VELETRI

Posology Pulmonary Arterial Hypertension VELETRI 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 is initiated at 2 ng/kg/min and increased by increments of 2 ng/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 ng/kg/min is not tolerated, a lower dose that is tolerated by the patient should be identified.

Long-term continuous infusion:

Long-term continuous infusion of VELETRI 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 ng/kg/min less than the maximum tolerated infusion rate determined during short-term dose-ranging.

If the maximum tolerated infusion rate is 5 ng/kg/min or less, the long-term infusion should be started at 1 ng/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 reactions due to excessive doses of VELETRI. 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 ng/kg/min increments at intervals sufficient to allow assessment of clinical response; these intervals should be 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.

Dosage decreases should be made gradually in 2 ng/kg/min decrements every 15 min or longer until the dose-limiting effects resolve. 4). g. ), infusion rates of VELETRI should be adjusted only under the direction of a physician. Renal Dialysis VELETRI 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 ng/kg/min intravenously for 15 mins • During dialysis: 4 ng/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 VELETRI 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 medicine therapy.

Paediatric population The safety and efficacy of VELETRI in children have not yet been established. Method of administration VELETRI long-term administration is administered via intravenous route through central venous catheter using an ambulatory infusion pump.

The patient must be adequately trained in all aspects of care of the central venous catheter, in the aseptic preparation of the VELETRI intravenous injectable solution, and in the preparation and change of the drug delivery reservoir of the infusion pump, and the extension set.

v. 6. 4 and the following as this should help to reduce the risk of catheter-related blood-stream infections. The care of the central venous catheter and the catheter exit site should follow established medical principles. 22 micron filter placed between the infusion pump and the central venous catheter must be used.

It is recommended to use filters with a hydrophilic polyethersulfone membrane. 6).

Preparation of VELETRI intravenous injectable solution:

The reconstituted solution should be examined prior to further dilution. Its use is forbidden in the presence of discolouration or particles. Reconstituted solutions should be immediately further diluted to the final concentration. 6.

VELETRI must not be administered as a bolus injection.

Adverse events are listed below by system organ class and frequency. 01%) and not known (cannot be estimated from the available data). g. v. catheter*, lassitude, chest tightness Investigations Unknown 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 ng/kg/min and below. 3 Bradycardia, sometimes accompanied by orthostatic hypotension, has occurred in healthy volunteers at doses of epoprostenol greater than 5 ng/kg/min.

v. administration of a dose of epoprostenol equivalent to 30 ng/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.

0 for a concentration of 3 000 ng/mL. Therefore, peripheral intravenous use should be restricted to short duration only, using low concentrations. 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.

VELETRI is a potent pulmonary and systemic vasodilator. The cardiovascular effects during infusion disappear within 30 min of the end of administration. 5). If excessive hypotension occurs during administration of VELETRI, the dose should be reduced or the infusion discontinued.

9). Blood pressure and heart rate should be monitored during administration of VELETRI. VELETRI may either decrease or increase heart rate. The change is thought to depend on both the basal heart rate and the infusion rate of VELETRI administered.

The effects of VELETRI on heart rate may be masked by concomitant use of drugs which affect cardiovascular reflexes. Extreme caution is advised in patients with coronary artery disease. 8). The solvent contains no preservative; consequently a vial should be used once only and then discarded.

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). VELETRI is infused continuously through a permanent indwelling central venous catheter via a small, portable infusion pump. Thus, therapy with VELETRI requires commitment by the patient to sterile drug reconstitution, drug administration, care of the permanent central venous catheter, and access to intense and ongoing patient education.

Aseptic conditions must be adhered to in preparing the drug and in the care of the catheter. Even brief interruptions in the delivery of VELETRI may result in rapid symptomatic deterioration. v. catheter and infusion pump should be carefully considered.

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

VELETRI 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. Sodium This medicinal product contains less than 1 mmol sodium (23 mg) per vial, that is to say essentially 'sodium--free'.

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