Dear [First_name_Last_name], |
Did you know there are 7-year survival estimates from the open-label extension study of GRIPHON in patients with pulmonary arterial hypertension (PAH, WHO Group I) receiving UPTRAVI® (selexipag)? |
INDICATION |
UPTRAVI® (selexipag) is indicated for the treatment of pulmonary arterial hypertension (PAH, WHO Group I) to delay disease progression and reduce the risk of hospitalization for PAH. |
Effectiveness was established in a long-term study in PAH patients with WHO Functional Class II-III symptoms. |
Patients had idiopathic and heritable PAH (58%), PAH associated with connective tissue disease (29%), and PAH associated with congenital heart disease with repaired shunts (10%). |
IMPORTANT SAFETY INFORMATION |
CONTRAINDICATIONS |
Concomitant use of strong inhibitors of CYP2C8 (eg, gemfibrozil) with UPTRAVI is contraindicated. |
Please see additional Important Safety Information below. |
This data includes long-term follow-up of patients who were treated with UPTRAVI in the placebo-controlled study (N=574), and the open-label extension study (N=330, of 574). |
These data are from long-term follow-up and an open-label extension study. These uncontrolled observations do not allow comparison with a control group not given UPTRAVI and cannot be used to determine the long-term effect of UPTRAVI on mortality. See the overall trial results and the open-label extension data in the link below. |
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IMPORTANT SAFETY INFORMATION (CONTINUED) |
WARNINGS AND PRECAUTIONS |
Pulmonary Veno-Occlusive Disease (PVOD) |
Should signs of pulmonary edema occur, consider the possibility of associated PVOD. If confirmed, discontinue UPTRAVI. |
ADVERSE REACTIONS |
Adverse reactions more frequent compared to placebo (≥3%) 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 and in none of the patients on placebo. |
DRUG INTERACTIONS |
CYP2C8 Inhibitors |
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. |
CYP2C8 Inducers |
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 Dosage |
Recommended starting dose is 200 mcg twice daily. 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 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. Revert back to twice daily dosing frequency of UPTRAVI when co-administration of moderate CYP2C8 inhibitor is stopped. |
Dosage Strengths |
UPTRAVI tablet strengths:
200, 400, 600, 800, 1000, 1200, 1400, and 1600 mcg. |
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cp-126160 |
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