Selexipag: new class of treatment for pulmonary artery hypertension reaches prescribers

Uptravi (selexipag), a prostacyclin receptor agonist for treating pulmonary artery hypertension, is now available in the UK.

Pulmonary arterial hypertension is a severe disease with a poor prognosis despite available treatment options. | SCIENCE PHOTO LIBRARY
Pulmonary arterial hypertension is a severe disease with a poor prognosis despite available treatment options. | SCIENCE PHOTO LIBRARY

Uptravi is indicated in adults for the long-term treatment of pulmonary artery hypertension (PAH) of WHO functional classes II-III. The drug can be given as combination therapy in patients who are insufficiently controlled on an endothelin receptor antagonist and/or a phosphodiesterase type 5 inhibitor, or as monotherapy in patients who are not candidates for these treatments.

Patients are started on a dose of 200 microgram twice daily, which is titrated at weekly intervals to the highest tolerable dose, up to a maximum of 1.6mg twice daily.

Prostacyclin receptor agonist

Further information
View Uptravi drug record
Summary of Product Characteristics
Manufacturer: Actelion
MIMS Cardiology Clinic

Selexipag targets the prostacyclin IP receptor, the same receptor targeted by prostacyclin and its analogues; however, it is a structurally distinct molecule.

Stimulation of the IP receptor leads to vasodilatory as well as antiproliferative and antifibrotic effects.

Reduced complication rate

Uptravi was approved on the basis of a randomised, placebo-controlled trial involving 1,156 patients with symptomatic PAH. The event-based, double-blind trial compared selexipag with placebo at individualised doses.

The primary endpoint was either death from any cause or a PAH-related complication within 7 days of the last dose.

Overall, 27.0% of patients receiving selexipag experienced an endpoint compared with 41.6% of those given placebo (hazard ratio 0.60 [99% CI 0.46-0.78]; p<0.001). Reduced disease progression and hospitalisation accounted for the majority of the treatment effect; there was no significant difference in mortality between the two groups.

Selexipag is not suitable for patients with severe hepatic impairment, pregnant or breastfeeding women, and individuals on dialysis. Because of its cardiovascular effects, the drug is also contraindicated in people with unstable angina, decompensated cardiac failure, severe arrhythmias, valvular defects, recent MI (within 6 months), or a recent stroke or TIA (within 3 months).

Consistent with the known side-effects of prostacyclin, the most common adverse effects of selexipag include headache, diarrhoea, nausea and vomiting, and jaw pain. These reactions are more frequent during the uptitration phase and are generally of mild to moderate intensity.

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