Epoprostenol
Class: Vasodilating Agents
VA Class: HS875
CAS Number: 61849-14-7
Brands: Flolan, Veletri
Medically reviewed by Drugs.com. Last updated on April 6, 2020.
Introduction
Vasodilator and platelet-aggregation inhibitor; a naturally occurring prostaglandin.1 2 5 10 21 41 60 61
Uses for Epoprostenol
Pulmonary Arterial Hypertension
Management of pulmonary arterial hypertension (PAH; WHO group 1) to improve exercise capacity; efficacy established principally in patients with NYHA/WHO functional class III or IV PAH (idiopathic, heritable, or associated with connective tissue diseases).1 5 6 14 48 60 61 Has been designated an orphan drug by FDA for treatment of PAH.4
Recommended as one of several treatment options for initial management of PAH in patients with NYHA/WHO functional class III or IV symptoms who are not candidates for calcium-channel blocker therapy or in whom such therapy failed.52 56 Generally considered treatment of choice for patients with NYHA/WHO class IV PAH because of demonstrated benefit on survival.52
Individualize choice of PAH therapy; consider factors such as disease severity, route of administration, potential adverse effects and costs of treatment, clinician experience, and patient preference.8 48 52 56
In patients with inadequate response to initial monotherapy, may consider combination therapy with an endothelin-receptor antagonist, phosphodiesterase (PDE) type 5 inhibitor, or soluble guanylate cyclase stimulator (added sequentially).52 Such combination therapy may provide additive and/or synergistic benefits by targeting different pathophysiologic pathways of disease.52 53 54 55
Safety and efficacy not systematically evaluated in patients with pulmonary hypertension associated with diseases other than scleroderma.1
Acute Respiratory Distress Syndrome
Has been used by oral inhalation (via nebulization) in patients with acute respiratory distress syndrome (ARDS)†, generally in those with refractory hypoxemia accompanied by pulmonary hypertension and right ventricular dysfunction.78 81 83 86 87 88 89 90 91
Treatment of ARDS is largely supportive; mechanical ventilation is the only intervention proven to reduce mortality.78 85 Selective pulmonary vasodilators such as inhaled epoprostenol may be used adjunctively to improve oxygenation; localized effects in lung parenchyma may improve ventilation-perfusion mismatch.77 78 79 80 81 82 83 84 91
Inhaled epoprostenol has been suggested as an alternative to nitric oxide due to its similar efficacy, lower potential for systemic adverse effects, lower cost, and ease of delivery (can be nebulized through the ventilator circuit).78 81 91
Substantially reduces mean pulmonary artery pressure and improves oxygenation; however, data demonstrating clinical benefit are lacking.78 83 88 89 90 91 Additional studies needed to evaluate potential role.88 89 90 91
Epoprostenol Dosage and Administration
Administration
Administer by IV infusion.1 Also has been administered by oral inhalation via nebulization† through the ventilator circuit in patients with ARDS† receiving mechanical ventilation.78 81 91
Restricted Distribution
Epoprostenol and controlled-infusion device used for drug administration available only through specialty pharmacies.3 62 Contact manufacturers for specific information.3 70
IV Administration
For IV infusion only.1 8 10 60
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 60 Consult manufacturer’s labeling for infusion-device specifications.1 60
Do not mix or administer in same IV line with other parenteral solutions or medications.1 60
Delivery system malfunctions (e.g., infusion-device failure, occluded catheter) may result in inadvertent overdosage or underdosage.1 60 To avoid potential interruptions in drug delivery, patient must have access to a backup IV infusion device and infusion sets.1 47 60 (See Abrupt Withdrawal under Cautions.) Consider use of a multi-lumen catheter if patient receives other IV drugs routinely.1 60
The epoprostenol sodium formulation containing sucrose and arginine excipients (Veletri) has prolonged stability compared with formulations containing glycine and mannitol (e.g., Flolan); however, these formulations are similar in terms of pharmacokinetic and pharmacodynamic effects.1 60 61 62 65 68
Reconstitution and Dilution
Reconstitute only with appropriate diluent specified by manufacturer; the drug is stable only when reconstituted as directed using the recommended diluent(s).1 60 61 See manufacturer’s labeling for details on reconstitution, preparation of solutions, and selection of drug concentration in solutions.1 60 61
Reconstitute epoprostenol sodium lyophilized powder for injection (Flolan or generic equivalent) only with sterile diluent provided by the respective manufacturer; do not reconstitute or mix with other parenteral solutions or medications.1 61 Further dilute solution with a sufficient volume of the same diluent to provide a final concentration compatible with the infusion pump (with respect to minimum and maximum flow rates and other infusion pump criteria) and capacity of the drug delivery reservoir.1 Typical drug reservoirs for long-term epoprostenol therapy contain a total reservoir volume of 100 mL.1
Following reconstitution (Flolan or generic equivalent), administer immediately or store under refrigeration at 2–8°C for ≤40 hours (if room temperature administration is planned) or ≤24 hours (if administration with a cold pouch is planned); protect solution from light.1 61 (See Storage under Stability.) May administer reconstituted solution for ≤8 hours at room temperature or for ≤24 hours with a cold pouch.1 Change gel packs in cold pouch every 12 hours.1
Reconstitute Veletri lyophilized powder for injection with sterile water for injection or 0.9% sodium chloride injection; do not reconstitute or mix with other parenteral solutions or medications.60 Further dilute solution immediately with a sufficient volume of the same diluent to provide a final concentration compatible with the infusion pump (with respect to minimum and maximum flow rates and other infusion pump criteria) and capacity of the drug delivery reservoir.60 Typical drug reservoirs used for long-term epoprostenol therapy contain a total reservoir volume of 100 mL.60
Following reconstitution and dilution of Veletri, administer immediately or store at 2–8°C for ≤8 days.60 May infuse at room temperature for periods of 24, 48, or 72 hours depending on final concentration of solution and timing of administration (immediately or after storage for ≤8 days at 2–8°C).60 62 65 66 (See Table 1.) Also may administer at higher temperatures (≤40°C) according to manufacturer's guidelines.60 (See Table 2.)
