Polivy

Antineoplastic Monoclonal Antibodies Targeting CD79
Antineoplastic Monoclonal Antibody-Drug Conjugates (ADCs)

Hazardous Drugs Classification
NIOSH (Draft) 2020 List: Table 1
Approved by FDA after NIOSH 2016 list published. The manufacturer recommends this drug be handled as a hazardous drug.
Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
Use double chemotherapy gloves and a protective gown. Prepare in a biological safety cabinet or compounding aseptic containment isolator with a closed system drug transfer device. Eye/face and respiratory protection may be needed during preparation and administration.
Emetic Risk
Minimal

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

Polatuzumab vedotin is available as single-use 30-mg and 140-mg lyophilized powder vials.
Premedicate with an antihistamine and antipyretic prior to the infusion.
If a planned dose is missed, administer as soon as possible, and adjust the schedule of administration to maintain a 21-day interval between doses.
Reconstitution:
Calculate the dose (mg) and the number of vials required.
Reconstitute the 30-mg vial with 1.8 mL of sterile water for injection and the 140-mg vial with 7.2 mL of sterile water for injection to yield a final vial concentration of 20 mg/mL.
Direct the stream of sterile water toward the wall of the vial and not directly at the cake or powder.
Gently swirl the vial to aid in dissolution; do not shake.
The vial solution should be colorless to slightly brown, clear to slightly opalescent, and free of visible particulates.
Storage following reconstitution: store for up to 48 hours refrigerated (2 to 8 degrees C or 36 to 46 degrees F) or up to 8 hours at room temperature (9 to 25 degrees C or 47 to 77 degrees F) prior to dilution. Do not freeze or expose to direct sunlight.
Dilution:
Dilute the calculated dose/volume in at least 50 mL of 0.45% sodium chloride injection, 0.9% sodium chloride injection, or 5% dextrose injection to achieve a final concentration of 0.72 mg/mL to 2.7 mg/mL.
Discard any unused portion left in the vial.
Gently mix by slowly inverting the infusion bag; do not shake.
Do not transport diluted admixture through an automated system (e.g. pneumatic tube or automated cart). If the admixture will be transported to a separate facility, remove air from the infusion bag to prevent aggregation; an infusion set with a vented spike is required to ensure accurate dosing during the infusion if air is removed.
Storage following dilution: For 0.45% sodium chloride injection diluent solutions, store up to 18 hours refrigerated or up to 4 hours at room temperature; for 0.9% sodium chloride injection diluent solutions, store up to 36 hours refrigerated or up to 4 hours at room temperature; or 5% dextrose injection diluent solutions, store up to 36 hours refrigerated or up to 6 hours at room temperature. Do not freeze or expose to direct sunlight.
Limit transportation to 24 hours at 2 to 8 degrees C or 30 minutes at 9 to 25 degrees C; the total storage plus transportation times of the diluted product should not exceed the usual storage duration times.
Intravenous (IV) infusion:
Use a dedicated infusion line containing a sterile, non-pyrogenic, low-protein binding in-line or add-on 0.2-or 0.22-micron filter and catheter for all infusions.
Administer the first IV infusion over 90 minutes; monitor patients for infusion-related reactions during the infusion and for at least 90 minutes following completion of the initial dose.
Administer subsequent infusions over 30 minutes if the previous infusion was well tolerated; monitor patients for infusion-related reactions during the infusion and for at least 30 minutes following the infusion.
Do not mix or administer with other drugs.

lymphopenia / Delayed / 12.0-44.0
neutropenia / Delayed / 39.0-42.0
thrombocytopenia / Delayed / 8.0-40.0
infection / Delayed / 0-32.0
anemia / Delayed / 14.0-24.0
hyperuricemia / Delayed / 0-18.0
sepsis / Delayed / 0-10.0
tumor lysis syndrome (TLS) / Delayed / 0-10.0
hypokalemia / Delayed / 6.0-9.0
leukopenia / Delayed / 0-8.0
diarrhea / Early / 3.9-8.0
pancytopenia / Delayed / 0-7.0
fatigue / Early / 0-5.0
nephrotoxicity / Delayed / 0-4.4
elevated hepatic enzymes / Delayed / 2.1-3.8
fever / Early / 1.4-2.9
vomiting / Early / 1.1-2.9
peripheral neuropathy / Delayed / 0-2.3
anorexia / Delayed / 1.1-2.2
weight loss / Delayed / 0-2.2
hypoalbuminemia / Delayed / 0-2.2
hypocalcemia / Delayed / 0-2.2
infusion-related reactions / Rapid / 0-2.2
constipation / Delayed / 0-1.4
abdominal pain / Early / 0-1.1
nausea / Early / 0-1.1
dyspnea / Early / 0-0.9
rash / Early / 0-0.7
progressive multifocal leukoencephalopathy / Delayed / 0-0.6
musculoskeletal pain / Early / 0-0.5
edema / Delayed / 0-0.5
headache / Early / 0-0.2
pulmonary edema / Early / Incidence not known

