Polatuzumab vedotin
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Handling and access
NIOSH hazardous drug
Table 1NIOSH lists polatuzumab vedotin as a hazardous drug. AHFS class: 10:00 antineoplastic agents.
- The package insert includes manufacturer's special handling information (MSHI). Follow it when preparing, administering, and disposing of this drug.
- Biologic (Biologics License Application).
Handle with the precautions your facility uses for hazardous drugs (USP <800>). NIOSH's Managing Hazardous Drug Exposures lists controls by drug form and activity.
Dosing in kidney impairment
This label has no separate kidney-impairment dosing section. Check warnings and clinical pharmacology in the full label.
Dosing in liver impairment
Hepatic Impairment Avoid the administration of POLIVY in patients with moderate or severe hepatic impairment (total bilirubin greater than 1.5 × ULN and any AST). Patients with moderate or severe hepatic impairment are likely to have increased exposure to MMAE, which may increase the risk of adverse reactions. POLIVY has not been studied in patients with moderate or severe hepatic impairment [see Clinical Pharmacology and Warnings and Precautions ].
No adjustment in the starting dose is required when administering POLIVY to patients with mild hepatic impairment (total bilirubin 1 to 1.5 × ULN or AST greater than ULN).
Preparation and administration
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Instructions for Preparation and Administration Reconstitute and further dilute POLIVY prior to intravenous infusion. POLIVY is a hazardous drug. Follow applicable special handling and disposal procedures. 1 Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
Reconstitution Reconstitute immediately before dilution. More than one vial may be needed for a full dose. Calculate the dose, the total volume of reconstituted POLIVY solution required, and the number of POLIVY vials needed. Using a sterile syringe, slowly inject one of the following diluents into the POLIVY vial using the volume provided in Table 4 : Sterile Water for Injection, USP Bacteriostatic Water for Injection, USP 0.9% Sodium Chloride Injection, USP 0.45% Sodium Chloride Injection, USP Direct the stream toward the inside wall of the vial to obtain a concentration of 20 mg/mL of polatuzumab vedotin-piiq. [See table below.] Swirl the vial gently until completely dissolved.
Do not shake . Inspect the reconstituted solution for discoloration and particulate matter. The reconstituted solution should appear colorless to slightly brown, clear to slightly opalescent, and free of visible particulates. Do not use if the reconstituted solution is discolored, is cloudy, or contains visible particulates.
Do not freeze or expose to direct sunlight. If needed, store unused reconstituted POLIVY solution prior to dilution according to the storage conditions and maximum durations specified in Table 5 based on the diluent used for reconstitution. Discard vial when cumulative storage time prior to dilution exceeds 168 hours. [See table below.] Dilution Dilute polatuzumab vedotin-piiq to a final concentration of 0.72 mg/mL to 2.7 mg/mL in an intravenous infusion bag with a minimum volume of 50 mL containing 0.9% Sodium Chloride Injection, USP, 0.45% Sodium Chloride Injection, USP, or 5% Dextrose Injection, USP.
Determine the volume of 20 mg/mL reconstituted solution needed based on the required dose. Withdraw the required volume of reconstituted solution from the POLIVY vial using a sterile syringe and dilute into the intravenous infusion bag. Discard any unused portion left in the vial. Gently mix the intravenous bag by slowly inverting the bag.
Do not shake . Inspect the intravenous bag for particulates and discard if present. If not used immediately, store the diluted POLIVY solution according to the storage conditions and maximum durations specified in Table 6 based on the diluents used for reconstitution and infusion. Discard if storage time exceeds these limits.
Do not freeze or expose to direct sunlight . [See table below.] 36 hours 6 hours Bacteriostatic Water for Injection, USP 0.9% Sodium Chloride Injection, USP 36 hours 4 hours 0.45% Sodium Chloride Injection, USP 18 hours 5% Dextrose Injection, USP 36 hours 0.9% Sodium Chloride Injection, USP 0.9% Sodium Chloride Injection, USP 72 hours 4 hours 0.45% Sodium Chloride Injection, USP 5% Dextrose Injection, USP 0.45% Sodium Chloride Injection, USP 0.9% Sodium Chloride Injection, USP 72 hours 4 hours 0.45% Sodium Chloride Injection, USP 5% Dextrose Injection, USP Limit transportation to 30 minutes at room temperature (9°C to 25°C) or 24 hours refrigerated at 2°C to 8°C (refer to instructions below).
The total storage plus transportation times of the diluted product should not exceed the storage duration specified in Table 6 . Agitation stress can result in aggregation. Limit agitation of diluted product during preparation and transportation to administration site. Do not transport diluted product through an automated system (e.g., pneumatic tube or automated cart).
If the prepared solution will be transported to a separate facility, remove air from the infusion bag to prevent aggregation. If air is removed, an infusion set with a vented spike is required to ensure accurate dosing during the infusion. No incompatibilities have been observed between POLIVY and intravenous infusion bags with product-contacting materials of polyvinyl chloride (PVC) or polyolefins (PO) such as polyethylene (PE) and polypropylene (PP).
