Overview of therapies targeting the prostacyclin pathway

PGI2 therapyApprovalWHO FC indicationMode of administrationFrequency of administrationHalf-lifeESC/ERS class of recommendation# and level of evidence for use as monotherapy [3, 17]
Flolan [18] (epoprostenol)++III–IVIntravenousContinuous<6 min [24]IAIA
Veletri+ [19, 20] (epoprostenol)++III–IVIntravenousContinuous
Remodulin [6, 21] (treprostinil)+##+II–IVIntravenousContinuous34 min [25]IIaCIIbC
Remodulin [6, 21] (treprostinil)+##+II–IVSubcutaneousContinuous85 min [25]IBIIbC
Tyvaso [8] (treprostinil)+IIIInhaled4 times per day, with each inhalation taking up to 3 min [8, 26]NAIBIIbC
Orenitram [11] (treprostinil)+II–IIIOral2–3 times per day3–4 h [24]IIbB
Ilomedin§ [7] (iloprost)III–IVIntravenousOver 6 h daily20–25 min [24]IIaCIIbC
Ventavis [9, 10] (iloprost)++III–IVInhaled6–9 times per day, with each inhalation taking 3–10 min, depending on dose and nebuliser device [9]IBIIbC
Dornerƒ [15] (beraprost)NAOral3–4 times per day45 min [24]IIbB
Uptravi [12, 13] (selexipag)++II–IIIOral2 times per day6.2–13.5 h¶¶ [12]IBIB
  • PGI2: prostaglandin I2 (prostacyclin); WHO FC: World Health Organization functional class; ESC: European Society of Cardiology; ERS: European Respiratory Society; NA: not available. #: I, evidence and/or general agreement that a given treatment or procedure is beneficial, useful or effective; II, conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of the given treatment or procedure; IIa, weight of evidence/opinion is in favour of usefulness/efficacy; IIb, usefulness/efficacy is less well established by evidence/opinion; III, evidence or general agreement that the given treatment or procedure is not useful/effective and in some cases may be harmful. : A, data derived from multiple randomised clinical trials or meta-analyses; B, data derived from a single randomised clinical trial or large nonrandomised studies; C, consensus of opinion of the experts, and/or small studies, retrospective studies or registries. +: known as Caripul in some countries. §: approved in New Zealand. ƒ: approved in Japan and South Korea [22], a modified-release version is available (Careload [14] and Berasus [23]) and can be administered twice per day. ##: approved in the European Union, except Ireland, Spain and the UK [21]. ¶¶: active selexipag metabolite.