Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
ENZALUTAMIDE vs APALUTAMIDE
Clinician-reviewed, head-to-head comparison of mechanism, dosing, pharmacokinetics, and safety profiles.
Last clinically reviewed: July 2026 · OpiCalc Medical Review Team
Androgen receptor inhibitor; binds to the androgen receptor and inhibits androgen receptor nuclear translocation, DNA binding, and coactivator recruitment.
Apalutamide is a nonsteroidal antiandrogen that inhibits androgen receptor (AR) nuclear translocation, DNA binding, and transcription of AR target genes. It also decreases AR-mediated tumor cell proliferation and increases apoptosis.
Treatment of metastatic castration-resistant prostate cancer,Treatment of metastatic castration-sensitive prostate cancer
Metastatic castration-sensitive prostate cancer (m CSPC),Non-metastatic castration-resistant prostate cancer (nm CRPC)
160 mg orally once daily
240 mg orally once daily with or without food.
Terminal elimination half-life is approximately 5.8 days (range 2.8–10.2 days) after steady state; supports once-daily dosing.
Terminal elimination half-life is approximately 3 days (72 hours) for apalutamide and 3–5 days for the active metabolite N-desmethyl-apalutamide. The long half-life supports once-daily dosing and requires approximately 2–3 weeks to reach steady state.
Primarily metabolized by CYP2C8 and CYP3A4; forms active metabolite N-desmethyl enzalutamide
Primarily metabolized by CYP2C8 and CYP3A4 to active metabolite N-desmethylapalutamide. Also involves glucuronidation by UGTs.
Primarily hepatic metabolism; ~70% of dose excreted in feces (as unchanged drug and metabolites), ~1% in urine as unchanged drug. Biliary excretion is a major route.
Apalutamide and its active metabolite N-desmethyl-apalutamide are eliminated primarily via hepatic metabolism and subsequent fecal excretion. Approximately 65% of the dose is recovered in feces (as unchanged drug and metabolites) and 24% in urine (primarily as metabolites). Renal excretion of unchanged drug is negligible.
97–98% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein.
Apalutamide is highly protein bound (>96%), primarily to albumin and alpha-1-acid glycoprotein. No significant displacement interactions are expected with other highly bound drugs.
Approximately 110 L (1.1 L/kg for a 70 kg patient); indicates extensive extravascular distribution.
Apparent volume of distribution (Vd/F) is approximately 200 L (2.7 L/kg for a 70 kg adult), indicating extensive distribution into tissues including the prostate and other androgen-responsive organs.
Oral bioavailability is not published; absorption is at least moderate based on systemic exposure. Food does not significantly affect absorption.
Oral bioavailability is not precisely determined due to lack of an intravenous formulation, but absorption is at least 90% based on mass balance studies. Food does not significantly affect absorption, so it can be taken with or without food.
No dose adjustment required for mild to moderate renal impairment (e GFR 30-89 m L/min). Insufficient data for severe renal impairment (e GFR <30 m L/min) or end-stage renal disease.
No dose adjustment required for mild to moderate renal impairment (e GFR 30-89 m L/min). For severe renal impairment (e GFR 15-29 m L/min), use with caution; no specific dose recommendation. Not studied in end-stage renal disease (e GFR <15 m L/min) or on hemodialysis.
No dose adjustment for mild hepatic impairment (Child-Pugh A). For moderate (Child-Pugh B): reduce dose to 80 mg once daily. Not recommended for severe (Child-Pugh C).
Mild hepatic impairment (Child-Pugh A): No dose adjustment. Moderate hepatic impairment (Child-Pugh B): Reduce dose to 120 mg once daily. Severe hepatic impairment (Child-Pugh C): Not recommended due to lack of data.
Not approved for use in pediatric patients; safety and efficacy not established.
Safety and efficacy not established; no approved pediatric dosing.
No specific dose adjustment required; elderly patients may be more susceptible to adverse effects such as falls, fractures, and hypertension. Monitor closely.
No specific dose adjustment required; consider comorbidities and potential for increased adverse effects based on renal and hepatic function.
