Enzalutamide Zentiva: Uses, Dosage & Side Effects

What Is Enzalutamide Zentiva and What Is It Used For?

Prostate cancer is the second most commonly diagnosed cancer in men worldwide and a leading cause of cancer-related death. The growth of prostate cancer cells is primarily driven by androgens (male sex hormones, principally testosterone and dihydrotestosterone) that bind to the androgen receptor (AR), a nuclear transcription factor. When androgens activate the AR, it translocates to the cell nucleus where it binds to DNA and triggers the transcription of genes that promote cell survival, proliferation, and resistance to apoptosis (programmed cell death). This fundamental dependency on androgen signaling makes the AR pathway the principal therapeutic target in prostate cancer management.

Enzalutamide Zentiva contains the active substance enzalutamide, a second-generation nonsteroidal antiandrogen that represents a significant advancement over older antiandrogens such as bicalutamide and flutamide. Unlike first-generation antiandrogens that primarily block androgen binding to the receptor, enzalutamide inhibits multiple steps in the AR signaling cascade. Specifically, enzalutamide competitively inhibits androgen binding to the AR with a 5- to 8-fold greater affinity than bicalutamide, prevents nuclear translocation of the activated receptor, and inhibits the association of the AR with DNA and co-activator proteins. This triple mechanism of action results in more complete suppression of AR-mediated signaling compared to earlier-generation drugs and is effective even in the setting of AR overexpression, a common resistance mechanism in castration-resistant disease.

Enzalutamide Zentiva is a generic formulation that has been approved by the European Medicines Agency (EMA) as a bioequivalent alternative to the originator product Xtandi (developed by Astellas Pharma and Pfizer). Bioequivalence studies have confirmed that Enzalutamide Zentiva delivers the same amount of active substance into the bloodstream as the reference product, ensuring identical therapeutic efficacy and safety. This provides patients and healthcare systems with a more affordable treatment option while maintaining the same clinical standards.

Enzalutamide Zentiva is indicated for three distinct clinical scenarios in prostate cancer management, each supported by pivotal phase III randomized controlled trial data:

• Metastatic castration-resistant prostate cancer (mCRPC): For men whose cancer has spread to other parts of the body and continues to progress despite medical or surgical castration. The AFFIRM trial demonstrated a 4.8-month improvement in median overall survival in men who had received prior chemotherapy with docetaxel (18.4 vs. 13.6 months; HR 0.63, p<0.001). The PREVAIL trial showed a 2.2-month overall survival benefit in chemotherapy-naive mCRPC patients (35.3 vs. 31.3 months; HR 0.77, p=0.0002), with a remarkable 81% reduction in the risk of radiographic progression.
• Non-metastatic castration-resistant prostate cancer (nmCRPC): For men at high risk of developing metastases (defined as PSA doubling time of 10 months or less) whose cancer is progressing despite castration but has not yet visibly spread. The PROSPER trial demonstrated a median metastasis-free survival of 36.6 months with enzalutamide versus 14.7 months with placebo (HR 0.29, p<0.001), representing a 71% reduction in the risk of metastasis or death.
• Metastatic hormone-sensitive prostate cancer (mHSPC): For men whose cancer has metastasized but is still responsive to hormone therapy. The ARCHES trial demonstrated that adding enzalutamide to ADT significantly improved radiographic progression-free survival (HR 0.39, p<0.001), and the final overall survival analysis confirmed a 34% reduction in the risk of death (HR 0.66, p<0.001).

In all three indications, enzalutamide has been shown to delay disease progression, reduce the need for subsequent therapies, maintain quality of life, and improve overall survival. These results have established enzalutamide as a cornerstone of modern prostate cancer treatment, as reflected in its prominent positioning in international clinical guidelines from the European Association of Urology (EAU), the National Comprehensive Cancer Network (NCCN), the European Society for Medical Oncology (ESMO), and the American Urological Association (AUA).

What Should You Know Before Taking Enzalutamide Zentiva?

