New drug,Selexipag (Uptravi) approved to treat pulmonary arterial hypertension.

On December 21, the U.S. Food and Drug Administration approved Uptravi (selexipag) tablets to treat adults with pulmonary arterial hypertension (PAH), a chronic, progressive, and debilitating rare lung disease that can lead to death or the need for transplantation.



  • UPTRAVI (selexipag) is a selective non-prostanoid IP prostacyclin receptor agonist.
  • The chemical name of selexipag is 2-{4-[(5,6-diphenylpyrazin-2-yl)(isopropyl)amino]butoxy}-N­ (methylsulfonyl) acetamide.
  • It has a molecular formula of C26H32N4O4S and a molecular weight of 496.62. Selexipag has the following structural formula:





Mechanism of Action

PAH is high blood pressure that occurs in the arteries that connect the heart to the lungs. It causes the right side of the heart to work harder than normal, which can lead to limitations on exercise ability and shortness of breath, among other more serious complications.

The drug acts by relaxing muscles in the walls of blood vessels to dilate (open) blood vessels and decrease the elevated pressure in the vessels supplying blood to the lungs.


Selexipag is an oral prostacyclin receptor (IP receptor) agonist that is structurally distinct from prostacyclin.

Selexipag is hydrolyzed by carboxylesterase 1 to yield its active metabolite, which is approximately 37-fold as potent as selexipag. Selexipag and the active metabolite are selective for the IP receptor versus other prostanoid receptors (EP1-4, DP, FP and TP).


Pulmonary Arterial Hypertension:

  • UPTRAVI is indicated for the treatment of pulmonary arterial hypertension (PAH, WHO Group I) to delay disease progression and reduce the risk of hospitalization for PAH.
  • Effectiveness was established in a long-term study in PAH patients with WHO Functional Class II-III symptoms.
  • Patients had idiopathic and heritable PAH (58%), PAH associated with connective tissue disease (29%), PAH associated with congenital heart disease with repaired shunts (10%).


Recommended Dosage

  • The recommended starting dose of UPTRAVI is 200 micrograms (mcg) given twice daily.
  • Tolerability may be improved when taken with food. Increase the dose in increments of 200 mcg twice daily, usually at weekly intervals, to the highest tolerated dose up to 1600 mcg twice daily.
  • If a patient reaches a dose that cannot be tolerated, the dose should be reduced to the previous tolerated dose.
  • Do not split, crush, or chew tablet.

Interruptions and Discontinuations

  • If a dose of medication is missed, patients should take a missed dose as soon as possible unless the next dose is within the next 6 hours.
  • If treatment is missed for 3 days or more, restart UPTRAVI at a lower dose and then retitrate..

Dosage Adjustment in Patients with Hepatic Impairment

  • No dose adjustment of UPTRAVI is necessary for patients with mild hepatic impairment (ChildPugh class A).
  • For patients with moderate hepatic impairment (Child-Pugh class B), the starting dose of UPTRAVI is 200 mcg once daily. Increase in increments of 200 mcg once daily at weekly intervals, as tolerated
  •  Avoid use of UPTRAVI in patients with severe hepatic impairment (Child-Pugh class C).


Pulmonary Veno-Occlusive Disease (PVOD)

Should signs of pulmonary edema occur, consider the possibility of associated PVOD. If confirmed, discontinue UPTRAVI.



Strong CYP2C8 inhibitors: increased exposure to selexipag and its active metabolite. Avoid concomitant use



Adverse reactions occurring more frequently (>5%) on UPTRAVI compared to placebo are headache, diarrhea, jaw pain, nausea, myalgia, vomiting, pain in extremity, and flushing.


Uptravi was granted orphan drug designation.

Orphan drug designation provides incentives such as tax credits, user fee waivers, and eligibility for exclusivity to assist and encourage the development of drugs for rare diseases.

Uptravi is marketed by San Francisco-based Actelion Pharmaceuticals US, Inc.


FDA Prescription label