selexipag + gemfibrozil

This is a **combination of selexipag and gemfibrozil**. Selexipag is a selective prostacyclin receptor (IP receptor) agonist indicated for the treatment of pulmonary arterial hypertension (PAH). It acts as a prodrug that, after metabolic activation primarily by CYP2C8, produces the active metabolite ACT-333679, which mediates vasodilation and inhibits smooth muscle cell proliferation in the pulmonary artery. Gemfibrozil is a lipid-lowering agent and a strong CYP2C8 inhibitor commonly used to manage hyperlipidemia. When co-administered, **gemfibrozil significantly increases the exposure (AUC and Cmax) of selexipag’s active metabolite (ACT-333679)** by inhibiting its metabolism, leading to increased risk of adverse effects such as headache, nausea, and vomiting. This combination is contraindicated due to the risk of severe adverse reactions and pharmacokinetic interaction.