IntravenousRefractory diffuse large B-cell lymphoma, Relapsed diffuse large B-cell lymphomaAdult: In combination with bendamustine and rituximab for the treatment of patients who are not candidates for haematopoietic stem cell transplant, or who had received at least 2 prior therapies: 1.8 mg/kg every 21 days for 6 cycles. Max: 240 mg/cycle. Doses to be given via infusion. Initial dose is infused over 90 minutes; if well tolerated, subsequent doses may be infused over 30 minutes. The 3 drugs may be administered in any order on day 1 of each cycle. Premedicate with antihistamine and antipyretic at least 30-60 minutes before infusion. Administer prophylaxis for Pneumocystis jirovecii pneumonia and herpes virus throughout treatment. Dose reduction and dosing interruption or discontinuation may be required according to individual safety and tolerability (refer to detailed product guideline).
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Moderate to severe hepatic impairment (bilirubin >1.5 times the upper limit of normal [ULN]): Contraindicated.
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Reconstitute vial labelled as 30 mg and 140 mg with 1.8 mL and 7.2 mL sterile water for inj respectively, to make a concentration of 20 mg/mL. Slowly add the diluent by directing the stream toward the inside wall of the vial. Gently swirl and do not shake. To prepare the solution for infusion, further dilute the reconstituted solution in at least 50 mL containing 0.9% NaCl, 0.45% NaCl, or dextrose 5% in water to obtain a final concentration of 0.72-2.7 mg/mL. Gently invert the bag to mix.
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Active severe infection. Moderate to severe hepatic impairment (bilirubin >1.5 times the ULN). Lactation. Concomitant administration with live or live-attenuated vaccines.
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Patient with high tumour burden and rapidly proliferative tumour; pre-existing peripheral neuropathy, liver disease, elevated baseline liver enzymes. Consider administration of prophylactic granulocyte colony-stimulating factor (G-CSF) for neutropenia and TLS prophylaxis based on local treatment guidelines as clinically needed. Mild hepatic impairment. Pregnancy.
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Significant: Severe myelosuppression (e.g. neutropenia, febrile neutropenia, thrombocytopenia, anaemia, lymphopenia); peripheral neuropathy, tumour lysis syndrome (TLS), reactivation of latent infection, infusion-related reactions (e.g. fever, chills, dyspnoea, flushing, hypotension, urticaria); hepatotoxicity consistent with hepatocellular injury, including elevated transaminases and/or bilirubin; progressive multifocal leucoencephalopathy (PML).
Blood and lymphatic system disorders: Leucopenia, pancytopenia.
Eye disorders: Blurred vision.
Gastrointestinal disorders: Nausea, vomiting, diarrhoea, constipation, abdominal pain.
General disorders and administration site conditions: Fatigue, asthenia.
Investigations: Decreased weight, increased serum lipase.
Metabolism and nutrition disorders: Hypokalaemia, decreased appetite, hypoalbuminaemia, hypocalcaemia, hypophosphataemia.
Musculoskeletal and connective tissue disorders: Arthralgia.
Nervous system disorders: Dizziness, gait disturbance, paraesthesia, hypoaesthesia.
Respiratory, thoracic and mediastinal disorders: Cough, pneumonitis, upper respiratory tract infection.
Skin and subcutaneous tissue disorders: Pruritus.
Potentially Fatal: Serious infections including opportunistic infections (e.g. pneumonia, including P. jirovecii and other fungal pneumonia; sepsis, bacteraemia, herpes virus infection, cytomegalovirus infection).
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This drug may cause dizziness, tiredness, and nerve damage; if affected, do not drive or operate machinery.
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Confirm pregnancy status in females of childbearing potential prior to starting therapy. Obtain CBC (before and throughout treatment) and LFTs. Perform hepatitis B virus screening with hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), total Ig or IgG, and antibody to hepatitis B surface antigen (anti-HBs) before initiation of therapy. Monitor for signs or symptoms of infusion-related reactions for at least 90 minutes after the 1st dose and at least 30 minutes after completion of subsequent doses. Assess for signs and symptoms of peripheral neuropathy, PML, TLS, and viral, fungal or bacterial infections.
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Strong CYP3A4 inducers (e.g. carbamazepine, phenobarbital, phenytoin, rifampicin) may decrease the exposure of unconjugated MMAE, the cytotoxic component of polatuzumab vedotin. Exposure to unconjugated MMAE may be increased with strong CYP3A4 inhibitors (e.g. ketoconazole, boceprevir, clarithromycin, cobicistat, indinavir, nefazodone), which may increase the risk of toxicities.
Potentially Fatal: May diminish the effects of live or live-attenuated vaccines.
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St. John’s wort may decrease the exposure of unconjugated MMAE.
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Description:
Mechanism of Action: Polatuzumab vedotin is a CD79b-directed antibody-drug conjugate consisting of CD79b-specific humanised IgG1 antibody, monomethyl auristatin E or MMAE (a microtubule disrupting agent), and a protease cleavable linker that covalently conjugates MMAE to polatuzumab antibody. The conjugate binds to CD79b (a B-cell specific cell surface protein usually expressed in mature B cell lymphomas), forms a complex that is internalised within the cell, and releases MMAE. The MMAE binds to the microtubules and disrupts the cellular microtubule network, thus inhibiting cell division and inducing apoptosis.
Pharmacokinetics:
Distribution: Volume of distribution: 3.15 L (antibody-conjugated MMAE [acMMAE]). Plasma protein binding: 71-77% (MMAE).
Metabolism: Expected to undergo catabolism into small peptides, amino acids, unconjugated MMAE, and unconjugated MMAE-related catabolites. MMAE is a substrate for CYP3A4.
Excretion: Terminal elimination half-life: acMMAE: Approx 12 days (at cycle 6); Unconjugated MMAE: Approx 4 days (following 1st dose).
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Store between 2-8°C. Unused reconstituted solution: May store between 2-8°C for up to 48 hours or between 9-25°C for up to 8 hours before dilution. Diluted solution for infusion: May store between 2-8°C for up to 36 hours (diluted in 0.9% NaCl), 18 hours (diluted in 0.45% NaCl), or 36 hours (diluted in dextrose 5% in water); or between 9-25°C for up to 4 hours (diluted in 0.9% or 0.45% NaCl), or 6 hours (diluted in dextrose 5% in water). Do not freeze. Protect from light or direct sunlight. Storage recommendations may vary among countries (refer to detailed product guideline). This is a cytotoxic drug. Follow applicable procedures for receiving, handling, administration, and disposal.
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L01FX14 - polatuzumab vedotin ; Belongs to the class of other monoclonal antibodies and antibody drug conjugates. Used in the treatment of cancer.
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Anon. Polatuzumab Vedotin. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 04/02/2021. Buckingham R (ed). Polatuzumab Vedotin. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 04/02/2021. Joint Formulary Committee. Polatuzumab vedotin. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 04/02/2021. Polivy 140 mg Powder for Concentrate for Solution for Infusion (Roche Hong Kong Ltd). MIMS Hong Kong. http://www.mims.com/hongkong. Accessed 04/02/2021. Polivy Injection, Powder, Lyophilized, for Solution (Genentech, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 04/02/2021. Polivy Powder for Concentrate for Solution for Infusion (Roche Registration GmbH). European Medicines Agency [online]. Accessed 04/02/2021.
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