Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug (or of another development program of a different formulation of the same drug) and may not reflect the rates observed in practice.

During the premarketing development of REQUIP XL, patients with advanced Parkinson’s disease received REQUIP XL or placebo as adjunctive therapy in 1 clinical trial. In a second trial, patients with early Parkinson’s disease were treated with REQUIP XL or the immediate-release formulation of REQUIP without L-dopa.

Advanced Parkinson’s Disease (With L-dopa): The most commonly observed adverse reactions (≥5% and numerically greater than placebo) in the 24-week, double-blind, placebo-controlled trial for the treatment of advanced Parkinson’s disease during treatment with REQUIP XL were, in order of decreasing incidence: dyskinesia, nausea, dizziness, hallucination, somnolence, abdominal pain/discomfort, and orthostatic hypotension.

Approximately 6% of 202 patients treated with REQUIP XL discontinued treatment due to adverse event(s) compared with 5% of 191 patients who received placebo. The adverse event most commonly causing discontinuation of treatment with REQUIP XL was hallucination (2%). 

Table 2 lists adverse reactions that occurred with a frequency of at least 2% (and were numerically greater than placebo) in patients with advanced Parkinson’s disease treated with REQUIP XL who participated in the 26-week, double-blind, placebo-controlled study. In this study, either REQUIP XL or placebo was used as an adjunct to L -dopa. Adverse reactions were generally mild or moderate in intensity. 

*Dose-related.

Although this study was not designed for optimally characterizing dose-related adverse reactions, there was a suggestion (based upon comparison of incidence of adverse reactions across dose ranges for REQUIP XL and placebo) that the incidence for dyskinesia, hypertension, and fall was dose-related to REQUIP XL. 

The incidence for many adverse reactions with REQUIP XL treatment was increased relative to placebo (i.e., REQUIP XL % - Placebo % = treatment difference ≥2%) in either the titration or maintenance phases of the study. During the titration phase, an increased incidence (shown in descending order of % treatment difference) was observed for dyskinesia, nausea, abdominal pain/discomfort, orthostatic hypotension, dizziness, vertigo, hypertension, peripheral edema, and dry mouth. During the maintenance phase, an increased incidence was observed for dyskinesia, nausea, dizziness, hallucination, somnolence, fall, hypertension, abnormal dreams, constipation, chest pain, bronchitis, and nasopharyngitis. Some adverse reactions developing in the titration phase persisted (≥7 days) into the maintenance phase. These “persistent” adverse reactions included dyskinesia, hallucination, orthostatic hypotension, and dry mouth.

The incidence of adverse reactions was not clearly different between women and men. 

Early Parkinson’s Disease (Without L-dopa): The most commonly observed adverse reactions (≥5%) in the 36-week early Parkinson’s disease trial during treatment with REQUIP XL were, in order of decreasing incidence: nausea (19%), somnolence (11%), abdominal pain/discomfort (7%), dizziness (6%), headache (6%), and constipation (5%). The type of adverse reactions and the frequency (i.e. incidence) with which they occurred were generally similar over the whole treatment period in this study of early Parkinson’s disease patients who were initially treated with REQUIP XL or the immediate-release formulation of REQUIP and subsequently crossed over to treatment with the other formulation. 

During the titration phase, an increased incidence with REQUIP XL compared with the immediate-release formulation of REQUIP (i.e., REQUIP XL % - REQUIP IR % = treatment difference ≥2%), shown in descending order of % treatment difference, was observed for: constipation, hallucination, vertigo, abdominal pain/discomfort, nausea, vomiting, fall, headache, diarrhea, pyrexia, and flatulence. During the maintenance phase, an increased incidence was observed for fall, myalgia, and sleep disorder. Several adverse reactions developing in the titration phase persisted (≥7 days) into the maintenance phase. These “persistent” adverse reactions included: constipation, hallucination, muscle spasms, flatulence, insomnia, sleep disorder, abdominal pain/discomfort, cough, and nasopharyngitis.