Enzalutamide Teva: Uses, Dosage & Side Effects

What Is Enzalutamide Teva and What Is It Used For?

Enzalutamide Teva contains the active substance enzalutamide, which belongs to a class of medications known as androgen receptor inhibitors or antiandrogens. Prostate cancer is one of the most common cancers in men worldwide, with the World Health Organization estimating approximately 1.4 million new cases and 375,000 deaths globally each year. The growth and survival of prostate cancer cells depend heavily on male hormones called androgens, primarily testosterone and dihydrotestosterone (DHT). These hormones exert their effects by binding to androgen receptors (AR) on prostate cancer cells, which then translocate to the cell nucleus and activate genes that promote cancer cell proliferation and survival.

Enzalutamide is a next-generation androgen receptor signaling inhibitor that was designed to overcome resistance mechanisms that limit the effectiveness of earlier antiandrogens such as bicalutamide and flutamide. Unlike first-generation antiandrogens, which only partially block androgen receptor signaling and can sometimes paradoxically activate the receptor (a phenomenon known as the antiandrogen withdrawal effect), enzalutamide inhibits the androgen receptor signaling pathway at three critical steps: it competitively blocks the binding of androgens to the androgen receptor with five to eight times greater affinity than bicalutamide; it prevents the nuclear translocation of the activated androgen receptor complex; and it inhibits the binding of the androgen receptor to DNA and the recruitment of coactivator proteins, even when the receptor is overexpressed or the gene is amplified.

This triple-action mechanism of action is particularly important because castration-resistant prostate cancer (CRPC) often develops through adaptations in the androgen receptor pathway. Even when circulating testosterone levels are suppressed to castrate levels through medical or surgical castration, prostate cancer cells can continue to grow by amplifying androgen receptor expression, producing androgens locally within tumour tissue, or generating constitutively active androgen receptor splice variants. Enzalutamide's ability to inhibit multiple steps in the signaling cascade makes it effective against many of these resistance mechanisms.

Enzalutamide Teva is a generic version of the originator product Xtandi, which was first approved by the U.S. Food and Drug Administration (FDA) in August 2012 for the treatment of mCRPC following chemotherapy, and subsequently received expanded approvals for additional indications. As a generic medicine, Enzalutamide Teva has been approved based on demonstrated bioequivalence to the originator product, meaning it delivers the same amount of active substance to the body at the same rate. Generic medicines must meet the same strict quality and manufacturing standards as the originator product.

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

• Metastatic castration-resistant prostate cancer (mCRPC): For patients whose cancer has spread to other parts of the body and continues to progress despite androgen deprivation therapy. The pivotal AFFIRM trial (post-chemotherapy) and PREVAIL trial (pre-chemotherapy) demonstrated significant improvements in overall survival and radiographic progression-free survival compared with placebo.
• Non-metastatic castration-resistant prostate cancer (nmCRPC): For patients at high risk of developing metastatic disease, defined by a rapidly rising prostate-specific antigen (PSA) with a PSA doubling time of 10 months or less. The PROSPER trial demonstrated a 71% reduction in the risk of metastasis or death compared with placebo.
• Metastatic hormone-sensitive prostate cancer (mHSPC): For patients with newly diagnosed metastatic prostate cancer that is still responsive to hormonal therapy. The ARCHES and ENZAMET trials showed significant improvements in radiographic progression-free survival and overall survival when enzalutamide was added to standard ADT.

In all approved indications, enzalutamide is used in combination with androgen deprivation therapy (either a gonadotropin-releasing hormone [GnRH] agonist or antagonist, or surgical castration). The combination of enzalutamide with ADT provides a more comprehensive suppression of androgen receptor signaling than either approach alone, leading to greater tumour control and improved patient outcomes.

What Should You Know Before Taking Enzalutamide Teva?

Contraindications

Enzalutamide Teva must not be used in the following situations:

• Hypersensitivity: Do not take Enzalutamide Teva if you are allergic to enzalutamide or to any of the other ingredients in the tablet formulation. If you experience signs of an allergic reaction such as skin rash, itching, swelling of the face, lips, or throat, or difficulty breathing, stop taking the medication and seek immediate medical attention.
• Women who are or may become pregnant: Enzalutamide Teva is not indicated for use in women. Enzalutamide may cause fetal harm based on its mechanism of action and findings in animal reproduction studies. Women who are pregnant or may become pregnant must not handle broken or crushed enzalutamide tablets without protective gloves, as the active substance can be absorbed through the skin.