Short excursions to higher temperatures (i.e., ≤40°C) are permitted for up to 2, 4, or 8 hours for solution concentrations of <15,000 ng/mL, 15,000–60,000 ng/mL, or >60,000 ng/mL, respectively.60 65
Final Concentration (ng/mL) |
Immediate Administration |
Administration After Storage at 2–8°C for ≤8 Days |
≥3000 to <15,000 (prepared using 0.5-mg vial) |
48 hours |
24 hours |
≥15,000 to <60,000 (prepared using 1.5-mg vials) |
48 hours |
48 hours |
≥60,000 (prepared using 1.5-mg vials) |
72 hours |
48 hours |
Final Concentration (ng/mL) |
Temperatures |
Immediate Administration |
Administration After Storage at 2–8°C for ≤8 Days |
<60,000 |
>25°C to 30°C |
24 hours |
24 hours |
≥60,000 |
>25°C to 30°C |
48 hours |
48 hours |
≥60,000 |
>30°C and ≤40°C |
24 hours |
Rate of Administration
Adjust infusion rates only under the direction of a physician, except in life-threatening situations (e.g., unconsciousness, collapse).1 60 Observe patient and monitor standing and supine BP and heart rate for several hours following changes in infusion rates.1 60 61
Avoid abrupt discontinuance or sudden large reductions in infusion rates.1 10 12 60 61 (See Abrupt Withdrawal under Cautions.) Consult manufacturer’s labeling for specific instructions on selection of infusion rate and drug concentration.1 60 61
Dosage
Available as epoprostenol sodium; dosage expressed in terms of epoprostenol.1 2 60
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 60 61
Pediatric Patients
Acute Respiratory Distress Syndrome†
Oral nebulization
Various dosages of inhaled epoprostenol have been used in clinical studies.81 91 Although initial dosage has varied, most protocols titrated dosage to response (usually with a 15- and 30-minute interval between doses).81 91 The most effective and safest dosage of inhaled epoprostenol that provides a clinically important increase in the partial pressure of oxygen in arterial blood (PaO2) and reduction in pulmonary artery pressure appears to be 30 ng/kg per minute in pediatric patients; higher dosages not shown to provide any additional benefit.91
Adults
Pulmonary Arterial Hypertension
Initiation and Titration of Therapy
Continuous IV InfusionInitially, 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 60 Maintain dosage at a level where pharmacologic effects are tolerated.1 60
Infusion rates may be calculated using the following formula:1 60
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 PAH associated with the scleroderma spectrum of diseases, 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 60
Long-term Therapy
Continuous IV InfusionDuring long-term 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 60
Adjust dosage in increments of 1–2 ng/kg per minute at intervals of ≥15 minutes.1 60 If dose-limiting adverse effects occur, decrease dosage gradually in decrements of 2 ng/kg per minute at intervals of ≥15 minutes until dose-limiting effects resolve; avoid abrupt withdrawal or sudden large reductions in infusion rates.1 10 12 60 (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
Limited data suggest that patients who are stable on Flolan therapy may be transitioned directly to the Veletri preparation at the same dosage without any change in clinical efficacy or tolerability.66 67
Acute Respiratory Distress Syndrome†
Oral Nebulization
Various dosages of inhaled epoprostenol have been used in clinical studies.81 91 Although initial dosage has varied, most protocols titrated dosage to response (usually with a 15- to 30-minute interval between doses).81 91 The most effective and safest dosage of inhaled epoprostenol that provides a clinically important increase in PaO2 and reduction in pulmonary artery pressure appears to be 20–30 ng/kg per minute in adults; higher dosages not shown to provide any additional benefit.91
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 60
Cautions for Epoprostenol
Contraindications
-
Long-term use in CHF due to severe left ventricular systolic dysfunction.1 60
-
Long-term use in patients who develop pulmonary edema during initial dosage titration.1 60
-
Known hypersensitivity to epoprostenol or structurally related drugs.1 60
Warnings/Precautions
Warnings
Solution and Drug Compatibility
Reconstitute and dilute using only the appropriate diluent specified by the manufacturer.1 60 61 (See Reconstitution and Dilution under Dosage and Administration.) Do not admix or infuse in the same IV line with other solutions or drugs.1 60
Abrupt Withdrawal
Avoid abrupt discontinuance or sudden large reductions in dosage.1 10 12 60
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 19 60
Patient should have access to a backup IV infusion device and infusion sets to avoid interruptions in drug delivery due to equipment malfunction.1 47 60
Sepsis
Aseptic technique must be used in routine catheter care and in the reconstitution and administration of drug solutions.1 64 Local infection and sepsis associated with drug delivery system (long-term indwelling central venous catheter) reported.1 2 5 10 11 12 19 28 41 60
General Precautions
Use Restrictions
Should be used only by qualified clinicians experienced in the diagnosis and management of PAH.1 23 60 Carefully establish the diagnosis of PAH before use.1 60
Consider referral of patients to specialized centers experienced in the management of pulmonary vascular diseases.10 11 16 18 23 31
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 60
Initial dosage titration should be performed in a medically supervised setting adequately equipped for physiologic monitoring and emergency care.1 60
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 long-term therapy and may be controlled with dosage reduction.1 60
Initial dosage titration has been performed with and without right heart catheterization in clinical studies.1 41 60
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 45 46 48 60
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 18 23 31 36 47 48 60
Weigh benefits versus risks of anticoagulation, particularly in patients with increased risk of bleeding.1 48 (See Hematologic Effects under Cautions.)
