epoprostenol (Rx)

>10%

Flushing (58%)

Jaw pain (54%)

Headache (49%)

Myalgia (44%)

Diarrhea (37%)

Nausea (32%)

Vomiting (32%)

Flu-like symptoms (25%)

Eczema (25%)

Rash (25%)

Urticaria (25%)

Hypotension (16%)

Anxiety (11%)

Nervousness (11%)

1-10%

Musculoskeletal pain (2%)

Hyperesthesia (1%)

Tachycardia (1%)

Frequency Not Defined

Hemorrhage

Thrombocytopenia

Postmarketing Reports

Blood and lymphatic: Anemia, hypersplenism, pancytopenia, splenomegaly, thrombocytopenia

Endocrine and Metabolic: Hyperthyroidism

Gastrointestinal: Hepatic failure

Respiratory, Thoracic, and Mediastinal: Pulmonary embolism

Cardiovascular: High output cardiac failure

Contraindications

Hypersensitivity to epoprostenol

Chronic use in patients with CHF due to left ventricular systolic dysfunction

Development of pulmonary edema during initial dose titration

Cautions

Initiate therapy in a setting with adequate personnel and equipment for physiologic monitoring and emergency care; dose initiation has been performed during right heart catheterization and without cardiac catheterization; during dose initiation, asymptomatic increases in pulmonary artery pressure coincident with increases in cardiac output reported rarely; in such cases, consider dose reduction, but such an increase does not imply that chronic treatment is contraindicated

Abrupt withdrawal (including interruptions in drug delivery) or sudden large reductions in dosage may result in symptoms associated with rebound pulmonary hypertension, including dyspnea, dizziness, and asthenia; in clinical trials, death attributable to interruption of therapy reported; avoid abrupt withdrawal

Use caution in patients with risk factors of bleeding

Serious blood stream infectiosn may develop from chronic infusions requiring an indwelling central venous catherer

Asymptomatic increase in pulmonary artery pressure

Some patients may develop pulmonary edema during dosing adjustments

Chronic use and dose adjustment

• During chronic use, deliver drug continuously on an ambulatory basis through a permanent indwelling central venous catheter; unless contraindicated
• Administer anticoagulant therapy to patients receiving therapy to reduce risk of pulmonary thromboembolism or systemic embolism through a patent foramen ovale
• To reduce risk of infection, use aseptic technique in reconstitution and administration of therapy and in routine catheter care
• Because drug is metabolized rapidly, even brief interruptions in delivery of drug may result in symptoms associated with rebound pulmonary hypertension including dyspnea, dizziness, and asthenia
• Intravenous therapy will likely be needed for prolonged periods, possibly years, so consider patient’s capacity to accept and care for a permanent intravenous catheter and infusion pump
• Adjust dosage during chronic use at first sign of recurrence or worsening of symptoms attributable to pulmonary hypertension or occurrence of adverse events associated with drug; following dosage adjustments, monitor standing and supine blood pressure and heart rate closely for several hours

Pregnancy

Limited published data from case series and case reports have not established an association with therapy and major birth defects, miscarriage or adverse maternal or fetal outcomes when treatment is used during pregnancy; there are risks to the mother and fetus from untreated pulmonary arterial hypertension; in animal reproduction studies, pregnant rats and rabbits received epoprostenol sodium during organogenesis at exposures of 2.5 and 4.8 times the maximum recommended human dose (MRHD), respectively, and there was no effect on the fetus

Pregnant women with untreated pulmonary arterial hypertension are at risk for heart failure, stroke, preterm delivery, and maternal and fetal death

Lactation

There are no data on presence of epoprostenol in either human or animal milk, effects on breastfed infant, or on milk production; the developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed child from drug or from underlying maternal condition

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Potent peripheral vasodilator of all vascular beds; also prevents platelet aggregation

Pharmacokinetics

Half-life: 3-6 min

Metabolism: rapidly hydrolyzed in blood to metabolites

Metabolite: 6-keto-prostaglandin F1-alpha (inactive), dihydro-prostaglandin F1-alpha metabolites (unknown activity)

Excretion: Urine (84%); feces (4%)

IV Preparation

Flolan

• 3000 ng/mL: 0.5 mg vial/5 mL mfr supplied sterile diluent; withdraw 3 mL; and add sufficient diluent to make 100 mL
• 5000 ng/mL: 0.5 mg vial/5 mL mfr supplied sterile diluent; withdraw entire vial; and add sufficient diluent to make 100 mL
• 10,000 ng/mL: two 0.5 mg vials each in 5 mL mfr supplied sterile diluent; withdraw entire vial; and add sufficient diluent to make 100 mL
• 15,000 ng/mL: 1.5 mg vial/5 mL mfr supplied sterile diluent; withdraw entire vial; and add sufficient diluent to make 100 mL
• Do not use preparation and administration materials containing polyethylene terephthalate (PET) or polyethylene terephthalate glycol (PETG); PET/PETG products may become damaged when used with Flolan’s mfr supplied with sterile diluent which is alkaline (pH 12)

Veletri

• Reconstituted in vial with only 5 mL of either sterile water for injection or 0.9% NaCl
• Further dilute reconstituted product with same diluent used for reconstitution
• Solutions of 15,000 ng/mL or above may be used for up to 25 hr at room temperature
• Lower concentrations may be used with pump reservoir changed q12hr at room temperature

IV Administration

Continuous IV infusion via central venous catheter using ambulatory infusion pump

Do not mix with any other parenteral medications or solutions prior or during administration

During treatment initiation, may be administered peripherally

Storage

Flolan

• Unopened vials are stable until date indicated on package when stored at room temperature (25 degrees C [77 degrees F]) in carton and protected from light
• Reconstituted vial: May be refrigerated (2-8 degrees C [36-46 degrees F]) for up to 48 hr
• Room temperature administration: When administered at room temperature, reconstituted solutions may be used for no longer than 8 hr
• Use with cold packs: May be administered for up to 24 hr with cold packs (change cold packs q12hr during infusion)
• Do not freeze
• Do not expose to direct sunlight

Veletri

• Unopened vials are stable until date indicated on package when stored at room temperature (25 degrees C [77 degrees F]) in carton and protected from light
• Reconstituted vial: May be refrigerated (2-8 degrees C [36-46 degrees F]) for as long as 5 days or held at up to 25 degrees C (77 degrees F) for up to 48 hr prior to use
• Final solutions of 15,000 ng/mL or above are stable at room temperature (25 degrees C) for up to 24 hr
• Less concentrated final solutions should be used for only 12 hr
• Cold packs are not needed during administration
• Do not freeze
• Do not expose to direct sunlight