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Generic Name: Epoprostenol Sodium
Class: Vasodilating Agents, Miscellaneous
VA Class: HS875
CAS Number: 61849-14-7


Vasodilator and platelet-aggregation inhibitor; a naturally occurring prostaglandin.1 2 5 10 17 21 41

Uses for Flolan

Pulmonary Arterial Hypertension

Long-term treatment of primary pulmonary hypertension (PPH; also known as idiopathic pulmonary arterial hypertension [IPAH]) and pulmonary hypertension associated with the scleroderma spectrum of disease (PH/SSD) in NYHA Class III and IV patients unresponsive to conventional therapy;1 5 6 14 17 48 designated an orphan drug by FDA for these uses.4

Considered treatment of choice by the American College of Chest Physicians (ACCP) and other experts for patients with NYHA functional class IV pulmonary arterial hypertension (PAH) who are not candidates for or who fail calcium-channel blocker therapy.8 11 16 17 18 31 41 44 47 48

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One of several options for the treatment of NYHA functional class III PAH.17 31 44 48 Patients with early NYHA functional class III PAH may be treated with an oral agent (endothelin-receptor antagonist [e.g., bosentan] or sildenafil);8 16 17 18 31 40 44 those with more advanced NYHA functional class III disease may require treatment with IV epoprostenol or a prostacyclin analog (sub-Q or IV treprostinil, inhaled iloprost).44

When selecting initial PAH therapy, consider factors such as NYHA functional class, disease severity, potential adverse effects, and patient preference.8 44 48

6 Safety and efficacy not systematically evaluated in patients with PH associated with diseases other than scleroderma.1

Flolan Dosage and Administration


Restricted Distribution Program

Available through restricted distribution program; not available through community pharmacies.3 Contact manufacturer for specific information.3

IV Administration

For IV use only.1 8 10

Administer by continuous IV infusion via a central venous catheter with a portable controlled-infusion device; peripheral IV catheter may be used temporarily until central venous access is established.1 2 39 Consult manufacturer’s labeling for infusion-device specifications.1

Do not dilute or administer with other parenteral solutions or medications.1

When administered at room temperature (without a cold pouch), administer a single reservoir of reconstituted solution over a period of no longer than 8 hours.1 When a cold pouch is employed during the infusion, administer a single reservoir of reconstituted solution over a period of no longer than 24 hours.1 (See Storage under Stability.)

Delivery system malfunctions (e.g., infusion-device failure, occluded catheter) may result in inadvertent overdosage or underdosage.1 To avoid potential interruptions in drug delivery, patient must have access to a backup IV infusion device and infusion sets.1 17 47 (See Abrupt Withdrawal under Cautions.) Consider use of a multi-lumen catheter if patient receives other IV drugs routinely.1

Adjust infusion rates only under the direction of a physician, except in life-threatening situations (e.g., unconsciousness, collapse).1 Observe and monitor standing and supine BP and heart rate in patients for several hours following changes in infusion rates.1


Reconstitute only with manufacturer-supplied diluent (Sterile Diluent for Flolan); see manufacturer’s labeling for details on reconstitution, preparation of solutions, and selection of drug concentration in solutions.1

Protect reconstituted solutions from light and refrigerate at 2–8°C prior to use; do not freeze.1

Rate of Administration

Avoid abrupt discontinuance or sudden large reductions in infusion rates.1 10 12 17 (See Abrupt Withdrawal under Cautions.) Consult manufacturer’s labeling for specific instructions on selection of infusion rate and drug concentration.1


Available as epoprostenol sodium; dosage expressed in terms of epoprostenol.1 2

Considerable interindividual variability in patient response; individualize dosage.7 8 10 41 48

Titrate dosages carefully until desired therapeutic effect achieved or intolerable adverse effects occur.1 10


Pulmonary Arterial Hypertension
Initiation and Titration of Therapy
Continuous IV Infusion

Initially, 2 ng/kg per minute (or a lower dose if not tolerated); increase in increments of 2 ng/kg per minute at intervals of ≥15 minutes until dose-limiting pharmacologic effects are elicited or a tolerance limit to the drug is established and further increases in the infusion rate are not clinically warranted.1 Maintain dosage at a level where pharmacologic effects are tolerated.1

