Epoprostenol - Warnings and Precautions

5 WARNINGS AND PRECAUTIONS • Do not abruptly lower the dose or withdraw dosing.

All dosing initiation and changes should be closely monitored. ( 5.2 , 5.3 ) 5.1 Dose Initiation Epoprostenol is a potent pulmonary and systemic vasodilator.

Initiate epoprostenol 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.

5.2 Chronic Use and Dose Adjustment During chronic use, deliver epoprostenol continuously on an ambulatory basis through a permanent indwelling central venous catheter.

Unless contraindicated, administer anticoagulant therapy to patients receiving epoprostenol to reduce the risk of pulmonary thromboembolism or systemic embolism through a patent foramen ovale.

To reduce the risk of infection, use aseptic technique in the reconstitution and administration of epoprostenol and in routine catheter care.

Because epoprostenol is metabolized rapidly, even brief interruptions in the delivery of epoprostenol may result in symptoms associated with rebound pulmonary hypertension including dyspnea, dizziness, and asthenia.

Intravenous therapy with epoprostenol will likely be needed for prolonged periods, possibly years, so consider the patient’s capacity to accept and care for a permanent intravenous catheter and infusion pump.

Based on clinical trials, the acute hemodynamic response (reduction in pulmonary artery resistance) to epoprostenol did not correlate well with improvement in exercise tolerance or survival during chronic use of epoprostenol.

Adjust dosage of epoprostenol during chronic use at the first sign of recurrence or worsening of symptoms attributable to pulmonary hypertension or the occurrence of adverse events associated with epoprostenol [see Dosage and Administration ] .

Following dosage adjustments, monitor standing and supine blood pressure and heart rate closely for several hours.

5.3 Withdrawal Effects Abrupt withdrawal (including interruptions in drug delivery) or sudden large reductions in dosage of epoprostenol may result in symptoms associated with rebound pulmonary hypertension, including dyspnea, dizziness, and asthenia.

In clinical trials, one Class III primary pulmonary hypertension patient’s death was judged attributable to the interruption of epoprostenol.

Avoid abrupt withdrawal.