Ropinirole: uses, appearance and warnings

Ropinirole tablets are a non-ergoline dopamine agonist indicated for the treatment of Parkinson’s disease (PD) and moderate-to-severe primary Restless Legs Syndrome (RLS). (1.1, 1.2) 1.1 Parkinson’s Disease Ropinirole tablets are indicated for the treatment of Parkinson’s disease. 1.2 Restless Legs Syndrome Ropinirole tablets are indicated for the treatment of moderate-to-severe primary Restless Legs Syndrome (RLS).

0.25 mg, white to off white coloured, modified oval shaped, biconvex, film-coated tablet debossed with “105” on one side and “RH” on the other side 0.5 mg, pale yellow coloured, modified oval shaped, biconvex, film-coated tablet debossed with “106” on one side and “RH” on the other side 1 mg, pale green coloured, modified oval shaped, biconvex, film-coated tablet debossed with “107” on one side and “RH” on the other side 2 mg, pink coloured, modified oval shaped, biconvex, film-coated tablet debossed with “110” on one side and “RH” on the other side 3 mg, purple coloured, modified oval shaped, biconvex, film-coated tablet debossed with “112” on one side and “RH” on the other side 4 mg, brown coloured, modified oval shaped, biconvex, film-coated tablet debossed with “114” on one side and “RH” on the other side 5 mg, pale blue coloured, modified oval shaped, biconvex, film-coated tablet debossed with “115” on one side and “RH” on the other side Tablets: 0.25 mg, 0.5 mg, 1 mg, 2 mg, 3 mg, 4 mg, and 5 mg (3)

Each modified oval shaped, biconvex film-coated tablet contains ropinirole hydrochloride, USP equivalent to the labeled amount of ropinirole as follows: 0.25 mg: white to off white coloured, modified oval shaped, biconvex, film-coated tablet debossed with “105” on one side and “RH” on the other side in bottles of 100 (NDC 69452-356-20), with a child-resistant closure. 0.5 mg: pale yellow coloured, modified oval shaped, biconvex, film-coated tablet debossed with “106” on one side and “RH” on the other side in bottles of 100 (NDC 69452-357-20), with a child-resistant closure. 1 mg: pale green coloured, modified oval shaped, biconvex, film-coated tablet debossed with “107” on one sideand “RH” on the other side in bottles of 100 (NDC 69452-358-20), with a child-resistant closure. 2 mg: pink coloured, modified oval shaped, biconvex, film-coated tablet debossed with “110” on one side and “RH” on the other side in bottles of 100 (NDC 69452-359-20), with a child-resistant closure. 3 mg: purple coloured, modified oval shaped, biconvex, film-coated tablet debossed with “112” on one side and “RH” on the other side in bottles of 100 (NDC 69452-360-20), with a child-resistant closure. 4 mg: brown coloured, modified oval shaped, biconvex, film-coated tablet debossed with “114” on one side and “RH” on the other side in bottles of 100 (NDC 69452-361-20), with a child-resistant closure. 5 mg: pale blue coloured, modified oval shaped, biconvex, film-coated tablet debossed with “115” on one side and“RH” on the other side in bottles of 100 (NDC 69452-362-20), with a child-resistant closure. Storage Store at 20°C to 25°C (68°F to 77°F) [see USP Controlled Room Temperature]. Protect from light and moisture. Close container tightly after each use.

Ropinirole is contraindicated in patients known to have a hypersensitivity/allergic reaction (including urticaria, angioedema, rash, pruritus) to ropinirole or to any of the excipients. History of hypersensitivity/allergic reaction (including urticaria, angioedema, rash, pruritus) to ropinirole or to any of the excipients

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 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, 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 and was more frequent in Parkinson's disease (up to 40% ropinirole, 6% placebo) than in RLS (12% ropinirole, 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, patients should be advised of the potential to develop drowsiness and specifically asked about factors that may increase the risk with ropinirole 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 should ordinarily be discontinued [see Dosage and Administration (2.2, 2.3)] . If a decision is made to continue ropinirole, 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 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 than in patients receiving placebo (early Parkinson’s disease without levodopa [L-dopa]: ropinirole 12%, placebo 1%; advanced Parkinson’s disease: ropinirole 3%, placebo 2%). Syncope was reported in 1% of patients treated with ropinirole 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, and were usually associated with a recent increase in dose. Because the trials conducted with ropinirole 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. 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 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 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. Most of these cases occurred more than 4 weeks after initiation of therapy with ropinirole 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 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 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 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 with healthy volunteers who received single doses on more than one occasion without titration, 7% had documented symptomatic orthostatic hypotension. …

The following adverse reactions are described in more detail in other sections of the label: • Hypersensitivity [ see Contraindications (4) ] • Falling asleep during activities of daily living and somnolence [ see Warnings and Precautions (5.1) ] • Syncope [ see Warnings and Precautions (5.2) ] • Hypotension/orthostatic hypotension [ see Warnings and Precautions (5.3) ] • Hallucinations/psychotic-like behavior [ see Warnings and Precautions (5.4) ] • Dyskinesia [ see Warnings and Precautions (5.5) ] • Impulse control/compulsive behaviors [ see Warnings and Precautions (5.6) ] • Withdrawal-emergent hyperpyrexia and confusion [ see Warnings and Precautions (5.7) ] • Withdrawal Symptoms [ see Warnings and Precautions (5.8) ] • Augmentation and early-morning rebound in RLS [ see Warnings and Precautions (5.9) ] • Fibrotic complications [ see Warnings and Precautions (5.10) ] • Retinal pathol …

Inhibitors or inducers of CYP1A2: May alter the clearance of ropinirole; dose adjustment of ropinirole may be required. (7.1, 12.3) Hormone replacement therapy (HRT): Starting or stopping HRT may require dose adjustment of ropinirole. (7.2, 12.3) Dopamine antagonists (e.g., neuroleptics, metoclopramide): May reduce efficacy of ropinirole. (7.3) 7.1 Cytochrome P450 1A2 Inhibitors and Inducers In vitro metabolism studies showed that cytochrome P450 1A2 (CYP1A2) is the major enzyme responsible for the metabolism of ropinirole. There is thus the potential for inducers or inhibitors of this enzyme to alter the clearance of ropinirole. Therefore, if therapy with a drug known to be a potent inducer or inhibitor of CYP1A2 is stopped or started during treatment with ropinirole, adjustment of the dose of ropinirole may be required. …