Foslevodopa+foscarbidopa for advanced Parkinson disease

Background:
The main pharmacological approach for managing Parkinson disease is enhancing dopaminergic stimulation in the striatum, primarily with oral levodopa, a dopamine precursor. People with advanced Parkinson disease often experience fluctuations in their response to oral levodopa, which can manifest as shorter response ('wearing off'), delayed response, no response, and involuntary movements (dyskinesias).¹

When motor symptoms are inadequately controlled with oral levodopa and other oral and transdermal drugs, patients may benefit from a 'device-assisted therapy'. Examples include subcutaneous apomorphine solution and intestinal levodopa gel, administered by infusion using a portable programmable pump.¹ Device-assisted drug therapies provide continuous stimulation of dopaminergic receptors in the brain, therefore reducing motor complications. Foslevodopa+foscarbidopa solution for subcutaneous infusion is a new device-assisted treatment option for advanced Parkinson disease.

Mechanism of action:
Foslevodopa (levodopa-4´-monophosphate) and foscarbidopa (carbidopa-4´-monophosphate) are highly soluble prodrugs that, upon subcutaneous infusion, rapidly undergo enzymatic conversion to levodopa and carbidopa. Levodopa is converted to dopamine in the brain, where it stimulates dopamine receptors and relieves symptoms of Parkinson disease. Carbidopa, which does not cross the blood–brain barrier, inhibits the extracerebral decarboxylation of levodopa to dopamine, thus making more levodopa available for transportation to the brain and reducing peripheral dopaminergic adverse effects.²

Clinical trials:
A 12-week phase 3 randomised, double-blind, active-controlled study compared foslevodopa+foscarbidopa continuous subcutaneous infusion (plus oral placebo) with levodopa+carbidopa oral immediate-release tablets (plus placebo infusion) in 141 patients (mean age 66 years) with advanced Parkinson disease and at least 2.5 hours of average daily 'off time'.³ All participants completed an oral levodopa+carbidopa dose stabilisation period before the main study. Patients randomised to the oral levodopa+carbidopa group were not allowed any further dose adjustments throughout the 12-week study period. Patients in the foslevodopa+foscarbidopa group had a 4-week dose optimisation period, after which their dose could not be adjusted over the next 8 weeks. Non–levodopa-containing concomitant drugs for Parkinson disease (e.g. dopamine agonists, monoamine oxidase B inhibitors, amantadine) were allowed to continue in both groups.

Compared with the oral levodopa+carbidopa group, patients who received subcutaneously infused foslevodopa+foscarbidopa had more 'on time without troublesome dyskinesia' (mean difference 1.75 hours per day, 95% confidence interval [CI] 0.46 to 3.05 hours), and less 'off time' (mean difference 1.79 hours per day, 95% CI 0.54 to 3.03 hours). Fewer patients in the foslevodopa+foscarbidopa infusion group had morning akinesia compared with the oral levodopa+carbidopa group (17% versus 63%). Withdrawal from the trial was more common in the foslevodopa+ foscarbidopa group (35.1%) than the levodopa+carbidopa group (7.5%), mostly due to adverse effects and difficulty with the drug delivery system.³

There have been no head-to-head clinical trials comparing foslevodopa+foscarbidopa with other device-assisted therapies,^1,4 but subcutaneously infused foslevodopa+foscarbidopa has been shown to be bioequivalent to intestinally infused levodopa+carbidopa gel in healthy adults.⁵

Dosage and administration:
Foslevodopa+foscarbidopa is administered subcutaneously, usually in the abdomen, as a continuous infusion (24 hours per day) using a portable infusion pump (Vyafuser^TM). The cannula should be replaced, and infusion site rotated, at least every 3 days.²

The recommended starting daily dose is determined by converting the patient's daily levodopa and catechol-O-methyl transferase (COMT) inhibitor (e.g. entacapone) intake to 'levodopa equivalents', then increasing it to account for 24-hour administration (detailed instructions are provided in the Product Information).² A loading dose can be administered immediately prior to commencing the infusion to quickly achieve symptomatic control when starting therapy in an 'off' state (or if the pump has been off for more than 3 hours). Patients initiating therapy in the 'on' state may start the infusion without a loading dose.²

Once the infusion is established, the dose is adjusted to reach a clinical response that maximises functional 'on' time and minimises 'troublesome dyskinesia' and 'off' episodes.²

If enabled by their healthcare professional, the infusion pump allows patients to self-administer an extra dose to manage acute 'off' symptoms experienced during continuous infusion (no more than once per hour). If 5 or more extra doses are used in a 24-hour period, a revision of the base continuous infusion rate should be considered.

