Key points
- Venetoclax (Venclexta) is a targeted tablet that removes the barrier blood cancer cells use to avoid dying [1].
- It is used in chronic lymphocytic leukaemia (CLL), and with azacitidine in acute myeloid leukaemia (AML) in older people or patients who cannot tolerate intensive chemotherapy [1].
- At the start of treatment, cancer cells may die suddenly and damage the kidneys; this is why the dose is increased gradually and plenty of water, a preventive medicine and regular blood tests are needed [1].
- In CLL, a fixed one-year course with an antibody controlled the disease longer than chemotherapy [2]; in AML, adding venetoclax helped patients live longer [3].
- It interacts with many medicines; do not eat grapefruit, Seville oranges or starfruit, and give your doctor a list of your medicines [1].
What is this drug and how does it work?
For physicians
Venetoclax, brand name Venclexta, is an oral targeted drug from the group of BCL-2 inhibitors [1]. BCL-2 is a protein that prevents natural cell death (apoptosis). In CLL and AML cells this protein is overproduced, helps the cancer cells survive and has been associated with resistance to chemotherapy [1].
Venetoclax binds directly to BCL-2, releases pro-apoptotic proteins such as BIM, and restarts apoptosis in the cancer cell by permeabilising the outer mitochondrial membrane and activating caspases [1]. Because the drug can kill a large number of cancer cells in a short time, it is started at a low dose and increased gradually [1].
In CLL, venetoclax is often given as fixed-duration treatment with an anti-CD20 antibody (obinutuzumab or rituximab) or with acalabrutinib [1]. The 2026 European Hematology Association (EHA) guideline prefers fixed-duration targeted treatment over continuous treatment in patients without a TP53 abnormality, and considers venetoclax with an anti-CD20 antibody one of the preferred treatments in relapsed CLL [6].
Which cancers is it used for?
Your doctor may prescribe this drug for:
- Previously untreated CLL/SLL [1, 2]
- Previously untreated CLL [1, 5]
- CLL/SLL that has come back or not responded to treatment [1, 4]
- Newly diagnosed AML [1, 3, 7]
Whether it suits you depends on the type and stage of your cancer and your test results. Details of each use are in the section for doctors.
For physicians
| Cancer | Treatment setting | Key evidence |
|---|---|---|
| Previously untreated CLL/SLL | With obinutuzumab; fixed duration of 12 28-day cycles [1] | CLL14 (patients with coexisting conditions): HR for progression-free survival 0.35; 24-month progression-free survival 88.2% vs 64.1% with chlorambucil and obinutuzumab [2] |
| Previously untreated CLL | With acalabrutinib (acalabrutinib cycles 1 to 14, venetoclax from cycle 3 to the end of cycle 14) [1] | AMPLIFY (patients without 17p deletion or TP53 mutation): 36-month progression-free survival 76.5% vs 66.5% with chemoimmunotherapy; HR 0.65 [5] |
| Relapsed or refractory CLL/SLL | With rituximab (venetoclax for 24 months) or as a single agent until disease progression [1] | MURANO: 2-year progression-free survival 84.9% vs 36.3% with bendamustine and rituximab; HR 0.17 [4] |
| Newly diagnosed AML | With azacitidine, decitabine or low-dose cytarabine in people aged 75 or over or unable to have intensive induction chemotherapy [1] | VIALE-A: median overall survival 14.7 vs 9.6 months (HR 0.66); composite complete remission 66.4% vs 28.3% [3]; the ELN 2022 guideline considers this combination the standard first-line treatment for these patients [7] |
The FDA label does not recommend venetoclax with bortezomib and dexamethasone in multiple myeloma outside clinical trials because of increased mortality in the BELLINI trial [1].
How it is taken and dose
Treatment regimens and doses: index5 regimens
- Take venetoclax once a day, with food and water, at about the same time each day [1].
- In the first weeks or days, the dose is increased gradually. To lower the risk of tumour lysis syndrome, your doctor prescribes a uric acid-lowering medicine (such as allopurinol) before you start, and from 2 days before the first dose and with each dose increase you should drink 6 to 8 glasses of water a day [1].
