Erleada (Apalutamide)
Androgen receptor inhibitor for the treatment of prostate cancer
Quick Facts About Erleada (Apalutamide)
Key Takeaways
- Erleada is an androgen receptor inhibitor that blocks testosterone from fueling prostate cancer growth, used alongside androgen deprivation therapy (ADT).
- Approved for two indications: non-metastatic castration-resistant prostate cancer (nmCRPC) and metastatic hormone-sensitive prostate cancer (mHSPC).
- The standard dose is 240 mg (four 60 mg tablets) taken once daily, with or without food. Do not crush or chew the tablets.
- Important safety concerns include risk of seizures, cardiovascular events, falls and fractures, and severe skin reactions (DRESS, SJS/TEN).
- Erleada is a strong CYP3A4 inducer and can significantly reduce the effectiveness of many other medications, including blood thinners, certain antibiotics, and other cancer treatments.
What Is Erleada and What Is It Used For?
Quick Answer: Erleada (apalutamide) is a prescription medicine that belongs to a class of drugs called androgen receptor inhibitors. It is used to treat prostate cancer in adult men by blocking the action of male sex hormones (androgens) that fuel cancer growth. It is always used together with androgen deprivation therapy (ADT).
Erleada (apalutamide) is a next-generation, non-steroidal androgen receptor inhibitor developed by Janssen Pharmaceuticals, a subsidiary of Johnson & Johnson. It was first approved by the U.S. Food and Drug Administration (FDA) in February 2018 for the treatment of non-metastatic castration-resistant prostate cancer (nmCRPC) and subsequently received approval from the European Medicines Agency (EMA). In 2019, the FDA expanded the approval to include metastatic hormone-sensitive prostate cancer (mHSPC).
Prostate cancer is one of the most common cancers in men worldwide, with approximately 1.4 million new cases diagnosed globally each year according to the World Health Organization (WHO). Many men with prostate cancer are initially treated with androgen deprivation therapy (ADT), which reduces testosterone levels in the body. However, over time, some prostate cancers can continue to grow even when testosterone levels are very low - a condition known as castration-resistant prostate cancer (CRPC). Erleada addresses this by directly blocking the androgen receptor, preventing any remaining androgens from stimulating cancer growth.
Erleada is approved for two specific clinical settings:
- Non-metastatic castration-resistant prostate cancer (nmCRPC): For men whose prostate cancer has not spread to other parts of the body but continues to grow despite very low testosterone levels (castration). These patients are typically identified by a rapidly rising prostate-specific antigen (PSA) level and are at high risk of developing metastases.
- Metastatic hormone-sensitive prostate cancer (mHSPC): For men whose prostate cancer has spread to other parts of the body and is still responsive to hormone therapy. In this setting, Erleada is combined with ADT to provide more intensive androgen blockade.
The mechanism of action of apalutamide involves directly binding to the ligand-binding domain of the androgen receptor. Unlike first-generation antiandrogens such as bicalutamide, apalutamide has a significantly higher binding affinity for the androgen receptor and does not exhibit agonist activity when the receptor is overexpressed. Once bound, apalutamide prevents the androgen receptor from translocating to the cell nucleus, binding to DNA, and activating genes that promote cancer cell growth and survival. This comprehensive blockade of androgen receptor signaling leads to decreased prostate cancer cell proliferation and increased programmed cell death (apoptosis).
Erleada's efficacy was demonstrated in two landmark phase III randomized clinical trials. The SPARTAN trial (NCT01946204) showed that apalutamide significantly delayed metastasis-free survival in men with nmCRPC by a median of over two years compared to placebo. The TITAN trial (NCT02489318) demonstrated that apalutamide combined with ADT significantly improved both overall survival and radiographic progression-free survival in men with mHSPC.
What Should You Know Before Taking Erleada?
Quick Answer: Before starting Erleada, your doctor needs to know about your full medical history, particularly any history of seizures, cardiovascular disease, or skin reactions. Erleada can cause serious side effects including seizures, heart problems, severe skin reactions, and fractures. Women who are or may become pregnant must not handle damaged tablets.
Contraindications
Erleada should not be used if you are allergic (hypersensitive) to apalutamide or any of the other ingredients in the tablets. Signs of an allergic reaction may include rash, itching, swelling of the face, lips, tongue or throat, and difficulty breathing. If you experience any of these symptoms, stop taking Erleada and seek immediate medical attention.
