Epoprostenol

Epoprostenol
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Gerald Chi

Disclaimer

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Overview

Epoprostenol is a prostaglandin that is FDA approved for the {{{indicationType}}} of pulmonary arterial hypertension. Common adverse reactions include bradyarrhythmia, chest pain, hypotension, tachycardia, flushing, abdominal pain, diarrhea, loss of appetite, nausea, vomiting, dizziness, and headache.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Pulmonary Arterial Hypertension

• Important Note: Epoprostenol sodium for injection must be reconstituted only with STERILE DILUENT for epoprostenol sodium for injection. Do not dilute reconstituted solutions of epoprostenol for injection or administer with other parenteral solutions or medications.

• Dosing Information

• Administer continuous chronic infusion of epoprostenol sodium for injection through a central venous catheter. Temporary peripheral intravenous infusion may be used until central access is established. Initiate chronic infusion of epoprostenol sodium for injection at 2 ng/kg/min and increase in increments of 2 ng/kg/min every 15 minutes or longer until dose-limiting pharmacologic effects are elicited or until a tolerance limit to the drug is established or further increases in the infusion rate are not clinically warranted (see Dosage Adjustments). If dose-limiting pharmacologic effects occur, then decrease the infusion rate until epoprostenol sodium for injection is tolerated. In clinical trials, the most common dose-limiting adverse events were nausea, vomiting, hypotension, sepsis, headache, abdominal pain, or respiratory disorder (most treatment-limiting adverse events were not serious). If the initial infusion rate of 2 ng/kg/min is not tolerated, identify a lower dose that is tolerated by the patient.

• In the controlled 12-week trial in PAH/SSD, for example, the dose increased from a mean starting dose of 2.2 ng/kg/min. During the first 7 days of treatment, the dose was increased daily to a mean dose of 4.1 ng/kg/min on day 7 of treatment. At the end of week 12, the mean dose was 11.2 ng/kg/min. The mean incremental increase was 2 to 3 ng/kg/min every 3 weeks.

• Dosage Adjustments

• Base changes in the chronic infusion rate on persistence, recurrence, or worsening of the patient's symptoms of pulmonary hypertension and the occurrence of adverse events due to excessive doses of epoprostenol sodium for injection. In general, expect increases in dose from the initial chronic dose.
• Consider increments in dose if symptoms of PAH persist or recur. Increase the infusion by 1- to 2-ng/kg/min increments at intervals sufficient to allow assessment of clinical response; these intervals should be at least 15 minutes. In clinical trials, incremental increases in dose occurred at intervals of 24 to 48 hours or longer. Following establishment of a new chronic infusion rate, observe the patient, and monitor standing and supine blood pressure and heart rate for several hours to ensure that the new dose is tolerated.
• During chronic infusion, the occurrence of dose-limiting pharmacological events may necessitate a decrease in infusion rate, but the adverse event may occasionally resolve without dosage adjustment. Make dosage decreases gradually in 2-ng/kg/min decrements every 15 minutes or longer until the dose-limiting effects resolve. Avoid abrupt withdrawal of epoprostenol sodium for injection or sudden large reductions in infusion rates. Except in life-threatening situations (e.g., unconsciousness, collapse, etc.), adjust infusion rates of epoprostenol sodium for injection only under the direction of a physician.
• In patients receiving lung transplants, doses of epoprostenol sodium for injection were tapered after the initiation of cardiopulmonary bypass.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Epoprostenol in adult patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Epoprostenol in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

• Safety and effectiveness in pediatric patients have not been established.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Epoprostenol in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Epoprostenol in pediatric patients.

Contraindications

• A large study evaluating the effect of epoprostenol on survival in NYHA Class III and IV patients with congestive heart failure due to severe left ventricular systolic dysfunction was terminated after an interim analysis of 471 patients revealed a higher mortality in patients receiving epoprostenol plus conventional therapy than in those receiving conventional therapy alone. The chronic use of epoprostenol in patients with congestive heart failure due to severe left ventricular systolic dysfunction is therefore contraindicated.
• Some patients with pulmonary hypertension have developed pulmonary edema during dose initiation, which may be associated with pulmonary veno-occlusive disease. Epoprostenol should not be used chronically in patients who develop pulmonary edema during dose initiation.
• Epoprostenol is also contraindicated in patients with known hypersensitivity to the drug or to structurally related compounds.

Warnings

• Description

Precautions

• Description

Adverse Reactions

Clinical Trials Experience

There is limited information regarding Clinical Trial Experience of Epoprostenol in the drug label.

