Key points
- Enzalutamide (Xtandi) is a tablet that blocks the effect of male hormone on prostate cancer cells; it is taken once a day [1].
- It is used for prostate cancer that has spread and, in high-risk men, when the PSA rises again after treatment [1].
- In several large studies it helped men live longer or delayed the spread of the disease [1, 2, 3, 4, 5, 6].
- The most common side effects: tiredness, muscle pain, hot flushes, constipation, poor appetite, diarrhoea, high blood pressure and falls or fractures [1].
- Seizures are rare (fewer than 1 in 100 people); if one happens, the drug is stopped for good [1].
- It interacts with many medicines; give your doctor a list of all your medicines and herbal remedies [1].
What is this drug and how does it work?
For physicians
The growth of most prostate cancers depends on male hormones (androgens, such as testosterone). Enzalutamide is an androgen receptor inhibitor that acts at several steps of this receptor's signalling pathway: it competitively blocks androgen binding to the receptor and so inhibits nuclear translocation of the receptor and its binding to DNA [1]. Its main metabolite (N-desmethyl enzalutamide) has similar activity [1].
Enzalutamide was first approved in the United States in 2012 and comes as 40 mg capsules and 40 and 80 mg tablets [1]. It is usually given with testosterone-lowering therapy (GnRH analogues such as leuprolide, or surgical removal of the testes) [1].
Which cancers is it used for?
Your doctor may prescribe this drug for:
- Prostate cancer that has spread and no longer responds to hormone therapy (mCRPC)
- Prostate cancer that has not spread but no longer responds to hormone therapy (nmCRPC)
- Prostate cancer that has spread but still responds to hormone therapy (mCSPC)
- Prostate cancer that has not spread and still responds to hormone therapy, with a high-risk rise in PSA (biochemical recurrence)
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 | Setting |
|---|---|
| Metastatic castration-resistant prostate cancer (mCRPC) | After docetaxel chemotherapy |
| Metastatic castration-resistant prostate cancer (mCRPC) | Before chemotherapy |
| Non-metastatic castration-resistant prostate cancer (nmCRPC) | Rising PSA with a doubling time ≤ 10 months |
| Metastatic castration-sensitive prostate cancer (mCSPC) | With testosterone-lowering therapy |
| Non-metastatic castration-sensitive prostate cancer with high-risk biochemical recurrence | After radical prostatectomy and/or radiotherapy; with leuprolide or alone |
All uses in this table are in the FDA label [1].
| Cancer | Key evidence |
|---|---|
| Metastatic castration-resistant prostate cancer (mCRPC), after docetaxel | AFFIRM [2]: median overall survival 18.4 vs 13.6 months with placebo; HR 0.63 [1] |
| Metastatic castration-resistant prostate cancer (mCRPC), before chemotherapy | PREVAIL [3]: lower risk of death (HR 0.71) and radiographic progression (HR 0.17) vs placebo [1] |
| Non-metastatic castration-resistant prostate cancer (nmCRPC) | PROSPER [4]: median metastasis-free survival 36.6 vs 14.7 months (HR 0.29); median overall survival 67.0 vs 56.3 months (HR 0.73) [1] |
| Metastatic castration-sensitive prostate cancer (mCSPC) | ARCHES [5]: lower risk of radiographic progression (HR 0.39) and death (HR 0.66) vs placebo [1] |
| Non-metastatic castration-sensitive prostate cancer with high-risk biochemical recurrence | EMBARK: 5-year metastasis-free survival 87.3% with enzalutamide + leuprolide vs 71.4% with leuprolide alone (HR 0.42); HR 0.63 for enzalutamide alone [6]. Improved overall survival with the combination (HR 0.60) [1] |
Figures are based on the FDA label (updated analyses) and may differ slightly from the original papers. HR: hazard ratio; a value below 1 means a lower risk of the event with enzalutamide. In TALAPRO-2, adding talazoparib to enzalutamide in first-line mCRPC also improved radiographic progression-free survival (HR 0.63) [7].
How it is taken and dosing
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Treatment regimens and doses: index3 regimens
- Enzalutamide is taken once a day, preferably at the same time each day; you can take it with or without food [1].
- Swallow the capsule or tablet whole with enough water. Do not chew, open or dissolve the capsule; do not cut, crush or chew the tablet [1]. If you have trouble swallowing, tell your doctor; a smaller tablet may be more suitable [1].
- If you have testosterone-lowering injections (such as leuprolide), keep having them during treatment with enzalutamide [1].
- Treatment usually continues until the disease progresses or side effects cannot be tolerated [1]. Never stop the drug or change the dose without talking to your doctor [1].
- Before starting and monitoring: assess predisposing factors for seizures and drugs that lower the seizure threshold; assess and manage cardiovascular risk factors (hypertension, diabetes, dyslipidaemia) and monitor for signs of ischaemic heart disease; assess the risk of falls and fractures and give bone-protective treatment according to guidelines. Effective contraception for men with a partner who could become pregnant, during treatment and for 3 months after the last dose [1].
