related reaction occurs, subsequent infusions may be administered over 30 minutes
    • Administer premedication for all cycles
    • Permanently discontinue if first grade 3 occurrence (eg, wheezing, bronchospasm, generalized urticaria), recurrent grade 2 wheezing or urticaria, or grade 3 symptoms
  • Grade 4
    • Stop infusion immediately; provide supportive care and permanently discontinue

Grade 3-4 neutropenia

  • Grade 3-4 severity on Day 1 of any cycle: Hold all treatment until ANC recovers to >1000/mcL
  • If primary cause is due to lymphoma, dose delay or reduction may not be needed
  • If ANC recovers to >1000/mcL on or before Day 7
    • Resume all treatment without any additional dose reductions
    • Consider granulocyte colony-stimulating factor (GCSF) prophylaxis for subsequent cycles, if not previously given
  • If ANC recovers to >1000/mcL after Day 7
    • Restart all treatment; consider GCSF 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 polatuzumab vedotin to 1.4 mg/kg

Grade 3-4 thrombocytopenia

  • Grade 3-4 severity on Day 1 of any cycle: Hold all treatment until platelets recover to >75,000/mcL
  • If primary cause is due to lymphoma, dose delay or reduction may not be needed
  • If platelets recover to >75,000/mcL on or before Day 7
    • Resume all treatment without any additional dose reductions
  • If platelets recover to >75,000/mcL after Day 7
    • Restart all treatment, with dose reduction of bendamustine
    • If dose reduction of bendamustine has already occurred, consider dose reduction of polatuzumab vedotin to 1.4 mg/kg

Renal impairment

  • Mild-to-moderate (CrCl 30-89 mL/min): No clinically significant differences in the pharmacokinetics of antibody-conjugated MMAE (acMMAE) or unconjugated monomethyl auristatin E (MMAE) were observed
  • Severe (CrCl 15-29 mL/min) or end-stage renal disease with or without dialysis: Pharmacokinetics are unknown

Hepatic impairment

  • Mild (bilirubin >ULN to ≤1.5x ULN or AST >ULN): No adjustment to starting dose
  • Moderate-to-severe (bilirubin >1.5x ULN): Avoid use; patients with moderate or severe hepatic impairment are likely to have increased exposure to MMAE, which may increase the risk of adverse reactions; use has not been studied in such patients

Safety and efficacy not established

Patients aged ≥65 had a higher incidence of serious adverse reactions than patients aged <65 years

Clinical studies did not include sufficient number of patients aged ≥65 years to determine whether they respond differently from younger patients

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Interactions

Interaction Checker

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              Serious - Use Alternative (4)

              • abametapir

                abametapir will increase the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP3A4 substrates. If not feasible, avoid use of abametapir.

              • fexinidazole

                fexinidazole will increase the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.

              • tucatinib

                tucatinib will increase the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.

              • voxelotor

                voxelotor will increase the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.

              Monitor Closely (57)

              • amobarbital

                amobarbital will decrease the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Polatuzumab undergoes catabolism to small peptides, amino acids, monomethyl auristatin E (MMAE), and unconjugated MMAE-related catabolites. MMAE is a CYP3A4 substrate. Coadministration of polatuzumab vedotin with a strong CYP3A4 inducer may decrease unconjugated MMAE AUC.

              • apalutamide

                apalutamide will decrease the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Polatuzumab undergoes catabolism to small peptides, amino acids, monomethyl auristatin E (MMAE), and unconjugated MMAE-related catabolites. MMAE is a CYP3A4 substrate. Coadministration of polatuzumab vedotin with a strong CYP3A4 inducer may decrease unconjugated MMAE AUC.

              • atazanavir

                atazanavir will increase the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Polatuzumab undergoes catabolism to small peptides, amino acids, monomethyl auristatin E (MMAE), and unconjugated MMAE-related catabolites. MMAE is a CYP3A4 substrate. Coadministration of polatuzumab vedotin with a strong CYP3A4 inhibitor may increase unconjugated MMAE AUC, which may increase polatuzumab vedotin toxicities.

              • bosentan

                bosentan will decrease the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Polatuzumab undergoes catabolism to small peptides, amino acids, monomethyl auristatin E (MMAE), and unconjugated MMAE-related catabolites. MMAE is a CYP3A4 substrate. Coadministration of polatuzumab vedotin with a strong CYP3A4 inducer may decrease unconjugated MMAE AUC.

