[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Pharmacology](https://durgical.com/en/pharmacology/) › [BCL-2 inhibitors (BH3 mimetics)](https://durgical.com/en/pharmacology/classes/bcl-2-inhibitors/) › Venetoclax # Venetoclax ## BH3 mimetics? BCL-2 inhibitors (BH3 mimetics) ## High alert? An error with this medicine can cause serious harm: double checks and protocols are used. Oral BCL-2 inhibitor that restores apoptosis in CLL and AML cells. Started with a slow dose ramp-up because of tumour lysis syndrome. Updated Nov 1, 2026 ## Quick facts **Group** [BCL-2 inhibitors (BH3 mimetics)](https://durgical.com/en/pharmacology/classes/bcl-2-inhibitors/) **Target** BCL-2, anti-apoptotic protein of the mitochondrial membrane **Used for** Chronic lymphocytic leukaemia **Key effects** Neutropenia · Diarrhoea · Fatigue **Monitor** Tumour lysis tests · Fluid intake · Signs of infection **ATC** L01XX52 No doses: the clinician sets them by the current guideline. On this page - The basics Mechanism of action - Indications - Adverse effects - Pharmacokinetics - Memory aid - Clinical What the labels mean - Safety Contraindications - Key interactions - What is monitored - Administration and safety - Pregnancy and breastfeeding - Nursing care - Study Test yourself - Connections Connections ## Mechanism of action ◆**BCL-2, anti-apoptotic protein of the mitochondrial membrane**Venetoclax ⓘ The crystal structure shows venetoclax in the BH3-binding groove of a human BCL-2 construct. **Target in 3D:** BCL-2, anti-apoptotic protein of the mitochondrial membrane. PDB structure 6O0K (RCSB PDB, public domain). [View the structure at RCSB PDB](https://www.rcsb.org/structure/6O0K) · Drag to rotate · pinch to zoom Venetoclax is a BH3 mimetic: it fills the groove of BCL-2 that normally holds pro-apoptotic BH3-only proteins such as BIM, BID and BAD, with high selectivity over other BCL-2 family members. The released BH3-only proteins move to the mitochondria and trigger BAX/BAK-dependent apoptosis. CLL cells overexpress BCL-2 to survive, so they are especially sensitive. - CLL and AML cells survive by overexpressing BCL-2 - Venetoclax fills the BH3 groove of BCL-2 - Freed BIM and other BH3 proteins activate BAX/BAK - Cytochrome c release and apoptosis ## Indications - Chronic lymphocytic leukaemia or small lymphocytic lymphoma in adults, alone or with obinutuzumab or rituximab. [Chronic lymphocytic leukaemia →](https://durgical.com/en/conditions/chronic-lymphocytic-leukaemia/) - Newly diagnosed acute myeloid leukaemia in adults aged 75 or older, or unfit for intensive chemotherapy, with azacitidine, decitabine or low-dose cytarabine. [Acute leukaemia (AML and ALL) →](https://durgical.com/en/conditions/acute-leukaemia/) ## Adverse effects ### Common - Neutropenia, anaemia, thrombocytopenia - Diarrhoea, nausea, vomiting, constipation - Upper respiratory tract infections - Fatigue - Swelling of the arms or legs ### Serious (rare, important) - Tumour lysis syndrome: hyperkalaemia, hyperphosphataemia, hypocalcaemia, hyperuricaemia, acute kidney injury - Severe neutropenia and serious infections - Embryo-fetal toxicity ## Contraindications - Some drugs must not be combined with it, especially strong CYP3A inhibitors while the dose is being increased - Caution in kidney disease, high uric acid, gout or abnormal potassium, phosphate or calcium (higher risk of tumour lysis) ## Key interactions **Strong CYP3A inhibitors (e.g. ketoconazole, clarithromycin)** Raise venetoclax levels several-fold and the risk of tumour lysis syndrome. **Strong CYP3A inducers (e.g. rifampicin, St John's wort)** Lower venetoclax levels and can cause loss of effect. **Grapefruit, Seville oranges and starfruit** Avoided: they inhibit CYP3A and raise levels. **Vaccines** Not given before, during or after treatment without checking with the doctor; live vaccines are avoided. ## What is monitored - Tumour lysis tests (potassium, phosphate, calcium, uric