- Interactions: avoid strong CYP2C8 inhibitors (such as gemfibrozil); if unavoidable, 80 mg once daily. Avoid strong CYP3A4 inducers (such as rifampicin); if unavoidable, 240 mg once daily. After stopping the interacting drug, return to the previous dose [1]. Enzalutamide is a strong CYP3A4 inducer and a moderate CYP2C9 and CYP2C19 inducer: avoid narrow-therapeutic-index substrates of these enzymes [1].
- Dose modification for toxicity: grade 3 or higher or intolerable toxicity: withhold for one week or until grade 2 or lower, then resume at the same or a reduced dose (120 or 80 mg) [1]. Discontinue permanently for seizure, PRES, serious hypersensitivity and grade 3 to 4 ischaemic heart disease [1].
- Administration: at the same time every day, capsule or tablet swallowed whole with enough water (capsules not opened, chewed or dissolved; tablets not cut or crushed). If swallowing is difficult, consider the smaller tablets, and if the patient cannot swallow, stop the drug [1].
- Kidney and liver: no dose adjustment is needed in mild to moderate renal impairment (creatinine clearance 30 mL/min or more) or in hepatic impairment of any severity (Child-Pugh A to C); severe renal impairment and end-stage renal disease have not been studied [1].
For physicians
Standard dosing (FDA label)
Castration-resistant prostate cancer (CRPC, metastatic or non-metastatic)
Before or after docetaxelCycle length: Continuous
Before or after docetaxel [1]
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Continuous | |||
| Enzalutamide | 160 mg | Oral | Once daily, every day (with or without food) |
| GnRH analogue | As per that drug's label | Injection | Continue concurrently (unless bilateral orchiectomy has been done) |
Metastatic castration-sensitive prostate cancer (mCSPC)
With androgen deprivation therapyCycle length: Continuous
With androgen deprivation therapy [1]
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Continuous | |||
| Enzalutamide | 160 mg | Oral | Once daily, every day (with or without food) |
| GnRH analogue | As per that drug's label | Injection | Continue concurrently (unless bilateral orchiectomy has been done) |
Non-metastatic castration-sensitive prostate cancer with high-risk biochemical recurrence (EMBARK)
After radical prostatectomy and/or radiotherapy; with or without a GnRH analogueCycle length: Continuous
After radical prostatectomy and/or radiotherapy; with or without a GnRH analogue [1]
Before prescribing: Shared safety points| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Continuous | |||
| Enzalutamide | 160 mg | Oral | Once daily, every day (with or without food) |
Restart: PSA 2.0 ng/mL or more after radical prostatectomy, or 5.0 ng/mL or more after primary radiotherapy [1].
Evidence: EMBARK (2026), EMBARK (2023)
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.
Side effects
Common side effects
The most common side effects:
- Tiredness and weakness in about half of patients [1].
- Back pain, joint pain, constipation, diarrhoea and poor appetite [1].
- Hot flushes, dizziness, headache and weight loss [1].
- High blood pressure; check your blood pressure regularly [1].
- Falls and fractures are more common; make your home safe and talk to your doctor about strengthening your bones [1].
For physicians
In pooled data from five placebo-controlled trials (AFFIRM, PROSPER, PREVAIL, ARCHES and EMBARK), the most common adverse reactions (≥ 10% and at least 2% more than placebo) were musculoskeletal pain, fatigue, hot flush, constipation, decreased appetite, diarrhoea, hypertension, haemorrhage, falls, fractures and headache [1]. In the same data, hypertension was reported in 14% (vs 7% with placebo), falls in 12% (vs 6%) and fractures in 13% (vs 6%) [1]. The table below shows the frequency of some adverse reactions in the PREVAIL trial (mCRPC patients before chemotherapy) [1].
| Adverse reaction | Enzalutamide (871 patients) | Placebo (844 patients) |
|---|---|---|
| Asthenia and fatigue | 47% | 33% |
| Back pain | 29% | 22% |
| Constipation | 23% | 17% |
| Arthralgia | 21% | 16% |
| Decreased appetite | 19% | 16% |
| Hot flush | 18% | 8% |
| Diarrhoea | 17% | 14% |
| Hypertension | 14% | 4.1% |
| Falls | 13% | 5% |
| Weight loss | 12% | 8% |
| Dizziness | 11% | 7% |
| Headache | 11% | 7% |
Source: the PREVAIL adverse reaction table in the FDA label [1]. In EMBARK, gynaecomastia was reported in 49% and breast tenderness in 35% of patients who took enzalutamide alone (without leuprolide) [1].
Serious side effects
These are less common but serious; tell your team early if you notice any sign of them:
- Seizures (rare); tell your doctor if you have had seizures or a head injury [1].
- A severe headache with confusion, sleepiness or vision problems [1].