              • butabarbital

                butabarbital will decrease the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Polatuzumab undergoes catabolism to small peptides, amino acids, monomethyl auristatin E (MMAE), and unconjugated MMAE-related catabolites. MMAE is a CYP3A4 substrate. Coadministration of polatuzumab vedotin with a strong CYP3A4 inducer may decrease unconjugated MMAE AUC.

              • butalbital

                butalbital will decrease the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Polatuzumab undergoes catabolism to small peptides, amino acids, monomethyl auristatin E (MMAE), and unconjugated MMAE-related catabolites. MMAE is a CYP3A4 substrate. Coadministration of polatuzumab vedotin with a strong CYP3A4 inducer may decrease unconjugated MMAE AUC.

              • carbamazepine

                carbamazepine will decrease the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Polatuzumab undergoes catabolism to small peptides, amino acids, monomethyl auristatin E (MMAE), and unconjugated MMAE-related catabolites. MMAE is a CYP3A4 substrate. Coadministration of polatuzumab vedotin with a strong CYP3A4 inducer may decrease unconjugated MMAE AUC.

              • cenobamate

                cenobamate will decrease the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.

              • chloramphenicol

                chloramphenicol will increase the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Polatuzumab undergoes catabolism to small peptides, amino acids, monomethyl auristatin E (MMAE), and unconjugated MMAE-related catabolites. MMAE is a CYP3A4 substrate. Coadministration of polatuzumab vedotin with a strong CYP3A4 inhibitor may increase unconjugated MMAE AUC, which may increase polatuzumab vedotin toxicities.

              • clarithromycin

                clarithromycin will increase the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Polatuzumab undergoes catabolism to small peptides, amino acids, monomethyl auristatin E (MMAE), and unconjugated MMAE-related catabolites. MMAE is a CYP3A4 substrate. Coadministration of polatuzumab vedotin with a strong CYP3A4 inhibitor may increase unconjugated MMAE AUC, which may increase polatuzumab vedotin toxicities.

              • cobicistat

                cobicistat will increase the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Polatuzumab undergoes catabolism to small peptides, amino acids, monomethyl auristatin E (MMAE), and unconjugated MMAE-related catabolites. MMAE is a CYP3A4 substrate. Coadministration of polatuzumab vedotin with a strong CYP3A4 inhibitor may increase unconjugated MMAE AUC, which may increase polatuzumab vedotin toxicities.

              • conivaptan

                conivaptan will increase the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Polatuzumab undergoes catabolism to small peptides, amino acids, monomethyl auristatin E (MMAE), and unconjugated MMAE-related catabolites. MMAE is a CYP3A4 substrate. Coadministration of polatuzumab vedotin with a strong CYP3A4 inhibitor may increase unconjugated MMAE AUC, which may increase polatuzumab vedotin toxicities.

              • dabrafenib

                dabrafenib will decrease the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Polatuzumab undergoes catabolism to small peptides, amino acids, monomethyl auristatin E (MMAE), and unconjugated MMAE-related catabolites. MMAE is a CYP3A4 substrate. Coadministration of polatuzumab vedotin with a strong CYP3A4 inducer may decrease unconjugated MMAE AUC.

              • darunavir

                darunavir will increase the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Polatuzumab undergoes catabolism to small peptides, amino acids, monomethyl auristatin E (MMAE), and unconjugated MMAE-related catabolites. MMAE is a CYP3A4 substrate. Coadministration of polatuzumab vedotin with a strong CYP3A4 inhibitor may increase unconjugated MMAE AUC, which may increase polatuzumab vedotin toxicities.

              • efavirenz

                efavirenz will decrease the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Polatuzumab undergoes catabolism to small peptides, amino acids, monomethyl auristatin E (MMAE), and unconjugated MMAE-related catabolites. MMAE is a CYP3A4 substrate. Coadministration of polatuzumab vedotin with a strong CYP3A4 inducer may decrease unconjugated MMAE AUC.

              • elagolix

                elagolix decreases levels of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed.