No incompatibilities have been observed with infusion sets or infusion aids with product-contacting materials of PVC, PE, polyurethane (PU), polybutadiene (PBD), acrylonitrile butadiene styrene (ABS), polycarbonate (PC), polyetherurethane (PEU), fluorinated ethylene propylene (FEP), or polytetrafluorethylene (PTFE), or with filter membranes composed of polyether sulfone (PES) or polysulfone (PSU).
Administration Administer POLIVY as an intravenous infusion only. Confirm patency of the intravenous line prior to infusion. Monitor for extravasation; if extravasation occurs, stop the infusion and manage medically [see Warnings and Precautions ]. Administer the initial dose of POLIVY over 90 minutes. Monitor patients for infusion-related reactions during the infusion and for a minimum of 90 minutes following completion of the initial dose.
If the previous infusion was well tolerated, the subsequent dose of POLIVY may be administered as a 30-minute infusion and patients should be monitored during the infusion and for at least 30 minutes after completion of the infusion. POLIVY must be administered using a dedicated infusion line equipped with a sterile, non-pyrogenic, low-protein-binding in-line or add-on filter (0.2- or 0.22-micron pore size) and a catheter.
Do not mix POLIVY with or administer as an infusion with other drugs.
| Adverse Reaction | Dosage ModificationStarting dose for POLIVY is 1.8 mg/kg. First dose reduction level is 1.4 mg/kg. Second dose reduction level is 1 mg/kg. No further dose reduction is recommended beyond 1 mg/kg. If further reduction needed discontinue POLIVY. |
|---|---|
| Toxicity graded per National Cancer Institute (NCI) Common Terminology for Adverse Events (CTCAE) version 4.0. | |
| Infusion-Related Reaction Grade 1–3 | Interrupt POLIVY infusion and give supportive treatment. For the first instance of Grade 3 wheezing, bronchospasm, or generalized urticaria, permanently discontinue POLIVY. For recurrent Grade 2 wheezing or urticaria, or for recurrence of any Grade 3 symptoms, permanently discontinue POLIVY. Otherwise, upon complete resolution of symptoms, infusion may be resumed at 50% of the rate achieved prior to interruption. In the absence of infusion related symptoms, the rate of infusion may be escalated in increments of 50 mg/hour every 30 minutes. For the next cycle, infuse POLIVY over 90 minutes. If no infusion-related reaction occurs, subsequent infusions may be administered over 30 minutes. Administer premedication for all cycles. |
| Infusion-Related Reaction Grade 4 | Stop POLIVY infusion immediately. Give supportive treatment. Discontinue POLIVY. |
| NeutropeniaSeverity on Day 1 of any cycle.,If primary cause is lymphoma, dosage delay or reduction may not be needed. Grade 3–4 | Hold all treatment until ANC recovers to greater than or equal to 1,000/microliter. Consider therapeutic G-CSF if neutropenia occurs after prophylactic G-CSF. If ANC recovers to greater than or equal to 1,000/microliter on or before Day 7, resume all treatment without any dose reductions. If ANC recovers to greater than or equal to 1,000/microliter after Day 7:resume all treatmentadminister prophylactic G-CSF in next cycle. If G-CSF was already given, consider a dose reduction of POLIVY. |
| Thrombocytopenia, Grade 3–4 | Hold all treatment until platelets recover to greater than or equal to 75,000/microliter. If platelets recover to greater than or equal to 75,000/microliter on or before Day 7, resume all treatment without any dose reductions. If platelets recover to greater than or equal to 75,000/microliter after Day 7:resume all treatment and consider a dose reduction of POLIVY. |
| Adverse Reaction | Dosage ModificationStarting dose for POLIVY is 1.8 mg/kg. First dose reduction level is 1.4 mg/kg. Second dose reduction level is 1 mg/kg. No further dose reduction is recommended beyond 1 mg/kg. If further reduction needed discontinue POLIVY. |
|---|---|
| Toxicity graded per NCI CTCAE version 4.0. | |
| Peripheral Neuropathy Grade 2–3 | Hold POLIVY dosing until improvement to Grade 1 or lower. If recovered to Grade 1 or lower on or before Day 14, restart POLIVY with the next cycle at a permanently reduced dose of 1.4 mg/kg. If a prior dose reduction to 1.4 mg/kg has occurred, discontinue POLIVY. If not recovered to Grade 1 or lower on or before Day 14, discontinue POLIVY. |
| Peripheral Neuropathy Grade 4 | Discontinue POLIVY. |
| Infusion-Related Reaction Grade 1–3 | Interrupt POLIVY infusion and give supportive treatment. For the first instance of Grade 3 wheezing, bronchospasm, or generalized urticaria, permanently discontinue POLIVY. For recurrent Grade 2 wheezing or urticaria, or for recurrence of any Grade 3 symptoms, permanently discontinue POLIVY. Otherwise, upon complete resolution of symptoms, infusion may be resumed at 50% of the rate achieved prior to interruption. In the absence of infusion related symptoms, the rate of infusion may be escalated in increments of 50 mg/hour every 30 minutes. For the next cycle, infuse POLIVY over 90 minutes. If no infusion-related reaction occurs, subsequent infusions may be administered over 30 minutes. Administer premedication for all cycles. |
