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Published in: Advances in Therapy 9/2019

Open Access 01-09-2019 | Parkinson's Disease | Review

Current Practices for Outpatient Initiation of Levodopa-Carbidopa Intestinal Gel for Management of Advanced Parkinson’s Disease in the United States

Authors: Fahd Amjad, Danish Bhatti, Thomas L. Davis, Odinachi Oguh, Rajesh Pahwa, Pavnit Kukreja, Jorge Zamudio, Leonard Verhagen Metman

Published in: Advances in Therapy | Issue 9/2019

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Abstract

In 2015, the US Food and Drug Administration approved levodopa-carbidopa intestinal gel (LCIG; also known as carbidopa-levodopa enteral suspension in the US) for the treatment of motor fluctuations in patients with advanced Parkinson’s disease. LCIG provides a continuous infusion of levodopa and carbidopa by means of a portable pump and percutaneous endoscopic gastrojejunostomy tube. The delivery system has a two-fold pharmacokinetic advantage over orally administered carbidopa/levodopa. First, levodopa is delivered in a continuous rather than intermittent, pulsatile fashion. Second, delivery to levodopa’s site of absorption in the jejunum bypasses the stomach, thereby avoiding issues with erratic gastric emptying. In blinded prospective clinical trials and observational studies, LCIG has been shown to significantly decrease “off” time, increase “on” time without troublesome dyskinesia, and reduce dyskinesia. Consistent with procedures in previous studies, LCIG initiation and titration in the pivotal US clinical trial were performed in the inpatient setting and followed a standardized protocol. In clinical practice, however, initiation and titration of LCIG have a great degree of flexibility and, in the US, almost always take place in the outpatient setting. Nonetheless, there remains a significant amount of clinician uncertainty regarding titration in outpatient clinical practice. This review aims to shed light on and provide guidance as to the current methods of titration in the outpatient setting, as informed by the medical literature and the authors’ experiences.

Funding

AbbVie, Inc.

