Epoprostenol (Flolan)

• Potent Prostacyclin Analog: Used primarily as continuous IV infusion for advanced pulmonary arterial hypertension (PAH) and right ventricular failure
• Mechanism of Action: Produces strong pulmonary vasodilation, some systemic vasodilation, and inhibits platelet aggregation, improving RV output and symptoms in PAH
• Ultra-Short Half-Life: Extremely short half-life (seconds) and chemical instability → must be given as continuous infusion via dedicated line and pump
• Critical Warning: Abrupt interruption can cause rebound pulmonary hypertension and cardiovascular collapse
• Dosing: In ng/kg/min, starting at low doses and titrated upward based on symptoms, hemodynamics, and side effects (flushing, headache, hypotension)
• Inhaled Use: Also used in ICU settings for inhaled epoprostenol (off-label) to improve V/Q matching and oxygenation in ARDS or severe RV failure

• Generic Name: Epoprostenol
• Brand Names: Flolan, Veletri, generics

Prostacyclin (PGI2) analog; potent pulmonary and systemic vasodilator; antiplatelet properties

Mechanism of Action:

• Epoprostenol is a synthetic analog of prostacyclin (PGI2), an endogenous prostanoid produced by endothelial cells
• Stimulates IP (prostacyclin) receptors on vascular smooth muscle → activation of adenylate cyclase → ↑ cAMP → smooth muscle relaxation and vasodilation, particularly in pulmonary circulation
• Inhibits platelet aggregation by increasing cAMP within platelets, reducing thrombosis in pulmonary vasculature but increasing bleeding risk
• Net effect: decreased pulmonary vascular resistance, improved right ventricular output, and improved exercise capacity and symptoms in PAH

Pharmacokinetics (IV):

• Onset: Very rapid due to IV administration and short half-life; hemodynamic effects seen within minutes of starting or changing dose
• Half-life: Extremely short, typically 3-6 minutes, requiring continuous infusion to maintain effect
• Metabolism: Primarily hydrolysis and enzymatic degradation in blood; inactive metabolites excreted renally
• Stability: Some formulations (e.g., Flolan) require reconstitution with specific diluent and cold packs; newer formulations (Veletri) are more stable at room temperature
• Critical Note: Abrupt interruption or pump failure can cause severe rebound pulmonary hypertension and cardiovascular collapse in patients dependent on the drug

Available Forms:

• Lyophilized powder for IV infusion: Reconstituted with specific diluent (Flolan) or normal saline (Veletri) to manufacturer-specified concentrations
• Dosing typically in ng/kg/min, with concentration and pump settings carefully calculated based on patient weight and desired dose
• Requires dedicated central or sometimes peripheral IV line and an ambulatory or ICU infusion pump with backup power and detailed instructions
• Inhaled formulations: Prepared by nebulizing epoprostenol solution into ventilator circuit or high-flow oxygen system (institution-specific protocols)

IV Epoprostenol for PAH (Adult) – Expert- and Protocol-Driven:

Contraindications:

• Hypersensitivity to epoprostenol or formulation components
• Severe left-sided heart failure or pulmonary edema without clear PAH component (risk of worsening pulmonary congestion)

Major Precautions:

• Systemic hypotension: epoprostenol can cause vasodilation and hypotension, especially during dose escalation or in volume-depleted patients
• Bleeding risk due to inhibition of platelet aggregation; use caution in patients with active bleeding or high bleeding risk
• Abrupt interruption can precipitate life-threatening rebound pulmonary hypertension and right heart failure; always have backup pumps and plans
• Requires close collaboration with pulmonary hypertension specialists; dosing and management are complex and highly individualized

Common:

• Flushing, headache
• Nausea, vomiting, diarrhea
• Jaw pain, myalgias
• Hypotension

Serious:

• Severe hypotension with syncope or shock
• Serious bleeding (e.g., GI, intracranial) due to antiplatelet effect
• Rebound pulmonary hypertension and right heart failure with abrupt interruption
• Catheter-related bloodstream infections and thrombosis from chronic central lines

Clinical Monitoring:

• Blood pressure (noninvasive or arterial line) and heart rate, especially during dose changes
• Symptoms of PAH and RV failure: dyspnea, peripheral edema, syncope, exercise tolerance
• Signs of bleeding, particularly in patients on concomitant anticoagulation
• Central line patency and infection surveillance in chronic infusion patients

• WHO Group 1 PAH: Long-term treatment of pulmonary arterial hypertension, particularly in advanced or high-risk patients (NYHA/WHO functional class III-IV)
• Acute PAH decompensation: RV failure and cardiogenic shock, often as continuation of home therapy in ICU or initiation/uptitration under expert guidance
• Inhaled epoprostenol (off-label): In ARDS or severe pulmonary hypertension to improve oxygenation and RV function (different formulation and approach than chronic IV PAH therapy)

• 1. Lexicomp. (2024). Epoprostenol: Drug information. Wolters Kluwer.
• 2. Galiè, N., Humbert, M., Vachiery, J.-L., et al. (2016). 2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. European Heart Journal, 37(1), 67–119. https://doi.org/10.1093/eurheartj/ehv317
• 3. Farkas, J. (2022). Right ventricular failure. EMCrit Project / IBCC. https://emcrit.org/ibcc/rvf/