Erleada is not indicated for use in women, and specifically must never be taken by women who are pregnant or who may become pregnant. Apalutamide can cause harm to a developing fetus. Women should not handle crushed or damaged Erleada tablets without protective gloves, as the active substance may be absorbed through the skin.
Erleada is not approved for use in children or adolescents under 18 years of age, as safety and efficacy have not been established in this population. The indication is limited to adult men with prostate cancer.
Warnings and Precautions
Several important warnings and precautions apply to Erleada treatment. Discuss these with your doctor before starting therapy:
- Seizures: Erleada has been associated with seizures. The risk may be higher in patients with a history of seizures, underlying brain injury, stroke, brain tumors, brain metastases, or alcoholism. Patients receiving medications that lower the seizure threshold may also be at increased risk. If you experience a seizure during treatment, Erleada should be permanently discontinued. Use with caution in patients with a history of seizure disorders.
- Cardiovascular events: Ischemic heart disease (including fatal events) and cerebrovascular events (stroke and transient ischemic attacks) have been reported in clinical trials. Patients with a history of cardiovascular disease should be carefully monitored. Your doctor should optimize management of cardiovascular risk factors such as hypertension, diabetes, and high cholesterol before and during treatment.
- Falls and fractures: Falls and fractures have been observed in patients treated with Erleada. Patients should be assessed for fracture risk and fall risk. Consider the use of bone-protective agents (such as bisphosphonates or denosumab) in patients at risk of osteoporosis. Bone density monitoring may be recommended.
- Severe cutaneous adverse reactions (SCARs): Severe skin reactions including Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), Stevens-Johnson Syndrome (SJS), and Toxic Epidermal Necrolysis (TEN) have been reported with Erleada. These reactions can be life-threatening or fatal. At the onset of signs or symptoms of a severe skin reaction, Erleada should be discontinued immediately and the patient should seek urgent medical evaluation.
- Interstitial lung disease: Cases of interstitial lung disease (ILD) and pneumonitis, including fatal cases, have been reported. If a patient develops new or worsening respiratory symptoms such as shortness of breath, cough, or fever, Erleada treatment should be interrupted and the patient evaluated promptly.
Pregnancy and Fertility
Erleada is not for use in women. For men taking Erleada who have female partners of childbearing potential, effective contraception must be used during treatment and for 3 months after the last dose. This is because apalutamide may be present in semen and could potentially harm a developing fetus.
Apalutamide may impair male fertility. Based on animal studies, apalutamide caused reduced fertility in male animals, and this effect was partially reversible. Men who wish to father children should discuss fertility preservation options with their doctor before starting treatment. If a female partner becomes pregnant during treatment, the patient should contact their doctor immediately.
- Chest pain, shortness of breath, or sudden onset of weakness or numbness (signs of cardiovascular events)
- Seizure or convulsion
- Widespread skin rash with blistering, peeling, fever, or mouth sores (signs of severe skin reaction)
- New or worsening cough, shortness of breath, or fever (signs of lung problems)
- Bone pain, especially after a fall (possible fracture)
How Does Erleada Interact with Other Drugs?
Quick Answer: Erleada (apalutamide) is a strong inducer of several liver enzymes (CYP3A4, CYP2C19, CYP2C9) and drug transporters (P-glycoprotein, BCRP). This means it can significantly reduce the blood levels and effectiveness of many other medications. It is essential to inform your doctor about all medications you are currently taking.
Apalutamide at steady state is a strong inducer of CYP3A4 and CYP2C19, a moderate inducer of CYP2C9, and an inducer of uridine 5'-diphospho-glucuronosyltransferase (UGT). It also inhibits BCRP and OATP1B1 and induces P-glycoprotein (P-gp). These properties mean that Erleada can significantly alter the blood levels of many other drugs, potentially reducing their effectiveness or changing their safety profile.
