Selexipag, a selective prostacyclin receptor agonist in pulmonary arterial hypertension: a pharmacology review

ABSTRACT

Introduction: Pulmonary hypertension is defined by a mean pulmonary artery pressure ≥25 mm Hg at rest. Management of pulmonary arterial hypertension (PAH) includes specific drug therapy with calcium channel blockers in vasoreactive patients, or drugs approved for PAH in non-reactive patients that target the endothelin, nitric-oxide and prostacyclin pathways.

Areas covered: The review covers receptor selectivity, pharmacokinetics, pharmacodynamics and adverse effects (AEs) of intravenous (IV) epoprostenol (synthetic prostacyclin); the prostacyclin analogs iloprost, beraprost, and treprostinil administered by IV, subcutaneous, inhaled or oral routes; and the oral selective prostacyclin receptor agonist selexipag.

Expert commentary: Development of a selective prostacyclin receptor agonist has aimed at identifying compounds with improved pharmacological properties. The high selectivity of selexipag, and its active metabolite ACT-333679, for the prostacyclin receptor, in conjunction with pharmacokinetic properties that reduce peak-trough fluctuations and the up-titration regimen used at the start of treatment, are collectively considered to minimize AEs associated with prostacyclin use. In a large phase 3 study, selexipag-associated AEs were consistent with those observed with drugs that target the prostacyclin pathway, and mainly mild to moderate in severity. The dosing flexibility afforded by oral selexipag may facilitate achieving the maximum therapeutic effect with acceptable tolerability in patients with PAH.

KEYWORDS:

• Pulmonary arterial hypertension
• prostacyclin receptor agonists
• pharmacology
• Selexipag

Declaration of interest

The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. Medical writing assistance was provided by Content Ed Net (Madrid, Spain), with funding from Actelion Pharmaceuticals. Actelion did not have any role in the collection, analysis, and interpretation of data or writing the report. The views expressed are therefore based on author’s opinions and do not represent the views of Actelion or the journal.

Additional information

Funding

This manuscript was funded by Actelion Pharmaceuticals.