Body as a Whole

Cardiovascular

Digestive

Endocrine

Hematologic and Lymphatic

Metabolic and Nutritional

Musculoskeletal

Neurologic

Respiratory

Skin and Hypersensitivy Reactions

Special Senses

Urogenital

Miscellaneous

Postmarketing Experience

There is limited information regarding Postmarketing Experience of Epoprostenol in the drug label.

Body as a Whole

Cardiovascular

Digestive

Endocrine

Hematologic and Lymphatic

Metabolic and Nutritional

Musculoskeletal

Neurologic

Respiratory

Skin and Hypersensitivy Reactions

Special Senses

Urogenital

Miscellaneous

Drug Interactions

• Drug

• Description

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA):

• Pregnancy Category

Pregnancy Category (AUS):

• Australian Drug Evaluation Committee (ADEC) Pregnancy Category

There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Epoprostenol in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Epoprostenol during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Epoprostenol with respect to nursing mothers.

Pediatric Use

There is no FDA guidance on the use of Epoprostenol with respect to pediatric patients.

Geriatic Use

There is no FDA guidance on the use of Epoprostenol with respect to geriatric patients.

Gender

There is no FDA guidance on the use of Epoprostenol with respect to specific gender populations.

Race

There is no FDA guidance on the use of Epoprostenol with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Epoprostenol in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Epoprostenol in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Epoprostenol in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Epoprostenol in patients who are immunocompromised.

Administration and Monitoring

Administration

• Intravenous

Administration

• Epoprostenol sodium for injection is administered by continuous intravenous infusion via a central venous catheter using an ambulatory infusion pump. During initiation of treatment, epoprostenol sodium for injection may be administered peripherally.
• The ambulatory infusion pump used to administer epoprostenol sodium for injection should: (1) be small and lightweight, (2) be able to adjust infusion rates in 2-ng/kg/min increments, (3) have occlusion, end-of-infusion, and low-battery alarms, (4) be accurate to ±6% of the programmed rate, and (5) be positive pressure-driven (continuous or pulsatile) with intervals between pulses not exceeding 3 minutes at infusion rates used to deliver epoprostenol sodium for injection. The reservoir should be made of polyvinyl chloride, polypropylene, or glass. The infusion pump used in the most recent clinical trials was the CADD-1 HFX 5100 (SIMS Deltec). A 60-inch microbore non-DEHP extension set with proximal antisyphon valve, low priming volume (0.9 mL), and in-line 0.22 micron filter was used during clinical trials.
• To avoid interruptions in drug delivery, the patient should have access to a backup infusion pump and intravenous infusion sets. Consider a multi-lumen catheter if other intravenous therapies are routinely administered.
• To facilitate extended use at ambient temperatures exceeding 20° to 25°C (68° to 77°F), a cold pouch with frozen gel packs was used in clinical trials (see DOSAGE AND ADMINISTRATION: Storage and Stability). The cold pouches and gel packs used in clinical trials were obtained from Palco Labs, Palo Alto, California. Any cold pouch used must be capable of maintaining the temperature of reconstituted epoprostenol sodium for injection between 2° and 8°C for 12 hours.

Reconstitution

• Epoprostenol sodium for injection is stable only when reconstituted with STERILE DILUENT for epoprostenol sodium for injection. Epoprostenol sodium for injection must not be reconstituted or mixed with any other parenteral medications or solutions prior to or during administration.
• Select a concentration for the solution of epoprostenol sodium for injection that is compatible with the infusion pump being used with respect to minimum and maximum flow rates, reservoir capacity, and the infusion pump criteria listed above. * When administered chronically, prepare epoprostenol sodium for injection in a drug delivery reservoir appropriate for the infusion pump with a total reservoir volume of at least 100 mL, using 2 vials of STERILE DILUENT for epoprostenol sodium for injection for use during a 24-hour period. Table 6 gives directions for preparing several different concentrations of epoprostenol sodium for injection.

This image is provided by the National Library of Medicine.

• Generally, 3,000 ng/mL and 10,000 ng/mL are satisfactory concentrations to deliver between 2 to 16 ng/kg/min in adults. Infusion rates may be calculated using the following formula:

This image is provided by the National Library of Medicine.

