selexipag selexipag selexipag, sold under the brand name uptravi, is a medication developed by actelion for the treatment of pulmonary arterial hypertension (pah). selexipag and its active metabolite, act-333679 (or mre-269, the free carboxylic acid), are agonists of the prostacyclin receptor, which leads to vasodilation in the pulmonary circulation. it is taken by mouth or administered intravenously. selexipagclinical datatrade namesuptraviother namesact-293987, ns-304license data us dailymed: selexipag us fda: selexipag routes ofadministrationby mouth, intravenousatc codeb01ac27 (who) legal statuslegal status au: s4 (prescription only) us: ℞-only eu: rx-only pharmacokinetic databioavailability49%protein binding99%metabolismactivation by carboxylesterases, inactivation by cyp2c8 and othersmetabolitesact-333679, the free acid (active metabolite)elimination half-life0.8–2.5 h (selexipag) and 6.2–13.5 h (act-333679)excretion93% faecesidentifiers iupac name 2--n-(methanesulfonyl)acetamide cas number475086-01-2pubchem cid9913767iuphar/bps7552drugbankdb11362chemspider8089417 yunii5exc0e384lkeggd09994 ychebichebi:90844 ychemblchembl238804 yecha infocard100.237.916 chemical and physical dataformulac26h32n4o4smolar mass496.63 g·mol−13d model (jsmol)interactive image smiles cc(c)n(ccccocc(=o)ns(=o)(=o)c)c1=cn=c(c(=n1)c2=cc=cc=c2)c3=cc=cc=c3 inchi inchi=1s/c26h32n4o4s/c1-20(2)30(16-10-11-17-34-19-24(31)29-35(3,32)33)23-18-27-25(21-12-6-4-7-13-21)26(28-23)22-14-8-5-9-15-22/h4-9,12-15,18,20h,10-11,16-17,19h2,1-3h3,(h,29,31) ykey:qxwzqturmxzvhj-uhfffaoysa-n ny (what is this?) (verify) it is available as a generic medication. contraindications in europe, use of selexipag together with strong inhibitors of the liver enzyme cyp2c8, such as gemfibrozil, is contraindicated because it increases concentrations of selexipag twofold, and its active metabolite 11-fold, potentially leading to more adverse effects. adverse effects the adverse effects of selexipag are similar to those of intravenous prostacyclins used for pulmonary arterial hypertension. common side effects include headache and jaw pain. an increased risk for hyperthyroidism has also been noted in people taking selexipag. pharmacology mechanism of action act-333679, the active metabolite selexipag and its active metabolite act-333679 act on the prostacyclin receptor of lung tissue, with the latter being 37-fold more potent. they are selective for the prostacyclin receptor. binding to this receptor leads to three major effects: increased vasodilation of the arteries, decreased cell proliferation and inhibition of platelet aggregation, all beneficial in the treatment of pulmonary arterial hypertension. pharmacokinetics selexipag is quickly absorbed from the gut and hydrolyzed in the intestines and the liver to act-333679 by carboxylesterases. absolute bioavailability is about 49%, most likely because of a high first-pass effect. highest concentrations in the blood plasma are reached after one to three hours for selexipag and after three to four hours for the active metabolite. when in the circulation, about 99% of both substances are bound to plasma proteins, namely to albumin and alpha-1-acid glycoprotein to equal amounts. the liver enzymes cyp2c8 and, to a lesser extent, cyp3a4, hydroxylate and dealkylate the active substance, thereby inactivating it. besides, act-333679 is glucuronidized by the enzymes ugt1a3 and ugt2b7. the terminal half-life of selexipag is 0.8 to 2.5 hours, that of the active metabolite is 6.2 to 13.5 hours. history the u.s. food and drug administration (fda) granted selexipag orphan drug status for pah. it was approved by the fda on 22 december 2015. in europe, the drug was approved in may 2016. society and culture economics the expected price for the drug in the us is $160,000 to $170,000 per patient before rebates.