VELETRI

What it is

VELETRI is a sterile, lyophilised powder for injection containing either 0.5 mg or 1.5 mg of epoprostenol (as sodium) . It is a white to off-white powder that must be reconstituted with either sterile water for injection or with sodium chloride 0.9% solution for injection . VELETRI for Injection is a sterile product formulated for intravenous administration .

Approved indications

VELETRI is indicated for the long-term treatment, via continuous intravenous infusion, in WHO functional class III or class IV patients with: — Idiopathic pulmonary arterial hypertension — Familial pulmonary arterial hypertension — Pulmonary arterial hypertension associated with the scleroderma spectrum of diseases

Dosing overview

The infusion is initiated at 2 ng/kg/min and increased by increments of 2 ng/kg/min every 15 minutes or longer until maximum haemodynamic benefit or dose-limiting pharmacological effects are elicited . 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, then the long-term infusion should be started at 1 ng/kg/min . 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 PAH 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 minutes .

Key safety warnings

Abrupt withdrawal of VELETRI or sudden large reductions in infusion rates must be avoided. An abrupt interruption of therapy can induce a rebound of pulmonary arterial hypertension resulting in dizziness, asthenia, increase in dyspnoea and may lead to death . VELETRI should be used only by clinicians experienced in the diagnosis and treatment of PAH. Short-term dose-ranging with VELETRI must be performed in a hospital setting with adequate personnel and equipment for haemodynamic monitoring and emergency care . Sterile technique must be adhered to in preparing the drug and in the care of the catheter as sepsis is a known associated risk with an indwelling central venous catheter and requires immediate access to expert medical care . Epoprostenol 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 . Extreme caution is advised in patients with coronary artery disease . Because of the high pH of the final infusion solutions, care should be taken to avoid extravasation during administration and consequent risk of tissue damage .

Contraindications

VELETRI is contraindicated in patients with known hypersensitivity to the drug . VELETRI is contraindicated in patients with congestive heart failure arising from severe left ventricular dysfunction, because it was found to increase mortality in such patients . VELETRI should not be used chronically in patients who develop pulmonary oedema during dose-ranging .

PBS listing

VELETRI is listed on the PBS in two strengths: 1.5 mg powder for intravenous infusion at A$59.33 ex-manufacturer price, and 500 microgram powder for intravenous infusion at A$33.28 ex-manufacturer price . Both strengths are restricted medicines requiring authority approval .

Regulatory history

VELETRI was first registered on the ARTG on 28 February 2014 with two registered variants: 500 microgram and 1.5 mg powder for injection vials . In November 2016, the PBAC recommended listing of the new diluent formulation without administration set for pulmonary arterial hypertension .