Drug Interactions between Liqrev and osilodrostat

MONITOR: Coadministration with weak inhibitors of CYP450 3A4 may increase the plasma concentrations of sildenafil, which is primarily metabolized by the isoenzyme. Pharmacokinetic models predict that this interaction may be more significant for oral rather than intravenous formulations of sildenafil, due at least partly to effects from first pass metabolism. An analysis of population pharmacokinetic data from clinical trials in adult pulmonary hypertension patients indicated a reduction in sildenafil clearance of approximately 30% when coadministered with mild CYP450 3A4 inhibitors. Sildenafil labeling does not currently report study data involving concurrent use with weak CYP450 3A4 inhibitors in pediatric pulmonary hypertension patients. Likewise, sildenafil products indicated for erectile dysfunction also focus on study data with more potent CYP450 3A4 inhibitors.

MANAGEMENT: Caution is advised if sildenafil is coadministered with weak CYP450 3A4 inhibitors. The significance of this interaction may be less for intravenous formulations of sildenafil and greater in patients with risk factors for adverse effects, such as those with renal impairment, hepatic impairment, and/or elderly patients. The presence of renal and/or hepatic dysfunction may necessitate adjustments of sildenafil's dose. If concurrent administration is necessary, patients should be monitored closely for adverse reactions and may benefit from initiating sildenafil at the lowest recommended dosage with slow, careful titration. Dosage adjustments may be necessary for sildenafil whenever a CYP450 3A4 inhibitor is added to or withdrawn from therapy based on efficacy and side effects. Patients should be advised to promptly notify their physician if they experience pain or tightness in the chest or jaw, irregular heartbeat, nausea, shortness of breath, visual disturbances, syncope, or prolonged erection (greater than 4 hours).