e-poe-PROSS-te-nole

Therapeutic Classification: vasodilators

Pharmacologic Classification: prostaglandins, vasodilators

• Pulmonary arterial hypertension (WHO Group 1).

• A prostaglandin that directly dilates pulmonary and systemic arterial vasculature.
• Also inhibits platelet aggregation.

• Improved exercise capacity.

Absorption: IV administration results in complete bioavailability.

Distribution: Unknown.

Metabolism/Excretion: Rapidly and extensively degraded in plasma; some metabolites are pharmacologically active.

Half-life: ≤6 min.

(hemodynamic effects)

†Following discontinuation.

Contraindicated in:

• Hypersensitivity to epoprostenol or similar compounds
• HF due to severe left ventricular systolic dysfunction
• Patients who develop pulmonary edema during dose initiation.

Use Cautiously in:

• OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk
• Lactation: Use while breastfeeding only if potential maternal benefit justifies potential risk to infant
• Pedi: Safety and effectiveness not established in children.
• Geri: Dose adjustments may be necessary in older adults

CV: chest pain, hypotension, tachycardia, bradycardia.

Derm: flushing, rash, sweating.

GI: abdominal pain, diarrhea, nausea, vomiting.

Hemat: bleeding, thrombocytopenia.

Local: injection site reactions.

MS: jaw pain, myalgia.

Neuro: anxiety, dizziness, headache, hypoesthesia/hyperesthesia/paresthesia.

Resp: dyspnea, pulmonary edema.

Misc: flu-like symptoms.

Drug-Drug:

• Additive hypotension may occur with antihypertensives, diuretics, or other vasodilators.
• Although concurrent use is common and accepted, risk of bleeding may be ↑ by anticoagulants or other agents affecting platelet function.
• May ↑ levels of digoxin.

• IV (Adults): Initiate at 2 ng/kg/min; may ↑ by 1–2 ng/kg/min every 15 min or longer until adequate clinical response. If dose-limiting adverse effects occur, infusion rate may be ↓ in decrements of 2 ng/kg/min at intervals of at least 15 min. Changes in infusion rate should be based upon persistence, recurrence, or worsening of symptoms and/or emergence of adverse reactions. Abrupt withdrawal or large reductions in infusion rate should be avoided.

(Generic available)

• Powder for injection: 0.5 mg/vial; 1.5 mg/vial;

• Monitor hemodynamic parameters (cardiac index, mean pulmonary arterial pressure, pulmonary vascular resistance, total pulmonary resistance, mean systemic arterial pressure) frequently during acute dose ranging and periodically during chronic infusion.
• Acute Dose Ranging: Monitor for dose-limiting side effects (nausea, vomiting, headache, hypotension, flushing, chest pain, anxiety, dizziness, bradycardia, dyspnea, abdominal pain, musculoskeletal pain, tachycardia) frequently.
• Chronic Infusion: Monitor BP (supine and standing) and heart rate closely for several hours after dose adjustments.
  • Make dose adjustments during chronic therapy at first sign of recurrence or worsening of symptoms of pulmonary hypertension or adverse effects of epoprostenol. Most common adverse effects occurring during chronic therapy include headache, jaw pain, flushing, diarrhea, nausea, vomiting, flu-like symptoms, and anxiety.

• May cause thrombocytopenia.

IV Administration:

