Drug Interactions between oxandrolone and seladelpar

MONITOR: Concomitant administration with moderate inhibitors of CYP450 2C9 may increase the concentration of seladelpar, which is primarily metabolized via this isoenzyme. A physiologically based pharmacokinetic (PBPK) model predicted that seladelpar's systemic exposure (AUC) would increase by 3.7-fold when coadministered with the strong CYP450 2C9 inhibitor sulfaphenazole. Similarly, individuals with genetic variants of CYP450 2C9 also have increases in the AUC of seladelpar. After a single dose of seladelpar (1 mg to 15 mg), dose-normalized AUC was 48% higher in CYP450 2C9 poor metabolizers (n=2) and 24% higher in CYP450 2C9 intermediate metabolizers (n=28) compared to normal metabolizers (n=84). Clinical data for seladelpar use in combination with less potent inhibitors of CYP450 2C9 or in patients with reduced CYP450 2C9 activity who are also taking a less potent CYP450 2C9 inhibitor are not available.

MANAGEMENT: Additional monitoring for adverse effects of seladelpar (e.g., abnormal liver tests) may be advisable if coadministration with a moderate CYP450 2C9 inhibitor is necessary. Theoretically, patients who have a reduction in the activity of CYP450 2C9 (e.g., poor or intermediate metabolizers) may be at an increased risk for experiencing side effects in the presence of a moderate CYP450 2C9 inhibitor as seladelpar's metabolism via CYP450 2C9 could be further reduced.