              • elvitegravir/cobicistat/emtricitabine/tenofovir DF

                elvitegravir/cobicistat/emtricitabine/tenofovir DF will increase the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Polatuzumab undergoes catabolism to small peptides, amino acids, monomethyl auristatin E (MMAE), and unconjugated MMAE-related catabolites. MMAE is a CYP3A4 substrate. Coadministration of polatuzumab vedotin with a strong CYP3A4 inhibitor may increase unconjugated MMAE AUC, which may increase polatuzumab vedotin toxicities.

              • enzalutamide

                enzalutamide will decrease the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Polatuzumab undergoes catabolism to small peptides, amino acids, monomethyl auristatin E (MMAE), and unconjugated MMAE-related catabolites. MMAE is a CYP3A4 substrate. Coadministration of polatuzumab vedotin with a strong CYP3A4 inducer may decrease unconjugated MMAE AUC.

              • etravirine

                etravirine will decrease the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Polatuzumab undergoes catabolism to small peptides, amino acids, monomethyl auristatin E (MMAE), and unconjugated MMAE-related catabolites. MMAE is a CYP3A4 substrate. Coadministration of polatuzumab vedotin with a strong CYP3A4 inducer may decrease unconjugated MMAE AUC.

              • fedratinib

                fedratinib will increase the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

              • fosphenytoin

                fosphenytoin will decrease the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Polatuzumab undergoes catabolism to small peptides, amino acids, monomethyl auristatin E (MMAE), and unconjugated MMAE-related catabolites. MMAE is a CYP3A4 substrate. Coadministration of polatuzumab vedotin with a strong CYP3A4 inducer may decrease unconjugated MMAE AUC.

              • grapefruit

                grapefruit will increase the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Polatuzumab undergoes catabolism to small peptides, amino acids, monomethyl auristatin E (MMAE), and unconjugated MMAE-related catabolites. MMAE is a CYP3A4 substrate. Coadministration of polatuzumab vedotin with a strong CYP3A4 inhibitor may increase unconjugated MMAE AUC, which may increase polatuzumab vedotin toxicities.

              • idelalisib

                idelalisib will increase the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Polatuzumab undergoes catabolism to small peptides, amino acids, monomethyl auristatin E (MMAE), and unconjugated MMAE-related catabolites. MMAE is a CYP3A4 substrate. Coadministration of polatuzumab vedotin with a strong CYP3A4 inhibitor may increase unconjugated MMAE AUC, which may increase polatuzumab vedotin toxicities.

              • indinavir

                indinavir will increase the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Polatuzumab undergoes catabolism to small peptides, amino acids, monomethyl auristatin E (MMAE), and unconjugated MMAE-related catabolites. MMAE is a CYP3A4 substrate. Coadministration of polatuzumab vedotin with a strong CYP3A4 inhibitor may increase unconjugated MMAE AUC, which may increase polatuzumab vedotin toxicities.

              • isoniazid

                isoniazid will increase the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Polatuzumab undergoes catabolism to small peptides, amino acids, monomethyl auristatin E (MMAE), and unconjugated MMAE-related catabolites. MMAE is a CYP3A4 substrate. Coadministration of polatuzumab vedotin with a strong CYP3A4 inhibitor may increase unconjugated MMAE AUC, which may increase polatuzumab vedotin toxicities.

              • istradefylline

                istradefylline will increase the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.

              • itraconazole

                itraconazole will increase the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Polatuzumab undergoes catabolism to small peptides, amino acids, monomethyl auristatin E (MMAE), and unconjugated MMAE-related catabolites. MMAE is a CYP3A4 substrate. Coadministration of polatuzumab vedotin with a strong CYP3A4 inhibitor may increase unconjugated MMAE AUC, which may increase polatuzumab vedotin toxicities.

              • ivosidenib

                ivosidenib will decrease the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Polatuzumab undergoes catabolism to small peptides, amino acids, monomethyl auristatin E (MMAE), and unconjugated MMAE-related catabolites. MMAE is a CYP3A4 substrate. Coadministration of polatuzumab vedotin with a strong CYP3A4 inducer may decrease unconjugated MMAE AUC.

              • ketoconazole

                ketoconazole will increase the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Polatuzumab undergoes catabolism to small peptides, amino acids, monomethyl auristatin E (MMAE), and unconjugated MMAE-related catabolites. MMAE is a CYP3A4 substrate. Coadministration of polatuzumab vedotin with a strong CYP3A4 inhibitor may increase unconjugated MMAE AUC, which may increase polatuzumab vedotin toxicities.

