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

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.FundingAbbVie, Inc.Plain Language SummaryPlain language summary available for this article.

The Long-Term Impact of Levodopa/Carbidopa Intestinal Gel on ‘Off’-time in Patients with Advanced Parkinson’s Disease: A Systematic Review

“…However, treatment patterns in routine practice are likely to vary between countries and centres. Several publications have provided detailed guidance on patient selection, dose conversion factors, and dose titration and adjustment [ 53 – 55 ], and with this guidance and experience, longer-term LCIG dose adjustment is relatively straightforward [ 56 , 57 ]. The individualisation of LCIG treatment regimens over time may be an important factor for maintaining the long-term reductions in ‘off’-time presented in this review.…”

Medical Management and Prevention of Motor Complications in Parkinson's Disease

“…Practices for candidate selection, initial titration and dose adjustments, and maintenance are described in a recent review article by Amjad et al [ 219 ]. The maximum recommended daily dose of CLES is 2000 mg of levodopa (i.e., one cassette per day) administered over 16 h [ 220 ].…”

<p>Levodopa-Carbidopa Intestinal Gel Infusion Therapy Discontinuation: A Ten-Year Retrospective Analysis of 204 Treated Patients</p>

“…31 Recently there have been published opinions that the initiation of therapy can be done with the help of telemedicine, under outpatient titration or even without the NJ testing phase. [43][44][45] Due to the potential of overlooking factors that would increase the dropout rate, our suggestion is that these options should be used only in cases where access to a tertiary center and implicitly the possibility of regular check-ups or the resolution of complications in an emergency regime is limited/ difficult (eg, large distances, already institutionalized patients, limitation of hospitalizations due to unforeseen circumstances, such as pandemics, etc. ).…”