- Blood tests in the first hours after new doses are very important; do not miss them. The medicine may be started in hospital or at the clinic so that you can be monitored [1].
- If you find it hard to swallow tablets, tell your doctor; the drug label gives a specific method for crushing the tablet and mixing it with water, apple juice, apple sauce or yoghurt [1].
- If less than 8 hours have passed since your usual time, take the missed dose as soon as possible; if more than 8 hours have passed, skip it and continue as scheduled the next day. If you vomit after taking it, do not take an extra dose [1].
- Never change the dose yourself or stop the medicine without your doctor's advice [1].
Before starting: assess tumour burden (including CT) and blood chemistry (potassium, uric acid, phosphorus, calcium, creatinine) and correct abnormalities; CLcr below 80 mL/min and splenomegaly increase the risk of TLS. Hydration and allopurinol (or a xanthine oxidase inhibitor) 2 to 3 days before the first dose [1]. Details of hydration and monitoring in CLL/SLL by tumour burden: see the table after the regimens.
Interactions (CLL and AML): strong CYP3A inhibitors are contraindicated in CLL at initiation and during the ramp-up; after that, posaconazole → 70 mg and other strong inhibitors → 100 mg. In AML: posaconazole on days 1 to 4: 10, 20, 50 and 70 mg; other strong inhibitors: 10, 20, 50 and 100 mg. Moderate CYP3A inhibitors or P-gp inhibitors: reduce by at least 50%. Return to the previous dose 2 to 3 days after stopping the inhibitor [1]. CYP3A inducers, P-gp substrates and warfarin: see the section Interactions, pregnancy and precautions.
For physicians
Dose and schedule (FDA label)
Venetoclax + obinutuzumab (CLL14)
Previously untreated (or treated) CLL/SLLCycle length: Every 28 days
Previously untreated (or treated) CLL/SLL
Before prescribing: Prescribing notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Cycle 1 | |||
| Obinutuzumab | Day 1: 100 mg; day 2: 900 mg; days 8 and 15: 1000 mg | IV | Days 1, 2, 8 and 15 |
| Cycles 2 to 6 | |||
| Obinutuzumab | 1000 mg | IV | Day 1 |
| From day 22 of cycle 1 (ramp-up ends on day 28 of cycle 2) | |||
| Venetoclax | Week 1: 20; week 2: 50; week 3: 100; week 4: 200; from week 5: 400 mg | Oral, with food and water | Once a day |
| Cycles 3 to 12 | |||
| Venetoclax | 400 mg | Oral | Daily |
Evidence: CLL14 (2024), CLL14 (2019)
Venetoclax + acalabrutinib (AMPLIFY)
Previously untreated CLLCycle length: Every 28 days
Previously untreated CLL
Before prescribing: Prescribing notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| From day 1 of cycle 1 | |||
| Acalabrutinib | 100 mg | Oral | About every 12 hours |
| From day 1 of cycle 3 | |||
| Venetoclax | Week 1: 20; week 2: 50; week 3: 100; week 4: 200; from week 5: 400 mg | Oral, with food and water | Once a day |
| After the ramp-up | |||
| Venetoclax | 400 mg | Oral | Daily |
Evidence: AMPLIFY (2025)
Venetoclax + rituximab (MURANO)
Relapsed or refractory CLL/SLLCycle length: Every 28 days
Relapsed or refractory CLL/SLL
Before prescribing: Prescribing notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| 5-week ramp-up | |||
| Venetoclax | Week 1: 20; week 2: 50; week 3: 100; week 4: 200; from week 5: 400 mg | Oral, with food and water | Once a day |
| After 7 days of venetoclax 400 mg | |||
| Rituximab | Cycle 1: 375 mg/m²; cycles 2 to 6: 500 mg/m² | IV | Day 1, 6 cycles |
Evidence: MURANO (2025), MURANO (2018)
Single-agent venetoclax