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Literature
1.
go back to reference Epstein M, Johnson DA, Hawes R, Schmulewitz N, Vanagunas AD, Gossen ER, et al. Long-term PEG-J tube safety in patients with advanced Parkinson’s disease. Clin Transl Gastroenterol. 2016;7:e159.CrossRefPubMedPubMedCentral Epstein M, Johnson DA, Hawes R, Schmulewitz N, Vanagunas AD, Gossen ER, et al. Long-term PEG-J tube safety in patients with advanced Parkinson’s disease. Clin Transl Gastroenterol. 2016;7:e159.CrossRefPubMedPubMedCentral
2.
go back to reference Othman AA, Rosebraugh M, Chatamra K, Locke C, Dutta S. Levodopa–carbidopa intestinal gel pharmacokinetics: lower variability than oral levodopa–carbidopa. J Parkinsons Dis. 2017;7(2):275–8.CrossRefPubMedPubMedCentral Othman AA, Rosebraugh M, Chatamra K, Locke C, Dutta S. Levodopa–carbidopa intestinal gel pharmacokinetics: lower variability than oral levodopa–carbidopa. J Parkinsons Dis. 2017;7(2):275–8.CrossRefPubMedPubMedCentral
3.
go back to reference Verghagen Metman L, Konitsiotis S, Chase TN. Pathophysiology of motor response complications in Parkinson’s disease: hypotheses on the why, where, and what. Mov Disord. 2000;15(1):3–8.CrossRef Verghagen Metman L, Konitsiotis S, Chase TN. Pathophysiology of motor response complications in Parkinson’s disease: hypotheses on the why, where, and what. Mov Disord. 2000;15(1):3–8.CrossRef
4.
go back to reference Kurth MC, Tetrud JW, Tanner CM, Irwin I, Stebbins GT, Goetz CG, et al. Double-blind, placebo-controlled, crossover study of duodenal infusion of levodopa/carbidopa in Parkinson’s disease patients with ‘on-off’ fluctuations. Neurology. 1993;43(9):1698–703.CrossRefPubMed Kurth MC, Tetrud JW, Tanner CM, Irwin I, Stebbins GT, Goetz CG, et al. Double-blind, placebo-controlled, crossover study of duodenal infusion of levodopa/carbidopa in Parkinson’s disease patients with ‘on-off’ fluctuations. Neurology. 1993;43(9):1698–703.CrossRefPubMed
5.
go back to reference Nyholm D, Nilsson Remahl AI, Dizdar N, Constantinescu R, Holmberg B, Jansson R, et al. Duodenal levodopa infusion monotherapy vs oral polypharmacy in advanced Parkinson disease. Neurology. 2005;64(2):216–23.CrossRefPubMed Nyholm D, Nilsson Remahl AI, Dizdar N, Constantinescu R, Holmberg B, Jansson R, et al. Duodenal levodopa infusion monotherapy vs oral polypharmacy in advanced Parkinson disease. Neurology. 2005;64(2):216–23.CrossRefPubMed
6.
go back to reference Olanow CW, Kieburtz K, Odin P, Espay AJ, Standaert DG, Fernandez HH, et al. Continuous intrajejunal infusion of levodopa–carbidopa intestinal gel for patients with advanced Parkinson’s disease: a randomised, controlled, double-blind, double-dummy study. Lancet Neurol. 2014;13(2):141–9.CrossRefPubMed Olanow CW, Kieburtz K, Odin P, Espay AJ, Standaert DG, Fernandez HH, et al. Continuous intrajejunal infusion of levodopa–carbidopa intestinal gel for patients with advanced Parkinson’s disease: a randomised, controlled, double-blind, double-dummy study. Lancet Neurol. 2014;13(2):141–9.CrossRefPubMed
7.
go back to reference Antonini A, Yegin A, Preda C, Bergmann L, Poewe W, Gloria Study Investigators. Global long-term study on motor and non-motor symptoms and safety of levodopa–carbidopa intestinal gel in routine care of advanced Parkinson’s disease patients; 12-month interim outcomes. Parkinsonism Relat Disord. 2015;21(3):231–5.CrossRefPubMed Antonini A, Yegin A, Preda C, Bergmann L, Poewe W, Gloria Study Investigators. Global long-term study on motor and non-motor symptoms and safety of levodopa–carbidopa intestinal gel in routine care of advanced Parkinson’s disease patients; 12-month interim outcomes. Parkinsonism Relat Disord. 2015;21(3):231–5.CrossRefPubMed
8.
go back to reference Fernandez HH, Standaert DG, Hauser RA, Lang AE, Fung VS, Klostermann F, et al. Levodopa–carbidopa intestinal gel in advanced Parkinson’s disease: final 12-month, open-label results. Mov Disord. 2015;30(4):500–9.CrossRefPubMed Fernandez HH, Standaert DG, Hauser RA, Lang AE, Fung VS, Klostermann F, et al. Levodopa–carbidopa intestinal gel in advanced Parkinson’s disease: final 12-month, open-label results. Mov Disord. 2015;30(4):500–9.CrossRefPubMed
