Levodopa 20mg/ml / Carbidopa 5mg/ml / Entacapone 20mg/ml intestinal gel 47ml cartridges

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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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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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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Background/Objectives: Non-motor symptoms (NMS) are highly prevalent in advanced Parkinson's disease (PD) and substantially affect quality of life. Continuous infusion therapies are established treatment options for motor fluctuations not controlled by oral medication, but their effects on NMS remain incompletely characterized. We aimed to evaluate the effects of continuous infusion therapies on NMS in advanced PD. Methods: A systematic review was conducted according to PRISMA guidelines. PubMed, Embase, and Cochrane were searched for English-language original studies published between January 2005 and 1 March 2026. Eligible studies included patients with PD treated with levodopa-carbidopa intestinal gel (LCIG), continuous subcutaneous apomorphine infusion (CSAI), subcutaneous levodopa formulations, or levodopa-entacapone-carbidopa intestinal gel (LECIG) and reported quantitative NMS outcomes. Due to methodological heterogeneity, results were synthesized qualitatively. Results: Fifty-four studies were included. Most evaluated LCIG (n = 38), followed by CSAI (n = 14), subcutaneous levodopa formulations (n = 6), and LECIG (n = 2). Overall, 4157 patients were assessed at baseline and 2919 at follow-up. Global non-motor burden improved in 33/45 (73.3%) baseline-to-follow-up comparisons. NMSS total score decreased from 84.4 ± 35.2 to 54.9 ± 17.6. The most consistent benefits were observed for sleep/fatigue and gastrointestinal symptoms. Sleep/fatigue outcomes improved in 26/31 (83.9%) baseline-to-follow-up comparisons. Cognitive outcomes were mostly stable, while cardiovascular, urinary, sexual, and mood-specific outcomes showed less consistent benefit. Conclusions: Continuous infusion therapies may be associated with reduced global non-motor burden in advanced PD, particularly sleep/fatigue and gastrointestinal symptoms. Evidence is strongest for LCIG, while data for CSAI, LECIG, and subcutaneous levodopa formulations remain limited.

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ObjectiveIPX203 is a newly approved oral carbidopa-levodopa formulation designed to prolong the therapeutic effect and reduce complications associated with the standard immediate-release formulation. Immediate-release carbidopa-levodopa remains the current standard of care but has a short duration of action. This study aimed to evaluate the efficacy and safety of IPX203 compared with immediate-release carbidopa-levodopa in patients with advanced Parkinson's disease.MethodsThis systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and was registered in the International Prospective Register of Systematic Reviews (registration number: CRD42024623230). A comprehensive search of PubMed/MEDLINE, Cochrane Central Register of Controlled Trials, Web of Science, ScienceDirect, Scopus, and Embase identified randomized controlled trials comparing IPX203 with immediate-release carbidopa-levodopa. The primary outcomes were changes from baseline in "Good On-time" (periods of effective symptom control with minimal dyskinesia) and "Off-time" (periods when medication effects wear off and symptoms return). Secondary outcomes included scores on Part III of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale and adverse events.ResultsA total of 466 records were screened, resulting in the inclusion of three randomized controlled trials involving 560 participants. Compared with immediate-release carbidopa-levodopa, IPX203 increased total "Good On-time" and reduced "Off-time." Scores on Part III of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale demonstrated greater improvement in motor function with IPX203. The incidence of adverse events was comparable between the two groups, although treatment-emergent adverse events and treatment discontinuations were more frequent in the IPX203 group.ConclusionCompared with immediate-release carbidopa-levodopa, IPX203 increased "Good On-time," reduced "Off-time," improved motor function as measured by Part III of the Movement Disorder Society-Unified Parkinson's Disease Rating Scale, and demonstrated a comparable safety profile.

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BackgroundLevodopa-carbidopa intestinal gel infusion (LCIG) is an effective therapy for advanced Parkinson's disease (PD). Opicapone (OPC) is an enzyme inhibitor that enhances the bioavailability of levodopa in the brain.ObjectivesThis study evaluates the effect of Opicapone addition in PD-LCIG patients, assessing its impact on motor fluctuations and dyskinesias. Secondly, the study analyses the impact of OPC on non-motor symptoms, LCIG dosage, and peripheral neuropathy.MethodsIn this pilot study, 22 PD patients on LCIG were randomized to receive OPC or not, based on persistent or reemergent fluctuations. The Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Unified Dyskinesia Rating Scale (UDysRS), Montreal Cognitive Assessment (MoCA), electroneurography (ENG), LCIG doses, homocysteine, vitamin B12, and folic acid levels were measured at baseline (T0) and after 12 months (T1).ResultsEleven patients added OPC (addOPC group), while 11 maintained standard treatment (nOPC group). At baseline, both groups had similar disease duration and severity. At T1, the addOPC group showed significant: (i) improvement in motor fluctuations evaluated by the MDS-UPDRS part IV; (ii) reduction in dyskinesias (UDyRS); (iii) decrease in LCIG infusion rate; (iv) improvement in motor and non-motor symptoms (MDS-UPDRS parts I-III); (v) increase in Vitamin B12. No significant differences were observed in the ENG data, and no serious adverse events occurred. Four addOPC patients (36%) discontinued OPC after 15 ± 2 months, mainly due to hallucinations.ConclusionsOPC addition appeared well tolerated and beneficial in reducing motor fluctuations, dyskinesia, and LCIG dose. Randomized controlled trials are needed to confirm these findings.

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Background: In levodopa-treated individuals with Parkinson's disease (PD) and end-of-dose motor fluctuations, the BIPARK-I randomized controlled trial (RCT) demonstrated that opicapone is noninferior to entacapone in reducing OFF-time. Furthermore, the BIPARK-II RCT demonstrated that opicapone is well tolerated and significantly reduces OFF-time compared with placebo. This study developed a cost-effectiveness model (CEM) of opicapone compared with entacapone from the perspective of the English National Health Service (NHS) and personal social services (PSS). Methods: The CEM used a Markov model with three health states, including "Results: The deterministic base case indicates that an individual treated with opicapone accrues fewer costs and more QALYs compared with each entacapone comparator and, therefore, is considered cost-effective. The PSA indicates that the probability that opicapone is cost-effective ranges from 87.2% to 98.0%, depending on the choice of entacapone comparator. Conclusions: Opicapone is cost-effective when compared with entacapone for levodopa-treated PD patients experiencing end-of-dose motor fluctuations. Trial Registration: ClinicalTrials.gov identifier: NCT01568073.

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