VYALEV

What it is

VYALEV contains foslevodopa and foscarbidopa. Each 1 mL of VYALEV contains foslevodopa 240 mg and foscarbidopa 12 mg, with foslevodopa and foscarbidopa being prodrugs equivalent to approximately 170 mg levodopa and 9 mg carbidopa per 1 mL. VYALEV is a solution for infusion in a glass vial. VYALEV is administered as a continuous subcutaneous infusion, 24 hours per day.

Approved indications

— Treatment of advanced idiopathic Parkinson's disease with severe motor fluctuations despite optimised alternative pharmacological treatment.

Dosing overview

The recommended starting daily dose of VYALEV is determined by converting the daily levodopa intake to levodopa equivalents and then increasing it to account for 24-hour administration, and may be adjusted to reach a clinical response that maximises the functional "On" time and minimises the number and duration of "Off" episodes and "On" episodes with troublesome dyskinesia. The maximum recommended daily dose of foslevodopa is 6000 mg (or 25 mL of VYALEV per day equivalent to approximately 4260 mg levodopa per day). VYALEV is administered subcutaneously, preferably in the abdomen, avoiding a 5 cm radius area from the navel. The infusion set (cannula) can remain in place for up to 3 days when the medication is infused continuously, and the infusion site should be rotated and a new infusion set used at least every 3 days.

Key safety warnings

All patients treated with VYALEV should be monitored carefully for the development of mental changes, depression with suicidal tendencies, and other serious mental changes. Higher frequency of hallucinations can occur in patients treated with dopamine agonists and/or other dopaminergic treatments containing levodopa including VYALEV. VYALEV may induce orthostatic hypotension and should be given cautiously to patients who are taking other medicinal products which may cause orthostatic hypotension. Patients with Parkinson's disease have a higher risk of developing melanoma than the general population, and patients and providers are advised to monitor for melanomas on a regular basis when using VYALEV, with periodic skin examinations performed by appropriately qualified individuals such as dermatologists. Dopamine Dysregulation Syndrome is an addictive disorder resulting in excessive use of the product seen in some patients treated with levodopa/carbidopa, and before initiation of treatment, patients and caregivers should be warned of the potential risk of developing it. VYALEV contains 42.4 mg (approximately 1.84 mmol) of sodium per mL equivalent to 2.1% of the WHO recommended maximum daily dietary intake of sodium, with the maximum daily dose containing 54% of the WHO recommended maximum daily intake, and VYALEV is high in sodium. Infusion site events have been reported in patients receiving VYALEV, and following aseptic techniques while using this medication and frequent rotation of the infusion site are recommended to reduce the risk.

Contraindications

VYALEV is contraindicated in patients with hypersensitivity to foslevodopa and/or foscarbidopa, its active metabolites levodopa and/or carbidopa or to any of the excipients; narrow-angle glaucoma; severe heart failure; acute stroke; severe cardiac arrhythmia; or conditions in which medication with adrenergic activity are contraindicated, such as pheochromocytoma, hyperthyroidism and Cushing's syndrome. Non-selective monoamine oxidase (MAO) inhibitors and selective MAO type A inhibitors are contraindicated for use with VYALEV, and these inhibitors must be discontinued at least two weeks prior to initiating therapy with VYALEV. Because levodopa may activate malignant melanoma, VYALEV should not be used in patients with suspicious undiagnosed skin lesions or a history of melanoma.

PBS listing

VYALEV has not been listed on the Pharmaceutical Benefits Scheme. In May 2024, the PBAC did not recommend listing due to concerns regarding discontinuations in the pivotal trial, uncertainty in cost minimisation inputs, and the need for a Risk Sharing Arrangement.

Regulatory history

VYALEV (foslevodopa 2400 mg/10 mL and foscarbidopa 120 mg/10 mL solution for subcutaneous infusion vial) was first listed on the ARTG on 2024-03-27. This medicinal product is subject to additional monitoring in Australia.