Practical management of oral treprostinil in patients with pulmonary arterial hypertension: Lessons from ADAPT, EXPEDITE, and expert consensus

Respir Med. 2024 Sep:231:107734. doi: 10.1016/j.rmed.2024.107734. Epub 2024 Jul 8.

Abstract

Background: Oral treprostinil is a prostacyclin analogue approved to treat pulmonary arterial hypertension (PAH) by delaying disease progression and improving exercise capacity. Higher doses of oral treprostinil correlate with increased treatment benefit. Titrations may be challenging due to common side effects of prostacyclin-class therapies.

Study design and methods: The multicenter, prospective, real-world, observational ADAPT Registry study followed adult patients with PAH for up to 78 weeks after initiating oral treprostinil (NCT03045029). Dosing, titration, and transitions of oral treprostinil were at the discretion of the prescriber. Patient-reported incidence and treatment of common side effects were collected to understand side effect management and tolerability. Insights from literature and expert recommendations were added to provide a consolidated resource for oral treprostinil use.

Results: In total, 139 participants in ADAPT completed ≥1 weekly survey; (median age 60.0 years, 76 % female). Median treatment duration of oral treprostinil was 13.1 months. During early therapy (Months 1-5), 62 % (78/126) of patients reported headache and diarrhea, and 40 % (50/126) reported nausea. At Month 6, many patients who reported side effects during early therapy reported an improvement (61 % headache, 44 % diarrhea, 70 % nausea). Common side effect treatments, including acetaminophen, loperamide, and ondansetron, were effective. Approximately one-quarter of patients reporting the most common side effects were untreated at Month 6.

Conclusion: Patient selection for, and initiation and titration of, oral treprostinil should be individualized and may include parenteral treprostinil induction-transition for faster titration. Assertive side effect management may help patients reach higher and more efficacious doses of oral treprostinil.

Keywords: Dosing; Orenitram; Patient selection; Prostacyclin; Pulmonary arterial hypertension; Side effects; Tolerability.

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Antihypertensive Agents* / administration & dosage
  • Antihypertensive Agents* / adverse effects
  • Antihypertensive Agents* / therapeutic use
  • Consensus
  • Epoprostenol* / administration & dosage
  • Epoprostenol* / adverse effects
  • Epoprostenol* / analogs & derivatives
  • Epoprostenol* / therapeutic use
  • Female
  • Headache / chemically induced
  • Humans
  • Hypertension, Pulmonary / drug therapy
  • Male
  • Middle Aged
  • Nausea / chemically induced
  • Prospective Studies
  • Pulmonary Arterial Hypertension* / drug therapy
  • Pulmonary Arterial Hypertension* / physiopathology
  • Registries
  • Treatment Outcome

Substances

  • treprostinil
  • Epoprostenol
  • Antihypertensive Agents