Before starting Erleada, your doctor needs a complete list of all prescription and non-prescription medications, herbal supplements, and vitamins you are taking. Your doctor may need to change the dose of other medications, monitor you more closely, or choose an alternative treatment. Key drug interactions are summarized in the table below.
| Drug / Class | Interaction Type | Effect | Recommendation |
|---|---|---|---|
| Warfarin | CYP2C9/CYP3A4 substrate | Reduced warfarin exposure; decreased anticoagulant effect | Monitor INR frequently; adjust warfarin dose as needed |
| Gemfibrozil | Strong CYP2C8 inhibitor | Increased apalutamide exposure | Avoid concomitant use; if unavoidable, reduce Erleada dose to 120 mg daily |
| Midazolam, triazolam (CYP3A4 substrates) | CYP3A4 induction | Up to 92% reduction in substrate exposure | Avoid or substitute with alternative agents not primarily metabolized by CYP3A4 |
| Omeprazole (CYP2C19 substrate) | CYP2C19 induction | Reduced omeprazole exposure by approximately 85% | Consider dose increase or alternative acid-suppressing therapy |
| Fexofenadine (P-gp substrate) | P-gp induction | Reduced fexofenadine exposure | Monitor for reduced efficacy; consider dose adjustment |
| Dabigatran (P-gp substrate) | P-gp induction | Potentially reduced dabigatran exposure and anticoagulant effect | Use with caution; monitor for signs of reduced anticoagulation |
| Rosuvastatin (BCRP/OATP1B1 substrate) | BCRP/OATP1B1 inhibition | Increased rosuvastatin exposure | Monitor for statin-related adverse effects; consider dose reduction |
| Hormonal contraceptives | CYP3A4 induction | Reduced efficacy of oral contraceptives | Female partners should use non-hormonal contraception or methods not affected by enzyme induction |
The list above is not exhaustive. Many other medications may be affected by Erleada's enzyme-inducing properties, including certain antifungals (itraconazole, voriconazole), HIV protease inhibitors, immunosuppressants (cyclosporine, tacrolimus), opioids (fentanyl), and cardiovascular medications. Always consult your prescribing oncologist or clinical pharmacist before starting, stopping, or changing any medication while taking Erleada.
Herbal supplements can also interact with Erleada. In particular, St. John's wort (Hypericum perforatum) should be avoided as it is also a CYP3A4 inducer and may compound the enzyme-inducing effects. Grapefruit juice is a CYP3A4 inhibitor but is unlikely to cause clinically significant interactions at typical dietary consumption levels.
What Is the Correct Dosage of Erleada?
Quick Answer: The recommended dose of Erleada is 240 mg (four 60 mg tablets) taken by mouth once daily. Tablets can be taken with or without food and should be swallowed whole. Erleada must always be used together with androgen deprivation therapy (ADT), either a GnRH analogue or after surgical castration.
Adults (Standard Dose)
Erleada 60 mg Film-Coated Tablets
- Dose: 240 mg once daily (four 60 mg tablets)
- Administration: Oral, swallowed whole
- Timing: Once daily, at approximately the same time each day
- With food: Can be taken with or without food
- Combination therapy: Must be used with a GnRH analogue or after surgical castration
Treatment with Erleada should continue until disease progression or unacceptable toxicity occurs. Your doctor will regularly monitor your PSA levels, imaging results, and overall health to assess treatment response and decide on continuing therapy.
In some cases, dose reduction may be necessary to manage side effects. If a dose reduction is required, the recommended reduced dose is 180 mg (three 60 mg tablets) once daily or 120 mg (two 60 mg tablets) once daily, depending on the severity of the side effect. Your doctor will guide you on the appropriate dose adjustment.
If you are taking Erleada with a strong CYP2C8 inhibitor (such as gemfibrozil), the dose of Erleada should be reduced to 120 mg (two 60 mg tablets) once daily. If the strong CYP2C8 inhibitor is discontinued, the Erleada dose should be returned to the dose used prior to initiation of the CYP2C8 inhibitor.
If You Cannot Swallow Tablets
If you have difficulty swallowing whole tablets, Erleada tablets can be mixed with applesauce using the following method:
- Place the required number of whole tablets into a small cup or bowl of applesauce (do not crush the tablets).
- Stir the mixture until the tablets have dispersed.
- Swallow the entire mixture immediately. Do not store it for later use.
- Rinse the cup or bowl with a small amount of water and drink the rinse to ensure you have taken the full dose.
Do not crush, break, or chew the Erleada tablets. The film-coating is designed to ensure consistent absorption and protect against degradation of the active ingredient. If the tablets are crushed, there is also a risk of skin exposure to the active substance for caregivers.
Missed Dose
If you forget to take Erleada at your usual time, take it as soon as you remember on the same day. If a whole day has passed (i.e., you do not remember until the next day), skip the missed dose and take your next dose at the regular time the following day. Do not take a double dose to make up for a missed dose.
