Epoprostenol Sodium

Pronunciation: E-poe-PROST-e-nol SOE-dee-um
Class: Peripheral vasodilator

Trade Names

Flolan
- Injection, lyophilized powder 0.5 mg
- Injection, lyophilized powder 1.5 mg

Veletri
- Injection, lyophilized powder 1.5 mg

Pharmacology

Direct vasodilation of pulmonary and systemic arterial vascular beds; inhibition of platelet aggregation.

Slideshow: Flashback: FDA Drug Approvals 2013

Pharmacokinetics

Metabolism

Rapidly hydrolyzed at neutral pH in blood and also undergoes enzymatic degradation. Metabolized to 2 primary active metabolites and several inactive metabolites.

Elimination

The half-life is approximately 6 min. Excreted mostly in the urine and a small amount in the feces.

Indications and Usage

Treatment of primary pulmonary hypertension (PPH) and pulmonary hypertension associated with scleroderma spectrum of disease in New York Heart Association (NYHA) class III and class IV patients who do not respond adequately to conventional therapy.

Contraindications

Long-term use in patients with CHF caused by severe left ventricular systolic dysfunction; long-term use in patients who develop pulmonary edema during dose initiation; hypersensitivity to structurally related compounds or to the drug or any component of the product.

Dosage and Administration

Continuous Chronic Infusion
Adults

IV Initiate infusion at 2 ng/kg/min and increase in increments of 2 ng/kg/min every 15 min or longer until dose-limiting pharmacologic effects are elicited or until a tolerance limit to the drug occurs or further increases are not clinically warranted. If dose-limiting pharmacologic effects occur, then decrease the infusion rate to an appropriate chronic infusion rate that is tolerated. If the initial infusion rate is not tolerated, identify a lower dose that is tolerated.

Increments

Increase infusion by 1 to 2 ng/kg/min increments at intervals sufficient to allow assessment of clinical response (15 min or more).

Decrements

Gradually make 2 ng/kg/min decrements every 15 min or longer until dose-limiting effects resolve. Avoid abrupt withdrawal or sudden large reductions in infusion rates.

General Advice

  • Reconstitute as directed using sterile diluent for epoprostenol. Do not reconstitute or mix with any other parenteral medications or solutions. Reconstitute Veletri using sterile water for injection or sodium chloride 0.9% injection.
  • Must be administered through a central venous catheter only. Temporary peripheral IV infusions may be used until central access is established.
  • Inspect for particulate matter and discoloration prior to administration.
  • Consider increments in dose if symptoms of pulmonary hypertension persist or recur after improving.
  • See manufacturer's prescribing information for recommendations on infusion rates.

Storage/Stability

  • Store unopened epoprostenol and diluent vials between 59° and 77°F. Store Veletri between 68° and 77°F. Protect from light.
  • Store reconstituted solution in refrigerator (36° to 46°F). Do not freeze. Protect from light.
  • Discard any solution that has been refrigerated for more than 48 h or has been frozen.
  • A single dose of Flolan can be administered over 8 h at room temperature, and then must be discarded.
  • Cold pouch administration can be used up to 24 h ( Flolan only).
  • Insulate solution from temperatures higher than 77°F and lower than 32°F.
  • Prior to use, store reconstituted Veletri in a refrigerator (36° to 46°F) for up to 5 days; it may be held at up to 77°F for up to 48 h. Do not freeze. Discard any reconstituted solution that has been frozen, refrigerated for longer than 5 days, or stored at room temperature for more than 48 h.
  • Do not reconstitute or mix with any other parenteral medications or solutions prior to or during administration.

Drug Interactions

Anticoagulants, antiplatelet drugs

May increase risk of bleeding. Clinical and laboratory monitoring is warranted.

Antihypertensives, diuretics, vasodilators

May cause additional reductions in BP. Monitor BP.

Digoxin

Digoxin concentrations may be increased after initiation of therapy with epoprostenol, which may be clinically important in patients prone to digoxin toxicity. Monitor digoxin concentrations and the clinical response. Adjust the digoxin dose as needed.

