Head-to-head clinical analysis & difference comparison: details on mechanism of action, dosing, half-life, interactions, and maternal-fetal safety.
FLOLAN vs HYDRALAZINE HYDROCHLORIDE
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.
Vasodilation of arterioles by direct relaxation of vascular smooth muscle, likely involving interference with calcium movement.
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
Hypertension,Heart failure (adjunctive therapy)
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.
Oral: Initiate with 10 mg 4 times daily for 2-4 days, then increase to 25 mg 4 times daily for the remainder of the week, then titrate to 50 mg 4 times daily. Maximum daily dose: 300 mg. Intravenous: 5-20 mg IV bolus, may repeat every 20-30 minutes as needed, or continuous IV infusion 0.5-10 mg/hour.
3–5 minutes (terminal elimination half-life; rapid inactivation necessitates continuous IV infusion).
The terminal elimination half-life of hydralazine is approximately 2–4 hours in patients with normal renal function, but it is prolonged in renal impairment (up to 7–16 hours). The antihypertensive effect often lasts longer than the half-life due to persistent binding to arteriolar receptors.
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).
Extensively metabolized in the liver via N-acetylation (N-acetyltransferase 2, NAT2) and subsequent conjugation; also metabolized by cytochrome P450 (CYP) enzymes.
Renal: 70% (as inactive metabolites); biliary/fecal: negligible.
Hydralazine is primarily metabolized in the liver via N-acetylation (polymorphic) and hydroxylation. Less than 10% of the dose is excreted unchanged in urine. The major metabolites are hydralazine pyruvic acid hydrazone and other conjugates, which are excreted renally. Fecal elimination is negligible.
Approximately 50% bound to albumin.
Approximately 85–90% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein.
0.03–0.1 L/kg; small Vd consistent with limited extravascular distribution.
1.5–1.8 L/kg. This large Vd indicates extensive distribution into tissues, including arteriolar smooth muscle.
Intravenous: 100% (only route of administration).
Oral bioavailability is about 26–50% due to significant first-pass metabolism. Bioavailability is higher in slow acetylators compared to rapid acetylators.
No specific dose adjustment required; monitor fluid and electrolyte balance due to potential hypotension.
Cr Cl 10-50 m L/min: Administer every 8 hours. Cr Cl <10 m L/min: Administer every 8-16 hours. Dose reduction may be necessary to avoid accumulation.
No specific dose adjustment required; consider reduced clearance in severe hepatic impairment (Child-Pugh class C) with cautious titration.
Child-Pugh Class A and B: No specific recommendations; use with caution. Child-Pugh Class C: Contraindicated due to risk of hepatotoxicity and reduced drug clearance.
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.
Oral: 0.75-1 mg/kg/day divided every 6-12 hours, maximum 5 mg/kg/day. Intravenous: 0.1-0.2 mg/kg/dose IV every 4-6 hours as needed, maximum 0.5 mg/kg/dose (20 mg).
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.
Initiate at lower doses (e.g., 10 mg 2-3 times daily) and titrate slowly due to increased risk of hypotension and drug accumulation; monitor renal function closely.
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.
May cause a syndrome resembling systemic lupus erythematosus (SLE), especially with prolonged use or high doses.
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.
May cause drug-induced lupus, peripheral neuritis (pyridoxine deficiency), myocardial infarction (precipitate angina), hypotension, tachycardia, and blood dyscrasias. Use with caution in patients with coronary artery disease, cerebrovascular disease, or renal impairment.
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.
Hypersensitivity to hydralazine, mitral valvular rheumatic heart disease, coronary artery disease, and idiopathic systemic lupus erythematosus.
No specific food interactions are reported for epoprostenol. Avoid excessive alcohol as it may worsen hypotension.
Hydralazine absorption is significantly increased when taken with food; it is recommended to take with meals for consistent effect. Avoid high-tyramine foods (aged cheeses, cured meats, fermented products) if combined with MAOIs, though hydralazine itself is not an MAOI. No specific dietary restrictions otherwise.
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.
First trimester: Limited human data; animal studies show no teratogenicity. Second/third trimester: Associated with maternal hypotension and potential fetal distress; no known structural anomalies.
