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Epoprostenol: Drug information

Epoprostenol: Drug information
(For additional information see "Epoprostenol: Patient drug information" and see "Epoprostenol: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Flolan;
  • Veletri
Brand Names: Canada
  • Caripul;
  • Flolan
Pharmacologic Category
  • Prostacyclin;
  • Prostaglandin;
  • Vasodilator
Dosing: Adult
Acute respiratory distress syndrome, moderate to severe, refractory

Acute respiratory distress syndrome, moderate to severe, refractory (off-label use/route):

Note: Based on limited data; optimal dosing strategy (eg, fixed-dose versus weight-based dosing) and titration unknown; titrate to lowest effective dose based on clinical response. There may be a dose-dependent improvement in oxygenation (Ref); initiating at a high dose and titrating down may be preferred to improve oxygenation in unstable patients. Refer to institutional policies and procedures.

Example regimens include:

Fixed-dose: Inhalation, continuous: Initial: Use a 20,000 ng/mL solution and nebulize at a rate of 8 mL/hour; titrate down based on clinical response by reducing the concentration to 10,000 ng/mL while continuing to nebulize at a rate of 8 mL/hour; discontinue based on clinical response (Ref).

Weight-based dose:

Inhalation, continuous: Initial: 50 ng/kg/minute (using ideal body weight); titrate down by 10 ng/kg/minute every 1 to 4 hours based on clinical response; maximum dose: 50 ng/kg/minute (Ref).

OR

Inhalation, continuous: Initial: 10 ng/kg/minute (using ideal body weight); titrate up by 10 to 20 ng/kg/minute every 15 minutes based on clinical response; once patient has stabilized and the decision to discontinue therapy, titrate down by 10 ng/kg/minute every 2 hours based on clinical response; maximum dose: 50 ng/kg/minute (Ref).

Acute vasodilator testing in patients with pulmonary arterial hypertension

Acute vasodilator testing in patients with pulmonary arterial hypertension (off-label use): Note: Acute vasodilator testing is recommended in patients with idiopathic, heritable, or drug-induced pulmonary arterial hypertension to assess eligibility for treatment with a calcium channel blocker (eg, ER nifedipine) (Ref).

IV: Initial: 2 ng/kg/minute; increase dose in increments of 2 ng/kg/minute every 10 to 15 minutes; dosing range during testing: 2 to 12 ng/kg/minute (Ref).

Postcardiothoracic surgery complicated by pulmonary hypertension, right ventricular dysfunction, or refractory hypoxemia

Postcardiothoracic surgery complicated by pulmonary hypertension, right ventricular dysfunction, or refractory hypoxemia (off-label use/route):

Note: Based on limited data, optimal dosing strategy and titration remains unknown; titrate to lowest effective dose based on response and tolerability; refer to institutional policies and procedures.

Fixed-dose: Inhalation, continuous: Use a 20,000 ng/mL solution and nebulize at a constant rate of 8 mL/hour; titrate down every 30 minutes to 4 hours based on clinical response by reducing the solution concentration to 10,000 ng/mL while continuing to nebulize at a constant rate of 8 mL/hour for every titration; titrate down further after another 30 minutes to 4 hours by reducing the solution concentration to 5,000 ng/mL, then 2,500 ng/mL; discontinue when the patient is clinically stable on the 2,500 ng/mL solution (Ref).

Weight-based dose: Inhalation, continuous: Initial: 10 to 50 ng/kg/minute based on ideal body weight; titrate by increasing or decreasing dose in increments of 10 ng/kg/minute every 30 minutes to 2 hours as tolerated based on clinical response; maximum dose: 50 ng/kg/minute. Weight-based dosing is extrapolated from studies in patients with acute respiratory distress syndrome (Ref).

Pulmonary arterial hypertension

Pulmonary arterial hypertension:

Note: Consult a pulmonary arterial hypertension specialist for all management decisions; choice of therapy is dependent on etiology, risk stratification, cardiopulmonary comorbidities, and response to other agents. Prostacyclin analogues are generally reserved for initial therapy in high-risk patients or used as adjunctive therapy in patients who continue to deteriorate on oral agents (Ref).

