Xtandi (Enzalutamide)
Androgen receptor inhibitor for the treatment of prostate cancer
Quick Facts about Xtandi
Key Takeaways about Xtandi
- Blocks androgen receptors: Xtandi works by preventing testosterone from binding to androgen receptors, stopping cancer cell growth in prostate cancer
- Three approved indications: Used for castration-resistant prostate cancer (metastatic and non-metastatic) and metastatic hormone-sensitive prostate cancer
- Once-daily dosing: The standard dose is 160 mg (four 40 mg or two 80 mg tablets) taken at the same time each day, with or without food
- Seizure risk: Seizures occur in approximately 0.6% of patients; tell your doctor about any history of seizures or medications that lower the seizure threshold
- Multiple drug interactions: Xtandi is a strong CYP3A4 inducer and interacts with many common medications; always inform your doctor about all medicines you take
What Is Xtandi and What Is It Used For?
Xtandi (enzalutamide) is an androgen receptor inhibitor used to treat prostate cancer in adult men. It blocks the action of male hormones (androgens) such as testosterone, which drive prostate cancer cell growth. Xtandi is approved for multiple stages of prostate cancer, from early castration-resistant disease to advanced metastatic cancer.
Xtandi contains the active substance enzalutamide, which belongs to a class of medications known as androgen receptor inhibitors. Prostate cancer is driven by male hormones called androgens, primarily testosterone and dihydrotestosterone (DHT). These hormones bind to androgen receptors on prostate cancer cells, promoting cell division and tumor growth. Even when testosterone levels are reduced through hormonal therapy or surgical castration, prostate cancer cells can continue to use residual androgens or develop mechanisms to activate androgen receptor signaling despite low hormone levels.
Enzalutamide was developed to address this challenge by targeting the androgen receptor at multiple points. Unlike earlier anti-androgens, enzalutamide has a significantly higher binding affinity for the androgen receptor and blocks three critical steps in the signaling pathway: it prevents testosterone from binding to the receptor, inhibits the movement of the activated receptor into the cell nucleus, and blocks the receptor from interacting with DNA to drive gene expression. This triple mechanism of action makes enzalutamide effective even in cancer cells that have developed resistance to other hormonal treatments.
Xtandi is approved and used in the following clinical settings for adult men with prostate cancer:
- Metastatic castration-resistant prostate cancer (mCRPC): Cancer that has spread to other parts of the body and no longer responds to hormonal therapy or surgical castration to lower testosterone levels. This includes patients both before and after chemotherapy with docetaxel.
- Non-metastatic castration-resistant prostate cancer (nmCRPC): Cancer that has not yet spread but shows rapidly rising prostate-specific antigen (PSA) levels despite hormonal therapy. These patients are at high risk for developing metastatic disease.
- Metastatic hormone-sensitive prostate cancer (mHSPC): Cancer that has spread but still responds to hormonal therapy. In this setting, Xtandi is used in combination with androgen deprivation therapy (ADT) to improve outcomes.
How Does Xtandi Work?
Xtandi works by comprehensively blocking the androgen receptor signaling pathway through three distinct mechanisms. First, it competitively inhibits androgen binding to androgen receptors, preventing testosterone and dihydrotestosterone from activating the receptor. Second, it prevents the translocation of the androgen receptor complex from the cytoplasm into the cell nucleus, a critical step required for the receptor to influence gene expression. Third, even if the receptor enters the nucleus, enzalutamide prevents it from binding to DNA and recruiting coactivators needed to switch on genes that promote cancer cell survival and proliferation.
This comprehensive blockade results in reduced proliferation of prostate cancer cells and can induce programmed cell death (apoptosis). The clinical benefit has been demonstrated across multiple large-scale randomized controlled trials, including the AFFIRM trial (post-chemotherapy mCRPC), the PREVAIL trial (pre-chemotherapy mCRPC), the PROSPER trial (nmCRPC), and the ARCHES trial (mHSPC), all of which showed significant improvements in overall survival or radiographic progression-free survival compared with placebo.