              • lopinavir

                lopinavir will increase the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Polatuzumab undergoes catabolism to small peptides, amino acids, monomethyl auristatin E (MMAE), and unconjugated MMAE-related catabolites. MMAE is a CYP3A4 substrate. Coadministration of polatuzumab vedotin with a strong CYP3A4 inhibitor may increase unconjugated MMAE AUC, which may increase polatuzumab vedotin toxicities.

              • lorlatinib

                lorlatinib will decrease the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Polatuzumab undergoes catabolism to small peptides, amino acids, monomethyl auristatin E (MMAE), and unconjugated MMAE-related catabolites. MMAE is a CYP3A4 substrate. Coadministration of polatuzumab vedotin with a strong CYP3A4 inducer may decrease unconjugated MMAE AUC.

              • lumacaftor/ivacaftor

                lumacaftor/ivacaftor will decrease the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Polatuzumab undergoes catabolism to small peptides, amino acids, monomethyl auristatin E (MMAE), and unconjugated MMAE-related catabolites. MMAE is a CYP3A4 substrate. Coadministration of polatuzumab vedotin with a strong CYP3A4 inducer may decrease unconjugated MMAE AUC.

              • mifepristone

                mifepristone will increase the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Polatuzumab undergoes catabolism to small peptides, amino acids, monomethyl auristatin E (MMAE), and unconjugated MMAE-related catabolites. MMAE is a CYP3A4 substrate. Coadministration of polatuzumab vedotin with a strong CYP3A4 inhibitor may increase unconjugated MMAE AUC, which may increase polatuzumab vedotin toxicities.

              • mitotane

                mitotane will decrease the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Polatuzumab undergoes catabolism to small peptides, amino acids, monomethyl auristatin E (MMAE), and unconjugated MMAE-related catabolites. MMAE is a CYP3A4 substrate. Coadministration of polatuzumab vedotin with a strong CYP3A4 inducer may decrease unconjugated MMAE AUC.

              • nafcillin

                nafcillin will decrease the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Polatuzumab undergoes catabolism to small peptides, amino acids, monomethyl auristatin E (MMAE), and unconjugated MMAE-related catabolites. MMAE is a CYP3A4 substrate. Coadministration of polatuzumab vedotin with a strong CYP3A4 inducer may decrease unconjugated MMAE AUC.

              • nefazodone

                nefazodone will increase the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Polatuzumab undergoes catabolism to small peptides, amino acids, monomethyl auristatin E (MMAE), and unconjugated MMAE-related catabolites. MMAE is a CYP3A4 substrate. Coadministration of polatuzumab vedotin with a strong CYP3A4 inhibitor may increase unconjugated MMAE AUC, which may increase polatuzumab vedotin toxicities.

              • nelfinavir

                nelfinavir will increase the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Polatuzumab undergoes catabolism to small peptides, amino acids, monomethyl auristatin E (MMAE), and unconjugated MMAE-related catabolites. MMAE is a CYP3A4 substrate. Coadministration of polatuzumab vedotin with a strong CYP3A4 inhibitor may increase unconjugated MMAE AUC, which may increase polatuzumab vedotin toxicities.

              • pentobarbital

                pentobarbital will decrease the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Polatuzumab undergoes catabolism to small peptides, amino acids, monomethyl auristatin E (MMAE), and unconjugated MMAE-related catabolites. MMAE is a CYP3A4 substrate. Coadministration of polatuzumab vedotin with a strong CYP3A4 inducer may decrease unconjugated MMAE AUC.

              • phenobarbital

                phenobarbital will decrease the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Polatuzumab undergoes catabolism to small peptides, amino acids, monomethyl auristatin E (MMAE), and unconjugated MMAE-related catabolites. MMAE is a CYP3A4 substrate. Coadministration of polatuzumab vedotin with a strong CYP3A4 inducer may decrease unconjugated MMAE AUC.

              • phenytoin

                phenytoin will decrease the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Polatuzumab undergoes catabolism to small peptides, amino acids, monomethyl auristatin E (MMAE), and unconjugated MMAE-related catabolites. MMAE is a CYP3A4 substrate. Coadministration of polatuzumab vedotin with a strong CYP3A4 inducer may decrease unconjugated MMAE AUC.