IV: Initial: 2 ng/kg/minute; a lower initial dose may be used if patient is intolerant of starting dose. Increase dose in increments of 1 to 2 ng/kg/minute at intervals of ≥15 minutes until dose-limiting side effects (eg, flushing, jaw pain, headache, hypotension, hypoxemia, nausea) are noted or further dose increase is not clinically warranted. Usual dose when used as monotherapy: 25 to 40 ng/kg/minute, however, significant patient variability in optimal dose exists (Ref).

Dose adjustment during chronic phase of treatment:

If symptoms persist or recur following initiation of therapy, increase dose in 1 to 2 ng/kg/minute increments at intervals of ≥15 minutes. May also increase dose at intervals of 24 to 48 hours or longer (eg, every 1 to 2 weeks). The need for increased doses should be expected with chronic use and occur more frequently during the first few months after initiation of therapy.

In case of dose-limiting adverse events (eg, hypotension, hypoxemia, severe nausea, vomiting), decrease dose in 2 ng/kg/minute decrements at intervals of ≥15 minutes until dose-limiting effects resolve. Avoid abrupt withdrawal or sudden large dose reductions. Adverse effects may resolve without dosage adjustment.

Lung transplant: In patients receiving lung transplant, epoprostenol may be tapered after cardiopulmonary bypass has been initiated.

Transitioning from SubQ treprostinil to IV epoprostenol:

Note: Transition should only occur under supervision of a clinician with expertise in pulmonary arterial hypertension and in a hospital setting to closely monitor vital signs, hemodynamic response, and clinical symptoms. Transition protocols are institution specific and must be individualized to patient needs. The following is only one example (utilized in a limited number of patients) for transitioning from SubQ treprostinil to IV epoprostenol. In general, epoprostenol dose is increased gradually while simultaneously decreasing the treprostinil dose to balance clinical worsening and dose limiting side effects (Ref).

Treprostinil dose reduction: First, reduce SubQ treprostinil by 5 ng/kg/minute, then initiate IV epoprostenol based on instructions below. Continue to reduce SubQ treprostinil dose by 5 ng/kg/minute every 5 hours; when SubQ treprostinil dose is reduced to ≤ 8 ng/kg/minute, then discontinue therapy completely 5 hours later (Ref).

Epoprostenol dose escalation: 2 hours after the initial SubQ treprostinil dose reduction, begin IV epoprostenol 2 ng/kg/minute; titrate by increasing dose 2 ng/kg/minute every 2 hours; if dose limiting side effects occur (eg, flushing, jaw pain, headache, hypotension, nausea), stop up-titration and consult the pulmonary arterial hypertension specialist overseeing the transition between agents (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Older Adult

Refer to adult dosing.

Dosing: Pediatric

(For additional information see "Epoprostenol: Pediatric drug information")

Note: Doses are expressed in units of nanograms (ng)/kg/minute.

Pulmonary hypertension

Pulmonary hypertension: Limited data available: Infants, Children, and Adolescents:

Continuous IV infusion: Initial: 1 to 2 nanograms/kg/minute; titrate to clinical effect (eg, improvement in pulmonary pressures or right ventricular mechanics) or dose-limiting side effects (eg, nausea, diarrhea, jaw pain, bone pain, headache); average effective dose: 80 nanograms/kg/minute; dose range: 40 to >150 nanograms/kg/minute in some patients. Note: Excessive epoprostenol can lead to a high-output state (hyperdynamic right ventricle with impact on cardiac output) and require a decrease in dose (Ref).

Inhalation: Very limited data available; efficacy results vary with patient age and etiology of pulmonary hypertension. Other factors that may impact efficacy include product formulation (eg, pH, dilution, stability) and the drug delivery system (eg, type of nebulizer, placement in ventilator circuit, ventilator settings) (Ref).

