EPOPROSTENOL SODIUM

Posology Epoprostenol is only indicated for continuous infusion by intravenous route. Pulmonary Arterial Hypertension Treatment should only be initiated and monitored by a physician experienced in the treatment of pulmonary arterial hypertension.

Short-term (acute) dose ranging:

This procedure should be conducted in a hospital with adequate resuscitation equipment. A short-term dose-ranging procedure administered via either a peripheral or central venous line is required to determine the long-term infusion rate.

The infusion rate is initiated at 2 nanograms/kg/min and increased by increments of 2 nanograms/kg/min every 15 min or longer until maximum haemodynamic benefit or dose-limiting pharmacological effects are elicited. If the initial infusion rate of 2 nanograms/kg/min is not tolerated, a lower dose which is tolerated by the patient should be identified.

Long-term continuous infusion Long-term continuous infusion of epoprostenol should be administered through a central venous catheter. Temporary peripheral intravenous infusions may be used until central access is established. Long-term infusions should be initiated at 4 nanogram/kg/min less than the maximum tolerated infusion rate determined during short-term dose-ranging.

. If the maximum tolerated infusion rate is 5 nanograms/kg/min or less, then the long-term infusion should be started at 1 nanogram/kg/min. Dose adjustments Changes in the long-term infusion rate should be based on persistence, recurrence or worsening of the patient's symptoms of pulmonary arterial hypertension or the occurrence of adverse events due to excessive doses of epoprostenol.

In general, the need for increases in dose from the initial long-term dose should be expected over time. Increases in dose should be considered if symptoms of pulmonary arterial hypertension persist, or recur after improving. The infusion rate should be increased by 1 to 2 nanograms/kg/min increments at intervals sufficient to allow assessment of clinical response; these intervals should be of at least 15 min.

Following establishment of a new infusion rate, the patient should be observed, and erect and supine blood pressure and heart rate monitored for several hours to ensure that the new dose is tolerated. During long-term infusion, the occurrence of dose-related pharmacological events similar to those observed during the dose-ranging period may necessitate a decrease in infusion rate, but the adverse reactions may occasionally resolve without dose adjustment.

Dose decreases should be made gradually in 2 nanogram/kg/min decrements every 15 minutes or longer until the dose-limiting effects resolve. 4). g. unconsciousness, collapse, etc) infusion rates of epoprostenol should be adjusted only under the direction of a physician.

Renal Dialysis Epoprostenol is suitable for continuous infusion only, either intravascularly or into the blood supplying the dialyser.

The following schedule of infusion has been found effective in adults:

Prior to dialysis: 4 nanograms/kg/min intravenously for 15 mins During dialysis: 4 nanograms/kg/min into the arterial inlet of the dialyser The infusion should be stopped at the end of dialysis. The recommended dose for renal dialysis should be exceeded only with careful monitoring of patient blood pressure.

Elderly There is no specific information on the use of epoprostenol in patients over 65 years for renal dialysis or pulmonary arterial hypertension. In general, dose selection for an elderly patient should be made carefully, reflecting the greater frequency of decreased hepatic, renal (in the case of pulmonary arterial hypertension) or cardiac function and of concomitant disease or other medicinal product therapy.

Paediatric population The safety and efficacy of epoprostenol in children younger than 18 years have not yet been established. Method of administration Preparation of epoprostenol intravenous injectable solution: Reconstituted solutions, prepared in real time, must not be administered over more than 12 hours when they are used at room temperature (between 15°C and 25°C).

They should be kept under 25°C and protected from light. It is possible to refrigerate epoprostenol reconstituted solutions, before they are used at room temperature, ranging between 2°C and 8°C and without exceeding 40 hour storage.

In this case, the solutions should not be used over more than 8 hours when administered at room temperature. The reconstituted solution should be examined prior to administration. Its use is forbidden in the presence of a discoloration or particles.

6). Epoprostenol must not be administered as a bolus injection.

Adverse events are listed below by system organ class and frequency. g. v. catheter*, lassitude, chest tightness Investigations Not known: Blood glucose increased * Associated with the delivery system for epoprostenol. 1 Catheter-related infections caused by organisms not always considered pathogenic (including micrococcus) have been reported.

2 Tachycardia has been reported as a response to epoprostenol at doses of 5 nanograms/kg/min and below. 3 Bradycardia, sometimes accompanied by orthostatic hypotension, has occurred in healthy volunteers at doses of epoprostenol greater than 5 nanograms/kg/min.

v. administration of a dose of epoprostenol equivalent to 30 nanograms/kg/min in healthy conscious volunteers. Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.

It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard) or search for MHRA Yellow Card in Google play or Apple App store.

Because of the high pH of the final infusion solutions, care should be taken to avoid extravasation during their administration and consequent risk of tissue damage. Epoprostenol is a potent pulmonary and systemic vasodilator. The cardiovascular effects during infusion disappear within 30 minutes of the end of administration.

5). If excessive hypotension occurs during administration of epoprostenol, the dose should be reduced or the infusion discontinued. 9). Blood pressure and heart rate should be monitored during administration of epoprostenol. Epoprostenol may either decrease or increase heart rate.

The change is thought to depend on both the basal heart rate and the concentration of epoprostenol administered. The effects of epoprostenol on heart rate may be masked by concomitant use of medicinal products which affect cardiovascular reflexes.

Extreme caution is advised in patients with coronary artery disease. 8). Pulmonary Arterial Hypertension Some patients with pulmonary arterial hypertension have developed pulmonary oedema during dose-ranging, which may be associated with pulmonary veno- occlusive disease.

3). Abrupt withdrawal or interruption of infusion must be avoided, except in life- threatening situations. 2). Epoprostenol is infused continuously through a permanent indwelling central venous catheter via a small, portable infusion pump.

Thus, therapy with epoprostenol requires commitment by the patient to sterile medicinal product reconstitution, medicinal product administration, care of the permanent central venous catheter, and access to intense and ongoing patient education.

Sterile technique must be adhered to in preparing the medicinal product and in the care of the catheter. Even brief interruptions in the delivery of epoprostenol may result in rapid symptomatic deterioration. v. catheter and infusion pump should be carefully considered.

Renal Dialysis The hypotensive effect of epoprostenol may be enhanced by the use of acetate buffer in the dialysis bath during renal dialysis. During renal dialysis with epoprostenol it should be ensured that the cardiac output increases more than minimally so that delivery of oxygen to peripheral tissue is not diminished.

Epoprostenol is not a conventional anticoagulant. Epoprostenol has been successfully used instead of heparin in renal dialysis but in a small proportion of dialyses clotting has developed in the dialysis circuit, requiring termination of dialysis.

When epoprostenol is used alone, measurements such as activated whole blood clotting time may not be reliable. Glycine buffer diluent contains no preservative; consequently a vial should be used once only and then discarded. This medicinal product contains sodium.

See section 2. 5% of the WHO recommended maximum daily intake of 2 g sodium for an adult. To be taken into consideration by patients on a controlled sodium diet.

1. • with congestive heart failure arising from severe left ventricular dysfunction. • Epoprostenol must not be used chronically in patients who develop pulmonary oedema during dose-ranging.