FLOLAN (epoprostenol sodium) for injection

FLOLAN (epoprostenol sodium) for injection

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FLOLAN (epoprostenol sodium) for injection

FLOLAN (epoprostenol sodium) for injection is sterile sodium salt that is a white or off-white powder formulated for intravenous (IV) administration. Each vial of FLOLAN contains epoprostenol sodium equivalent to either 0.5 mg (500,000 ng) or 1.5 mg (1,500,000 ng) epoprostenol, 3.76 mg glycine, 50 mg mannitol, and 2.93 mg sodium chloride. Sodium hydroxide may have been added to adjust pH.

Epoprostenol (PGI2, PGX, prostacyclin), a metabolite of arachidonic acid, is a naturally occurring prostaglandin with potent vasodilatory activity and inhibitory activity of platelet aggregation. The chemical name of epoprostenol is (5Z,9α,11α,13E,15S)-6,9-epoxy-11,15­ dihydroxyprosta-5,13-dien-1-oic acid. Epoprostenol sodium has a molecular weight of 374.45 and a molecular formula of C20H31NaO5.

Indications and usage

FLOLAN is a prostacyclin vasodilator indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group I) to improve exercise capacity. Studies establishing effectiveness included predominantly (97%) patients with NYHA Functional Class III-IV symptoms and etiologies of idiopathic or heritable PAH (49%) or PAH associated with connective tissue diseases (51%).

Mechanism of Action

Epoprostenol has 2 major pharmacological actions: (1) direct vasodilation of pulmonary and systemic arterial vascular beds and (2) inhibition of platelet aggregation.

Dosage and administration

Initiate intravenous infusions of FLOLAN at 2 ng/kg/min. Alter 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.

During dose initiation, asymptomatic increases in pulmonary artery pressure coincident with increases in cardiac output may occur. In such cases, consider dose reduction, but such an increase does not imply that chronic treatment is contraindicated.

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 vasodilatory reactions. In general, expect progressive increases in dose.

If dose-related adverse reactions occur, make dose decreases gradually in 2-ng/kg/min decrements every 15 minutes or longer until the dose-limiting effects resolve. Avoid abrupt withdrawal of FLOLAN or sudden large reductions in infusion rates

Contraindications

FLOLAN is contraindicated in patients with heart failure caused by reduced left ventricular ejection fraction

FLOLAN is contraindicated in patients with a hypersensitivity to the drug or any of its ingredients.

Warnings and precautions

Pulmonary Edema: If the patient develops pulmonary edema during initiation with FLOLAN, discontinue therapy and do not readminister. Consider the possibility of associated pulmonary veno-occlusive disease in such patients.

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Rebound Pulmonary Hypertension following Abrupt Withdrawal: Avoid abrupt withdrawal (including interruptions in drug delivery) or sudden large reductions in dosage of FLOLAN because symptoms associated with rebound pulmonary hypertension (e.g., dyspnea, dizziness, and asthenia) may occur. In clinical trials, one Class III patient’s death was judged attributable to the interruption of FLOLAN.

Vasodilation: FLOLAN is a potent pulmonary and systemic vasodilator and can cause hypotension and other reactions such as flushing, nausea, vomiting, dizziness, and headache. Monitor blood pressure and symptoms regularly during initiation and after dose change

Increased Risk for Bleeding: FLOLAN is a potent inhibitor of platelet aggregation. Therefore, expect an increased risk for hemorrhagic complications, particularly for patients with other risk factors for bleeding.

Side effects

Blood and Lymphatic: Anemia, hypersplenism, pancytopenia, splenomegaly, thrombocytopenia.

Cardiac: High output cardiac failure.

Endocrine and Metabolic: Hyperthyroidism.

Gastrointestinal: Hepatic failure.

Respiratory, Thoracic, and Mediastinal: Pulmonary embolism.

Use in specific populations

Pregnancy: Limited published data from case series and case reports have not established an association with FLOLAN and major birth defects, miscarriage or adverse maternal or fetal outcomes when FLOLAN is used during pregnancy. There are risks to the mother and fetus from untreated pulmonary arterial hypertension

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 the presence of epoprostenol in either human or animal milk, the effects on the breastfed infant, or the effect on milk production.

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for FLOLAN and any potential adverse effects on the breastfed child from epoprostenol or from the underlying maternal condition.

Pediatric Use: Safety and effectiveness in pediatric patients have not been established.

Overdosage

Hypoxemia, hypotension, and respiratory arrest leading to death have been reported in clinical practice following overdosage of FLOLAN.

Excessive doses of FLOLAN were associated with flushing, headache, hypotension, tachycardia, nausea, vomiting, and diarrhea during clinical trials.

Treatment: Discontinue or reduce dose of FLOLAN.

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