hyperamylasemia / Delayed / 0-24.0
pneumonitis / Delayed / 0-10.0
hypophosphatemia / Delayed / 0-9.0
antibody formation / Delayed / 1.4-6.0
blurred vision / Early / 0-1.2
hypotonia / Delayed / Incidence not known
hyperesthesia / Delayed / Incidence not known
oral ulceration / Delayed / Incidence not known
stomatitis / Delayed / Incidence not known
bone pain / Delayed / Incidence not known
fluid retention / Delayed / Incidence not known
peripheral edema / Delayed / Incidence not known

alopecia / Delayed / 0-24.0
cough / Delayed / 0-15.0
dysgeusia / Early / 0-14.0
dizziness / Early / 0-13.0
arthralgia / Delayed / 0-7.0
paresthesias / Delayed / Incidence not known
hyporeflexia / Delayed / Incidence not known
hypoesthesia / Delayed / Incidence not known
dysesthesia / Delayed / Incidence not known
sinusitis / Delayed / Incidence not known
pharyngitis / Delayed / Incidence not known
rhinitis / Early / Incidence not known
laryngitis / Delayed / Incidence not known
myalgia / Early / Incidence not known
back pain / Delayed / Incidence not known
urticaria / Rapid / Incidence not known
chills / Rapid / Incidence not known
pruritus / Rapid / Incidence not known

Polivy

Rx

CD79b-directed antibody and microtubule inhibitor conjugate
Used in combination with other chemotherapy drugs for adults with diffuse large B-cell lymphoma or high-grade B-cell lymphoma
Severe myelosuppression, infection, and hepatotoxicity have been reported

1.8 mg/kg IV on day 1 repeated every 21 days for 6 cycles; administer in combination with bendamustine (90 mg/m2 IV on days 1 and 2) and rituximab (375 mg/m2 IV on day 1). Premedicate with an antihistamine and antipyretic 30 to 60 minutes prior to polatuzumab vedotin. Hold therapy if an infusion-related reaction occurs; an infusion rate reduction or therapy discontinuation may be necessary depending on the severity of the reaction. Administer Pneumocystis jiroveci pneumonia and herpes virus prophylaxis during polatuzumab vedotin therapy. Consider prophylactic granulocyte colony stimulating factor use. Therapy interruption, a dose reduction, or discontinuation may be necessary in patients who severe develop toxicity. The primary endpoint of complete response (CR) rate at the end of treatment, assessed by an independent review committee (IRC), was significantly improved in a randomly assigned cohort of transplant ineligible patients with relapsed or refractory DLBCL who received polatuzumab vedotin plus bendamustine and rituximab (BR) compared with BR alone (40% v 17.5%; p = 0.026) in a randomized phase 2 trial (n = 80; GO29365 trial). At a median follow-up time of 22.3 months, the median progression-free survival (PFS; 9.5 months vs. 3.7 months; hazard ratio (HR) = 0.36; 95% CI, 0.21 to 0.63) and overall survival (OS; 12.4 months vs. 4.7 months; HR = 0.42; 95% CI, 0.24 to 0.75) times were also significantly improved in the polatuzumab vedotin-containing arm. In 106 additional patients who received polatuzumab vedotin plus BR in a single-arm extension cohort (median follow-up, 15.2 months), the IRC-assessed CR rate was 38.7%, the median PFS time was 6.6 months, and the median OS time was 12.5 months. In a pooled analysis of 152 patients (median age, 69 years; range, 24 to 94 years) who received polatuzumab vedotin plus BR, the median number of prior therapies was 2 (range, 1 to 7 therapies).

1.8 mg/kg IV on day 1 repeated every 21 days for 6 cycles. In a randomized clinical trial, polatuzumab vedotin was administered in combination with rituximab (375 mg/m2 IV on day 1 for 8 cycles), cyclophosphamide (750 mg/m2 IV on day 1), doxorubicin (50 mg/m2 IV on day 1) plus prednisone (100 mg PO daily) on days 1, 2, 3, 4, and 5. Premedicate with an antihistamine and antipyretic 30 to 60 minutes prior to polatuzumab vedotin. Hold therapy if an infusion-related reaction occurs; an infusion rate reduction or therapy discontinuation may be necessary depending on the severity of the reaction. Administer Pneumocystis jiroveci pneumonia and herpes virus prophylaxis during polatuzumab vedotin therapy. Prophylactic granulocyte colony stimulating factor use is recommended. Therapy interruption, a dose reduction, or discontinuation may be necessary in patients who develop severe toxicity.