- Heart problems: chest pain or pressure, shortness of breath [1].
- An allergic reaction: swelling of the face, lips, tongue or throat [1].
- Difficulty swallowing the tablet or capsule, and severe skin reactions [1].
For physicians
Enzalutamide has no boxed warning, but the FDA label lists these important warnings [1]:
- Seizure: occurred in 0.6% of patients in eight randomised trials and in 2.2% of patients with predisposing factors for seizures. If a seizure occurs, the drug must be stopped permanently [1].
- Posterior reversible encephalopathy syndrome (PRES): presents with symptoms such as seizures, headache, lethargy, confusion and visual disturbance, and requires stopping the drug [1].
- Hypersensitivity reactions: including swelling of the face (0.5%), tongue or lips; pharyngeal oedema has also been reported after marketing [1].
- Ischaemic heart disease: in 3.5% of patients on enzalutamide vs 2% on placebo; grade 3–4 events in 1.8% vs 1.1% [1].
- Falls and fractures: assessment of fracture and fall risk and use of bone-targeted agents according to guidelines is recommended [1].
- Dysphagia or choking: because of the size of the capsule or tablet, severe and even fatal cases have been reported [1].
- Severe cutaneous adverse reactions (such as Stevens-Johnson syndrome, TEN and DRESS) have been reported after marketing [1].
- Enzalutamide may falsely raise digoxin levels with some laboratory methods [1].
When should I call my doctor?
Call your doctor or go to the emergency department straight away if you have [1]:
- A seizure or loss of consciousness
- A severe headache, confusion, reduced alertness, or sudden blurred or reduced vision
- Swelling of the face, lips, tongue or throat
- Chest pain or pressure or any sign of a heart attack
- A fall, severe dizziness or bone pain that could be a fracture
- Difficulty swallowing the tablet or capsule
- A widespread rash, blistering or peeling skin
Interactions, pregnancy and precautions
- Other medicines: the cholesterol drug gemfibrozil raises the level of enzalutamide, and the tuberculosis drug rifampicin lowers it [1]. Enzalutamide itself also reduces the effect of many other medicines, such as the sedative midazolam and the blood thinner warfarin [1]. Tell your doctor and pharmacist about all prescription, over-the-counter and herbal medicines [1].
- Missed dose: take it as soon as you remember; if you miss the whole day, take your usual dose the next day and never take more than the prescribed dose in one day [1].
- Pregnancy and contraception: enzalutamide can harm an unborn baby. Men whose partner could become pregnant should use effective contraception during treatment and for 3 months after the last dose, and use a condom if the partner is pregnant [1]. The drug may reduce male fertility [1].
- Bone health and fall prevention: talk to your doctor about a bone density check and bone-strengthening medicines [1].
- Driving and risky activities: because of the risk of seizures, take care with activities where a sudden loss of consciousness could seriously harm you or others [1].
- Blood pressure and heart: check your blood pressure regularly and manage heart risk factors (diabetes, cholesterol) [1].
Frequently asked questions
Should I take enzalutamide with food?
It does not matter; this drug can be taken with or without food. What matters is taking it at the same time every day, swallowed whole with enough water [1].
Do I stop my hormone injections when I start enzalutamide?
No. In castration-resistant and metastatic castration-sensitive prostate cancer, testosterone-lowering therapy (or a past removal of the testes) must continue. Only in high-risk biochemical recurrence may your doctor prescribe enzalutamide with or without the injections [1].
How common are tiredness and hot flushes?
What should I do if I forget a day?
Take it as soon as you remember that day. If the whole day has passed, take your usual dose the next day and do not double the dose [1].
Can I stop treatment for a while?
Scientific evidence
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Key studies
2 itemsImproved Outcomes with Enzalutamide in Biochemically Recurrent Prostate Cancer
Talazoparib plus enzalutamide in men with first-line metastatic castration-resistant prostate cancer (TALAPRO-2): a randomised, placebo-controlled, phase 3 trial
Clinical guidelines
1 itemAdvanced and metastatic prostate cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up
Related cancer types
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.
- 1XTANDI (enzalutamide) capsules and tablets — Prescribing Information
- 2Increased Survival with Enzalutamide in Prostate Cancer after Chemotherapy
- 3Enzalutamide in Metastatic Prostate Cancer before Chemotherapy
- 4Enzalutamide in Men with Nonmetastatic, Castration-Resistant Prostate Cancer
- 5ARCHES: A Randomized, Phase III Study of Androgen Deprivation Therapy With Enzalutamide or Placebo in Men With Metastatic Hormone-Sensitive Prostate Cancer
- 6
- 7Talazoparib plus enzalutamide in men with first-line metastatic castration-resistant prostate cancer (TALAPRO-2): a randomised, placebo-controlled, phase 3 trial
This page is based on reputable scientific sources and was last updated on 27 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.
Printed from the website; the full and up-to-date version: https://drdabiri.com/en/drugs/enzalutamide/