ROPINIROLE HYDROCHLORIDE

ROPINIROLE HYDROCHLORIDE- ropinirole hydrochloride tablet, film coated
Cardinal Health 107, LLC

1 INDICATIONS AND USAGE

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).

2 DOSAGE AND ADMINISTRATION

2.1 General Dosing Recommendations

Ropinirole tablets can be taken with or without food [see Clinical Pharmacology (12.3)]. If a significant interruption in therapy with ropinirole tablets have occurred, retitration of therapy may be warranted.

2.2 Dosing for Parkinson’s Disease

Week	Dosage	Total Daily Dose
1	0.25 mg 3 times daily	0.75 mg
2	0.5 mg 3 times daily	1.5 mg
3	0.75 mg 3 times daily	2.25 mg
4	1 mg 3 times daily	3 mg

Ropinirole tablets should be discontinued gradually over a 7-day period in patients with Parkinson’s disease [see Warnings and Precautions (5.8)]. The frequency of administration should be reduced from three times daily to twice daily for 4 days. For the remaining 3 days, the frequency should be reduced to once daily prior to complete withdrawal of ropinirole tablets.

Renal Impairment

No dose adjustment is necessary in patients with moderate renal impairment (creatinine clearance of 30 to 50 mL/min). The recommended initial dose of ropinirole for patients with end-stage renal disease on hemodialysis is 0.25 mg three times a day. Further dose escalations should be based on tolerability and need for efficacy. The recommended maximum total daily dose is 18 mg/day in patients receiving regular dialysis. Supplemental doses after dialysis are not required. The use of ropinirole tablets in patients with severe renal impairment without regular dialysis has not been studied.

2.3 Dosing for Restless Legs Syndrome

The recommended adult starting dose for RLS is 0.25 mg once daily 1 to 3 hours before bedtime. After 2 days, if necessary, the dose can be increased to 0.5 mg once daily, and to 1 mg once daily at the end of the first week of dosing, then as shown in Table 2 as needed to achieve efficacy. Titration should be based on individual patient therapeutic response and tolerability, up to a maximum recommended dose of 4 mg daily. For RLS, the safety and effectiveness of doses greater than 4 mg once daily have not been established.

Table 2. Dose Titration Schedule of ropinirole tablets for Restless Legs Syndrome

Day/Week	Dose to be taken once daily 1 to 3 hours before bedtime
Days 1 and 2	0.25 mg
Days 3 to 7	0.5 mg
Week 2	1 mg
Week 3	1.5 mg
Week 4	2 mg
Week 5	2.5 mg
Week 6	3 mg
Week 7	4 mg

When discontinuing ropinirole tablets in patients with RLS, gradual reduction of the daily dose is recommended [see Warnings and Precautions (5.8, 5.9)].

Renal Impairment
No dose adjustment is necessary in patients with moderate renal impairment (creatinine clearance of 30 to 50 mL/min). The recommended initial dose of ropinirole for patients with end-stage renal disease on hemodialysis is 0.25 mg once daily. Further dose escalations should be based on tolerability and need for efficacy. The recommended maximum total daily dose is 3 mg/day in patients receiving regular dialysis. Supplemental doses after dialysis are not required. The use of ropinirole tablets in patients with severe renal impairment without regular dialysis has not been studied.

3 DOSAGE FORMS AND STRENGTHS

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0.25 mg, white tablets debossed with “H” on one side and “121” on other side

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0.5 mg, yellow tablets debossed with “H” on one side and “122” on other side

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1 mg, green tablets debossed with “H” on one side and “123” on other side

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2 mg, Peach tablets debossed with “H” on one side and “124” on other side

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3 mg, Purple tablets debossed with “H” on one side and “125” on other side

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4 mg, Pale brown tablets debossed with “H” on one side and “126” on other side

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5 mg, Blue tablets debossed with “H” on one side and “127” on other side

4 CONTRAINDICATIONS

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

5 WARNINGS AND PRECAUTIONS

5.1 Falling Asleep during Activities of Daily Living and Somnolence

Patients treated with ropinirole tablets 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 tablets, 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 tablets and was more frequent in Parkinson’s disease (up to 40% ropinirole tablets, 6% placebo) than in Restless Legs Syndrome (12% ropinirole tablets, 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 tablets, patients should be advised of the potential to develop drowsiness and specifically asked about factors that may increase the risk with ropinirole tablets 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 tablets should ordinarily be discontinued [see Dosage and Administration (2.2, 2.3)]. If a decision is made to continue ropinirole tablets, 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.