Continuous nebulization: 20 to 50 nanograms/kg/minute; dosing based on a small prospective trial of 14 children (median age: 54 months) with acute lung injury who received either aerosolized saline or inhaled epoprostenol administered in incremental doses (10, 20, 30, 40, and 50 nanograms/kg/minute); significant improvement of the oxygenation index was observed at the 30 nanograms/kg/minute dose level and values close to significant at the 20, 40, and 50 nanograms/kg/minute dose were observed; eight of the 14 children were considered responders to therapy with an improvement in oxygenation, and the calculated number needed to treat was 1.8 (95% CI, 1.2 to 3.2); during the trial, no significant changes in respiratory or systemic cardiovascular variables (eg, HR, MAP, arterial pH) or ventilator settings were reported (Ref). A very small retrospective descriptive analysis (n=20, infants: n=7) using a dose of 50 nanograms/kg/minute reported minimal decrease in oxygenation index (baseline: 29.6 ± 15; with inhaled epoprostenol: 25.6 ± 17.8); however, the subset of term neonates (n=13) experienced significant improvement in oxygenation index and echocardiogram findings (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

>10%:

Cardiovascular: Flushing (23% to 58%), tachycardia (1% to 43%), hypotension (13% to 27%), chest pain (11%)

Central nervous system: Headache (46% to 83%), dizziness (8% to 83%), chills (≤25%), anxiety (≤21%), nervousness (≤21%), hyperesthesia (≤12%), hypoesthesia (≤12%), paresthesia (≤12%), agitation (11%)

Dermatologic: Dermal ulcer (39%), eczema (≤10% to ≤25%), skin rash (≤10% to ≤25%), urticaria (≤10% to ≤25%)

Gastrointestinal: Nausea and vomiting (32% to 67%), anorexia (25% to 66%), diarrhea (37% to 50%)

Infection: Sepsis (≤25%)

Neuromuscular & skeletal: Musculoskeletal pain (3% to 84%), arthralgia (≤84%), neck pain (≤84%), jaw pain (54% to 75%), myalgia (44%), hyperkinesia (≤21%), tremor (≤21%)

Respiratory: Flu-like symptoms (≤25%)

Miscellaneous: Fever (≤25%)

1% to 10%:

Cardiovascular: Bradycardia (5%)

Dermatologic: Diaphoresis (1%)

Gastrointestinal: Abdominal pain (5%), dyspepsia (1%)

Neuromuscular & skeletal: Back pain (2%)

Respiratory: Dyspnea (2%)

<1%, postmarketing, and/or case reports: Anemia, cardiac failure, fatigue, hemorrhage, hepatic failure, hypersplenism, hyperthyroidism, increased pulmonary artery pressure, pallor, pancytopenia, pulmonary edema, pulmonary embolism, splenomegaly, thrombocytopenia

Contraindications

Hypersensitivity to epoprostenol, to structurally related compounds, or any component of the formulation; chronic use in patients with heart failure due to severe left ventricular systolic dysfunction; chronic use in patients who develop pulmonary edema during dose initiation (Caripul [Canadian product], Flolan [Canadian product], and Veletri only).

Warnings/Precautions

Concerns related to adverse effects:

• Pulmonary edema: Some patients with PAH have developed pulmonary edema during dosing adjustment and acute vasodilator testing (an off-label use), which may be associated with concomitant heart failure (LV systolic dysfunction with significantly elevated left heart filling pressures) or pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis. If pulmonary edema develops during therapy initiation, discontinue and do not readminister.

• Rebound pulmonary hypertension: Avoid abrupt interruptions or large sudden reductions in dosage; may result in rebound pulmonary hypertension (eg, dyspnea, hypoxia, dizziness, asthenia). Back-up medication and pump and infusion sets in the patient-care area are essential to prevent treatment interruptions.

• Vasodilation: Systemic epoprostenol is a potent pulmonary and systemic vasodilator and can cause hypotension and other reactions, such as flushing, nausea, vomiting, dizziness, and headache. Inhaled administration may result in minimal systemic absorption and potentially decrease risk of vasodilation when compared to systemic therapy. Monitor BP and symptoms regularly during initiation and after dose change.

