Drugs Details

Drugs Info of Requip, Requip XL
Drugs Details
  • Drugs Type  : FDA
  • Date : 25th Mar 2015 03:39 am
  • Brand Name : Requip, Requip XL
  • Generic Name : ropinirole (oral) (Pronunciation: roe PIN i role)
Descriptions

REQUIP (ropinirole) is an orally administered non-ergoline dopamine agonist. It is supplied as the hydrochloride salt of ropinirole 4-[2-(dipropylamino)ethyl]-1,3-dihydro-2H-indol-2-one and has an empirical formula of C16H24N2O•HCl. The molecular weight is 296.84 (260.38 as the free base).

The structural formula is:

 

REQUIP XL
  (ropinirole) Structural Formula Illustration

Ropinirole hydrochloride is a white to yellow solid with a melting range of 243° to 250°C and a solubility of 133 mg/mL in water. REQUIP XL (ropinirole extended release tablets) Extended-Release Tablets are formulated as a three-layered tablet with a central, active-containing, slow-release layer, and 2 placebo outer layers acting as barrier layers which control the surface area available for drug release. Each biconvex, capsule-shaped tablet contains 2.28 mg, 4.56 mg, 6.84 mg, 9.12 mg, or 13.68 mg ropinirole hydrochloride equivalent to ropinirole 2 mg, 4 mg, 6 mg, 8 mg, or 12 mg, respectively. Inactive ingredients consist of carboxymethylcellulose sodium, colloidal silicon dioxide, glyceryl behenate, hydrogenated castor oil, hypromellose, lactose monohydrate, magnesium stearate, maltodextrin, mannitol, povidone, and one or more of the following: FD&C Yellow No. 6 aluminum lake, FD&C Blue No. 2 aluminum lake, ferric oxides (black, red, yellow), polyethylene glycol 400, titanium dioxide.

What are the possible side effects of ropinirole (Requip, Requip XL)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have any of these serious side effects:

  • feeling like you might pass out;
  • fever, stiff muscles, confusion, sweating, fast or uneven heartbeats (especially if you stop taking ropinirole or use a lower dose);
  • hallucinations;
  • tremors (uncontrolled shaking); or
  • tight feeling in your chest, trouble breathing.

Call your doctor...

Read All Potential Side Effects and See Pictures of Requip XL »

What are the precautions when taking ropinirole extended release tablets (Requip XL)?

Before taking ropinirole, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: heart disease, low blood pressure, sleep disorder (such as sleep apnea, narcolepsy), mental/mood disorder, liver problems.

Some people taking ropinirole have reported falling asleep suddenly during usual daily activities (such as talking on the phone, driving). In some cases, sleep occurred without feelings of drowsiness beforehand. This effect may occur at any time during treatment, including up to 1 year after...

Read All Potential Precautions of Requip XL »

This monograph has been modified to include the generic and brand name in many instances.

Indications

Parkinson's Disease

REQUIP XL (ropinirole extended-release tablets) is indicated for the treatment of the signs and symptoms of idiopathic Parkinson's disease.

Dosage Administration

General Dosing Considerations

  • REQUIP XL (ropinirole extended release tablets) Extended-Release Tablets are taken once daily, with or without food. Taking REQUIP XL (ropinirole extended release tablets) with food may reduce the occurrence of nausea; this has not been established in controlled clinical trials [see CLINICAL PHARMACOLOGY].
  • Tablets must be swallowed whole and must not be chewed, crushed, or divided.
  • If a significant interruption in therapy with REQUIP XL (ropinirole extended release tablets) has occurred, retitration of therapy may be warranted.

Dosing for Parkinson's Disease

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, depending on therapeutic response and tolerability, up to a maximally recommended dose of 24 mg/day.

In clinical trials, dosage was initiated at 2 mg/day and gradually titrated based on individual 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. Caution should be exercised 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]. Due to the flexible dosing design used in clinical studies, specific dose response information could not be determined.

