From the Guidelines
Selexipag is recommended for the treatment of pulmonary arterial hypertension (PAH) in patients with systemic sclerosis (SSc) due to its proven efficacy in reducing morbidity and mortality, as demonstrated in a high-quality RCT 1.
Key Points
- Selexipag has been shown to be well-tolerated in the PAH-SSc subgroup, with a risk reduction of 44% (HR 0.56; 95% CI 0.34 to 0.91) favoring selexipag compared to placebo for the primary composite endpoint of morbidity/mortality in patients with PAH-SSc 1.
- The medication can be used in patients with SSc-PAH who are either on no treatment or on stable doses of PDE-5i, ERAs, or both.
- Selexipag works as a selective prostacyclin receptor agonist, helping to dilate blood vessels in the lungs and reduce the workload on the heart.
Dosage and Administration
- The typical starting dose of selexipag is 200 micrograms twice daily, which is gradually increased weekly to the highest tolerated dose, usually between 200-1600 micrograms twice daily.
- Selexipag should be taken with food to improve tolerability, and doses should be approximately 12 hours apart.
Important Considerations
- Common side effects of selexipag include headache, jaw pain, muscle pain, diarrhea, nausea, and vomiting, which often improve with continued use as the body adjusts to the medication.
- It is essential not to suddenly stop taking selexipag, as this could worsen PAH symptoms.
- Selexipag offers a convenient oral treatment option for long-term management of PAH in patients with SSc, differing from other PAH treatments like epoprostenol or iloprost that require continuous infusion or inhalation.
From the FDA Drug Label
Selexipag tablets are indicated for the treatment of pulmonary arterial hypertension (PAH, WHO Group I) to delay disease progression and reduce the risk of hospitalization for PAH. The main use of selexipag is to treat pulmonary arterial hypertension (PAH), specifically to:
- Delay disease progression
- Reduce the risk of hospitalization for PAH 2 Key points about selexipag include:
- It is a prostacyclin receptor agonist 2
- It is used to treat PAH, WHO Group I 2
From the Research
Overview of Selexipag
- Selexipag is an orally active, first-in-class, selective prostacyclin IP receptor agonist 3, 4, 5, 6, 7
- It is approved for the long-term treatment of pulmonary arterial hypertension (PAH) in adult patients with WHO functional class II or III 3, 4, 6
Efficacy of Selexipag
- Selexipag significantly reduced the risk of the primary composite endpoint of all-cause death or a complication related to PAH versus placebo in patients with PAH 3, 4, 5, 6, 7
- The treatment effect was largely driven by significant reductions in disease progression and hospitalization for PAH 3, 5, 7
- Selexipag also improved exercise capacity, as measured by the 6-minute walk distance 5, 7
Safety and Tolerability of Selexipag
- Selexipag was generally well tolerated, with an adverse event profile consistent with other therapies targeting the prostacyclin pathway 3, 4, 5, 6
- The most common adverse effects associated with selexipag were headache, diarrhea, jaw pain, and nausea 4, 5, 6
Pharmacology and Pharmacokinetics of Selexipag
- Selexipag is rapidly hydrolyzed to a long-acting metabolite that binds with high selectivity to IP receptors, resulting in vasodilation, inhibition of platelet aggregation, and antiinflammatory effects 6
- Selexipag has a high selectivity for the IP2-receptor and differs from conventional prostacyclin analogues in its chemical structure 5
Clinical Significance of Selexipag
- Selexipag is a valuable addition to PAH therapeutics, especially by reducing PAH-related hospitalizations and improving quality of life in PAH patients 5
- Selexipag offers distinct pharmacologic advantages over other agents for the treatment of PAH, including oral administration and a relatively long half-life 6