If you regularly forget to take your medication, consider setting a daily alarm or using a pill organizer. Consistent daily dosing is important for maintaining effective drug levels in your blood and maximizing the therapeutic benefit of treatment.
Overdose
There is no specific antidote for apalutamide overdose. If you take more than the prescribed dose, stop taking Erleada and contact your doctor or go to your nearest hospital emergency department immediately. In the event of an overdose, treatment should be symptomatic and supportive. Given apalutamide's high protein binding (approximately 96%), hemodialysis is unlikely to significantly remove the drug from the circulation.
Erleada is not approved for use in children or adolescents under 18 years of age. The safety and efficacy of apalutamide in pediatric patients have not been established. Prostate cancer does not occur in children, and the hormonal effects of Erleada make it unsuitable for pediatric use.
What Are the Side Effects of Erleada?
Quick Answer: Like all medicines, Erleada can cause side effects, although not everyone experiences them. The most common side effects include fatigue, skin rash, joint pain, decreased appetite, hypertension, hot flushes, diarrhea, fractures, falls, and weight loss. Some side effects can be serious and require immediate medical attention.
Side effects are listed below according to how common they are. The frequencies are based on data from the SPARTAN and TITAN clinical trials and post-marketing surveillance:
Very Common (may affect more than 1 in 10 people)
- Fatigue (tiredness, lack of energy)
- Skin rash (including maculopapular rash, generalized rash)
- Arthralgia (joint pain)
- Decreased appetite
- Hypertension (high blood pressure)
- Hot flush (sudden feeling of warmth)
- Diarrhea
- Fractures (broken bones)
- Falls
- Weight loss
Common (may affect up to 1 in 10 people)
- Muscle spasms
- Pruritus (itching)
- Alopecia (hair loss or thinning)
- Dysgeusia (altered sense of taste)
- Hypercholesterolemia (high cholesterol)
- Hypertriglyceridemia (high triglycerides)
- Ischemic heart disease (reduced blood flow to the heart)
- Cerebrovascular accident / Transient ischemic attack (stroke/mini-stroke)
- Hypothyroidism (underactive thyroid)
- Neutropenia (low white blood cell count)
- Nausea
- Peripheral edema (swelling in hands/feet)
Uncommon (may affect up to 1 in 100 people)
- Seizures (convulsions)
- Lichenoid skin reactions
- Restless legs syndrome
Rare / Not known (cannot be estimated from available data)
- Interstitial lung disease / Pneumonitis
- Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)
- Stevens-Johnson Syndrome (SJS)
- Toxic Epidermal Necrolysis (TEN)
- Agranulocytosis (dangerously low white blood cells)
- QT prolongation (heart rhythm abnormality)
Skin rash is one of the most characteristic side effects of Erleada. It typically appears within the first few months of treatment and is most commonly a maculopapular rash. In clinical trials, approximately 24% of patients experienced rash. Most cases were grade 1 or 2 (mild to moderate) and could be managed with antihistamines, topical corticosteroids, or dose interruption. Rash led to permanent discontinuation in approximately 5% of patients. Your doctor may recommend prophylactic dermatology consultation if you develop early signs of rash.
Fatigue is the most frequently reported side effect overall, affecting approximately 30% of patients. This can range from mild tiredness to more significant exhaustion that affects daily activities. Regular exercise, adequate sleep, and energy conservation strategies may help manage fatigue. Your doctor may also check for other contributing factors such as anemia or thyroid dysfunction.
Hypertension occurs in a significant proportion of patients and should be monitored regularly. Your doctor will check your blood pressure at each visit and may start or adjust blood pressure medications as needed. Home blood pressure monitoring may also be recommended.
- Seizure or convulsion (involuntary shaking or loss of consciousness)
- Chest pain, arm pain, shortness of breath, or sudden severe headache (possible heart attack or stroke)
- Widespread blistering skin rash, peeling skin, sores in the mouth, eyes, or genitals, or high fever (signs of DRESS, SJS, or TEN)
- New or worsening shortness of breath or persistent cough (possible interstitial lung disease)
- Sudden weakness or numbness on one side of the body, difficulty speaking, or vision changes (signs of stroke)
- Signs of infection with high fever and severe low white blood cell count (possible agranulocytosis)
How Should You Store Erleada?
