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Pronunciation
(e poe PROST en ole)
Generic Available (U.S.)
Yes
Index Terms
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 (1-800-935-6526) or TheraCom, Inc (1-877-356-5264).
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Use: Labeled Indications
Treatment of pulmonary arterial hypertension (PAH) (WHO Group I) in patients with NYHA Class III or IV symptoms to improve exercise capacity
Use: Unlabeled
Acute vasodilator testing in pulmonary arterial hypertension (PAH)
Inhalation: Intraoperative treatment of pulmonary hypertension in patients undergoing cardiac surgery with cardiopulmonary bypass; post-cardiothoracic surgery pulmonary hypertension, right ventricular dysfunction, or refractory hypoxemia
Pregnancy Risk Factor
B
Pregnancy Considerations
Teratogenic effects were not reported in animal studies. There are no adequate and well-controlled studies in pregnant women. Women with IPAH are encouraged to avoid pregnancy.
Lactation
Excretion in breast milk unknown/use caution
Contraindications
Hypersensitivity to epoprostenol or to structurally-related compounds; chronic use in patients with heart failure due to severe left ventricular systolic dysfunction; patients who develop pulmonary edema during dose initiation
Warnings/Precautions
Concerns related to adverse effects:
• Pulmonary edema: Some patients with PAH have developed pulmonary edema during dosing adjustment and acute vasodilator testing (not an approved 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.
• Rebound pulmonary hypertension: Abrupt interruptions or large sudden reductions in dosage may result in rebound pulmonary hypertension. Avoid abrupt withdrawal. Immediate access to medication or pump and infusion sets is essential to prevent treatment interruptions.
Disease-related concerns:
• Conditions that increase bleeding risk: Epoprostenol is an inhibitor of platelet aggregation. Use with caution in patients with risk factors for bleeding.
Concurrent drug therapy issues:
• Anticoagulants: During chronic use, unless contraindicated, anticoagulants should be coadministered to reduce the risk of thromboembolism.
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 I.V. infusion of epoprostenol via a chronic indwelling central venous catheter (CVC) has been associated with local infections and serious blood stream infections.
Adverse Reactions
Note: Adverse events reported during dose initiation and escalation include flushing (58%), headache (49%), nausea/vomiting (32%), hypotension (16%), anxiety/nervousness/agitation (11%), chest pain (11%); dizziness, abdominal pain, bradycardia, musculoskeletal pain, dyspnea, back pain, diaphoresis, dyspepsia, hypoesthesia/paresthesia, and tachycardia are also reported. Although some adverse reactions may be related to the underlying disease state, abdominal pain, anxiety/nervousness/agitation, arthralgia, bleeding, bradycardia, diarrhea, diaphoresis, flu-like syndrome, flushing, headache, hypotension, jaw pain, nausea, pain, pulmonary edema, rash, tachycardia, thrombocytopenia, and vomiting are clearly contributed to epoprostenol. The following adverse events have been reported during chronic administration for idiopathic or heritable PAH:
>10%:
Cardiovascular: Tachycardia (35% to 43%), flushing (23% to 42%), hypotension (13%)
Central nervous system: Dizziness (83%), headache (46% to 83%), chills/fever/sepsis/flu-like syndrome (25%), anxiety/nervousness/tremor (21%)
Dermatologic: Skin ulcer (39%), eczema/rash/urticaria (25%)
Gastrointestinal: Nausea/vomiting (41% to 67%), anorexia (66%), diarrhea (37% to 50%)
Local: Injection site reactions: Infection (18%), pain (11%)
Neuromuscular & skeletal: Pain/neck pain/arthralgia (84%), jaw pain (54% to 75%), arthritis (52%), myalgia (44%), musculoskeletal pain (35%), hypoesthesia/hyperesthesia/paresthesia (5% to 12%)
<1%, postmarketing, and/or case reports: Anemia, fatigue, hepatic failure, hypersplenism, hyperthyroidism, pallor, pancytopenia, pulmonary embolism, splenomegaly, thrombocytopenia
Metabolism/Transport Effects
None known.
