Concomitant use of strong inhibitors of CYP2C8 (eg, gemfibrozil) with UPTRAVI® is contraindicated.
Hypersensitivity to the active substance or to any of the excipients is contraindicated.
WARNINGS AND PRECAUTIONS
Pulmonary Edema with Pulmonary Veno-Occlusive Disease (PVOD)
Should signs of pulmonary edema occur, consider the possibility of associated PVOD. If confirmed, discontinue UPTRAVI®.
Adverse reactions more frequent compared to placebo (≥3%) seen with UPTRAVI® Tablets are headache (65% vs 32%), diarrhea (42% vs 18%), jaw pain (26% vs 6%), nausea (33% vs 18%), myalgia (16% vs 6%), vomiting (18% vs 9%), pain in extremity (17% vs 8%), flushing (12% vs 5%), arthralgia (11% vs 8%), anemia (8% vs 5%), decreased appetite (6% vs 3%), and rash (11% vs 8%).
These adverse reactions are more frequent during the dose titration phase.
Hyperthyroidism was observed in 1% (n=8) of patients on UPTRAVI® Tablets and in none of the patients on placebo.
Concomitant administration with gemfibrozil, a strong inhibitor of CYP2C8, doubled exposure to selexipag and increased exposure to the active metabolite by approximately 11-fold. Concomitant use of UPTRAVI® with strong inhibitors of CYP2C8 is contraindicated.
Concomitant administration of UPTRAVI® with clopidogrel, a moderate inhibitor of CYP2C8, had no relevant effect on the exposure to selexipag and increased the exposure to the active metabolite by approximately 2.7-fold. Reduce the dosing of UPTRAVI® to once daily in patients on a moderate CYP2C8 inhibitor.
Concomitant administration with an inducer of CYP2C8 and UGT 1A3 and 2B7 enzymes (rifampin) halved exposure to the active metabolite. Increase UPTRAVI® dose, up to twice, when co-administered with rifampin. Reduce UPTRAVI® when rifampin is stopped.
DOSAGE AND ADMINISTRATION
Recommended starting dose is 200 mcg twice daily for UPTRAVI® Tablets. Tolerability may be improved when taken with food. Increase by 200 mcg twice daily, usually at weekly intervals, to the highest tolerated dose up to 1600 mcg twice daily. If dose is not tolerated, reduce to the previous tolerated dose.
Patients With Hepatic Impairment
For patients with moderate hepatic impairment (Child-Pugh class B), the starting dose of UPTRAVI® Tablets is 200 mcg once daily. Increase by 200 mcg once daily at weekly intervals, as tolerated. Avoid use of UPTRAVI® in patients with severe hepatic impairment (Child-Pugh class C).
Co-administration With Moderate CYP2C8 Inhibitors
When co-administered with moderate CYP2C8 inhibitors (eg, clopidogrel, deferasirox and teriflunomide), reduce the dosing of UPTRAVI® to once daily.
UPTRAVI® tablet strengths:
200, 400, 600, 800, 1000, 1200, 1400, and 1600 mcg.
Additional Important Safety Information for UPTRAVI® IV
Use UPTRAVI® for injection in patients who are temporarily unable to take oral therapy.
Administer UPTRAVI® for injection twice daily by intravenous infusion at a dose that corresponds to the patient’s current dose of UPTRAVI® Tablets (see Table 1 in full Prescribing Information). Administer UPTRAVI® for injection as an 80-minute intravenous infusion.
Adverse Reactions: Infusion-site reactions (infusion-site erythema/redness, pain and swelling) were reported with UPTRAVI® for injection.
Please see full Prescribing Information.