The pH of the diluted "ready-to-use solution" decreases with dilution, and ranges from 12.0 for a concentration of 90,000 ng/mL, 11.7 for a concentration of 45,000 ng/mL to 11.0 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.
The medicinal product contains less than 1 mmol sodium (23 mg) per vial, i.e. essentially sodium free.
Veletri is a potent pulmonary and systemic vasodilator. The cardiovascular effects during infusion disappear within 30 min of the end of administration.
Veletri is a potent inhibitor of platelet aggregation, therefore an increased risk for haemorrhagic complications should be considered, particularly for patients with other risk factors for bleeding (see Interactions).
If excessive hypotension occurs during administration of Veletri, the dose should be reduced or the infusion discontinued. Hypotension may be profound in overdose and may result in loss of consciousness (see Overdosage).
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.
Elevated serum glucose levels have been reported (see Adverse Reactions).
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. Veletri must not be used chronically in patients who develop pulmonary oedema during dose initiation (see Contraindications).
Abrupt withdrawal or interruption of infusion must be avoided, except in life-threatening situations. An abrupt interruption of therapy can induce a rebound of pulmonary arterial hypertension, resulting in dizziness, asthenia, increase dyspnoea, and may lead to death (see Dosage & Administration).
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. The decision to administer Veletri for pulmonary arterial hypertension should be based upon the patient's understanding that there is a high likelihood that therapy with Veletri will be needed for prolonged periods, possibly years, and the patient's ability to accept and care for a permanent i.v. catheter and infusion pump should be carefully considered.
Effects on ability to drive and use machines: Pulmonary arterial hypertension and its therapeutic management may affect the ability to drive and operate machinery.