Dosage Titration
Dosage adjustments during long-term use should be made immediately upon occurrence of dose-limiting adverse effects or worsening of symptoms associated with pulmonary hypertension.1 60 Following dosage adjustments, standing and supine BP and heart rate should be monitored closely for several hours.1 60 (See Dosage and Administration.)
Aggressive dosage titrations to overcome tachyphylaxis may result in elevated cardiac output and/or high output heart failure.47 48 Monitor PAH symptoms, exercise capacity, adverse effects, and hemodynamic function frequently when making dosage adjustments.1 47 48 60 Some experts recommend that periodic cardiac catheterizations be considered to prevent underdosing or overdosing of drug.47 48 Weigh risks versus benefits of cardiac catheterization.1 60
Specific Populations
Pregnancy
Safety and efficacy during labor, vaginal delivery, or cesarean section have not been established.1 60
Lactation
Not known whether epoprostenol is distributed into milk; use with caution in nursing women.1 60
Pediatric Use
Safety and efficacy not established in pediatric patients.1 43 60
Geriatric Use
Clinical studies did not include sufficient numbers of patients ≥65 years of age to determine whether geriatric patients respond differently than younger patients.1 60
Common Adverse Effects
Patients with idiopathic or heritable PAH:1 60 61 dizziness,1 2 60 61 headache,1 2 5 7 8 9 10 11 12 18 20 60 61 nausea,1 2 6 8 9 10 11 20 60 61 vomiting,1 2 5 9 11 20 60 61 jaw pain,1 5 6 7 8 9 10 11 12 18 20 60 61 myalgia,1 60 61 flushing,1 2 5 7 8 9 10 18 20 60 61 diarrhea,1 5 6 7 8 9 10 11 12 60 61 tachycardia,1 2 60 nonspecific musculoskeletal pain,1 2 10 11 12 18 20 60 chills/fever/sepsis/flu-like symptoms,1 60 61 anxiety/nervousness/tremor,1 60 61 hypoesthesia/hyperesthesia/paresthesia.1 60 61
Patients with PAH associated with the scleroderma spectrum of diseases: pain/neck pain/arthralgia,1 60 61 jaw pain,1 60 61 anorexia,1 60 61 diarrhea,1 60 61 headache,1 60 61 nausea/vomiting,1 60 61 skin ulcer,1 60 61 eczema/rash/urticaria,1 60 61 flushing,1 60 61 hypotension.1 60 61
Interactions for Epoprostenol
In clinical studies, epoprostenol was used concomitantly with digoxin, diuretics, anticoagulants, oral vasodilators, and supplemental oxygen.1 5 6 7 19 20 60 61
Specific Drugs
Drug |
Interaction |
Comments |
---|---|---|
Anticoagulants |
||
Antiplatelet agents |
||
Digoxin |
Potential decreased clearance of digoxin; possible digoxin toxicity1 60 61 |
Clinically important elevations in digoxin concentration may occur upon initiation of epoprostenol therapy in patients prone to digoxin toxicity1 60 61 |
Diuretics |
Changes in furosemide clearance not considered clinically important1 60 61 |
|
Hypotensive agents |
||
Vasodilators |
Epoprostenol Pharmacokinetics
Chemical assays with sufficient sensitivity and specificity to assess the in vivo pharmacokinetics of epoprostenol in humans not currently available.1 60 61
Distribution
Extent
Animal studies indicate a small volume of distribution (357 mL/kg).1 60 61
Elimination
Metabolism
Rapidly hydrolyzed at neutral pH in blood and also subject to enzymatic degradation.1 2 60 61 Metabolized to 2 primary metabolites, 6-keto-PGF1α (formed by spontaneous degradation) and 6,15-diketo-13,14-dihydro-PGF1α (enzymatically formed); data in animals indicate that both metabolites have pharmacologic activity orders of magnitude less than parent drug.1 2 60 61 Extensively metabolized; 14 additional minor metabolites isolated from urine.1 60 61
Elimination Route
82% in urine and 4% in feces.1 2 60 61
Half-life
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 60 61
Special Populations
No gender difference observed in in vitro (human plasma) half-life based on inhibition of platelet aggregation.1 60 61
Stability
Storage
Parenteral
Powder for Injection
Flolan: 15–25°C in original carton; protect from light.1 Store Sterile Diluent for Flolan at 15–25°C; do not freeze.1
Epoprostenol sodium injection (generic): 15–30°C in original carton; protect from light.61 Store diluent for epoprostenol sodium for injection at 20–25°C; do not freeze.61
Veletri: 20–25°C in original carton; protect from light.60 Single-use vials; discard unused portions.60
Reconstituted solutions of Flolan and epoprostenol sodium (generic): Store at 2–8°C for ≤48 hours; protect from light and do not freeze.1 61 Discard solutions if frozen or stored at 2–8°C for >48 hours.1 (See Reconstitution and Dilution under Dosage and Administration.)
