The Role of Intravenous Selexipag in Managing PAH and Bridging Gaps in Oral Treatment: A Narrative Review.

Abstract

Pulmonary arterial hypertension (PAH) is a rare and potentially fatal condition characterized by progressive increases in blood pressure in the arteries of the lungs. Oral selexipag, approved by the Food and Drug Administration (FDA) in 2015 for the treatment of PAH, targets prostacyclin receptors on pulmonary arterial vascular smooth muscle and endothelial cells to improve blood flow through the lungs and reduce pulmonary vascular resistance. Oral selexipag is effective, but may be discontinued due to factors like side effects, emergency conditions, or inability to take oral medication, potentially leading to severe adverse events, such as rebound pulmonary hypertension and right heart failure. To address treatment interruptions, intravenous (IV) selexipag was introduced as an alternative for patients who are temporarily unable to take oral medications. IV selexipag bypasses hepatic metabolism, requiring a 12.5% higher dose compared to the oral form to achieve similar therapeutic effects. It is administered via IV infusion twice daily over 80 minutes, typically for short-term use. However, caution is needed when prescribing selexipag to patients with hepatic or renal issues, and it is contraindicated with strong CYP2C8 inhibitors. A Phase III clinical trial confirmed that switching between oral and IV selexipag was safe, with comparable efficacy and tolerability, though it was limited by small sample size and short duration. Given the risks of treatment interruption and the complexity of managing PAH, this review provides essential insights into the practical use of IV selexipag as a bridging therapy. Furthermore, it calls for larger clinical trials to refine dosing strategies, explore long-term outcomes, and identify patient populations most likely to benefit from IV selexipag.