Disease-related concerns:

• Conditions that increase bleeding risk: Systemic epoprostenol is a potent inhibitor of platelet aggregation. Use with caution in patients with other risk factors for bleeding. There is insufficient evidence to suggest that inhaled epoprostenol increases the risk of bleeding (Buckley 2010; Rao 2018).

Other warnings/precautions:

• Appropriate Use: Initiation or transition to epoprostenol requires specialized cardiopulmonary monitoring in a critical care setting where clinicians are experienced in advanced management of pulmonary arterial hypertension.

• Infection: Chronic continuous IV infusion of epoprostenol via a chronic indwelling central venous catheter (CVC) has been associated with local infections and serious blood stream infections.

Warnings: Additional Pediatric Considerations

Although the use of anticoagulants in adult patients with primary pulmonary hypertension has been shown to improve survival, such efficacy has not been demonstrated in pediatric patients. Some studies have reported the routine use of warfarin in pediatric patients receiving long-term (chronic) infusions of epoprostenol for pulmonary hypertension (Barst 1999; Rosenzweig 1999), while other studies have routinely discontinued anticoagulants prior to the initiation of epoprostenol therapy (Higenbottam 1993). Epoprostenol is a potent inhibitor of platelet aggregation; monitor patients for bleeding, especially those with other risk factors or medications which may increase the risk for hemorrhage. Further studies are needed to assess the risks and benefits of routine anticoagulation in pediatric patients treated with epoprostenol.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution Reconstituted, Intravenous:

Flolan: 0.5 mg (1 ea); 1.5 mg (1 ea)

Veletri: 0.5 mg (1 ea); 1.5 mg (1 ea)

Generic: 0.5 mg (1 ea [DSC]); 1.5 mg (1 ea [DSC])

Solution Reconstituted, Intravenous [preservative free]:

Generic: 0.5 mg (1 ea); 1.5 mg (1 ea)

Generic Equivalent Available: US

Yes

Pricing: US

Solution (reconstituted) (Epoprostenol Sodium Intravenous)

0.5 mg (per each): $28.10

1.5 mg (per each): $56.21

Solution (reconstituted) (Flolan Intravenous)

0.5 mg (per each): $22.43

1.5 mg (per each): $54.17

Solution (reconstituted) (Veletri Intravenous)

0.5 mg (per each): $29.51

1.5 mg (per each): $59.02

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Intravenous:

Caripul: 0.5 mg (1 ea); 1.5 mg (1 ea)

Flolan: 0.5 mg (1 ea); 1.5 mg (1 ea)

Prescribing and Access Restrictions

Orders for epoprostenol are distributed by two sources in the United States. Information on orders or reimbursement assistance may be obtained from either Accredo Health, Inc (1-866-344-4874) or CVS Caremark (1-877-242-2738).

Administration: Adult

IV: For IV use via an infusion pump. Use infusion sets with an in-line 0.22 micron filter. When administered on an ongoing basis, must be infused through a central venous catheter. Peripheral infusion may be used temporarily until central line is established. Do not administer as a bolus injection. Avoid abrupt withdrawal (including interruptions in delivery) or sudden large reductions in dosing. The ambulatory infusion pump should be small and lightweight, be able to adjust infusion rates in 2 ng/kg/minute increments, have occlusion, end of infusion, and low battery alarms, have ± 6% accuracy of the programmed rate, and have positive continuous or pulsatile pressure with intervals ≤3 minutes between pulses. The reservoir should be made of polyvinyl chloride, polypropylene, or glass. Immediate access to back up pump, infusion sets and medication is essential to prevent treatment interruptions. Consult manufacturer's labeling for infusion rate example calculations.

Flolan-specific administration considerations: Avoid administration materials containing polyethylene terephthalate (PET) or polyethylene terephthalate glycol (PETG); consult administration set manufacturer to confirm compatibility with highly alkaline solutions (eg, pH 12 sterile diluent for Flolan).