Drug Interactions
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
Antihypertensives: Prostacyclin Analogues may enhance the hypotensive effect of Antihypertensives. Risk C: Monitor therapy
Antiplatelet Agents: Prostacyclin Analogues may enhance the antiplatelet effect of Antiplatelet Agents. Risk C: Monitor therapy
Storage
Injection for reconstitution:
Flolan®: Prior to use, store vials at 15°C to 25°C (59°F to 77°F); do not freeze. Protect from light. Following reconstitution, solution must be stored under refrigeration at 2°C to 8°C (36°F to 46°F) if not used immediately; do not freeze. Protect from light. Total storage and infusion time must not exceed 48 hours for reconstituted solutions. Each reservoir of solution may be refrigerated for ≤40 hours and infused at room temperature over ≤8 hours; alternatively, each reservoir may be refrigerated for ≤24 hours and infused with the use of a cold pouch over ≤24 hours (gel packs must be changed every 12 hours).
Veletri®: Prior to use, store vials at 20°C to 25°C (68°F to 77°F); do not freeze. Protect from light. Following reconstitution, vials may be stored under refrigeration at 2°C to 8°C (36°F to 46°F) up to 5 days, stored at room temperature of 25°C (77°F) up to 48 hours, or immediately diluted (see table) and added to a drug delivery reservoir.
Diluted solutions which have been immediately added to a drug delivery reservoir may be administered immediately or stored at 2°C to 8°C (36°F to 46°F) for 1-7 days (dependent on concentration and time to initiation); do not freeze. Protect from light.
If administered immediately, the following maximum durations of administration at room temperature according to solution concentration are recommended:
≥3000 to <6000 ng/mL: 12 hours
≥6000 to <30,000 ng/mL: 24 hours
≥30,000 ng/mL: 72 hours
If stored at 2°C to 8°C (36°F to 46°F) for 1 day, the following maximum durations of administration at room temperature according to solution concentration are recommended:
<6000 ng/mL: Do not use
≥6000 to <12,000 ng/mL: 12 hours
≥12,000 to <30,000 ng/mL: 24 hours
≥30,000 ng/mL: 48 hours
If stored at 2°C to 8°C (36°F to 46°F) for 7 days, the following maximum durations of administration at room temperature according to solution concentration are recommended:
<9000 ng/mL: Do not use
≥9000 to <30,000 ng/mL: 12 hours
≥30,000 ng/mL: 24 hours
If using previously reconstituted and stored vials, each vial must be further diluted (see table) prior to adding to the drug delivery reservoir. Each reservoir diluted to a concentration ≥15,000 ng/mL can be administered at room temperature for up to 24 hours; if lower concentrations are used, pump reservoirs should be changed every 12 hours.
Reconstitution
Preparation of Epoprostenol Infusion
To make solution with concentration:
Flolan®
Instructions
Veletri®
Instructions
Note: Flolan® may only be prepared with sterile diluent provided.
Note: Veletri® may only be prepared with sterile water for injection (SWFI) or NS.
3000 ng/mL
Dissolve one 0.5 mg vial with 5 mL supplied diluent, withdraw 3 mL, and add to a sufficient volume of supplied diluent to make a total of 100 mL.
Dissolve one 1.5 mg vial with 5 mL of SWFI or NS, withdraw 1 mL, and add to a sufficient volume of the identical diluent to make a total of 100 mL.
5000 ng/mL
Dissolve one 0.5 mg vial with 5 mL supplied diluent, withdraw entire vial contents, and add to a sufficient volume of supplied diluent to make a total of 100 mL.
6000 ng/mL
Dissolve one 1.5 mg vial with 5 mL of SWFI or NS, withdraw 2 mL, and add to a sufficient volume of the identical diluent to make a total of 100 mL.
9000 ng/mL
Dissolve one 1.5 mg vial with 5 mL of SWFI or NS, withdraw 3 mL, and add to a sufficient volume of the identical diluent to make a total of 100 mL.
10,000 ng/mL
Dissolve two 0.5 mg vials each with 5 mL supplied diluent, withdraw entire vial contents, and add to a sufficient volume of supplied diluent to make a total of 100 mL.
12,000 ng/mL
Dissolve one 1.5 mg vial with 5 mL of SWFI or NS, withdraw 4 mL, and add to a sufficient volume of the identical diluent to make a total of 100 mL.
15,000 ng/mL
Dissolve one 1.5 mg vial with 5 mL supplied diluent, withdraw entire vial contents, and add to a sufficient volume of supplied diluent to make a total of 100 mL.