Contraindications

Enzalutamide Zentiva is contraindicated in patients with a known hypersensitivity to the active substance enzalutamide or to any of the excipients contained in the formulation. It should not be used in women, and must particularly not be taken by women who are or may become pregnant. Enzalutamide can cause fetal harm and has the potential for embryo-fetal toxicity based on its mechanism of action as an androgen receptor inhibitor. Although enzalutamide tablets are film-coated, women who may be pregnant should avoid handling broken or crushed tablets without protective gloves, as the active substance could be absorbed through the skin.

Warnings and Precautions

Several important warnings and precautions must be considered before and during treatment with enzalutamide:

• Seizure risk: Seizures have been reported in approximately 0.5% of patients treated with enzalutamide in clinical trials. The mechanism is thought to be related to inhibition of the GABA-A receptor-chloride channel complex. Enzalutamide should be used with caution in patients with a history of seizures or predisposing conditions such as underlying brain injury, stroke, primary brain tumors, brain metastases, or alcoholism. Medications that lower the seizure threshold (e.g., certain antidepressants, tramadol, theophylline) should be carefully evaluated when co-administered with enzalutamide. If a seizure occurs during treatment, enzalutamide should be permanently discontinued.
• Posterior reversible encephalopathy syndrome (PRES): Rare cases of PRES have been reported in patients receiving enzalutamide. Symptoms may include headache, altered mental status, seizures, visual disturbances, and hypertension. An MRI is required for diagnosis, and if PRES is confirmed, enzalutamide should be discontinued.
• Ischemic heart disease: An increased incidence of ischemic heart disease, including fatal events, has been observed with enzalutamide compared to placebo in some clinical trials. Patients with a history of cardiovascular disease should be monitored closely. Risk factors for heart disease should be managed according to standard clinical practice, including control of blood pressure, lipid levels, and blood glucose.
• Falls and fractures: Falls and fractures have been reported more frequently in patients treated with enzalutamide compared to placebo. Patients should be assessed for fall and fracture risk before starting treatment, and bone health should be monitored. Supplementation with calcium and vitamin D, and consideration of bone-protective therapy (e.g., denosumab, bisphosphonates) may be appropriate in patients at increased risk of fractures.
• Hypertension: Hypertension has been observed more frequently with enzalutamide therapy. Blood pressure should be monitored regularly and managed with antihypertensive medications as needed.
• Hypersensitivity reactions: Hypersensitivity reactions, including facial edema, tongue edema, lip edema, and pharyngeal edema, have been reported with enzalutamide use. Enzalutamide should be discontinued if serious hypersensitivity reactions occur.

Pregnancy and Breastfeeding

Enzalutamide Zentiva is indicated exclusively for adult men and is not for use in women. However, it is critically important that female partners of men taking enzalutamide understand the reproductive risks. Enzalutamide can cause fetal harm due to its mechanism of action, and it is present in semen. Therefore, men who are sexually active with a woman of childbearing potential must use a condom and another effective method of contraception during treatment and for 3 months after the last dose of enzalutamide. If the patient's female partner becomes or is suspected of being pregnant, the treating physician should be contacted immediately.

Men taking enzalutamide should be counseled that the medication may affect fertility. Animal studies have shown effects on the male reproductive system, including reduced organ weights and changes in sperm morphology. Men who wish to father children should discuss fertility preservation options (such as sperm banking) with their oncologist before starting treatment.

How Does Enzalutamide Zentiva Interact with Other Drugs?

Drug interactions are a particularly important consideration with enzalutamide because it has a powerful effect on several hepatic drug-metabolizing enzyme systems. Enzalutamide and its active metabolite N-desmethyl enzalutamide are both potent inducers of cytochrome P450 enzymes, which means they accelerate the metabolism and elimination of many other drugs from the body. This can lead to reduced plasma concentrations and diminished therapeutic effects of co-administered medications. The magnitude of this enzyme induction is clinically significant and can affect treatment outcomes across multiple therapeutic areas.

Enzalutamide itself is metabolized primarily by CYP2C8 (with a minor contribution from CYP3A4), meaning that drugs which inhibit or induce these enzymes can alter enzalutamide blood levels. Additionally, enzalutamide is a substrate for the P-glycoprotein (P-gp) efflux transporter and may be affected by P-gp inhibitors and inducers.

