No

Plasma Volume Expander, Colloid; Prostaglandin

Long-term intravenous treatment of primary pulmonary hypertension associated with the scleroderma spectrum of disease in NYHA Class III and IV patients who are not responsive to conventional therapy

B

Chronic use in patients with CHF due to severe left ventricular systolic dysfunction; hypersensitivity to epoprostenol or to structurally-related compounds

Abrupt interruptions or large sudden reductions in dosage may result in rebound pulmonary hypertension; some patients with primary pulmonary hypertension have developed pulmonary edema during dose ranging, which may be associated with pulmonary veno-occlusive disease; during chronic use, unless contraindicated, anticoagulants should be coadministered to reduce the risk of thromboembolism

>10%:

Cardiovascular: Flushing, tachycardia, shock, syncope, heart failure

Central nervous system: Fever, chills, anxiety, nervousness, dizziness, headache, hyperesthesia, pain

Gastrointestinal: Diarrhea, nausea, vomiting

Neuromuscular & skeletal: Jaw pain, myalgia, tremor, paresthesia

Respiratory: Hypoxia

Miscellaneous: Sepsis, flu-like symptoms

1% to 10%:

Cardiovascular: Bradycardia, hypotension, angina pectoris, edema, arrhythmias, pallor, cyanosis, palpitations, cerebrovascular accident, myocardial ischemia, chest pain

Central nervous system: Seizures, confusion, depression, insomnia

Dermatologic: Pruritus, rash

Endocrine & metabolic: Hypokalemia, weight change

Gastrointestinal: Abdominal pain, anorexia, constipation

Hematologic: Hemorrhage

Hepatic: Ascites

Neuromuscular & skeletal: Arthralgias, bone pain, weakness

Hematologic: Disseminated intravascular coagulation

Ocular: Amblyopia

Respiratory: Cough increase, dyspnea, epistaxis, pleural effusion

Miscellaneous: Diaphoresis

Symptoms of overdose include headache, hypotension, tachycardia, nausea, vomiting, diarrhea, and flushing

If any of these symptoms occur, the infusion rate should be reduced until the symptoms subside; if symptoms do not subside should then consider drug discontinuation; no fatal events have been reported following overdosage with epoprostenol

Increased toxicity: The hypotensive effects of epoprostenol may be exacerbated by other vasodilators, diuretics, or by using acetate in dialysis fluids. Patients treated with anticoagulants and epoprostenol should be monitored for increased bleeding risk because of shared effects on platelet aggregation.

Refrigerate ampuls; protect from freezing; prepare fresh solutions every 24 hours;

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.

Steady state levels are reached in about 15 minutes with continuous infusions

Metabolism: Rapidly hydrolyzed at neutral pH in blood and is subject to some enzymatic degradation to one active metabolite, and 13 inactive metabolites

Half-life: 2.7-6 minutes

Elimination: 12% excreted unchanged in urine

I.V.: The drug is administered by continuous intravenous infusion via a central venous catheter using an ambulatory infusion pump; during dose ranging it may be administered peripherally

Continuous chronic infusion: Initial: 4 ng/kg/minute less than the maximum-tolerated infusion rate determined during acute dose ranging

If maximum-tolerated infusion rate is <5 ng/kg/minute, the chronic infusion rate should be 1/2 the maximum-tolerated acute infusion rate

Dosage adjustments: Dose adjustments in the chronic infusion rate should be based on persistence, recurrence, or worsening of patient symptoms of pulmonary hypertension

If symptoms persist or recur after improving, the infusion rate should be increased by 1-2 ng/kg/minute increments, every 15 minutes or greater; following establishment of a new chronic infusion rate, the patient should be observed and vital signs monitored.

Preparation of infusion: To make 100 mL of solution with the following concentrations:

3000 ng/mL:

Dissolve one 0.5 mg vial with 5 mL supplied diluent, withdraw 3 mL, and add to sufficient 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 a sufficient volume of 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 a sufficient volume of 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 a sufficient volume of diluent to make a total of 100 mL.

Using an ambulatory infusion pump, administer a chronic continuous infusion of epoprostenol through a central venous catheter. A peripheral intravenous catheter may be used during acute dose-ranging until central access is established. Consider a multilumen catheter if other intravenous therapies are routinely administered. During extended use at ambient temperatures exceeding 25°C (77°F), cold pouches with frozen gel packs were used during clinical trials.

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 less than or equal to 3 minutes between pulses. The reservoir should be made of polyvinyl chloride, polypropylene, or glass. The infusion pumps used in clinical trials were CADD-1 HFX 5100 (Pharmacia Deltec), Walk-Med 410 C (Medfusion, Inc) and the Auto Syringe AS2F (Baxter HealthCare).

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.

Anxiety, nervousness are common; may cause confusion, insomnia, or depression

Hypotensive effects may be exacerbated by low potency antipsychotics (chlorpromazine) and TCAs

No information available to require special precautions

No effects or complications reported

Therapy on this drug will probably be prolonged, possibly for years. You may experience mild headache, nausea or vomiting, and some muscular pains (use of a mild analgesia may be recommended by your prescriber). 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, or any onset of unresolved diarrhea. Breast-feeding precautions: Consult prescriber if breast-feeding.

Monitor arterial pressure; assess all vital functions; hypoxia, flushing, and tachycardia may indicate overdose. Epoprostenol must be reconstituted with manufacturer-supplied sterile diluent only and when given on an ongoing basis, it must be infused through a permanent indwelling central venous catheter via a portable infusion pump. Instruct patient to report ADRs since dosage adjustments may be necessary.

Injection, as sodium: 0.5 mg/vial and 1.5 mg/vial, each supplied with 50 mL of sterile diluent

Cremona G and Higenbottam T, "Role of Prostacyclin in the Treatment of Primary Pulmonary Hypertension," Am J Cardiol, 1995, 75(3):67A-71A.

Jones DK, Higenbottam TW, and Wallwork J, "Treatment of Primary Pulmonary Hypertension Intravenous Epoprostenol (Prostacyclin)," Br Heart J 1987, 57(3):270-8.

Rich S, "Prostacyclin and Primary Pulmonary Hypertension," Ann Intern Med, 1994, 121(6):463-4.

Rich S, "The Medical Treatment of Primary Pulmonary Hypertension. Proven and Promising Strategies," Chest, 1994, 105(2 Suppl):17S-20S.

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.