In the PREVAIL trial, enzalutamide reduced the risk of death by 29% and the risk of radiographic progression or death by 81% in men with metastatic castration-resistant prostate cancer who had not previously received chemotherapy. These results led to the expansion of its approved indications beyond the post-chemotherapy setting.
What Should You Know Before Taking Xtandi?
Before starting Xtandi, your doctor must assess your seizure risk, liver and kidney function, cardiovascular health, and current medications. Xtandi is contraindicated in women who are or may become pregnant. Several serious warnings apply, including seizure risk, posterior reversible encephalopathy syndrome (PRES), secondary malignancies, and cardiovascular complications.
Contraindications
Xtandi must not be taken if you are allergic (hypersensitive) to enzalutamide or any of the other ingredients in the tablet. Signs of an allergic reaction may include skin rash, swelling of the face, tongue, lips, or throat, and difficulty breathing. If you experience any of these symptoms, stop taking Xtandi and seek immediate medical attention.
Xtandi must not be taken by women who are pregnant or who may become pregnant, as it can cause harm to the developing fetus. Women who are breastfeeding must also not take this medicine. Xtandi is indicated exclusively for use in adult men with prostate cancer and must not be used in children or adolescents.
Warnings and Precautions
Several important warnings and precautions should be considered before and during treatment with Xtandi. Discuss the following with your healthcare provider:
Seizures have been reported in approximately 6 out of 1,000 patients taking Xtandi, compared with fewer than 3 out of 1,000 patients taking placebo. The risk of seizures is higher if you take more than the recommended dose, if you are taking other medications that lower the seizure threshold, or if you have a history of seizures, traumatic brain injury, stroke, brain tumors, or alcoholism. If you experience a seizure during treatment, contact your doctor immediately. Your doctor may decide that you should stop taking Xtandi.
- Posterior Reversible Encephalopathy Syndrome (PRES): Rare reports of PRES, a condition affecting the brain, have been reported in patients treated with Xtandi. Symptoms include seizures, worsening headache, confusion, blindness, or other vision problems. PRES is generally reversible, but if you develop these symptoms, contact your doctor immediately.
- Secondary malignancies: New cancers, including bladder cancer and colorectal cancer, have been reported in patients treated with Xtandi. Contact your doctor promptly if you notice signs of gastrointestinal bleeding, blood in your urine, or a frequent urgent need to urinate.
- Cardiovascular disease: Xtandi may increase the risk of heart rhythm abnormalities (arrhythmias), including QT prolongation. Tell your doctor if you have any heart conditions or if you take medications for heart rhythm disorders. Regular monitoring may be required.
- Severe skin reactions: Serious skin reactions including Stevens-Johnson syndrome and erythema multiforme have been reported. If you develop a rash with blistering, peeling skin, or sores in the mouth, stop taking Xtandi and seek emergency medical care immediately.
- Falls and fractures: Fatigue and dizziness caused by Xtandi can increase the risk of falls, which may lead to fractures. This is especially important for elderly patients and those with bone metastases or osteoporosis.
- Liver problems: Tell your doctor if you have any liver disease. Your doctor may monitor your liver function during treatment.
- Kidney problems: Inform your doctor if you have kidney disease, as dose adjustments may be needed.
If you are taking blood-thinning medications (anticoagulants) such as warfarin, your doctor may need to monitor your blood clotting more frequently, as Xtandi can reduce the effectiveness of these medications.
Pregnancy, Breastfeeding, and Fertility
Xtandi is not intended for use in women. However, it is critical that male patients taking Xtandi understand the reproductive precautions. Enzalutamide can potentially harm an unborn child. If you are sexually active with a woman who is or may become pregnant, you must use a condom and another effective method of contraception during treatment and for 3 months after your last dose. If your partner is already pregnant, use a condom to protect the unborn child.
Xtandi may affect male fertility. Damaged or broken tablets should not be handled by anyone other than the patient or their caregiver. Women who are or may become pregnant should not handle broken tablets without protective gloves.
Driving and Operating Machinery
Xtandi may have a moderate effect on the ability to drive and use machines. Seizures have been reported in patients taking this medication. If you are at higher risk for seizures, discuss with your doctor whether it is safe for you to drive or operate heavy machinery during treatment.
