Table 4.

Clinically Established and Other Potentially Significant Drug Interactions: Prostacyclin Pathway Drugs

PAH Drug	Interacting Drug	Mechanism	Effect	Recommendation
Treprostinil diethanolamine (oral formulation)	Gemfibrozil	CYP2C8 inhibition, increases treprostinil diethanolamine levels	Twofold increase in treprostinil diethanolamine concentrations	Reduce the starting dose of treprostinil diethanolamine to 0.125 mg twice daily and increase by 0.125-mg twice daily increments not more frequently than every 3-4 d
Selexipag	Clopidogrel	Moderate CYP2C8 inhibition, increases selexipag levels	Approximately threefold increase in selexipag concentrations	Reduce dose of selexipag to once daily
	Leflunomide	Moderate CYP2C8 inhibition, active metabolite teriflunomide increases selexipag levels	Expect similar effect to clopidogrel	Dose reduce selexipag to once daily
	Deferasirox	Moderate CYP2C8 inhibition, increases selexipag levels	Expect similar effect to clopidogrel	Dose reduce selexipag to once daily
	Gemfibrozil	Strong CYP2C8 inhibition, increases selexipag levels	11-fold increase in selexipag concentrations	Strong inhibitors are contraindicated
	Rifampin	CYP3A4 induction, decreases selexipag concentration	Decrease in active metabolite of selexipag by 50%	Dose of selexipag should be doubled when starting rifampin and then reduced when rifampin is stopped

PAH = pulmonary arterial hypertension.