CLL/SLLCycle length: Daily
CLL/SLL
Before prescribing: Prescribing notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| 5-week ramp-up | |||
| Venetoclax | Week 1: 20; week 2: 50; week 3: 100; week 4: 200; from week 5: 400 mg | Oral, with food and water | Once a day |
[1]
Venetoclax + azacitidine or decitabine or low-dose cytarabine (VIALE-A)
Newly diagnosed AML at age 75 or over or with coexisting conditions that preclude intensive induction chemotherapyCycle length: Every 28 days
Newly diagnosed AML at age 75 or over or with coexisting conditions that preclude intensive induction chemotherapy
Before prescribing: Prescribing notes| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Cycle 1 ramp-up | |||
| Venetoclax | Day 1: 100; day 2: 200; day 3: 400 mg; then 400 (with azacitidine or decitabine) or 600 mg (with cytarabine) from day 4 | Oral, with food | Daily, days 1 to 28 |
| Option A | |||
| Azacitidine | 75 mg/m² | IV or subcutaneous | Days 1 to 7 |
| Option B | |||
| Decitabine | 20 mg/m² | IV | Days 1 to 5 |
| Option C | |||
| Low-dose cytarabine | 20 mg/m² | Subcutaneous | Days 1 to 10 |
White cell count below 25×10⁹/L before starting (cytoreduction before treatment if needed). Before remission, usually do not interrupt because of cytopenias (bone marrow assessment is recommended) [1, 3].
Evidence: VIALE-A (2024), VIALE-A (2020)
Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.
Administration: with food and water, at the same time every day; the tablet can be crushed and taken immediately with 120 mL of water, apple juice, apple sauce or yoghurt. A missed dose can be taken within 8 hours; after that it is skipped. Do not take an extra dose after vomiting [1].
Kidney and liver: CLcr 15 mL/min or more and Child-Pugh A and B: no adjustment (but the risk of TLS is higher with renal impairment); Child-Pugh C: reduce the daily dose by 50% and monitor more closely [1].
Dose adjustment in CLL (stepwise reduction on resumption: 400 → 300 → 200 → 100 → 50 → 20 → 10 mg) [1]:
- Blood chemistry changes suggesting TLS: do not give the next day's dose; resolved within 24 to 48 hours: same dose; more than 48 hours or clinical TLS: resume at a lower dose.
- Grade 3 to 4 non-haematological toxicity, or grade 3 neutropenia with infection or fever, or grade 4 haematological toxicity (except lymphopenia): first occurrence, hold until grade 1 or baseline and resume at the same dose; later occurrences at a lower dose. If a dose below 100 mg is needed for more than 2 weeks, consider stopping. (For the combination with acalabrutinib, see the separate table in the label.)
- Interruption of more than 1 week during the ramp-up or more than 2 weeks afterwards: reassess TLS risk and, if needed, restart at a lower dose.
Dose adjustment in AML: grade 4 neutropenia or thrombocytopenia before remission: usually no interruption. First occurrence after remission lasting at least 7 days: delay the next cycle until grade 1 or 2 and resume at the same dose; later occurrences: same dose but each cycle 7 days shorter (for example 21 days instead of 28). Grade 3 to 4 non-haematological toxicity not responding to supportive care: hold until grade 1 or baseline and resume at the same dose [1].
Monitoring: blood chemistry according to TLS risk (table below); in AML before the dose, 6 to 8 hours after each new dose during the ramp-up and 24 hours after reaching the final dose; frequent CBC until cytopenias resolve; signs of infection [1].