When REQUIP XL (ropinirole extended release tablets) is administered as adjunct therapy to L-dopa, the concurrent dose of L-dopa may be decreased gradually as tolerated. In the placebo-controlled advanced Parkinson's disease study, the L-dopa dose was reduced once patients reached a dose of REQUIP XL (ropinirole extended release tablets) of 8 mg/day. Overall, L-dopa dose reduction was sustained in 93% of patients treated with REQUIP XL (ropinirole extended release tablets) and in 72% of patients on placebo. On average the L-dopa dose was reduced by 34% in patients treated with REQUIP XL [see Clinical Studies]. REQUIP XL (ropinirole extended release tablets) should be discontinued gradually over a 7–day period.

Switching From Immediate-Release Ropinirole Tablets to REQUIP XL

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

Table 1. Conversion from Immediate-Release REQUIP to REQUIP XL

Immediate-Release Ropinirole Tablets Total Daily Dose (mg) REQUIP XL Tablets Total Daily Dose (mg)
0.75 to 2.25 2
3 to 4.5 4
6 6
7.5 to 9 8
12 12
15 to 18 16
21 20
24 24

Following conversion to REQUIP XL (ropinirole extended release tablets) , the dose may be adjusted depending on therapeutic response and tolerability [see DOSAGE AND ADMINISTRATION].

How Supplied

Dosage Forms And Strengths

  • 2 mg, pink, biconvex, capsule-shaped, film-coated, tablets debossed with “GS” and “3V2”
  • 4 mg, light brown, biconvex, capsule-shaped, film-coated, tablets debossed with “GS” and “WXG”
  • 6 mg, white, biconvex, capsule-shaped, film-coated, tablets debossed with "GS" and "11F"
  • 8 mg, red, biconvex, capsule-shaped, film-coated, tablets debossed with “GS” and “5CC”
  • 12 mg, green, biconvex, capsule-shaped, film-coated, tablets debossed with "GS" and "YX7"

Each biconvex, capsule-shaped, film-coated tablet contains ropinirole hydrochloride equivalent to the labeled amount of ropinirole as follows:

  • 2 mg: pink tablets debossed with “GS” and “3V2”, in bottles of 30 (NDC 0007–4885–13) and 90 (NDC 0007-4885-59).
  • 4 mg: light brown tablets debossed with “GS” and “WXG”, in bottles of 30 (NDC 0007–4887–13) and 90 (NDC 0007-4887-59).
  • 6 mg: white tablets debossed with "GS" and "11F", in bottles of 30 (NDC 0007-4883-13) and 90 (NDC 0007-4883-59).
  • 8 mg: red tablets debossed with “GS” and “5CC”, in bottles of 30 (NDC 0007-4888-13) and 90 (NDC 0007-4888-59).
  • 12 mg: green tablets debossed with "GS" and "YX7", in bottle of 30 (NDC 0007-4882-13).

Storage

Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature].

Dispense in a tight, light-resistant container as defined in the USP.

GlaxoSmithKline Research Triangle Park, NC 27709.

This monograph has been modified to include the generic and brand name in many instances.

Side Effects

The following adverse reactions are described in more detail in the WARNINGS AND PRECAUTIONS section of the label:

  • Falling asleep during activities of daily living
  • Syncope
  • Symptomatic hypotension, hypotension, postural/orthostatic hypotension
  • Elevation of blood pressure and changes in heart rate
  • Hallucination
  • Dyskinesia
  • Major psychotic disorders
  • Events with dopaminergic therapy
  • Retinal pathology

Clinical Trial Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug (or of another development program of a different formulation of the same drug) and may not reflect the rates observed in practice.

During the premarketing development of REQUIP XL (ropinirole extended release tablets) , patients with advanced Parkinson's disease received REQUIP XL (ropinirole extended release tablets) or placebo as adjunctive therapy in 1 clinical trial. In a second trial, patients with early Parkinson's disease were treated with REQUIP XL (ropinirole extended release tablets) or the immediate-release formulation of REQUIP without L-dopa.

Advanced Parkinson's Disease (With L-dopa)

The most commonly observed adverse reactions ( ≥ 5% and numerically greater than placebo) in the 24-week, double-blind, placebo-controlled trial for the treatment of advanced Parkinson's disease during treatment with REQUIP XL (ropinirole extended release tablets) were, in order of decreasing incidence: dyskinesia, nausea, dizziness, hallucination, somnolence, abdominal pain/discomfort, and orthostatic hypotension.