Warnings and Precautions

Before starting Enzalutamide Teva, discuss the following conditions and risk factors with your healthcare provider:

• Seizure history or risk factors: Enzalutamide crosses the blood-brain barrier and may lower the seizure threshold. Patients with a history of seizure, structural brain damage (including brain metastases), stroke, transient ischemic attack, or conditions predisposing to seizures should be carefully evaluated. Concomitant medications that lower the seizure threshold should be reviewed. If a seizure occurs during treatment, enzalutamide must be permanently discontinued.
• Cardiovascular disease: Ischemic heart disease, including fatal events, has been reported in clinical trials with enzalutamide. Patients with a history of myocardial infarction, unstable angina, coronary artery disease, heart failure, or cerebrovascular accident should be closely monitored. Optimise cardiovascular risk factors (hypertension, diabetes, hyperlipidemia) before and 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 rapidly evolving symptoms including headache, seizure, visual disturbance, confusion, and altered mental status, often in association with elevated blood pressure. If PRES is suspected, diagnosis should be confirmed by brain imaging (MRI) and enzalutamide should be discontinued.
• Falls and fractures: An increased incidence of falls and fractures has been observed in patients taking enzalutamide, likely related to the effects of profound androgen suppression on bone mineral density and muscle mass. Assess fracture and fall risk before starting treatment and monitor regularly. Consider bone-protective agents (such as denosumab or zoledronic acid) and calcium and vitamin D supplementation as appropriate.
• Hypersensitivity reactions: Hypersensitivity reactions manifesting as facial or tongue oedema, lip oedema, or pharyngeal oedema have been reported. Discontinue enzalutamide if a serious hypersensitivity reaction occurs.

Pregnancy and Breastfeeding

Enzalutamide Teva is indicated only for adult men and must not be taken by women. Based on its mechanism of action (androgen receptor inhibition), enzalutamide has the potential to cause serious harm to a developing fetus. In animal studies, enzalutamide caused adverse developmental effects including reduced anogenital distance, hypospadias, and other reproductive organ abnormalities in male offspring.

Women of childbearing potential who are partners of men being treated with enzalutamide should use highly effective contraception during treatment and for 3 months after the last dose. If enzalutamide is taken during pregnancy or if the patient’s female partner becomes pregnant, the patient should inform their doctor immediately. Women who are pregnant or may become pregnant should not handle broken or crushed enzalutamide tablets without protective gloves.

It is not known whether enzalutamide or its metabolites are present in human semen. A condom is required during and for 3 months after treatment if the patient’s partner is pregnant. A condom plus another effective form of birth control is required during and for 3 months after treatment if the patient’s partner is of childbearing potential.

Fertility

Enzalutamide may impair male fertility. Animal studies have shown reduced fertility parameters including decreased sperm counts and testicular weights. These effects may be irreversible. Men who wish to father children should discuss fertility preservation options (such as sperm banking) with their doctor before starting enzalutamide treatment.

Driving and Operating Machinery

Enzalutamide may influence the ability to drive and use machines due to its potential side effects, including fatigue, dizziness, cognitive disturbance, and the risk of seizure. Patients experiencing these symptoms should be cautious when driving, cycling, or operating machinery. If a seizure occurs, the patient must not drive or operate heavy machinery until cleared to do so by their treating physician.

How Does Enzalutamide Teva Interact with Other Drugs?

Enzalutamide has a complex drug interaction profile that is clinically significant and requires careful attention from prescribers and pharmacists. Unlike monoclonal antibodies or many newer targeted therapies, enzalutamide is extensively metabolized by hepatic cytochrome P450 (CYP) enzymes and is also a potent inducer of several CYP enzymes and drug transporters. This dual role as both a substrate and an inducer creates the potential for both increased enzalutamide exposure (when co-administered with CYP inhibitors) and decreased exposure of other drugs (when enzalutamide induces their metabolism).

Enzalutamide is primarily metabolized by CYP2C8, with a minor contribution from CYP3A4, to form the active metabolite N-desmethyl enzalutamide, which has similar pharmacological activity. Both enzalutamide and its active metabolite are strong inducers of CYP3A4 and moderate inducers of CYP2C9, CYP2C19, and UGT1A1. Additionally, enzalutamide may induce P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), multidrug resistance-associated protein 2 (MRP2), and organic anion transporting polypeptide 1B1 (OATP1B1).

