Is levodopa-carbidopa intestinal gel over- or under-utilized? A review of current evidence.
Main Article Content
Abstract
Levodopa-carbidopa intestinal gel (LCIG) is one of the alternative treatment options for advanced Parkinson disease (PD) patients who experience motor fluctuations and insufficient control of their symptoms despite optimized combinations of oral medications. LCIG is continuously infused through a portable pump into the proximal small intestine, and has been proven to reduce “off” time as well as increase “on” time without significantly worsening troublesome dyskinesias. In addition, growing data also suggest improvement in some non-motor symptoms and the patient’s quality of life. The most common side effects of LCIG are procedural/device-related complications which can be frequent, especially within the first month of device placement, but generally mild and transient in nature. Interestingly, despite its clear efficacy and general safety and tolerability, it has not been utilized by providers to the same extent as other advanced therapies, such as deep brain stimulation surgery (DBS). In this review article, we discuss the evidence supporting LCIG’s efficacy, safety, adverse effects, tolerability, cost-effectiveness as well as potential contraindications. Furthermore, we also re-evaluate LCIG’s indications, utilization and potential limitations.
Keywords:
Levodopa-carbidopa intestinal gel, Parkinson disease, levodopa, motor fluctuations
Article Details
How to Cite
RASAMEESORAJ, Tanaporn et al.
Is levodopa-carbidopa intestinal gel over- or under-utilized? A review of current evidence..
Medical Research Archives, [S.l.], v. 6, n. 2, feb. 2018.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/1595>. Date accessed: 19 apr. 2024.
doi: https://doi.org/10.18103/mra.v6i2.1595.
Section
Review Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
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Lowin, J., Bergman, A., Chaudhuri, K. R., Findley, L. J., Roeder, C., Schifflers, M., . . . Morris, S. (2011). A cost-effectiveness analysis of levodopa/carbidopa intestinal gel compared to standard care in late stage Parkinson's disease in the UK. J Med Econ, 14(5), 584-593. doi:10.3111/13696998.2011.598201
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Nyholm, D., Askmark, H., Gomes-Trolin, C., Knutson, T., Lennernas, H., Nystrom, C., & Aquilonius, S. M. (2003). Optimizing levodopa pharmacokinetics: intestinal infusion versus oral sustained-release tablets. Clin Neuropharmacol, 26(3), 156-163.
Nyholm, D., Nilsson Remahl, A. I., Dizdar, N., Constantinescu, R., Holmberg, B., Jansson, R., . . . Askmark, H. (2005). Duodenal levodopa infusion monotherapy vs oral polypharmacy in advanced Parkinson disease. Neurology, 64(2), 216-223. doi:10.1212/01.wnl.0000149637.70961.4c
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Rascol, O., Brooks, D. J., Korczyn, A. D., De Deyn, P. P., Clarke, C. E., Lang, A. E., & Abdalla, M. (2006). Development of dyskinesias in a 5-year trial of ropinirole and L-dopa. Mov Disord, 21(11), 1844-1850. doi:10.1002/mds.20988
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Sage, J. I., & Mark, M. H. (1994). Pharmacokinetics of continuous-release carbidopa/levodopa. Clin Neuropharmacol, 17 Suppl 2, S1-6.
