UPTRAVI

The pharmacokinetics of selexipag and its active metabolite have been studied primarily in healthy subjects. The pharmacokinetics of selexipag and the active metabolite, after both single- and multiple-dose oral administration, were dose-proportional up to a single dose of 800 mcg and multiple doses of up to 1800 mcg twice daily. The pharmacokinetics of selexipag and the active metabolite, after multiple-dose intravenous administration, were dose-proportional in the tested dose range from 450 to...

14.1 Efficacy of UPTRAVI Tablets in Patients with Pulmonary Arterial Hypertension The effect of UPTRAVI tablets on progression of PAH was demonstrated in a multi-center, double-blind, placebo-controlled, parallel group, event-driven study (GRIPHON) in 1,156 patients with symptomatic (WHO Functional Class I [0.8%], II [46%], III [53%], and IV [1%]) PAH. Patients were randomized to either placebo (N=582), or UPTRAVI tablets (N=574). The dose was increased in weekly intervals by increments of 200 mcg twice a day to the highest tolerated dose up to 1600 mcg twice a day. The primary study endpoint ...

Adverse reactions occurring more frequently (≥5%) on UPTRAVI compared to placebo are headache, diarrhea, jaw pain, nausea, myalgia, vomiting, pain in extremity, and flushing. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Janssen at 1-800-526-7736 (1-800-JANSSEN) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be di...

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 )

Pulmonary edema in patients with pulmonary veno-occlusive disease. If confirmed, discontinue treatment. ( 5.1 ) 5.1 Pulmonary Edema with Pulmonary Veno-Occlusive Disease Should signs of pulmonary edema occur, consider the possibility of associated pulmonary veno-occlusive disease. If confirmed, discontinue UPTRAVI.

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 ( 2.6 , 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 ...