XTANDI

Enzalutamide achieves steady-state by Day 28 and its AUC accumulates approximately 8.3-fold relative to a single dose. At steady-state, the mean (%CV) maximum concentration (C max ) for enzalutamide and N-desmethyl enzalutamide are 16.6 µg/mL (23%) and 12.7 µg/mL (30%), respectively, and the mean (%CV) minimum concentrations (C min ) are 11.4 µg/mL (26%) and 13.0 µg/mL (30%), respectively. Enzalutamide showed approximately dose proportional pharmacokinetics over the daily dose range of 30 (0.2 t...

The efficacy of XTANDI in patients with CRPC (N = 4692), mCSPC (N = 1150), or nmCSPC with high‑risk BCR (N = 1068) was demonstrated in six randomized, multicenter clinical trials. Patients received concomitant GnRH therapy or had prior bilateral orchiectomy, unless otherwise indicated. AFFIRM (NCT00974311): XTANDI versus Placebo in Metastatic CRPC Following Chemotherapy In AFFIRM, a total of 1199 patients who had received prior docetaxel-based chemotherapy were randomized 2:1 to receive either XTANDI orally at a dose of 160 mg once daily (N = 800) or placebo orally once daily (N = 399). Study ...

The following is discussed in more detail in other sections of the labeling:

• Seizure [see Warnings and Precautions ( 5.1 )]
• Posterior Reversible Encephalopathy Syndrome (PRES) [see Warnings and Precautions ( 5.2 )]
• Hypersensitivity [see Warnings and Precautions ( 5.3 )]
• Ischemic Heart Disease [see Warnings and Precautions ( 5.4 )]
• Falls and Fractures [see Warnings and Precautions ( 5.5 )]
• Dysphagia or Choking [see Warnings and Precautions ( 5.7 )] The most common adverse reactions (≥...

None. None. ( 4 )

• Seizure occurred in 0.6% of patients receiving XTANDI. In patients with predisposing factors, seizures were reported in 2.2% of patients. Permanently discontinue XTANDI in patients who develop a seizure during treatment. ( 5.1 )
• Posterior reversible encephalopathy syndrome (PRES): Discontinue XTANDI. ( 5.2 )
• Hypersensitivity: Discontinue XTANDI. ( 5.3 )
• Ischemic Heart Disease: Optimize management of cardiovascular risk factors. Discontinue XTANDI for Grade 3-4 adverse reactions ( 5.4 )
• ...

7 DRUG INTERACTIONS

• Strong CYP2C8 Inhibitors: Avoid strong CYP2C8 inhibitors. If coadministration cannot be avoided, reduce the dosage of XTANDI. ( 2.3 , 7.1 )
• Strong CYP3A4 Inducers: Avoid strong CYP3A4 inducers. If coadministration cannot be avoided, increase the dosage of XTANDI. ( 2.3 , 7.1 )
• Avoid coadministration with certain CYP3A4, CYP2C9, or CYP2C19 substrates for which a minimal de...