Infusion rates may be calculated using the following formula:1

Infusion rate (mL/hr) = [dose (ng/kg per min) × wt (in kg) × 60 min/hr] / final concentration of epoprostenol solution (ng/mL)

In clinical studies in patients with PH/SSD, the average initial dosage of 2.2 ng/kg per minute was increased during the first week of therapy to 4.1 ng/kg per minute on day 7, and the mean dosage was 11.2 ng/kg per minute by the end of week 12; incremental increases in dosage averaged 2–3 ng/kg per minute every 3 weeks.1

Chronic Therapy
Continuous IV Infusion

During chronic infusion, dosage increases generally are required based on persistence, recurrence, or worsening of disease symptoms; dosage reductions may be needed because of adverse effects.1

Adjust dosage in increments of 1–2 ng/kg per minute at intervals of ≥15 minutes.1 If dose-limiting adverse effects occur, decrease dosage gradually in decrements of 2 ng/kg per minute at intervals of ≥15 minutes; avoid abrupt withdrawal or sudden large reductions in infusion rates.1 10 12 17 (See Abrupt Withdrawal under Cautions.)

Prolonged therapy may cause tachyphylaxis and require periodic dosage adjustments.7 10 35 41 47 (See Dosage Titration under Cautions.)

In clinical studies, therapy was tapered in patients receiving lung transplants after initiation of cardiopulmonary bypass.1

Special Populations

Geriatric Patients

Select initial dosage in geriatric patients with caution (at low end of dosage range) and titrate carefully because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.1

Cautions for Flolan


  • Chronic use in CHF due to severe left ventricular systolic dysfunction.1

  • Chronic use in patients who develop pulmonary edema during initial dosage titration.1

  • Known hypersensitivity to epoprostenol or structurally related drugs.1



Solution and Drug Compatibility

Reconstitute and dilute using only the diluent supplied by the manufacturer (Sterile Diluent for Flolan).1 Do not admix or infuse in the same IV line with other solutions or drugs.1

Abrupt Withdrawal

Avoid abrupt discontinuance or sudden large reductions in dosage.1 10 12 17

Because of the drug’s rapid metabolism, abrupt withdrawal (including interruptions in drug delivery), sudden large reductions in dosage, or even brief interruptions in drug delivery may result in symptoms associated with rebound pulmonary hypertension, e.g., dyspnea, dizziness, asthenia, and/or death.1 8 10 17 19

If central venous access is disrupted (e.g., clogging or dislodgement of catheter), patients should seek medical care immediately; may reinstitute IV infusion via peripheral catheter until central venous access is reestablished.17

Patient should have access to a backup IV infusion device and infusion sets to avoid interruptions in drug delivery due to equipment malfunction.1 17 47


Aseptic technique must be used in routine catheter care and in the reconstitution and administration of drug solutions.1 Local infection and sepsis associated with drug delivery system (chronic indwelling central venous catheter) reported.1 2 5 10 11 12 17 19 28 41

General Precautions

Use Restrictions

Should be used only by qualified clinicians experienced in the diagnosis and management of PAH.1 17 23 Carefully establish the diagnosis of PAH before use.1

Consider referral of patients to specialized centers experienced in the management of pulmonary vascular diseases.10 11 16 17 18 23 31 44

Decision to initiate therapy must include careful consideration of the high likelihood that therapy will be needed for prolonged periods, possibly years, and of the patient’s ability to accept and care for a permanent IV catheter and infusion device.1 17

Initial dosage titration should be performed in a medically supervised setting adequately equipped for physiologic monitoring and emergency care.1 17

Increases in Pulmonary Arterial Pressure

Asymptomatic increases in pulmonary artery pressure coincident with increases in cardiac output reported rarely during initial dosage titration; such increases in pulmonary artery pressure do not necessarily preclude chronic therapy and may be controlled with dosage reduction.1

Initial dosage titration has been performed with and without right heart catheterization in clinical studies; consider risk versus potential benefit of cardiac catheterization in patients with PH.1 41

