Dosing & Uses
Dosage Forms & Strengths
capsule
- 40mg
tablet
- 40mg
- 80mg
Prostate Cancer
Indicated for treatment of castration-resistant prostate cancer (CRPC) and metastatic castration-sensitive prostate cancer (mCSPC)
160 mg PO qDay
Dosage Modifications
Dosage modifications based on drug-related toxicities
- Grade ≥3 toxicity or an intolerable side effect: Withhold for 1 week or until symptoms improve to Grade ≤2, then resume at same or reduced dose (eg, 120 mg or 80 mg), if necessary
Concomitant strong CYP2C8 inhibitors
- Avoid use
- If coadministration unavoidable, reduce enzalutamide dose to 80 mg qDay
- If strong inhibitor discontinued, return enzalutamide to dose before initiating the strong CYP2C8 inhibitor
Concomitant strong CYP3A4 inducers
- Avoid use
- If coadministration unavoidable, increase enzalutamide dose from 160 mg to 240 mg qDay
- If strong inducer discontinued, return enzalutamide to dose before initiating the strong CYP3A4 inducer
Renal impairment
- Mild-to-moderate (CrCl 30-89 mL/min): No dosage adjustment necessary
- Severe (CrCl <30 mL/min) and end-stage renal disease: Not assessed
Hepatic impairment
- Mild-to-severe (Child Pugh A to C): No dosage adjustment necessary
Dosing Considerations
Patients receiving enzalutamide should also receive a gonadotropin-releasing hormone (GnRH) analog concurrently or should have had bilateral orchiectomy
Safety and efficacy not established
Interactions
Interaction Checker
No Results

Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor

Adverse Effects
>10%
All grades
- Asthenic conditions (47-51%)
- Back pain (26-29%)
- Constipation (23%)
- Diarrhea (22%)
- Arthralgia (21%)
- Hot flush (18-20%)
- Decreased appetite (19%)
- Upper respiratory tract infection (16%)
- Peripheral edema (12-15%)
- Musculoskeletal pain (15%)
- Hypertension (6.4-14%)
- Falls (4.6-13%)
- Headache (11-12%)
- Decreased weight (12%)
- Dyspnea (11%)
- Dizziness (9.5-11%)
1-10% H3
All grades
- Muscular weakness (9.8%)
- Insomnia (8.2-8.8%)
- Hematuria (6.9-8.8%)
- Nonpathologic fractures (4-8.8%)
- Lower respiratory tract and lung infection (7.9-8.5%)
- Dysgeusia (7.6%)
- Spinal cord compression and cauda equina syndrome (7.4%)
- Anxiety (6.5%)
- Pollakiuria (4.8%)
- Pruritus (3.8%)
- Dry skin (3.5%)
- Epistaxis (3.3%)
Grade 3-4
- Asthenic conditions (3.4-9%)
- Hypertension (7.2%)
- Spinal cord compression and cauda equina syndrome (6.6%)
- Paresthesia (6.6%)
- Back pain (2.5-5.3%)
- Mental impairment disorders (4.3-5.7%)
- Hypoesthesia (4%)
- Gynecomastia (3.4%)
- Arthralgia (1.6-2.5%)
- Lower respiratory tract and lung infection (1.5-2.4%)
- Hypertension (2.1%)
- Restless leg syndrome (2.1%)
- Nonpathologic fractures (1.4-2.1%)
- Hematuria (1.3-1.8%)
- Falls (0.3-1.6%)
- Muscular weakness (1.5%)
- Musculoskeletal pain (1.3%)
- Diarrhea (0.3-1.1%)
- Peripheral edema (0.2-1%)
<1%
Grade 3-4
- Headache (0.2-0.9%)
- Decreased weight (0.8%)
- Constipation (0.7%)
- Dyspnea (0.6%)
- Dizziness (0.3-0.5%)
- Mental impairment disorders (0.3%)
- Hypoesthesia (0.3%)
- Anxiety (0.3%)
- Decreased appetite (0.3%)
- Epistaxis (0.1%)
- Hot flush (0.1%)
- Dysgeusia (0.1%)
- Restless leg syndrome (0.1%)
- Insomnia (0.1%)
Postmarketing Reports
Body as a whole: Hypersensitivity (edema of the face, tongue, lip, or pharynx)
Gastrointestinal disorders: Vomiting
Neurological disorders: Posterior reversible encephalopathy syndrome (PRES)
Skin and subcutaneous tissue disorders: Rash, severe cutaneous adverse reactions (including Stevens-Johnson syndrome (SJS), erythema multiforme, toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalized exanthematous pustulosis (AGEP))
Warnings
Contraindications
None
Cautions
Seizure occurred in patients receiving enzalutamide in randomized clinical trials; advise patients of risk of engaging in activities where sudden loss of consciousness could cause serious harm to themselves or others; permanently discontinue therapy in patients who develop seizure during treatment
Posterior reversible encephalopathy syndrome (PRES) reported with use; discontinue therapy in patients who develop PRES
