Recommended Dosing for Uptravi (Selexipag) in Pulmonary Arterial Hypertension
The recommended dosing for Uptravi (selexipag) starts at 200 micrograms twice daily, with gradual titration in 200 microgram increments at weekly intervals to the highest tolerated dose up to 1,600 micrograms twice daily. 1
Initial Dosing and Titration
- Starting dose: 200 micrograms twice daily
- Titration schedule: Increase by 200 micrograms twice daily, usually at weekly intervals
- Maximum dose: Up to 1,600 micrograms twice daily, based on individual tolerability
- Administration: Take with food to improve tolerability 1
- Tablet form: Do not split, crush, or chew tablets 1
Individualized Dosing Approach
The maintenance dose of selexipag should be determined by individual tolerability. In the GRIPHON trial, patients were categorized into three dose groups:
- Low dose: 200-400 micrograms twice daily
- Medium dose: 600-1000 micrograms twice daily
- High dose: 1200-1600 micrograms twice daily 2
Real-world data from the SPHERE registry showed that the median maintenance dose achieved was 1,200 micrograms twice daily (interquartile range: 800-1,600 micrograms twice daily) 3, suggesting most patients can tolerate doses in the medium to high range.
Special Populations
Hepatic Impairment
- Mild impairment (Child-Pugh class A): No dose adjustment necessary
- Moderate impairment (Child-Pugh class B): Start at 200 micrograms once daily and increase in increments of 200 micrograms once daily at weekly intervals
- Severe impairment (Child-Pugh class C): Avoid use 1
Drug Interactions
- With moderate CYP2C8 inhibitors (e.g., clopidogrel, deferasirox, teriflunomide): Reduce dosing to once daily
- With strong CYP2C8 inhibitors (e.g., gemfibrozil): Concomitant use is contraindicated 1
Missed Doses and Interruptions
- If a dose is missed, take it as soon as possible unless the next scheduled dose is within 6 hours
- If treatment is interrupted for 3 days or more: Restart at a lower dose and then retitrate 1
Monitoring and Management of Side Effects
Common adverse reactions (occurring in ≥5% of patients) include:
- Headache
- Diarrhea
- Jaw pain
- Nausea
- Myalgia
- Vomiting
- Pain in extremity
- Flushing 1
These side effects are typically dose-dependent and may require temporary dose reduction during titration to improve tolerability. The goal remains achieving the highest tolerated dose for each patient.
Clinical Efficacy Considerations
Selexipag is indicated for PAH patients with WHO Functional Class II-III symptoms to delay disease progression and reduce the risk of hospitalization for PAH 1. The GRIPHON trial demonstrated that selexipag significantly reduced the risk of the primary composite endpoint of all-cause death or PAH-related complications compared to placebo 4.
While the 2019 CHEST guideline noted insufficient evidence to make a recommendation for or against selexipag use 5, the FDA approval and more recent clinical experience support its role in PAH management, particularly as part of combination therapy.