Dissolve one 1.5 mg vial with 5 mL of SWFI or NS, withdraw entire vial contents, and add to a sufficient volume of the identical diluent to make a total of 100 mL.
20,000 ng/mL
Dissolve two 0.5 mg vials each with 5 mL supplied diluent, withdraw entire vial contents, and add to a sufficient volume of supplied diluent to make a total of 50 mL (DeWet, 2004).
30,000 ng/mL
Dissolve two 1.5 mg vials each with 5 mL of SWFI or NS, withdraw entire vial contents, and add to a sufficient volume of the identical diluent to make a total of 100 mL.
Table has been converted to the following text.
Preparation of Epoprostenol Infusion
Note: Flolan® may only be prepared with sterile diluent provided. Veletri® may only be prepared with sterile water for injection (SWFI) or NS.
To make solution with the following concentrations:
3000 ng/mL:
Flolan®: Dissolve one 0.5 mg vial with 5 mL supplied diluent, withdraw 3 mL, and add to a sufficient volume of supplied diluent to make a total of 100 mL.
Veletri®: Dissolve one 1.5 mg vial with 5 mL of SWFI or NS, withdraw 1 mL, and add to a sufficient volume of the identical diluent to make a total of 100 mL.
5000 ng/mL: Flolan®: Dissolve one 0.5 mg vial with 5 mL supplied diluent, withdraw entire vial contents, and add to a sufficient volume of supplied diluent to make a total of 100 mL.
6000 ng/mL: Veletri®: Dissolve one 1.5 mg vial with 5 mL of SWFI or NS, withdraw 2 mL, and add to a sufficient volume of the identical diluent to make a total of 100 mL.
9000 ng/mL: Veletri®: Dissolve one 1.5 mg vial with 5 mL of SWFI or NS, withdraw 3 mL, and add to a sufficient volume of the identical diluent to make a total of 100 mL.
10,000 ng/mL: Flolan®: Dissolve two 0.5 mg vials each with 5 mL supplied diluent, withdraw entire vial contents, and add to a sufficient volume of supplied diluent to make a total of 100 mL.
12,000 ng/mL: Veletri®: Dissolve one 1.5 mg vial with 5 mL of SWFI or NS, withdraw 4 mL, and add to a sufficient volume of the identical diluent to make a total of 100 mL.
15,000 ng/mL:
Flolan®: Dissolve one 1.5 mg vial with 5 mL supplied diluent, withdraw entire vial contents, and add to a sufficient volume of supplied diluent to make a total of 100 mL.
Veletri®: Dissolve one 1.5 mg vial with 5 mL of SWFI or NS, withdraw entire vial contents, and add to a sufficient volume of the identical diluent to make a total of 100 mL.
20,000 ng/mL: Flolan®: Dissolve two 0.5 mg vials each with 5 mL supplied diluent, withdraw entire vial contents, and add to a sufficient volume of supplied diluent to make a total of 50 mL (DeWet, 2004).
30,000 ng/mL: Veletri®: Dissolve two 1.5 mg vials each with 5 mL of SWFI or NS, withdraw entire vial contents, and add to a sufficient volume of the identical diluent to make a total of 100 mL.
Compatibility
Flolan®: Only prepare with sterile diluent provided. Veletri®: Only prepare with SWFI or NS. Per manufacturer, do not mix or administer with any other drugs or solutions prior to or during administration.
Compatibility in Y-site administration: Compatible: Bivalirudin.
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.
Pharmacodynamics/Kinetics
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%)
Dosage
I.V.:
Pulmonary arterial hypertension (PAH): Children (unlabeled use) and Adults: Initial: 2 ng/kg/minute; a lower initial dose may be used if patient is intolerant of starting dose. Increase dose in increments of 2 ng/kg/minute at intervals of ≥15 minutes until dose-limiting side effects (eg, flushing, jaw pain, headache, hypotension, nausea) are noted or response to epoprostenol plateaus. Usual optimal dose (monotherapy): 25-40 ng/kg/minute (McLaughlin, 2009); significant patient variability in optimal dose exists. Maximum dose with chronic therapy has not been defined; however, doses as high as 195 ng/kg/minute have been described in children (Rosenzweig, 1999).