Major Interactions

Minor Interactions

In addition to the major interactions listed above, enzalutamide can reduce the effectiveness of numerous other medications metabolized by CYP3A4, CYP2C9, CYP2C19, CYP1A2, or transported by P-glycoprotein. These include, but are not limited to:

• Theophylline and caffeine (CYP1A2 substrates): Reduced plasma levels may require dose adjustments in patients using theophylline for asthma or COPD management.
• Certain statins (atorvastatin, simvastatin; CYP3A4 substrates): May have reduced cholesterol-lowering efficacy. Rosuvastatin may be a better alternative as it is not primarily metabolized by CYP3A4.
• Opioid analgesics (fentanyl, oxycodone; CYP3A4 substrates): May have reduced analgesic efficacy. Dose adjustments or alternative pain management strategies may be needed.
• Certain antidepressants (CYP2C19 and CYP1A2 substrates): Citalopram, escitalopram, and duloxetine may have reduced plasma levels. Monitor clinical response and adjust doses accordingly.
• Antifungal agents (itraconazole, voriconazole; CYP3A4 substrates): Reduced antifungal levels may compromise treatment efficacy in patients with fungal infections.

What Is the Correct Dosage of Enzalutamide Zentiva?

Adults

The standard recommended dose for all approved indications (mCRPC, nmCRPC, and mHSPC) is 160 mg of enzalutamide taken orally once daily. This corresponds to four film-coated tablets of 40 mg each. The tablets should be swallowed whole with a glass of water and must not be split, crushed, or chewed. Enzalutamide can be taken with or without food, as food does not significantly affect its bioavailability. It is advisable to take the medication at approximately the same time each day to maintain consistent blood levels.

Treatment with enzalutamide should continue alongside androgen deprivation therapy (ADT), typically in the form of a GnRH agonist (e.g., leuprorelin, goserelin) or GnRH antagonist (e.g., degarelix, relugolix), unless the patient has undergone bilateral orchiectomy (surgical castration). This combination ensures maximal suppression of the androgen receptor pathway.

Dose Adjustments

Dose modification or temporary interruption may be necessary in several situations. If a patient experiences grade 3 or higher toxicity (severe side effects) or an intolerable adverse reaction, treatment should be withheld for one week or until symptoms improve to grade 2 or lower, after which it may be resumed at the same dose or a reduced dose of 120 mg (three tablets) or 80 mg (two tablets) daily if warranted. In patients who require concomitant treatment with a strong CYP2C8 inhibitor (such as gemfibrozil), the dose of enzalutamide should be reduced to 80 mg (two tablets) once daily.

No dose adjustment is required for patients with mild or moderate hepatic impairment (Child-Pugh A or B). However, enzalutamide is not recommended for patients with severe hepatic impairment (Child-Pugh C), as it has not been studied in this population. Similarly, no dose adjustment is required for patients with mild or moderate renal impairment. Caution is advised in patients with severe renal impairment or end-stage renal disease, as data are limited.

Children

Enzalutamide Zentiva is not indicated for use in children or adolescents. Prostate cancer does not occur in this population, and there is no relevant pediatric indication for this medication. The safety and efficacy of enzalutamide in patients under 18 years of age have not been established.

Elderly

No dose adjustment is required based on age alone. In the pivotal clinical trials, approximately 40% of patients were aged 75 years or older. The pharmacokinetics of enzalutamide are not significantly affected by age, and the safety and efficacy profile in elderly patients was consistent with that observed in the overall study population. However, elderly patients may be more susceptible to certain adverse effects such as falls, fractures, and cognitive changes, and should be monitored accordingly.

Missed Dose

If a dose of enzalutamide is missed, it should be taken as soon as it is remembered on the same day. If the entire day has been missed, the patient should take the regular dose the next day at the usual time. A double dose should never be taken to make up for a missed dose. If a patient vomits after taking the dose, the dose should not be repeated; instead, the next scheduled dose should be taken at the usual time.

Overdose

There is no specific antidote for enzalutamide overdose. In the event of an overdose, treatment should be symptomatic and supportive. Patients who take more than the prescribed dose should contact their healthcare provider or local poison control center immediately. Overdose may increase the risk of seizures, and close neurological monitoring is warranted. Given the long half-life of enzalutamide (approximately 5.8 days) and its active metabolite (7.8 to 8.6 days), the effects of an overdose may be prolonged, and extended observation may be necessary.

