Levodopa 50mg / Carbidopa 12.5mg / Entacapone 200mg tablets

BackgroundDevice-aided therapies, such as levodopa-and apomorphine-based infusion pumps, are widely used for managing patients with Parkinson's disease (PD) with symptoms inadequately controlled by oral medications. Cognitive impairment is a critical factor in selecting an appropriate therapy; however, the effects of levodopa/carbidopa intestinal gel (LCIG) and continuous subcutaneous apomorphine infusion (CSAI) on cognitive function remain debated.ObjectiveThe aim of this review is twofold: i) to provide a comprehensive analysis of the short-term benefits of device-aided infusion therapies on cognitive function, and ii) to evaluate their impact on long-term cognitive trajectories.MethodsA systematic literature search was conducted following PRISMA guidelines in PubMed, CINAHL, Cochrane, EMBASE, and MEDLINE. Narrative synthesis was applied to summarize results.ResultsOut of 1911 studies, 33 were included in this systematic review according to the selected criteria. No studies examined the effects of the newly introduced Foslevodopa/Foscarbidopa (LDp/CDp) nor levodopa/entacapone/carbidopa intestinal gel (LECIG) pump therapy. Seventeen studies addressed the short-term effects of CSAI; seven reported cognitive slowing and two were suggestive of positive effects. Only two studies assessed its impact on long-term cognitive trajectory, showing no significant changes. Thirteen studies examined LCIG's short-term effects; seven reported cognitive changes, with some decreases in executive functions. Two studies explored its long-term cognitive impact, with one reporting improvements.ConclusionsThe cognitive effects of device-aided treatments in PD show substantial variability, and their impact on cognitive function, processing speed, attention, and memory is inconsistent, with some studies reporting impairments and others indicating stability or slight improvements. The heterogeneity in study designs, neuropsychological assessments and coexisting vascular and amyloid pathology further complicates interpretation, underscoring the need for more controlled investigations.

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BackgroundMotor fluctuations represent a major therapeutic challenge in Parkinson's disease, particularly among individuals on long-term levodopa therapy. Although diverse pharmacological and device-aided strategies are available, their comparative efficacy, functional benefits, and real-world accessibility-especially in low- and middle-income countries (LMICs)-remain inadequately characterised.MethodologyWe conducted a systematic review of randomised controlled trials, comparative effectiveness studies, and high-quality observational cohorts evaluating pharmacological, surgical, and experimental interventions for motor fluctuations in Parkinson's disease. PubMed and Scopus were searched through 31 May 2025. Eligible studies enrolled adults with idiopathic Parkinson's disease experiencing motor fluctuations despite levodopa therapy and reported outcomes related to OFF/ON-time duration, functional disability (UPDRS-II), and health-related quality of life (PDQ-39 or EQ-5D). Risk of bias was assessed using validated tools, and the certainty of evidence was graded using the GRADE approach. In parallel, we conducted a comparative analysis of drug accessibility across nine Latin American countries (Argentina, Brazil, Chile, Colombia, Costa Rica, Guatemala, Mexico, Panama, and Peru) and the United States, assessing marketing authorisation status and Purchasing Power Parity (PPP)-adjusted prices per Defined Daily Dose (DDD).ResultsNinety-two studies met the inclusion criteria. High-certainty evidence supports the efficacy of extended-release levodopa (IPX066), opicapone, pramipexole, rotigotine, and safinamide in reducing OFF-time, although improvements in functional disability and quality of life were modest or inconsistent. Moderate-certainty evidence supports device-aided therapies, including levodopa-carbidopa intestinal gel (LCIG), subcutaneous foslevodopa-foscarbidopa, and continuous apomorphine infusion, which achieved larger effects on OFF-time and functional outcomes. Deep brain stimulation (DBS) of the globus pallidus internus was adequate but limited by cost and availability in LMICs. The Latin American analysis revealed substantial cross-country disparities: the United States had the widest therapeutic portfolio (19 approved drugs) and generally lower PPP-adjusted prices for advanced formulations. In contrast, several newer therapies-such as IPX066, opicapone, istradefylline, and foslevodopa-foscarbidopa-were unavailable in most Latin American markets, and price differentials for controlled-release or add-on therapies were often several-fold higher after PPP adjustment.ConclusionWhile multiple pharmacological and device-based interventions effectively reduce OFF-time in Parkinson's disease, their real-world impact is constrained by uneven global access and affordability. The Latin American region exemplifies these disparities, with limited regulatory availability, heterogeneous pricing, and insufficient inclusion of novel agents in national formularies. Integrating efficacy evidence with accessibility analyses highlights the need for coordinated regional policies-centred on price regulation, health technology assessment, and equitable funding mechanisms-to ensure that advances in treatment translate into meaningful improvements in function and quality of life for patients with Parkinson's disease worldwide.

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BackgroundMany Parkinson's disease patients receiving oral levodopa/carbidopa experience a troublesome wearing off effect. Higher doses to mitigate OFF-time are limited by adverse effects occurring at peak dopamine levels, particularly dyskinesia. A novel strategy to reduce OFF-time without increasing peak dopamine levels is the continuous subcutaneous infusion of levodopa/carbidopa, or their prodrug equivalents foslevodopa/foscarbidopa.ObjectivesAssess whether subcutaneous infusion therapies safely reduce OFF-time and improve quality of life scores compared to oral levodopa/carbidopa.MethodsWe searched MEDLINE, Embase, CENTRAL and ICTRP up to 28th October 2024 for clinical trials comparing subcutaneous infusions of levodopa or foslevodopa to oral levodopa in Parkinson's disease.ResultsScreening of 1114 records identified seven studies in which 725 patients received subcutaneous infusion regimens of levodopa/carbidopa (ND0612) (407 patients) or foslevodopa/foscarbidopa (318 patients). Moderate quality evidence indicated subcutaneous infusion reduced the daily duration of OFF-time by 1.98 h (p = 0.0004). Moderate quality evidence indicated improvements in health-related quality of life score PDQ-39 (p = 0.0003) and sleep score PDSS-2 (p = 0.02), but an increase in the rate of treatment-emergent adverse events, mostly related to the infusion site (p = 0.04).ConclusionsSubcutaneous infusion therapies produce a clinically and statistically significant reduction in the duration of OFF-time experienced by patients with Parkinson's disease, compared to oral levodopa/carbidopa. Patient experience is improved by a statistically, but not clinically, significant degree. There are increased adverse events, mostly related to the infusion site. Overall, subcutaneous infusion regimens could provide a meaningful alternative for Parkinson's disease patients who experience severe motor fluctuations with existing levodopa formulations.

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