Enzalutamide Viatris: Uses, Dosage & Side Effects

What Is Enzalutamide Viatris and What Is It Used For?

Enzalutamide Viatris contains the active substance enzalutamide, a second-generation nonsteroidal antiandrogen that targets the androgen receptor (AR) signaling pathway at multiple points. Prostate cancer is fundamentally driven by androgens—male sex hormones, primarily testosterone and dihydrotestosterone (DHT)—that bind to the androgen receptor in prostate cells, activating gene transcription that promotes cell growth, proliferation, and survival. Even in castration-resistant prostate cancer, where the disease progresses despite very low circulating testosterone levels achieved through surgical or medical castration, the androgen receptor pathway remains active and continues to drive tumor growth through various adaptive mechanisms including AR overexpression, AR gene amplification, and intratumoral androgen synthesis.

Enzalutamide was specifically designed to overcome the limitations of first-generation antiandrogens such as bicalutamide. Unlike these older agents, enzalutamide inhibits the androgen receptor signaling pathway at three critical steps: it competitively blocks the binding of androgens to the androgen receptor with 5 to 8-fold greater affinity than bicalutamide; it prevents the nuclear translocation of the activated androgen receptor complex; and it inhibits the binding of the activated androgen receptor to DNA (chromatin), thereby suppressing androgen-driven gene transcription. Critically, enzalutamide has no agonist activity, meaning it does not partially activate the androgen receptor as some first-generation antiandrogens can, particularly in the setting of AR overexpression.

The clinical development of enzalutamide has been supported by several landmark randomized controlled trials that have established its role across the spectrum of advanced prostate cancer. These trials have fundamentally changed the standard of care for men with this disease:

• AFFIRM trial: This phase III study enrolled 1,199 men with metastatic castration-resistant prostate cancer (mCRPC) who had previously received chemotherapy with docetaxel. Enzalutamide demonstrated a statistically significant improvement in median overall survival compared to placebo (18.4 months vs. 13.6 months; hazard ratio 0.63). This trial led to the initial regulatory approval of enzalutamide in both the United States and Europe.
• PREVAIL trial: This phase III study included 1,717 men with mCRPC who were chemotherapy-naive. Enzalutamide significantly improved both radiographic progression-free survival (not reached vs. 3.9 months; hazard ratio 0.19) and overall survival (35.3 months vs. 31.3 months; hazard ratio 0.77) compared to placebo. This expanded the indication to include patients with mCRPC regardless of prior chemotherapy status.
• PROSPER trial: This study enrolled 1,401 men with high-risk non-metastatic castration-resistant prostate cancer (nmCRPC), defined by a rapidly rising prostate-specific antigen (PSA) despite castrate testosterone levels. Enzalutamide significantly improved metastasis-free survival (36.6 months vs. 14.7 months; hazard ratio 0.29) and overall survival compared to placebo.
• ARCHES trial: This study included 1,150 men with metastatic hormone-sensitive prostate cancer (mHSPC). Enzalutamide plus androgen deprivation therapy significantly improved radiographic progression-free survival compared to placebo plus androgen deprivation therapy (not reached vs. 19.4 months; hazard ratio 0.39), leading to approval in the mHSPC setting.

Enzalutamide Viatris is a generic version of the original brand-name product Xtandi (manufactured by Astellas Pharma and Pfizer). As a generic medicine, it contains the same active ingredient at the same strength, in the same dosage form, and has been demonstrated to be bioequivalent to the reference product through rigorous pharmacokinetic studies. This means it is absorbed into the body at the same rate and to the same extent as the originator product, ensuring equivalent clinical efficacy and safety. Enzalutamide Viatris has been approved by the European Medicines Agency (EMA) and meets the same stringent quality, safety, and efficacy standards required of all authorized medicines in the European Union.

What Should You Know Before Taking Enzalutamide Viatris?