Inhalation, continuous (off-label route): May be administered via jet nebulizer connected to the inspiratory limb of the ventilator near the endotracheal tube or via face mask with a Venturi attachment for aerosolization with a bypass oxygen flow of 2 to 3 L/minute, or via high flow nasal cannula or noninvasive positive pressure ventilation with an oxygen flow of 50 L/minute (Ref). Note: Flolan or Veletri may be used for this route of administration (Ref). If using Flolan glycine buffer diluent (used in Flolan), may cause ventilator valve malfunction; it has been recommended to check and/or change expiratory filters every 2 to 4 hours (Ref).

Administration: Pediatric

Continuous IV infusion: For IV use via an infusion pump. Use infusion sets with an in-line 0.22 micron filter. Must be infused through a central venous catheter; peripheral infusion may be used temporarily until central line is established. Infuse through a dedicated lumen exclusive of any other drugs; consider a multilumen catheter if other IV medications are routinely administered. Avoid abrupt withdrawal, interruptions in delivery, or sudden large reductions in dosing. Patients should have access to a back-up infusion pump and infusion sets. Patients may be discharged using an ambulatory infusion pump. Appropriate ambulatory infusion pump should be small and lightweight; be able to adjust infusion rates in 2 nanograms/kg/minute increments; have occlusion, end of infusion, and low battery alarms; have ±6% accuracy of the programmed rate; and have positive continuous or pulsatile pressure with intervals ≤3 minutes between pulses. The reservoir should be made of polypropylene, polyvinyl chloride, or glass. Immediate access to back-up pump, infusion sets, and medication is essential to prevent treatment interruptions. Consult manufacturer's labeling for infusion rate example calculations.

Flolan-specific administration considerations: Avoid administration materials containing polyethylene terephthalate (PET) or polyethylene terephthalate glycol (PETG); consult administration set manufacturer to confirm compatibility with highly alkaline solutions (eg, pH 12 sterile diluent for Flolan).

Inhalation: Nebulization: Administer via nebulization device connected as close to the mask or endotracheal tube in the inspiratory limb of the noninvasive ventilation (ie, BiPAP) or invasive ventilation circuit, respectively (Ref). Administration via an anesthesia machine intraoperatively with inhaled nitric oxide has also been described (Ref).

Use: Labeled Indications

Pulmonary arterial hypertension: Treatment of pulmonary arterial hypertension (PAH) (WHO Group I) in patients with NYHA Class III or IV symptoms to improve exercise capacity.

Use: Off-Label: Adult

Acute respiratory distress syndrome, refractory moderate to severe; Acute vasodilator testing in pulmonary arterial hypertension; Postcardiothoracic surgery complicated by pulmonary hypertension, right ventricular dysfunction, or refractory hypoxemia

Medication Safety Issues
High alert medication:

The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error.

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): Prostacyclin Analogues may enhance the antiplatelet effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider therapy modification

Amisulpride (Oral): May enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy

Anticoagulants: Prostacyclin Analogues may enhance the adverse/toxic effect of Anticoagulants. Specifically, the antiplatelet effects of these agents may lead to an increased risk of bleeding with the combination. Risk C: Monitor therapy

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor therapy

Arginine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Blood Pressure Lowering Agents: Prostacyclin Analogues may enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Blood Pressure Lowering Agents: May enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Bromperidol: May diminish the hypotensive effect of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Risk X: Avoid combination

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Digoxin: Epoprostenol may increase the serum concentration of Digoxin. Risk C: Monitor therapy

DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Risk C: Monitor therapy

Herbal Products with Blood Pressure Lowering Effects: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy

Levodopa-Foslevodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Foslevodopa. Risk C: Monitor therapy

Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy

Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider therapy modification

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Risk C: Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Silodosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Thrombolytic Agents: May enhance the adverse/toxic effect of Prostacyclin Analogues. Specifically, the antiplatelet effects of prostacyclin analogues may lead to an increased risk of bleeding when combined with thrombolytic agents. Risk C: Monitor therapy

Pregnancy Considerations

Information related to the use of epoprostenol in pregnancy is limited (Geohas 2003; Kawabe 2018; Martinez 2013; Smith 2012; Timofeev 2013); however, the manufacturer notes adverse maternal or fetal outcomes have not been associated with its use based on the available data.

