Pulmonary vasodilator · Prostacyclin · Vasodilator
Epoprostenol (Flolan)
Also called Flolan, Veletri, prostacyclin, iEPO
Indications
- Pulmonary arterial hypertension (WHO group 1, NYHA class III–IV) by continuous IV infusion, to improve exercise capacity (label)
- Refractory hypoxemia in ARDS, inhaled: better oxygenation without proven survival benefit (off-label)
- Acute RV failure and pulmonary hypertension after cardiac surgery, LVAD implant or heart or lung transplant, inhaled (off-label)
- Acute pulmonary vasoreactivity testing during right heart catheterization (off-label)
Dosing
Epoprostenol (inhaled) drip card and mL/h converterStart: 50 ng/kg/min by ideal (predicted) body weight, by continuous vibrating mesh nebulization (range 10–50). At 30,000 ng/mL that is 0.1 mL/h per kg (Li 2021). Fixed-rate setups hold about 8 mL/h with a weight-matched concentration (375 ng/mL per kg: 26,250 ng/mL for 70 kg; Siobal 2003)
Mechanism of action
Epoprostenol is synthetic prostacyclin (PGI₂), the endothelial prostanoid. It binds the IP receptor on vascular smooth muscle and platelets; Gs activates adenylyl cyclase, and the rise in cAMP and protein kinase A activity lowers intracellular calcium and inhibits myosin light-chain kinase, relaxing pulmonary and systemic arterioles and blocking platelet aggregation. Inhaled, it reaches only ventilated alveoli and dilates the vessels serving them, which improves ventilation–perfusion matching and lowers PVR with little systemic effect.
Pharmacology
- Cardiovascular: IV lowers pulmonary and systemic vascular resistance and raises cardiac output; flushing, headache, hypotension and tachycardia limit the dose
- Respiratory: inhaled lowers PVR and improves oxygenation; IV can worsen shunt by dilating vessels in unventilated lung
- Hematologic: inhibits platelet aggregation, adding to bleeding with anticoagulants or low platelets
- GI: nausea, vomiting and diarrhea (diarrhea in 37–50% on long-term IV, label)
- Other: jaw and musculoskeletal pain; rebound pulmonary hypertension with dyspnea, dizziness and weakness after abrupt withdrawal (label)
Pharmacokinetics
| Onset | Minutes, IV or inhaled |
|---|---|
| Duration | Effects fade within minutes of stopping, so any gap causes rebound |
| Half-life | 6 min or less in vivo, based on about 6 min in human blood at 37 °C (label) |
| Distribution | Small Vd, 357 mL/kg in animals (label) |
| Clearance | High, 93 mL/kg/min in animals (label) |
| Metabolism | Spontaneous hydrolysis to 6-keto-PGF₁α and enzymatic breakdown to 6,15-diketo-13,14-dihydro-PGF₁α, both orders of magnitude less active (label) |
| Elimination | Urine 82% and feces 4% of a radiolabeled dose over a week (label) |
| Routes | Continuous IV for PAH; continuous nebulization off-label |
Chemistry
- Prostacyclin sodium, (5Z,9α,11α,13E,15S)-6,9-epoxy-11,15-dihydroxyprosta-5,13-dien-1-oic acid, C₂₀H₃₁NaO₅, MW 374.45 (label): a bicyclic enol ether made from arachidonic acid
- The enol ether hydrolyzes at neutral pH, so it is formulated alkaline (reconstituted pH 11–13) and degrades faster as pH falls (labels)
- Veletri uses arginine and sucrose and the Gland generic glycine and sucrose, stable 48 h at 25 °C from 3,000 to under 60,000 ng/mL and 72 h at 60,000 or more (labels); Flolan's original glycine–mannitol mix lasts about 8 h (Klingbeil 2026)
- Keep out of direct sunlight and never mix with other drugs (labels)
Adverse effects and cautions
In the one-pagers
- ARDSAdjuncts: what, when and the evidence: Inhaled NO or epoprostenol: Rescue for oxygenation or RV failure only: Better P/F at 24 h, no survival gain, more renal failure (Cochrane 2016)
- Cardiorespiratory Look-Alikes and Special PatientsSpecial physiology and equipment: PAH on IV or SC prostacyclin: Pump stopped: rebound pulmonary hypertension, RV failure, syncope: Restart with the backup pump; avoid hypoxia and hypotension; small boluses only; no nitro; PH center
- LVAD BasicsSelection, implant and the early postoperative course: The first week is about the right ventricle. Unloading pulls the septum leftward and removes its help to RV contraction while pump flow raises venous return to an RV still facing high pulmonary pressures; it dilates, the LV under-fills, and flow and PI fall with a high CVP. INTERMACS counts right heart failure as needing an RVAD, prolonged inh
- Pulmonary EmbolismSupporting the failing RV: Dobutamine for low output once MAP holds; inhaled NO or epoprostenol as a bridge
- Common EMS MedicationsChest pain and breathing: Ask about PDE-5 inhibitors: no nitro within 24 h of sildenafil or vardenafil, or 48 h of tadalafil (ACC/AHA 2025); many protocols use 48 h for all. Avoid with IV epoprostenol or treprostinil.
- EMT By-Complaint Quick PagesChest pain: the 12-lead and the drugs: Nitroglycerin: the patient's own 0.4 mg SL, repeated per protocol only while SBP stays over 100; never within 48 h of sildenafil, vardenafil or tadalafil, or with IV epoprostenol or treprostinil (NASEMSO). See prehospital-stroke-stemi for the right-ventricular infarct caution.
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Sources
- FDA label: Veletri (2022)
- FDA label: Epoprostenol for injection (Gland, 2026)
- Li 2021 (inhaled epoprostenol concentrations)
- Block 2021 (delivery interruptions)
For education and exam preparation only. Follow your institution’s protocols. Typical adult values for study. Follow your local protocols and medical direction.