POLIVY Powder for Concentrate for Solution for Infusion

POLIVY Powder for Concentrate for Solution for Infusion is used for: B-Cell Lymphoma

Diffuse Large B-Cell Lymphoma Indicated in combination with bendamustine and a rituximab product for treatment of patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after >2 prior therapies Administer every 21-day cycle for 6 cycles Day 1 Rituximab product 375 mg/m² IV PLUS Bendamustine 90 mg/m² IV PLUS Polatuzumab vedotin 1.8 mg/kg IV May administer drugs in any sequence on Day 1 Day 2 Bendamustine 90 mg/m² IV Hepatic impairment Mild (bilirubin >ULN to ?1.5x ULN or AST >ULN): No adjustment to starting dose Moderate-to-severe (bilirubin >1.5x ULN): Avoid use; patients with moderate or severe hepatic impairment are likely to have increased exposure to MMAE, which may increase the risk of adverse reactions; use has not been studied in such patients

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

IV Preparation Polatuzumab vedotin is a cytotoxic drug; follow applicable special handling and disposal procedures Visually inspect for particulate matter and discoloration prior to administration, whenever solution and container permit Reconstitution Reconstitute immediately before dilution Calculate dose, total volume of reconstituted solution required, and number of vials needed Reconstitute each 140-mg vial by slowly injecting 7.2 mL of sterile water for injection with the stream directed toward the inside wall of the vial to obtain a concentration of 20 mg/mL of polatuzumab vedotin Gently swirl vial until completely dissolved; do not shake Inspect reconstituted solution for discoloration and particulate matter; should appear colorless to slightly brown, clear to slightly opalescent, and free of visible particulates Do not use if the reconstituted solution is discolored, cloudy, or contains visible particulates; do not freeze or expose to direct sunlight Dilution Dilute polatuzumab vedotin to a final concentration of 0.72-2.7 mg/mL in at least a 50-mL IV infusion bag containing 0.9% NaCl, 0.45% NaCl, or D5W Withdraw the required volume of reconstituted solution and dilute into IV infusion bag Discard any unused portion left in the vial Gently mix IV bag by slowly inverting the bag; do not shake Visually inspect IV bag for particulates and discard if present Limit agitation of diluted product during preparation and transportation to administration site Do not transport diluted product If prepared solution will be transported to a separate facility, remove air from the infusion bag to prevent aggregation If air is removed, an infusion set with a vented spike is required to ensure accurate dosing during infusion through an automated system (eg, pneumatic tube, automated cart) IV Administration IV infusion only Administer via dedicated infusion line equipped with sterile, nonpyrogenic, low-protein-binding in-line or add-on filter (0.2- or 0.22-micron pore size) and catheter Initial dose: Infuse over 90 minutes; monitor patients for infusion-related reactions during infusion and for at least 90 minutes following completion of initial dose Subsequent doses (if previous infusion was well tolerated): Infuse over 30 minutes; monitor during infusion and for at least 30 minutes after completion of infusion Premedication If not already premedicated for rituximab product, administer an antihistamine and antipyretic at least 30-60 minutes before polatuzumab vedotin for potential infusion-related reactions Administer prophylaxis for Pneumocystis jiroveci pneumonia and herpes virus during treatment Consider prophylactic GCSF administration for neutropenia Administer tumor lysis syndrome prophylaxis for patients at increased risk of tumor lysis syndrome

Infusion-related reactions reported; delayed infusion-related reactions may occur as late as 24 hr after receiving polatuzumab Serious or severe myelosuppression (eg, neutropenia, thrombocytopenia, anemia) may occur; monitor complete blood cell count during treatment Fatal and/or serious infections reported, including opportunistic infections such as sepsis, pneumonia (including Pneumocystis jiroveci and other fungal pneumonia), herpes virus infection, and cytomegalovirus infection; closely monitor for signs and symptoms of infection Progressive multifocal leukoencephalopathy (PML) reported after treatment; monitor for new or worsening neurological, cognitive, or behavioral changes; hold polatuzumab and any concomitant chemotherapy if PML is suspected, and permanently discontinue if diagnosis is confirmed Patients with high tumor burden and rapidly proliferative tumor may be at increased risk of tumor lysis syndrome; closely monitor and take appropriate measures, including tumor lysis syndrome prophylaxis Serious cases of hepatotoxicity that were consistent with hepatocellular injury, including elevations of transaminases and/or bilirubin, have occurred; preexisting liver disease, elevated baseline liver enzymes, and concomitant medications may increase the risk of hepatotoxicity; monitor liver enzymes and bilirubin level Based on the mechanism of action and findings from animal studies, fetal harm may occur when administered to a pregnant woman 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)

Pregnancy Based on findings from animal studies and its mechanism of action, fetal harm may occur No data available for pregnant women to inform a drug-associated risk Verify pregnancy status in females of reproductive potential before initiating treatment Advise pregnant women of potential fetal risks Animal data In animal reproduction studies, administration of the small molecule component of polatuzumab vedotin, MMAE, to pregnant rats during organogenesis at exposures below the clinical exposure at the recommended dose of 1.8 mg/kg every 21 days resulted in embryofetal mortality and structural abnormalities Contraception Females of reproductive potential: Use effective contraception during treatment and for 3 months after the final dose Males with female partners of reproductive potential: Based on genotoxicity findings, use effective contraception during treatment and for at least 5 months after the final dose Infertility Based on findings from animal studies, male fertility may be impaired; reversibility is unknown Lactation There is no information regarding the presence of polatuzumab vedotin-piiq in human milk, the effects on the breastfed child, or milk production Because of potential for serious adverse reactions in a breastfed children, advise women not to breastfeed during treatment and for at least 2 months after last dose

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

Side effects of Polatuzumab vedotin : >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%)

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

POLIVY 140mg/7ml Powder for Concentrate for Solution for Infusion manufactured by F. Hoffmann-La Roche Ltd.. Its generic name is Polatuzumab vedotin. POLIVY is availble in United Arab Emirates. Farmaco UAE drug index information on POLIVY Powder for Concentrate for Solution for Infusion is not intended for diagnosis, medical advice or treatment; neither intended to be a substitute for the exercise of professional judgment.