Reconstituted solutions of Veletri: Store at 2–8°C for ≤8 days if not used immediately.60 Protect from direct sunlight.60 Stability of reconstituted solutions of Veletri is temperature and concentration dependent.60 64 65 (See Reconstitution and Dilution under Dosage and Administration.)
Compatibility
For information on systemic interactions resulting from concomitant use, see Interactions.
Parenteral
Drug and Solution Compatibility
Do not dilute or administer with other parenteral solutions or drugs.1 60 61
Actions
-
Direct vasodilation of pulmonary and systemic arterial vascular beds and inhibition of platelet aggregation.1 2 10 60 61
-
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 60 61
-
Produces dose-related decreases in pulmonary vascular resistance, total pulmonary resistance, and mean systemic arterial pressure.1 2 41 60 61
-
Associated with improvement in survival, exercise capacity, and quality of life assessments.1 2 5 6 47 48 60 61
-
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 60 61
-
Additional pharmacologic effects observed in animals include bronchodilation, inhibition of gastric acid secretion, and decreased gastric emptying.1 60 61
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 60 61
-
Importance of advising patient that therapy probably will be needed for prolonged periods, possibly years.1 60 61
-
Importance of careful consideration of patient’s ability to accept and care for a permanent central venous catheter and infusion device.1 60 61
-
Importance of advising patients that abrupt withdrawal or sudden interruptions in drug delivery may result in symptoms associated with rebound pulmonary hypertension (e.g., dyspnea, dizziness, asthenia) and/or death.1 10 60 61
-
Importance of advising patient that sterile technique must be adhered to in drug preparation and catheter care to prevent sepsis.1 60 61 64
-
Importance of reconstitution only with the appropriate diluent specified by the manufacturer.1 60 61
-
Importance of patient informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1 60 61
-
Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.1 60 61
-
Importance of informing patients of other important precautionary information.1 60 61 (See Cautions.)
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Epoprostenol sodium for injection is available only through specialty pharmacies. (See Restricted Distribution under Dosage and Administration.)
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Routes |
Dosage Forms |
Strengths |
Brand Names |
Manufacturer |
---|---|---|---|---|
Parenteral |
For injection, for IV infusion |
0.5 mg (of epoprostenol)* |
Epoprostenol Sodium for Injection (available with diluent) |
|
Flolan (available with diluent) |
GlaxoSmithKline |
|||
Veletri |
Actelion |
|||
1.5 mg (of epoprostenol)* |
Epoprostenol Sodium for Injection (available with diluent) |
|||
Flolan (available with diluent) |
GlaxoSmithKline |
|||
Veletri |
Actelion |
AHFS DI Essentials™. © Copyright 2021, Selected Revisions April 6, 2020. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
† Use is not currently included in the labeling approved by the US Food and Drug Administration.
References
1. GlaxoSmithKline. Flolan prescribing information. Research Triangle Park, NC; 2011 Mar.
2. Herner SJ, Mauro LS. Epoprostenol in primary pulmonary hypertension. Ann Pharmacotherapy. 1999; 33:340-7.
3. GlaxoSmithKline. Research Triangle Park, NC. Personal communication.
4. Food and Drug Administration. Orphan designations pursuant to Section 526 of the Federal Food and Cosmetic Act as amended by the Orphan Drug Act (P.L. 97-414). Rockville, MD; 2004 March 28. From FDA web site (http://www.fda.gov/ForIndustry/DevelopingProductsforRareDiseasesConditions/HowtoapplyforOrphanProductDesignation/default.htm).