              • ponesimod

                ponesimod and polatuzumab vedotin both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

              • posaconazole

                posaconazole will increase the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Polatuzumab undergoes catabolism to small peptides, amino acids, monomethyl auristatin E (MMAE), and unconjugated MMAE-related catabolites. MMAE is a CYP3A4 substrate. Coadministration of polatuzumab vedotin with a strong CYP3A4 inhibitor may increase unconjugated MMAE AUC, which may increase polatuzumab vedotin toxicities.

              • primidone

                primidone will decrease the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Polatuzumab undergoes catabolism to small peptides, amino acids, monomethyl auristatin E (MMAE), and unconjugated MMAE-related catabolites. MMAE is a CYP3A4 substrate. Coadministration of polatuzumab vedotin with a strong CYP3A4 inducer may decrease unconjugated MMAE AUC.

              • ribociclib

                ribociclib will increase the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • rifabutin

                rifabutin will decrease the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Polatuzumab undergoes catabolism to small peptides, amino acids, monomethyl auristatin E (MMAE), and unconjugated MMAE-related catabolites. MMAE is a CYP3A4 substrate. Coadministration of polatuzumab vedotin with a strong CYP3A4 inducer may decrease unconjugated MMAE AUC.

              • rifampin

                rifampin will decrease the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Polatuzumab undergoes catabolism to small peptides, amino acids, monomethyl auristatin E (MMAE), and unconjugated MMAE-related catabolites. MMAE is a CYP3A4 substrate. Coadministration of polatuzumab vedotin with a strong CYP3A4 inducer may decrease unconjugated MMAE AUC.

              • rifapentine

                rifapentine will decrease the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Polatuzumab undergoes catabolism to small peptides, amino acids, monomethyl auristatin E (MMAE), and unconjugated MMAE-related catabolites. MMAE is a CYP3A4 substrate. Coadministration of polatuzumab vedotin with a strong CYP3A4 inducer may decrease unconjugated MMAE AUC.

              • ritonavir

                ritonavir will increase the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Polatuzumab undergoes catabolism to small peptides, amino acids, monomethyl auristatin E (MMAE), and unconjugated MMAE-related catabolites. MMAE is a CYP3A4 substrate. Coadministration of polatuzumab vedotin with a strong CYP3A4 inhibitor may increase unconjugated MMAE AUC, which may increase polatuzumab vedotin toxicities.

              • rucaparib

                rucaparib will increase the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.

              • saquinavir

                saquinavir will increase the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Polatuzumab undergoes catabolism to small peptides, amino acids, monomethyl auristatin E (MMAE), and unconjugated MMAE-related catabolites. MMAE is a CYP3A4 substrate. Coadministration of polatuzumab vedotin with a strong CYP3A4 inhibitor may increase unconjugated MMAE AUC, which may increase polatuzumab vedotin toxicities.

              • secobarbital

                secobarbital will decrease the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Polatuzumab undergoes catabolism to small peptides, amino acids, monomethyl auristatin E (MMAE), and unconjugated MMAE-related catabolites. MMAE is a CYP3A4 substrate. Coadministration of polatuzumab vedotin with a strong CYP3A4 inducer may decrease unconjugated MMAE AUC.

              • siponimod

                siponimod and polatuzumab vedotin both increase immunosuppressive effects; risk of infection. Use Caution/Monitor. Caution if coadministered because of additive immunosuppressive effects during such therapy and in the weeks following administration. When switching from drugs with prolonged immune effects, consider the half-life and mode of action of these drugs to avoid unintended additive immunosuppressive effects.

              • St John's Wort

                St John's Wort will decrease the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Polatuzumab undergoes catabolism to small peptides, amino acids, monomethyl auristatin E (MMAE), and unconjugated MMAE-related catabolites. MMAE is a CYP3A4 substrate. Coadministration of polatuzumab vedotin with a strong CYP3A4 inducer may decrease unconjugated MMAE AUC.

              • stiripentol

                stiripentol, polatuzumab vedotin. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Polatuzumab undergoes catabolism to small peptides, amino acids, monomethyl auristatin E (MMAE), and unconjugated MMAE-related catabolites. MMAE is a CYP3A4 substrate. Coadministration of polatuzumab vedotin with stiripentol (both a strong CYP3A4 inhibitor and inducer) may increase or decrease unconjugated MMAE AUC.

