Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
FLOLAN vs ISMO
Clinician-reviewed, head-to-head comparison of mechanism, dosing, pharmacokinetics, and safety profiles.
Last clinically reviewed: July 2026 · OpiCalc Medical Review Team
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.
Isosorbide mononitrate is a nitrate that dilates coronary arteries and peripheral veins. It acts by releasing nitric oxide, which activates guanylate cyclase, increasing c GMP levels, leading to smooth muscle relaxation and vasodilation.
Pulmonary arterial hypertension (PAH) (WHO Group I) in NYHA Class III-IV patients to improve exercise capacity and hemodynamics,Pulmonary arterial hypertension in patients who require chronic IV therapy,Off-label: Severe Raynaud's phenomenon, primary pulmonary hypertension in neonates, and as a bridge to lung transplantation
Prevention of angina pectoris due to coronary artery disease,Off-label: Treatment of acute angina (immediate-release forms)
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.
20 mg orally twice daily, 7 hours apart (e.g., 8 AM and 3 PM) to minimize nitrate tolerance.
3–5 minutes (terminal elimination half-life; rapid inactivation necessitates continuous IV infusion).
Terminal elimination half-life is approximately 5-6 hours. In elderly patients or those with hepatic impairment, half-life may be prolonged (up to 8-10 hours), warranting dose adjustment.
Epoprostenol undergoes rapid hydrolysis at neutral p H 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).
Primarily metabolized in the liver by denitration; minor metabolism via glucuronidation. Metabolites are inactive.
Renal: 70% (as inactive metabolites); biliary/fecal: negligible.
Primarily renal; 80-90% of the dose is excreted as inactive metabolites (isosorbide mononitrate and isosorbide dinitrate) in urine. Less than 1% is excreted unchanged. Fecal excretion is minimal.
Approximately 50% bound to albumin.
Approximately 30% bound to plasma proteins, primarily albumin.
0.03–0.1 L/kg; small Vd consistent with limited extravascular distribution.
Vd is 0.6-0.9 L/kg, indicating distribution into total body water. Higher Vd may be observed in patients with heart failure.
Intravenous: 100% (only route of administration).
Oral: 90-100% (sustained-release formulations). Sublingual: high but variable; generally effective due to extensive absorption.
No specific dose adjustment required; monitor fluid and electrolyte balance due to potential hypotension.
No dose adjustment required for GFR ≥30 m L/min. For GFR <30 m L/min, consider reducing dose to 10 mg twice daily due to potential accumulation of active metabolite.
No specific dose adjustment required; consider reduced clearance in severe hepatic impairment (Child-Pugh class C) with cautious titration.
No dose adjustment in Child-Pugh A or B. For Child-Pugh C, reduce dose to 10 mg twice daily and monitor for hypotension.
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.
Safety and efficacy not established; no standard dosing recommendations.
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.
Start at 10 mg twice daily with gradual titration based on tolerance and renal function. Monitor for hypotension and dizziness.
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.
Do not use with phosphodiesterase-5 (PDE-5) inhibitors (e.g., sildenafil, tadalafil) due to risk of severe hypotension.
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.
Hypotension and reflex tachycardia may occur,Caution in patients with volume depletion or hypotension,May cause headaches; tolerance may develop with prolonged use,Abrupt withdrawal may increase angina frequency
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.
Concurrent use of PDE-5 inhibitors,Severe anemia,Closed-angle glaucoma,Hypersensitivity to isosorbide mononitrate or nitrates,Acute myocardial infarction with low filling pressures
No specific food interactions are reported for epoprostenol. Avoid excessive alcohol as it may worsen hypotension.
Alcohol may enhance hypotension risk. Avoid high-fat meals if extended-release formulation, as they may affect absorption. No other significant food interactions.
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.
ISMO (isosorbide mononitrate) is categorized as FDA Pregnancy Category C. In animal studies, reduced fetal survival and growth retardation were observed at high doses. No adequate human studies exist. Use only if potential benefit justifies risk. First trimester: Theoretical risk of hemodynamic effects; avoid unless necessary. Second/third trimester: May cause fetal hypoxia due to maternal hypotension; monitor fetal heart rate. Peripartum: May exacerbate uterine relaxation and postpartum hemorrhage if used near delivery.
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.
Excretion into human milk is unknown. Due to risk of infant methemoglobinemia and hypotension, caution is advised. M/P ratio: Not available. American Academy of Pediatrics considers nitrate derivatives compatible with breastfeeding, but monitor infant for cyanosis and lethargy.
Pregnancy may alter pharmacokinetics; increase in plasma volume may require dose adjustments. No formal studies; titrate dose based on clinical response (e.g., symptoms of pulmonary arterial hypertension). Monitor for signs of overdose (hypotension, tachycardia) or underdose (worsening dyspnea).