• Tables 7 through 10 provide infusion delivery rates for doses up to 16 ng/kg/min based upon patient weight, drug delivery rate, and concentration of the solution of epoprostenol sodium for injection to be used. These tables may be used to select the most appropriate concentration of epoprostenol sodium for injection that will result in an infusion rate between the minimum and maximum flow rates of the infusion pump and that will allow the desired duration of infusion from a given reservoir volume. Higher infusion rates, and therefore, more concentrated solutions may be necessary with long-term administration of epoprostenol sodium for injection.

This image is provided by the National Library of Medicine.

Monitoring

There is limited information regarding Monitoring of Epoprostenol in the drug label.

• Description

IV Compatibility

There is limited information regarding IV Compatibility of Epoprostenol in the drug label.

Overdosage

Acute Overdose

Signs and Symptoms

• Description

Management

• Description

Chronic Overdose

There is limited information regarding Chronic Overdose of Epoprostenol in the drug label.

Pharmacology

Mechanism of Action

Structure

This image is provided by the National Library of Medicine.

Pharmacodynamics

There is limited information regarding Pharmacodynamics of Epoprostenol in the drug label.

Pharmacokinetics

There is limited information regarding Pharmacokinetics of Epoprostenol in the drug label.

Nonclinical Toxicology

There is limited information regarding Nonclinical Toxicology of Epoprostenol in the drug label.

Clinical Studies

There is limited information regarding Clinical Studies of Epoprostenol in the drug label.

How Supplied

• Epoprostenol sodium for injection is supplied as a sterile freeze-dried powder in 10 mL flint glass vials with gray butyl rubber closures, individually packaged in a carton.

This image is provided by the National Library of Medicine.

• Store the vials of epoprostenol sodium for injection at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Protect from light. Retain in carton until time of use. Discard unused portion.
• The STERILE DILUENT for Epoprostenol Sodium for Injection is supplied in flint glass vials containing 50 mL diluent with butyl rubber closures.

This image is provided by the National Library of Medicine.

• Storage and Stability

• Unopened vials of epoprostenol sodium for injection are stable until the date indicated on the package when stored at 20° to 25°C (68° to 77°F) and protected from light in the carton. Unopened vials of STERILE DILUENT for epoprostenol sodium for injection are stable until the date indicated on the package when stored at 20° to 25°C (68° to 77°F).
• Prior to use, reconstituted solutions of epoprostenol sodium for injection must be protected from light and must be refrigerated at 2° to 8°C (36° to 46°F) if not used immediately. Do not freeze reconstituted solutions of epoprostenol sodium for injection. Discard any reconstituted solution that has been frozen. Discard any reconstituted solution if it has been refrigerated for more than 48 hours.
• During use, a single reservoir of reconstituted solution of epoprostenol sodium for injection can be administered at room temperature for a total duration of 8 hours, or it can be used with a cold pouch and administered up to 24 hours with the use of 2 frozen 6 oz gel packs in a cold pouch. When stored or in use, insulate reconstituted epoprostenol sodium for injection from temperatures greater than 25°C (77°F) and less than 0°C (32°F), and do not expose to direct sunlight.

• Use at Room Temperature

• Prior to use at room temperature, 15° to 25°C (59° to 77°F), reconstituted solutions of epoprostenol sodium for injection may be stored refrigerated at 2° to 8°C (36° to 46°F) for no longer than 40 hours. When administered at room temperature, reconstituted solutions may be used for no longer than 8 hours. This 48-hour period allows the patient to reconstitute a 2-day supply (200 mL) of epoprostenol sodium for injection. Each 100 mL daily supply may be divided into 3 equal portions. Two of the portions are stored refrigerated at 2° to 8°C (36° to 46°F) until they are used.

• Use with a Cold Pouch

• Prior to infusion with the use of a cold pouch, solutions may be stored refrigerated at 2° to 8°C (36° to 46°F) for up to 24 hours. When a cold pouch is employed during the infusion, reconstituted solutions of epoprostenol sodium for injection may be used for no longer than 24 hours. Change gel packs every 12 hours. Reconstituted solutions may be kept at 2° to 8°C (36° to 46°F), either in refrigerated storage or in a cold pouch or a combination of the two, for no more than 48 hours.
• Inspect parenteral drug products for particulate matter and discoloration prior to administration whenever solution and container permit. If either occurs, do not administer.

Storage

There is limited information regarding Epoprostenol Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Patient Counseling Information of Epoprostenol in the drug label.

Precautions with Alcohol

• Alcohol-Epoprostenol interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

• Veletri®
• Flolan®

Look-Alike Drug Names

• N/A

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

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