Hematologic Effects

Inhibits platelet aggregation; potential risk of hemorrhage, particularly in patients with increased risk of bleeding (e.g., concomitant antiplatelet or anticoagulant therapy, congenital heart disease, scleroderma).1 17 45 46 48

Prophylaxis of Thromboembolism

Unless contraindicated, administer concomitant anticoagulant therapy to reduce the risk of pulmonary thromboembolism or systemic embolism associated with the permanent indwelling central venous catheter.1 16 17 18 23 31 36 47 48

Weigh benefits versus risks of anticoagulation, particularly in patients with increased risk of bleeding.1 17 48 (See Hematologic Effects under Cautions.)

Dosage Titration

Dosage adjustments during chronic use should be made immediately upon occurrence of dose-limiting adverse effects or worsening of symptoms associated with pulmonary hypertension.1 Following dosage adjustments, standing and supine BP and heart rate should be monitored closely for several hours.1 (See Dosage and Administration.)

Aggressive dosage titrations to overcome tachyphylaxis may result in elevated cardiac output and/or high output heart failure.17 47 48 Monitor PAH symptoms, exercise capacity, adverse effects, and hemodynamic function frequently when making dosage adjustments.1 47 48 Consider periodic cardiac catheterizations to prevent underdosing or overdosing of drug.47 48 Weigh risks versus benefits of cardiac catheterization.1

Specific Populations


Category B.1

Safety and efficacy during labor, vaginal delivery, or cesarean section have not been established.1


Not known whether epoprostenol is distributed into milk;1 use with caution in nursing women.1

Pediatric Use

Safety and efficacy not established in pediatric patients.1 43

Limited experience in pediatric patients suggests clinical response generally is similar to that of adults; higher dosages of epoprostenol may be required.17

Geriatric Use

Clinical studies did not include sufficient numbers of patients 65 years of age or older to determine whether geriatric patients respond differently than younger patients.1

Common Adverse Effects

Flushing,1 2 5 7 8 9 10 17 18 20 jaw pain,1 5 6 7 8 9 10 11 12 17 18 20 headache,1 2 5 7 8 9 10 11 12 17 18 20 nausea,1 2 6 8 9 10 11 17 20 vomiting,1 2 5 9 11 20 hypotension,1 2 11 tachycardia,1 2 chest pain,1 anxiety/nervousness,1 dizziness,1 2 bradycardia,1 2 influenza-like symptoms,1 rash,1 dyspnea,1 abdominal pain,1 2 musculoskeletal pain.1 2 10 11 12 17 18 20

Interactions for Flolan

In clinical studies, epoprostenol was used concomitantly with digoxin, diuretics, anticoagulants, oral vasodilators, and supplemental oxygen.1 5 6 7 19 20

Specific Drugs





Potential for increased risk of bleeding1

Use with caution1

Antiplatelet agents

Potential for increased risk of bleeding1

Use with caution1


Potential decreased clearance of digoxin; possible digoxin toxicity1

Use with caution, especially during initiation of therapy and in patients prone to digoxin toxicity1


Potential decreased clearance of furosemide1

Possible additive hypotensive effect1

Changes in furosemide clearance not considered clinically important1

Use with caution1

Hypotensive agents

Possible additive hypotensive effect1

Use with caution1


Possible additive hypotensive effect1

Use with caution1

Flolan Pharmacokinetics

Chemical assays with sufficient sensitivity and specificity to assess the in vivo human pharmacokinetics of epoprostenol are not currently available.1



Animal studies indicate a small volume of distribution (357 mL/kg).1



Rapidly hydrolyzed at neutral pH in blood and also subject to enzymatic degradation.1 2 Metabolized to 2 primary metabolites, 6-keto-PGF (formed by spontaneous degradation) and 6,15-diketo-13,14-dihydro-PGF (enzymatically formed); data in animals indicate that both metabolites have pharmacologic activity orders of magnitude less than parent drug.1 2 Fourteen additional minor metabolites have been isolated from urine.1

Elimination Route

As metabolites via renal excretion.1 2


In vitro, approximately 6 minutes in human blood at 37°C and pH 7.4; in vivo, expected to be ≤6 minutes.1 2 10