No specific dose adjustments for ISMO in pregnancy are established due to lack of pharmacokinetic studies. However, pregnancy-induced hemodynamic changes (increased plasma volume, cardiac output) may reduce efficacy; consider dose titration based on clinical response. Avoid doses >60 mg/day to minimize hypotensive risk. Use immediate-release formulations for flexible dosing if needed.
FLOLAN (epoprostenol) is a prostacyclin used for pulmonary arterial hypertension (PAH). It has a very short half-life (3-5 minutes) and must be administered via continuous IV infusion. Abrupt interruption can cause life-threatening rebound pulmonary hypertension. The drug is unstable at room temperature; requires ice packs during administration. Dose titration is done based on symptoms and side effects (e.g., jaw pain, flushing, headache, diarrhea).
ISMO (isosorbide mononitrate) is a nitrate used for angina prophylaxis, not for acute attacks. Tolerance develops with sustained use; maintain a 10-12 hour nitrate-free interval to prevent tolerance. Do not use with phosphodiesterase-5 inhibitors (e.g., sildenafil) due to risk of profound hypotension. Contraindicated in severe anemia, increased intracranial pressure, or hypertrophic obstructive cardiomyopathy. Discontinue if blurred vision or dry mouth occurs.
This medication is given continuously through an intravenous (IV) line using a portable infusion pump.,Never stop the infusion suddenly; sudden stoppage can cause severe worsening of your condition.,Keep the medication cold (with ice packs) during infusion; it degrades at room temperature.,Report any signs of infection at the IV site, such as redness, swelling, or pain.,Common side effects include headache, jaw pain, flushing, nausea, and diarrhea; these may improve over time.
Take as prescribed to prevent angina; do not use for acute attacks.,May cause headache, dizziness, or hypotension; rise slowly from sitting.,Avoid taking erectile dysfunction drugs (e.g., sildenafil, tadalafil) as severe blood pressure drop can occur.,Do not stop abruptly to avoid rebound angina.,Store in original container away from light and moisture.
No interactions on record
"Bosentan, a dual endothelin receptor antagonist and an inducer of CYP3A4 and CYP2C9, reduces systemic exposure to vismodegib, a Hedgehog pathway inhibitor primarily metabolized by CYP3A4. This interaction leads to decreased serum concentrations of vismodegib, potentially diminishing its antitumor efficacy in patients with advanced basal cell carcinoma. Concomitant use may require vismodegib dose adjustment or alternative therapies to avoid therapeutic failure."
"Vismodegib inhibits CYP3A4, which is the primary enzyme responsible for metabolizing nilotinib. Concomitant administration may lead to increased nilotinib plasma concentrations, elevating the risk of QT interval prolongation, torsades de pointes, hepatotoxicity, and myelosuppression. Clinical vigilance is warranted due to the narrow therapeutic index of nilotinib."
"Vismodegib, a hedgehog pathway inhibitor, is a moderate inhibitor of CYP2C9, the primary enzyme responsible for metabolizing tolbutamide. Concomitant use can significantly decrease tolbutamide clearance, leading to elevated plasma concentrations and prolonged hypoglycemic effects. This increases the risk of severe hypoglycemia, especially in diabetic patients, and may require dose adjustment of tolbutamide."
Explore head-to-head clinical comparisons of other medications in the same therapeutic classes.
Common clinical questions about FLOLAN vs ISMO, answered by our medical review team.
FLOLAN is a Prostacyclin Vasodilator that works by 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.. ISMO is a Nitrate Vasodilator that works by Isosorbide mononitrate is a nitrate that dilates coronary arteries and peripheral veins. It acts by releasing nitric oxide, which activates guanylate cyclase, increasing c GMP levels, leading to smooth muscle relaxation and vasodilation.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between FLOLAN and ISMO depend on the specific clinical indication. These are agents from distinct pharmacological classes and are not directly interchangeable by dose. A physician or clinical pharmacist should guide any therapeutic switching decisions.
The standard adult dose of FLOLAN is: 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.. The standard adult dose of ISMO is: 20 mg orally twice daily, 7 hours apart (e.g., 8 AM and 3 PM) to minimize nitrate tolerance.. Dosing should always be individualized based on indication, renal and hepatic function, age, and other patient factors.
No direct drug-drug interaction has been formally documented between FLOLAN and ISMO in current clinical databases. However, individual patient risk factors including other medications, organ function, and comorbidities should always be evaluated by a qualified healthcare provider.
The maternal-fetal safety profiles differ. FLOLAN is classified as Category C. 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 . ISMO is classified as Category C. ISMO (isosorbide mononitrate) is categorized as FDA Pregnancy Category C. In animal studies, reduced fetal survival and growth retardation were observed at high doses. No adequate . Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.