5. Barst RJ, Rubin LJ, Long WA et al for the Primary Pulmonary Hypertension Study Group. A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension. N Engl J Med. 1996; 334:296-302. http://www.ncbi.nlm.nih.gov/pubmed/8532025?dopt=AbstractPlus
6. Badesch DB, Tapson VF, McGoon MD et al. Continuous intravenous epoprostenol for pulmonary hypertension due to the scleroderma spectrum of disease: a randomized, controlled trial. Ann Intern Med. 2000; 132:425-34. http://www.ncbi.nlm.nih.gov/pubmed/10733441?dopt=AbstractPlus
7. Rubin LJ, Mendoza J, Hood M et al. Treatment of primary pulmonary hypertension with continuous intravenous prostacyclin (epoprostenol): results of a randomized trial. Ann Intern Med. 1990; 112:485-91. http://www.ncbi.nlm.nih.gov/pubmed/2107780?dopt=AbstractPlus
8. Humbert M, Sitbon O, Simonneau G. Treatment of pulmonary arterial hypertension. N Engl J Med. 2004; 351:1425-36. http://www.ncbi.nlm.nih.gov/pubmed/15459304?dopt=AbstractPlus
9. Paramothayan NS, Lasserson TJ, Wells AU et al. Prostacyclin for pulmonary hypertension in adults. Cochrane Database Syst Rev. 2005; 2:CD002994.
10. Badesch DB, McLaughlin VV, Delcroix M et al. Prostanoid therapy for pulmonary arterial hypertension. J Am Coll Cardiol. 2004; 43(Suppl S):S56-61. http://www.ncbi.nlm.nih.gov/pubmed/15194179?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=2803067&blobtype=pdf
11. Hoeper MM. Drug treatment of pulmonary arterial hypertension: current and future agents. Drugs. 2005; 65:1337-54. http://www.ncbi.nlm.nih.gov/pubmed/15977967?dopt=AbstractPlus
12. Olschewski H, Rose F, Schermuly R et al. Prostacyclin and its analogues in the treatment of pulmonary hypertension. Pharmacol Ther. 2004; 102:139-53. http://www.ncbi.nlm.nih.gov/pubmed/15163595?dopt=AbstractPlus
13. Rich S, Rubin LJ, Abenhaim L et al. Executive summary from the World Health Organization world symposium on primary pulmonary hypertension 1998. World Health Organization publication. Evian, France: 1998 Sep 6-10.
14. Simonneau G, Galiè N, Rubin LJ et al. Clinical classification of pulmonary hypertension. J Am Coll Cardiol. 2004; 43(Suppl S):S5-12. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=2803067&blobtype=pdf
15. Newman JH. Treatment of primary pulmonary hypertension—the next generation. N Engl J Med. 2002; 346:933-5. http://www.ncbi.nlm.nih.gov/pubmed/11907295?dopt=AbstractPlus
16. Galiè N, Seeger W, Naeije R et al. Comparative analysis of clinical trials and evidence-based treatment algorithm in pulmonary arterial hypertension. J Am Coll Cardiol. 2004; 43(Suppl S):S81-88. http://www.ncbi.nlm.nih.gov/pubmed/15194183?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=2803067&blobtype=pdf
18. Lee SH, Rubin LJ. Current treatment strategies for pulmonary arterial hypertension. J Intern Med. 2005; 258:199-215. http://www.ncbi.nlm.nih.gov/pubmed/16115293?dopt=AbstractPlus
19. McLaughlin VV, Shillington A, Rich S. Survival in primary pulmonary hypertension: the impact of epoprostenol therapy. Circulation. 2002; 106:1477-82. http://www.ncbi.nlm.nih.gov/pubmed/12234951?dopt=AbstractPlus
20. Sitbon O, Humbert M, Nunes H et al. Long-term intravenous epoprostenol infusion in primary pulmonary hypertension: prognostic factors and survival. J Am Coll Cardiol. 2002; 40:780-8. http://www.ncbi.nlm.nih.gov/pubmed/12204511?dopt=AbstractPlus
21. Higenbottam TW, Laude EA. Endothelial dysfunction providing the basis for the treatment of pulmonary hypertension: Giles F. Filley lecture. Chest. 1998; 114(Suppl):S72-79. http://www.ncbi.nlm.nih.gov/pubmed/9676644?dopt=AbstractPlus
22. Fishman AP. Epoprostenol (prostacyclin) and pulmonary hypertension. Ann Intern Med. 2000; 132:500-2. http://www.ncbi.nlm.nih.gov/pubmed/10733452?dopt=AbstractPlus
23. Rubin LJ, Badesch DB. Evaluation and management of the patient with pulmonary arterial hypertension. Ann Intern Med. 2005;143:282-92.