Contraindications

Enzalutamide Viatris must not be used in individuals who are hypersensitive (allergic) to the active substance enzalutamide or to any of the excipients listed in the formulation. Allergic reactions to enzalutamide, while uncommon, can occur and may include skin rash, facial swelling, or difficulty breathing. If you experience any signs of an allergic reaction, discontinue the medication and contact your healthcare provider immediately.

Enzalutamide is contraindicated in women. The medication is indicated solely for use in adult men with prostate cancer. Women who are pregnant or may become pregnant must not handle damaged or opened enzalutamide tablets, as the active substance can be absorbed through the skin and may cause harm to the developing fetus. Enzalutamide is an antiandrogen that could potentially interfere with normal fetal development, particularly the development of male genital organs in a male fetus. Intact film-coated tablets may be handled normally, as the coating prevents direct contact with the active substance.

Warnings and Precautions

Before starting treatment with enzalutamide, discuss the following important safety considerations with your healthcare provider:

• Seizures: Seizures occurred in approximately 0.5% of patients treated with enzalutamide in clinical trials. The risk may be increased in patients with predisposing factors including a history of seizures or epilepsy, underlying brain lesions or brain metastases, prior stroke or transient ischemic attack, Alzheimer’s disease, or concurrent use of medications that lower the seizure threshold (such as certain antidepressants, antipsychotics, or tramadol). If you have any of these risk factors, your doctor will carefully weigh the potential benefits against the risks before prescribing enzalutamide.
• Posterior Reversible Encephalopathy Syndrome (PRES): Rare cases of PRES have been reported in patients receiving enzalutamide. PRES is a neurological condition that presents with rapidly evolving symptoms including headache, seizures, visual disturbances, confusion, and altered mental status. If PRES is suspected, treatment with enzalutamide should be discontinued. Diagnosis is typically confirmed by brain magnetic resonance imaging (MRI).
• Ischemic heart disease: Cases of ischemic heart disease, including myocardial infarction, have been reported in patients taking enzalutamide. If you have a history of heart disease, high blood pressure, diabetes, or high cholesterol, your doctor should monitor you closely. Seek immediate medical attention if you experience chest pain, shortness of breath, or arm pain during treatment.
• Falls and fractures: Enzalutamide treatment has been associated with an increased incidence of falls and fractures. This risk is particularly relevant in elderly patients and those with osteoporosis or bone metastases. Evaluate patients for risk of falls and fractures before initiating treatment. Consider measures to reduce fracture risk, such as bone-protective agents (bisphosphonates or denosumab), calcium and vitamin D supplementation, and fall prevention strategies.
• Hypersensitivity reactions: Hypersensitivity reactions manifesting as symptoms including facial edema, tongue edema, lip edema, and pharyngeal edema have been observed with enzalutamide use. Patients should be counseled regarding the symptoms of hypersensitivity and instructed to seek immediate medical attention if any occur.

Women and Children

Enzalutamide is not indicated for use in women or children. It has not been studied in female patients with cancer or in pediatric populations. Women of childbearing potential should avoid handling damaged or opened enzalutamide tablets. If a pregnant woman is inadvertently exposed to the active substance through handling broken tablets, she should immediately wash the affected area with soap and water and consult her healthcare provider.

Pregnancy and Breastfeeding

Enzalutamide is not indicated for use in women. There are no clinical data on the use of enzalutamide in pregnant women. Based on its mechanism of action as an androgen receptor inhibitor, enzalutamide could cause fetal harm if administered to a pregnant woman or if a pregnant woman is exposed to the active substance. Animal studies have shown that enzalutamide can cause adverse reproductive effects. Men taking enzalutamide who are sexually active with women of childbearing potential should use effective contraception during treatment and for three months after the last dose. It is not known whether enzalutamide or its metabolites are present in semen; therefore, barrier contraception (condoms) is recommended to prevent potential fetal exposure.

