Pregnancy Category: X
Pharmacologic: androgen receptor inhibitors
Pharmacologic: androgen receptor inhibitors
Management of metastatic castration-resistant prostate cancer in patients previously treated with docetaxel.
Acts as an androgen receptor inhibitor, preventing the binding of androgen; also inhibits androgen nuclear translocation and DNA interaction.
Decreases proliferation and induces cell death of prostate cancer cells.
Decreased growth and spread of prostate cancer.
Absorption: Well absorbed following oral administration.
Protein Binding: Enalutamide—97–98%; N-desmethylenzalutamide—95%.
Metabolism and Excretion: Extensively metabolized by the liver (CYP2C8 and CYP3A4 enzyme systems); one metabolite (N-desmethylenzalutamide) has antineoplastic activity. Metabolites are primarily renally excreted, only minimal amounts as unchanged drug.
Half-life: Enalutamide—5.8 days; N-desmethylenzalutamide—7.8–8.6 days.
Time/action profile (improved survival)
Contraindicated in: Pregnancy (may cause fetal harm) or women with child-bearing potential.
Use Cautiously in: History of seizures, underlying brain pathology, cerebrovascular accident, transient ischemic attack (within 12 mo), brain metastases or brain arteriovenous malformation (may increase risk of seizures); Geriatric: elderly may be more sensitive to drug effects; Pediatric: Safe and effective in children has not been established.
Adverse Reactions/Side Effects
Central nervous system
- seizures (life-threatening)
- spinal cord compression/cauda equina syndrome (life-threatening)
- headache (most frequent)
- weakness (most frequent)
- mental impairment disorders
Ear, Eye, Nose, Throat
- peripheral edema (most frequent)
- diarrhea (most frequent)
- urinary frequency
- hot flush (most frequent)
- dry skin
- arthralgia (most frequent)
- musculoskeletal pain (most frequent)
- muscular stiffness
- musular weakness
Drug-Drug interactionStrong inhibitors of the CYP2C8 enzyme system (including gemfibrozil ) may ↑ blood levels and the risk of adverse reactions/toxicity and should be avoided; if concurrent administration is necessary, dose of enzalutamide should be ↓.Strong/moderate inducers of the CYP3A4 or CYP2C8 enzyme systems (including rifampin ) may alter levels and response and should be avoided.Substrates of the CYP3A4, CYP2C9 (including warfarin) and CYP2C19 systems that have narrow therapeutic indexes should be avoided as their levels and activity may be decreased; careful monitoring is recommended.Concurrent use of drugs that ↓ seizure threshold may ↑ risk of seizures.
Oral (Adults) 160 mg (four 40-mg capsules) once daily; if ≥Grade 3 toxicity or intolerable adverse reactions occur, discontinue for 1 wk and resume at the same or lower dose (80 or 120 mg). Concurrent use of strong CYP2C8 inhibitors—80 mg once daily.
Capsules: 40 mg
- Monitor for seizures. Implement seizure precautions.
- Lab Test Considerations: May cause hematuria.
Potential Nursing DiagnosesActivity intolerance
- Oral: Administer 4 capsules once daily without regard to food. Swallow capsules whole; do not open, dissolve, or chew.
- If ≥Grade 3 toxicity or intolerable side effects occur, withhold dose for 1 wk or until symptoms improve to <Grade 2, then resume at same or reduced dose (120 mg or 80 mg).
- Instruct patient to take enzalutamide as directed at the same time each day. Take missed doses as soon as remembered within the same day. If a whole day is missed, omit dose and take next day's scheduled dose; do not double doses. Advise patient not to interrupt, modify dose, or stop taking enzalutamide without consulting health care professional.
- May cause seizures, dizziness, mental impairment, paresthesia, hypoesthesia, falls, and hallucinations. Caution patient to avoid driving and other activities requiring alertness until response to medication is known. Notify health care professional immediately if loss of consciousness or seizure occurs.
- Inform patient of common side effects associated with enzalutamide: asthenia/fatigue, back pain, diarrhea, arthralgia, hot flush, peripheral edema, musculoskeletal pain, headache, upper and lower respiratory infection, muscular weakness, dizziness, insomnia, spinal cord compression, cauda equina syndrome, hematuria, paresthesia, anxiety, and hypertension. Notify health care professional if falls or problems thinking clearly, or if side effects are bothersome.
- Caution patients that enzalutamide is teratogenic. Advise patient to avoid pregnancy and breast feeding during and for 3 mo following completion of therapy. Male patients should use a condom if having sex with a pregnant woman, and a condom and another effective method of birth control should be used if having sex with a woman of child-bearing potential.
- Decreased growth and spread of prostate cancer.