的CYP3A4诱导剂和适度的CYP2C9和CYP2C19诱导剂。避免使用治疗指数窄的CYP3A4、CYP2C9和CYP2C19底物，因为XTANDI可能减少这些药物的血浆暴露。如果XTANDI与华法林（CYP2C9底物）联合使用，则进行额外的INR监测。
1）：https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b129fdc9-1d8e-425c-a5a9-8a2ed36dfbdf
2）：http://www.astellasoncology.com/us/news/fda-approves-supplemental-new-drug-application-for-xtandi-capsules.html
Xtandi(enzalutamide)capsules 40mg
Manufacturer:
Astellas Pharma and Medivation
Pharmacological Class:
Androgen receptor inhibitor.
Active Ingredient(s):
Enzalutamide 40mg; caps.
Indication(s):
Treatment of metastatic castration-resistant prostate cancer in patients who have previously received docetaxel.
Pharmacology:
Enzalutamide is an androgen receptor inhibitor that acts on different steps in the androgen receptor signaling pathway. Enzalutamide has been shown to competitively inhibit androgen binding to androgen receptors and inhibit androgen receptor nuclear translocation and interaction with DNA.
Clinical Trials:
The efficacy and safety of Xtandi in patients with metastatic castration-resistant prostate cancer who had received prior docetaxel-based therapy were assessed in a randomized, placebo-controlled, multicenter phase 3 clinical trial. The primary endpoint was overall survival. A total of 1199 patients were randomized 2:1 to receive either Xtandi 160mg once daily (N=800) or placebo orally once daily (N=399). All patients continued androgen deprivation therapy. Patients were allowed, but not required to continue or initiate glucocorticoids. Study treatment continued until disease progression (evidence of radiographic progression, a skeletal- related event, or clinical progression), initiation of new systemic antineoplastic treatment, unacceptable toxicity, or withdrawal. Patients with a history of seizure, taking medicines known to decrease the seizure threshold, or with other risk factors for seizure were not eligible.
The pre-specified interim analysis at the time of 520 events showed a statistically significant improvement in overall survival in patients on the Xtandi arm compared to patients on the placebo arm (number of deaths: 38.5% for Xtandi vs. 53.1% for placebo; median survival: 18.4 months for Xtandi vs. 13.6 months for placebo; P-value: <0.0001; HR: 0.63).
Legal Classification:
Rx
Adults:
Swallow whole. 160mg once daily. Dose modifications: ≥Grade 3 toxicity or intolerable side effect: withhold dosing for 1 week or until symptoms improve to ≤Grade 2, then resume at same or reduced dose, if warranted. Concomitant strong CYP2C8 inhibitors: avoid if possible. If co-administration necessary, reduce Xtandi dose to 80mg once daily; if inhibitor is discontinued, return Xtandi dose to dose used prior to initiation of inhibitor.
Children:
Not established.
Contraindication(s):
Pregnancy (Cat.X).
Warnings/Precautions:
Seizure risk. Severe renal or hepatic impairment. Nursing mothers.
Interaction(s):
Potentiated by strong CYP2C8 inhibitors (eg, gemfibrozil), CYP3A4 inhibitors (itraconazole). May be antagonized by CYP2C8 inducers (eg, rifampin), CYP3A4 inducers (eg, carbamazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, bosentan, efavirenz, etravirine, modafinil, nafcillin, St. John’s Wort). Antagonizes midazolam (CYP3A4 substrate), warfarin (CYP2C9 substrate), and om |