How Does Xtandi Interact with Other Drugs?
Xtandi has significant drug interactions due to its ability to induce liver enzymes (particularly CYP3A4, CYP2C9, and CYP2C19). This can reduce the blood levels and effectiveness of many other medications. Additionally, certain drugs can increase enzalutamide blood levels or raise the risk of seizures when taken together.
Enzalutamide is a potent inducer of CYP3A4 and a moderate inducer of CYP2C9, CYP2C19, and P-glycoprotein (P-gp). This means it can significantly accelerate the metabolism of many other drugs, potentially reducing their effectiveness. It is essential to inform your doctor about all medications you are taking, including prescription drugs, over-the-counter medicines, herbal supplements, and vitamins. Do not start or stop any medication without consulting the prescribing physician.
Drugs That May Increase Seizure Risk
The following classes of medications may increase the risk of seizures when taken together with Xtandi:
- Respiratory medications: aminophylline, theophylline
- Antidepressants: bupropion, amitriptylin, desipramine, doxepin, imipramine, maprotiline, mirtazapine
- Antipsychotics: clozapine, olanzapine, risperidone, ziprasidone, chlorpromazine, lithium
- Opioid analgesics: pethidine (meperidine)
Major Drug Interactions
| Drug / Drug Class | Interaction Type | Clinical Effect | Action Required |
|---|---|---|---|
| Gemfibrozil | CYP2C8 inhibitor increases enzalutamide levels | Increased enzalutamide exposure and toxicity risk | Avoid combination or reduce dose |
| Warfarin, Acenocoumarol | Xtandi induces CYP2C9 metabolism | Reduced anticoagulant effect; increased clotting risk | Monitor INR frequently; dose adjustment |
| Midazolam, Diazepam | CYP3A4 induction reduces benzodiazepine levels | Reduced sedative and anxiolytic effect | May need dose increase; monitor response |
| Omeprazole | CYP2C19 induction reduces PPI levels | Reduced acid suppression | Consider alternative or higher dose |
| Docetaxel, Cabazitaxel | CYP3A4 induction accelerates chemotherapy metabolism | Reduced chemotherapy effectiveness | Discuss with oncologist; dose adjustment |
| Fentanyl, Tramadol | CYP3A4 induction reduces opioid levels | Reduced pain relief | Monitor pain control; adjust dose |
| Digoxin | P-gp induction reduces digoxin levels | Reduced cardiac glycoside effect | Monitor digoxin levels |
| Tacrolimus | CYP3A4 induction reduces tacrolimus levels | Risk of organ rejection in transplant patients | Monitor drug levels closely; avoid if possible |
| Dabigatran | P-gp induction reduces dabigatran levels | Reduced anticoagulation; stroke risk | Consider alternative anticoagulant |
| Levothyroxine | Enzyme induction increases thyroid hormone metabolism | Reduced thyroid hormone levels | Monitor thyroid function; adjust dose |
Additional Interaction Considerations
Xtandi may also affect heart rhythm medications such as quinidine, procainamide, amiodarone, and sotalol. It can increase the risk of arrhythmias when used with other QT-prolonging drugs including methadone, moxifloxacin, and certain antipsychotic medications. Statins such as atorvastatin and simvastatin are metabolized by CYP3A4, and their levels may be reduced by Xtandi. Calcium channel blockers including diltiazem, felodipine, nicardipine, nifedipine, and verapamil may also have reduced effectiveness. HIV protease inhibitors such as indinavir and ritonavir, antibiotics like clarithromycin and doxycycline, antiepileptics including carbamazepine, clonazepam, phenytoin, primidone, and valproic acid, and corticosteroids such as dexamethasone and prednisolone are all subject to interactions with Xtandi.
Always carry a list of all your medications and share it with every healthcare provider involved in your care. Never start or stop any medication without discussing it with the doctor who prescribed Xtandi.
What Is the Correct Dosage of Xtandi?
The recommended dose of Xtandi is 160 mg (four 40 mg tablets or two 80 mg tablets) taken orally once daily at the same time each day. Tablets should be swallowed whole with water and can be taken with or without food. Do not modify the dose without consulting your doctor.
