Dosing & Uses
Dosage Forms & Strengths
injection, lyophilized powder for reconstitution
- 30mgvial (single-dose vial)
- 140mg/vial (single-dose vial)
Diffuse Large B-Cell Lymphoma
Previously untreated
Indicated in combination with a rituximab product, cyclophosphamide, doxorubicin, and prednisone (R-CHP) for 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
Administer every 21-day cycle for 6 cycles
-
Day 1
- Prednisone 10 mg PO, THEN
- Polatuzumab vedotin 1.8 mg/kg IV PLUS
- Cyclophosphamide 750 mg/m2 IV PLUS
- Doxorubicin 50 mg/m2 IV PLUS
- Rituximab product 375 mg/m2 IV PLUS
- May administer drugs in any sequence after administration of prednisone on Day 1
-
Days 2-5
- Prednisone 100 mg PO qDay
Relapsed or refractory
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
- Polatuzumab vedotin 1.8 mg/kg IV PLUS
- Rituximab product 375 mg/m² IV PLUS
- Bendamustine 90 mg/m² IV
- May administer drugs in any sequence on Day 1
-
Day 2
- Bendamustine 90 mg/m² IV
Dosage Modifications
Dose reduction schedule
- First reduction: 1.4 mg/kg
- Second reduction: 1 mg/kg
- No further dose reduction recommended beyond 1 mg/kg
Peripheral neuropathy (previously untreated DLBCL, NOS or HGBL)
- Continue R-CHP if polatuzumab vedotin withheld
- If sensory and motor neuropathy are concurrent, follow guidance for most severe neuropathy
- If grade of sensory and motor neuropathy are the same, follow guidance for motor neuropathy
-
Peripheral sensory neuropathy
- Grade 1: None
- Grade 2: If resolves to Grade <1 before next scheduled dose, resume at same dose level; if Grade 2 persists at next scheduled dose, reduce 1 dose level
- Grade 3: Withhold until Grade <2 and reduce 1 dose level
- Grade 4: Permanently discontinue
-
Peripheral motor neuropathy
- Grade 1: None
- Grade 2 or 3: Withhold until Grade <1 and reduce 1 dose level
- Grade 4: Permanently discontinue
Peripheral neuropathy (r/r DLBCL, NOS)
-
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
- Permanently discontinue for first Grade 3 occurrence (eg, wheezing, bronchospasm, generalized urticaria), recurrent grade 2 wheezing or urticaria, or grade any recurrent Grade 3 symptoms
- Upon complete resolution of symptoms, resume infusion at 50% of the rate achieved before interrupting; if no infusion-related reaction occurs, infusion rate may be titrated in increments of 50 mg/hr q30min
- For the next cycle, infuse over 90 minutes; if no infusion-related reaction occurs, subsequent infusions may be administered over 30 minutes
- Administer premedication for all cycles
-
Grade 4
- Stop infusion immediately; provide supportive care and permanently discontinue
Grade 3-4 neutropenia (previously untreated DLBCL, NOS or HGBL)
- 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
-
If ANC recovers to >1000/mcL after Day 7
- Restart all treatment
- Administer granulocyte colony-stimulating factor (G-CSF) prophylaxis for next cycle
- If G-CSF already given, consider polatuzumab vedotin dose reduction
Grade 3-4 neutropenia (r/r DLBCL, NOS)
- 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 G-CSF prophylaxis for subsequent cycles, if not previously given
-
If ANC recovers to >1000/mcL after Day 7
- Restart all treatment; consider G-CSF 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 (previously untreated DLBCL, NOS or HGBL)
- 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 dose reductions
- If platelets recover to >75,000/mcL after Day 7: Restart all treatment and consider polatuzumab dose reduction
Grade 3-4 thrombocytopenia (r/r DLBCL, NOS)
- 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 (total bilirubin 1 to 1.5 × 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
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (0)
Serious - Use Alternative (3)
- 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 (59)
- 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.
- ceritinib
ceritinib will increase the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- 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.
- levoketoconazole
levoketoconazole 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 (4)
- acetazolamide
acetazolamide will increase the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- anastrozole
anastrozole will increase the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- cyclophosphamide
cyclophosphamide will increase the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- larotrectinib
larotrectinib will increase the level or effect of polatuzumab vedotin by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
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%)
Warnings
Contraindications
None
Cautions
Infusion-related reactions reported; delayed infusion-related reactions may occur as late as 24 hr after receiving polatuzumab; administer an antihistamine and antipyretic prior to administration and monitor patients closely throughout infusion; if an infusion-related reaction occurs, interrupt infusion and institute appropriate medical management
Serious or severe myelosuppression (eg, neutropenia, thrombocytopenia, anemia) may occur; monitor complete blood cell count during treatment; cytopenias may require delay, dose reduction, or discontinuation of therapy; administer prophylactic G-CSF for neutropenia in patients receiving therapy plus R-CHP; consider prophylactic G-CSF administration in patients receiving this drug plus bendamustine and a rituximab product
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; administer prophylaxis for Pneumocystis jiroveci pneumonia and herpesvirus; administer prophylactic G-CSF for neutropenia as recommended
Progressive multifocal leukoencephalopathy (PML) reported after treatment with this drug plus bendamustine and obinutuzumab; 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
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 in animal studies with MMAE-containing antibody-drug conjugates (ADCs), this drug may impair female fertility; the effect on fertility is reversible
- 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.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
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
- Administer prophylactic G-CSF for neutropenia in patients receiving polatuzumab vedotin plus R-CHP; consider prophylactic GCSF administration for neutropenia for polatuzumab vedotin plus bendamustine and rituximab
- 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
Images
Formulary
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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.
- Manage and view all your plans together – even plans in different states.
- Compare formulary status to other drugs in the same class.
- Access your plan list on any device – mobile or desktop.
