Oral Chronic lymphocytic leukaemia, Small lymphocytic lymphoma
Adult: As monotherapy: 5-week dose titration schedule: Week 1: 20 mg once daily; week 2: 50 mg once daily; week 3: 100 mg once daily; week 4: 200 mg once daily; week 5 and thereafter: 400 mg once daily. In combination with obinutuzumab: Treatment lasts for a total of 12 cycles with each cycle containing 28 days; obinutuzumab treatment begins on day 1 of cycle 1; then the 5-week dose titration schedule must be started on day 22 of cycle 1; the schedule will be completed at the end of cycle 2. After the completion of the schedule, venetoclax is given as 400 mg once daily from day 1 of cycle 3 to the end of cycle 12. In combination with rituximab (after the 5-week dose titration schedule): 400 mg once daily. Continue treatment for 24 months from day 1 of cycle 1 of rituximab. Dose reduction, dosing interruption, or discontinuation may be required according to individual safety and tolerability; treatment recommendations may vary between countries (refer to local or country-specific product guidelines).
Oral Acute myeloid leukaemia
Adult: In newly diagnosed patients with comorbidities who are ineligible for intensive chemotherapy: Day 1: 100 mg once daily; day 2: 200 mg once daily; day 3: 400 mg once daily; day 4 and thereafter: 400 mg once daily in combination with a hypomethylating agent (e.g. azacitidine or decitabine) or 600 mg once daily in combination with low dose cytarabine. Continue treatment until disease progression or unacceptable toxicity occurs.
What are the brands available for Venetoclax in Hong Kong?
Chronic lymphocytic leukaemia; Small lymphocytic lymphoma:
Patients taking strong CYP3A inhibitors: Initiation and dose-titration phase: Contraindicated. Steady daily dose after the dose-titration phase: ≤100 mg (or by at least 75% if the dose is already modified for other reasons). Patients taking moderate CYP3A inhibitor: All phases of dose administration: Reduce the dose by at least 50%.
Acute myeloid leukaemia:
Patients taking strong CYP3A inhibitors: Initiation and dose titration phase: Day 1: 10 mg; day 2: 20 mg; day 3: 50 mg; day 4 and thereafter: ≤100 mg. Steady daily dose after the titration phase: ≤100 mg (or by at least 75% if the dose is already modified for other reasons). Patients taking moderate CYP3A inhibitor: All phases of dose administration: Reduce the dose by at least 50%. Dosage and treatment recommendations may vary among individual products and between countries (refer to specific product guidelines).
Hepatic Impairment
Severe (Child-Pugh class C): Reduce the daily dose by 50%.
Administration
Venetoclax Should be taken with food. Swallow whole, do not chew/crush/break.
Contraindications
Concomitant use with strong CYP3A inhibitor at initiation and during the dose titration phase (particularly in patients with chronic lymphocytic leukaemia or small lymphocytic leukaemia).
Special Precautions
Patient with risk factors for tumour lysis syndrome (e.g. circulating blasts, high leukaemia burden in the bone marrow, elevated LDH levels, reduced renal function [CrCl <80 mL/min], tumour burden, splenomegaly). Concomitant use with moderate and strong CYP3A inhibitors (particularly in patients with acute myeloid leukaemia). Hepatic and renal impairment. Pregnancy and lactation.
Adverse Reactions
Significant: Bone marrow suppression (e.g. neutropenia, thrombocytopenia, anaemia), kidney failure requiring dialysis. Blood and lymphatic system disorders: Febrile neutropenia, lymphopenia. Gastrointestinal disorders: Diarrhoea, vomiting, nausea, constipation, stomatitis, abdominal pain. General disorders and administration site conditions: Fatigue, asthenia, fever. Investigations: Weight decreased; blood creatinine, bilirubin and AST increased. Metabolism and nutrition disorders: Hyperkalaemia, hyperphosphataemia, hypocalcaemia, hyperuricaemia, oedema, decreased appetite. Musculoskeletal and connective tissue disorders: Arthralgia, musculoskeletal pain. Nervous system disorders: Headache, dizziness, syncope. Renal and urinary disorders: UTI. Respiratory, thoracic and mediastinal disorders: URTI, dyspnoea, cough. Vascular disorders: Hypotension. Potentially Fatal: Tumour lysis syndrome, serious infections (e.g. pneumonia and sepsis).
