Continuous subcutaneous foslevodopa/foscarbidopa infusion for the treatment of motor fluctuations in Parkinson’s disease: Considerations for initiation and maintenance

Clinical Parkinsonism & Related Disorders, Journal Year: 2024, Volume and Issue: 10, P. 100239 - 100239

Published: Jan. 1, 2024

As Parkinson's disease (PD) advances, management is challenged by an increasingly variable and inconsistent response to oral dopaminergic therapy, requiring special considerations the provider. Continuous 24 h/day subcutaneous infusion of foslevodopa/foscarbidopa (LDp/CDp) provides steady stimulation that can reduce symptom fluctuation. Our aim review initiation, optimization, maintenance LDp/CDp identify possible challenges, share potential mitigations. Review available clinical trial data for practical regarding patients during therapy based on investigator experience. be done without hospitalization in clinic setting. offer more precise control than medications, showing improvements motor fluctuations both daytime nighttime hours. Challenges include infusion-site adverse events which early detection prompt may required, as well systemic (eg, hallucinations) require adjustment rate or other interventions. A learning curve should anticipated with initiation expectation setting care partners key successful therapy. represents a promising therapeutic option individuals PD. Individualized dose optimization hours, coupled patient education, recognition certain (plus their appropriate management) are required success this minimally invasive highly efficacious

Language: Английский

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Levodopa Pharmacokinetics in Switching from Levodopa/Carbidopa Intestinal Gel to Continuous Subcutaneous Foslevodopa/Foscarbidopa Infusion in a Patient with Parkinson's Disease: a case report

Journal of Movement Disorders, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 6, 2025

Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor symptoms including bradykinesia, rigidity, tremor, and postural instability [1].In advanced stages, PD patients often suffer from fluctuations due to narrowed therapeutic window, some of whom will be suitable candidates for device-aided therapies

Language: Английский

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Neutrophil‐Rich Infusion Site Reactions After Continuous Subcutaneous Application of Foslevodopa/Foscarbidopa

Movement Disorders, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 11, 2025

We read with great interest the article by Yoshihara et al.,1 which provides insight into histopathologic features of cutaneous side effects caused continuous subcutaneous injection foslevodopa/foscarbidopa. Using a similar approach, we analyzed skin biopsies from two female patients Parkinson's disease (PD) who developed an inflammatory site reaction 11 and 13 weeks, respectively, after initiating treatment Notably, our findings differ those reported al., revealing neutrophil-rich infiltrate. Akinetic-rigid type, duration 24 years, Hoen Yahr scale (H&Y) 4 ON, 5 OFF severe motor fluctuations dyskinesia, optic hallucinations PD dementia, previously treated apomorphine for 3 immediate change to foslevodopa/foscarbidopa due not well-controlled increasing delusion. Good improvement dyskinesia. After weeks (foslevodopa total dose 2592 mg, day rate 0.50 mL/hr, night 0.35 cannula frequency [initially] days) oval, tender, poorly demarked, dome-shaped, erythematous swelling was noted around infusion (Fig. 1A,B). Patient denied itching or pain. 15 H&Y 6 months (cessation insufficient persistent nausea), start 8 later very good She painless, plaque measuring cm in diameter 2861 0.52 0.45 2 days, relevant concomitant medication opicapone 50 mg 1×/day). Histopathologic examination both cases revealed patchy infiltrate deep dermis extending tissue, composed primarily neutrophils mixed lymphocytes few eosinophils 1C,D). In contrast findings, al. described adverse reactions as lymphocyte-dominant infiltrates adipose tissue. Interestingly, eosinophil-rich panniculitis has been observed response subcutaneously administered apomorphine,2 suggesting that cellular components immune responses drug application may vary significantly. This notion is supported fact broad clinical spectrum effects, including erythema, edema, cellulitis, panniculitis, nodule formation, abscess regimens.3, Infusion can be minimized following best practices, rotating sites, using sterile technique, ensuring proper skincare hygiene, monitoring reactions, educating their caregivers.5 However, further studies involving larger cohorts are needed better understand pathophysiology, identify risk factors, explore potential prevention strategies effects. Research Project: A. Conception Design, B. Organization, C. Execution; (2) Statistical Analysis: Execution, Review Critique; (3) Manuscript Preparation: Writing First Draft, Critique. D.W.: 1A, 1C, 2B, 3A, 3B. S.H.: D.W. received honoraria advisory boards speaker engagements AbbVie, BIAL, Ever Pharma, Stadapharm. S.H. AbbVie. The data support this study available corresponding author upon reasonable request.