Mild hepatic impairment (total bilirubin level of 1 to 1.5 times the ULN or AST level more than the ULN): No initial dosage adjustment.Moderate or severe hepatic impairment (total bilirubin level greater than 1.5 times the ULN and any AST level): Avoid use.

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

Adagrasib: (Moderate) Monitor for increased polatuzumab vedotin toxicity during coadministration of adagrasib due to the risk of elevated exposure to the cytotoxic component of polatuzumab vedotin, MMAE. MMAE is metabolized by CYP3A and adagrasib is a strong CYP3A inhibitor. Strong CYP3A inhibitors are predicted to increase the exposure of MMAE by 45%.
Amoxicillin; Clarithromycin; Omeprazole: (Moderate) Monitor for increased polatuzumab vedotin toxicity during coadministration of clarithromycin due to the risk of elevated exposure to the cytotoxic component of polatuzumab vedotin, MMAE. MMAE is metabolized by CYP3A4; clarithromycin is a strong CYP3A4 inhibitor. Strong CYP3A4 inhibitors are predicted to increase the exposure of MMAE by 45%.
Apalutamide: (Moderate) Monitor for decreased polatuzumab vedotin efficacy during coadministration of apalutamide due to the risk of decreased exposure to the cytotoxic component of polatuzumab vedotin, MMAE. MMAE is metabolized by CYP3A4; apalutamide is a strong CYP3A4 inducer. Strong CYP3A4 inducers are predicted to decrease the exposure of MMAE by 63%.
Atazanavir: (Moderate) Monitor for increased polatuzumab vedotin toxicity during coadministration of atazanavir due to the risk of elevated exposure to the cytotoxic component of polatuzumab vedotin, MMAE. MMAE is metabolized by CYP3A4; atazanavir is a strong CYP3A4 inhibitor. Strong CYP3A4 inhibitors are predicted to increase the exposure of MMAE by 45%.
Atazanavir; Cobicistat: (Moderate) Monitor for increased polatuzumab vedotin toxicity during coadministration of atazanavir due to the risk of elevated exposure to the cytotoxic component of polatuzumab vedotin, MMAE. MMAE is metabolized by CYP3A4; atazanavir is a strong CYP3A4 inhibitor. Strong CYP3A4 inhibitors are predicted to increase the exposure of MMAE by 45%. (Moderate) Monitor for increased polatuzumab vedotin toxicity during coadministration of cobicistat due to the risk of elevated exposure to the cytotoxic component of polatuzumab vedotin, MMAE. MMAE is metabolized by CYP3A4; cobicistat is a strong CYP3A4 inhibitor. Strong CYP3A4 inhibitors are predicted to increase the exposure of MMAE by 45%.
Carbamazepine: (Moderate) Monitor for decreased polatuzumab vedotin efficacy during coadministration of carbamazepine due to the risk of decreased exposure to the cytotoxic component of polatuzumab vedotin, MMAE. MMAE is metabolized by CYP3A4; carbamazepine is a strong CYP3A4 inducer. Strong CYP3A4 inducers are predicted to decrease the exposure of MMAE by 63%.
Ceritinib: (Moderate) Monitor for increased polatuzumab vedotin toxicity during coadministration of ceritinib due to the risk of elevated exposure to the cytotoxic component of polatuzumab vedotin, MMAE. MMAE is metabolized by CYP3A4; ceritinib is a strong CYP3A4 inhibitor. Strong CYP3A4 inhibitors are predicted to increase the exposure of MMAE by 45%.
Chloramphenicol: (Moderate) Monitor for increased polatuzumab vedotin toxicity during coadministration of chloramphenicol due to the risk of elevated exposure to the cytotoxic component of polatuzumab vedotin, MMAE. MMAE is metabolized by CYP3A4; chloramphenicol is a strong CYP3A4 inhibitor. Strong CYP3A4 inhibitors are predicted to increase the exposure of MMAE by 45%.
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Clarithromycin: (Moderate) Monitor for increased polatuzumab vedotin toxicity during coadministration of clarithromycin due to the risk of elevated exposure to the cytotoxic component of polatuzumab vedotin, MMAE. MMAE is metabolized by CYP3A4; clarithromycin is a strong CYP3A4 inhibitor. Strong CYP3A4 inhibitors are predicted to increase the exposure of MMAE by 45%.