Standard Adult Dosage
Adults (Standard Dose)
Dose: 160 mg once daily
How to take: Four 40 mg tablets or two 80 mg tablets, taken at the same time each day
With food: Can be taken with or without food
Administration: Swallow tablets whole with sufficient water. Do not split, crush, or chew the tablets.
Xtandi is typically prescribed alongside androgen deprivation therapy (medical or surgical castration). Your doctor will determine the most appropriate treatment combination for your specific situation. The tablets should not be handled by anyone other than the patient or their caregiver. Pregnant women or women who may become pregnant must not handle broken or damaged tablets without wearing protective gloves.
Dose Adjustments
In certain situations, your doctor may consider adjusting the dose of Xtandi:
- Strong CYP2C8 inhibitors: If you are taking a strong CYP2C8 inhibitor (such as gemfibrozil), your doctor may reduce the dose to 80 mg once daily.
- Hepatic impairment: No dose adjustment is needed for mild hepatic impairment. For moderate hepatic impairment, limited data are available and caution is advised. Xtandi has not been studied in patients with severe hepatic impairment.
- Renal impairment: No dose adjustment is needed for mild to moderate renal impairment. Caution is advised in severe renal impairment or end-stage renal disease.
- Elderly patients: No dose adjustment is required based on age alone, though elderly patients should be monitored for increased risk of falls and fractures.
Children
Xtandi is not approved for use in children or adolescents. There is no relevant indication for enzalutamide in the pediatric population, and safety and efficacy have not been established in patients under 18 years of age.
Missed Dose
If you forget to take Xtandi at the usual time, take your regular dose as soon as you remember. If you have missed an entire day, take your normal dose the next day. If you miss more than one day, contact your doctor immediately for guidance. Do not take a double dose to make up for a missed dose, as this may increase the risk of side effects, particularly seizures.
Overdose
If you take more tablets than prescribed, stop taking Xtandi and contact your doctor or go to the nearest emergency department. Taking more than the recommended dose may increase the risk of seizures and other serious adverse events. There is no specific antidote for enzalutamide overdose, and treatment is supportive.
Do not stop taking Xtandi unless your doctor tells you to do so. Even if you feel well, discontinuing treatment without medical supervision may allow the cancer to progress. If you have questions about your treatment, speak with your oncologist or urologist.
What Are the Side Effects of Xtandi?
Like all medications, Xtandi can cause side effects, though not everyone experiences them. The most common side effects include fatigue, falls, fractures, hot flashes, and high blood pressure. Serious but less common side effects include seizures, posterior reversible encephalopathy syndrome (PRES), and severe skin reactions.
Side effects are categorized below by how frequently they occur. The frequency categories used are based on international medical convention. It is important to report any new or worsening symptoms to your healthcare provider promptly.
Very Common
- Fatigue and asthenia (weakness)
- Falls
- Bone fractures
- Hot flashes (vasomotor symptoms)
- Hypertension (high blood pressure)
Common
- Headache
- Anxiety
- Dry skin and itching (pruritus)
- Memory impairment and difficulty concentrating
- Ischemic heart disease (coronary artery blockage)
- Gynecomastia (breast enlargement in men)
- Breast tenderness and nipple pain
- Restless legs syndrome
- Cognitive impairment (difficulty thinking clearly)
- Altered taste (dysgeusia)
Uncommon
- Hallucinations
- Low white blood cell count (leukopenia)
- Elevated liver enzymes in blood tests
Rare
- Seizures (convulsions)
- Posterior reversible encephalopathy syndrome (PRES)
Not Known
- Muscle pain, cramping, and weakness
- Back pain
- QT prolongation (changes on ECG)
- Difficulty swallowing, including choking
- Nausea and stomach upset
- Erythema multiforme (target-shaped skin lesions)
- Stevens-Johnson syndrome (severe skin reaction with blistering, peeling, and mucosal sores)
- Rash, vomiting, swelling of face/lips/tongue/throat
- Decreased platelet count (increased bleeding or bruising risk)
- Diarrhea and decreased appetite
Contact your doctor or seek emergency medical care immediately if you experience: a seizure; sudden severe headache with confusion or vision changes (possible PRES); severe skin rash with blistering, peeling, or mouth sores (possible Stevens-Johnson syndrome); signs of a serious allergic reaction such as swelling of the face, lips, tongue, or throat; chest pain or irregular heartbeat; or blood in your urine or stool.
