Enzalutamide Hexal: Uses, Dosage & Side Effects

What Is Enzalutamide Hexal and What Is It Used For?

Enzalutamide Hexal contains the active substance enzalutamide, a second-generation androgen receptor (AR) signaling inhibitor that represents a major advancement in the treatment of prostate cancer. Prostate cancer is the second most commonly diagnosed cancer in men worldwide, with approximately 1.4 million new cases diagnosed annually according to the World Health Organization (WHO). While early-stage prostate cancer can often be cured with surgery or radiation, advanced prostate cancer that has spread beyond the prostate gland or that continues to progress despite standard hormonal therapy remains a significant clinical challenge.

The growth of prostate cancer cells is primarily driven by androgens, particularly testosterone and dihydrotestosterone (DHT), which bind to the androgen receptor (AR) inside prostate cancer cells. When an androgen binds to the AR, it triggers a cascade of events: the receptor undergoes a conformational change, translocates into the cell nucleus, binds to specific DNA sequences called androgen response elements (AREs), and activates the transcription of genes that promote cell survival, proliferation, and tumor growth. Standard androgen deprivation therapy (ADT) – achieved through either surgical castration (bilateral orchiectomy) or medical castration using gonadotropin-releasing hormone (GnRH) agonists or antagonists – reduces circulating testosterone to very low levels. However, prostate cancer cells can adapt to this low-testosterone environment through multiple mechanisms, including AR overexpression, AR mutations that broaden ligand specificity, intratumoral androgen synthesis, and constitutively active AR splice variants. This leads to the development of castration-resistant prostate cancer (CRPC), in which the AR signaling pathway remains active despite castrate levels of testosterone.

Enzalutamide was specifically designed to target the AR signaling pathway at multiple critical steps. Unlike first-generation antiandrogens such as bicalutamide, which primarily block androgen binding to the AR but can have partial agonist activity (particularly in the setting of AR overexpression), enzalutamide is a pure antagonist that inhibits the AR at three key points: (1) it competitively inhibits androgen binding to the AR with 5- to 8-fold higher binding affinity than bicalutamide; (2) it prevents nuclear translocation of the activated AR; and (3) it blocks binding of the AR to DNA and impairs co-activator recruitment, thereby preventing AR-mediated gene transcription. This triple mechanism of action makes enzalutamide significantly more effective than first-generation antiandrogens in suppressing AR-driven tumor growth.

Enzalutamide Hexal is approved for the following indications in adult men:

• Metastatic castration-resistant prostate cancer (mCRPC): Treatment of adult men whose disease has progressed despite androgen deprivation therapy and has spread to other parts of the body. Enzalutamide can be used both before and after docetaxel chemotherapy in this setting.
• Non-metastatic castration-resistant prostate cancer (nmCRPC): Treatment of adult men at high risk of developing metastases, defined as a prostate-specific antigen doubling time (PSA-DT) of 10 months or less, whose disease has progressed despite ADT but has not yet spread to other organs on conventional imaging.
• Metastatic hormone-sensitive prostate cancer (mHSPC): Treatment of adult men with newly diagnosed metastatic prostate cancer that still responds to hormone therapy, in combination with ADT. This indication expands the use of enzalutamide to an earlier stage of the disease.

The efficacy of enzalutamide has been established in four major phase III clinical trials that together enrolled more than 8,000 patients:

