Overview
11 DESCRIPTION UPTRAVI contains selexipag, a 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 C 26 H 32 N 4 O 4 S and a molecular weight of 496.62.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Selexipag is a 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 (EP 1–4 , DP, FP, and TP). 12.2 Pharmacodynamics Cardiac Electrophysiology At the maximum tolerated dose of 1,600 mcg UPTRAVI tablets twice daily, UPTRAVI does not prolong the QT interval to any clinically relevant extent. Platelet Aggregation Both selexipag and its active metabolite caused concentration-dependent inhibition of platelet aggregation in vitro with an IC 50 of 5.5 µM and 0.
Indications
- 1 INDICATIONS AND USAGE UPTRAVI is a prostacyclin receptor agonist indicated for the treatment of pulmonary arterial hypertension (PAH, WHO Group I): In adults to delay disease progression and reduce the risk of hospitalization for PAH. ( 1.1 ) In pediatric patients aged 2 years and older. UPTRAVI reduces NT-proBNP and is expected to delay disease progression and reduce the risk of hospitalization for PAH. ( 1.1 ) 1.1 Pulmonary Arterial Hypertension Adult Patients UPTRAVI is indicated for the treatment of pulmonary arterial hypertension in adults (PAH, WHO Group I) to delay disease...
Common Doses
- 200 mcg
- 600 mcg
- 100 mcg
- 800 mcg
Dosage
2 DOSAGE AND ADMINISTRATION Adult patients: UPTRAVI tablets starting dose: 200 mcg orally twice daily. Increase the dose by 200 mcg orally twice daily at weekly intervals to the highest tolerated dose up to 1,600 mcg orally twice daily. ( 2.1 ) Pediatric patients: See Full Prescribing Information for recommended starting dose, titration increments, and maximum allowed dose based on body weight category. ( 2.1 ) Maintenance dose is determined by tolerability. ( 2.
Contraindications
- 4 CONTRAINDICATIONS Hypersensitivity to the active substance or to any of the excipients. Concomitant use of strong inhibitors of CYP2C8 (e.g., gemfibrozil) [see Drug Interactions (7.1) and Clinical Pharmacology (12.3) ] . Concomitant use with strong CYP2C8 inhibitors. ( 4 , 7.1 , 12.3 ) Hypersensitivity to the active substance or to any of the excipients. ( 4 )
Side Effects
- 6 ADVERSE REACTIONS Adverse reactions in adult and pediatric patients occurring more frequently (≥5%) on UPTRAVI compared to placebo are headache, diarrhea, jaw pain, nausea, myalgia, vomiting, pain in extremity, and flushing. Additional adverse reaction occurring in pediatric patients more frequently (≥5%) on UPTRAVI compared to placebo is abdominal pain. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Actelion at 1-800-526-7736 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.
Interactions
- 7 DRUG INTERACTIONS Moderate CYP2C8 inhibitors (e.g., clopidogrel, deferasirox and teriflunomide) increase exposure to the active metabolite of UPTRAVI. Reduce the dosing of UPTRAVI to once daily. ( 2.7 , 7.1 , 12.3 ) CYP2C8 inducers (e.g., rifampin) decrease exposure to the active metabolite. Increase up to twice the dose of UPTRAVI. ( 7.2 , 12.3 ) 7.1 CYP2C8 Inhibitors Concomitant administration with gemfibrozil, a strong inhibitor of CYP2C8, doubled the exposure to selexipag and increased exposure to the active metabolite by approximately 11-fold.