Selexipag

Overview

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.[1–4] WP

The most common side effects include headache, diarrhea, nausea and vomiting, jaw pain, myalgia (muscle pain), pain in the limbs, arthralgia (joint pain) and flushing.[2] WP

It is available as a generic medication.[5] WP

Drug class

prostacyclin receptor agonist WP

From the Wikipedia article's infobox.

Uses, dosage and effects

Medical uses

Selexipag is indicated for the treatment of pulmonary arterial hypertension.[1][2] WP

Risks and side effects

Contraindications

In the European Union, 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.[2][6] WP

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.[7] WP

Pharmacology

Mechanism of action

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.[7] WP

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.[7] WP

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.[7] WP

History

History

The U.S. Food and Drug Administration (FDA) granted selexipag orphan drug designation for pulmonary arterial hypertension and for the treatment of chronic thromboembolic pulmonary hypertension. It was approved by the FDA in December 2015.[1][8][9][10] WP

In the European Union, the drug was approved in May 2016.[2][7] WP

Legal status

Economics

The expected price for the drug in the US is $160,000 to $170,000 per patient before rebates.[11] WP

Chemistry

Formula

C26H32N4O4S PC

CAS number

475086-01-2 PC

Molar mass (g/mol)

496.6 PC

IUPAC name (computed by PubChem)

2-[4-[(5,6-diphenylpyrazin-2-yl)-propan-2-ylamino]butoxy]-N-methylsulfonylacetamide PC

SMILES

CC(C)N(CCCCOCC(=O)NS(=O)(=O)C)C1=CN=C(C(=N1)C2=CC=CC=C2)C3=CC=CC=C3 PC

InChIKey

QXWZQTURMXZVHJ-UHFFFAOYSA-N PC

PubChem CID

9913767

Harm reduction information

No harm reduction data is on file for this compound yet. That means no dose, timing or combination data from PsychonautWiki or TripSit. Please don't guess a dose from similar compounds. If you have taken it and feel unwell, contact emergency services or a poison control center.

User reports

Pop culture

No references added yet.

Sources

1. Journal / agency Uptravi- selexipag tablet, coated Uptravi Titration Pack- selexipag kit
2. Journal / agency Uptravi EPAR. 1 July 2022
3. Journal / agency Sitbon O, Morrell N. Pathways in pulmonary arterial hypertension: the future is here. European Respiratory Review. December 2012. doi:10.1183/09059180.00004812 · PMID 23204120 · PMC9487224
4. Other Uptravi (selexipag) Receives FDA Approval for Intravenous Use in Adult Patients with Pulmonary Arterial Hypertension (PAH). 30 July 2021
5. Journal / agency Competitive Generic Therapy Approvals. 29 June 2023
6. Other Information des Bundesamtes für Sicherheit im Gesundheitswesen zu Uptravi. 2017-06-07
7. Journal / agency Uptravi: Authorisation details. 2016-05-12
8. Journal / agency Selexipag Orphan Drug Designations and Approvals. 1 January 2013
9. Journal / agency Selexipag Orphan Drug Designations and Approvals. 1 January 2013
10. Journal / agency Uptravi Tablets. 28 January 2016
11. Other Actelion sees Uptravi price of $160,000-170,000/patient. 2016-01-05

Text and values on this page are quoted from Wikipedia (CC BY-SA 4.0), PubChem (public domain). Each value links to the exact revision it came from.