Approximately 6% of 202 patients treated with REQUIP XL (ropinirole extended release tablets) discontinued treatment due to adverse event(s) compared with 5% of 191 patients who received placebo. The adverse event most commonly causing discontinuation of treatment with REQUIP XL (ropinirole extended release tablets) was hallucination (2%).

Table 2 lists adverse reactions that occurred with a frequency of at least 2% (and were numerically greater than placebo) in patients with advanced Parkinson's disease treated with REQUIP XL (ropinirole extended release tablets) who participated in the 26-week, double-blind, placebo-controlled study. In this study, either REQUIP XL (ropinirole extended release tablets) or placebo was used as an adjunct to L -dopa. Adverse reactions were generally mild or moderate in intensity.

Table 2. Treatment-Emergent Adverse Reaction Incidence in a Double-Blind, Placebo-Controlled Trial in Advanced Stage Parkinson's Disease (With L-dopa) (Events ≥ 2% of Patients Treated with REQUIP XL (ropinirole extended release tablets) and > % with Placebo)

Body System/Adverse Reaction REQUIP XL (ropinirole extended release tablets)
(n = 202)
%
Placebo
(n = 191)
%
Ear and labyrinth disorders
  Vertigo 4 2
Gastrointestinal disorders
  Nausea 11 4
  Constipation 4 2
  Abdominal pain/discomfort 6 3
  Diarrhea 3 2
  Dry mouth 2 < 1
General disorders
  Edema peripheral 4 1
Injury, poisoning, and procedural complication
  Fall* 2 1
Musculoskeletal and connective tissue disorders
  Back pain 3 2
Nervous system disorders
  Dyskinesia* 13 3
  Dizziness 8 3
  Somnolence 7 4
Psychiatric disorders
  Hallucination 8 2
  Anxiety 2 1
Vascular disorders
  Orthostatic hypotension 5 1
  Hypotension 2 0
  Hypertension* 3 2
*Dose-related.

Although this study was not designed for optimally characterizing dose-related adverse reactions, there was a suggestion (based upon comparison of incidence of adverse reactions across dose ranges for REQUIP XL (ropinirole extended release tablets) and placebo) that the incidence for dyskinesia, hypertension, and fall was dose-related to REQUIP XL (ropinirole extended release tablets) .

The incidence for many adverse reactions with REQUIP XL (ropinirole extended release tablets) treatment was increased relative to placebo (i.e., REQUIP XL (ropinirole extended release tablets) % Placebo % = treatment difference ≥ 2%) in either the titration or maintenance phases of the study. During the titration phase, an increased incidence (shown in descending order of % treatment difference) was observed for dyskinesia, nausea, abdominal pain/ discomfort, orthostatic hypotension, dizziness, vertigo, hypertension, peripheral edema, and dry mouth. During the maintenance phase, an increased incidence was observed for dyskinesia, nausea, dizziness, hallucination, somnolence, fall, hypertension, abnorma dreams, constipation, chest pain, bronchitis, and nasopharyngitis. Some adverse reactions developing in the titration phase persisted ( ≥ 7 days) into the maintenance phase. These “persistent” adverse reactions included dyskinesia, hallucination, orthostatic hypotension, and dry mouth.

The incidence of adverse reactions was not clearly different between women and men.

Early Parkinson's Disease (Without L -dopa)

The most commonly observed adverse reactions ( > 5%) in the 36-week early Parkinson's disease trial during treatment with REQUIP XL (ropinirole extended release tablets) were, in order of decreasing incidence: nausea (19%), somnolence (11%), abdominal pain/discomfort (7%), dizziness (6%), headache (6%), and constipation (5%). The type of adverse reactions and the frequency (i.e. incidence) with which they occurred were generally similar over the whole treatment period in this study of early Parkinson's disease patients who were initially treated with REQUIP XL (ropinirole extended release tablets) or the immediate-release formulation of REQUIP and subsequently crossed over to treatment with the other formulation.

