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.
Quick facts
- Group
- BCL-2 inhibitors (BH3 mimetics)
- 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.
Mechanism of action
The crystal structure shows venetoclax in the BH3-binding groove of a human BCL-2 construct.
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 →
- 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) →
Adverse effects
Common
- Neutropenia, anaemia, thrombocytopenia
- Diarrhoea, nausea, vomiting, constipation
- Upper respiratory tract infections
- Fatigue
- Swelling of the arms or legs
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.
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.
Connections
← Back to the class: BCL-2 inhibitors (BH3 mimetics)
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 (MedlinePlus (U.S. National Library of Medicine), 2026); Venetoclax - NCI (National Cancer Institute, 2026); ATCDDD - ATC/DDD Index (WHO Collaborating Centre for Drug Statistics Methodology, 2026).
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Representative model, for educational purposes only.