9.
go back to reference Slevin JT, Fernandez HH, Zadikoff C, Hall C, Eaton S, Dubow J, et al. Long-term safety and maintenance of efficacy of levodopa–carbidopa intestinal gel: an open-label extension of the double-blind pivotal study in advanced Parkinson’s disease patients. J Parkinsons Dis. 2015;5(1):165–74.PubMed Slevin JT, Fernandez HH, Zadikoff C, Hall C, Eaton S, Dubow J, et al. Long-term safety and maintenance of efficacy of levodopa–carbidopa intestinal gel: an open-label extension of the double-blind pivotal study in advanced Parkinson’s disease patients. J Parkinsons Dis. 2015;5(1):165–74.PubMed
10.
go back to reference Standaert DG, Rodriguez RL, Slevin JT, Lobatz M, Eaton S, Chatamra K, et al. Effect of levodopa–carbidopa intestinal gel on non-motor symptoms in patients with advanced Parkinson’s disease. Mov Disord Clin Pract. 2017;4(6):829–37.CrossRefPubMedPubMedCentral Standaert DG, Rodriguez RL, Slevin JT, Lobatz M, Eaton S, Chatamra K, et al. Effect of levodopa–carbidopa intestinal gel on non-motor symptoms in patients with advanced Parkinson’s disease. Mov Disord Clin Pract. 2017;4(6):829–37.CrossRefPubMedPubMedCentral
11.
go back to reference Antonini A, Poewe W, Chaudhuri KR, Jech R, Pickut B, Pirtosek Z, et al. Levodopa–carbidopa intestinal gel in advanced Parkinson’s: final results of the GLORIA registry. Parkinsonism Relat Disord. 2017;45:13–20.CrossRefPubMed Antonini A, Poewe W, Chaudhuri KR, Jech R, Pickut B, Pirtosek Z, et al. Levodopa–carbidopa intestinal gel in advanced Parkinson’s: final results of the GLORIA registry. Parkinsonism Relat Disord. 2017;45:13–20.CrossRefPubMed
12.
go back to reference Kruger R, Lingor P, Doskas T, Henselmans JML, Danielsen EH, de Fabregues O, et al. An observational study of the effect of levodopa–carbidopa intestinal gel on activities of daily living and quality of life in advanced Parkinson’s disease patients. Adv Ther. 2017;34(7):1741–52.CrossRefPubMedPubMedCentral Kruger R, Lingor P, Doskas T, Henselmans JML, Danielsen EH, de Fabregues O, et al. An observational study of the effect of levodopa–carbidopa intestinal gel on activities of daily living and quality of life in advanced Parkinson’s disease patients. Adv Ther. 2017;34(7):1741–52.CrossRefPubMedPubMedCentral
13.
go back to reference De Fabregues O, Dot J, Abu-Suboh M, Hernandez-Vara J, Ferre A, Romero O, et al. Long-term safety and effectiveness of levodopa–carbidopa intestinal gel infusion. Brain Behav. 2017;7(8):e00758.CrossRefPubMedPubMedCentral De Fabregues O, Dot J, Abu-Suboh M, Hernandez-Vara J, Ferre A, Romero O, et al. Long-term safety and effectiveness of levodopa–carbidopa intestinal gel infusion. Brain Behav. 2017;7(8):e00758.CrossRefPubMedPubMedCentral
14.
go back to reference Odin P, Ray Chaudhuri K, Slevin JT, Volkmann J, Dietrichs E, Martinez-Martin P, et al. Collective physician perspectives on non-oral medication approaches for the management of clinically relevant unresolved issues in Parkinson’s disease: consensus from an international survey and discussion program. Parkinsonism Relat Disord. 2015;21(10):1133–44.CrossRefPubMed Odin P, Ray Chaudhuri K, Slevin JT, Volkmann J, Dietrichs E, Martinez-Martin P, et al. Collective physician perspectives on non-oral medication approaches for the management of clinically relevant unresolved issues in Parkinson’s disease: consensus from an international survey and discussion program. Parkinsonism Relat Disord. 2015;21(10):1133–44.CrossRefPubMed
15.
go back to reference Dowell P, Lyons K, Pahwa R. Clinical experience with initiation of carbidopa/levodopa enteral suspension in Parkinson’s disease patients with cognitive impairment. Mov Disord. 2017;32(Suppl 2):S287. Dowell P, Lyons K, Pahwa R. Clinical experience with initiation of carbidopa/levodopa enteral suspension in Parkinson’s disease patients with cognitive impairment. Mov Disord. 2017;32(Suppl 2):S287.
16.