              • tazemetostat

                tazemetostat will decrease the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              • tipranavir

                tipranavir will increase the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Polatuzumab undergoes catabolism to small peptides, amino acids, monomethyl auristatin E (MMAE), and unconjugated MMAE-related catabolites. MMAE is a CYP3A4 substrate. Coadministration of polatuzumab vedotin with a strong CYP3A4 inhibitor may increase unconjugated MMAE AUC, which may increase polatuzumab vedotin toxicities.

              • voriconazole

                voriconazole will increase the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Polatuzumab undergoes catabolism to small peptides, amino acids, monomethyl auristatin E (MMAE), and unconjugated MMAE-related catabolites. MMAE is a CYP3A4 substrate. Coadministration of polatuzumab vedotin with a strong CYP3A4 inhibitor may increase unconjugated MMAE AUC, which may increase polatuzumab vedotin toxicities.

              Minor (0)

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                Adverse Effects

                All grades of severity listed unless otherwise indicated

                >10%

                Lymphocyte count decreased (87%)

                Creatinine increased (87%)

                Neutrophil count decreased (78%)

                Neutrophil count decreased, grade ≥3 (61%)

                Hemoglobin decreased (78%)

                Platelet count decreased (76%)

                Neutropenia (49%)

                Thrombocytopenia (49%)

                Anemia (47%)

                Calcium decreased (44%)

                Neutropenia, grade ≥3 (42%)

                Thrombocytopenia, grade ≥3 (40%)

                Peripheral neuropathy (40%)

                Diarrhea (38%)

                SGPT/ALT increased (38%)

                SGOT/AST increased (36%)

                Lipase increased (36%)

                Phosphorus decreased (33%)

                Pyrexia (33%)

                Platelet count decreased, grade ≥3 (31%)

                Decreased appetite (27%)

                Anemia, grade ≥3 (24%)

                Amylase increased (24%)

                Potassium decreased (24%)

                Pneumonia (22%)

                Dyspnea (19%)

                Vomiting (18%)

                Infusion-related reactions (18%)

                Hemoglobin decreased, grade ≥3 (18%)

                Pneumonia, grade ≥3 (16%)

                Hypokalemia (16%)

                Decreased weight (16%)

                Upper respiratory tract infection (16%)

                Lymphopenia (13%)

                Upper respiratory tract infection (13%)

                Hypoalbuminemia (13%)

                Dizziness (13%)

                Lower respiratory tract infection (10%)

                Herpes virus infection (12%)

                Hypocalcemia (11%)

                1-10%

                Hypokalemia, grade ≥3 (9%)

                Calcium decreased, grade ≥3 (9%)

                Hypophosphatemia (9%)

                Lipase increased, grade ≥3 (9%)

                Potassium decreased, grade ≥3 (7%)

                Phosphorus decreased, grade ≥3 (7%)

                Pancytopenia (7%)

                Elevated transaminase (7%)

                Lipase increase (7%)

                Arthralgia (7%)

                Diarrhea, grade ≥3 (4.4%)

                Pneumonitis (1.7-4.4%)

                Creatinine increased (4.4%)

                Vomiting, grade ≥3 (2.2%)

                Infusion-related reaction, grade ≥3 (2.2%)

                Pyrexia, grade ≥3 (2.2%)

                Decreased appetite, grade ≥3 (2.2%)

                Decreased weight, grade ≥3 (2.2%)

                Hypoalbuminemia, grade ≥3 (2.2%)

                Hypocalcemia, grade ≥3 (2.2%)

                Blurred vision (1.2%)

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                Warnings

                Contraindications

                None

                Cautions

                Infusion-related reactions reported; delayed infusion-related reactions may occur as late as 24 hr after receiving polatuzumab

                Serious or severe myelosuppression (eg, neutropenia, thrombocytopenia, anemia) may occur; monitor complete blood cell count during treatment

                Fatal and/or serious infections reported, including opportunistic infections such as sepsis, pneumonia (including Pneumocystis jiroveci and other fungal pneumonia), herpes virus infection, and cytomegalovirus infection; closely monitor for signs and symptoms of infection

                Progressive multifocal leukoencephalopathy (PML) reported after treatment; monitor for new or worsening neurological, cognitive, or behavioral changes; hold polatuzumab and any concomitant chemotherapy if PML is suspected, and permanently discontinue if diagnosis is confirmed

