When Were Oral PPAs Considered for PAH Patients in Common Clinical Scenarios?

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When Were Oral PPAs Considered for PAH Patients in Common Clinical Scenarios?

Program Information

Program Information

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A panel of PAH specialists convened to develop consensus opinions on clinical scenarios in which they considered adding oral PPAs in PAH therapy. 

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  • Overview

    Please see the full Prescribing Information here.

    This program is intended for US healthcare professionals only and is not certified for continuing medical education. Sponsored by the Janssen Pharmaceutical Companies of Johnson & Johnson, the marketer and distributor of UPTRAVI® (selexipag).

    Although there is currently no cure, the treatment of pulmonary arterial hypertension (PAH) has evolved substantially and its impact on patients varies based on clinical factors, including etiology, functional class, and hemodynamic parameters.

    Dr. Jennifer Caudle is joined by pulmonologist Dr. Victor Tapson, Professor of Medicine at Cedars-Sinai Medical Center, to discuss results from the Prostacyclin International Expert Panel consensus survey on common clinical scenarios in which they considered adding oral prostacyclin pathway agents in patients with PAH.

    The Prostacyclin International Expert Panel was not a consensus conference such as one held by a task force convened for the purpose of developing treatment guidelines. The Prostacyclin International Expert Panel opinion survey statements are not intended to be formal treatment guidelines or recommendations, and survey results presented here must be validated with rigorous prospective studies. The Prostacyclin International Expert Panel opinion survey statements cannot replace assessment and/or clinical decision-making by a qualified healthcare practitioner for an individual patient. These statements do not address all possible clinical situations, nor do these statements account for additional individual patient factors not specifically stated.

    Funding for the Prostacyclin International Expert Panel was provided by Actelion to support the use of independent providers of Delphi methodology expertise and nominal group technique, survey creation, data analysis, medical communication, and meeting management. Actelion played no role in the literature search and analysis, development of surveys used to gather consensus, or data analysis. No Actelion employees were present at the face-to-face meeting during which consensus statements were finalized. The current manuscript was drafted, critically reviewed, and edited solely by the authors with support from an independent professional medical communications agency. Actelion reviewed the final manuscript only to ensure accuracy of UPTRAVI background information; no edits were made to the manuscript based on this review.


    Concomitant use of strong inhibitors of CYP2C8 (eg, gemfibrozil) with UPTRAVI is contraindicated.

    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%) 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.

    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.

    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.

    Please see full Prescribing Information.

    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%).

    ©2021 Actelion Pharmaceuticals US, Inc. All rights reserved. cp-139232v3 0221
Programs 9/16/21