Apalutamide

Rashes (usually macular or maculo-papular) were reported in nearly one-fourth of patients who received apalutamide; including some that were grade 3 or 4. Rash onset usually occurred at median of 82 days and typically resolved within a median of 60 days in most patients. Some patients required systemic corticosteroids to manage rash. Rash recurred in approximately half of patients who were re-challenged with apalutamide.

Fall and fractures have occurred in patients receiving apalutamide. Grade 3 or 4 fractures have been reported. In a clinical study, the median time to onset of fracture was ~10 months (range: ~0.6 to 32 months); the study did not perform routine bone density assessments or osteoporosis treatment with bone modifying agents. Evaluate patients for fall and fracture risk. Patients at risk for fractures should be monitored and managed according to established management guidelines. Consider the use of bone modifying agents.

Based on exposure-QT analysis in an uncontrolled, single-arm dedicated QTc interval assessment study, a concentration-dependent increase in QTcF was noted with apalutamide (and the active metabolite). The maximum mean QTcF change from baseline was 12.4 msec.

Seizures occurred in patients receiving apalutamide. It is not known if antiepileptic medications can prevent apalutamide-related seizures. In a clinical study, a small number of patients experienced seizures, with the onset occurring from ~12 months to 16 months after treatment initiation. Patients with a history of seizure, predisposing factors for seizure, or receiving medications known to reduce seizure threshold or to induce seizures were excluded from the study. There is no experience in reinitiating apalutamide in patients who experienced a seizure. Advise patients of the risk of seizures during apalutamide treatment and of the risk of engaging in activities where sudden loss of consciousness could cause serious harm to themselves or others. Discontinue apalutamide permanently if seizures develop during treatment.

Hypothyroidism and elevated thyroid stimulating hormone (TSH) have been reported with apalutamide; the median onset was ~4 months (there were no grade 3 or 4 hypothyroid events). Thyroid replacement therapy was initiated in some patients; if clinically indicated, thyroid replacement therapy should be initiated and/or dose-adjusted. Disease-related concerns:

Androgen-deprivation therapy may increase the risk for cardiovascular disease (Levine 2010). Concurrent drug therapy issues:

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.