Language: Английский

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Invasive therapies for Parkinson’s disease: an adapted excerpt from the guidelines of the German Society of Neurology

Journal of Neurology, Journal Year: 2025, Volume and Issue: 272(3)

Published: Feb. 22, 2025

Abstract Background Parkinson’s disease (PD) is characterized by hypokinetic motor symptoms, tremor, and various non-motor symptoms with frequent fluctuations of in advanced stages. Invasive therapies, such as deep brain stimulation (DBS), ablative continuous subcutaneous or intrajejunal delivery dopaminergic drugs via pump therapies are available for the management this complex symptomatology may also impact symptoms. The recent update clinical guideline on PD German Neurological Society (Deutsche Gesellschaft für Neurologie e.V.; DGN) offers clear guidance indications applications these treatment options. Methods committee formulated diagnostic questions invasive structured them according to PICOS framework (Population–Intervention–Comparisons–Outcome–Studies). A systematic literature review was conducted. Questions were addressed using findings from consented committee. Results Specific recommendations given regarding (i) optimal timing starting (ii) application DBS, (iii) use PD, (iv) procedures, selecting most appropriate therapy individual patient characteristics. Conclusion This an adapted excerpt chapters novel PD. Clear options provided.

Language: Английский

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Subcutaneous Levodopa: A New Engine for the Vintage Molecule

Neurology and Therapy, Journal Year: 2024, Volume and Issue: 13(4), P. 1055 - 1068

Published: June 14, 2024

The management of Parkinson's disease (PD) continues to evolve with advancements in non-oral levodopa-based therapies aiming provide continuous drug delivery (CDD). Such address the challenges posed by emergence motor fluctuations, dyskinesias, and non-motor fluctuations (NMF) associated oral levodopa administration contributing define advanced stage PD. key focus this review is placed on subcutaneous foslevodopa/foscarbidopa (Foslevodopa/foscarbidopa) infusion, showcasing its recent clinical availability efficacy providing delivery. While an overview other CDD systems, such as intrajejunal levodopa–carbidopa infusion levodopa–entacapone–carbidopa we highlight current promising evidence for Foslevodopa/foscarbidopa improve, example, "on time" without troublesome dyskinesia reducing "off people Additionally, demonstrates potential managing early morning off periods, sleep quality symptoms. Moreover, options ND0612 DIZ102/DIZ101 are discussed, their pharmacokinetics/pharmacodynamics, efficacy, safety profiles. these present new therapeutic avenues, long-term observational studies warranted elucidate impact existing PD therapies. Overall, provides insights into evolving landscape offers a pragmatic approach integration practice.

Language: Английский

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Continuous Subcutaneous Foslevodopa‐Foscarbidopa in Parkinson's Disease: A Mini‐Review of Current Scope and Future Outlook

Movement Disorders Clinical Practice, Journal Year: 2024, Volume and Issue: 11(10), P. 1188 - 1194

Published: July 11, 2024

Abstract Background Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by motor and non‐motor symptoms, primarily because of the impairment dopaminergic neurons. Long‐term use levodopa, standard PD treatment, often results in fluctuating therapeutic effects dyskinesia, necessitating alternative therapies. Objectives This review aims to synthesize current insights clinical experiences with foslevodopa‐foscarbidopa, focusing on its pharmacokinetics, efficacy, safety profile, evaluate potential transforming therapy. Methods A systematic literature search was conducted up November 2023 using databases PubMed, Web Science, Cochrane Library. The yielded eight eligible articles, including pharmacological studies, case reports, observational controlled trials. No language restrictions were applied. Results Foslevodopa foscarbidopa, as prodrugs levodopa carbidopa, exhibited excellent chemical stability solubility, facilitating continuous subcutaneous infusion. Clinical trials demonstrated that these maintain stable levels, thereby addressing limitations oral Phase 1 3 studies indicated significant improvements function quality life advanced patients. However, higher incidence treatment‐emergent adverse events, mainly infusion site reactions, observed compared Conclusions Foslevodopa‐foscarbidopa emerges promising for offering sustained symptom control. Its efficacy managing fluctuations dyskinesia makes it viable option spectrum. Future research should focus long‐term safety, economic impact, broader accessibility. now commercially distributed many countries Europe Japan.

