Epoprostenol

Epoprostenol is synthetic prostacyclin given by continuous intravenous infusion for severe pulmonary arterial hypertension (group 1), usually functional class III to IV or high-risk disease. It has the strongest survival evidence in severe disease, but it needs a central venous catheter and a pump, and sudden interruption can be fatal.

Classification. Prostacyclin (prostanoid), pulmonary and systemic vasodilator, antiplatelet.

Mechanism. Stimulates prostacyclin receptors, raising cyclic AMP in vascular smooth muscle (vasodilatation) and platelets (inhibition of aggregation), and reduces vascular smooth muscle proliferation.

Pharmacokinetics. Chemically unstable in blood. Half-life under 6 minutes, with effects gone within minutes of stopping. Hydrolysed to inactive metabolites excreted in urine.

Specialist, severe PAH, adults and children. Continuous intravenous infusion through a central line, with a spare pump and infusion set available at all times.

• Dose-ranging in hospital: start 2 ng/kg/minute and increase by 2 ng/kg/minute every 15 minutes or longer until dose-limiting effects appear (flushing, headache, nausea, hypotension).

• Chronic start: 4 ng/kg/minute less than the highest tolerated dose, or 2 ng/kg/minute if the tolerated dose is under 5 ng/kg/minute. Many centres start at 2 ng/kg/minute without dose-ranging.

• Increase by 1 to 2 ng/kg/minute every few days to weeks, directed by symptoms, haemodynamics and adverse effects.

• Usual maintenance 20 to 40 ng/kg/minute after months of titration; higher doses are used in some patients.

Emergency. A rescue option for critically ill patients in a critical care setting, with invasive monitoring.

First-line, alternative. First-line in high-risk PAH. Alternative: subcutaneous or intravenous treprostinil when central line care is difficult.

Loading. No bolus loading dose.

Contraindications. Congestive heart failure from severe left ventricular systolic dysfunction, pulmonary oedema during dose initiation (suggests veno-occlusive disease), hypersensitivity.

Serious adverse effects. Rebound pulmonary hypertension with abrupt interruption, catheter-related bloodstream infection and thrombosis, pulmonary oedema, thrombocytopenia, bleeding, high-output heart failure at high doses, ascites, hypotension.

Common adverse effects. Jaw pain, flushing, headache, nausea, diarrhoea, leg pain, anxiety.

Interactions. Antihypertensives, diuretics and vasodilators add hypotension. Anticoagulants and antiplatelets raise bleeding risk.

Common prescribing errors. Interrupting the infusion (empty reservoir, kinked line, pump failure, flat battery). Stopping suddenly. Switching diluent or formulation without a dose check. Using a peripheral line for long-term infusion.

Special groups.

• Pregnancy: used in life-threatening PAH under specialist care; limited data. Breastfeeding: no data; use under specialist advice.

• Children: weight-based, same schedule.

• Older adults: titrate with care.

• Kidney and liver impairment: no adjustment; monitor adverse effects.

• East Africa: rarely available. Continuity of drug and pump supply, sterile catheter care and a tunnelled central line are the limiting factors.

Formulations. Lyophilised powder for reconstitution in 0.5 mg and 1.5 mg vials, with a specific diluent for some products and sodium chloride 0.9% for others.

Preparation. Reconstitute and dilute exactly as the product requires. The diluent sets the pH and stability: one formulation is stable for 8 hours at room temperature (24 hours with a cold pouch), while another is stable for 24 hours at room temperature. Use a dedicated pump with a reservoir, an in-line filter where the product requires one, and a backup pump.

Baseline. Platelet count, haemoglobin, renal function, liver function, right heart catheter results, functional class, 6 minute walk distance, NT-proBNP.

Monitoring. Blood pressure and heart rate during titration. Platelet count periodically. Catheter site and signs of infection. Clinical and haemodynamic review every 3 to 6 months.

Stop and reduce rules. Reduce the rate for hypotension, severe nausea or jaw pain that does not settle. Never stop abruptly; wean slowly only under specialist care. Stop for pulmonary oedema. Therapeutic drug monitoring is not used.

Referral and escalation. Manage in a PAH centre. Treat any interruption as an emergency: restart on the spare pump and arrange urgent care.