• AFFIRM trial: This landmark study randomized 1,199 patients with mCRPC who had previously received docetaxel chemotherapy to enzalutamide 160 mg/day or placebo. Enzalutamide demonstrated a 37% reduction in the risk of death (hazard ratio 0.63), with median overall survival of 18.4 months versus 13.6 months for placebo. The trial was stopped early because of the clear survival benefit.
• PREVAIL trial: This study randomized 1,717 chemotherapy-naive patients with mCRPC to enzalutamide or placebo. Enzalutamide reduced the risk of death by 29% (HR 0.71) and reduced the risk of radiographic progression or death by 81% (HR 0.19). Median overall survival was 35.3 months versus 31.3 months.
• PROSPER trial: This study enrolled 1,401 patients with nmCRPC at high risk of metastasis (PSA-DT ≤ 10 months). Enzalutamide extended metastasis-free survival by 22 months compared with placebo (36.6 vs. 14.7 months; HR 0.29) and subsequently demonstrated an overall survival benefit (67.0 vs. 56.3 months; HR 0.73).
• ARCHES trial: This study randomized 1,150 patients with mHSPC to enzalutamide plus ADT or placebo plus ADT. Enzalutamide reduced the risk of radiographic progression or death by 61% (HR 0.39) and later demonstrated an overall survival benefit (not reached vs. not reached; HR 0.66).

Enzalutamide Hexal is a generic formulation of enzalutamide. Generic medicines undergo rigorous regulatory evaluation, including bioequivalence studies that demonstrate the generic product delivers the same amount of active ingredient to the body at the same rate as the reference product. This ensures that Enzalutamide Hexal provides the same therapeutic benefit as the originator product while being available at a more accessible cost, thereby improving access to this important cancer treatment for patients worldwide.

What Should You Know Before Taking Enzalutamide Hexal?

Contraindications

Enzalutamide Hexal must not be used if you are allergic (hypersensitive) to enzalutamide or to any of the other ingredients in the tablet. The excipients include hypromellose acetate succinate, microcrystalline cellulose, colloidal anhydrous silica, croscarmellose sodium, magnesium stearate, and a film-coating containing hypromellose, talc, macrogol 8000, titanium dioxide (E171), and iron oxide yellow (E172). If you have previously experienced an allergic reaction to any antiandrogen medication, discuss this with your doctor before starting enzalutamide.

Enzalutamide Hexal is not indicated for use in women. It is contraindicated in women who are or may become pregnant, as it may cause harm to the developing fetus or loss of pregnancy. The mechanism of action of enzalutamide – androgen receptor inhibition – can interfere with fetal development, particularly the development of male reproductive organs during the critical window of sexual differentiation.

Warnings and Precautions

Before starting Enzalutamide Hexal, discuss the following with your healthcare provider:

• History of seizures or epilepsy: Enzalutamide may lower the seizure threshold. Use with extreme caution if you have a history of seizures, brain injury, brain tumors, brain metastases, stroke, transient ischemic attack, or any condition that may predispose to seizures. Concomitant use of medications that lower the seizure threshold (e.g., certain antidepressants, antipsychotics, tramadol) increases the risk.
• Cardiovascular disease: Ischemic heart disease, including myocardial infarction and angina, has been reported with enzalutamide use. Hypertension is a very common side effect. Patients with pre-existing cardiovascular conditions should be carefully monitored. Blood pressure should be checked regularly during treatment.
• Posterior reversible encephalopathy syndrome (PRES): Rare cases of PRES have been reported with enzalutamide. PRES is a neurological condition that can present with headache, confusion, visual disturbances, and seizures. If PRES is suspected, treatment should be discontinued and appropriate medical evaluation performed, including brain imaging (MRI).
• Liver problems: Enzalutamide is metabolized by the liver, and cases of hepatotoxicity have been reported. Your doctor may monitor liver function tests before and during treatment. Inform your doctor if you have a history of liver disease, hepatitis, or jaundice.
• Falls and fractures: Enzalutamide treatment is associated with an increased risk of falls and bone fractures. This may be related to the combined effects of androgen deprivation on bone density, age-related factors, and drug-related fatigue or dizziness. Assess patients for fall and fracture risk before and during treatment, and consider bone-protective therapy where appropriate.
• Hypersensitivity reactions: Angioedema and allergic reactions have been reported. If you develop swelling of the face, tongue, lip, or throat, or severe skin reactions, discontinue enzalutamide and seek immediate medical attention.

