Flolan Infusion Of Epoprestenol 500 mcg, 1500 mcg

/ GSK

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.
Following establishment of a new chronic infusion rate, measure standing and supine blood pressure for several hours.
Taper doses of FLOLAN after initiation of cardiopulmonary bypass in patients receiving lung transplants.
See prescribing information for full details.

Long-term intravenous treatment of primary arterial pulmonary hypertension and arterial pulmonary hypertension associated with the scleroderma spectrum of disease in NYHA Class III and Class IV patients who do not respond adequately to conventional therapy.

Patients with heart failure caused by reduced left ventricular ejection fraction.
Patients with a hypersensitivity to the drug or any of its ingredients.

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.
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.

See prescribing information for full details.

Additional reductions in blood pressure may occur when administered with diuretics, antihypertensive agents, or other vasodilators. When other antiplatelet agents or anticoagulants are used concomitantly, there is the potential to increase the risk of bleeding. However, patients receiving infusions in clinical trials were maintained on anticoagulants without evidence of increased bleeding. In clinical trials, it was used with digoxin, diuretics, anticoagulants, oral vasodilators, and supplemental oxygen.
In a pharmacokinetic substudy in patients with congestive heart failure receiving furosemide or digoxin in whom therapy was initiated, apparent oral clearance values for furosemide (n = 23) and digoxin (n = 30) were decreased by 13% and 15%, respectively, on the second day of therapy and had returned to baseline values by day 87. The change in furosemide clearance value is not likely to be clinically significant. However, patients on digoxin may show elevations of digoxin concentrations after initiation of therapy, which although transient may be clinically significant in patients prone to digoxin toxicity.
For full details see prescribing information.

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.
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.
See prescribing information for full details.

Signs and Symptoms: 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.
One patient with PAH/SSD accidentally received 50 mL of an unspecified concentration of FLOLAN. The patient vomited and became unconscious with an initially unrecordable blood pressure. FLOLAN was discontinued and the patient regained consciousness within seconds.
Single intravenous doses of FLOLAN at 10 and 50 mg/kg (2,703 and 27,027 times the recommended acute phase human dose based on body surface area) were lethal to mice and rats, respectively. Symptoms of acute toxicity were hypoactivity, ataxia, loss of righting reflex, deep slow breathing, and hypothermia.
Treatment: Discontinue or reduce dose of FLOLAN.