Sanchez-Castaneda, C., Campdelacreu, J., Miro, J., Juncadella, M., Jauma, S., & Calopa, M. (2010). Cognitive improvement after duodenal levodopa infusion in cognitively impaired Parkinson's disease patients. Prog Neuropsychopharmacol Biol Psychiatry, 34(1), 250-251. doi:10.1016/j.pnpbp.2009.10.021
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Standaert, D. G., Rodriguez, R. L., Slevin, J. T., Lobatz, M., Eaton, S., Chatamra, K., . . . Benesh, J. Effect of Levodopa-carbidopa Intestinal Gel on Non-motor Symptoms in Patients with Advanced Parkinson's Disease. Movement Disorders Clinical Practice, n/a-n/a. doi:10.1002/mdc3.12526
Stocchi, F., Rascol, O., Kieburtz, K., Poewe, W., Jankovic, J., Tolosa, E., . . . Olanow, C. W. (2010). Initiating levodopa/carbidopa therapy with and without entacapone in early Parkinson disease: the STRIDE-PD study. Ann Neurol, 68(1), 18-27. doi:10.1002/ana.22060
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Antonini, A., Yegin, A., Preda, C., Bergmann, L., & Poewe, W. (2015). 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, 21(3), 231-235. doi:10.1016/j.parkreldis.2014.12.012
Bohlega, S., Abou Al-Shaar, H., Alkhairallah, T., Al-Ajlan, F., Hasan, N., & Alkahtani, K. (2015). Levodopa-Carbidopa Intestinal Gel Infusion Therapy in Advanced Parkinson's Disease: Single Middle Eastern Center Experience. Eur Neurol, 74(5-6), 227-236. doi:10.1159/000442151
Caceres-Redondo, M. T., Carrillo, F., Lama, M. J., Huertas-Fernandez, I., Vargas-Gonzalez, L., Carballo, M., & Mir, P. (2014). Long-term levodopa/carbidopa intestinal gel in advanced Parkinson's disease. J Neurol, 261(3), 561-569. doi:10.1007/s00415-013-7235-1
Clarke, C. E., Worth, P., Grosset, D., & Stewart, D. (2009). Systematic review of apomorphine infusion, levodopa infusion and deep brain stimulation in advanced Parkinson's disease. Parkinsonism Relat Disord, 15(10), 728-741. doi:10.1016/j.parkreldis.2009.09.005
DANMODIS, Danish Movement Disorder Society. SWEMODIS, Swedish Movement Disorder Society (2008). Duodopa: Scandinavian Consensus I. Treatment with levodopa/carbidopa gel (Duodopa®) in patients with Parkinson’s disease. Retrieved from http://info.parkinsonforbundet.se/wp-content/uploads/duodopakonsensus-20081.pdf
Devos, D. (2009). Patient profile, indications, efficacy and safety of duodenal levodopa infusion in advanced Parkinson's disease. Mov Disord, 24(7), 993-1000. doi:10.1002/mds.22450
Eggert, K., Schrader, C., Hahn, M., Stamelou, M., Russmann, A., Dengler, R., . . . Odin, P. (2008). Continuous jejunal levodopa infusion in patients with advanced parkinson disease: practical aspects and outcome of motor and non-motor complications. Clin Neuropharmacol, 31(3), 151-166. doi:10.1097/wnf.0b013e31814b113e
Ehlers, C., Honig, H., Odin, P. (2015). Improvement of individual quality of life in caregivers and patients under L‐dopa/carbidopa duodenal infusion therapy [abstract]. Movement Disorders, 30(Suppl 1), 4139.
Fasano, A., Ricciardi, L., Lena, F., Bentivoglio, A. R., & Modugno, N. (2012). Intrajejunal levodopa infusion in advanced Parkinson's disease: long-term effects on motor and non-motor symptoms and impact on patient's and caregiver's quality of life. Eur Rev Med Pharmacol Sci, 16(1), 79-89.
Fernandez, H. H., & Odin, P. (2011). Levodopa-carbidopa intestinal gel for treatment of advanced Parkinson's disease. Curr Med Res Opin, 27(5), 907-919. doi:10.1185/03007995.2011.560146
Fernandez, H. H., Standaert, D. G., Hauser, R. A., Lang, A. E., Fung, V. S., Klostermann, F., . . . Espay, A. J. (2015). Levodopa-carbidopa intestinal gel in advanced Parkinson's disease: final 12-month, open-label results. Mov Disord, 30(4), 500-509. doi:10.1002/mds.26123
Gauthier, S., & Amyot, D. (1992). Sustained release antiparkinson agents: controlled release levodopa. Can J Neurol Sci, 19(1 Suppl), 153-155.
Hardie, R. J., Lees, A. J., & Stern, G. M. (1984). On-off fluctuations in Parkinson's disease. A clinical and neuropharmacological study. Brain, 107 ( Pt 2), 487-506.