Women, Pregnancy, and Reproductive Precautions

Enzalutamide Hexal is not indicated for use in women. Women who are or may become pregnant must not handle broken, crushed, or damaged enzalutamide tablets without protective gloves, as the active substance may be absorbed through the skin and could potentially harm an unborn child. Intact film-coated tablets do not pose a risk from casual contact.

Male patients whose female partners are of childbearing potential must use highly effective contraception (e.g., condom plus another reliable method) during treatment with enzalutamide and for 3 months after the last dose. This precaution is necessary because enzalutamide is present in semen. If the female partner becomes pregnant, the treating doctor should be informed immediately. Animal studies have shown that enzalutamide can cause embryo-fetal toxicity and adverse effects on male reproductive organs at exposures similar to or below the human therapeutic dose.

Driving and Operating Machinery

Enzalutamide may affect your ability to drive and operate machinery. Fatigue, cognitive disturbances, dizziness, and visual disturbances have been reported during treatment. Furthermore, there is a risk of seizures, which can occur without warning. Patients should be advised of this risk and should exercise caution when driving or using machines, particularly during the initial weeks of treatment and following any dose adjustments. If you experience a seizure, stop driving and using machines and contact your healthcare provider immediately.

How Does Enzalutamide Hexal Interact with Other Drugs?

Enzalutamide has a complex drug interaction profile that requires careful attention from both patients and prescribers. Unlike many targeted cancer therapies that have minimal enzyme-inducing potential, enzalutamide is one of the most potent enzyme inducers encountered in oncology practice. Understanding these interactions is essential for safe and effective treatment, particularly given that prostate cancer patients are often older men with multiple comorbidities requiring several concomitant medications.

The drug interaction potential of enzalutamide stems from its effects on the cytochrome P450 (CYP) enzyme system and certain drug transporters. Specifically, enzalutamide and its active metabolite N-desmethyl enzalutamide are:

• Strong inducers of CYP3A4: This is the most clinically significant interaction. CYP3A4 is responsible for the metabolism of approximately 50% of all clinically used drugs. Induction of CYP3A4 by enzalutamide can dramatically reduce the plasma concentrations and therapeutic efficacy of co-administered CYP3A4 substrates.
• Moderate inducers of CYP2C9 and CYP2C19: These enzymes metabolize important drugs including warfarin (CYP2C9), phenytoin (CYP2C9), and several proton pump inhibitors (CYP2C19).
• Inducers of P-glycoprotein (P-gp), BCRP, MRP2, and OATP1B1: These drug transporters affect the absorption, distribution, and elimination of many drugs.
• Substrates of CYP2C8 (major) and CYP3A4 (minor): Inhibitors of CYP2C8 can increase enzalutamide exposure.

Major Interactions

Other Interactions of Note

Due to the breadth and significance of enzalutamide’s drug interactions, it is essential that patients provide their oncologist, urologist, and pharmacist with a comprehensive list of all medications, supplements, and herbal products they are taking. This should include over-the-counter medications, vitamins, and herbal remedies such as St. John’s wort (which is itself a CYP3A4 inducer and should be avoided). Dose adjustments, alternative medications, or enhanced monitoring may be necessary for many concomitant drugs when enzalutamide is initiated, modified, or discontinued.

What Is the Correct Dosage of Enzalutamide Hexal?

Enzalutamide Hexal should be used exactly as directed by your oncologist or urologist. The medication is taken by mouth (orally) as film-coated tablets. Each tablet contains 40 mg of enzalutamide, and the standard daily dose requires four tablets. The tablets should be swallowed whole with a glass of water and should not be crushed, broken, or chewed. Enzalutamide can be taken with or without food, as food does not significantly affect its absorption. It is important to take the medication at approximately the same time each day to maintain consistent blood levels.

Adults

In all indications, enzalutamide is used in combination with androgen deprivation therapy (ADT). For patients who have not been surgically castrated, medical castration with a GnRH agonist or antagonist should be continued during the entire course of enzalutamide treatment. This combination ensures maximum suppression of the androgen-driven signaling that fuels prostate cancer growth.