2.7 minutes (animal studies).1

Special Populations

No gender difference observed in in vitro (human plasma) half-life based on inhibition of platelet aggregation.1




Powder for Injection

15–25°C; protect from light.1

Store diluent (Sterile Diluent for Flolan) at 15–25°C.1

Store drug and diluent vials in carton to protect from light until used.1

Store reconstituted solution under refrigeration at 2–8°C and protect from light; do not freeze.1 When stored or in use, do not expose to temperatures >25°C.1 Discard reconstituted solutions that have been frozen or stored at 2–8°C for longer than 48 hours.1

Prior to infusion at room temperature (15–25°C), store reconstituted solutions under refrigeration at 2–8°C for up to 40 hours.1 When administered at room temperature, administer a single reservoir of reconstituted solution over a period of no longer than 8 hours.1

Prior to infusion using an appropriate cold pouch (e.g., those used in clinical trials were obtained from Palco Labs, Palo Alto, CA), store reconstituted solutions under refrigeration at 2–8°C for up to 24 hours.1 When a cold pouch is employed during the infusion, administer a single reservoir of reconstituted solution over a period of no longer than 24 hours.1 Change gel packs in cold pouch every 12 hours.1 Keep reconstituted solution at 2–8°C under refrigeration or in a cold pouch (or a combination of the two) for a total duration of no longer than 48 hours.1


For information on systemic interactions resulting from concomitant use, see Interactions.


Drug and Solution Compatibility

Do not dilute or administer with other parenteral solutions or drugs.1


  • Direct vasodilation of pulmonary and systemic arterial vascular beds and inhibition of platelet aggregation.1 2 10

  • May have antiproliferative effects on the intimal layer of precapillary arteries.2 5 8 9 11 12 18 19 20 22 25 26 27 31 32 35 41

  • Produces dose-related increases in cardiac index and stroke volume.1 2 41

  • Produces dose-related decreases in pulmonary vascular resistance, total pulmonary resistance, and mean systemic arterial pressure.1 2 41

  • Associated with improvement in survival, exercise capacity, and quality of life assessments.1 2 5 6 47 48

  • Effect on heart rate varies with dose in animals; vagally mediated bradycardia at lower doses and reflex tachycardia in response to direct vasodilation and hypotension at higher doses.1 2

  • No major effects on cardiac conduction in animals.1

  • Additional pharmacologic effects observed in animals include bronchodilation, inhibition of gastric acid secretion, and decreased gastric emptying.1

Advice to Patients

  • Importance of advising patient that therapy is infused continuously through a permanent indwelling central venous catheter via a portable infusion device and requires sustained commitment to drug reconstitution, drug administration, and care of the permanent central venous catheter.1

  • Importance of advising patient that therapy probably will be needed for prolonged periods, possibly years.1

  • Importance of careful consideration of patient’s ability to accept and care for a permanent central venous catheter and infusion device.1

  • Importance of advising patients that abrupt withdrawal or sudden interruptions in drug delivery may result in symptoms associated with rebound PH (e.g., dyspnea, dizziness, asthenia) and/or death.1 10 17

  • Importance of advising patient to seek medical care immediately if central venous access is disrupted (e.g., clogging or dislodgement of the catheter).17

  • Importance of advising patient that sterile technique must be adhered to in drug preparation and catheter care to prevent sepsis.1

  • Importance of reconstitution only with accompanying diluent (Sterile Diluent for Flolan).1

  • Importance of patient informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1

  • Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)


Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Distribution of epoprostenol sodium is restricted. (See Restricted Distribution Program under Dosage and Administration.)

Epoprostenol Sodium


Dosage Forms


Brand Names



For injection, for IV infusion

0.5 mg (of epoprostenol)

Flolan (available with diluent)

GlaxoSmithKline, (distributed by Gilead)

1.5 mg (of epoprostenol)

Flolan (available with diluent)

GlaxoSmithKline, (distributed by Gilead)

AHFS DI Essentials. © Copyright, 2004-2016, Selected Revisions June 1, 2009. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.


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