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.
Hydralazine is excreted into breast milk in small amounts (M/P ratio ~0.8). Considered compatible with breastfeeding by AAP; monitor infant for hypotension or drowsiness.
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).
Increased clearance in pregnancy may require higher doses to achieve same antihypertensive effect; start low and titrate based on blood pressure response.
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).
Hydralazine is a direct-acting arterial vasodilator; its antihypertensive effect is limited by reflex tachycardia and fluid retention, so it is typically used in combination with a beta-blocker and a diuretic. Slow acetylators are at increased risk of drug-induced lupus, especially with doses >200 mg/day. Administer with food to enhance bioavailability; onset of action occurs within 20-30 minutes IV. For hypertensive urgency, IV hydralazine 5-20 mg every 20-30 min is used, but avoid in suspected myocardial ischemia due to reflex tachycardia.
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 exactly as prescribed, with food or milk to increase absorption.,Do not stop abruptly; sudden cessation can cause severe rebound hypertension.,Report symptoms like chest pain, rapid heartbeat, joint pain, rash, or fever to your doctor.,Avoid alcohol and other antihypertensives unless approved by your doctor.,Inform your doctor if you become pregnant or plan to become pregnant.,May cause dizziness; rise slowly from sitting or lying down.
No interactions on record
"Oxaprozin, a nonsteroidal anti-inflammatory drug (NSAID), can reduce the antihypertensive efficacy of hydralazine, a direct-acting vasodilator. NSAIDs inhibit prostaglandin synthesis, which can lead to sodium and fluid retention and increased vascular resistance, thereby counteracting the vasodilatory effects of hydralazine. This interaction may result in diminished blood pressure control and require dosage adjustments or alternative therapies."
"Hydralazine, a direct-acting vasodilator, may reduce the antihypertensive efficacy of nonsteroidal anti-inflammatory drugs (NSAIDs) like sulindac. NSAIDs inhibit cyclooxygenase-mediated prostaglandin synthesis, leading to sodium retention and increased vascular tone, which can antagonize the vasodilatory effects of hydralazine. This interaction may result in elevated blood pressure and diminished control of hypertension in patients receiving both agents."
"Hydralazine, a direct-acting vasodilator, may reduce the antihypertensive efficacy of Tolfenamic acid, a nonsteroidal anti-inflammatory drug (NSAID) that non-selectively inhibits cyclooxygenase (COX) enzymes. The interaction arises because Tolfenamic acid's inhibition of COX-2 reduces synthesis of vasodilatory prostaglandins (e.g., prostacyclin) in the vascular endothelium, which counteracts the vasodilation induced by Hydralazine. Clinically, this can lead to blunted blood pressure reduction, potentially requiring dose adjustments or alternative therapies to maintain adequate hypertension control."
Explore head-to-head clinical comparisons of other medications in the same therapeutic classes.
Common clinical questions about FLOLAN vs HYDRALAZINE HYDROCHLORIDE, 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.. HYDRALAZINE HYDROCHLORIDE is a Vasodilator that works by Vasodilation of arterioles by direct relaxation of vascular smooth muscle, likely involving interference with calcium movement.. They differ in pharmacokinetic profiles, FDA-approved indications, and side effect profiles.
Potency comparisons between FLOLAN and HYDRALAZINE HYDROCHLORIDE 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 HYDRALAZINE HYDROCHLORIDE is: Oral: Initiate with 10 mg 4 times daily for 2-4 days, then increase to 25 mg 4 times daily for the remainder of the week, then titrate to 50 mg 4 times daily. Maximum daily dose: 300 mg. Intravenous: 5-20 mg IV bolus, may repeat every 20-30 minutes as needed, or continuous IV infusion 0.5-10 mg/hour.. 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 HYDRALAZINE HYDROCHLORIDE 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 . HYDRALAZINE HYDROCHLORIDE is classified as Category A/B. First trimester: Limited human data; animal studies show no teratogenicity. Second/third trimester: Associated with maternal hypotension and potential fetal distress; no known stru. Always consult a maternal-fetal medicine specialist before taking either drug during pregnancy or lactation.