Major Interactions

Additional Interaction Considerations

Due to the broad enzyme-inducing effect of enzalutamide, a wide range of commonly used medications may be affected. Categories of drugs that may have reduced efficacy when used with enzalutamide include:

• Opioid analgesics: Fentanyl, oxycodone, and methadone (CYP3A4 substrates) may have significantly reduced plasma levels, potentially leading to inadequate pain control. Pain management strategies may need to be adjusted.
• Cardiovascular drugs: Certain calcium channel blockers (e.g., amlodipine, felodipine), anticoagulants (warfarin, apixaban, rivaroxaban), and statins (atorvastatin, simvastatin) may have reduced levels. Monitor cardiovascular parameters closely.
• Immunosuppressants: Ciclosporin, tacrolimus, and sirolimus (CYP3A4 substrates) may have significantly reduced levels, potentially leading to organ rejection in transplant recipients. Therapeutic drug monitoring is essential.
• Antiviral agents: Many HIV protease inhibitors and hepatitis C antivirals are CYP3A4 substrates and may have reduced efficacy. Consult with an HIV or hepatology specialist before starting enzalutamide.
• Corticosteroids: Dexamethasone and other corticosteroids (CYP3A4 substrates) may have reduced levels. This is clinically relevant as corticosteroids are frequently used alongside enzalutamide in oncology settings.

Before starting enzalutamide, your oncologist or pharmacist should conduct a thorough review of all current medications, including prescription drugs, over-the-counter medications, herbal supplements, and nutritional products. St. John’s wort (Hypericum perforatum) should be avoided as it may further complicate the already complex enzyme induction profile. The interaction potential of enzalutamide makes it one of the most challenging oncology medications to manage from a polypharmacy perspective, and regular medication reviews should be performed throughout treatment.

What Is the Correct Dosage of Enzalutamide Teva?

Enzalutamide Teva should always be taken exactly as prescribed by your oncologist. The dosing is consistent across all approved indications (mCRPC, nmCRPC, and mHSPC), which simplifies treatment initiation and management. Treatment with enzalutamide should be initiated and supervised by a specialist physician experienced in the medical treatment of prostate cancer.

Adults

The four 40 mg tablets should be swallowed whole with a glass of water and should not be chewed, dissolved, or crushed. Taking the tablets at approximately the same time each day helps maintain consistent blood levels. There is no clinically significant effect of food on enzalutamide absorption, so the tablets can be taken with or without meals. Treatment should continue until disease progression, unacceptable toxicity, or the decision to stop is made by the treating oncologist.

Dose Modifications

If a patient experiences a Grade 3 or higher adverse event, or an intolerable side effect, the dose may be reduced or treatment temporarily interrupted:

• First dose reduction: 120 mg once daily (three 40 mg tablets)
• Second dose reduction: 80 mg once daily (two 40 mg tablets)
• If the adverse event resolves to Grade 1 or less, treatment may be resumed at the same or a reduced dose at the discretion of the oncologist.
• If a seizure occurs during treatment, enzalutamide must be permanently discontinued.

Special Populations

Children and Adolescents

There is no relevant use of Enzalutamide Teva in the paediatric population. Prostate cancer does not occur in children. Enzalutamide Teva is not indicated for use in patients under 18 years of age.

Missed Dose

If you miss a dose or forget to take your tablets at the usual time, take the missed dose as soon as you remember on the same day. If you miss an entire day’s dose, take your normal dose (160 mg) the following day. Do not take a double dose to make up for a missed dose. If you miss more than one day of treatment, inform your oncologist. Using a pill organiser or setting a daily alarm on your phone 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 oncologist or emergency services immediately. In clinical trials, single doses of up to 600 mg have been administered without dose-limiting toxicity, but higher doses may increase the risk of seizures. Treatment of overdose should be symptomatic and supportive. Given the long half-life of enzalutamide (approximately 5.8 days), supportive measures may need to continue for several days. Enzalutamide is highly protein-bound (approximately 97–98%) and is unlikely to be significantly removed by haemodialysis.

What Are the Side Effects of Enzalutamide Teva?

Like all medicines, Enzalutamide Teva can cause side effects, although not everyone who takes it will experience them. The side effect profile of enzalutamide has been characterised through large-scale clinical trials involving thousands of patients, as well as extensive post-marketing surveillance data. Understanding the potential side effects and their frequency helps patients and healthcare providers make informed treatment decisions and enables prompt recognition and management of adverse events.

