Dosing & Uses
Dosage Forms & Strengths
capsule
- 40mg
Prostate Cancer
Indicated for treatment of castration-resistant prostate cancer
160 mg PO qDay
Also see Administration
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 the same or reduced dose (eg, 120 mg or 80 mg), if necessary
Concomitant strong CYP2C8 inhibitors
- Avoided if possible
- If must be coadministered with a strong CYP2C8 inhibitor, reduce enzalutamide dose to 80 mg qDay
- If coadministration of the strong inhibitor is discontinued, reestablish enzalutamide to the dose used prior to initiation of the strong CYP2C8 inhibitor
Concomitant strong CYP3A4 inducers
- Avoided if possible
- If must be coadministered with a strong CYP3A4 inducer, increase enzalutamide dose from 160 mg to 240 mg qDay
- If coadministration of the strong inducer is discontinued, reestablish enzalutamide to the dose used prior to initiation of the strong CYP3A4 inducer
Renal impairment
- Mild-to-moderate: No initial dosage adjustment is necessary
- Severe (CrCl <30 mL/min) and end-stage renal disease: Not assessed
Hepatic impairment
- Mild-to-severe: No initial dosage adjustment is 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
All grades of severities unless otherwise indicated
>10%
Hyperglycemia (78%)
Asthenic conditions (40-51%)
Hypermagnesemia (26%)
Back pain (26%)
Diarrhea (22%)
Arthralgia (21%)
Hot flush (13-20%)
Hyponatremia (16%)
Peripheral edema (15%)
Musculoskeletal pain (15%)
Hypertension (6.4-14%)
Nausea (11-14%)
Constipation (9.1-13%)
Diarrhea (12%)
Dizziness (9.5-12%)
Upper respiratory tract infection (11-12%)
Fall (11%)
Weight loss (11%)
1-10%
Muscular weakness (9.8%)
Fractures (9.8%)
Insomnia (8.8%)
Lower respiratory tract and lung infection (8.5%)
Neutropenia (8.2%)
Spinal cord compression and cauda equina syndrome (7.4%)
Hematuria (6.9%)
Paresthesia (6.6%)
Anxiety (2.8-6.5%)
Decreased weight (5.9%)
Pollakiuria (4.8%)
Fall (4.6%)
Cognitive and attention disorders (4.6%)
Mental impairment disorders (4.3%)
Nonpathologic fractures (4%)
Hypoesthesia (4%)
Pruritus (3.8%)
Dry skin (3.5%)
Epistaxis (3.3%)
Hyperglycemia, Grade 3-4 (2.9%)
Musculoskeletal stiffness (2.6%)
Fractures, Grade 3-4 (2%)
Hyponatremia, Grade 3-4 (1.3%)
Fall, Grade 3-4 (1.3%)
<1%
Neutropenia, Grade 3-4
Decreased appetite, Grade 3-4
Dizziness, Grade 3-4
Headache, Grade 3-4
Cognitive and attention disorders, Grade 3-4
Hot flush, Grade 3-4
Nausea, Grade 3-4
Constipation, Grade 3-4
Decreased weight, Grade 3-4
Anxiety, Grade 3-4
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
Warnings
Contraindications
None
Cautions
Because of risk of seizure associated with enzalutamide use, 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 more commonly in the enzalutamide arm compared to placebo arm (2.7% vs 1.2%); 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 been 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)
Administration
Oral Administration
May administer with or without food
Swallow capsule whole; do not chew, dissolve, or open the capsules
Storage
Store capsules at 20-25°C (68-77°F) in a dry place and keep the container tightly closed; excursions permitted from 15-30°C (59-86°F)
Images
Patient Handout
Formulary
Adding plans allows you to compare formulary status to other drugs in the same class.
To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.
Adding plans allows you to:
- View the formulary and any restrictions for each plan.
- Manage and view all your plans together – even plans in different states.
- Compare formulary status to other drugs in the same class.
- Access your plan list on any device – mobile or desktop.