During the titration phase, an increased incidence with REQUIP XL (ropinirole extended release tablets) compared with the immediate-release formulation of REQUIP (i.e., REQUIP XL (ropinirole extended release tablets) % - REQUIP IR % = treatment difference > 2%), shown in descending order of % treatment difference, was observed for: constipation, hallucination, vertigo, abdominal pain/discomfort, nausea, vomiting, fall, headache, diarrhea, pyrexia, and flatulence. During the maintenance phase, an increased incidence was observed for fall, myalgia, and sleep disorder. Several adverse reactions developing in the titration phase persisted ( > 7 days) into the maintenance phase. These “persistent” adverse reactions included: constipation, hallucination, muscle spasms, flatulence, insomnia, sleep disorder, abdominal pain/discomfort, cough, and nasopharyngitis.

Adverse Reactions Observed During the Clinical Development of the Immediate-Release Formulation of REQUIP for Parkinson's Disease (Advanced and Early)

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug (or of another development program of a different formulation of the same drug) and may not reflect the rates observed in practice.

In patients with advanced Parkinson's disease who were treated with the immediate-release formulation of REQUIP, the most common adverse reactions ( ≥ 5% treatment difference from placebo; presented in order of decreasing treatment difference frequency) were dyskinesia (21%), somnolence (12%), nausea (12%), dizziness (10%), confusion (7%), hallucinations (6%), headache (5%), and increased sweating (5%). In patients with early Parkinson's disease who were treated with the immediate-release formulation of REQUIP, the most common adverse reactions ( > 5% treatment difference from placebo; presented in order of decreasing treatment difference frequency) were nausea (38%), somnolence (34%), dizziness (18%), syncope (11%), viral infection (8%), fatigue (7%), leg edema (6%), asthenia (5%), and dyspepsia (5%).

Read the Requip XL (ropinirole extended release tablets) Side Effects Center for a complete guide to possible side effects

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Interactions

P450 Interaction

In vitrometabolism studies showed that 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.

Coadministration of ciprofloxacin, an inhibitor of CYP1A2, with immediate-release ropinirole increased the AUC of ropinirole by 84% on average and Cmax by 60% [see CLINICAL PHARMACOLOGY].

Cigarette smoking is expected to increase the clearance of ropinirole since CYP1A2 is known to be induced by smoking. In one study in patients with Restless Legs Syndrome, cigarette smokers had an approximate 30% lower Cmax and a 38% lower AUC than did nonsmokers, when those parameters were normalized for dose.

There is no evidence of interaction between ropinirole and other CYP1A2 substrates (e.g., theophylline).

Ropinirole and its circulating metabolites do not inhibit or induce P450 enzymes therefore ropinirole is unlikely to affect the pharmacokinetics of other drugs by a P450 mechanism [see CLINICAL PHARMACOLOGY].

L-dopa

Coadministration of carbidopa + L-dopa (SINEMET ) with immediate-release ropinirole had no effect on the steady-state pharmacokinetics of ropinirole. Oral administration of immediate-release ropinirole increased mean steady-state Cmax of L-dopa by 20%, but its AUC was unaffected [see CLINICAL PHARMACOLOGY].

Estrogens

Population pharmacokinetic analysis revealed that higher doses of estrogens (usually associated with hormone replacement therapy [HRT]) reduced the oral clearance of ropinirole by approximately 35%. Dosage adjustment is not needed for initiating REQUIP XL (ropinirole extended release tablets) in patients on estrogen therapy because patients are individually titrated with REQUIP XL (ropinirole extended release tablets) to tolerance or adequate effect. If estrogen therapy is stopped or started during treatment with REQUIP XL (ropinirole extended release tablets) , then adjustment of the dose of REQUIP XL may be required.

Dopamine Antagonists

Since ropinirole is a dopamine agonist, it is possible that dopamine antagonists such as neuroleptics (e.g., phenothiazines, butyrophenones, thioxanthenes) or metoclopramide may diminish the effectiveness of REQUIP XL (ropinirole extended release tablets) . Patients with a history or presence of major psychotic disorders should be treated with dopamine agonists only if the potential benefits outweigh the risks.

Drug Abuse And Dependence

Controlled Use

Ropinirole is not a controlled substance.

Dependence

Animal studies and human clinical trials with ropinirole did not reveal any potential for drug-seeking behavior or physical dependence.

