Makindo Medical Notes

About 💊

• Foslevodopa / Foscarbidopa (ABBV-951; brand name Vyalev / Produodopa) is a continuous subcutaneous infusion formulation of levodopa and carbidopa.
• It is licensed in the UK for advanced Parkinson’s disease when motor fluctuations cannot be adequately controlled by oral medication.
• Recommended by NICE TA934 (2024) as an option in advanced PD when oral regimens or apomorphine are unsuitable.
• Delivered by a small worn pump infusing 24 hours/day via a subcutaneous cannula — a less invasive alternative to levodopa–carbidopa intestinal gel (Duodopa).

Mechanism ⚙️

• Both are phosphate prodrugs of levodopa and carbidopa, highly water-soluble, allowing subcutaneous delivery.
• Once absorbed, tissue phosphatases cleave the phosphate groups, releasing active levodopa and carbidopa.
• Carbidopa inhibits peripheral DOPA decarboxylase, allowing more levodopa to reach the brain.
• The result is stable plasma levodopa levels with minimal peaks and troughs — mimicking continuous dopaminergic stimulation.

Clinical Effects 🎯

• Improves “off” time and increases “on” time without troublesome dyskinesia compared with best oral therapy.
• Particularly valuable for patients with severe motor fluctuations or early morning akinesia despite optimal oral regimens.
• Also shown to improve sleep continuity and nocturia symptoms in some studies.

Dosing & Administration 💉

• Delivered as a 24-hour continuous subcutaneous infusion.
• Begun with a loading rate to reach steady levodopa levels, then adjusted to a personalised maintenance rate.
• The pump reservoir is changed daily; the cannula site is rotated every few days.
• Careful titration is required to avoid over-infusion and dyskinesia.

Adverse Effects ⚠️

• Infusion-site reactions (pain, erythema, induration) are most common — usually mild but occasionally lead to site change.
• Typical levodopa-related effects: nausea, orthostatic hypotension, hallucinations, dyskinesias.
• Device issues: line blockage, pump alarms, local infection — require patient training and regular review.
• No new systemic safety signals compared with standard levodopa/carbidopa.

Place in Therapy 🩺

• For patients with advanced PD and motor fluctuations despite optimized oral therapy.
• Alternative when intestinal gel or deep brain stimulation (DBS) are unsuitable or declined.
• Provides the benefits of continuous dopaminergic delivery without gastrointestinal surgery.
• Must be initiated under specialist supervision with support from Parkinson’s nurse specialists.

UK Context 🇬🇧

• Approved by NICE (TA934) and NHS England in 2024 for advanced PD.
• Roll-out underway across specialist centres, supported by training pathways and pump-loan programmes.
• Cost-effectiveness modelling suggests parity or advantage over LCIG in appropriate patients.

Teaching Point 🧠:
Foslevodopa/foscarbidopa represents the next step in “continuous dopaminergic stimulation” — a major principle in managing advanced Parkinson’s disease. By flattening plasma peaks, it reduces motor fluctuation and dyskinesia. As a subcutaneous 24-h infusion, it bridges the gap between oral therapy and invasive intestinal infusions, offering a practical, evidence-based option for patients struggling with unpredictable “off” periods.

References 🔗

• NICE TA934: Foslevodopa/Foscarbidopa for Advanced Parkinson’s Disease
• NHS England News (2024): 24-hour wearable infusion for PD
• Odin et al., Lancet Neurology 2022
• Hauser et al., Mov Disord 2021