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Epoprostenol

Medically reviewed by Drugs.com. Last updated on Sep 27, 2020.

Pronunciation

(e poe PROST en ole)

Index Terms

  • Epoprostenol Sodium
  • Epoprostenol Sodium (Arginine)
  • PGI2
  • PGX
  • Prostacyclin

Dosage Forms

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

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); 1.5 mg (1 ea)

Brand Names: U.S.

  • Flolan
  • Veletri

Pharmacologic Category

  • Prostacyclin
  • Prostaglandin
  • Vasodilator

Pharmacology

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.

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

Excretion

Urine (84%); feces (4%)

Half-Life Elimination

~6 minutes

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.

Off Label Uses

Acute respiratory distress syndrome, refractory moderate to severe

Data from a limited number of patients studied suggest that inhaled epoprostenol (iEPO) may be beneficial for the treatment of refractory hypoxia secondary to acute respiratory distress syndrome. In these retrospective studies, iEPO was found to be equally as effective as inhaled nitric oxide for this indication [Ammar 2015], [Buckley 2020], [Torbic 2013].

Acute vasodilator testing in pulmonary arterial hypertension

Based on the American College of Cardiology Foundation/American Heart Association (ACCF/AHA) expert consensus document on pulmonary hypertension, epoprostenol may be used as an alternative agent (inhaled nitric oxide is preferred) for acute vasodilator testing to identify those patients with pulmonary arterial hypertension with a better prognosis and who will likely have a sustained response to oral calcium channel blockers (eg, high-dose ER nifedipine) which have been shown to increase survival. Response to acute vasodilator testing is currently defined as a reduction in mean pulmonary artery pressure (mPAP) of ≥10 mm Hg, to an absolute mPAP <40 mm Hg, with an unchanged or increased cardiac output. Of note, acute vasodilator testing is not recommended and may be harmful in patients with significantly elevated left heart filling pressures [ACCF/AHA [McLaughlin 2009]].

Guidelines from the European Society of Cardiology and the European Respiratory Society recommends testing only in patients with idiopathic, heritable, or drug-induced PAH [ESC/ERS [Galiè 2016]].

Post-cardiothoracic surgery complicated by pulmonary hypertension, right ventricular dysfunction, or refractory hypoxemia

A prospective, open-label trial of cardiac surgery patients who developed postoperative pulmonary hypertension, right heart dysfunction, or refractory hypoxemia supports the use of inhaled epoprostenol for improving hemodynamic parameters and hypoxemia (De Wet 2004). A small prospective randomized trial and 2 retrospective studies in cardiac surgery patients displayed similar improvements in hemodynamic parameters [Fattouch 2005], [Groves 2014], [McGinn 2016].

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).

Dosing: Adult

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

Inhalation, continuous: 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: 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 within 4 to 6 hours as tolerated (Buckley 2020).

Weight-based: Initial: 10 or 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 (Ammar 2015; Dzierba 2014; Torbic 2013).

Acute vasodilator testing in patients with pulmonary arterial hypertension (off-label use): Note: Acute vasodilator testing should only be done in patients who might be considered candidates for calcium channel blocker therapy.

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 (ACCF/AHA [McLaughlin 2009]; ESC/ERS [Galiè 2016])

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

Inhalation, continuous: 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: 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 (De Wet 2004; McGinn 2016).

Weight-based dose: 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 (Ammar 2015; Dzierba 2014; Sabato 2017; Torbic 2013).

Pulmonary arterial hypertension:

Note: A clinician with expertise in pulmonary arterial hypertension should be consulted for all management decisions. Epoprostenol is the recommended prostacyclin in high risk patients with severe symptoms (eg, World Health Organization functional class IV) (ACCP [Klinger 2019]; Galie 2019).

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 (ACCF/AHA [McLaughlin 2009]).

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 (Alkukhun 2014; Mouratoglou 2020; Reisbig 2005).

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 (Mouratoglou 2020).

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 (Mouratoglou 2020).

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

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

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

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 (AHA/ATS [Abman 2015]).

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) (Davis 2017).

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 (Dahlem 2004). 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 (Brown 2012).

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

Reconstitution

Preparation of Epoprostenol Infusion

To make solution with concentration:

Flolan

Instructions

Veletri or Caripul

Instructions

Note: Flolan may only be prepared with sterile diluent provided. If using pH 12 sterile diluent for Flolan, then avoid materials containing polyethylene terephthalate (PET) or polyethylene terephthalate glycol (PETG) for preparation.

Note: Veletri or Caripul 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 0.5 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.

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.

Dissolve one 0.5 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.

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.

Dissolve two 0.5 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.

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 (De Wet 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.

Administration

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: If Flolan reconstituted using pH 12 sterile diluent for Flolan, then 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 (Ammar 2018; De Wet 2004; Dzierba 2014). Note: Flolan or Veletri may be used for this route of administration (Hawn 2018; Rao 2018; Torbic 2016). 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 (De Wet 2004; Dzierba 2014).