Read the Requip XL Drug Interactions Center for a complete guide to possible interactions

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This monograph has been modified to include the generic and brand name in many instances.

Warnings

Included as part of the PRECAUTIONS section.

Precautions

Falling Asleep During Activities of Daily Living

Patients treated with ropinirole have reported falling asleep while engaged in activities of daily living, including the operation of motor vehicles, 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 of these events have been reported more than 1 year after initiation of treatment.

Among the 613 patients who received REQUIP XL (ropinirole extended release tablets) in clinical trials, there were 5 cases of sudden onset of sleep and 2 cases of motor vehicle accident in which it is not known if falling asleep was a contributing factor.

During the 6-month trial in advanced Parkinson's disease, somnolence was reported in 7% (14 of 202) of patients receiving REQUIP XL (ropinirole extended release tablets) compared with 4% (7 of 191) of patients receiving placebo. During the 36-week trial in early Parkinson's disease, somnolence was reported in 11% (16 of 140) of patients receiving REQUIP XL compared with 15% (22 of 149) of patients receiving the immediate-release formulation of REQUIP [see ADVERSE REACTIONS]. However, because dose-response was not systematically studied with REQUIP XL (ropinirole extended release tablets) , the occurrence of somnolence at the highest recommended doses may be higher than these reported frequencies [see ADVERSE REACTIONS].

Many clinical experts believe that falling asleep while engaged in activities of daily living always occurs in a setting of preexisting somnolence, although patients may not give such a history. For this reason, prescribers should continually 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 REQUIP XL (ropinirole extended release tablets) , patients should be advised of the potential to develop drowsiness and specifically asked about factors that may increase the risk with REQUIP XL (ropinirole extended release tablets) such as concomitant sedating medications, the presence of sleep disorders, and concomitant medications that increase ropinirole plasma levels (e.g., ciprofloxacin) [see DRUG INTERACTIONS]. 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, etc.), REQUIP XL should ordinarily be discontinued [see DOSAGE AND ADMINISTRATION for guidance in discontinuing REQUIP XL (ropinirole extended release tablets) ]. If a decision is made to continue REQUIP XL (ropinirole extended release 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.

Syncope

Syncope, sometimes associated with bradycardia, was observed during treatment with ropinirole in Parkinson's disease patients. In a placebo-controlled study involving patients with advanced Parkinson's disease, syncope occurred in 2 of the 202 patients (1%) who received REQUIP XL (ropinirole extended release tablets) , and in none of the 191 patients who received placebo.

Because the study of REQUIP XL (ropinirole extended release tablets) excluded patients with significant cardiovascular disease, it is not known to what extent the estimated incidence figure applies to patients with Parkinson's disease in clinical practice. Therefore, patients with significant cardiovascular disease should be treated with caution.

Hypotension

Dopamine agonists, in clinical studies and clinical experience, appear to impair the systemic regulation of blood pressure, with resulting postural hypotension, especially during dose escalation. In addition, patients with Parkinson's disease appear to have an impaired capacity to respond to a postural challenge. For these reasons, patients being treated with dopaminergic agonists ordinarily (1) require careful monitoring for signs and symptoms of postural hypotension, especially during dose escalation, and (2) should be informed of this risk [see Patient Counseling Information].

In a placebo-controlled trial involving patients with advanced Parkinson's disease, hypotension was reported as an adverse event in 5 of 202 patients (2%) receiving REQUIP XL (ropinirole extended release tablets) and in none of the 191 patients receiving placebo. Orthostatic hypotension was reported as an adverse event in 5% of patients receiving REQUIP XL (ropinirole extended release tablets) , and in 1% of placebo recipients.

An analysis of the randomized, double-blinded, placebo-controlled study in advanced Parkinson's disease was conducted using a variety of adverse event terms possibly suggestive of hypotension, including hypotension, orthostatic hypotension, dizziness, vertigo, and blood pressure decreased. This analysis showed a higher incidence of these events with REQUIP XL (ropinirole extended release tablets) (7%, 15 of 202) vs. placebo (3%, 6 of 191). This increased incidence was observed in a setting in which patients were very carefully titrated, and patients with clinically relevant cardiovascular disease or symptomatic orthostatic hypotension at baseline had been excluded from this study. Orthostatic vital signs (semi-supine to standing) were monitored throughout the study in the advanced Parkinson's disease study and changes related to REQUIP XL (ropinirole extended release tablets) (compared with placebo) from baseline were assessed.