If significant side effects occur, the dose of enzalutamide may be reduced in steps:

• First dose reduction: 120 mg/day (three 40 mg tablets)
• Second dose reduction: 80 mg/day (two 40 mg tablets)

Treatment may also be temporarily interrupted (withheld) for 1 week or until side effects resolve to Grade 1 or baseline, after which treatment can be resumed at the same or a reduced dose. If a side effect recurs at the reduced dose, or if a side effect of Grade 3 or higher occurs despite dose reduction, enzalutamide should be permanently discontinued. Your doctor will guide you on dose modifications based on the specific side effects you experience.

Children and Adolescents

Enzalutamide Hexal is not indicated for use in children or adolescents. Prostate cancer is an adult disease, and there is no relevant indication for enzalutamide in the pediatric population. Safety and efficacy have not been established in patients under 18 years of age.

Elderly Patients

No dose adjustment is required based on age alone. In clinical trials, approximately 40% of patients treated with enzalutamide were aged 75 years or older, and no overall differences in safety or efficacy were observed between older and younger patients. However, elderly patients are more likely to have comorbidities that may increase the risk of falls, fractures, and cardiovascular events, so careful monitoring is recommended. Additionally, elderly patients may be more susceptible to fatigue and cognitive effects. Assess frailty and functional status before and during treatment.

Renal and Hepatic Impairment

No dose adjustment is needed for patients with mild or moderate kidney impairment. Enzalutamide has not been studied in patients with severe kidney impairment or end-stage renal disease requiring dialysis; use with caution in these populations. For patients with mild hepatic impairment (Child-Pugh A), no dose adjustment is necessary. Enzalutamide has not been adequately studied in patients with moderate or severe hepatic impairment (Child-Pugh B or C), and its use is not recommended in these groups due to the potential for increased drug exposure and toxicity. Liver function tests should be monitored periodically during treatment.

Missed Dose

If you forget to take your daily dose of Enzalutamide Hexal, take it as soon as you remember on the same day. If you have missed the entire day’s dose, take your usual dose the next day at the regular time. Do not take a double dose to make up for a missed dose. If you miss several consecutive doses, contact your doctor for guidance. Keeping a daily medication diary or setting a phone alarm can help ensure consistent dosing.

Overdose

There is no specific antidote for enzalutamide overdose. In the event of an overdose, stop taking the medication and contact your doctor or go to the nearest emergency department immediately. Symptoms of overdose may include an increased risk of seizures and severe fatigue. Treatment is supportive and symptomatic. In clinical trials, single doses up to 600 mg were administered without life-threatening adverse events. However, any overdose should be taken seriously given the seizure risk. Due to the long half-life of enzalutamide (approximately 5.8 days), symptoms may persist for an extended period after overdose.

What Are the Side Effects of Enzalutamide Hexal?

Like all medicines, Enzalutamide Hexal can cause side effects, although not everybody gets them. The following information is based on data from the pivotal clinical trials (AFFIRM, PREVAIL, PROSPER, ARCHES) and post-marketing surveillance involving tens of thousands of patient-years of exposure. It is important to be aware of potential side effects so that you can recognize them early and report them to your healthcare provider. Many side effects can be managed effectively with dose adjustments, treatment interruption, or supportive medications.

Side effects are classified by how often they occur:

Fatigue is the most frequently reported side effect and can range from mild tiredness to severe exhaustion that significantly affects daily activities. It is important to distinguish fatigue caused by enzalutamide from fatigue due to the underlying cancer, anemia, depression, or other factors. Regular exercise (as tolerated), adequate rest, and good nutrition can help manage treatment-related fatigue. Severe fatigue that impairs your quality of life should be discussed with your doctor, as a dose reduction may be appropriate.