The infusion pump also allows for 2 alternative infusion rate options to be programmed for patient use, to account for changes in functional demand (e.g. lower dosage at night-time or increased dosage for prolonged intense activity).

The maximum recommended foslevodopa dose is 6000 mg per day, which is equivalent to 4260 mg of levodopa.²

Adverse effects:
Adverse effects are consistent with those experienced with oral levodopa (e.g. hallucinations, nausea, orthostatic hypotension, falls, anxiety, insomnia and sudden sleep onset); however, the incidence may be higher with subcutaneous foslevodopa due to its higher bioavailability.⁵ Infusion-site events are common and may include pain, erythema, oedema, bruising, nodule, infection and cellulitis.²

Precautions:
Precautions are consistent with oral levodopa. For example, use foslevodopa+foscarbidopa with caution in people with psychosis or cardiovascular disease, and those who are taking other drugs that have dopamine receptor–blocking properties or may cause orthostatic hypotension. Monitor for the development of serious mental changes including depression with suicidal tendencies.²

Practice points:
Initiation of foslevodopa+foscarbidopa, like other device-assisted therapies, requires neurologist involvement, usually through a specialist movement disorder centre. Oral levodopa and COMT inhibitors should not be used concomitantly with foslevodopa+foscarbidopa. Other oral and transdermal drugs for Parkinson disease can be used concurrently if required.²

Place in therapy:
Device-assisted therapies are considered when patients have severe motor fluctuations despite optimised oral and topical drug treatment. Foslevodopa+foscarbidopa provides an alternative to apomorphine for subcutaneous infusion,⁴ and it may be preferred over levodopa+carbidopa intestinal gel infusion because subcutaneous infusion is less invasive and easier to discontinue if response is insufficient or adverse effects occur (intestinal infusion requires surgical placement of a percutaneous endoscopic gastrostomy tube with jejunal extension).¹

This new drug comment was finalised on 17 February 2026. It was prepared by Rohan Elliott, Senior Clinical Editor, Australian Prescriber, and reviewed by Nadia Mouchaileh, Senior Aged Care Pharmacist, Austin Health, Melbourne.

At the time this new drug comment was prepared, the Australian Public Assessment Report was available from the Therapeutic Goods Administration. The sponsor did not provide the Clinical Evaluation Report.

This article is peer reviewed.

 

References

1. Mouchaileh N, Cameron J. Device-assisted therapies for Parkinson disease. Aust Prescr 2025;48:10-7.
2. Therapeutic Goods Administration. Australian Product Information - VYALEV foslevodopa 2400 mg/10 mL and foscarbidopa 120 mg/10 mL solution for subcutaneous infusion vial. Department of Health, Disability and Ageing; 2024. [cited 2026 Feb 17]
3. Soileau MJ, Aldred J, Budur K, Fisseha N, Fung VS, Jeong A, et al. Safety and efficacy of continuous subcutaneous foslevodopa-foscarbidopa in patients with advanced Parkinson's disease: a randomised, double-blind, active-controlled, phase 3 trial. Lancet Neurol 2022;21:1099-109.
4. Aubignat M, Tir M. Continuous subcutaneous foslevodopa-foscarbidopa in Parkinson's disease: a mini-review of current scope and future outlook. Mov Disord Clin Pract 2024;11:1188-94.
5. Therapeutic Goods Administration. Australian Public Assessment Report for Vyalev. 2024. [cited 2026 Feb 17]

 

The new drug comments in Australian Prescriber are prepared by the editors and reviewed by subject matter experts. Some of the views expressed on newly approved products should be regarded as preliminary, as there may be limited published data at the time of publication, and little experience in Australia of their safety or efficacy. Before new drugs are prescribed, it is important that more detailed information is obtained from the approved product information, a medicines information centre or some other appropriate source.

Report all suspected adverse reactions to new drugs to enable continued monitoring of their benefit–harm balance.