Storage

Flolan: Prior to use, store intact vials and diluent at 15°C to 25°C (59°F to 77°F); do not freeze. Protect from light. Following reconstitution, solution must be stored at 2°C to 8°C (36°F to 46°F) if not used immediately; do not freeze. Protect from light. Storage and administration limits for reconstituted solution are dependent on type of diluent use during reconstitution:

Sterile diluent for Flolan: When used at 15°C to 25°C (59°F to 77°F), reconstituted solutions are stable for up to 8 hours following reconstitution or removal from refrigerator. May also be stored for up to 40 hours at 2°C to 8°C (36°F to 46°F) before use. When used with a cold pack, reconstituted solutions are stable for up to 24 hours; may also be stored at 2°C to 8°C (36°F to 46°F) before use as long as the total time of refrigerated storage and infusion does not exceed 48 hours. Change cold packs every 12 hours.

pH 12 sterile diluent for Flolan: Freshly prepared reconstituted solutions or reconstituted solutions that have been stored at 2°C to 8°C (36°F to 46°F) for no longer than 8 days can be administered up to 72 hours at up to 25°C (77°F); 48 hours at up to 30°C (86°F); 24 hours at up to 35°C (95°F); 12 hours at up to 40°C (104°F).

Veletri and Caripul [Canadian product]:

Veletri: Prior to use, store intact vials at 20°C to 25°C (68°F to 77°F); do not freeze. Protect from light. Reconstituted vials must be further diluted prior to use.

Caripul [Canadian product]: Prior to use, store intact vials at 15°C to 30°C (59°F to 86°F); do not freeze. Reconstituted vials must be further diluted prior to use.

Reconstituted solutions of Veletri or Caripul immediately diluted with NS to a final concentration within a drug delivery reservoir may be administered immediately or stored at 2°C to 8°C (36°F to 46°F) for up to 8 days; do not freeze. Protect from light.

If administered immediately, the following maximum durations of administration at room temperature (25°C [77°F]) according to solution concentration are recommended:

US labeling (Veletri):

3,000 to <15,000 ng/mL: 48 hours

15,000 to <60,000 ng/mL: 48 hours

≥60,000 ng/mL: 72 hours

Canadian labeling (Caripul):

3,000 to <15,000 ng/mL: 48 hours

≥15,000: 48 hours

If stored at 2°C to 8°C (36°F to 46°F) for up to 8 days (Veletri or Caripul), the following maximum durations of administration at room temperature (25°C [77°F]) according to solution concentration are recommended:

3,000 to <15,000 ng/mL: 24 hours

15,000 to <60,000 ng/mL: 48 hours

≥60,000 ng/mL: 48 hours

Short excursions at 40°C (104°F) are permitted as follows:

Solution concentration <15,000 ng/mL: Up to 2 hours

Solution concentration 15,000 to <60,000 ng/mL: Up to 4 hours

Solution concentration ≥60,000 ng/mL: Up to 8 hours

The following maximum durations of administration at temperatures >25°C to 40°C (>77°F up to 104°F) administered either immediately or after up to 8 days storage at 2°C to 8°C (36°F to 46°F) according to solution concentration are recommended:

Use at temperature >25°C to 30°C (>77°F up to 86°F):

US labeling (Veletri):

<60,000 ng/mL: 24 hours

≥60,000 ng/mL: 48 hours

Canadian labeling (Caripul): All concentrations: 24 hours

Use at temperature up to 40°C (104°F):

US labeling (Veletri): ≥60,000 ng/mL: 24 hours (immediately administered after preparation)

Drug Interactions

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

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. 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. Consider therapy modification

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

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

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

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

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

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

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

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

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

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

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

Herbs (Hypotensive Properties): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Monitor therapy

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

Levodopa-Containing Products: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. Monitor therapy

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

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

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

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

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

Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. 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. Consider therapy modification

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

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

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

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

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

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

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.

Monitoring Parameters

Monitor for improvements in pulmonary function, decreased exertional dyspnea, fatigue, syncope and chest pain, blood pressure, pulmonary vascular resistance, pulmonary arterial pressure and quality of life. Following establishment of a new chronic infusion rate, measure standing and supine blood pressure 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.

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.

Patient Education

What is this drug used for?

• It is used to treat high blood pressure in the lungs.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Anxiety

• Back pain

• Diarrhea

• Flushing

• Lack of appetite

• Jaw pain

• Bone pain

• Muscle pain

• Joint pain

• Nausea

• Vomiting

• Flu-like symptoms

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Infection

• Bleeding like vomiting blood or vomit that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding.

• Shortness of breath

• Severe dizziness

• Passing out

• Severe headache

• Dark urine

• Chest pain

• Fast heartbeat

• Slow heartbeat

• Abnormal heartbeat

• Pale skin

• Tremors

• Abnormal movements

• Severe loss of strength and energy

• Burning or numbness feeling

• Abdominal swelling

• Skin sores

• Injection site redness

• Swelling

• Severe irritation

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.