EPOPROSTENOL

Posology Pulmonary arterial hypertension Epoprostenol is only indicated for continuous infusion by intravenous route. 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. v. infusions may be used until central access is established. Long-term infusions should be initiated at 4 nanograms/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. Dosage 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 reaction 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 dosage adjustment.

Adverse events are listed in the following table by system organ class and frequency. Frequencies are defined as: very common (≥1/10), common (≥ 1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥ 1/10,000 to <1/1000), very rare (<1/10,000) and not known (cannot be estimated from the available data).

g. v. catheter*, lassitude, chest tightness Investigations Not known Blood glucose increased * Associated with the delivery system for epoprostenol 1 Cathether-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 the Google Play or Apple App Store.

4. The osmolality of the diluted solution is between 150 and 350 mOsm/kg. 1). 1). 2 Posology and method of administration Posology Pulmonary arterial hypertension Epoprostenol is only indicated for continuous infusion by intravenous route.

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.

v. infusions may be used until central access is established. Long-term infusions should be initiated at 4 nanograms/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.

Dosage 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 reaction 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.

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