Ropinirole Hydrochloride (Page 5 of 6)

DRUG ABUSE AND DEPENDENCE

CONTROLLED SUBSTANCE CLASS

Ropinirole Hydrochloride is not a controlled substance.
Physical and Psychological Dependence
Animal studies and human clinical trials with Ropinirole Hydrochloride Tablets did not reveal any potential for drug-seeking behavior or physical dependence.

OVERDOSAGE

In the Parkinson’s disease program, there have been patients who accidentally or intentionally took more than their prescribed dose of ropinirole. The largest overdose reported in the Parkinson’s disease clinical trials was 435 mg taken over a 7-day period (62.1 mg/day). Of patients who received a dose greater than 24 mg/day, reported symptoms included adverse events commonly reported during dopaminergic therapy (nausea, dizziness), as well as visual hallucinations, hyperhidrosis, claustrophobia, chorea, palpitations, asthenia, and nightmares. Additional symptoms reported for doses of 24 mg or less or for overdoses of unknown amount included vomiting, increased coughing, fatigue, syncope, vasovagal syncope, dyskinesia, agitation, chest pain, orthostatic hypotension, somnolence, and confusional state.

Overdose Management
It is anticipated that the symptoms of overdose with Ropinirole Hydrochloride Tablets will be related to its dopaminergic activity. General supportive measures are recommended. Vital signs should be maintained, if necessary. Removal of any unabsorbed material (e.g., by gastric lavage) should be considered.

DOSAGE AND ADMINISTRATION

General Dosing Considerations for Parkinson’s Disease and RLS
Ropinirole Hydrochloride Tablets can be taken with or without food. Patients may be advised that taking Ropinirole Hydrochloride Tablets 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 Ropinirole Hydrochloride Tablets 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 Ropinirole Hydrochloride Tablets 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, Ropinirole Hydrochloride Tablets 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 Ropinirole Hydrochloride Tablets 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 Ropinirole Hydrochloride Tablets are 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 Ropinirole Hydrochloride Tablets and in 57% of patients on placebo. On average the L-dopa dose was reduced by 31% in patients treated with Ropinirole Hydrochloride Tablets.
Ropinirole Hydrochloride Tablets 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 Ropinirole Hydrochloride Tablets.
Dosing for Restless Legs Syndrome
In all clinical trials, the dose for Ropinirole Hydrochloride Tablets 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, Ropinirole Hydrochloride Tablets were discontinued without a taper.

HOW SUPPLIED

Tablets
Each circular, biconvex, film-coated tablet contains ropinirole hydrochloride as follows:
0.25 mg: white tablets debossed with “H” on one side and “121” on other side in bottles of 100 (NDC 23155-121-01).
0.5 mg: yellow tablets debossed with “H” on one side and “122” on other side in bottles of 100 (NDC 23155-122-01).
1 mg: green tablets debossed with “H” on one side and “123” on other side in bottles of 100 (NDC 23155-123-01).
2 mg: Peach tablets debossed with “H” on one side and “124” on other side in bottles of 100 (NDC 23155-124-01).
3 mg: Purple tablets debossed with “H” on one side and “125” on other side in bottles of 100 (NDC 23155-125-01).
4 mg: Pale brown tablets debossed with “H” on one side and “126” on other side in bottles of 100 (NDC 23155-126-01).
5 mg: Blue tablets debossed with “H” on one side and “127” on other side in bottles of 100 (NDC 23155-127-01).

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].

Manufactured for:
Heritage Pharmaceuticals Inc. Edison, NJ08837
1.866.901.DRUG (3784)
Manufactured by:
Alembic Limited (Formulation Division),
Village Panelav, P. O. Tajpura, Near Baska,
Taluka-Halol, Panchmahal, Gujarat, India.
SINEMET is a registered trademark of Merck & Co., Inc.
Revised: 04/2010