DESCRIPTION
MECHANISM OF ACTION
• Pure androgen receptor (AR) antagonist that acts on different steps in the androgen receptor signaling pathway.
• Competitively inhibits androgen binding to ARs and by inhibiting AR nuclear translocation and co-activator recruitment of the ligand-receptor complex.
• Inhibits the androgen-AR pathway at the receptor and post-receptor ligand binding level.
• N-desmethyl enzalutamide metabolite exhibits similar antitumor activity to enzalutamide.
ABSORPTION
Rapidly absorbed following oral administration. Peak plasma levels observed 0.5–3 hours after oral ingestion.
Steady-state drug levels achieved by day 28 following daily dosing. Co-administration with food does not alter the extent of absorption.
DISTRIBUTION
Mean apparent volume of distribution after a single oral dose is 110 L (29% CV). Extensive binding (97%–98%) to plasma proteins, primarily albumin.
N-desmethyl enzalutamide metabolite also exhibits extensive binding to plasma proteins (95%).
INDICATIONS
1. FDA-approved for metastatic castration-resistant prostate cancer in patients who have received prior chemotherapy containing docetaxel.
2. FDA-approved for first-line treatment of metastatic castration-resistant prostate cancer.
DOSAGE RANGE
Recommended dose is 160 mg PO once daily.
DRUG INTERACTIONS
1. Co-administration with strong CYP2C8 inhibitors, such as gemfibrozil, increases the plasma drug concentrations of both enzalutamide and
N-desmethyl enzalutamide.
2. Co-administration with strong or moderate CYP2C8 inducers (e.g., rifampin) may alter the plasma exposure of enzalutamide.
3. Co-administration with strong CYP3A4 inhibitors (e.g., itraconazole) may increase the plasma drug concentration of enzalutamide and N-desmethyl enzalutamide.
4. Co-administration with strong CYP3A4 inducers (e.g., carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine) and moderate CYP3A4 inducers (e.g., bosentan, efavirenz, etravirine, modafinil, nafcillin) and St. John’s Wort may decrease the plasma drug concentration of enzalutamide.
SPECIAL CONSIDERATIONS
1. No initial dosage adjustment is necessary for patients with mild or moderate renal impairment. Has not been studied in patients with severe renal impairment (CrCL < 30 mL/min) or end-stage renal disease.
2. No initial dosage adjustment is necessary for patients with mild or moderate hepatic impairment. Patients with severe hepatic impairment (Child-Pugh Class C) have not been evaluated.
3. Closely monitor patients for seizure activity. It is unclear as to which patients are at increased risk for developing seizures.
4. Enzalutamide should not be handled by females who are or who may become pregnant. Male patients with female partners of reproductive potential should use effective contraception during treatment and for 3 months after the last dose of drug.
TOXICITY 1
Asthenia and fatigue occur in 50% of patients.
TOXICITY 2
Musculoskeletal adverse events occur including back pain, arthralgia, musculoskeletal pain, muscle weakness, musculoskeletal stiffness, and non-pathologic bone fractures.
TOXICITY 3
Diarrhea occurs in about 20% of patients and is usually mild.
TOXICITY 4
Hot flashes occur in 20% of patients.
TOXICITY 5
Peripheral edema.
TOXICITY 6
Seizures occur rarely in < 1% of patients, which usually resolve upon discontinuation of therapy.
SPECIFICATION
Login To Comment