The frequency of any orthostatic hypotension at any time during the study was 38% for REQUIP XL (ropinirole extended release tablets) vs. 31% for placebo for mild to moderate systolic blood pressure decrements ( ≥ 20 mm Hg), 63% for REQUIP XL (ropinirole extended release tablets) vs. 58% for placebo for mild to moderate diastolic blood pressure decrements ( ≥ 10 mm Hg), 10% for REQUIP XL (ropinirole extended release tablets) vs. 7% for placebo for severe diastolic blood pressure decrements ( ≥ 20 mm Hg), and 23% for REQUIP XL (ropinirole extended release tablets) vs. 19% for placebo for mild to moderate combined systolic and diastolic blood pressure decrements.

Significant decrements in blood pressure unrelated to standing were also reported in some patients taking REQUIP XL (ropinirole extended release tablets) . In the semi-supine position, the frequency was 10% for REQUIP XL (ropinirole extended release tablets) vs. 8% for placebo for severe systolic blood pressure decrease ( ≥ 40 mm Hg), and was 25% for REQUIP XL (ropinirole extended release tablets) vs. 21% for placebo for severe diastolic blood pressure decrease ( ≥ 20 mm Hg).

The increased incidence for hypotension and/or orthostatic hypotension was observed in both the titration and maintenance phases and in some cases persisted into the maintenance period after developing in the titration phase.

Elevation of Blood Pressure and Changes in Heart Rate

In the placebo-controlled study in advanced Parkinson's disease, there were no clear effects of REQUIP XL (ropinirole extended release tablets) on average changes in blood pressure or heart rate compared with placebo. However, there was an increased incidence of patients treated with REQUIP XL (ropinirole extended release tablets) who met various outlier criteria, as described below.

In the semi-supine position, the frequency was 8% for REQUIP XL (ropinirole extended release tablets) vs. 5% for placebo for severe systolic blood pressure increase ( ≥ 40 mm Hg). In the standing position, the frequency was 9% for REQUIP XL (ropinirole extended release tablets) vs. 6% for placebo for severe systolic blood pressure increase ( ≥ 40 mm Hg).

In the semi-supine position, the frequency was 23% for REQUIP XL (ropinirole extended release tablets) vs. 18% for placebo for moderate pulse increase ( ≥ 15 beats/ minute), and 19% for REQUIP XL (ropinirole extended release tablets) vs. 17% for placebo for moderate pulse decrease ( ≥ 15 beats/minute). In the standing position, the frequency was 2% for REQUIP XL (ropinirole extended release tablets) vs. < 1% for placebo for severe pulse increase ( > 30 beats/minute), and 24% for REQUIP XL (ropinirole extended release tablets) vs. 19% for placebo for moderate pulse decrease ( ≥ 15 beats/minute).

The increased incidence for various elevations of systolic and/or diastolic blood pressure and/or changes in pulse was observed in both the titration and maintenance phases as well as persisting into the maintenance period after developing in the titration phase. Elevation of blood pressure and/or changes in heart rate in patients taking REQUIP XL (ropinirole extended release tablets) should be considered when treating patients with cardiovascular disease.

Hallucination

In the double-blind, placebo-controlled, advanced Parkinson's disease trial 8% (17 of 202) of patients receiving REQUIP XL (ropinirole extended release tablets) reported hallucination compared with 2% (4 of 191) patients receiving placebo. Hallucination led to discontinuation of treatment in 2% (4 of 202) of patients on REQUIP XL (ropinirole extended release tablets) and 1% (2 of 191) of patients on placebo.

The incidence of hallucination is increased in patients over age 65. Coadministration of entacapone and L-dopa with ropinirole may also increase the risk of hallucination. In a placebo-controlled clinical trial, hallucination occurred in 0 of 43 patients taking entacapone plus L-dopa, in 9 of 155 patients taking REQUIP XL (ropinirole extended release tablets) plus L-dopa (6%), and in 7 of 47 patients taking entacapone with REQUIP XL (ropinirole extended release tablets) plus L-dopa (15%).