Adverse Reactions

Cardiovascular

Vascular disorder (95%); palpitations (63%); tachycardia (43%); heart failure (31%); arrhythmia (27%); angina pectoris, hemorrhage (19%); hypotension (16%); bradycardia (15%); syncope (13%); supraventricular tachycardia (8%); shock (5%); cerebrovascular accident, MI (4%); myocardial ischemia (2%).

CNS

Dizziness, headache (83%); anxiety/nervousness/tremor (21%); hyperesthesia/hypesthesia/paresthesia (12%); agitation (11%); insomnia (9%); convulsion, somnolence (4%).

Dermatologic

Collagen disorder (82%); flushing (58%); sweating (41%); skin ulcer (39%); pallor (32%); eczema/rash/urticaria (25%); pruritus (4%).

EENT

Amblyopia (8%); vision abnormality (4%).

GI

Nausea/vomiting (67%); anorexia (66%); esophageal reflux/gastritis (61%); diarrhea (50%); abdominal pain (27%); ascites (23%); constipation (6%); flatulence (5%); abdominal enlargement (4%); dyspepsia (1%).

Genitourinary

UTI (7%); hematuria (5%).

Hematologic-Lymphatic

Hemorrhage (19%); thrombocytopenia (4%); anemia, hypersplenism, pancytopenia, splenomegaly (postmarketing).

Metabolic-Nutritional

Edema/peripheral edema/genital edema (79%); hypercalcemia (48%); weight reduction (45%); hypokalemia, weight gain (6%); hyperkalemia (4%); hyperthyroidism (postmarketing).

Musculoskeletal

Pain/neck pain/arthralgia (84%); jaw pain (75%); arthritis (52%); myalgia (44%); nonspecific musculoskeletal pain (35%); back pain (13%); leg cramps (5%).

Respiratory

Dyspnea (90%); cough increased (82%); hypoxia (55%); cyanosis (54%); epistaxis (9%); pleural effusion, respiratory disorder (7%); pharyngitis, pneumonia (5%); pneumothorax, pulmonary edema, sinusitis (4%).

Miscellaneous

Asthenia (87%); chest pain (67%); chills/fever/flu-like symptoms/sepsis (25%); infection/rhinitis, local infection at injection site (21%); injection-site pain (13%); hepatic failure; pulmonary embolism.

Precautions

Pregnancy

Category B . Placental transfer is unknown; however, it is unlikely that clinically significant amounts reach the fetus.

Lactation

Undetermined.

Children

Safety and efficacy not established.

Elderly

Use caution in dose selection, reflecting greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Abrupt withdrawal

May result in symptoms associated with rebound pulmonary hypertension, including asthenia, dizziness, and dyspnea.

Hemorrhagic complications

Because epoprostenol is a potent platelet inhibitor, increased risk for hemorrhagic complications may exist, particularly in patients with other risk factors for bleeding.

Permanent indwelling central venous catheter

Unless contraindicated, administer anticoagulant therapy to reduce the risk of pulmonary thromboembolism or systemic embolism.

Overdosage

Symptoms

Diarrhea, flushing, headache, hypotension, nausea, tachycardia, vomiting.

Patient Information

  • Instruct patient and family that therapy for PPH may be required for months and even years and that commitment is required for drug reconstitution, drug administration, and proper care of the permanent central venous catheter.
  • Instruct patient that the medication is infused continuously through a permanent indwelling central venous catheter by an infusion pump.
  • Warn patient that even brief interruptions in the delivery of the medication will result in rapid return of symptoms.
  • Provide appropriate instructions for home administration (eg, mixing, administration, rate, catheter care).
  • Advise patient that this therapy is added to, and does not replace, other therapy that has been prescribed for PPH.
  • Advise patients not to change the dose or discontinue therapy unless advised by their health care provider.

Copyright © 2009 Wolters Kluwer Health.

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