go back to reference Fasano A, Liu LW, Poon YY, Lang AE. Initiating intrajejunal infusion of levodopa/carbidopa intestinal gel: an outpatient model. Mov Disord. 2015;30(4):598–9.CrossRefPubMed Fasano A, Liu LW, Poon YY, Lang AE. Initiating intrajejunal infusion of levodopa/carbidopa intestinal gel: an outpatient model. Mov Disord. 2015;30(4):598–9.CrossRefPubMed
17.
go back to reference Aldred J, Davis T, Zamudio J, Kukreja P, Bergmann L, Li M, et al. Titration of levodopa–carbidopa intestinal gel in US patients with advanced Parkinson’s disease. Mov Disord. 2018;33(Suppl 1):S93. Aldred J, Davis T, Zamudio J, Kukreja P, Bergmann L, Li M, et al. Titration of levodopa–carbidopa intestinal gel in US patients with advanced Parkinson’s disease. Mov Disord. 2018;33(Suppl 1):S93.
18.
go back to reference Solla P, Fasano A, Cannas A, Mulas CS, Marrosu MG, Lang AE, et al. Dopamine agonist withdrawal syndrome (DAWS) symptoms in Parkinson’s disease patients treated with levodopa–carbidopa intestinal gel infusion. Parkinsonism Relat Disord. 2015;21(8):968–71.CrossRefPubMed Solla P, Fasano A, Cannas A, Mulas CS, Marrosu MG, Lang AE, et al. Dopamine agonist withdrawal syndrome (DAWS) symptoms in Parkinson’s disease patients treated with levodopa–carbidopa intestinal gel infusion. Parkinsonism Relat Disord. 2015;21(8):968–71.CrossRefPubMed
19.
go back to reference Lew MF, Slevin JT, Kruger R, Martinez Castrillo JC, Chatamra K, Dubow JS, et al. Initiation and dose optimization for levodopa–carbidopa intestinal gel: insights from phase 3 clinical trials. Parkinsonism Relat Disord. 2015;21(7):742–8.CrossRefPubMed Lew MF, Slevin JT, Kruger R, Martinez Castrillo JC, Chatamra K, Dubow JS, et al. Initiation and dose optimization for levodopa–carbidopa intestinal gel: insights from phase 3 clinical trials. Parkinsonism Relat Disord. 2015;21(7):742–8.CrossRefPubMed
20.
go back to reference Boyd JT, Zadikoff C, Benesh JA, Zamudio J, Robieson WZ, Kukreja P. Safety and efficacy of levodopa–carbidopa monotherapy in patients with advanced Parkinson’s disease. J Neuro Sci. 2017;381(Suppl):182–3.CrossRef Boyd JT, Zadikoff C, Benesh JA, Zamudio J, Robieson WZ, Kukreja P. Safety and efficacy of levodopa–carbidopa monotherapy in patients with advanced Parkinson’s disease. J Neuro Sci. 2017;381(Suppl):182–3.CrossRef
21.
go back to reference Corvol JC, Artaud F, Cormier-Dequaire F, Rascol O, Durif F, Derkinderen P, et al. Longitudinal analysis of impulse control disorders in Parkinson disease. Neurology. 2018;91(3):e189–201.CrossRefPubMedPubMedCentral Corvol JC, Artaud F, Cormier-Dequaire F, Rascol O, Durif F, Derkinderen P, et al. Longitudinal analysis of impulse control disorders in Parkinson disease. Neurology. 2018;91(3):e189–201.CrossRefPubMedPubMedCentral
22.
go back to reference Catalan MJ, Molina-Arjona JA, Mir P, Cubo E, Arbelo JM, Martinez-Martin P, et al. Improvement of impulse control disorders associated with levodopa–carbidopa intestinal gel treatment in advanced Parkinson’s disease. J Neurol. 2018;265(6):1279–87.CrossRefPubMed Catalan MJ, Molina-Arjona JA, Mir P, Cubo E, Arbelo JM, Martinez-Martin P, et al. Improvement of impulse control disorders associated with levodopa–carbidopa intestinal gel treatment in advanced Parkinson’s disease. J Neurol. 2018;265(6):1279–87.CrossRefPubMed
23.
go back to reference Evans AH, Pavese N, Lawrence AD, Tai YF, Appel S, Doder M, et al. Compulsive drug use linked to sensitized ventral striatal dopamine transmission. Ann Neurol. 2006;59(5):852–8.CrossRefPubMed Evans AH, Pavese N, Lawrence AD, Tai YF, Appel S, Doder M, et al. Compulsive drug use linked to sensitized ventral striatal dopamine transmission. Ann Neurol. 2006;59(5):852–8.CrossRefPubMed
24.
go back to reference Tomlinson CL, Stowe R, Patel S, Rick C, Gray R, Clarke CE. Systematic review of levodopa dose equivalency reporting in Parkinson’s disease. Mov Disord. 2010;25(15):2649–53.CrossRefPubMed Tomlinson CL, Stowe R, Patel S, Rick C, Gray R, Clarke CE. Systematic review of levodopa dose equivalency reporting in Parkinson’s disease. Mov Disord. 2010;25(15):2649–53.CrossRefPubMed