Quick Answer: Store Erleada in its original packaging to protect from moisture. No special temperature requirements apply. Keep the medicine out of the sight and reach of children. Do not use after the expiry date printed on the package.
Erleada tablets are moisture-sensitive. Always store them in the original bottle or blister packaging with the cap tightly closed or blisters intact. Do not transfer tablets to a different container such as a daily pill organizer for extended periods, as this may expose them to excessive moisture and affect their stability.
No special temperature storage conditions are required for Erleada. Store at room temperature (typically below 30 degrees Celsius / 86 degrees Fahrenheit). Avoid storing in areas of high humidity such as bathrooms. Keep the tablets in a dry location.
Keep this medicine out of the sight and reach of children. The child-resistant container closure provides an additional layer of safety, but secure storage is always recommended. Do not use Erleada after the expiry date which is stated on the bottle label, blister packaging, or outer carton 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. Apalutamide is an endocrine-active substance, and improper disposal could potentially contaminate water sources. Many pharmacies and hospitals have pharmaceutical waste collection programs. These measures will help protect the environment.
What Does Erleada Contain?
Quick Answer: Each Erleada film-coated tablet contains 60 mg of the active substance apalutamide. The tablets are yellowish-green to greyish-green, oblong-shaped, approximately 17 mm long by 9 mm wide, and engraved with "AR 60" on one side.
Active substance: Each film-coated tablet contains 60 mg of apalutamide.
Other ingredients (excipients):
- Tablet core: Silicified microcrystalline cellulose, croscarmellose sodium, hypromellose 2910 (15 mPa.s), magnesium stearate, colloidal anhydrous silica, and purified water (removed during processing).
- Film-coating: Hypromellose 2910 (6 mPa.s), titanium dioxide (E171), macrogol 400, iron oxide yellow (E172), and iron oxide black (E172). The combination of these colorants gives the tablet its characteristic yellowish-green to greyish-green appearance.
Appearance: Erleada tablets are yellowish-green to greyish-green, oblong-shaped film-coated tablets. Each tablet is approximately 17 mm long and 9 mm wide. One side is engraved with "AR 60" for identification. The tablets have a smooth film-coating and a biconvex shape.
Packaging options: Erleada is available in bottles containing 112 film-coated tablets (28-day supply at the recommended daily dose of 240 mg). Each bottle includes a desiccant to protect against moisture. Erleada may also be available in blister packs in some markets. The packaging includes a patient information leaflet with detailed instructions for use.
Frequently Asked Questions About Erleada
References
- European Medicines Agency (EMA). Erleada (apalutamide) - Summary of Product Characteristics. Last updated 2025. Available at: https://www.ema.europa.eu/en/medicines/human/EPAR/erleada
- U.S. Food and Drug Administration (FDA). ERLEADA (apalutamide) Prescribing Information. Janssen Products, LP. 2024. Available at: FDA Prescribing Information
- Smith MR, Saad F, Chowdhury S, et al. Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer (SPARTAN trial). N Engl J Med. 2018;378(15):1408-1418. doi:10.1056/NEJMoa1715546
- Chi KN, Agarwal N, Bjartell A, et al. Apalutamide for Metastatic, Castration-Sensitive Prostate Cancer (TITAN trial). N Engl J Med. 2019;381(1):13-24. doi:10.1056/NEJMoa1903307
- Smith MR, Saad F, Chowdhury S, et al. Apalutamide and Overall Survival in Prostate Cancer (SPARTAN final analysis). Eur Urol. 2021;79(1):150-158. doi:10.1016/j.eururo.2020.08.011
- Chi KN, Chowdhury S, Bjartell A, et al. Apalutamide in Patients With Metastatic Castration-Sensitive Prostate Cancer: Final Survival Analysis of the TITAN Trial. J Clin Oncol. 2021;39(20):2294-2303. doi:10.1200/JCO.20.03488
- Parker C, Castro E, Fizazi K, et al. Prostate cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2020;31(9):1119-1134. doi:10.1016/j.annonc.2020.06.011
- National Comprehensive Cancer Network (NCCN). Clinical Practice Guidelines in Oncology: Prostate Cancer. Version 4.2024. Available at: https://www.nccn.org
- World Health Organization (WHO). Global Cancer Observatory - Prostate Cancer Fact Sheet. 2024. Available at: https://gco.iarc.who.int
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