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

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. Plain Language Summary Plain language summary available for this article. Plain Language Summary Results from recent studies have shown that continuous infusion of levodopa-carbidopa intestinal gel (LCIG) into the jejunum (a part of the small intestine) effectively manages the motor and nonmotor complications (e.g., tremor, extreme stiffness in arms and legs, difficulty walking, and impaired balance) experienced by patients with advanced Parkinson's disease (PD). LCIG is administered by a portable pump directly into the patient's jejunum by a permanent tube that is inserted surgically. LCIG therapy is beneficial to advanced PD patients over orally administered carbidopa/levodopa for two reasons. First, oral carbidopa/levodopa moves from the stomach to the small intestine where it is intermittently absorbed into the blood stream. LCIG is administered continuously and offers better symptom control for longer. Results from clinical trials and observational studies have shown that LCIG significantly decreases "off" time (poor motor control) and increases "on" time (good motor control) in advanced PD patients without troublesome dyskinesia, which results from the higher doses of oral levodopa required to treat the symptoms. Second, LCIG is absorbed in the jejunum, thereby bypassing the stomach where problems can occur because of inconsistent stomach emptying. In the US, titration of LCIG is performed mostly in an outpatient setting. Some clinicians may view titration of LCIG to be too complex and variable, so they avoid using LCIG therapy for their PD patients. Fortunately, emerging data and clinicians' expanding experience with LCIG have shown that titration can be easily managed in an outpatient setting, allowing for more customized therapeutic regimens for patients.