| Tumour burden | Hydration | Uric acid-lowering drug | Blood chemistry monitoring |
|---|---|---|---|
| Low: all nodes below 5 cm and ALC below 25×10⁹/L | Oral 1.5 to 2 litres | Allopurinol | Outpatient; first 20 and 50 mg doses: before the dose, at 6 to 8 hours and at 24 hours; later ramp-up doses: before the dose [1] |
| Medium: any node 5 to below 10 cm or ALC 25×10⁹/L or more | Oral 1.5 to 2 litres, and consider IV | Allopurinol | Outpatient as above; with CLcr below 80, consider admission for the first 20 and 50 mg doses [1] |
| High: any node 10 cm or more, or ALC 25×10⁹/L or more with any node 5 cm or more | Oral 1.5 to 2 litres and IV 150 to 200 mL per hour | Allopurinol; with a high baseline uric acid, consider rasburicase | Admission for the first 20 and 50 mg doses: before the dose, at 4, 8, 12 and 24 hours; later doses as an outpatient: before the dose, at 6 to 8 and 24 hours [1] |
Blood chemistry: potassium, uric acid, phosphorus, calcium and creatinine, with prompt review of results. In patients at risk, monitor at 6 to 8 and 24 hours at each dose increase.
Side effects
For physicians
In the CLL/SLL safety population of the FDA label, the most common side effects (20% or more) were neutropenia, thrombocytopenia, anaemia, diarrhoea, nausea, upper respiratory tract infection, cough, musculoskeletal pain, fatigue and oedema [1]. In combination with acalabrutinib (AMPLIFY trial), headache (35%), diarrhoea (33%), musculoskeletal pain (25%) and COVID-19 (21%) were the most common [1]. The table below shows the frequency of some side effects in two key trials, according to the FDA label [1].
| Side effect | CLL14: venetoclax + obinutuzumab (212 people) | VIALE-A: venetoclax + azacitidine (283 people) |
|---|---|---|
| Low neutrophils (neutropenia) | 60% (grade 3 or higher: 56%) [1] | Low neutrophils on laboratory tests: 98% [1] |
| Febrile neutropenia | 6% [1] | 42% [1] |
| Diarrhoea | 28% [1] | 43% [1] |
| Nausea | 19% [1] | 44% [1] |
| Vomiting | 10% [1] | 30% [1] |
| Fatigue | 21% [1] | 31% [1] |
| Pneumonia (lung infection) | 9% [1] | 33% [1] |
| Anaemia | 17% [1] | Low haemoglobin on laboratory tests: 61% [1] |
| Swelling (oedema) | Not reported | 27% [1] |
| Bleeding | Not reported | 27% [1] |
"Not reported" means this side effect is not listed in the label table for that trial. VIALE-A patients were older and had AML, and some side effects are due to the disease itself and to azacitidine.
Serious side effects
These side effects are less common but serious; if you notice any sign of them, tell your team early:
- Tumour lysis syndrome: in the first days and with each dose increase, cancer cells die quickly and may damage the kidneys. The dose is raised slowly over several weeks; drink plenty of water, have your blood tests exactly on time, and report nausea, fever, chills, muscle cramps, palpitations, confusion or passing little urine straight away [1].
- Serious infection such as a lung or blood infection: a temperature of 38 °C, chills or cough [1].
- Harm to an unborn baby [1].
For physicians
The FDA label for venetoclax has no boxed warning, but raises these important warnings [1]:
- Tumour lysis syndrome (TLS): rapid breakdown of cancer cells can raise blood potassium, uric acid and phosphorus, and fatal cases and renal failure needing dialysis have been reported. Laboratory changes can occur 6 to 8 hours after the first dose and each dose increase, and have been reported even after a single 20 mg dose. With the 5-week ramp-up and preventive measures, the rate of TLS in single-agent CLL trials was about 2%, whereas with a faster ramp-up and a higher starting dose it had reached 13% (with deaths and renal failure). In AML with venetoclax and azacitidine (VIALE-A) the rate was 1.1% [1].
- Severe neutropenia: in CLL, grade 3 or 4 neutropenia occurred in 63 to 64% of patients (alone or with obinutuzumab or rituximab), and in AML worsening neutrophil counts were seen in 95 to 100% of patients [1].
- Serious and fatal infections such as pneumonia and sepsis; in VIALE-A, serious adverse reactions were reported in 83% of patients, most often febrile neutropenia (30%), pneumonia (22%) and sepsis (19%) [1].
- Embryo-fetal toxicity: based on animal studies and the mechanism of action [1].
- Increased mortality in multiple myeloma: when venetoclax (outside approved uses) was added to bortezomib and dexamethasone [1].