Cobicistat: (Moderate) Monitor for increased polatuzumab vedotin toxicity during coadministration of cobicistat due to the risk of elevated exposure to the cytotoxic component of polatuzumab vedotin, MMAE. MMAE is metabolized by CYP3A4; cobicistat is a strong CYP3A4 inhibitor. Strong CYP3A4 inhibitors are predicted to increase the exposure of MMAE by 45%.
Darunavir: (Moderate) Monitor for increased polatuzumab vedotin toxicity during coadministration of darunavir due to the risk of elevated exposure to the cytotoxic component of polatuzumab vedotin, MMAE. MMAE is metabolized by CYP3A4; darunavir is a strong CYP3A4 inhibitor. Strong CYP3A4 inhibitors are predicted to increase the exposure of MMAE by 45%.
Darunavir; Cobicistat: (Moderate) Monitor for increased polatuzumab vedotin toxicity during coadministration of cobicistat due to the risk of elevated exposure to the cytotoxic component of polatuzumab vedotin, MMAE. MMAE is metabolized by CYP3A4; cobicistat is a strong CYP3A4 inhibitor. Strong CYP3A4 inhibitors are predicted to increase the exposure of MMAE by 45%. (Moderate) Monitor for increased polatuzumab vedotin toxicity during coadministration of darunavir due to the risk of elevated exposure to the cytotoxic component of polatuzumab vedotin, MMAE. MMAE is metabolized by CYP3A4; darunavir is a strong CYP3A4 inhibitor. Strong CYP3A4 inhibitors are predicted to increase the exposure of MMAE by 45%.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Monitor for increased polatuzumab vedotin toxicity during coadministration of cobicistat due to the risk of elevated exposure to the cytotoxic component of polatuzumab vedotin, MMAE. MMAE is metabolized by CYP3A4; cobicistat is a strong CYP3A4 inhibitor. Strong CYP3A4 inhibitors are predicted to increase the exposure of MMAE by 45%. (Moderate) Monitor for increased polatuzumab vedotin toxicity during coadministration of darunavir due to the risk of elevated exposure to the cytotoxic component of polatuzumab vedotin, MMAE. MMAE is metabolized by CYP3A4; darunavir is a strong CYP3A4 inhibitor. Strong CYP3A4 inhibitors are predicted to increase the exposure of MMAE by 45%.
Delavirdine: (Moderate) Monitor for increased polatuzumab vedotin toxicity during coadministration of delavirdine due to the risk of elevated exposure to the cytotoxic component of polatuzumab vedotin, MMAE. MMAE is metabolized by CYP3A4; delavirdine is a strong CYP3A4 inhibitor. Strong CYP3A4 inhibitors are predicted to increase the exposure of MMAE by 45%.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Monitor for increased polatuzumab vedotin toxicity during coadministration of cobicistat due to the risk of elevated exposure to the cytotoxic component of polatuzumab vedotin, MMAE. MMAE is metabolized by CYP3A4; cobicistat is a strong CYP3A4 inhibitor. Strong CYP3A4 inhibitors are predicted to increase the exposure of MMAE by 45%.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Monitor for increased polatuzumab vedotin toxicity during coadministration of cobicistat due to the risk of elevated exposure to the cytotoxic component of polatuzumab vedotin, MMAE. MMAE is metabolized by CYP3A4; cobicistat is a strong CYP3A4 inhibitor. Strong CYP3A4 inhibitors are predicted to increase the exposure of MMAE by 45%.
Enzalutamide: (Moderate) Monitor for decreased polatuzumab vedotin efficacy during coadministration of enzalutamide due to the risk of decreased exposure to the cytotoxic component of polatuzumab vedotin, MMAE. MMAE is metabolized by CYP3A4; enzalutamide is a strong CYP3A4 inducer. Strong CYP3A4 inducers are predicted to decrease the exposure of MMAE by 63%.
Fosamprenavir: (Moderate) Monitor for increased polatuzumab vedotin toxicity during coadministration of fosamprenavir due to the risk of elevated exposure to the cytotoxic component of polatuzumab vedotin, MMAE. MMAE is metabolized by CYP3A4; fosamprenavir is a strong CYP3A4 inhibitor. Strong CYP3A4 inhibitors are predicted to increase the exposure of MMAE by 45%.