None
None.
Seizure risk,Posterior reversible encephalopathy syndrome (PRES),Hypersensitivity reactions including angioedema,Increased risk of falls and fractures,Embryo-fetal toxicity
Seizures: Discontinue permanently if seizure occurs during treatment.,Fractures and Falls: Increased risk of bone fractures and falls; assess bone density and manage accordingly.,Cardiovascular Events: Increased risk of hypertension, cardiac ischemia, and heart failure; monitor cardiovascular status.,Hypothyroidism: Monitor thyroid function before and during treatment; replacement therapy may be needed.,Embryo-Fetal Toxicity: Can cause fetal harm; advise males with female partners of reproductive potential to use effective contraception.
Pregnancy,Concomitant use with strong CYP2C8 inhibitors or inducers,Concomitant use with strong CYP3A4 inducers
Pregnancy (can cause fetal harm),Women of reproductive potential (unless using effective contraception)
No significant food interactions. Avoid grapefruit juice as it may increase enzalutamide levels (minor interaction). Take with or without food.
Avoid grapefruit and grapefruit juice due to potential CYP3A4 interaction. No other specific dietary restrictions; can be taken with or without food.
Enzalutamide is contraindicated in pregnancy. Based on its mechanism of action (androgen receptor inhibitor), there is a high risk of fetal harm, particularly male pseudohermaphroditism and impaired reproductive development. Use should be avoided in all trimesters. Women of childbearing potential must use effective contraception during treatment and for 1 month after the last dose.
Apalutamide is contraindicated in pregnancy. Based on its mechanism of androgen receptor inhibition, it may cause fetal harm, including feminization of male fetuses and developmental abnormalities. Adequate animal reproduction studies have not been conducted; however, in rats, fetal malformations were observed at exposures below human clinical exposures. Effective contraception is required for females of reproductive potential during treatment and for 3 months after the last dose.
No human data available. Enzalutamide and its active metabolite are likely excreted into human milk. Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended during treatment and for 1 month after the last dose. M/P ratio is unknown.
It is unknown whether apalutamide or its metabolites are excreted in human milk. Due to potential for serious adverse reactions in breastfed infants, breastfeeding is not recommended during treatment and for at least 3 months after the last dose. M/P ratio is not available.
Enzalutamide is contraindicated in pregnancy; therefore, no dose adjustments are recommended. If exposure occurs, discontinue the drug and manage according to clinical judgment. Pregnancy induces metabolic changes (e.g., increased hepatic clearance, plasma volume expansion) that could theoretically reduce exposure, but no data exist to support a specific dose adjustment.
No dosing adjustments have been established for pregnancy. Apalutamide is not indicated for use in pregnant women. Physiological changes in pregnancy may alter pharmacokinetics, but no data are available to guide dose modifications.
Monitor for seizure risk, especially in patients with predisposing factors; enzalutamide may cause hypertension, so check blood pressure regularly; it significantly induces CYP3A4, reducing efficacy of oral contraceptives and other CYP3A4 substrates; use with caution in patients with history of cardiovascular disease; discontinue 5 half-lives before starting another antiandrogen.
Apalutamide is an androgen receptor inhibitor used for non-metastatic castration-resistant prostate cancer (nm CRPC). It is a strong CYP3A4 inducer and moderate CYP2C8 inhibitor, requiring careful management of drug interactions. Monitor thyroid function and blood pressure. Concomitant use with warfarin or other anticoagulants may necessitate increased monitoring due to reduced efficacy. Apalutamide can cause seizures; avoid in patients with history of seizure disorders. Baseline and periodic serum lipid profiles and glucose levels are recommended. Dose reduction in severe hepatic impairment (Child-Pugh C) is suggested.
Take the capsules whole, with or without food, at the same time each day.,Do not crush, chew, or open the capsules.,Report any signs of seizure (e.g., convulsions, loss of consciousness) to your doctor immediately.,Enzalutamide may raise your blood pressure; have it checked regularly.,Use effective non-hormonal contraception during treatment and for 3 months after stopping; hormonal contraceptives may not work.,This drug may cause fatigue, falls, and fractures; avoid activities requiring alertness until you know how it affects you.,Notify your doctor if you experience chest pain, shortness of breath, or leg swelling.,Seek immediate medical attention for symptoms of posterior reversible encephalopathy syndrome (PRES): headache, confusion, visual disturbances.