Patient Counseling Information
This drug may cause dizziness and fatigue, if affected, do not drive or operate machinery. Women of childbearing potential must use effective methods of contraception during and for 30 days after treatment.
Monitoring Parameters
Screen for pregnancy status before treatment initiation in women of childbearing potential. Monitor CBC with differential; blood chemistries (e.g. K, phosphorous, Ca, creatinine, uric acid). Assess for tumour lysis syndrome through tumour burden evalutaion (e.g. radiographic evaluation); signs and symptoms of infection; adverse reactions (in patients with hepatic impairment).
Drug Interactions
May increase exposure and risk of tumour lysis syndrome with P-gp inhibitors (e.g. amiodarone, captopril, carvedilol, ciclosporin, felodipine, quercetin, quinidine, ranolazine, ticagrelor). May decrease the serum concentration and therapeutic effect with moderate (e.g. bosentan, efavirenz, etravirine, modafinil, nafcillin) and strong (e.g. carbamazepine, phenytoin, rifampicin) CYP3A4 inducers. May diminish the therapeutic effect of live vaccines. May increase the serum concentration of P-gp substrates (e.g. digoxin, everolimus, sirolimus). Potentially Fatal: Increased serum concentration and risk of tumour lysis syndrome with strong (e.g. itraconazole, ketoconazole, posaconazole, voriconazole, clarithromycin, ritonavir) and moderate (e.g. ciprofloxacin, diltiazem, erythromycin, fluconazole, verapamil) CYP3A inhibitors.
Food Interaction
Increased absorption with food. May increase the plasma concentration with grapefruit products, Seville oranges, and starfruit. May decrease the serum concentration and therapeutic effect with St. John's wort.
Action
Description: Mechanism of Action: Venetoclax, an antineoplastic agent, is a potent and selective inhibitor of B-cell chronic lymphoma 2 (BCL-2). BCL-2 is an anti-apoptopic protein which is overexpressed in chronic lymphocytic leukaemia (CLL) and acute myeloid leukaemia (AML) cells, mediating tumour cell survival and associated with chemotherapy resistance. By blocking this protein's inhibitory effects, subsequent displacement of pro-apoptotic proteins, mitochondrial outer membrane permeabilisation and caspase activation occur, thereby restoring the normal apoptotic process. Pharmacokinetics: Absorption: Increased absorption with food. Time to peak plasma concentration: 5-8 hours. Distribution: Plasma protein binding: Highly protein bound. Metabolism: Metabolised in the liver, mainly by CYP3A4 into M27 (major metabolite). Excretion: Mainly via faeces (>99.9%; approx 21% as unchanged drug); urine (<0.1%). Elimination half-life: Approx 26 hours.
Chemical Structure
Venetoclax Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 49846579, Venetoclax. https://pubchem.ncbi.nlm.nih.gov/compound/Venetoclax. Accessed Nov. 26, 2024.
Storage
Store at or below 30°C. Protect from moisture. This is a cytotoxic drug. Follow applicable procedures for receiving, handling, administration, and disposal.
L01XX52 - venetoclax ; Belongs to the class of other antineoplastic agents. Used in the treatment of cancer.
References
AbbVie Limited. Venclexta 10 mg, 50 mg and 100 mg Tablets data sheet 8 July 2024. Medsafe. http://www.medsafe.govt.nz. Accessed 16/10/2024.Anon. Venetoclax. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 16/10/2024.Brayfield A, Cadart C (eds). Venetoclax. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 16/10/2024.Joint Formulary Committee. Venetoclax. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 16/10/2024.Venclexta Film-coated Tablets 10 mg, 50 mg, 100 mg (AbbVie Sdn Bhd). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 16/10/2024.Venclexta Tablet, Film Coated (AbbVie Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 16/10/2024.Venclyxto 10 mg Film-coated Tablets (AbbVie Ltd). MHRA. https://products.mhra.gov.uk. Accessed 16/10/2024.Venetoclax. UpToDate Lexidrug, Lexi-Drugs Multinational Online. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 16/10/2024.
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