• Anticoagulant therapy is usually administered concurrently, unless contraindicated, to decrease the risk of pulmonary or systemic embolism.
  • Administer via peripheral infusion during acute dose ranging and by chronic continuous infusion via central venous catheter using a programmable ambulatory infusion pump for chronic administration.
  • Do not use preparation and administration materials containing polyethylene terephthalate or polyethylene terephthalate glycol; may become damaged when used with epoprostenol and diluent.
• Continuous Infusion: Reconstitution: For either the 3000- or 5000-ng/mL concentration, dissolve contents of one 0.5-mg vial with 5 mL of pH 12 sterile diluent for Flolan, or for Veletri, sterile water for injection or 0.9% NaCl. Withdraw 3 mL for the 3000-ng/mL concentration and the entire vial contents for the 5000-ng/mL concentration and add to a sufficient quantity of pH 12 sterile diluent to make a total of 100 mL. Concentration: 3000 ng/mL or 5000 ng/mL.Reconstitution: For the 10,000-ng/mL concentration, dissolve the contents of two 0.5-mg vials with 5 mL each of pH 12 sterile diluent for Flolan, or for Veletri, sterile water for injection or 0.9% NaCl. Withdraw the entire vial contents, and add to a sufficient quantity of sterile diluent to make a total of 100 mL. x Concentration: 10,000 ng/mL.
  Diluent: For the 15,000-ng/mL concentration, dissolve the contents of the 1.5-mg vial with 5 mL of pH 12 sterile diluent for Flolan or with 5 mL of 0.9% NaCl or Sterile Water for Injection if using Veletri. Withdraw the entire contents of the vial, and add to a sufficient quantity of pH 12 sterile diluent to make a total of 100 mL; use same diluent as for reconstitution with Veletri. Use only pH 12 sterile diluent provided by manufacturer for dilution (except with Veletri). Do not reconstitute or mix with any other parenteral medications or solutions. Concentration: 15,000 ng/mL.
  • Do not use materials containing polyethylene terephthalate or polyethylene terephthalate glycol for preparation or administration; may become damaged when used with Flolan prepared with pH 12 sterile diluent for Flolan.
  • May require more than one solution strength during acute dose ranging. Usually 3000 and 10,000 ng/mL are used to deliver an infusion rate between 2–16 ng/kg/min.
  • Unopened vials and reconstituted solutions must be protected from light. Reconstituted solutions are stable for 8 hr at room temperature or 48 hr if refrigerated. Do not freeze. Discard any reconstituted solution that has been frozen, has been refrigerated more than 48 hr, or has been at room temperature for more than 8 hr.
  • Solutions have been administered while in cold pouches. May be administered while in cold pouches with frozen gel packs over 24 hr, with gel packs changed every 12 hr.
• Rate: Infusion rate usually ranges from 2–16 ng/kg/min in adults.

• Home Care Issues: Instruct patient on reconstitution, administration, and care of the permanent central venous catheter.
• Advise patient of the importance of continuous therapy. Inform patient that even brief interruptions of the infusion may cause symptoms of rebound pulmonary hypertension (dyspnea, dizziness, asthenia). Provide patient with access to a backup infusion pump and intravenous infusion sets to prevent potential interruptions in drug delivery. Also inform patients that therapy may be prolonged, possibly lasting years.
• Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

• Increase in cardiac index and stroke volume and decrease in pulmonary vascular resistance, total pulmonary resistance, and mean systemic arterial pressure in patients with pulmonary arterial hypertension.

Flolan, Veletri

Caripul

NDC Code^*

• 0173- GlaxoSmithKline LLC
  • 0173-0517- FLOLAN
    • 0173-0517-00- 1 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION in 1 CARTON (0173-0517-00)

• 0173- GlaxoSmithKline LLC
  • 0173-0519- FLOLAN
    • 0173-0519-00- 1 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION in 1 CARTON (0173-0519-00)

• 0703- Teva Parenteral Medicines, Inc.
  • 0703-1985- Epoprostenol Sodium
    • 0703-1985-01- 1 VIAL in 1 CARTON (0703-1985-01) > 1 INJECTION, POWDER, FOR SOLUTION in 1 VIAL

• 0703- Teva Parenteral Medicines, Inc.
  • 0703-1995- Epoprostenol Sodium
    • 0703-1995-01- 1 VIAL in 1 CARTON (0703-1995-01) > 1 INJECTION, POWDER, FOR SOLUTION in 1 VIAL

• 66215- Actelion Pharmaceuticals US, Inc.
  • 66215-402- Veletri
    • 66215-402-01- 1 VIAL in 1 CARTON (66215-402-01) > 10 mL in 1 VIAL

• 66215- Actelion Pharmaceuticals US, Inc.
  • 66215-403- Veletri
    • 66215-403-01- 1 VIAL in 1 CARTON (66215-403-01) > 10 mL in 1 VIAL