Fatigue is the most commonly reported side effect of Xtandi and can significantly affect quality of life. Mild to moderate physical activity, adequate rest, and structured daily routines can help manage fatigue. Falls are also common, particularly in elderly patients, and may be related to fatigue, dizziness, or muscle weakness. Your healthcare team can recommend fall prevention strategies. Hypertension should be monitored regularly and treated as needed, as uncontrolled high blood pressure increases the risk of cardiovascular events.
Cognitive effects, including memory impairment, difficulty concentrating, and confusion, have been reported by some patients. These symptoms are generally mild to moderate and reversible upon discontinuation. If you notice significant changes in your mental function, discuss these with your doctor. Hot flashes are a very common side effect associated with androgen deprivation and anti-androgen therapy and typically do not require treatment, though strategies are available if they become bothersome.
How Should You Store Xtandi?
Store Xtandi at room temperature. Keep the tablets in their original packaging until use. No special storage conditions are required. Always store medicines out of the sight and reach of children.
Xtandi film-coated tablets should be stored in their original blister packaging to protect them from moisture. There are no special temperature requirements for storage. Do not use the tablets after the expiry date printed on the blister pack and outer carton after "EXP." The expiry date refers to the last day of that month.
Do not dispose of medications via wastewater or household waste. Ask your pharmacist about the proper way to dispose of medications that are no longer needed. These measures help to protect the environment. Unused or expired medication should be returned to a pharmacy for safe disposal in accordance with local regulations.
What Does Xtandi Contain?
Xtandi tablets contain enzalutamide as the active ingredient, available in 40 mg and 80 mg strengths. The tablets contain less than 1 mmol (23 mg) of sodium per tablet and are essentially sodium-free.
Active Ingredient
Each Xtandi 40 mg film-coated tablet contains 40 mg of enzalutamide. Each Xtandi 80 mg film-coated tablet contains 80 mg of enzalutamide.
Inactive Ingredients
The tablet core contains: hypromellose acetate succinate, microcrystalline cellulose, colloidal anhydrous silica, croscarmellose sodium, and magnesium stearate. The film coating contains: hypromellose, talc, macrogol 8000, titanium dioxide (E171), and yellow iron oxide (E172).
Appearance and Pack Sizes
Xtandi 40 mg film-coated tablets are yellow, round, and embossed with "E 40." Each carton contains 112 tablets in 4 wallet blister packs of 28 tablets each. Xtandi 80 mg film-coated tablets are yellow, oval, and embossed with "E 80." Each carton contains 56 tablets in 4 wallet blister packs of 14 tablets each.
This medicine contains less than 1 mmol (23 mg) sodium per film-coated tablet, meaning it is essentially sodium-free. This is relevant for patients on sodium-restricted diets.
Frequently Asked Questions about Xtandi
Xtandi (enzalutamide) is a second-generation androgen receptor inhibitor that differs from older anti-androgens like bicalutamide by having a higher binding affinity and blocking multiple steps in the androgen receptor pathway. Unlike abiraterone (Zytiga), which reduces androgen production by inhibiting CYP17A1, Xtandi directly blocks the androgen receptor. Both drugs are effective for castration-resistant prostate cancer, but they work through different mechanisms. Your oncologist will determine which medication is most appropriate based on your specific disease characteristics and overall health.
While there is no absolute contraindication to alcohol consumption with Xtandi, caution is advised. Alcohol can lower the seizure threshold and may increase the risk of seizures, which is already a known side effect of enzalutamide. Alcohol may also worsen fatigue and dizziness. Discuss alcohol consumption with your doctor, who may recommend limiting or avoiding alcohol during treatment.
