Epoprostenol

VELETRI is indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) to improve exercise capacity. Studies establishing effectiveness included predominantly patients with NYHA Functional Class III–IV symptoms and etiologies of idiopathic or heritable PAH or PAH associated with connective tissue diseases. VELETRI is a prostacyclin vasodilator indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) to improve exercise capacity.

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

Important Note: Reconstitute VELETRI only as directed with Sterile Water for Injection, USP, or Sodium Chloride 0.9% Injection, USP. Do not dilute reconstituted solutions of VELETRI or administer it with other parenteral solutions or medications. Dosage - Infusion of VELETRI should be initiated at 2 ng/kg/min and increased in increments of 2 ng/kg/min every 15 minutes or longer until dose-limiting pharmacologic effects are elicited or until a tolerance limit to the drug is established. - If symptoms of pulmonary hypertension persist or recur after improving - the infusion should be increased 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.

A large study evaluating the effect of epoprostenol on survival in NYHA Class III and IV patients with congestive heart failure due to severe left ventricular systolic dysfunction was terminated after an interim analysis of 471 patients revealed a higher mortality in patients receiving epoprostenol plus conventional therapy than in those receiving conventional therapy alone. The chronic use of VELETRI in patients with congestive heart failure due to severe left ventricular systolic dysfunction is therefore contraindicated. Some patients with pulmonary hypertension have developed pulmonary edema during dose initiation, which may be associated with pulmonary veno-occlusive disease.

Do not abruptly lower the dose or withdraw dosing. All dosing initiation and changes should be closely monitored. Dose Initiation VELETRI is a potent pulmonary and systemic vasodilator. Initiate VELETRI 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 occurred rarely. In such cases, consider dose reduction, but such an increase does not imply that chronic treatment is contraindicated. Chronic Use and Dose Adjustment During chronic use, deliver VELETRI continuously on an ambulatory basis through a permanent indwelling central venous catheter.

Most common adverse reactions during: - Dose Initiation and Escalation: Nausea, vomiting, headache, hypotension, flushing, chest pain, anxiety, dizziness, bradycardia, dyspnea, abdominal pain, musculoskeletal pain, and tachycardia - Chronic Dosing: Headache, jaw pain, flushing, diarrhea, nausea and vomiting, flu-like symptoms, and anxiety/nervousness, or www.fda.gov/medwatch.

Additional reductions in blood pressure may occur when VELETRI is administered with diuretics, antihypertensive agents, or other vasodilators. When other antiplatelet agents or anticoagulants are used concomitantly, there is the potential for VELETRI to increase the risk of bleeding. However, patients receiving infusions of epoprostenol in clinical trials were maintained on anticoagulants without evidence of increased bleeding. In clinical trials, epoprostenol was used with digoxin, diuretics, anticoagulants, oral vasodilators, and supplemental oxygen.

and Stability Unopened vials of VELETRI are stable until the date indicated on the package when stored at 68° to 77°F (20° to 25°C). Reconstitution, Table 1: Maximum duration of administration (hours) at room temperature (77°F/25°C) of fully diluted solutions in the drug delivery reservoir.