Dose adjustment during chronic phase of treatment:
If PAH symptoms persist or recur following improvement, increase dose in 1-2 ng/kg/minute increments at intervals of ≥15 minutes. May also increase dose at intervals of 24-48 hours or longer (eg, every 1-2 weeks). Note: The need for increased doses should be expected with chronic use; incremental increases occur more frequently during the first few months after the drug is initiated.
In case of dose-limiting pharmacologic events (eg, hypotension, severe nausea, vomiting), decrease dose in 2 ng/kg/minute decrements at intervals of ≥15 minutes. Avoid abrupt withdrawal or sudden large dose reductions. Note: Adverse event may resolve without dosage adjustment.
Lung transplant: In patients receiving lung transplants, epoprostenol may be tapered after sequential lung transplantation once the allografts have been reperfused. If cardiopulmonary bypass utilized, epoprostenol may be tapered after pump perfusion has been initiated.
Acute vasodilator testing in patients with PAH (unlabeled use; McLaughlin, 2009): Adults: Note: Acute vasodilator testing should only be done in patients who might be considered candidates for calcium channel blocker therapy.
Initial: 2 ng/kg/minute; increase dose in increments of 2 ng/kg/minute every 10-15 minutes; dosing range during testing: 2-10 ng/kg/minute
Inhalation (unlabeled route): Adults:
Intraoperative pulmonary hypertension during cardiac surgery with cardiopulmonary bypass (CPB) (unlabeled use): Note: Institution-specific protocols vary.
Administration after induction of anesthesia before incision: 60 mcg (4 mL of 15,000 ng/mL concentration) via jet nebulizer; effect persists for ~25 minutes (Hache, 2003)
or
Intraoperative administration: Nebulization via ventilator circuit: Using a 15,000 ng/mL concentration and an oxygen flow of 8 L/minute, begin administration via jet nebulizer 5 minutes prior to weaning from CPB; discontinue at least 60 minutes after CPB weaned (Fattouch, 2006)
Post-cardiothoracic surgery pulmonary hypertension, right ventricular dysfunction, or refractory hypoxemia (unlabeled use) (DeWet, 2004): Note: May need to change ventilator filter every 2 hours due to glycine buffer diluent; may cause ventilator valve malfunction. Tidal volume delivered by ventilator may require adjustment.
Nebulization via ventilator circuit: Using a 20,000 ng/mL concentration, prime nebulizer chamber with 15 mL; administer remainder at a constant rate of 8 mL/hour; delivers ~38 ng/kg/minute (based on a 70 kg patient); set oxygen flow at 2-3 L/minute; wean as tolerated. Note: Although not achieved with this regimen, in general, doses >50 ng/kg/minute do not provide additional benefit and may increase the risk of hypotension.
or
Nebulization via facemask with Venturi attachment: Using a 20,000 ng/mL concentration, prime nebulizer chamber with 15 mL; set oxygen flow at 2-3 L/minute; 8 mL/hour will be nebulized; wean as tolerated.
Weaning procedure: Reduce dose by 50% every 2-4 hours (ie, 20,000 ng/mL to 10,000 ng/mL to 5000 ng/mL) until a concentration of 2500 ng/mL is reached; carefully discontinue once patient remains stable on this concentration for at least 4 hours.
Administration: I.V.
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.
Administration: Inhalation
Inhalation is an unlabeled route of administration.
Intraoperative administration: Administer via jet nebulizer connected to the inspiratory limb of the ventilator near the endotracheal tube with a bypass oxygen flow of 8 L/minute to achieve administration of a high proportion of small particles (Fattouch, 2006; Hache, 2003).
Post-cardiothoracic surgery: May also 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 2-3 L/minute (De Wet, 2004). Note: Glycine buffer diluent may cause ventilator valve malfunction; it has been recommended that filters be changed on the ventilator every 2 hours; may also use a ventilator heating coil (De Wet, 2004).
Administration: I.V. Detail
When given on an ongoing basis, must be infused through a central venous catheter. Peripheral infusion may be used temporarily until central line is established. Infuse using an infusion pump. Avoid abrupt withdrawal (including interruptions in delivery) or sudden large reductions in dosing.
pH: 10.2-10.8
Monitoring Parameters
Monitor for improvements in pulmonary function, decreased exertional dyspnea, fatigue, syncope and chest pain, pulmonary vascular resistance, pulmonary arterial pressure and quality of life. 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.