Driving and Operating Machinery

Enzalutamide may have a moderate influence on the ability to drive and use machines. Adverse reactions reported with enzalutamide include cognitive disorders (such as memory impairment and attention disturbance), fatigue, asthenia, dizziness, and, rarely, seizures. Patients should be advised about the potential for these side effects, which could impair their ability to safely operate a vehicle or machinery. Patients who experience these symptoms should refrain from driving or operating machinery until the symptoms resolve.

How Does Enzalutamide Viatris Interact with Other Drugs?

Drug interactions with enzalutamide are clinically significant and require careful attention from both patients and healthcare providers. Enzalutamide is extensively metabolized by CYP2C8 and CYP3A4 enzymes and is a potent inducer of several cytochrome P450 enzymes. This dual role as both a substrate and an inducer creates the potential for complex pharmacokinetic interactions that can affect either enzalutamide levels or the levels of concomitant medications.

Effect of Other Drugs on Enzalutamide

Medications that inhibit CYP2C8 can increase plasma concentrations of enzalutamide. Co-administration with gemfibrozil (a strong CYP2C8 inhibitor) increased the AUC of enzalutamide plus its active metabolite (N-desmethyl enzalutamide) by approximately 2.2-fold. If co-administration with a strong CYP2C8 inhibitor is unavoidable, the dose of enzalutamide should be reduced from 160 mg to 80 mg once daily. Conversely, strong CYP3A4 inducers such as rifampicin can decrease plasma concentrations of enzalutamide, potentially reducing its efficacy.

Effect of Enzalutamide on Other Drugs

Enzalutamide is a strong inducer of CYP3A4 and a moderate inducer of CYP2C9 and CYP2C19. At steady state, enzalutamide can dramatically reduce the plasma concentrations of drugs that are substrates of these enzymes, potentially leading to loss of therapeutic effect. This is one of the most important clinical considerations when prescribing enzalutamide.

Herbal Products and Supplements

St. John’s wort (Hypericum perforatum) should be avoided during treatment with enzalutamide. St. John’s wort is a potent CYP3A4 inducer and may further reduce plasma concentrations of drugs metabolized by CYP3A4 when used in combination with enzalutamide. Grapefruit and Seville oranges should also be discussed with your doctor, as they contain compounds that can inhibit CYP3A4 and may potentially increase enzalutamide plasma levels, although this interaction is not expected to be clinically significant with the oral formulation.

What Is the Correct Dosage of Enzalutamide Viatris?

Adults

The recommended dose of Enzalutamide Viatris is 160 mg (four 40 mg film-coated tablets) taken orally once daily. The tablets should be swallowed whole with water and should not be crushed, split, dissolved, or chewed, as this may affect the release and absorption of the active substance and could lead to increased local exposure. Enzalutamide can be taken with or without food; food does not have a clinically meaningful effect on the extent of absorption, although a high-fat meal may slightly delay the time to peak concentration without affecting overall exposure.

Treatment with enzalutamide is continuous—patients take the medication every day without treatment breaks or cycles. Therapy should continue until disease progression, unacceptable toxicity, or the decision to discontinue by the patient and physician. Enzalutamide must be taken concurrently with androgen deprivation therapy (either a GnRH agonist, GnRH antagonist, or prior bilateral orchiectomy), as it is not indicated as a monotherapy.

Dose Modifications for Adverse Reactions

If a patient experiences a grade 3 or higher adverse reaction, or an intolerable side effect, treatment should be withheld for one week or until symptoms improve to grade 2 or lower, then resumed at the same dose or a reduced dose of 120 mg (three tablets) or 80 mg (two tablets) once daily, as determined by the treating physician. If a seizure occurs during treatment, enzalutamide must be permanently discontinued.

Missed Dose

If you forget to take enzalutamide at your usual time, take it as soon as you remember on the same day. If an entire day is missed, resume the regular dose the following day. Do not take a double dose to make up for a missed dose. Taking more than the prescribed amount may increase the risk of seizures and other adverse effects. If you accidentally take more than the recommended dose, contact your doctor or pharmacist immediately.

