enzalutamide  

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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