When should I call my doctor?
If you have any of these symptoms, especially in the first weeks of treatment, after any dose increase or after restarting the medicine, contact your doctor or treatment team straight away [1]:
- Fever, chills or any sign of infection
- Nausea or vomiting, confusion or agitation, shortness of breath
- Seizures or an irregular heartbeat
- Dark or cloudy urine
- Unusual tiredness, muscle or bone pain, or joint pain
Also tell your doctor if you become pregnant or think you might be pregnant [1].
Interactions, pregnancy and precautions
- Other medicines: some medicines, such as antifungals (ketoconazole, posaconazole) and the HIV medicine ritonavir, raise the amount of venetoclax and increase the risk of kidney damage from rapid breakdown of cancer cells. Medicines such as rifampicin (a tuberculosis drug) weaken it and should not be taken with it [1]. Ask your doctor or pharmacist before taking any new medicine, over-the-counter medicine, vitamin or herbal product [1].
- Foods: during treatment do not eat grapefruit or grapefruit products, Seville oranges or starfruit, because they raise the amount of the medicine in the blood [1].
- Warfarin and digoxin: venetoclax increases the effect of the blood thinner warfarin, so clotting tests should be done more often; if you take the heart medicine digoxin, take it at least 6 hours before venetoclax [1].
- Pregnancy and contraception: pregnancy status is checked before starting. Women who could become pregnant should use effective contraception during treatment and for 30 days after the last dose. Venetoclax may impair male fertility [1].
- Breastfeeding: do not breastfeed during treatment and for 1 week after the last dose [1].
- Vaccines: live vaccines should not be given before, during or after treatment until B cells recover, and the response to other vaccines may be weaker [1]. The EHA guideline recommends vaccination against pneumococcus, shingles (varicella zoster), hepatitis B, influenza and COVID-19 in patients with CLL under follow-up [6].
- Keep the tablets in their original packaging [1].
Frequently asked questions
Why does venetoclax start at a low dose and go up slowly?
Venetoclax can kill cancer cells very quickly. Increasing the dose gradually (5 weeks in CLL and 3 to 4 days in AML) reduces the tumour burden step by step and lowers the risk of tumour lysis syndrome [1].
Will I have to take venetoclax for the rest of my life?
Not necessarily. In CLL, venetoclax is taken for 12 cycles with obinutuzumab, 24 months with rituximab and until the end of cycle 14 with acalabrutinib. Single-agent treatment in CLL and treatment of AML continue as long as the medicine works and side effects are tolerable [1].
How much water should I drink?
Can I drink grapefruit juice or Seville orange juice?
No. Grapefruit, Seville oranges (bitter oranges) and starfruit contain substances that raise the level of venetoclax in the blood and should be avoided throughout treatment [1].
What should I do if I miss a dose?
If less than 8 hours have passed since your usual time, take the dose as soon as possible. If more than 8 hours have passed, skip it and take the next dose at the usual time the next day. Never take two doses together [1].
Scientific evidence
Show detailsHide
Key studies
5 itemsEHA Guidelines on management of chronic lymphocytic leukemia and Richter transformation
iwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL
Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN
Azacitidine and Venetoclax in Previously Untreated Acute Myeloid Leukemia
Venetoclax and Obinutuzumab in Patients with CLL and Coexisting Conditions
Related cancer types
Treatment regimens (physicians)
References
7 referencesShow all references, 6 with a study cardClose the reference list
Numbers in the text, such as [1], refer to these sources. Sources with a “Study card” button are summarised in the site’s evidence library.
- 1VENCLEXTA (venetoclax) tablets, for oral use — Prescribing Information
- 2
- 3
- 4
- 5
- 6EHA Guidelines on management of chronic lymphocytic leukemia and Richter transformation
- 7Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN
This page is based on reputable scientific sources and was last updated on 28 October 2026. The content of this website is for educational and informational purposes only and does not replace consultation, diagnosis or treatment by a specialist physician. Consult your treating physician about any treatment decision.
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