Posology

Veletri 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 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. Temporary peripheral i.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 less than 5 ng/kg/min, the long-term infusion should be started at one-half the maximum tolerated infusion rate.

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. Abrupt withdrawal of Veletri or sudden large reductions in infusion rates should be avoided due to the risk of potentially fatal rebound effect (see section 4.4). Except in life-threatening situations (e.g. unconsciousness, collapse, etc.), 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 prepar