24. Stiebellehner L, Petkov V, Vonbank K et al. Long-term treatment with oral sildenafil in addition to continuous IV epoprostenol in patients with pulmonary arterial hypertension. Chest. 2003; 123:1293-5. http://www.ncbi.nlm.nih.gov/pubmed/12684325?dopt=AbstractPlus
25. Hoeper MM, Dinh-Xuan AT. Combination therapy for pulmonary arterial hypertension: still more questions than answers. Eur Respir J. 2004; 24: 339-40. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=1430385&blobtype=pdf
26. Wharton J, Davie N, Upton PD et al. Prostacyclin analogues differentially inhibit growth of distal and proximal human pulmonary artery smooth muscle cells. Circulation. 2000; 102:3130-6. http://www.ncbi.nlm.nih.gov/pubmed/11120706?dopt=AbstractPlus
27. Sakamaki F, Kyotani S, Nagaya N et al. Increased plasma P-selectin and decreased thrombomodulin in pulmonary arterial hypertension were improved by continuous prostacyclin therapy. Circulation. 2000; 102:2720-5. http://www.ncbi.nlm.nih.gov/pubmed/11094038?dopt=AbstractPlus
28. Humbert M, Sanchez O, Fartoukh M et al. Short-term and long-term epoprostenol (prostacyclin) therapy in pulmonary hypertension secondary to connective tissue diseases: results of a pilot study. Eur Respir J. 1999; 13:1351-6. http://www.ncbi.nlm.nih.gov/pubmed/10445611?dopt=AbstractPlus
29. Rubin LJ Diagnosis and management of pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines. Chest. 2004; 126 (Suppl):S7-10.
30. Peacock AJ for the National Pulmonary Hypertension Services of UK and Ireland. Treatment of pulmonary hypertension. BMJ. 2003; 326:835-6. http://www.ncbi.nlm.nih.gov/pubmed/12702599?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=1125759&blobtype=pdf
31. Galiè N, Torbicki A, Barst R et al for the Task Force on Diagnosis and Treatment of Pulmonary Arterial Hypertension of the European Society of Cardiology. Guidelines on diagnosis and treatment of pulmonary arterial hypertension. Eur Heart J. 2004; 25:2243-78. http://www.ncbi.nlm.nih.gov/pubmed/15589643?dopt=AbstractPlus
32. Budhiraja R, Tuder RM, Hassoun PM. Endothelial dysfunction in pulmonary hypertension. Circulation. 2004; 109:159-65. http://www.ncbi.nlm.nih.gov/pubmed/14734504?dopt=AbstractPlus
33. Weir EK, Rubin LJ, Ayres SM et al. The acute administration of vasodilators in primary pulmonary hypertension. Experience from the National Institutes of Health Registry on Primary Pulmonary Hypertension. Am Rev Respir Dis. 1989; 140:1623-30. http://www.ncbi.nlm.nih.gov/pubmed/2690706?dopt=AbstractPlus
34. Galiè N, Ussia G, Passarelli P et al. Role of pharmacologic tests in the treatment of primary pulmonary hypertension. Am J Cardiol. 1995; 75:A55-62. http://www.ncbi.nlm.nih.gov/pubmed/7840056?dopt=AbstractPlus
35. McLaughlin VV, Genthner DE, Panella MM et al. Reduction in pulmonary vascular resistance with long-term epoprostenol (prostacyclin) therapy in primary pulmonary hypertension. N Engl J Med. 1998; 338:273-7. http://www.ncbi.nlm.nih.gov/pubmed/9445406?dopt=AbstractPlus
36. Rubin LJ. Primary pulmonary hypertension. N Engl J Med. 1997; 336:111-7. http://www.ncbi.nlm.nih.gov/pubmed/8988890?dopt=AbstractPlus
37. Barst RJ, McGoon M, Torbicki A et al. Diagnosis and differential assessment of pulmonary arterial hypertension. J Am Coll Cardiol. 2004; 43(Suppl S):S40–7. http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=2803067&blobtype=pdf
38. Raffy O, Azarian R, Brenot F et al. Clinical significance of the pulmonary vasodilator response during short-term infusion of prostacyclin in primary pulmonary hypertension. Circulation. 1996; 93:484-8. http://www.ncbi.nlm.nih.gov/pubmed/8565165?dopt=AbstractPlus
39. Sitbon O, Brenot F, Denjean A et al. Inhaled nitric oxide as a screening vasodilator agent in primary pulmonary hypertension: a dose-response study and comparison with prostacyclin. Am J Respir Crit Care Med. 1995; 151:384-9. http://www.ncbi.nlm.nih.gov/pubmed/7842196?dopt=AbstractPlus
40. Provencher S, Jais X, Yaici A et al. Clinical challenges in pulmonary hypertension: Roger S. Mitchell lecture. Chest. 2005; 128(Suppl):S622-628. http://www.ncbi.nlm.nih.gov/pubmed/16373880?dopt=AbstractPlus
41. Galiè N, Manes A, Branzi A. Prostanoids for pulmonary arterial hypertension. Am J Respir Med. 2003; 2:123-37. http://www.ncbi.nlm.nih.gov/pubmed/14720012?dopt=AbstractPlus
42. Sitbon O, Humbert M, Jagot JL et al. Inhaled nitric oxide as a screening agent for safely identifying responders to oral calcium-channel blockers in primary pulmonary hypertension. Eur Respir J. 1998; 12:265-70. http://www.ncbi.nlm.nih.gov/pubmed/9727772?dopt=AbstractPlus
