Prescribing information For Healthcare Professionals Only

ACTIVE INGREDIENT(S): Epoprostenol

Please refer to the Summary of Product Characteristics (SmPC) before prescribing.

INDICATION(S): Pulmonary Arterial Hypertension (PAH): Veletri is indicated for the treatment of PAH (idiopathic or heritable PAH and PAH associated with connective tissue diseases) in patients with WHO Functional Class III–IV symptoms to improve exercise capacity. Renal Dialysis: Veletri is indicated for use in haemodialysis (HD) in emergency situations when use of heparin carries a high risk of causing or exacerbating bleeding or when heparin is otherwise contraindicated.

DOSAGE & ADMINISTRATION: Veletri is only indicated for continuous infusion by intravenous route (i.v). PAH: Treatment should only be initiated and monitored by a physician experienced in the treatment of PAH. 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 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 (CVC). 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 PAH or the occurrence of adverse reactions (AEs) due to excessive doses of Veletri. Increases in dose should be considered if symptoms of PAH persist or recur after improving. Increase infusion rate by 1- 2 ng/kg/min increments at a minimum interval of 15 mins to allow assessment of clinical response. After establishing a new infusion rate, observe patient and monitor erect and supine blood pressure and heart rate for several hours to ensure 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, adverse reactions may resolve without dosage adjustment. Dosage decreases should be made 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 . Except in life-threatening situations e.g. unconsciousness, collapse, infusion rates of Veletri should be adjusted only under the direction of a physician. Suitable ambulatory pumps and accessories to be used for the administration of VELETRI are provided in section 6.6 of SmPC. Renal Dialysis: Veletri is suitable for continuous infusion only, either intravascularly or into the blood supplying the dialyser. Adult infusion rate: Pre-dialysis: 4 ng/kg/min i.v for 15 mins. During dialysis: 4 ng/kg/min into the arterial line to the dialyser. Stop infusion at the end of dialysis. If exceeding the recommended dose carefully monitor the patient’s blood pressure. Elderly: There is no specific information on the use of Veletri in patients over 65 years for renal dialysis or  PAH. Dose selection for an elderly patient should be made carefully, reflecting the potential decreased hepatic, renal or cardiac function and concomitant disease and medicine therapy. Paediatric population: Safety and efficacy of Veletri in children has not yet been established.

CONTRAINDICATIONS: Hypersensitivity to the active substance or  excipients. In congestive heart failure arising from severe left ventricular dysfunction. Veletri must not be used chronically in patients who develop pulmonary oedema during dose‑ranging.

SPECIAL WARNINGS & PRECAUTIONS: The pH of the diluted 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. Avoid extravasation during administration. 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, hence, potential risk for bleeding, particularly for patients with other risk factors for bleeding. If excessive hypotension occurs during administration the dose should be reduced or the infusion discontinued. Hypotension may be profound in overdose and may result in loss of  consciousness. 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. PAH: Some patients may develop 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. Avoid abrupt withdrawal or interruption of infusion except in life-threatening situations. Abrupt interruption of therapy can induce a rebound of PAH, resulting in dizziness, asthenia, increase dyspnoea, and death. Renal dialysis: The hypotensive effect of Veletri may be enhanced by the use of acetate buffer in the dialysate. 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.

SIDE EFFECTS: Very common; headache, facial flushing, nausea, vomiting, diarrhoea, jaw pain and pain (unspecified). Common; sepsis, septicaemia, decreased platelets, potential bleeding from various sites, anxiety, nervousness, tachycardia, bradycardia, hypotension, abdominal colic, rash, arthralgia, injection site pain and chest pain. Other side effects: Local infection, high output cardiac failure, pulmonary oedema, splenomegaly, hypersplenism, ascites and blood glucose increase. Refer to SmPC for other side effects.

PREGNANCY: There are limited data from the use of epoprostenol in pregnant women. Given the absence of alternative medicines, epoprostenol can be used in those women who choose to continue their pregnancy, despite the known risk of pulmonary arterial hypertension during pregnancy.

LACTATION: It is unknown if epoprostenol or its metabolites are excreted in human milk. A risk to the breastfeeding child cannot be excluded. Breastfeeding should be discontinued during treatment with Veletri.

INTERACTIONS: When administering to patients receiving concomitant anticoagulants, anticoagulant monitoring is advisable. The vasodilator effects of Veletri may augment or be augmented by concomitant use of other vasodilators. As reported with other prostaglandin analogues, Veletri may reduce the thrombolytic efficacy of tissue plasminogen activator (t-PA) by increasing hepatic clearance of t-PA. Concomitant use of NSAIDS or antiplatelet drugs may increase risk of bleeding. Transient elevation of digoxin levels may be clinically significant in patients prone to digoxin toxicity. Refer to SmPC for full details of interactions.

LEGAL CATEGORY: Prescription Only Medicine (POM)

FURTHER INFORMATION IS AVAILABLE FROM THE MARKETING AUTHORISATION HOLDER: Janssen-Cilag Limited, 50-100 Holmers Farm Way, High Wycombe, Buckinghamshire, HP12 4EG, UK.

Prescribing information last revised: March 2020