Ropinirole

Dose Selection

Ziprasidone hydrochloride capsules should be administered at an initial daily dose of 20 mg twice daily with food. In some patients, daily dosage may subsequently be adjusted on the basis of individual clinical status up to 80 mg twice daily. Dosage adjustments, if indicated, should generally occur at intervals of not less than 2 days, as steady-state is achieved within 1 to 3 days. In order to ensure use of the lowest effective dose, patients should ordinarily be observed for improvement for several weeks before upward dosage adjustment. 

Efficacy in schizophrenia was demonstrated in a dose range of 20 mg to 100 mg twice daily in short-term, placebo-controlled clinical trials. There were trends toward dose response within the range of 20 mg to 80 mg twice daily, but results were not consistent. An increase to a dose greater than 80 mg twice daily is not generally recommended. The safety of doses above 100 mg twice daily has not been systematically evaluated in clinical trials [see Clinical Studies (14.1)]. 

Maintenance Treatment 

While there is no body of evidence available to answer the question of how long a patient treated with ziprasidone should remain on it, a maintenance study in patients who had been symptomatically stable and then randomized to continue ziprasidone or switch to placebo demonstrated a delay in time to relapse for patients receiving ziprasidone hydrochloride capsules [see Clinical Studies (14.1)].  No additional benefit was demonstrated for doses above 20 mg twice daily. Patients should be periodically reassessed to determine the need for maintenance treatment.

Oral

Dosage adjustments are generally not required on the basis of age, gender, race, or renal or hepatic impairment. Ziprasidone hydrochloride capsules are not approved for use in children or adolescents.

When there is urgent need, therapy in the hospitalized patient may be initiated intramuscularly or as a rapid intravenous bolus injection directly into the vein.  Hydralazine Hydrochloride Injection should be used only when the drug cannot be given orally.  The usual dose is 20 to 40 mg, repeated as necessary.

Certain patients (especially those with marked renal damage) may require a lower dose.   Blood pressure should be checked frequently.  It may begin to fall within a few minutes after injection, with the average maximal decrease occurring in 10 to 80 minutes.  In cases where there has been increased intracranial pressure, lowering the blood pressure may increase cerebral ischemia.  Most patients can be transferred to oral hydralazine hydrochloride within 24 to 48 hours.

The product should be used immediately after the vial is opened.  The product should not be added to infusion solutions.  Hydralazine Hydrochloride Injection may discolor upon contact with metal; discolored solutions should be discarded. 

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

The starting dose is 2 mg taken once daily for 1 to 2 weeks, followed by increases of 2 mg/day at 1-week or longer intervals as appropriate, based on therapeutic response and tolerability. The maximum recommended dose of ropinirole extended-release tablets is 24 mg/day.

In clinical trials, dosage was initiated at 2 mg/day and gradually titrated based on individual patient therapeutic response and tolerability. Doses greater than 24 mg/day have not been studied in clinical trials. Patients should be assessed for therapeutic response and tolerability at a minimal interval of 1 week or longer after each dose increment. Monitor patients during dose titration because too rapid a rate of titration may lead to dose selection that may not provide additional benefit, but that may increase the risk of adverse reactions [see Clinical Studies (14.2)]. Due to the flexible dosing design used in clinical trials, specific dose-response information could not be determined.

Ropinirole extended-release tablets should be discontinued gradually over a 7-day period.

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 extended-release tablets for patients with end-stage renal disease on hemodialysis is 2 mg once daily. 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 extended-release tablets in patients with severe renal impairment without regular dialysis has not been studied.

Patients may be switched directly from immediate-release ropinirole to ropinirole extended-release tablets. The initial dose of ropinirole extended-release tablets should most closely match the total daily dose of the immediate-release formulation of ropinirole, as shown in Table 1.

Table 1. Conversion from Immediate-Release Ropinirole Tablets to Ropinirole Extended-Release Tablets

Following conversion to ropinirole extended-release tablets, the dose may be adjusted depending on therapeutic response and tolerability [see Dosage and Administration (2.2)].

Ropinirole extended-release tablets are designed to release medication over a 24-hour period. If rapid gastrointestinal transit occurs, there may be risk of incomplete release of medication and medication residue being passed in the stool.

Adults and children 2 years of age and older: Dissolve entire contents of one tube in the mouth every 6 hours, up to 3 times a day.
Children younger than 2 years of age: Ask a doctor.

Ropinirole tablets USP can be taken with or without food. Patients may be advised that taking ropinirole tablets USP 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 tablets USP has occurred, retitration of therapy may be warranted.

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.

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 tablets USP in patients with severe renal impairment has not been studied.

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 tablets USP should be titrated with caution in these patients.

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.