Take apalutamide with or without food, at the same time each day.,Do not crush, chew, or split tablets; swallow whole.,Avoid grapefruit and grapefruit juice during treatment.,Report signs of seizure, high blood pressure, or thyroid abnormalities to healthcare provider immediately.,Use effective contraception during treatment and for 3 months after last dose; apalutamide may reduce hormonal contraceptive effectiveness.,Inform all healthcare providers of apalutamide use due to potential drug interactions.,May cause fatigue, dizziness, or hot flashes; avoid driving if affected.,Store at room temperature away from moisture and heat.
"Rifaximin is a non-systemic antibiotic with minimal oral absorption (<0.4%), thus is not expected to significantly affect systemic drug metabolism. However, in vitro studies suggest rifaximin can induce the expression of CYP3A4, the major enzyme responsible for the metabolism of enzalutamide. Although clinical data are limited, coadministration could theoretically decrease enzalutamide exposure, reducing its efficacy in treating prostate cancer; conversely, the baseline description suggests an increase, but evidence is conflicting."
"Enzalutamide, a potent CYP3A4 inducer, significantly reduces the exposure of diclofenac, a CYP2C9 substrate, by increasing its hepatic metabolism. This interaction can lead to subtherapeutic diclofenac concentrations, thereby diminishing its analgesic and anti-inflammatory efficacy. Clinically, patients may experience inadequate pain control or exacerbation of inflammatory conditions, such as arthritis, when these agents are coadministered."
"Enzalutamide, a potent androgen receptor inhibitor, significantly induces CYP3A4 and other drug-metabolizing enzymes. Dienogest, a progestin used in endometriosis and contraception, is primarily metabolized by CYP3A4. Coadministration leads to markedly reduced dienogest plasma concentrations, potentially diminishing its therapeutic efficacy in managing endometriosis symptoms or contraceptive effectiveness."
No interactions on record
Explore head-to-head clinical comparisons of other medications in the same therapeutic classes.
Common clinical questions about ENZALUTAMIDE vs APALUTAMIDE, answered by our medical review team.
ENZALUTAMIDE is a Androgen Receptor Inhibitor that works by Androgen receptor inhibitor; binds to the androgen receptor and inhibits androgen receptor nuclear translocation, DNA binding, and coactivator recruitment.. APALUTAMIDE is a Androgen Receptor Inhibitor that works by Apalutamide is a nonsteroidal antiandrogen that inhibits androgen receptor (AR) nuclear translocation, DNA binding, and transcription of AR target genes. It also decreases AR-mediated tumor cell proliferation and increases apoptosis.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between ENZALUTAMIDE and APALUTAMIDE depend on the specific clinical indication. These are both Androgen Receptor Inhibitor agents and are not directly interchangeable by dose. A physician or clinical pharmacist should guide any therapeutic switching decisions.
The standard adult dose of ENZALUTAMIDE is: 160 mg orally once daily. The standard adult dose of APALUTAMIDE is: 240 mg orally once daily with or without food.. Dosing should always be individualized based on indication, renal and hepatic function, age, and other patient factors.
No direct drug-drug interaction has been formally documented between ENZALUTAMIDE and APALUTAMIDE in current clinical databases. However, individual patient risk factors including other medications, organ function, and comorbidities should always be evaluated by a qualified healthcare provider.
The maternal-fetal safety profiles differ. ENZALUTAMIDE is classified as Category D/X. Enzalutamide is contraindicated in pregnancy. Based on its mechanism of action (androgen receptor inhibitor), there is a high risk of fetal harm, particularly male pseudohermaphrod. APALUTAMIDE is classified as Category C. Apalutamide is contraindicated in pregnancy. Based on its mechanism of androgen receptor inhibition, it may cause fetal harm, including feminization of male fetuses and development. Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.