Fosphenytoin: (Moderate) Monitor for decreased polatuzumab vedotin efficacy during coadministration of fosphenytoin due to the risk of decreased exposure to the cytotoxic component of polatuzumab vedotin, MMAE. MMAE is metabolized by CYP3A4; fosphenytoin is a strong CYP3A4 inducer. Strong CYP3A4 inducers are predicted to decrease the exposure of MMAE by 63%.
Grapefruit juice: (Moderate) Advise patients to avoid grapefruit juice while taking polatuzumab vedotin due to the risk of elevated exposure to the cytotoxic component of polatuzumab vedotin, MMAE. MMAE is metabolized by CYP3A4; grapefruit juice is a strong CYP3A4 inhibitor. Strong CYP3A4 inhibitors are predicted to increase the exposure of MMAE by 45%.
Idelalisib: (Moderate) Monitor for increased polatuzumab vedotin toxicity during coadministration of idelalisib due to the risk of elevated exposure to the cytotoxic component of polatuzumab vedotin, MMAE. MMAE is metabolized by CYP3A4; idelalisib is a strong CYP3A4 inhibitor. Strong CYP3A4 inhibitors are predicted to increase the exposure of MMAE by 45%.
Indinavir: (Moderate) Monitor for increased polatuzumab vedotin toxicity during coadministration of indinavir due to the risk of elevated exposure to the cytotoxic component of polatuzumab vedotin, MMAE. MMAE is metabolized by CYP3A4; indinavir is a strong CYP3A4 inhibitor. Strong CYP3A4 inhibitors are predicted to increase the exposure of MMAE by 45%.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Moderate) Monitor for decreased polatuzumab vedotin efficacy during coadministration of rifampin due to the risk of decreased exposure to the cytotoxic component of polatuzumab vedotin, MMAE. MMAE is metabolized by CYP3A4; rifampin is a strong CYP3A4 inducer. Rifampin is predicted to decrease the exposure of MMAE by 63%.
Isoniazid, INH; Rifampin: (Moderate) Monitor for decreased polatuzumab vedotin efficacy during coadministration of rifampin due to the risk of decreased exposure to the cytotoxic component of polatuzumab vedotin, MMAE. MMAE is metabolized by CYP3A4; rifampin is a strong CYP3A4 inducer. Rifampin is predicted to decrease the exposure of MMAE by 63%.
Itraconazole: (Moderate) Monitor for increased polatuzumab vedotin toxicity during coadministration of itraconazole due to the risk of elevated exposure to the cytotoxic component of polatuzumab vedotin, MMAE. MMAE is metabolized by CYP3A4; itraconazole is a strong CYP3A4 inhibitor. Strong CYP3A4 inhibitors are predicted to increase the exposure of MMAE by 45%.
Ketoconazole: (Moderate) Monitor for increased polatuzumab vedotin toxicity during coadministration of ketoconazole due to the risk of elevated exposure to the cytotoxic component of polatuzumab vedotin, MMAE. MMAE is metabolized by CYP3A4; ketoconazole is a strong CYP3A4 inhibitor. Ketoconazole is predicted to increase the exposure of MMAE by 45%.
Lansoprazole; Amoxicillin; Clarithromycin: (Moderate) Monitor for increased polatuzumab vedotin toxicity during coadministration of clarithromycin due to the risk of elevated exposure to the cytotoxic component of polatuzumab vedotin, MMAE. MMAE is metabolized by CYP3A4; clarithromycin is a strong CYP3A4 inhibitor. Strong CYP3A4 inhibitors are predicted to increase the exposure of MMAE by 45%.
Levoketoconazole: (Moderate) Monitor for increased polatuzumab vedotin toxicity during coadministration of ketoconazole due to the risk of elevated exposure to the cytotoxic component of polatuzumab vedotin, MMAE. MMAE is metabolized by CYP3A4; ketoconazole is a strong CYP3A4 inhibitor. Ketoconazole is predicted to increase the exposure of MMAE by 45%.
Lopinavir; Ritonavir: (Moderate) Monitor for increased polatuzumab vedotin toxicity during coadministration of ritonavir due to the risk of elevated exposure to the cytotoxic component of polatuzumab vedotin, MMAE. MMAE is metabolized by CYP3A4; ritonavir is a strong CYP3A4 inhibitor. Strong CYP3A4 inhibitors are predicted to increase the exposure of MMAE by 45%.