1

2

3

0.25 mg 3 times daily

0.5 mg 3 times daily

0.75 mg 3 times daily

0.75 mg

1.5 mg

2.25 mg

When ropinirole tablets USP 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 and in 57% of patients on placebo. On average the L-dopa dose was reduced by 31% in patients treated with ropinirole hydrochloride.

Ropinirole tablets USP 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 tablets USP.

In all clinical trials, the dose for ropinirole tablets USP 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.

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

Ropinirole tablets USP can be taken with or without food. Patients may be advised that taking ropinirole tablets USP 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 tablets USP has occurred, retitration of therapy may be warranted.

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.

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 tablets USP in patients with severe renal impairment has not been studied.

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 tablets USP should be titrated with caution in these patients.

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.

1

2

3

0.25 mg 3 times daily

0.5 mg 3 times daily

0.75 mg 3 times daily

0.75 mg

1.5 mg

2.25 mg

When ropinirole tablets USP 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 and in 57% of patients on placebo. On average the L-dopa dose was reduced by 31% in patients treated with ropinirole hydrochloride.

Ropinirole tablets USP 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 tablets USP.

In all clinical trials, the dose for ropinirole tablets USP 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.

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

Ropinirole can be taken with or without food. Patients may be advised that taking ropinirole 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 has occurred, retitration of therapy may be warranted.

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.

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 in patients with severe renal impairment has not been studied.

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 should be titrated with caution in these patients.

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 three 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.

Week

Dosage

Total Daily Dose

1

0.25 mg three times daily

0.75 mg

2

0.5 mg three times daily

1.5 mg

3

0.75 mg three times daily

2.25 mg

4

1 mg three times daily

3 mg

When ropinirole 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 ropinirole and in 57% of patients on placebo. On average the L-dopa dose was reduced by 31% in patients treated with ropinirole.

Ropinirole for Parkinson’s disease patients should be discontinued gradually over a 7-day period. 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.

In all clinical trials, the dose for ropinirole 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.

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 was discontinued without a taper.

Ropinirole can be taken with or without food. Patients may be advised that taking ropinirole 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 has occurred, retitration of therapy may be warranted.

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

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

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 should be titrated with caution in these patients.

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 three 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.

Week

Dosage

Total Daily Dose

1

0.25 mg three times daily

0.75 mg

2

0.5 mg three times daily

1.5 mg

3

0.75 mg three times daily

2.25 mg

4

1 mg three times daily

3 mg

When ropinirole 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 ropinirole and in 57% of patients on placebo. On average the L-dopa dose was reduced by 31% in patients treated with ropinirole.

Ropinirole for Parkinson’s disease patients should be discontinued gradually over a 7-day period. 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.

In all clinical trials, the dose for ropinirole 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.

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 was discontinued without a taper.

Ropinirole can be taken with or without food. Patients may be advised that taking ropinirole 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 has occurred, retitration of therapy may be warranted.

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

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

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 should be titrated with caution in these patients.

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 three 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.

Week

Dosage

Total Daily Dose

1

0.25 mg three times daily

0.75 mg

2

0.5 mg three times daily

1.5 mg

3

0.75 mg three times daily

2.25 mg

4

1 mg three times daily

3 mg

When ropinirole 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 ropinirole and in 57% of patients on placebo. On average the L-dopa dose was reduced by 31% in patients treated with ropinirole.

Ropinirole for Parkinson’s disease patients should be discontinued gradually over a 7-day period. 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.

In all clinical trials, the dose for ropinirole 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.

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 was discontinued without a taper.

Ropinirole can be taken with or without food. Patients may be advised that taking ropinirole 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 has occurred, retitration of therapy may be warranted.

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

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

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 should be titrated with caution in these patients.

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 three 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.

Week

Dosage

Total Daily Dose

1

0.25 mg three times daily

0.75 mg

2

0.5 mg three times daily

1.5 mg

3

0.75 mg three times daily

2.25 mg

4

1 mg three times daily

3 mg

When ropinirole 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 ropinirole and in 57% of patients on placebo. On average the L-dopa dose was reduced by 31% in patients treated with ropinirole.

Ropinirole for Parkinson’s disease patients should be discontinued gradually over a 7-day period. 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.

In all clinical trials, the dose for ropinirole 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.

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 was discontinued without a taper.

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

The recommended starting dose for Parkinson’s disease is 0.25 mg three times daily. Based on individual patient therapeutic response and tolerability, if necessary, the dose should then be titrated with weekly increments as described in Table 1. After Week 4, if necessary, the daily dose 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 up to a maximum recommended total daily dose of 24 mg/day (8 mg three times daily). Doses greater than 24 mg/day have not been tested in clinical trials.

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 hydrochloride should be discontinued gradually over a 7-day period in patients with Parkinson’s disease. 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 hydrochloride.

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 hydrochloride in patients with severe renal impairment without regular dialysis has not been studied.

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.

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

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

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 hydrochloride in patients with severe renal impairment without regular dialysis has not been studied.