                Patients with high tumor burden and rapidly proliferative tumor may be at increased risk of tumor lysis syndrome; closely monitor and take appropriate measures, including tumor lysis syndrome prophylaxis

                Serious cases of hepatotoxicity that were consistent with hepatocellular injury, including elevations of transaminases and/or bilirubin, have occurred; preexisting liver disease, elevated baseline liver enzymes, and concomitant medications may increase the risk of hepatotoxicity; monitor liver enzymes and bilirubin level

                Based on the mechanism of action and findings from animal studies, fetal harm may occur when administered to a pregnant woman (see Pregnancy)

                Peripheral neuropathy

                • Peripheral neuropathy, including severe cases, may occur as early as the first cycle of treatment and is a cumulative effect; may exacerbate preexisting peripheral neuropathy
                • Monitor for symptoms of peripheral neuropathy (eg, hypoesthesia, hyperesthesia, paresthesia, dysesthesia, neuropathic pain, burning sensation, weakness, gait disturbance)

                Drug interactions overview

                • MMAE is a CYP3A4 substrate
                • Strong CYP3A inhibitors
                  • Concomitant use with a strong CYP3A4 inhibitor may increase unconjugated MMAE AUC, which may increase polatuzumab vedotin toxicities
                  • Monitor for signs of toxicity
                • Strong CYP3A inducers
                  • Concomitant use with a strong CYP3A4 inducer may decrease unconjugated MMAE AUC
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                Pregnancy

                Pregnancy

                Based on findings from animal studies and its mechanism of action, fetal harm may occur

                No data available for pregnant women to inform a drug-associated risk

                Verify pregnancy status in females of reproductive potential before initiating treatment

                Advise pregnant women of potential fetal risks

                Animal data

                • In animal reproduction studies, administration of the small molecule component of polatuzumab vedotin, MMAE, to pregnant rats during organogenesis at exposures below the clinical exposure at the recommended dose of 1.8 mg/kg every 21 days resulted in embryofetal mortality and structural abnormalities

                Contraception

                • Females of reproductive potential: Use effective contraception during treatment and for 3 months after the final dose
                • Males with female partners of reproductive potential: Based on genotoxicity findings, use effective contraception during treatment and for at least 5 months after the final dose

                Infertility

                • Based on findings from animal studies, male fertility may be impaired; reversibility is unknown

                Lactation

                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 potential for serious adverse reactions in a breastfed children, advise women not to breastfeed during treatment and for at least 2 months after last dose

                Pregnancy Categories

                A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

                B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

                C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

                D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

                X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

                NA: Information not available.

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                Pharmacology

                Mechanism of Action

                CD79b-directed antibody-drug conjugate (ADC) consisting of three components: the humanized immunoglobulin G1 (IgG1) monoclonal antibody specific for human CD79b, the small molecule antimitotic agent MMAE, and a protease cleavable linker maleimidocaproyl-valine-citrulline-p-aminobenzyloxycarbonyl (mc-vc-PAB)

                MMAE is an antimitotic agent covalently attached to the antibody via a cleavable linker

                Monoclonal antibody binds to CD79b, a B-cell specific surface protein, which is a component of the B-cell receptor

                Upon binding CD79b, polatuzumab vedotin-piiq is internalized, and linker is cleaved by lysosomal proteases to enable intracellular delivery of MMAE

                MMAE binds to microtubules and kills dividing cells by inhibiting cell division and inducing apoptosis

                Absorption

                Peak plasma concentration: 803 ng/mL (acMMAE); 6.82 ng/mL (unconjugated MMAE)

                AUC: 1860 ng·day/mL (acMMAE); 52.3 ng·day/mL (unconjugated MMAE)

                Cycle 3 acMMAE AUC were predicted to increase by ~30% over Cycle 1 AUC, and achieved >90% of the Cycle 6 AUC

                Distribution

                Vd (based on population PK analysis): 3.15 L (acMMAE)

                Protein bound (human): 71-77% (MMAE)

                Metabolism

                Has not been studied in humans

                Expected to undergo catabolism to small peptides, amino acids, unconjugated MMAE, and unconjugated MMAE-related catabolites

                MMAE is a CYP3A4 substrate

                Elimination

                Half-life: ~12 days (acMMAE at Cycle 6); ~4 days (unconjugated MMAE ~ 4 days after the first infusion)

                Clearance: 0.9 L/day

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                Administration