Lumacaftor; Ivacaftor: (Moderate) Monitor for decreased polatuzumab vedotin efficacy during coadministration of lumacaftor; ivacaftor due to the risk of decreased exposure to the cytotoxic component of polatuzumab vedotin, MMAE. MMAE is metabolized by CYP3A4; lumacaftor; ivacaftor is a strong CYP3A4 inducer. Strong CYP3A4 inducers are predicted to decrease the exposure of MMAE by 63%.
Lumacaftor; Ivacaftor: (Moderate) Monitor for decreased polatuzumab vedotin efficacy during coadministration of lumacaftor; ivacaftor due to the risk of decreased exposure to the cytotoxic component of polatuzumab vedotin, MMAE. MMAE is metabolized by CYP3A4; lumacaftor; ivacaftor is a strong CYP3A4 inducer. Strong CYP3A4 inducers are predicted to decrease the exposure of MMAE by 63%.
Mifepristone: (Moderate) Monitor for increased polatuzumab vedotin toxicity during coadministration of mifepristone due to the risk of elevated exposure to the cytotoxic component of polatuzumab vedotin, MMAE. MMAE is metabolized by CYP3A4; mifepristone is a strong CYP3A4 inhibitor. Strong CYP3A4 inhibitors are predicted to increase the exposure of MMAE by 45%. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
Mitotane: (Moderate) Monitor for decreased polatuzumab vedotin efficacy during coadministration of mitotane due to the risk of decreased exposure to the cytotoxic component of polatuzumab vedotin, MMAE. MMAE is metabolized by CYP3A4; mitotane is a strong CYP3A4 inducer. Strong CYP3A4 inducers are predicted to decrease the exposure of MMAE by 63%.
Nefazodone: (Moderate) Monitor for increased polatuzumab vedotin toxicity during coadministration of nefazodone due to the risk of elevated exposure to the cytotoxic component of polatuzumab vedotin, MMAE. MMAE is metabolized by CYP3A4; nefazodone is a strong CYP3A4 inhibitor. Strong CYP3A4 inhibitors are predicted to increase the exposure of MMAE by 45%.
Nelfinavir: (Moderate) Monitor for increased polatuzumab vedotin toxicity during coadministration of nelfinavir due to the risk of elevated exposure to the cytotoxic component of polatuzumab vedotin, MMAE. MMAE is metabolized by CYP3A4; nelfinavir is a strong CYP3A4 inhibitor. Strong CYP3A4 inhibitors are predicted to increase the exposure of MMAE by 45%.
Nirmatrelvir; Ritonavir: (Moderate) Monitor for increased polatuzumab vedotin toxicity during coadministration of ritonavir due to the risk of elevated exposure to the cytotoxic component of polatuzumab vedotin, MMAE. MMAE is metabolized by CYP3A4; ritonavir is a strong CYP3A4 inhibitor. Strong CYP3A4 inhibitors are predicted to increase the exposure of MMAE by 45%.
Phenobarbital: (Moderate) Monitor for decreased polatuzumab vedotin efficacy during coadministration of phenobarbital due to the risk of decreased exposure to the cytotoxic component of polatuzumab vedotin, MMAE. MMAE is metabolized by CYP3A4; phenobarbital is a strong CYP3A4 inducer. Strong CYP3A4 inducers are predicted to decrease the exposure of MMAE by 63%.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Monitor for decreased polatuzumab vedotin efficacy during coadministration of phenobarbital due to the risk of decreased exposure to the cytotoxic component of polatuzumab vedotin, MMAE. MMAE is metabolized by CYP3A4; phenobarbital is a strong CYP3A4 inducer. Strong CYP3A4 inducers are predicted to decrease the exposure of MMAE by 63%.
Phenytoin: (Moderate) Monitor for decreased polatuzumab vedotin efficacy during coadministration of phenytoin due to the risk of decreased exposure to the cytotoxic component of polatuzumab vedotin, MMAE. MMAE is metabolized by CYP3A4; phenytoin is a strong CYP3A4 inducer. Strong CYP3A4 inducers are predicted to decrease the exposure of MMAE by 63%.
