Prostate Cancer
Androgen receptor inhibitor indicated for the treatment of metastatic castration-resistant prostate cancer in patients who have previously received docetaxel
160 mg PO qDay
Dosage Modifications
≥Grade 3 toxicity or an intolerable side effect: Withhold dose for 1 week or until symptoms improve to ≤Grade 2, then resume at the same or a reduced dose (120 mg or 80 mg), if warranted
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, re-establish enzalutamide to the dose used prior to initiation of the strong CYP2C8 inhibitor
Dosing Considerations
May administer with or without food
Swallow capsule whole; do not chew, dissolve, or open the capsules
Drug Interactions
Contraindicated (2)
- elvitegravir/cobicistat/emtricitabine/tenofovir
- lumefantrine
Serious - Use Alternative (1)
- bosutinib
Pregnancy & Lactation
Pregnancy Category: X
Not indicated for use in women
Can cause fetal harm when administered to a pregnant woman based on its mechanism of action
Lactation: Unknown whether distributed in breast milk
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 (active metabolite)
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)
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