                IV Compatibilities

                0.9% NaCl

                0.45% NaCl

                Dextrose 5%

                IV Preparation

                Polatuzumab vedotin is a cytotoxic drug; follow applicable special handling and disposal procedures

                Visually inspect for particulate matter and discoloration prior to administration, whenever solution and container permit

                Reconstitution

                • Reconstitute immediately before dilution
                • Calculate dose, total volume of reconstituted solution required, and number of vials needed
                • Reconstitute each 140-mg vial by slowly injecting 7.2 mL of sterile water for injection with the stream directed toward the inside wall of the vial to obtain a concentration of 20 mg/mL of polatuzumab vedotin
                • Gently swirl vial until completely dissolved; do not shake
                • Inspect reconstituted solution for discoloration and particulate matter; should appear colorless to slightly brown, clear to slightly opalescent, and free of visible particulates
                • Do not use if the reconstituted solution is discolored, cloudy, or contains visible particulates; do not freeze or expose to direct sunlight

                Dilution

                • Dilute polatuzumab vedotin to a final concentration of 0.72-2.7 mg/mL in at least a 50-mL IV infusion bag containing 0.9% NaCl, 0.45% NaCl, or D5W
                • Withdraw the required volume of reconstituted solution and dilute into IV infusion bag
                • Discard any unused portion left in the vial
                • Gently mix IV bag by slowly inverting the bag; do not shake
                • Visually inspect IV bag for particulates and discard if present
                • Limit agitation of diluted product during preparation and transportation to administration site
                • Do not transport diluted product
                • If 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 infusion through an automated system (eg, pneumatic tube, automated cart)

                IV Administration

                IV infusion only

                Administer via dedicated infusion line equipped with sterile, nonpyrogenic, low-protein-binding in-line or add-on filter (0.2- or 0.22-micron pore size) and catheter

                Initial dose: Infuse over 90 minutes; monitor patients for infusion-related reactions during infusion and for at least 90 minutes following completion of initial dose

                Subsequent doses (if previous infusion was well tolerated): Infuse over 30 minutes; monitor during infusion and for at least 30 minutes after completion of infusion

                Premedication

                • If not already premedicated for rituximab product, administer an antihistamine and antipyretic at least 30-60 minutes before polatuzumab vedotin for potential infusion-related reactions
                • Administer prophylaxis for Pneumocystis jiroveci pneumonia and herpes virus during treatment
                • Consider prophylactic GCSF administration for neutropenia
                • Administer tumor lysis syndrome prophylaxis for patients at increased risk of tumor lysis syndrome

                Missed dose

                • If a planned dose is missed, administer as soon as possible
                • Adjust dosing schedule to maintain a 21-day interval between doses

                Storage

                Unused vial: Store refrigerated at 2-8°C (36-46°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

                Reconstituted vial: Refrigerate at 2-8°C (36-46°F) for up to 48 hr or at room temperature (9-25°C [47-77°F]) up to a maximum of 8 hr prior to dilution; discard vial when cumulative storage time prior to dilution exceeds 48 hr

                Diluted solution

                • 0.9% NaCl: Store for up to 24 hr at 2-8°C (36-46°F) or up to 4 hr at room temperature (9-25°C [47-77°F])
                • 0.45% NaCl: Store for up to 18 hr at 2-8°C (36-46°F) or up to 4 hr at room temperature (9-25°C [47-77°F])
                • Dextrose 5%: Store up to 36 hr at 2-8°C (36-46°F) or up to 6 hr at room temperature (9-25°C [47-77°F])
                • Limit transportation to 30 minutes at 9-25°C (47-77°F) or 12 hr at 2-8°C (36-46°F)
                • Protect from light; do not freeze; do not shake
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                Images

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                Patient Handout

                A Patient Handout is not currently available for this monograph.
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                Formulary

                FormularyPatient Discounts

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                To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

                Adding plans allows you to:

                • View the formulary and any restrictions for each plan.
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                • Compare formulary status to other drugs in the same class.
                • Access your plan list on any device – mobile or desktop.

                The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

                Tier Description
                1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
                2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
                3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
                4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
                5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
                6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
                NC NOT COVERED – Drugs that are not covered by the plan.
                Code Definition
                PA Prior Authorization
                Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
                QL Quantity Limits
                Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
                ST Step Therapy
                Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
                OR Other Restrictions
                Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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                Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.