Posaconazole: (Moderate) Monitor for increased polatuzumab vedotin toxicity during coadministration of posaconazole due to the risk of elevated exposure to the cytotoxic component of polatuzumab vedotin, MMAE. MMAE is metabolized by CYP3A4; posaconazole is a strong CYP3A4 inhibitor. Strong CYP3A4 inhibitors are predicted to increase the exposure of MMAE by 45%.
Primidone: (Moderate) Monitor for decreased polatuzumab vedotin efficacy during coadministration of primidone due to the risk of decreased exposure to the cytotoxic component of polatuzumab vedotin, MMAE. MMAE is metabolized by CYP3A4; primidone is a strong CYP3A4 inducer. Strong CYP3A4 inducers are predicted to decrease the exposure of MMAE by 63%.
Ribociclib: (Moderate) Monitor for increased polatuzumab vedotin toxicity during coadministration of ribociclib due to the risk of elevated exposure to the cytotoxic component of polatuzumab vedotin, MMAE. MMAE is metabolized by CYP3A4; ribociclib is a strong CYP3A4 inhibitor. Strong CYP3A4 inhibitors are predicted to increase the exposure of MMAE by 45%.
Ribociclib; Letrozole: (Moderate) Monitor for increased polatuzumab vedotin toxicity during coadministration of ribociclib due to the risk of elevated exposure to the cytotoxic component of polatuzumab vedotin, MMAE. MMAE is metabolized by CYP3A4; ribociclib is a strong CYP3A4 inhibitor. Strong CYP3A4 inhibitors are predicted to increase the exposure of MMAE by 45%.
Rifampin: (Moderate) Monitor for decreased polatuzumab vedotin efficacy during coadministration of rifampin due to the risk of decreased exposure to the cytotoxic component of polatuzumab vedotin, MMAE. MMAE is metabolized by CYP3A4; rifampin is a strong CYP3A4 inducer. Rifampin is predicted to decrease the exposure of MMAE by 63%.
Ritonavir: (Moderate) Monitor for increased polatuzumab vedotin toxicity during coadministration of ritonavir due to the risk of elevated exposure to the cytotoxic component of polatuzumab vedotin, MMAE. MMAE is metabolized by CYP3A4; ritonavir is a strong CYP3A4 inhibitor. Strong CYP3A4 inhibitors are predicted to increase the exposure of MMAE by 45%.
Saquinavir: (Moderate) Monitor for increased polatuzumab vedotin toxicity during coadministration of saquinavir due to the risk of elevated exposure to the cytotoxic component of polatuzumab vedotin, MMAE. MMAE is metabolized by CYP3A4; saquinavir is a strong CYP3A4 inhibitor. Strong CYP3A4 inhibitors are predicted to increase the exposure of MMAE by 45%.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
St. John's Wort, Hypericum perforatum: (Moderate) Monitor for decreased polatuzumab vedotin efficacy during coadministration of St. John's Wort due to the risk of decreased exposure to the cytotoxic component of polatuzumab vedotin, MMAE. MMAE is metabolized by CYP3A4; St. John's Wort is a strong CYP3A4 inducer. Strong CYP3A4 inducers are predicted to decrease the exposure of MMAE by 63%.
Tipranavir: (Moderate) Monitor for increased polatuzumab vedotin toxicity during coadministration of tipranavir/ritonavir due to the risk of elevated exposure to the cytotoxic component of polatuzumab vedotin, MMAE. MMAE is metabolized by CYP3A4; tipranavir boosted with ritonavir is a strong CYP3A4 inhibitor. Strong CYP3A4 inhibitors are predicted to increase the exposure of MMAE by 45%.
Vonoprazan; Amoxicillin; Clarithromycin: (Moderate) Monitor for increased polatuzumab vedotin toxicity during coadministration of clarithromycin due to the risk of elevated exposure to the cytotoxic component of polatuzumab vedotin, MMAE. MMAE is metabolized by CYP3A4; clarithromycin is a strong CYP3A4 inhibitor. Strong CYP3A4 inhibitors are predicted to increase the exposure of MMAE by 45%.
Voriconazole: (Moderate) Monitor for increased polatuzumab vedotin toxicity during coadministration of voriconazole due to the risk of elevated exposure to the cytotoxic component of polatuzumab vedotin, MMAE. MMAE is metabolized by CYP3A4; voriconazole is a strong CYP3A4 inhibitor. Strong CYP3A4 inhibitors are predicted to increase the exposure of MMAE by 45%.

