Why must Uptravi (selexipag) be titrated slowly?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: March 5, 2025View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

From the Guidelines

UPTRAVI (selexipag) must be titrated slowly to minimize side effects while achieving an effective therapeutic dose, with a recommended starting dose of 200 mcg twice daily and weekly increases of 200 mcg twice daily until reaching the highest tolerated dose, not exceeding 1600 mcg twice daily, as supported by the dosing guidelines outlined in the 2023 study published in Nature Reviews Rheumatology 1. The importance of slow titration lies in the management of dose-dependent side effects such as headache, diarrhea, jaw pain, nausea, and flushing, which are commonly associated with prostacyclin analogues like selexipag.

  • These side effects are typically most pronounced during the initial titration phase and often decrease in intensity over time as the body develops tolerance.
  • The slow titration approach allows for the adjustment of the dose based on the patient's tolerance, ensuring that the therapeutic benefits of selexipag in treating pulmonary arterial hypertension are maximized while minimizing adverse effects.
  • The mechanism of action of selexipag, which involves the selective activation of the prostacyclin (IP) receptor to cause vasodilation and inhibit platelet aggregation, underscores the need for careful dose adjustment to achieve optimal clinical benefit without compromising patient safety and quality of life.
  • As noted in the study, the dosing of selexipag, like other pulmonary hypertension-specific therapies, requires careful consideration of the potential risks and benefits, including the monitoring of liver enzymes and hemoglobin levels due to the risk of hepatotoxicity and anemia associated with certain therapies 1.

From the FDA Drug Label

Your healthcare provider will slowly increase your dose to find the dose of selexipag tablets that is right for you. If you have side effects, your healthcare provider may tell you to change your dose of selexipag tablets.

Selexipag (Uptravi) must be titrated slowly to find the right dose for the patient and to manage potential side effects. This approach allows the healthcare provider to monitor the patient's response to the medication and adjust the dose as needed to minimize adverse reactions.

From the Research

Dose Titration of Uptravi (Selexipag)

  • Uptravi (selexipag) must be titrated slowly due to its dose-dependent adverse-effect profile, which includes nausea, vomiting, diarrhea, headache, and musculoskeletal pain 2.
  • The recommended initial selexipag dosage is 200 μg twice daily, and it can be increased as tolerated up to a maximum dose of 1600 μg twice daily 3, 4.
  • Slow dose titration is a common strategy used to reduce the risk of adverse events and improve tolerability, as seen in other medications such as topiramate 5.
  • Although there is no direct evidence on the titration of selexipag in the provided studies, the general principle of slow dose titration to minimize adverse effects can be applied 6.
  • The studies on selexipag focus on its efficacy and safety in the treatment of pulmonary arterial hypertension, rather than the specific titration schedule 2, 3, 4.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Selexipag for the treatment of pulmonary arterial hypertension.

American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists, 2017

Research

Selexipag: A Review in Pulmonary Arterial Hypertension.

American journal of cardiovascular drugs : drugs, devices, and other interventions, 2017

Research

Selexipag for the Treatment of Pulmonary Arterial Hypertension.

The New England journal of medicine, 2015

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.