Hot flushes are a direct consequence of the combined effects of ADT and enzalutamide on androgen levels and are experienced by a large proportion of patients. They typically present as sudden, intense sensations of heat affecting the upper body and face, often accompanied by sweating and sometimes followed by chills. Management strategies include avoiding triggers (hot drinks, spicy food, alcohol), wearing layered clothing, and in some cases, pharmacological interventions such as low-dose venlafaxine or gabapentin may be considered.

Hypertension should be monitored regularly, as it occurs in approximately 10–15% of patients and can increase the risk of cardiovascular events. Blood pressure should be checked at each clinic visit, and home blood pressure monitoring may be recommended. Existing antihypertensive therapy may need to be optimized, and new antihypertensive medications may need to be initiated. Note that some antihypertensive medications (particularly calcium channel blockers metabolized by CYP3A4) may have reduced efficacy when co-administered with enzalutamide.

Falls and fractures represent an important clinical concern in the prostate cancer population, which consists predominantly of older men who may already have reduced bone density from long-term ADT. Enzalutamide appears to further increase this risk, likely through a combination of muscle weakness, fatigue, dizziness, and cognitive effects. Patients should be assessed for fall risk before starting treatment, and bone density monitoring and bone-protective agents (such as denosumab or zoledronic acid) should be considered where appropriate. Vitamin D and calcium supplementation may also be recommended.

How Should You Store Enzalutamide Hexal?

Proper storage of Enzalutamide Hexal is important to ensure the medication remains effective and safe throughout its shelf life. The tablets should be stored at room temperature, not exceeding 30°C (86°F). They should be kept in the original blister packaging or bottle to protect from moisture and light. Do not transfer the tablets to a different container unless advised by your pharmacist.

Do not use Enzalutamide Hexal after the expiry date stated on the carton and blister or bottle after “EXP.” The expiry date refers to the last day of that month. If you notice any visible changes in the appearance of the tablets (such as discoloration, crumbling, or unusual odor), do not take them and return them to your pharmacist.

Keep this medicine out of the sight and reach of children. Due to the potential harm to developing fetuses, particular care should be taken to ensure that women who are or may become pregnant do not handle damaged or broken tablets. Store the medication securely to prevent accidental access by other household members.

Do not dispose of unused or expired enzalutamide tablets via household waste or by flushing them down the toilet. As an anticancer medication, enzalutamide requires special disposal to prevent environmental contamination. Return any unused tablets to your pharmacist for safe disposal through the local pharmaceutical waste collection system. This helps protect the environment and prevents accidental exposure.

What Does Enzalutamide Hexal Contain?

Active Ingredient

The active substance is enzalutamide. Each film-coated tablet contains 40 mg of enzalutamide. Enzalutamide is a non-steroidal androgen receptor inhibitor with the chemical name 4-{3-[4-cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-thioxoimidazolidin-1-yl}-2-fluoro-N-methylbenzamide. It has a molecular formula of C₂₁H₁₆F₄N₄O₂S and a molecular weight of 464.44 g/mol. Enzalutamide is a white to off-white crystalline powder that is practically insoluble in water.

Inactive Ingredients (Excipients)

The other ingredients in Enzalutamide Hexal 40 mg film-coated tablets include:

• Tablet core: Hypromellose acetate succinate, microcrystalline cellulose, colloidal anhydrous silica, croscarmellose sodium, magnesium stearate
• Film coating: Hypromellose, talc, macrogol 8000, titanium dioxide (E171), iron oxide yellow (E172)

The film-coated tablets are yellow, round, biconvex, and may be debossed with an identifying mark. The coating serves to protect the tablet contents, improve swallowability, and provide visual identification. None of the excipients are derived from animal sources, and the tablets do not contain lactose or gluten. If you have known allergies or intolerances to any of the listed ingredients, inform your doctor or pharmacist before starting treatment.

Packaging

Enzalutamide Hexal 40 mg film-coated tablets are available in blister packs or HDPE bottles. Not all pack sizes may be marketed in your country. Each package contains a patient information leaflet with complete usage instructions. Always read the patient information leaflet before starting treatment and keep it for future reference.