Holloway, R. G., Shoulson, I., Fahn, S., Kieburtz, K., Lang, A., Marek, K., . . . Watts, A. (2004). Pramipexole vs levodopa as initial treatment for Parkinson disease: a 4-year randomized controlled trial. Arch Neurol, 61(7), 1044-1053. doi:10.1001/archneur.61.7.1044
Honig, H., Antonini, A., Martinez-Martin, P., Forgacs, I., Faye, G. C., Fox, T., . . . Chaudhuri, K. R. (2009). Intrajejunal levodopa infusion in Parkinson's disease: a pilot multicenter study of effects on nonmotor symptoms and quality of life. Mov Disord, 24(10), 1468-1474. doi:10.1002/mds.22596
Lang, A. E., Rodriguez, R. L., Boyd, J. T., Chouinard, S., Zadikoff, C., Espay, A. J., . . . Dubow, J. (2016). Integrated safety of levodopa-carbidopa intestinal gel from prospective clinical trials. Mov Disord, 31(4), 538-546. doi:10.1002/mds.26485
Lowin, J., Bergman, A., Chaudhuri, K. R., Findley, L. J., Roeder, C., Schifflers, M., . . . Morris, S. (2011). A cost-effectiveness analysis of levodopa/carbidopa intestinal gel compared to standard care in late stage Parkinson's disease in the UK. J Med Econ, 14(5), 584-593. doi:10.3111/13696998.2011.598201
Lowin, J., Sail, K., Baj, R., Jalundhwala, Y. J., Marshall, T. S., Konwea, H., & Chaudhuri, K. R. (2017). The cost-effectiveness of levodopa/carbidopa intestinal gel compared to standard care in advanced Parkinson's disease. J Med Econ, 20(11), 1207-1215. doi:10.1080/13696998.2017.1379411
Martinez-Martin, P., Reddy, P., Katzenschlager, R., Antonini, A., Todorova, A., Odin, P., . . . Chaudhuri, K. R. (2015). EuroInf: a multicenter comparative observational study of apomorphine and levodopa infusion in Parkinson's disease. Mov Disord, 30(4), 510-516. doi:10.1002/mds.26067
Merola, A., Espay, A. J., Romagnolo, A., Bernardini, A., Rizzi, L., Rosso, M., . . . Lopiano, L. (2016). Advanced therapies in Parkinson's disease: Long-term retrospective study. Parkinsonism Relat Disord, 29, 104-108. doi:10.1016/j.parkreldis.2016.05.015
Merola, A., Romagnolo, A., Zibetti, M., Bernardini, A., Cocito, D., & Lopiano, L. (2016). Peripheral neuropathy associated with levodopa-carbidopa intestinal infusion: a long-term prospective assessment. Eur J Neurol, 23(3), 501-509. doi:10.1111/ene.12846
Nyholm, D., Askmark, H., Gomes-Trolin, C., Knutson, T., Lennernas, H., Nystrom, C., & Aquilonius, S. M. (2003). Optimizing levodopa pharmacokinetics: intestinal infusion versus oral sustained-release tablets. Clin Neuropharmacol, 26(3), 156-163.
