FLOLAN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for FLOLAN (FLOLAN).

How it works

Epoprostenol is a prostaglandin I2 (prostacyclin) analogue that directly vasodilates pulmonary and systemic arterial beds, inhibits platelet aggregation, and has antiproliferative effects on vascular smooth muscle.

What the body does with it

Metabolism	Epoprostenol undergoes rapid hydrolysis at neutral pH and is also metabolized by enzymes including 15-hydroxyprostaglandin dehydrogenase to inactive metabolites (6-keto-PGF1alpha, 6,15-diketo-PGF1alpha, and 6,15-diketo-13,14-dihydro-PGF1alpha).
Excretion	Renal: 70% (as inactive metabolites); biliary/fecal: negligible.
Half-life	3–5 minutes (terminal elimination half-life; rapid inactivation necessitates continuous IV infusion).
Protein binding	Approximately 50% bound to albumin.
Volume of Distribution	0.03–0.1 L/kg; small Vd consistent with limited extravascular distribution.
Bioavailability	Intravenous: 100% (only route of administration).
Onset of Action	Intravenous: immediate (within 30 seconds).
Duration of Action	Short; clinical effects last 3–5 minutes after infusion cessation due to rapid hydrolysis.

Classification & Brands

Dosing & administration

Initial: 4 ng/kg/min via continuous IV infusion, then titrated in increments of 1-2 ng/kg/min at intervals of at least 15 minutes based on clinical response. Typical maintenance dose: 20-40 ng/kg/min; range: 10-80 ng/kg/min.

Dosage form	INJECTABLE
Renal impairment	No specific dose adjustment required; monitor fluid and electrolyte balance due to potential hypotension.
Liver impairment	No specific dose adjustment required; consider reduced clearance in severe hepatic impairment (Child-Pugh class C) with cautious titration.
Pediatric use	Initial: 2 ng/kg/min via continuous IV infusion, titrate by 1-2 ng/kg/min every 15 minutes as tolerated. Maximum dose not established; typical range 5-40 ng/kg/min.
Geriatric use	No specific dose adjustment; start at lower end of dosing range (4 ng/kg/min) and titrate cautiously due to increased sensitivity to hemodynamic effects.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for FLOLAN (FLOLAN).

Breastfeeding	Epoprostenol is not recommended during breastfeeding. No data on presence in human milk, effects on the breastfed infant, or milk production. Due to potential for serious adverse reactions (e.g., hypotension, bleeding), breastfeeding should be discontinued during treatment.
Teratogenic Risk	FDA Pregnancy Category B. No evidence of teratogenicity in animal studies; however, no adequate and well-controlled studies in pregnant women. Epoprostenol is a potent vasodilator and inhibitor of platelet aggregation; theoretical risk of hemorrhage in the fetus. Use only if clearly needed.

Warnings & precautions

■ FDA Black Box Warning

FLOLAN is a potent vasodilator and must be administered by continuous IV infusion through a permanent central venous catheter. Abrupt discontinuation or sudden large dose reductions may result in worsening pulmonary hypertension and death. Only clinicians experienced in PAH treatment should prescribe FLOLAN.

Side Effect Profile

Serious Effects

Absolute Contraindications

Long-term use in patients with pulmonary veno-occlusive disease (PVOD), hypersensitivity to epoprostenol or structurally related drugs, or severe left ventricular systolic dysfunction (NYHA Class III-IV heart failure) due to risk of pulmonary edema.

Clinical Precautions

Precautions

Do not abruptly discontinue infusion (risk of rebound pulmonary hypertension), monitor for pulmonary edema (if suspect veno-occlusive disease), may cause bleeding complications (due to antiplatelet effects), monitor for sepsis/thrombosis from chronic IV catheter, use caution in patients with hepatic or renal impairment.

Clinical Tips & Counseling

Drug interactions

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FLOLAN

Clinical safety rating: caution

Comprehensive clinical and safety monograph for FLOLAN (FLOLAN).

How it works

What the body does with it

Metabolism	Epoprostenol undergoes rapid hydrolysis at neutral pH and is also metabolized by enzymes including 15-hydroxyprostaglandin dehydrogenase to inactive metabolites (6-keto-PGF1alpha, 6,15-diketo-PGF1alpha, and 6,15-diketo-13,14-dihydro-PGF1alpha).
Excretion	Renal: 70% (as inactive metabolites); biliary/fecal: negligible.
Half-life	3–5 minutes (terminal elimination half-life; rapid inactivation necessitates continuous IV infusion).
Protein binding	Approximately 50% bound to albumin.
Volume of Distribution	0.03–0.1 L/kg; small Vd consistent with limited extravascular distribution.
Bioavailability	Intravenous: 100% (only route of administration).
Onset of Action	Intravenous: immediate (within 30 seconds).
Duration of Action	Short; clinical effects last 3–5 minutes after infusion cessation due to rapid hydrolysis.

Classification & Brands

Dosing & administration

Dosage form	INJECTABLE
Renal impairment	No specific dose adjustment required; monitor fluid and electrolyte balance due to potential hypotension.
Liver impairment	No specific dose adjustment required; consider reduced clearance in severe hepatic impairment (Child-Pugh class C) with cautious titration.
Pediatric use	Initial: 2 ng/kg/min via continuous IV infusion, titrate by 1-2 ng/kg/min every 15 minutes as tolerated. Maximum dose not established; typical range 5-40 ng/kg/min.
Geriatric use	No specific dose adjustment; start at lower end of dosing range (4 ng/kg/min) and titrate cautiously due to increased sensitivity to hemodynamic effects.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for FLOLAN (FLOLAN).

Breastfeeding	Epoprostenol is not recommended during breastfeeding. No data on presence in human milk, effects on the breastfed infant, or milk production. Due to potential for serious adverse reactions (e.g., hypotension, bleeding), breastfeeding should be discontinued during treatment.
Teratogenic Risk	FDA Pregnancy Category B. No evidence of teratogenicity in animal studies; however, no adequate and well-controlled studies in pregnant women. Epoprostenol is a potent vasodilator and inhibitor of platelet aggregation; theoretical risk of hemorrhage in the fetus. Use only if clearly needed.