Dyskinesia

REQUIP XL (ropinirole extended release tablets) may potentiate the dopaminergic side effects of L-dopa and may cause and/or exacerbate preexisting dyskinesia in patients treated with L-dopa for Parkinson's disease. Decreasing the dose of a dopaminergic drug may ameliorate this side effect.

Major Psychotic Disorders

Patients with a major psychotic disorder should ordinarily not be treated with REQUIP XL (ropinirole extended release tablets) because of the risk of exacerbating the psychosis. In addition, many treatments for psychosis may decrease the effectiveness of REQUIP XL [see DRUG INTERACTIONS] .

Events Reported With Dopaminergic Therapy

Withdrawal-Emergent Hyperpyrexia and Confusion

Although not reported during the clinical development of ropinirole, a symptom complex resembling the neuroleptic malignant syndrome (characterized by elevated temperature, muscular rigidity, altered consciousness, and autonomic instability), with no other obvious etiology, has been reported in association with rapid dose reduction, withdrawal of, or changes in dopaminergic therapy. Therefore, it is recommended that the dose be tapered at the end of treatment with REQUIP XL as a prophylactic measure [see DOSAGE AND ADMINISTRATION].

Fibrotic Complications

Cases of retroperitoneal fibrosis, pulmonary infiltrates, pleural effusion, pleural thickening, pericarditis, and cardiac valvulopathy have been reported in some patients treated with ergot-derived dopaminergic agents. While these complications may resolve when the drug is discontinued, complete resolution does not always occur.

Although these adverse reactions are believed to be related to the ergoline structure of these compounds, whether other, nonergot derived dopamine agonists, such as REQUIP or REQUIP XL (ropinirole extended release tablets) , can cause them is unknown.

A small number of reports have been received of possible fibrotic complications, including pleural effusion, pleural fibrosis, interstitial lung disease, and cardiac valvulopathy, in the development program and postmarketing experience for ropinirole. In the clinical development program (N=613), 2 patients treated with REQUIP XL (ropinirole extended release tablets) had pleural effusion. While the evidence is not sufficient to establish a causal relationship between ropinirole and these fibrotic complications, a contribution of ropinirole cannot be completely ruled out in rare cases.

Melanoma

Some epidemiologic studies have shown that patients with Parkinson's disease have a higher risk (perhaps 2- to 4-fold higher) of developing melanoma than the general population. Whether the observed increased risk was due to Parkinson's disease or other factors, such as drugs used to treat Parkinson's disease, was unclear. Ropinirole is one of the dopamine agonists used to treat Parkinson's disease. Although ropinirole has not been associated with an increased risk of melanoma specifically, its potential role as a risk factor has not been systematically studied. In the clinical development program (N=613), one patient treated with REQUIP XL (ropinirole extended release tablets) and also levodopa/carbidopa developed melanoma. Patients using REQUIP XL (ropinirole extended release tablets) should be made aware of these results and undergo periodic dermatologic screening.

Retinal Pathology

Human

Because of observations made in albino rats (see below), ocular electroretinogram (ERG) assessments were conducted during a 2-year, double-blind, multicenter, flexible-dose, L-dopa controlled clinical study of immediate-release ropinirole in patients with Parkinson's disease. A total of 156 patients (78 on immediate-release ropinirole, mean dose 11.9 mg/day and 78 on L-dopa, mean dose 555.2 mg/day) were evaluated for evidence of retinal dysfunction through electroretinograms. There was no clinically meaningful difference between the treatment groups in retinal function over the duration of the study.

Albino Rats

Retinal degeneration was observed in albino rats in the 2-year carcinogenicity study at all doses tested (equivalent to 0.6 to 20 times the maximum recommended human dose (MRHD) of 24 mg/day on a mg/m2 basis), but was statistically significant at the highest dose (50 mg/kg/day). Retinal degeneration was not observed in pigmented rats after 3 months in a 2-year carcinogenicity study in albino mice, or in 1-year studies in monkeys or albino rats. The potential significance of this effect for humans has not been established, but cannot be disregarded because disruption of a mechanism that is universally present in vertebrates (e.g., disk shedding) may be involved.