Language: Английский

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What was first and what is next in selecting device-aided therapy in Parkinson’s disease? Balancing evidence and experience

Journal of Neural Transmission, Journal Year: 2024, Volume and Issue: 131(11), P. 1307 - 1320

Published: May 15, 2024

Language: Английский

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Improved Sleep Correlates with Improved Quality of Life and Motor Symptoms with Foslevodopa/Foscarbidopa

Movement Disorders Clinical Practice, Journal Year: 2024, Volume and Issue: 11(7), P. 861 - 866

Published: March 11, 2024

Abstract Background Foslevodopa/foscarbidopa is a subcutaneous infusion of levodopa/carbidopa prodrugs. Objectives Assess correlations between sleep and efficacy from interim data phase 3 trial foslevodopa/foscarbidopa (NCT03781167). Methods Pearson (Parkinson's Disease Sleep Scale‐2 [PDSS‐2]) quality life (QoL; Parkinson's Questionnaire‐39), motor experiences daily living (m‐EDL; Movement Disorder Society‐Unified Scale Part II), “Off”/“On” times were calculated for baseline week 26 improvements. Regression analyses adjusted PDSS‐2 score. Results Baseline correlated moderately with QoL ( r = 0.44, P < 0.001) weakly m‐EDL 0.28; 0.001). improvement improved “Off” time 0.37; 0.36; demonstrated significant positive associations sleep, time, QoL, m‐EDL. Conclusions Improved was associated time.

Language: Английский

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Advanced therapies in Parkinson’s disease: an individualized approach to their indication

Journal of Neural Transmission, Journal Year: 2024, Volume and Issue: 131(11), P. 1285 - 1293

Published: April 13, 2024

Device aided therapies (DAT) comprising the intrajejunal administration of levodopa/carbidopa intestinal gel (LCIG) and levodopa/carbidopa/entacapone (LECIG), continuous subcutaneous application foslevodopa/foscarbidopa or apomorphine infusion (CSAI) deep brain stimulation (DBS) are used to treat Parkinson's disease with insufficient symptom alleviation under intensified pharmacotherapy. These DAT significantly differ in their efficacy profiles, indication, invasiveness, contraindications, potential side effects. Usually, evaluation all these procedures is conducted simultaneously at same point time. However, as progression burden extremely heterogeneous, clinical experience shows that patients reach individual milestones for a certain therapy different points course. Therefore, advocating an individualized each DAT, requiring ongoing evaluation. This necessitates that, during consultation, current symptomatology should be analyzed, suitability assessed. work represents critical interdisciplinary appraisal terms profiles compares regarding periprocedural considerations well motor- non-motor deficits, supporting personalized approach.

Language: Английский

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Levodopa infusion therapies for Parkinson disease

Current Opinion in Neurology, Journal Year: 2024, Volume and Issue: 37(4), P. 409 - 413

Published: May 23, 2024

Purpose of review to recent progress in the development and use continuous levodopa therapies Parkinson disease (PD). Recent findings Levodopa/Carbidopa intestinal gel (LCIG) is a therapy which widely used United States, Europe other countries effective at reducing ‘off’ time. work has shown that LCIG can be useful managing dyskinesias improve nonmotor symptoms quality life. Several studies have good long-term effectiveness LCIG. data support cost-effectiveness this treatment strategy. Subcutaneous (SC) delivery newer strategy avoids need for surgically placed gastric tube. Two different products enabling SC are development: ND0612 foslevodopa/foscarbidopa. Both recently been reduce time randomized, double-blind trials. Adverse effects primarily related skin reactions infusion site. Summary Continuous treat motor fluctuations cannot managed with standard oral therapies. They may also symptoms, overall life patients advanced PD.

Language: Английский

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