Uptravi for Clinicians
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%).
Primary Endpoint: Time to First PAH Disease Progression Event in GRIPHON
Time to first disease progression event
The treatment effect was established early and maintained over the entire treatment period.
Summary of primary endpoint events:
REVEAL Risk Score
Calculate the risk score for your patients and decide if you need to escalate therapy (those with intermediate or high risk). Click here.
Uptravi is the only oral prostacyclin pathway therapy proven to reduce the risk of hospitalization for PAH
GRIPHON trial: Hospitalization for PAH as the first event
Hospitalization as first event up to end of treatment:
After you, as the treating healthcare professional (HCP), have made the decision to prescribe UPTRAVI, Actelion offers 2 distinct and complementary resources for UPTRAVI patients during their dose adjustment (titration) phase.
You must check “yes” on the enrollment form for each optional support resource available for your patient.
1. SP IN-HOME NURSE VISITS
During the enrollment process, you, as the treating HCP, can choose a specific number of nurse visits or a visit during each dose change until your patient titrates to their personal dose of UPTRAVI.
Within 48 hours of your patient’s receipt of their first UPTRAVI shipment, an SP Nurse can make an in-home visit.
During these visits with your patient, the nurse can:
The information provided in the visits should reinforce information you, as the treating HCP, have given your patient.
2. SP DOSE CHANGE TELEPHONE CALLS
An SP Pharmacist is available to call the patient at each dose change with UPTRAVI until the patient’s personal dose (maintenance dose) is achieved.
Important Safety Information
Please see the full data at:
Concomitant use of strong inhibitors of CYP2C8 (eg, gemfibrozil) with UPTRAVI is contraindicated.
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 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.
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. 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.
UPTRAVI tablet strengths:
200, 400, 600, 800, 1000, 1200, 1400, and 1600 mcg.