Patient Education
Therapy on this drug will probably be long-term. You may experience mild headache, nausea, vomiting, diarrhea, weight loss, nervousness, dizziness, or muscular pains. Report immediately any signs or symptoms of acute or severe headache; back pain; increased difficult breathing; flushing; fever or chills; any unusual bleeding or bruising; chest pain; palpitations; difficulty breathing; increased pain, irritation, or pus formed at I.V. site; or any onset of unresolved diarrhea.
Anesthesia and Critical Care Concerns/Other Considerations
Pulmonary Hypertension Related to Cardiopulmonary Bypass (CPB): Inhaled epoprostenol has been used to reduce pulmonary artery pressures in both pulmonary hypertension patients undergoing cardiac surgery (Fattouch, 2006; Hache, 2003) and postoperative cardiac surgery patients who have developed pulmonary hypertension, right heart dysfunction, or refractory hypoxemia (De Wet, 2004). Epoprostenol is effective in reducing pulmonary artery pressure and improving oxygenation. Inhaled epoprostenol does not produce systemic manifestations such as hypotension at doses ≤50 ng/kg/minute (Van Heerden, 2000) and may be a cost effective strategy in both of these patient populations.
Cardiovascular Considerations
The primary role of epoprostenol is in the treatment of pulmonary arterial hypertension (PAH) in patients unresponsive to other therapy. Response to initial therapy is evaluated in a controlled setting before chronic therapy is administered. The role of epoprostenol in the treatment of heart failure confers a negative impact on cardiovascular morbidity and mortality. Clinical trials showed improvement of heart failure symptoms and exercise tolerance, but an increase in mortality. Therefore, use in severe heart failure is contraindicated.
Acute vasodilator testing: Epoprostenol may be used for acute vasodilator testing to identify those patients with PAH with a better prognosis and who will likely have a sustained response to oral calcium channel blockers (eg, high-dose extended-release nifedipine) which have been shown to increase survival (McLaughlin, 2009; Rich, 1992). Response to acute vasodilator testing is currently defined as a reduction in mean pulmonary artery pressure (mPAP) of ≥10 mm Hg, to a mPAP ≤40 mm Hg, with an unchanged or increased cardiac output (McLaughlin, 2009). Of note, acute vasodilator testing is not recommended and may be harmful in patients with significantly elevated left heart filling pressures.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported. Epoprostenol is an inhibitor of platelet aggregation and may enhance the risk of bleeding with other antiplatelet agents (such as aspirin and/or NSAIDs).
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
Anxiety, nervousness are common; may cause confusion, insomnia, or depression
Mental Health: Effects on Psychiatric Treatment
Hypotensive effects may be exacerbated by low potency antipsychotics (chlorpromazine) and TCAs
Nursing: Physical Assessment/Monitoring
Assess patient's or caregiver's ability to manage a central venous catheter in the home setting. Clinicians should routinely review with patient the importance of infection control practices for the management of a central venous catheter. Institutional: Continuous pulmonary and hemodynamic arterial monitoring, INR. Home therapy: Avoid sudden rate reduction or abrupt withdrawal or interruption of therapy. Monitor for improved pulmonary function and quality of life.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Injection, powder for reconstitution: 0.5 mg, 1.5 mg
Flolan®: 0.5 mg, 1.5 mg
Veletri®: 1.5 mg
References
Badesch DB, Abman SH, Simonneau G, et al, “Medical Therapy for Pulmonary Arterial Hypertension: Updated ACCP Evidence-Based Clinical Practice Guidelines,” Chest, 2007, 131(6):1917-28.
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, 21;132(6):425-34.
Barst RJ, Maislin G, and Fishman AP, “Vasodilator Therapy for Primary Pulmonary Hypertension in Children,” Circulation, 1999, 99(9):1197-208.
Barst RJ, Rubin LJ, Long WA, et al, “A Comparison of Continuous Intravenous Epoprostenol (Prostacyclin) With Conventional Therapy for Primary Pulmonary Hypertension. The Primary Pulmonary Hypertension Study Group,” N Engl J Med, 1996, 334(5):296-302.
