ropinirole hydrochloride

Important safety information

Sudden onset of sleep and somnolence may occur (5.1) Syncope may occur (5.2) Hypotension, including orthostatic hypotension may occur (5.3) May cause hallucinations and psychotic-like behaviors (5.4) May cause or exacerbate dyskinesia (5.5) May cause problems with impulse control or compulsive behaviors (5.6) 5.1 Falling Asleep during Activities of Daily Living and Somnolence Patients treated with ropinirole hydrochloride have reported falling asleep while engaged in activities of daily living, including driving or operating machinery, which sometimes resulted in accidents. Although many of these patients reported somnolence while on ropinirole hydrochloride, some perceived that they had no warning signs, such as excessive drowsiness, and believed that they were alert immediately prior to the event. Some have reported these events more than 1 year after initiation of treatment. In controlled clinical trials, somnolence was commonly reported in patients receiving ropinirole hydrochloride and was more frequent in Parkinson's disease (up to 40% ropinirole hydrochloride, 6% placebo) than in RLS (12% ropinirole hydrochloride, 6% placebo) [see Adverse Reactions (6.1) ] . It has been reported that falling asleep while engaged in activities of daily living usually occurs in a setting of pre-existing somnolence, although patients may not give such a history. For this reason, prescribers should reassess patients for drowsiness or sleepiness, especially since some of the events occur well after the start of treatment. Prescribers should also be aware that patients may not acknowledge drowsiness or sleepiness until directly questioned about drowsiness or sleepiness during specific activities. Before initiating treatment with ropinirole hydrochloride, patients should be advised of the potential to develop drowsiness and specifically asked about factors that may increase the risk with ropinirole hydrochloride such as concomitant sedating medications or alcohol, the presence of sleep disorders (other than RLS), and concomitant medications that increase ropinirole plasma levels (e.g., ciprofloxacin) [see Drug Interactions (7.1) ] . If a patient develops significant daytime sleepiness or episodes of falling asleep during activities that require active participation (e.g., driving a motor vehicle, conversations, eating), ropinirole hydrochloride should ordinarily be discontinued [see Dosage and Administration (2.2, 2.3) ] . If a decision is made to continue ropinirole hydrochloride, patients should be advised to not drive and to avoid other potentially dangerous activities. There is insufficient information to establish that dose reduction will eliminate episodes of falling asleep while engaged in activities of daily living. 5.2 Syncope Syncope, sometimes associated with bradycardia, was observed in association with treatment with ropinirole hydrochloride in both patients with Parkinson’s disease and patients with RLS. In controlled clinical trials in patients with Parkinson’s disease, syncope was observed more frequently in patients receiving ropinirole hydrochloride than in patients receiving placebo (early Parkinson’s disease without levodopa [L-dopa]: ropinirole hydrochloride 12%, placebo 1%; advanced Parkinson’s disease: ropinirole hydrochloride 3%, placebo 2%). Syncope was reported in 1% of patients treated with ropinirole hydrochloride for RLS in 12-week, placebo-controlled clinical trials compared with 0.2% of patients treated with placebo [see Adverse Reactions (6.1) ] . Most cases occurred more than 4 weeks after initiation of therapy with ropinirole hydrochloride and were usually associated with a recent increase in dose. Because the trials conducted with ropinirole hydrochloride excluded patients with significant cardiovascular disease, patients with significant cardiovascular disease should be treated with caution. Approximately 4% of patients with Parkinson’s disease enrolled in Phase 1 trials had syncope following a 1-mg dose of ropinirole hydrochloride. In 2 trials in patients with RLS that used a forced-titration regimen and orthostatic challenge with intensive blood pressure monitoring, 2% of RLS patients treated with ropinirole hydrochloride compared with 0% of patients receiving placebo reported syncope. In Phase 1 trials including healthy volunteers, the incidence of syncope was 2%. Of note, 1 subject with syncope developed hypotension, bradycardia, and sinus arrest; the subject recovered spontaneously without intervention. 5.3 Hypotension/Orthostatic Hypotension Patients with Parkinson’s disease may have impaired ability to respond normally to a fall in blood pressure after standing from lying down or seated position. Patients on ropinirole hydrochloride should be monitored for signs and symptoms of orthostatic hypotension, especially during dose escalation, and should be informed of the risk for syncope and hypotension [see Patient Counseling Information (17) ] . Although the clinical trials were not designed to systematically monitor blood pressure, there were individual reported cases of orthostatic hypotension in early Parkinson’s disease (without L-dopa) in patients treated with ropinirole hydrochloride. Most of these cases occurred more than 4 weeks after initiation of therapy with ropinirole hydrochloride and were usually associated with a recent increase in dose. In 12-week, placebo-controlled trials of patients with RLS, the adverse event orthostatic hypotension was reported by 4 of 496 patients (0.8%) treated with ropinirole hydrochloride compared with 2 of 500 patients (0.4%) receiving placebo. In 2 Phase 2 trials in patients with RLS, 14 of 55 patients (25%) receiving ropinirole hydrochloride experienced an adverse event of hypotension or orthostatic hypotension compared with none of the 27 patients receiving placebo. In these trials, 11 of the 55 patients (20%) receiving ropinirole hydrochloride and 3 of the 26 patients (12%) who had post-dose blood pressure assessments following placebo experienced an orthostatic blood pressure decrease of at least 40 mm Hg systolic and/or at least 20 mm Hg diastolic. In Phase 1 trials of ropinirole hydrochloride with healthy volunteers who received single doses on more than one occasion without titration, 7% had documented symptomatic orthostatic hypotension. These episodes appeared mainly at doses above 0.8 mg, and these doses are higher than the starting doses recommended for patients with either Parkinson’s disease or with RLS. In most of these individuals, the hypotension was accompanied by bradycardia but did not develop into syncope [see Warnings and Precautions (5.2) ] . Although dizziness is not a specific manifestation of hypotension or orthostatic hypotension, patients with hypotension or orthostatic hypotension frequently reported dizziness. In controlled clinical trials, dizziness was a common adverse reaction in patients receiving ropinirole hydrochloride and was more frequent in patients with Parkinson’s disease or with RLS receiving ropinirole hydrochloride than in patients receiving placebo (early Parkinson’s disease without L-dopa: ropinirole hydrochloride 40%, placebo 22%; advanced Parkinson’s disease: ropinirole hydrochloride 26%, placebo 16%; RLS: ropinirole hydrochloride 11%, placebo 5%). Dizziness of sufficient severity to cause trial discontinuation of ropinirole hydrochloride was 4% in patients with early Parkinson’s disease without L-dopa, 3% in patients with advanced Parkinson’s disease, and 1% in patients with RLS [see Adverse Reactions (6.1) ]. 5.4 Hallucinations/Psychotic-Like Behavior In double-blind, placebo-controlled, early-therapy trials in patients with Parkinson’s disease who were not treated with L-dopa, 5.2% (8 of 157) of patients treated with ropinirole hydrochloride reported hallucinations, compared with 1.4% of patients on placebo (2 of 147). Among those patients receiving both ropinirole hydrochloride and L-dopa in advanced Parkinson’s disease trials,…