Hypersensitivity reactions, including edema of the face, tongue, or lip have been observed; pharyngeal edema reported in postmarketing cases; advise patients who experience any symptoms of hypersensitivity to temporarily discontinue treatment and promptly seek medical care; permanently discontinue drug for serious hypersensitivity reactions
In clinical studies, ischemic heart disease occurred; monitor for signs and symptoms of ischemic heart disease; optimize management of cardiovascular risk factors (eg, hypertension, diabetes, or dyslipidemia); discontinue treatment for Grade 3-4 ischemic heart disease
Falls and fractures occurred; evaluate patients for fracture and fall risk; monitor and manage patients at risk for fractures according to established treatment guidelines and consider use of bone-targeted agents; routine bone density assessment and treatment of osteoporosis with bone-targeted agents were not performed in the studies
Safety and efficacy not established in females (see Pregnancy)
Drug interaction overview
- CYP2C8 substrate; avoid coadministration with strong CYP2C8 inhibitors (see Dosage Modifications)
- Enzalutamide is a strong CYP3A4 inducer and a moderate CYP2C9 and CYP2C19 inducer; shown to reduce the plasma exposure to midazolam (CYP3A4 substrate), warfarin (CYP2C9 substrate), and omeprazole (CYP2C19 substrate); caution if coadministered with narrow therapeutic index drugs that are substrates of the aforementioned CYP isoenzymes
Pregnancy & Lactation
Pregnancy
Safety and efficacy not established in females
Drug should not be handled by females who are or may become pregnant
Animal data
- Based on animal reproductive studies and mechanism of action, enzalutamide may cause fetal harm and loss of pregnancy
- There are no human data on use in pregnant females
- In animal reproduction studies, oral administration of enzalutamide in pregnant mice during organogenesis caused adverse developmental effects at doses lower than the maximum recommended human dose
Contraception
- Based on findings in animal reproduction studies, advise male patients with female partners of reproductive potential to use effective contraception during treatment and for 3 months after the final dose
Infertility
- Based on animal studies, may impair fertility in males of reproductive potential
Lactation
Not indicated for use in females; unknown whether distributed in breast milk
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Androgen receptor inhibitor; competitively inhibits androgen binding to androgen receptors; also inhibits androgen receptor nuclear translocation and interaction with DNA resulting in decreased proliferation and induced cell death
Major metabolite, N-desmethyl enzalutamide, exhibited similar in vitro activity to enzalutamide
Absorption
Peak plasma time: 1 hr
Peak plasma concentration (steady-state): 16.6 mcg/mL (parent compound); 12.7 mcg/mL (N-desmethyl enzalutamide)
Steady-state achieved by Day 28
Distribution
Protein Bound: 97-98% (parent compound); 95% (active metabolite)
Vd: 110 L
Metabolism
Metabolized by liver by CYP2C8 and CYP3A4; CYP2C8 is primarily responsible for the formation of the active metabolite (N-desmethyl enzalutamide)
Metabolites: N-desmethyl enzalutamide (active); carboxylic acid metabolite (inactive)
Strong CYP3A4 inducer; CYP2C9 and CYP2C19 moderate inducer
Elimination
Excretion: 14% feces, 71% urine (as inactive metabolites)
Half-life (single 160-mg oral dose): 5.8 days (metastatic CRPC patients); 7.8-8.6 days (healthy adults)
Clearance: 0.56 L/hr
Administration
Oral Administration
May administer with or without food
Swallow capsules or tablets whole; do not chew, dissolve, or open capsules or crush tablets
Storage
Capsules or tablets
Store at 20-25ºC (68-77ºF) in a dry place and keep the container tightly closed; excursions permitted from 15-30ºC (59-86ºF)
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Patient Handout
Formulary
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