Cremona G and Higenbottam T, “Role of Prostacyclin in the Treatment of Primary Pulmonary Hypertension,” Am J Cardiol, 1995, 75(3):67A-71A.
De Wet CJ, Affleck DG, Jacobsohn E, et al, “Inhaled Prostacyclin is Safe, Effective, and Affordable in Patients with Pulmonary Hypertension, Right Heart Dysfunction, and Refractory Hypoxemia After Cardiothoracic Surgery,” J Thorac Cardiovasc Surg, 2004, 127(4):1058-67.
Fattouch K, Sbraga F, Sampognaro R, et al, “Treatment of Pulmonary Hypertension in Patients Undergoing Cardiac Surgery With Cardiopulmonary Bypass: A Randomized, Prospective, Double-Blind Study,” J Cardiovasc Med (Hagerstown), 2006, 7(2):119-23.
Haché, M, Denault A, Bélisle S, et al, “Inhaled Epoprostenol (Prostacyclin) and Pulmonary Hypertension Before Cardiac Surgery,” J Thorac Cardiovasc Surg, 2003, 125(3):642-9
Higenbottam TW, Spiegelhalter D, Scott JP, et al, “Prostacyclin (Epoprostenol) and Heart-Lung Transplantation as Treatments for Severe Pulmonary Hypertension,” Br Heart J, 1994, 70:366-70.
Jones DK, Higenbottam TW, and Wallwork J, “Treatment of Primary Pulmonary Hypertension Intravenous Epoprostenol (Prostacyclin),” Br Heart J 1987, 57(3):270-8.
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,” Circulation, 2009, 119(16):2250-94.
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(5):273-7.
McLaughlin VV, Shillington A, and Rich S, “Survival in Primary Pulmonary Hypertension: The Impact of Epoprostenol Therapy,” Circulation, 2002, 106(12):1477-82.
Nakayama T, Shimada H, Takatsuki S, et al, “Efficacy and Limitations of Continuous Intravenous Epoprostenol Therapy for Idiopathic Pulmonary Arterial Hypertension in Japanese Children,” Circ J, 2007, 71(11):1785-90.
Rich S, Kaufmann E, and Levy PS, “The Effect of High Doses of Calcium-channel Blockers on Survival in Primary Pulmonary Hypertension,” N Engl J Med, 1992, 327(2):76-81.
Rosenzweig EB and Barst RJ, “Idiopathic Pulmonary Arterial Hypertension in Children,” Curr Opin Pediatr, 2005, 17(3):372-80.
Rosenzweig EB, Kerstein D, and Barst RJ, "Long-Term Prostacyclin for Pulmonary Hypertension With Associated Congenital Heart Defects," Circulation, 1999, 99(14):1858-65.
Rosenzweig EB, Widlitz AC, and Barst RJ, “Pulmonary Arterial Hypertension in Children,” Pediatr Pulmonol, 2004, 38(1):2-22.
Rubin LJ, Groves BM, Reeves JT, et al, “Prostacyclin-Induced Acute Pulmonary Vasodilation in Primary Pulmonary Hypertension,” Circulation, 1982, 66(2):334-8.
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(40):780-8.
Sueta CA, Gheorghiade M, Adams KF, et al, “Safety and Efficacy of Epoprostenol in Patients With Severe Congestive Heart Failure. Epoprostenol Multicenter Research Group,” Am J Cardiol, 1995, 75(3):34A-43A.
van Heerden PV, Barden A, Michalopaoulos N, et al, “Dose-Response to Inhaled Aerosolized Prostacyclin for Hypoxemia Due to ARDS,” Chest, 2000, 117(3):819-27.
Walmrath D, Schneider T, Pilch J, et al, “Aerosolised Prostacyclin in Adult Respiratory Distress Syndrome,” Lancet, 1993, 342(8877):961-2.
Widlitz A and Barst RJ, “Pulmonary Arterial Hypertension in Childrenl,”Eur Respir J, 2003, 21(1):155-76.
Zwissler, B, Kemming G, Habler O, et al, “Inhaled Prostacyclin (PGI2) Versus Inhaled Nitric Oxide in Adult Respiratory Distress Syndrome,” Am J Respir Crit Care Med, 1996, 154(6 Pt 1):1671-7.
International Brand Names
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Last full review/revision January 2012
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