25.
go back to reference Pahwa R, Lyons KE. Outpatient titration of carbidopa/levodopa enteral suspension (Duopa). Int J Neurosci. 2017;127(5):459–65.CrossRefPubMed Pahwa R, Lyons KE. Outpatient titration of carbidopa/levodopa enteral suspension (Duopa). Int J Neurosci. 2017;127(5):459–65.CrossRefPubMed
27.
go back to reference Willows T, Dizdar N, Nyholm D, Widner H, Grenholm P, Schmiauke U, et al. Initiation of levodopa–carbidopa intestinal gel infusion using telemedicine (video communication system) facilitates efficient and well-accepted home titration in patients with advanced Parkinson’s disease. J Parkinsons Dis. 2017;7(4):719–28.CrossRefPubMedPubMedCentral Willows T, Dizdar N, Nyholm D, Widner H, Grenholm P, Schmiauke U, et al. Initiation of levodopa–carbidopa intestinal gel infusion using telemedicine (video communication system) facilitates efficient and well-accepted home titration in patients with advanced Parkinson’s disease. J Parkinsons Dis. 2017;7(4):719–28.CrossRefPubMedPubMedCentral
28.
go back to reference Klostermann F, Jugel C, Marzinzik F. Jejunal levodopa infusion in long-term DBS patients with Parkinson’s disease. Mov Disord. 2011;26(12):2298–9.CrossRefPubMed Klostermann F, Jugel C, Marzinzik F. Jejunal levodopa infusion in long-term DBS patients with Parkinson’s disease. Mov Disord. 2011;26(12):2298–9.CrossRefPubMed
29.
go back to reference Burack MA, Santiago A, Biglan K, Barbano R. Levodopa–carbidopa intestinal gel therapy (LCIG) choices and clinical outcomes in DBS-eligible versus palliative stage PD patients. Parkinson Study Group Annual Meeting; September 17–19; Portland, Oregon; 2016. Burack MA, Santiago A, Biglan K, Barbano R. Levodopa–carbidopa intestinal gel therapy (LCIG) choices and clinical outcomes in DBS-eligible versus palliative stage PD patients. Parkinson Study Group Annual Meeting; September 17–19; Portland, Oregon; 2016.
30.
go back to reference Kumar N, Murgai A, Naranian T, Jog M, Fasano A. Levodopa–carbidopa intestinal gel therapy after deep brain stimulation. Mov Disord. 2018;33(2):334–5.CrossRefPubMed Kumar N, Murgai A, Naranian T, Jog M, Fasano A. Levodopa–carbidopa intestinal gel therapy after deep brain stimulation. Mov Disord. 2018;33(2):334–5.CrossRefPubMed
31.
go back to reference Regidor I, Benita V, de Pedro MD, Ley L, Martinez Castrillo JC. Duodenal levodopa infusion for long-term deep brain stimulation-refractory symptoms in advanced Parkinson disease. Clin Neuropharmacol. 2017;40(3):103–7.CrossRefPubMed Regidor I, Benita V, de Pedro MD, Ley L, Martinez Castrillo JC. Duodenal levodopa infusion for long-term deep brain stimulation-refractory symptoms in advanced Parkinson disease. Clin Neuropharmacol. 2017;40(3):103–7.CrossRefPubMed
32.
go back to reference Blaze RL, Tan J, Evans AH. Quantitative assessment of advanced therapies in Parkinson’s disease using the Parkinson kinetigraph (PKG). Mov Disord. 2016;31(Suppl 2):S189. Blaze RL, Tan J, Evans AH. Quantitative assessment of advanced therapies in Parkinson’s disease using the Parkinson kinetigraph (PKG). Mov Disord. 2016;31(Suppl 2):S189.
33.
go back to reference Margolesky J, Luca C. Personal KinetiGraph devices assessing efficacy of continuous enteral carbidopa/levodopa infusion therapy. Mov Disord. 2017;32(Suppl 2):S267. Margolesky J, Luca C. Personal KinetiGraph devices assessing efficacy of continuous enteral carbidopa/levodopa infusion therapy. Mov Disord. 2017;32(Suppl 2):S267.
Metadata
Title
Current Practices for Outpatient Initiation of Levodopa-Carbidopa Intestinal Gel for Management of Advanced Parkinson’s Disease in the United States
Authors
Fahd Amjad
Danish Bhatti
Thomas L. Davis
Odinachi Oguh
Rajesh Pahwa
Pavnit Kukreja
Jorge Zamudio
Leonard Verhagen Metman
Publication date
01-09-2019
Publisher
Springer Healthcare
Published in
Advances in Therapy / Issue 9/2019
Print ISSN: 0741-238X
Electronic ISSN: 1865-8652
DOI
https://doi.org/10.1007/s12325-019-01014-4

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