The duration of Xtandi treatment varies depending on how well the cancer responds and how well you tolerate the medication. Many patients take Xtandi for months to years. Treatment typically continues for as long as it provides clinical benefit, meaning the cancer is controlled and side effects remain manageable. Your doctor will monitor your progress with regular PSA blood tests and imaging studies to determine whether treatment should continue.
Weight changes are not among the most commonly reported side effects of Xtandi. However, because Xtandi is used in combination with androgen deprivation therapy, which itself can cause metabolic changes including weight gain, fat redistribution, and loss of muscle mass, some patients may experience body composition changes during treatment. Maintaining physical activity and a balanced diet can help manage these effects. Discuss any significant weight changes with your healthcare provider.
Because enzalutamide is a potent enzyme inducer, it can potentially interact with herbal medicines and food supplements, particularly St. John's wort (which is also an enzyme inducer and could further reduce levels of co-administered drugs). Always tell your doctor or pharmacist about any supplements, vitamins, or herbal products you are taking. Some supplements may interfere with the effectiveness or safety of your cancer treatment.
Swallowing difficulties have been reported with Xtandi, including choking events. These were more common with the older capsule formulation than the current film-coated tablets. The tablets should be swallowed whole with plenty of water. If you consistently have difficulty swallowing the tablets, contact your doctor before modifying the tablets in any way. Do not crush, split, or chew the tablets. Your doctor may suggest alternative strategies or formulations to help with administration.
References and Medical Sources
All information in this article is based on internationally recognized medical guidelines, regulatory approvals, and peer-reviewed clinical research. The following sources were used:
- European Medicines Agency (EMA). Summary of Product Characteristics: Xtandi (enzalutamide). EMA/EPAR, 2025. Available at: ema.europa.eu/en/medicines/human/EPAR/xtandi
- U.S. Food and Drug Administration (FDA). Xtandi (enzalutamide) Prescribing Information. FDA, 2025.
- Scher HI, Fizazi K, Saad F, et al. Increased Survival with Enzalutamide in Prostate Cancer after Chemotherapy. N Engl J Med. 2012;367(13):1187-1197. doi:10.1056/NEJMoa1207506
- Beer TM, Armstrong AJ, Rathkopf DE, et al. Enzalutamide in Metastatic Prostate Cancer before Chemotherapy. N Engl J Med. 2014;371(5):424-433. doi:10.1056/NEJMoa1405095
- Hussain M, Fizazi K, Saad F, et al. Enzalutamide in Men with Nonmetastatic, Castration-Resistant Prostate Cancer (PROSPER). N Engl J Med. 2018;378(26):2465-2474. doi:10.1056/NEJMoa1800536
- Armstrong AJ, Szmulewitz RZ, Petrylak DP, et al. ARCHES: A Randomized, Phase III Study of Androgen Deprivation Therapy with Enzalutamide or Placebo in Men with Metastatic Hormone-Sensitive Prostate Cancer. J Clin Oncol. 2019;37(32):2974-2986. doi:10.1200/JCO.19.00799
- National Comprehensive Cancer Network (NCCN). NCCN Clinical Practice Guidelines in Oncology: Prostate Cancer. Version 4.2025.
- European Association of Urology (EAU). EAU Guidelines on Prostate Cancer. 2025 Edition.
- World Health Organization (WHO). WHO Model List of Essential Medicines. 23rd List, 2023.
- British National Formulary (BNF). Enzalutamide Monograph. BMJ Group and Pharmaceutical Press, 2025.
About the Medical Editorial Team
This article has been written and reviewed by the iMedic Medical Editorial Team, consisting of licensed physicians with specialist qualifications in oncology, urology, and clinical pharmacology. Our editorial process follows the GRADE evidence framework and is based on current international guidelines from the EMA, FDA, NCCN, and EAU.
All medical claims in this article are based on Level 1A evidence from randomized controlled trials and systematic reviews published in peer-reviewed journals.
This content has no commercial funding and is not sponsored by any pharmaceutical company. Our editorial team maintains full independence from industry influence.
This article is reviewed and updated regularly to reflect the latest clinical evidence, regulatory updates, and treatment guideline changes.
This page is designed to meet WCAG 2.2 Level AAA accessibility standards, ensuring medical information is available to all users regardless of ability.