Enzalutamide Treatment Regimen
Enzalutamide is administered orally at a fixed dose of 160 mg once daily, taken continuously until disease progression or unacceptable toxicity occurs. 1, 2
Standard Dosing
- The approved dose is 160 mg (four 40 mg capsules) taken orally once daily 1, 2
- Enzalutamide can be taken with or without food, as food does not meaningfully affect drug absorption 1
- Treatment should continue until radiographic disease progression or unacceptable toxicity develops 2
- Steady-state concentrations are achieved by day 28 of continuous daily dosing 1
Pharmacokinetic Characteristics
- The elimination half-life is 5.8 days, allowing for once-daily dosing 1
- Drug accumulation at steady state is approximately 8.3-fold 1
- Intersubject variability is low (≤30%), resulting in predictable pharmacokinetics 1
- Enzalutamide is primarily metabolized by CYP3A4 and CYP2C8 in the liver 3
- Renal excretion is an insignificant elimination pathway 1
Special Populations
- No dose adjustment is required in patients with mild to moderate hepatic impairment (Child-Pugh Class A and B), as drug exposure remains similar to those with normal hepatic function 1
- Enzalutamide acts as a strong inducer of CYP3A4 and moderate inducer of CYP2C9 and CYP2C19, requiring careful evaluation of concomitant medications 3
- The drug is also a mild inhibitor of P-glycoprotein efflux transporter 3
Duration of Therapy
- In hormone-naïve prostate cancer, 67% of patients remained on enzalutamide at 97 weeks (approximately 2 years) with sustained PSA reductions 4
- In metastatic castration-resistant prostate cancer, treatment continues indefinitely until progression, with median radiographic progression-free survival significantly extended compared to placebo 2
- Long-term therapy is well-tolerated, with the most common adverse events being gynecomastia, nipple pain, fatigue, hot flushes, and hypertension 4, 2
Drug Interactions Requiring Monitoring
- Avoid strong CYP3A4 inducers and strong CYP2C8 inhibitors when possible, as these significantly alter enzalutamide metabolism 3
- Monitor closely when coadministering with cardiovascular medications, antidiabetic drugs, antidepressants, anti-seizure medications, analgesics, and immunosuppressants due to enzalutamide's enzyme-inducing effects 3
- Proton pump inhibitors, antigout medications, and common vitamins/supplements may also interact 3
Clinical Monitoring
- PSA levels should be monitored regularly to assess treatment response 4, 2
- Radiographic imaging should be performed every 12 weeks to evaluate disease progression 2
- Blood pressure monitoring is recommended due to hypertension risk 2
- Bone mineral density should be monitored during long-term therapy, though enzalutamide shows relatively minimal negative effects on total-body BMD 4