43. Myogen, Overland Park, KS: Personal communication.
45. Gilead, Foster City, CA: Personal communication.
46. Ogawa A, Matsubara H, Fujio H et al. Risk of alveolar hemorrhage in patients with primary pulmonary hypertension: anticoagulation and epoprostenol therapy. Circ J. 2005; 69: 216-20. http://www.ncbi.nlm.nih.gov/pubmed/15671616?dopt=AbstractPlus
47. Hackman AM, Lackner TE. Pharmacotherapy for idiopathic pulmonary arterial hypertension during the past 25 years. Pharmacotherapy. 2006; 26:68-94. http://www.ncbi.nlm.nih.gov/pubmed/16506350?dopt=AbstractPlus
48. Chin KM, Rubin LJ. Pulmonary arterial hypertension. J Am Coll Cardiol. 2008; 51:1527-38. http://www.ncbi.nlm.nih.gov/pubmed/18420094?dopt=AbstractPlus
49. Caremark Specialty Pharmacy Services. Specialty trends alert. May 2008. From Caremark website http://www.caremart.com. Accessed 2008 Oct. 31.
50. Teva, Philadelphia, PA: Personal communication.
52. Galiè N, Corris PA, Frost A et al. Updated treatment algorithm of pulmonary arterial hypertension. J Am Coll Cardiol. 2013; 62(25 Suppl):D60-72. http://www.ncbi.nlm.nih.gov/pubmed/24355643?dopt=AbstractPlus
53. Channick RN. Combination therapy in pulmonary arterial hypertension. Am J Cardiol. 2013; 111(8 Suppl):16C-20C. http://www.ncbi.nlm.nih.gov/pubmed/23558025?dopt=AbstractPlus
54. Zhu B, Wang L, Sun L et al. Combination therapy improves exercise capacity and reduces risk of clinical worsening in patients with pulmonary arterial hypertension: a meta-analysis. J Cardiovasc Pharmacol. 2012; 60:342-6. http://www.ncbi.nlm.nih.gov/pubmed/22691882?dopt=AbstractPlus
55. Gokhman R, Smithburger PL, Kane-Gill SL et al. Pharmacologic and Pharmacokinetic Rationale for Combination Therapy in Pulmonary Arterial Hypertension. J Cardiovasc Pharmacol. 2010; :. http://www.ncbi.nlm.nih.gov/pubmed/20838230?dopt=AbstractPlus
56. McLaughlin VV, Archer SL, Badesch DB et al. ACCF/AHA 2009 expert consensus document on pulmonary hypertension a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association developed in collaboration with the American College of Chest Physicians; American Thoracic Society, Inc.; and the Pulmonary Hypertension Association. J Am Coll Cardiol. 2009; 53:1573-619. http://www.ncbi.nlm.nih.gov/pubmed/19389575?dopt=AbstractPlus
60. Actelion. Veletri(epoprostenol for injection) prescribing information. South San Francisco, CA; 2012 Jun.
61. Teva. Epoprostenol sodium for injection prescribing information. Sellersville, PA; 2011 Oct.
62. Actelion. South San Francisco, CA: Personal communication.
63. Simonneau G, Gatzoulis MA, Adatia I et al. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol. 2013; 62(25 Suppl):D34-41. http://www.ncbi.nlm.nih.gov/pubmed/24355639?dopt=AbstractPlus
64. Fuentes A, Coralic A, Dawson KL. A new epoprostenol formulation for the treatment of pulmonary arterial hypertension. Am J Health Syst Pharm. 2012; 69:1389-93. http://www.ncbi.nlm.nih.gov/pubmed/22855104?dopt=AbstractPlus
65. Lambert O, Bandilla D. Stability and preservation of a new formulation of epoprostenol sodium for treatment of pulmonary arterial hypertension. Drug Des Devel Ther. 2012; 6:235-44. http://www.ncbi.nlm.nih.gov/pubmed/23049244?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=3459691&blobtype=pdf
66. Sitbon O, Delcroix M, Bergot E et al. EPITOME-2: An open-label study assessing the transition to a new formulation of intravenous epoprostenol in patients with pulmonary arterial hypertension. Am Heart J. 2014; 167:210-7. http://www.ncbi.nlm.nih.gov/pubmed/24439982?dopt=AbstractPlus
67. Tamura Y, Ono T, Fukuda K et al. Evaluation of a new formulation of epoprostenol sodium in Japanese patients with pulmonary arterial hypertension (EPITOME4). Adv Ther. 2013; 30:459-71. http://www.ncbi.nlm.nih.gov/pubmed/23653230?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=3680653&blobtype=pdf
68. Nicolas LB, Gutierrez MM, Dingemanse J. Comparative pharmacokinetic, pharmacodynamic, safety, and tolerability profiles of 3 different formulations of epoprostenol sodium for injection in healthy men. Clin Ther. 2013; 35:440-9. http://www.ncbi.nlm.nih.gov/pubmed/23498778?dopt=AbstractPlus
69. Nicolas LB, Krause A, Gutierrez MM et al. Integrated pharmacokinetics and pharmacodynamics of epoprostenol in healthy subjects. Br J Clin Pharmacol. 2012; 74:978-89. http://www.ncbi.nlm.nih.gov/pubmed/22515646?dopt=AbstractPlus http://www.pubmedcentral.nih.gov/picrender.fcgi?tool=pmcentrez&artid=3522811&blobtype=pdf
70. Actelion. Prescribing Veletri (epoprostenol) for injection. South San Francisco, CA. Available at: http://www.veletri.com/patient-getting-veletri.asp. Accessed 2014 Apr 8.
