After 4 to 6 years of oral levodopa, up to three-quarters of patients may experience motor fluctuations, dyskinesias, and nonmotor symptoms. Couple this with the drug’s short half-life and erratic absorption, and this leads to fluctuating levodopa concentrations.

Levodopa/carbidopa intestinal gel (L/C IG) was designed to provide continuous delivery of levodopa to the upper intestine. The drug is indicated for a maximum of one cassette (2,000 mg) daily over 16 hours. A 24-hour administration period of L/C IG would not only offer greater convenience than a 16-hour dosing interval but might also help with nighttime and early morning symptoms. However, data are limited on 24-hour dosing of L/C IG.

To help define the efficacy and safety of 24-hour dosing of L/C IG, a subanalysis of data from COSMOS (COmedication Study assessing Mono- and cOmbination therapy with levodopa-carbidopa inteStinal gel), a multinational, retrospective, cross-sectional, postmarketing observational study in patients with advanced PD administered L/C IG in routine practice setting was performed.

This real-world study gathered data from medical records and at a single visit of patients treated with L/C IG for >12 months. The Unified Parkinson’s Disease Rating Scale was utilized to assess for “off” time, dyskinesia duration, and dyskinesias both before L/C IG initiation and at follow-up. The presence, severity rating, and frequency rating of motor, nonmotor, and treatment-related symptoms were assessed at both time periods.

Real-world data were obtained at the patient visit on 401 patients, of which 35 (9%) were receiving 24-hour L/C IG and 366 (91%) were administered 16-hour L/C IG. The reasons that the patients’ clinicians switched patients from 16-hour dosing to 24-hour dosing included the presence of nocturnal/morning akinesia (53.7%), sleep problems (36.6%), and biphasic dyskinesia (12.2%).

Upon follow-up, there were no differences between the 16-hour and 24-hour infusion groups with respect to “off” time, dyskinesia duration, or dyskinesia severity. The prevalence from baseline to follow-up for balance disturbances and dysphagia did not improve in the 24-hour group, and dysphagia and hypophonia were not reduced in the 16-hour group. While both groups saw an increase in prevalence in dysphagia, this increase was smaller in the 24-hour group than in the 16-hour group (5.7% vs. 7.7%, respectively). Balance problems demonstrated a small decrease in the 16-hour group (-2.7%), but the opposite was seen in the 24-hour group (+2.9%). Freezing gait severity and frequency were significantly improved in the 24-hour group compared with the 16-hour group (P = .038).

While there were reductions in nonmotor symptoms such as anxiety, pain, depression, and constipation between the 16-hour and 24-hour groups, fatigue was only improved in the 24-hour group. The severity of both daytime and night urinary incontinence and frequency of cognitive impairment were more significantly improved in the 24-hour versus the 16-hour group (P  = .006 and P = .014, respectively). Treatment-related symptoms did not differ between the groups in terms of prevalence, severity, or frequency.

At 12 months, significantly more patients receiving the 24-hour infusion compared with the shorter infusion were on L/C IG monotherapy (43.8% vs. 30.1%, P = .0300), although the number of add-on medications decreased in both groups over time.

The regression analysis showed that patients who were younger, those with fewer motor symptoms, those with a longer duration of “off” time, those with shorter times in dyskinesia, and those with less severe dyskinesias were more likely to receive the 24-hour L/C IG infusion.

Adverse effects occurred in 31.4% of the 24-hour group and 27.3% in the 16-hour group, with the most common events being stoma-site discharge and pneumoperitoneum in both groups. Hallucinations occurred in 2.9% in those in the longer administration group compared with 0.8% in the shorter administration time group.

The authors concluded that 24-hour L/C IG administration may be a useful treatment option in select patients with advanced PD. More studies are needed to determine the impact of this dosing regimen on adherence. Pharmacists can play a role by helping to identify patients who may be more likely to benefit from the longer administration time.

The content contained in this article is for informational purposes only. The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk.

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