Requip (Ropinirole Hydrochloride) - Indications and Dosage

INDICATIONS AND USAGE

Parkinson’s Disease

REQUIP is indicated for the treatment of the signs and symptoms of idiopathic Parkinson’s disease.

The effectiveness of REQUIP was demonstrated in randomized, controlled trials in patients with early Parkinson’s disease who were not receiving concomitant L-dopa therapy as well as in patients with advanced disease on concomitant L-dopa (see CLINICAL PHARMACOLOGY: Clinical Trials).

Restless Legs Syndrome

REQUIP is indicated for the treatment of moderate-to-severe primary Restless Legs Syndrome (RLS).

Key diagnostic criteria for RLS are: an urge to move the legs usually accompanied or caused by uncomfortable and unpleasant leg sensations; symptoms begin or worsen during periods of rest or inactivity such as lying or sitting; symptoms are partially or totally relieved by movement such as walking or stretching at least as long as the activity continues; and symptoms are worse or occur only in the evening or night. Difficulty falling asleep may frequently be associated with moderate-to-severe RLS.

DOSAGE AND ADMINISTRATION

General Dosing Considerations for Parkinson's Disease and RLS

REQUIP can be taken with or without food. Patients may be advised that taking REQUIP with food may reduce the occurrence of nausea. However, this has not been established in controlled clinical trials.

If a significant interruption in therapy with REQUIP has occurred, retitration of therapy may be warranted.

Geriatric Use

Pharmacokinetic studies demonstrated a reduced clearance of ropinirole in the elderly (see CLINICAL PHARMACOLOGY). Dose adjustment is not necessary since the dose is individually titrated to clinical response.

Renal Impairment

The pharmacokinetics of ropinirole were not altered in patients with moderate renal impairment (see CLINICAL PHARMACOLOGY). Therefore, no dosage adjustment is necessary in patients with moderate renal impairment. The use of REQUIP in patients with severe renal impairment has not been studied.

Hepatic Impairment

The pharmacokinetics of ropinirole have not been studied in patients with hepatic impairment. Since patients with hepatic impairment may have higher plasma levels and lower clearance, REQUIP should be titrated with caution in these patients.

Dosing for Parkinson’s Disease

In all clinical studies, dosage was initiated at a subtherapeutic level and gradually titrated to therapeutic response. The dosage should be increased to achieve a maximum therapeutic effect, balanced against the principal side effects of nausea, dizziness, somnolence, and dyskinesia.

The recommended starting dose for Parkinson’s disease is 0.25 mg 3 times daily. Based on individual patient response, dosage should then be titrated with weekly increments as described in Table 5. After week 4, if necessary, daily dosage may be increased by 1.5 mg/day on a weekly basis up to a dose of 9 mg/day, and then by up to 3 mg/day weekly to a total dose of 24 mg/day. Doses greater than 24 mg/day have not been tested in clinical trials.

Table 5. Ascending-Dose Schedule of REQUIP 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

When REQUIP is administered as adjunct therapy to L-dopa, the concurrent dose of L-dopa may be decreased gradually as tolerated. L-dopa dosage reduction was allowed during the advanced Parkinson’s disease (with L-dopa) study if dyskinesias or other dopaminergic effects occurred. Overall, reduction of L-dopa dose was sustained in 87% of patients treated with REQUIP and in 57% of patients on placebo. On average the L-dopa dose was reduced by 31% in patients treated with REQUIP.

REQUIP for Parkinson’s disease patients should be discontinued gradually over a 7-day period. The frequency of administration should be reduced from 3 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 REQUIP.

Dosing for Restless Legs Syndrome

In all clinical trials, the dose for REQUIP was initiated at 0.25 mg once daily, 1 to 3 hours before bedtime. Patients were titrated based on clinical response and tolerability.

The recommended adult starting dosage for RLS is 0.25 mg once daily, 1 to 3 hours before bedtime. After 2 days, the dosage 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 6 as needed to achieve efficacy. For RLS, the safety and effectiveness of doses greater than 4 mg once daily have not been established.

Table 6. Dose Titration Schedule for RLS

Day/Week	Dosage to be taken once daily, 1 to 3 hours before bedtime
Days 1 and 2	0.25 mg
Days 3-7	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

In clinical trials of patients being treated for RLS with doses up to 4 mg once daily, REQUIP was discontinued without a taper.

HOW SUPPLIED

Tablets

Each pentagonal film-coated TILTAB^® tablet with beveled edges contains ropinirole hydrochloride as follows:

0.25 mg: white tablets imprinted with “SB” and “4890” in bottles of 100 (NDC 0007-4890-20).

0.5 mg: yellow tablets imprinted with “SB” and “4891” in bottles of 100 (NDC 0007-4891-20).

1 mg: green tablets imprinted with “SB” and “4892” in bottles of 100 (NDC 0007-4892-20).

2 mg: pale yellowish-pink tablets imprinted with “SB” and “4893” in bottles of 100 (NDC 0007-4893-20).

3 mg: pale to moderate reddish-purple tablets, imprinted with “SB” and“4895” in bottles of 100 (NDC 0007-4895-20).

4 mg: pale brown tablets imprinted with “SB” and “4896” in bottles of 100 (NDC 0007-4896-20).

5 mg: blue tablets imprinted with “SB” and “4894” in bottles of 100 (NDC 0007-4894-20).

STORAGE: Protect from light and moisture. Close container tightly after each use.

Store at controlled room temperature 20°-25°C (68°-77°F) [see USP].

2-Week Starter Kit for Treatment of Moderate-to-Severe Primary Restless Legs Syndrome

0.25 mg, white tablets imprinted with “SB” and “4890”, 0.5 mg, yellow tablets imprinted with “SB” and “4891”, and 1 mg, green tablets imprinted with “SB” and “4892”, in blisterpack of 2, 0.25 mg tablets, 5, 0.5 mg tablets, and 7, 1 mg tablets (NDC 0007-4898-14).

STORAGE: Store at controlled room temperature 20°-25°C (68°-77°F) [see USP]. Protect from light and moisture.

GlaxoSmithKline

Research Triangle Park, NC 27709

SINEMET is a registered trademark of Merck & Co., Inc.

©2006, GlaxoSmithKline. All rights reserved.

October 2006 RQ: L15

PHARMACIST DETACH HERE AND GIVE INSTRUCTIONS TO PATIENT