Polatuzumab Vedotin/Polivy Intravenous Inj Pwd: 30mg, 140mg

1.8 mg/kg IV every 21 days.

1.8 mg/kg IV every 21 days.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Polatuzumab vedotin is a CD79b-directed antibody-drug conjugate (ADC) consisting of 3 components including the humanized IgG1 monoclonal antibody specific for human CD79b; the small molecule anti-mitotic agent monomethyl auristatin E (MMAE); and a protease-cleavable linker, maleimidocaproyl-valine-citrulline-p-aminobenzyloxycarbonyl (mc-vc-PAB), that covalently attaches MMAE to the polatuzumab antibody. The anticancer activity of polatuzumab vedotin is due to the binding of the ADC to CD79b expressing B-cells followed by the internalization of the ADC-CD79b complex, and the release of MMAE via selective proteolytic cleavage. MMAE inhibits cell division and induces apoptosis in rapidly dividing cells by binding to microtubules.[64290]

Polatuzumab vedotin is administered intravenously. It is a CD79b-directed antibody-drug conjugate (ADC) consisting of 3 components including the humanized IgG1 monoclonal antibody specific for human CD79b; the small molecule anti-mitotic agent monomethyl auristatin E (MMAE); and a protease-cleavable linker that covalently attaches MMAE to the polatuzumab antibody. The pharmacokinetics of the antibody-conjugated MMAE (acMMAE) and unconjugated MMAE (the cytotoxic component of polatuzumab vedotin) were evaluated. In vitro, the protein binding of MMAE ranges from 71% to 77% and the blood to plasma ratio is 0.79 to 0.98. For acMMAE, the estimated central volume of distribution is 3.15 L, the terminal half-life is 12 (range, 4.5 to 36.7) days at the end of cycle 6, and the predicted clearance is 0.9 L/day. The terminal half-life of unconjugated MMAE is 3.74 (range, 1.58 to 10.1) days after the first polatuzumab vedotin dose. Polatuzumab vedotin likely undergoes catabolism to small peptides, amino acids, unconjugated MMAE, and unconjugated MMAE-related catabolites.
Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4, P-gp
MMAE is a substrate of CYP3A4. Potent inhibitors or inducers of CYP3A4 may alter MMAE exposure; therefore, close monitoring is recommended if polatuzumab vedotin is coadministered with a strong CYP3A4 inhibitor or inducer. Based on physiologically-based pharmacokinetic (PBPK) modeling predictions, MMAE is not expected to affect exposure to midazolam, a sensitive CYP3A4 substrate. MMAE is a P-glycoprotein (P-gp) substrate in vitro.

Following the first dose of polatuzumab vedotin 1.8 mg/kg IV in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), the geometric mean Cmax and AUC values for the antibody-conjugated MMAE (acMMAE) were 688 (coefficient of variation (CV), 15%) ng/mL and 2,040 (CV, 35%) ng X day/mL, respectively; the geometric mean Cmax and AUC values for the unconjugated MMAE were 3.19 (CV, 57%) ng/mL and 31 (CV, 56%) ng X day/mL, respectively. Following the first dose of polatuzumab vedotin 1.8 mg/kg IV in patients with newly diagnosed DLBCL, the geometric mean Cmax and AUC values for the acMMAE were 587 (CV, 15%) ng/mL and 1,690 (CV, 22%) ng X day/mL, respectively; the geometric mean Cmax and AUC values for the unconjugated MMAE were 2.45 (CV, 46%) ng/mL and 20.8 (CV, 50%) ng X day/mL, respectively. Plasma exposures of acMMAE and unconjugated MMAE were dose proportional over a range of 0.1 to 2.4 mg/kg. Compared with cycle 1 values, acMMAE AUC values were predicted to increase by about 30% at cycle 3 and greater than 90% at cycle 6. Unconjugated MMAE AUC values were less than 3% of the acMMAE AUC values and unconjugated MMAE Cmax and AUC values were predicted to decrease after repeated every-3-week dosing.[64290]

Polatuzumab vedotin may cause fetal harm if administered during pregnancy based on its mechanism of action and data from animal studies. Females of reproductive potential should be advised to avoid becoming pregnant while receiving polatuzumab vedotin. If a woman becomes pregnant while taking this drug, she should be apprised of the potential hazard to the fetus. In a study in pregnant rats, embryo-fetal toxicities including death and structural abnormalities (e.g., protruding tongue, malrotated limbs, gastroschisis, and agnathia) were observed at polatuzumab vedotin doses that resulted in maternal exposure that was about 0.5-fold the human exposure at the recommended dose.

Counsel patients about the reproductive risk and contraception requirements during polatuzumab vedotin treatment. Pregnancy testing should be performed prior to starting polatuzumab vedotin in female patients of reproductive potential. These patients should use effective contraception and avoid pregnancy during and for 3 months after polatuzumab vedotin therapy. Women who become pregnant while receiving polatuzumab vedotin should be apprised of the potential hazard to the fetus. Additionally, male patients with a female partner of reproductive potential should use effective contraception during therapy and for 5 months after therapy due to the risk of male-mediated teratogenicity. Polatuzumab vedotin may cause reversible infertility in females based on findings in animal studies with other MMAE-containing antibody-drug conjugates. It may also impair male fertility based on data from animal studies.