Overdose

There is no specific antidote for enzalutamide overdose. In the event of an overdose, treatment should be stopped and general supportive measures initiated. Seizure risk is of particular concern in overdose situations. Based on the pharmacokinetic profile of enzalutamide (long half-life of approximately 5.8 days and extensive protein binding), dialysis is unlikely to be effective in significantly removing the drug from the body. In clinical trials, doses up to 600 mg per day were studied. At these higher doses, the incidence of seizures was increased. No life-threatening events were reported in overdose situations during clinical development.

What Are the Side Effects of Enzalutamide Viatris?

Like all medicines, Enzalutamide Viatris can cause side effects, although not everybody gets them. The following side effects have been reported in clinical trials and post-marketing surveillance. The frequencies are based on pooled data from controlled clinical trials (AFFIRM, PREVAIL, TERRAIN, PROSPER, and ARCHES). Patients should report any new or worsening symptoms to their healthcare provider promptly.

Fatigue and asthenia are the most frequently reported adverse reactions during enzalutamide treatment. These symptoms are typically mild to moderate in severity and are manageable with supportive care measures. In clinical trials, fatigue led to treatment discontinuation in only about 1% of patients. Hot flashes are also very common and are related to the hormonal effects of treatment; they are generally mild and tend to improve over time or can be managed with supportive measures.

Hypertension occurred more frequently in patients treated with enzalutamide compared to placebo in clinical trials. Blood pressure should be monitored regularly during treatment, particularly in patients with pre-existing cardiovascular conditions. Falls and fractures are of particular concern in the elderly population. A bone health assessment, including bone density evaluation, should be considered before starting treatment, and bone-protective agents (bisphosphonates, denosumab) should be used as clinically appropriate.

Cognitive-related adverse events, including memory impairment and attention disturbance, have been reported in clinical trials. These effects were generally mild and did not typically require treatment discontinuation. However, patients and caregivers should be aware of these potential effects and should inform the healthcare team if cognitive symptoms develop or worsen during treatment.

How Should You Store Enzalutamide Viatris?

Enzalutamide Viatris should be stored at temperatures not exceeding 30°C (86°F). No special storage conditions are required beyond keeping the medication at room temperature. The tablets should be kept in the original blister packaging or bottle to protect them from moisture and light. Do not remove tablets from their packaging until you are ready to take them.

Do not use this medicine after the expiry date which is stated on the carton, blister, or bottle after "EXP." The expiry date refers to the last day of that month. Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use, as proper disposal helps protect the environment and prevents accidental exposure to others.

Keep this medicine out of the sight and reach of children. Given that enzalutamide is an antiandrogen medication used in cancer treatment, particular care should be taken to ensure that children, adolescents, and women (especially those who are pregnant or may become pregnant) do not handle damaged or opened tablets. Intact film-coated tablets can be handled normally as the film coating prevents direct contact with the active substance.

What Does Enzalutamide Viatris Contain?

The active substance in Enzalutamide Viatris is enzalutamide. Each film-coated tablet contains 40 mg of enzalutamide. The recommended daily dose of 160 mg is achieved by taking four tablets.

The other ingredients (excipients) in the tablet core typically include:

• Hypromellose acetate succinate (film-forming agent)
• Microcrystalline cellulose (filler)
• Silica, colloidal anhydrous (glidant)
• Croscarmellose sodium (disintegrant)
• Magnesium stearate (lubricant)
• Sodium lauryl sulfate (wetting agent)

The film coating contains:

• Hypromellose (film former)
• Titanium dioxide (E171, colorant)
• Macrogol (plasticizer)
• Iron oxide yellow (E172, colorant)

The tablets are round, yellow to yellowish-brown, film-coated tablets debossed with identification markings. The film coating serves to protect the active substance from degradation, aid in swallowing, and prevent handling exposure to the active ingredient. Patients with known hypersensitivity to any of these excipients should inform their healthcare provider before starting treatment. The product does not contain lactose, gluten, or tartrazine.