acid, creatinine) before the first dose and around each dose increase - Complete blood count throughout treatment - Fluid intake and urine output during the ramp-up - Signs of infection ## Administration and safety - Oral, once a day with a meal and water at about the same time each day. - The dose is increased in steps (ramp-up); the right strength for each step is checked carefully. - Extra fluids are taken before and on the days of the first dose and each dose increase. - Swallowed whole; not crushed, chewed or split unless the product instructions allow it. - Hazardous oral chemotherapy: handled with gloves and kept away from children; caregivers who are pregnant avoid handling it. ## Pregnancy and breastfeeding May cause fetal harm; a pregnancy test is done before starting and pregnancy is avoided during and for a time after treatment; breastfeeding is avoided. ## Nursing care - Before each ramp-up step, review the tumour lysis labs and report abnormal results before the dose. - Encourage oral fluids and record intake and output. - Ask about fever, confusion, palpitations, cramps or dark urine. - Teaching: avoid grapefruit, Seville oranges, starfruit and St John's wort; report fever or infection; do not repeat a dose after vomiting. ## Pharmacokinetics **Absorption** Oral; absorption rises several-fold when taken with a meal. **Metabolism** Liver, by CYP3A4/5. **Elimination** Almost entirely in the faeces. **Half-life** About 18 to 26 hours. ## Memory aid «VENETOclax VETOes BCL-2»: veto the survival protein and the cell dies, so start slowly because the dead cells can flood the blood (tumour lysis). ## Test yourself Think of the answer, then tap the question to see it. ## What does venetoclax inhibit? BCL-2, an anti-apoptotic protein; venetoclax is a BH3 mimetic. ## Why is venetoclax started with a gradual dose ramp-up? To reduce the risk of tumour lysis syndrome from rapid death of leukaemic cells. ## Which foods are avoided with venetoclax and why? Grapefruit, Seville oranges and starfruit, because they inhibit CYP3A and raise its levels. ## In AML, which drugs is venetoclax combined with? Azacitidine, decitabine or low-dose cytarabine. [Add to my cards (4)](https://durgical.app/estudiar/?add=/en/pharmacology/venetoclax/) [More Pharmacology questions →](https://durgical.com/en/practice/?f=pharmacology) ## What the labels mean **High alert** An error with this medicine can cause serious harm: double checks and protocols are used. ## Connections ## Related drugs 5 - [Azacitidine](https://durgical.com/en/pharmacology/azacitidine/) - [Rituximab](https://durgical.com/en/pharmacology/rituximab/) - [Ibrutinib](https://durgical.com/en/pharmacology/ibrutinib/) - [Allopurinol](https://durgical.com/en/pharmacology/allopurinol/) - [Rasburicase](https://durgical.com/en/pharmacology/rasburicase/) ## Related conditions 2 - [Chronic lymphocytic leukaemia](https://durgical.com/en/conditions/chronic-lymphocytic-leukaemia/) - [Acute leukaemia (AML and ALL)](https://durgical.com/en/conditions/acute-leukaemia/) [← Back to the class: BCL-2 inhibitors (BH3 mimetics)](https://durgical.com/en/pharmacology/classes/bcl-2-inhibitors/) Educational content on how drugs work; not a prescribing guide and no substitute for a health professional's advice. No doses are given. Sources: [Venetoclax: MedlinePlus Drug Information](https://medlineplus.gov/druginfo/meds/a616028.html) (MedlinePlus (U.S. National Library of Medicine), 2026); [Venetoclax - NCI](https://www.cancer.gov/about-cancer/treatment/drugs/venetoclax) (National Cancer Institute, 2026); [ATCDDD - ATC/DDD Index](https://atcddd.fhi.no/atc_ddd_index/?code=L01XX52) (WHO Collaborating Centre for Drug Statistics Methodology, 2026). ## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake Representative model, for educational purposes only. --- Source: https://durgical.com/en/pharmacology/venetoclax/ License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/pharmacology/venetoclax/