77. Gebistorf F, Karam O, Wetterslev J et al. Inhaled nitric oxide for acute respiratory distress syndrome (ARDS) in children and adults. Cochrane Database Syst Rev. 2016; :CD002787. http://www.ncbi.nlm.nih.gov/pubmed/27347773?dopt=AbstractPlus
78. Alessandri F, Pugliese F, Ranieri VM. The Role of Rescue Therapies in the Treatment of Severe ARDS. Respir Care. 2018; 63:92-101. http://www.ncbi.nlm.nih.gov/pubmed/29066591?dopt=AbstractPlus
79. Griffiths MJD, McAuley DF, Perkins GD et al. Guidelines on the management of acute respiratory distress syndrome. BMJ Open Respir Res. 2019; 6:e000420. http://www.ncbi.nlm.nih.gov/pubmed/31258917?dopt=AbstractPlus
80. Papazian L, Aubron C, Brochard L et al. Formal guidelines: management of acute respiratory distress syndrome. Ann Intensive Care. 2019; 9:69. http://www.ncbi.nlm.nih.gov/pubmed/31197492?dopt=AbstractPlus
81. Cherian SV, Kumar A, Akasapu K et al. Salvage therapies for refractory hypoxemia in ARDS. Respir Med. 2018; 141:150-158. http://www.ncbi.nlm.nih.gov/pubmed/30053961?dopt=AbstractPlus
82. Cheifetz IM. Pediatric ARDS. Respir Care. 2017; 62:718-731. http://www.ncbi.nlm.nih.gov/pubmed/28546374?dopt=AbstractPlus
83. Tamburro RF, Kneyber MC, Pediatric Acute Lung Injury Consensus Conference Group. Pulmonary specific ancillary treatment for pediatric acute respiratory distress syndrome: proceedings from the Pediatric Acute Lung Injury Consensus Conference. Pediatr Crit Care Med. 2015; 16(5 Suppl 1):S61-72. http://www.ncbi.nlm.nih.gov/pubmed/26035366?dopt=AbstractPlus
84. Pipeling MR, Fan E. Therapies for refractory hypoxemia in acute respiratory distress syndrome. JAMA. 2010; 304:2521-7. http://www.ncbi.nlm.nih.gov/pubmed/21139113?dopt=AbstractPlus
85. Fan E, Brodie D, Slutsky AS. Acute Respiratory Distress Syndrome: Advances in Diagnosis and Treatment. JAMA. 2018; 319:698-710. http://www.ncbi.nlm.nih.gov/pubmed/29466596?dopt=AbstractPlus
86. Walmrath D, Schneider T, Pilch J et al. Aerosolised prostacyclin in adult respiratory distress syndrome. Lancet. 1993; 342:961-2. http://www.ncbi.nlm.nih.gov/pubmed/8105216?dopt=AbstractPlus
87. Ammar MA, Bauer SR, Bass SN et al. Noninferiority of Inhaled Epoprostenol to Inhaled Nitric Oxide for the Treatment of ARDS. Ann Pharmacother. 2015; 49:1105-12. http://www.ncbi.nlm.nih.gov/pubmed/26187741?dopt=AbstractPlus
88. Afshari A, Bastholm Bille A, Allingstrup M. Aerosolized prostacyclins for acute respiratory distress syndrome (ARDS). Cochrane Database Syst Rev. 2017; 7:CD007733. http://www.ncbi.nlm.nih.gov/pubmed/28806480?dopt=AbstractPlus
89. Dahlem P, van Aalderen WM, de Neef M et al. Randomized controlled trial of aerosolized prostacyclin therapy in children with acute lung injury. Crit Care Med. 2004; 32:1055-60. http://www.ncbi.nlm.nih.gov/pubmed/15071401?dopt=AbstractPlus
90. Fuller BM, Mohr NM, Skrupky L et al. The use of inhaled prostaglandins in patients with ARDS: a systematic review and meta-analysis. Chest. 2015; 147:1510-1522. http://www.ncbi.nlm.nih.gov/pubmed/25742022?dopt=AbstractPlus
91. Searcy RJ, Morales JR, Ferreira JA et al. The role of inhaled prostacyclin in treating acute respiratory distress syndrome. Ther Adv Respir Dis. 2015; 9:302-12. http://www.ncbi.nlm.nih.gov/pubmed/26294418?dopt=AbstractPlus
More about epoprostenol
- Side Effects
- During Pregnancy
- Dosage Information
- Drug Interactions
- Pricing & Coupons
- En Español
- 3 Reviews
- Drug class: agents for pulmonary hypertension