What Are the Side Effects of Enzalutamide Zentiva?

Like all medications, Enzalutamide Zentiva can cause side effects, although not everyone experiences them. The side effect profile of enzalutamide has been well characterized through extensive clinical trial data involving thousands of patients across the AFFIRM, PREVAIL, PROSPER, and ARCHES trials, as well as post-marketing surveillance. Understanding the frequency and nature of potential side effects helps patients and their healthcare teams make informed treatment decisions and enables early recognition and management of adverse events.

The side effects are classified below by frequency according to the standard medical classification system: very common (affects more than 1 in 10 patients), common (affects 1 in 10 to 1 in 100 patients), uncommon (affects 1 in 100 to 1 in 1,000 patients), and rare (affects fewer than 1 in 1,000 patients).

It is important to note that many of these side effects are also associated with androgen deprivation therapy itself and with the underlying prostate cancer. Fatigue, hot flushes, and bone-related complications are common in men receiving ADT regardless of whether they are also taking enzalutamide. However, clinical trial data show that the incidence of these effects is higher when enzalutamide is added to ADT compared to ADT alone.

If you experience any side effects, particularly those that are severe, persistent, or concerning, you should inform your oncologist promptly. Many side effects can be managed effectively with dose adjustments, supportive medications, or lifestyle modifications. For example, hot flushes may respond to venlafaxine or medroxyprogesterone, and bone health can be supported with calcium, vitamin D, and bone-protective agents. Regular monitoring of blood pressure, liver function tests, and bone density should be part of the ongoing care plan.

How Should You Store Enzalutamide Zentiva?

Enzalutamide Zentiva film-coated tablets should be stored at a temperature not exceeding 30°C (86°F). No special storage conditions beyond this temperature requirement are necessary. The tablets should be kept in their original packaging (blister packs within the carton) to protect them from moisture and light until the time of use.

As with all medications, Enzalutamide Zentiva must be kept out of the reach and sight of children. The expiry date printed on the blister and the outer carton should be checked before taking the medication, and any remaining tablets should not be used after this date. The expiry date refers to the last day of that month.

Do not dispose of unused or expired enzalutamide tablets in household waste or via wastewater. Because enzalutamide is an active pharmaceutical agent that could potentially harm the environment, medicines should be returned to a pharmacy or local waste collection point for safe disposal according to local regulations. This responsible approach to medication disposal helps to protect the environment and prevent accidental exposure.

What Does Enzalutamide Zentiva Contain?

The active ingredient in Enzalutamide Zentiva is enzalutamide. Each film-coated tablet contains exactly 40 mg of enzalutamide. Enzalutamide is a nonsteroidal compound with the chemical name 4-{3-[4-cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-sulfanylideneimidazolidin-1-yl}-2-fluoro-N-methylbenzamide, with a molecular formula of C₂₁H₁₆F₄N₄O₂S and a molecular weight of 464.44 g/mol.

The tablet core typically contains the following excipients: microcrystalline cellulose (filler/binder), croscarmellose sodium (disintegrant), hypromellose (binder), magnesium stearate (lubricant), and colloidal anhydrous silica (glidant). The film coating contains hypromellose, titanium dioxide (E171, a white colorant), macrogol (polyethylene glycol, a plasticizer), and iron oxide yellow (E172, a colorant). These excipients are standard pharmaceutical ingredients used to ensure the tablet has appropriate mechanical properties, disintegration characteristics, and appearance.

The 40 mg film-coated tablets are typically round, yellow, and debossed with identifying markings for easy identification. The exact physical appearance may vary slightly depending on the specific manufacturing batch, but the active substance content and bioequivalence to the reference product (Xtandi) are ensured through rigorous pharmaceutical quality controls in accordance with European Medicines Agency (EMA) requirements.

Patients with known allergies to any of the listed excipients should inform their healthcare provider before starting treatment. In particular, patients with rare hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption should be aware if lactose is included as an excipient (refer to the specific product leaflet provided with the medication for the definitive excipient list).