The safety data presented below are derived from the pooled analysis of five randomised, placebo-controlled, phase III clinical trials (AFFIRM, PREVAIL, TERRAIN, PROSPER, and ARCHES) that included over 3,900 patients treated with enzalutamide 160 mg daily plus ADT. The median duration of treatment exposure across these studies ranged from approximately 12 to 34 months.

Fatigue and asthenia are the most frequently reported side effects with enzalutamide and are also the most common reasons for dose modification. In clinical trials, fatigue of any grade was reported in approximately 33–40% of patients receiving enzalutamide versus 23–29% of patients receiving placebo. Grade 3 or 4 fatigue occurred in approximately 3–6% of patients. Fatigue may improve with regular mild exercise, adequate sleep hygiene, and structured energy management. In some cases, dose reduction from 160 mg to 120 mg or 80 mg daily may be necessary.

Hypertension is reported in approximately 10–15% of patients and requires regular blood pressure monitoring. New-onset hypertension should be treated with standard antihypertensive therapy. Pre-existing hypertension should be optimally controlled before starting enzalutamide.

Falls and fractures are clinically important side effects that reflect the cumulative effect of androgen deprivation on bone mineral density and muscle function. In the PREVAIL trial, falls occurred in 11% of enzalutamide-treated patients versus 4% in the placebo group. Fractures occurred in approximately 10% of patients. Risk reduction strategies include bone density monitoring, calcium and vitamin D supplementation, consideration of bisphosphonates or denosumab, and fall prevention measures such as physiotherapy, home safety assessments, and avoidance of sedating medications where possible.

Cognitive disorders including memory impairment, amnesia, disturbance in attention, and cognitive disorder have been reported in approximately 4–5% of patients. These effects are likely related to the central nervous system activity of enzalutamide. Patients should be informed about this potential side effect and encouraged to report any cognitive changes to their treatment team.

How Should You Store Enzalutamide Teva?

Proper storage of Enzalutamide Teva is important to maintain the quality, safety, and efficacy of the medication throughout the treatment period. As an oral solid dosage form, film-coated tablets are generally more stable than biological products, but they still require appropriate storage conditions to prevent degradation.

• Temperature: Store below 30°C (86°F). Do not store above this temperature. Avoid exposure to excessive heat or direct sunlight, which may accelerate degradation of the active substance.
• Moisture protection: Keep the tablets in the original blister packaging or bottle to protect them from moisture. Do not transfer tablets to a separate container unless it provides equivalent moisture protection.
• Keep out of reach of children: Store Enzalutamide Teva in a secure location where children and other household members cannot access it. Enzalutamide is a cytotoxic-like medication that can cause harm if ingested by others.
• Expiration date: Do not use Enzalutamide Teva after the expiration date printed on the packaging (“EXP”). The expiration date refers to the last day of that month.
• Disposal: Do not dispose of unused or expired tablets in household waste or down the drain. Return them to your pharmacy for safe disposal in accordance with local regulations for handling of cytotoxic-like medications.
• Handling precautions: Intact film-coated tablets can be handled without gloves. However, crushed or broken tablets should not be handled without protective gloves, particularly by women of childbearing potential, as enzalutamide can be absorbed through the skin.

When traveling with Enzalutamide Teva, keep the medication in its original packaging with the prescription label visible. Do not expose it to extreme temperatures during travel. If traveling by air, carry the medication in your hand luggage rather than checked baggage to avoid exposure to extreme temperatures in the cargo hold.

What Does Enzalutamide Teva Contain?

Understanding the full composition of your medication is important, particularly if you have known allergies or intolerances to specific pharmaceutical ingredients. Below is a detailed breakdown of the composition of Enzalutamide Teva 40 mg film-coated tablets.

Active Ingredient

The active substance is enzalutamide, a non-steroidal androgen receptor inhibitor. Each film-coated tablet contains exactly 40 mg of enzalutamide. The standard daily dose of 160 mg requires the administration of four tablets.

Inactive Ingredients (Excipients)

Appearance and Pack Sizes

Enzalutamide Teva 40 mg film-coated tablets are round, biconvex tablets. They are supplied in blister packs or HDPE bottles. Pack sizes may vary by country but commonly include 112 tablets (28-day supply at the standard 160 mg daily dose). Not all pack sizes may be available in every country.

Marketing Authorization Holder and Manufacturer

Enzalutamide Teva is manufactured and marketed by Teva Pharmaceuticals. As a generic medicine, it has been approved based on demonstrated bioequivalence to the originator product Xtandi (originally developed by Astellas Pharma and Pfizer). The marketing authorization is held by Teva in the relevant regulatory territories.