| Infusion-Related Reaction Grade 4 | Stop POLIVY infusion immediately. Give supportive treatment. Permanently discontinue POLIVY. |
| NeutropeniaSeverity on Day 1 of any cycle.,If primary cause is lymphoma, dosage delay or reduction may not be needed. Grade 3–4 | Hold all treatment until ANC recovers to greater than 1,000/microliter. If ANC recovers to greater than 1,000/microliter on or before Day 7, resume all treatment without any additional dose reductions. Consider granulocyte colony-stimulating factor prophylaxis for subsequent cycles, if not previously given. If ANC recovers to greater than 1,000/microliter after Day 7:restart all treatment. Consider granulocyte colony-stimulating factor prophylaxis for subsequent cycles, if not previously given. If prophylaxis was given, consider dose reduction of bendamustine.if dose reduction of bendamustine has already occurred, consider dose reduction of POLIVY to 1.4 mg/kg. |
| Thrombocytopenia, Grade 3–4 | Hold all treatment until platelets recover to greater than 75,000/microliter. If platelets recover to greater than 75,000/microliter on or before Day 7, resume all treatment without any additional dose reductions. If platelets recover to greater than 75,000/microliter after Day 7:restart all treatment, with dose reduction of bendamustine.if dose reduction of bendamustine has already occurred, consider dose reduction of POLIVY to 1.4 mg/kg. |
| Strength | Volume of Diluent Required for Reconstitution |
|---|---|
| 30 mg vial | 1.8 mL |
| 140 mg vial | 7.2 mL |
Drug interactions
Check polatuzumab vedotin against a medication listLabel text (2 paragraphs)
Concomitant use of strong CYP3A inhibitors or inducers has the potential to affect the exposure to unconjugated monomethyl auristatin E (MMAE). ( 7.1 )
7.1 Effects of Other Drugs on POLIVY Strong CYP3A Inhibitors Concomitant use with a strong CYP3A4 inhibitor may increase unconjugated MMAE AUC [see Clinical Pharmacology (12.3) ] , which may increase POLIVY toxicities. Monitor patients for signs of toxicity. Strong CYP3A Inducers Concomitant use with a strong CYP3A4 inducer may decrease unconjugated MMAE AUC [see Clinical Pharmacology (12.3) ] .
Contraindications
None. None. ( 4 )
Safety data
Reported adverse events (FAERS)
Liver injury (LiverTox)
E*Likelihood score E*: Suspected but unproven cause of clinically significant liver injury and possibly reactivation of hepatitis B.
Polatuzumab vedotin is a humanized monoclonal antibody conjugate which is used in the therapy of diffuse large B cell or high grade B cell lymphomas. Polatuzumab vedotin has been linked to transient mild-to-moderate serum enzyme elevations during therapy but has not been implicated in cases of clinically apparent liver injury with jaundice.
ABCDEA: well known cause; E: unlikely cause. [HD]: high doses only.
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Risk Summary Based on findings from animal studies and its mechanism of action [see Clinical Pharmacology (12.1) ] , POLIVY can cause fetal harm. There are no available data in pregnant women to inform the drug-associated risk. In animal reproduction studies, administration of the small molecule component of POLIVY, MMAE, to pregnant rats during organogenesis at exposures below the clinical exposure at the recommended dose of 1.8 mg/kg POLIVY every 21 days resulted in embryo-fetal mortality and structural abnormalities (see Data ) . Advise a pregnant woman of the potential risks to a fetus.
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2–4% and 15–20%, respectively. Data Animal Data No embryo-fetal development studies in animals have been performed with polatuzumab vedotin-piiq.
In an embryo-fetal developmental study in pregnant rats, administration of two intravenous doses of MMAE, the small molecule component of POLIVY, on gestational days 6 and 13 caused embryo-fetal mortality and structural abnormalities, including protruding tongue, malrotated limbs, gastroschisis, and agnathia compared to controls at a dose of 0.2 mg/kg (approximately 0.5-fold the human area under the curve [AUC] at the recommended dose).
Breastfeeding (LactMed)
No information is available on the clinical use of polatuzumab vedotin during breastfeeding. Because polatuzumab is a large protein molecule with a molecular weight of about 150,000 Da, the amount in milk is likely to be very low. It is also likely to be partially destroyed in the infant's gastrointestinal tract and absorption by the infant is probably minimal. Vedotin (monomethyl auristatin E) is a small-molecule anticancer drug that might enter milk and be absorbed by the infant. Because of the potential for serious adverse reactions in the breastfed infant, the manufacturer recommends that breastfeeding be discontinued during enfortumab vedotin therapy and for 2 months after the last dose.
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
Price ladder
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