Untreated pulmonary arterial hypertension (PAH) is associated with adverse pregnancy outcomes, including heart failure, stroke, preterm delivery, and maternal and fetal death.

Breastfeeding Considerations

It is not known if epoprostenol is present in breast milk. According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother.

Monitoring Parameters

Monitor for improvements in pulmonary function and oxygenation, decreased exertional dyspnea, fatigue, syncope and chest pain, BP, pulmonary vascular resistance, pulmonary arterial pressure, and quality of life. Following establishment of a new chronic infusion rate, measure standing and supine BP for several hours. In addition, the pump device and catheters should be monitored frequently to avoid “system” related failure. Monitor arterial pressure; assess all vital functions. Hypoxia, flushing, and tachycardia may indicate overdose.

Mechanism of Action

Epoprostenol is also known as prostacyclin and PGI2. It is a strong vasodilator of all vascular beds. In addition, it is a potent endogenous inhibitor of platelet aggregation. The reduction in platelet aggregation results from epoprostenol's activation of intracellular adenylate cyclase and the resultant increase in cyclic adenosine monophosphate concentrations within the platelets. Additionally, it is capable of decreasing thrombogenesis and platelet clumping in the lungs by inhibiting platelet aggregation.

Pharmacokinetics (Adult Data Unless Noted)

Metabolism: Rapidly hydrolyzed; subject to some enzymatic degradation; forms two active metabolites (6-keto-prostaglandin F1α and 6,15-diketo-13,14-dihydro-prostaglandin F1α) with minimal activity and 14 inactive metabolites.

Half-life elimination: ≤6 minutes.

Excretion: Urine (84%); feces (4%).

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AE) United Arab Emirates: Flolan;
  • (AR) Argentina: Epoprostenol Normon | Veletri;
  • (AT) Austria: Dynovas | Flolan;
  • (AU) Australia: Epoprostenol myx | Flolan | Veletri;
  • (BE) Belgium: Epoprostenol | Flolan | Veletri;
  • (CH) Switzerland: Veletri;
  • (CO) Colombia: Veletri;
  • (CZ) Czech Republic: Flolan | Veletri;
  • (DE) Germany: Epoprostenol Rotexmedica | Veletri;
  • (ES) Spain: Dynovase | Epoprostenol Normon | Epoprostenol sandoz | Epoprostenol Teva | Flolan | Veletri;
  • (FR) France: Epoprostenol Arrow | Epoprostenol Panpharma | Epoprostenol sandoz | Flolan | Veletri;
  • (GB) United Kingdom: Cyclo prostin | Epoprostenol | Flolan | Veletri;
  • (HU) Hungary: Veletri;
  • (IE) Ireland: Flolan | Veletri;
  • (IT) Italy: Caripul | Epoprostenolo PH&T | Flolan;
  • (JP) Japan: Epoprostenol | Flolan;
  • (KW) Kuwait: Flolan;
  • (NL) Netherlands: Epoprostenol | Flolan | Veletri;
  • (NO) Norway: Epoprostenol campuspharma | Flolan;
  • (NZ) New Zealand: Veletri;
  • (PL) Poland: Epoprostenol drehm | Flolan | Veletri;
  • (PR) Puerto Rico: Epoprostenol;
  • (PT) Portugal: Veletri;
  • (RO) Romania: Epoprostenol;
  • (SA) Saudi Arabia: Veletri;
  • (SE) Sweden: Epoprostenol campuspharma | Epoprostenol ebb;
  • (SG) Singapore: Flolan;
  • (SI) Slovenia: Flolan;
  • (SK) Slovakia: Veletri
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