BETHESDA, MD 04 September 2012—FDA on August 31 announced the approval of enzalutamide oral capsules for the treatment of advanced prostate cancer.
Enzalutamide will be marketed by Astellas Pharma US Inc. of Northbrook, Illinois, and Medivation Inc. of San Francisco. The companies expect the drug to be available in mid-September under the brand name Xtandi.
According to the labeling (PDF) for enzalutamide, the drug is indicated for use in men with metastatic castration-resistant prostate cancer who have previously been treated with docetaxel.
The labeling describes enzalutamide as an androgen receptor inhibitor that alters steps in the androgen receptor signaling pathway.
The recommended dosage of enzalutamide is four 40-mg capsules taken once daily with or without food. The capsules must be swallowed whole and not chewed, dissolved, or opened.
If severe or intolerable adverse events occur during enzalutamide treatment, therapy should be discontinued for a week or until the symptoms improve to a mild-to-moderate level. Therapy can then be resumed at the same dosage or reduced to 120 or 80 mg/day, according to the labeling.
In clinical trails, the most common serious adverse event that led to discontinuation of treatment was seizure, which affected 0.9% of enzalutamide recipients.
People with a history of seizure or conditions that increase the risk for seizure were excluded from clinical trials of enzalutamide, and it is not known how the drug affects such patients.
The most frequently reported adverse events associated with enzalutamide therapy in clinical trials included weakness, fatigue, pain, diarrhea, hot flush, tissue swelling, respiratory tract infection, dizziness, spinal cord compression, insomnia, blood in urine, tingling sensation, anxiety, and hypertension.
The labeling recommends against the concomitant use of enzalutamide and strong inhibitors of cytochrome P-450 (CYP) isoenzyme 2C8. If concurrent use is necessary, the enzalutamide dosage should be reduced to 80 mg/day. The dosage should be restored to its previous level if the CYP2C8 inhibitor is discontinued.
Also to be avoided, according to the labeling, is concomitant use of enzalutamide and strong or moderate inducers of CYP3A4 or CYP2C8 or substrates of CYP3A4, CYP2C9, or CYP2C19 with a narrow therapeutic index. The International Normalized Ratio should be monitored more often than usual if warfarin must be taken during enzalutamide therapy.
Enzalutamide 40-mg capsules will be sold in bottles of 120 each that should be kept tightly closed and stored at room temperature.