Nyholm, D., Nilsson Remahl, A. I., Dizdar, N., Constantinescu, R., Holmberg, B., Jansson, R., . . . Askmark, H. (2005). Duodenal levodopa infusion monotherapy vs oral polypharmacy in advanced Parkinson disease. Neurology, 64(2), 216-223. doi:10.1212/01.wnl.0000149637.70961.4c
Nyholm, D., Odin, P., Johansson, A., Chatamra, K., Locke, C., Dutta, S., & Othman, A. A. (2013). Pharmacokinetics of levodopa, carbidopa, and 3-O-methyldopa following 16-hour jejunal infusion of levodopa-carbidopa intestinal gel in advanced Parkinson's disease patients. Aaps j, 15(2), 316-323. doi:10.1208/s12248-012-9439-1
Olanow, C. W., Kieburtz, K., Odin, P., Espay, A. J., Standaert, D. G., Fernandez, H. H., . . . Antonini, A. (2014). 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, 13(2), 141-149. doi:10.1016/s1474-4422(13)70293-x
Olanow, C. W., Stern, M. B., & Sethi, K. (2009). The scientific and clinical basis for the treatment of Parkinson disease (2009). Neurology, 72(21 Suppl 4), S1-136. doi:10.1212/WNL.0b013e3181a1d44c
Palhagen, S. E., Sydow, O., Johansson, A., Nyholm, D., Holmberg, B., Widner, H., . . . Marshall, T. S. (2016). Levodopa-carbidopa intestinal gel (LCIG) treatment in routine care of patients with advanced Parkinson's disease: An open-label prospective observational study of effectiveness, tolerability and healthcare costs. Parkinsonism Relat Disord, 29, 17-23. doi:10.1016/j.parkreldis.2016.06.002
Pickut, B. A., van der Linden, C., Dethy, S., Van De Maele, H., & de Beyl, D. Z. (2014). Intestinal levodopa infusion: the Belgian experience. Neurol Sci, 35(6), 861-866. doi:10.1007/s10072-013-1612-5
Politis, M., Sauerbier, A., Loane, C., Pavese, N., Martin, A., Corcoran, B., . . . Piccini, P. (2017). Sustained striatal dopamine levels following intestinal levodopa infusions in Parkinson's disease patients. Mov Disord, 32(2), 235-240. doi:10.1002/mds.26848
Rascol, O., Brooks, D. J., Korczyn, A. D., De Deyn, P. P., Clarke, C. E., Lang, A. E., & Abdalla, M. (2006). Development of dyskinesias in a 5-year trial of ropinirole and L-dopa. Mov Disord, 21(11), 1844-1850. doi:10.1002/mds.20988
Rascol, O., & Perez-Lloret, S. (2009). Rotigotine transdermal delivery for the treatment of Parkinson's disease. Expert Opin Pharmacother, 10(4), 677-691. doi:10.1517/14656560902746041
Reddy, P., Martinez-Martin, P., Rizos, A., Martin, A., Faye, G. C., Forgacs, I., . . . Chaudhuri, K. R. (2012). Intrajejunal levodopa versus conventional therapy in Parkinson disease: motor and nonmotor effects. Clin Neuropharmacol, 35(5), 205-207. doi:10.1097/WNF.0b013e3182613dea
Regidor, I., Benita, V., Del Alamo de Pedro, M., Ley, L., & Martinez Castrillo, J. C. (2017). Duodenal Levodopa Infusion for Long-Term Deep Brain Stimulation-Refractory Symptoms in Advanced Parkinson Disease. Clin Neuropharmacol, 40(3), 103-107. doi:10.1097/wnf.0000000000000216
Sage, J. I., & Mark, M. H. (1994). Pharmacokinetics of continuous-release carbidopa/levodopa. Clin Neuropharmacol, 17 Suppl 2, S1-6.
Sanchez-Castaneda, C., Campdelacreu, J., Miro, J., Juncadella, M., Jauma, S., & Calopa, M. (2010). Cognitive improvement after duodenal levodopa infusion in cognitively impaired Parkinson's disease patients. Prog Neuropsychopharmacol Biol Psychiatry, 34(1), 250-251. doi:10.1016/j.pnpbp.2009.10.021
Sensi, M., Preda, F., Trevisani, L., Contini, E., Gragnaniello, D., Capone, J. G., . . . Quatrale, R. (2014). Emerging issues on selection criteria of levodopa carbidopa infusion therapy: considerations on outcome of 28 consecutive patients. J Neural Transm (Vienna), 121(6), 633-642. doi:10.1007/s00702-013-1153-3
Slevin, J. T., Fernandez, H. H., Zadikoff, C., Hall, C., Eaton, S., Dubow, J., . . . Benesh, J. (2015). 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, 5(1), 165-174. doi:10.3233/jpd-140456
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