Binding to Melanin

Ropinirole binds to melanin-containing tissues (i.e., eyes, skin) in pigmented rats. After a single dose, long-term retention of drug was demonstrated, with a half-life in the eye of 20 days.

Patient Counseling Information

See FDA-Approved Patient Labeling

Physicians should instruct their patients to read the Patient Information leaflet before starting therapy with REQUIP XL (ropinirole extended release tablets) and to reread it upon prescription renewal for new information regarding the use of REQUIP XL (ropinirole extended release tablets) .

Dosing Instructions

  • Patients should be instructed to take REQUIP XL (ropinirole extended release tablets) only as prescribed. If a dose is missed, patients should be advised not to double their next dose.
  • REQUIP XL (ropinirole extended release tablets) can be taken with or without food. Taking REQUIP XL (ropinirole extended release tablets) with food may reduce the occurrence of nausea [see DOSAGE AND ADMINISTRATION]
  • REQUIP XL (ropinirole extended release tablets) Tablets should be swallowed whole. They should not be chewed, crushed, or divided [see DOSAGE AND ADMINISTRATION]
  • Ropinirole is the active ingredient that is in both REQUIP XL (ropinirole extended release tablets) and REQUIP Tablets (the immediate-release formulation). Ask your patient if they are taking another medication containing ropinirole.

Postural (Orthostatic) Hypotension

Patients should be advised that they may develop postural (orthostatic) hypotension with or without symptoms such as dizziness, nausea, syncope, and sometimes sweating. Hypotension and/or orthostatic symptoms may occur more frequently during initial therapy or with an increase in dose at any time (cases have been seen after weeks of treatment). Accordingly, patients should be cautioned against standing up rapidly after sitting or lying down, especially if they have been doing so for prolonged periods, and especially at the initiation of treatment with REQUIP XL [see WARNINGS AND PRECAUTIONS].

Elevation of Blood Pressure and Changes in Heart Rate

Patients should be alerted to the possibility of increases in blood pressure during treatment with REQUIP XL (ropinirole extended release tablets) . Exacerbation of hypertension may occur. Medication dose adjustment may be necessary if elevation of blood pressure is sustained over multiple evaluations. Patients with cardiovascular disease, who may not tolerate marked changes in heart rate, should also be alerted to the possibility that they may experience significant increases or decreases in heart rate during treatment with REQUIP XL (ropinirole extended release tablets) [see WARNINGS AND PRECAUTIONS].

Sedating Effects

Patients should be alerted to the potential sedating effects caused by REQUIP XL (ropinirole extended release tablets) , including somnolence and the possibility of falling asleep while engaged in activities of daily living. Since somnolence is a frequent adverse reaction with potentially serious consequences, patients should neither drive a car nor engage in other potentially dangerous activities until they have gained sufficient experience with REQUIP XL (ropinirole extended release tablets) to gauge whether or not it affects their mental and/or motor performance adversely. Patients should be advised that if increased somnolence or episodes of falling asleep during activities of daily living (e.g., conversations, eating, driving a motor vehicle, etc.) are experienced at any time during treatment, they should not drive or participate in potentially dangerous activities until they have contacted their physician.

Because of possible additive effects, caution should be advised when patients are taking other sedating medications, alcohol, or other CNS depressants (e.g., benzodiazepines, antipsychotics, antidepressants, etc.) in combination with REQUIP XL or when taking concomitant medications that increase plasma levels of ropinirole (e.g., ciprofloxacin) [see WARNINGS AND PRECAUTIONS].

Hallucinations

Patients should be informed they may experience hallucinations (unreal visions, sounds, or sensations) while taking ropinirole. The elderly are at greater risk than younger patients with Parkinson's disease; and the risk is greater in patients who are taking ropinirole with L-dopa or taking higher doses of ropinirole, and may also be further increased in patients taking any other drugs that increase dopaminergic tone [see WARNINGS AND PRECAUTIONS].

Impulse Control Symptoms Including Compulsive Behaviors

There have been reports of patients experiencing intense urges to gamble, increased sexual urges, and other intense urges and the inability to control these urges while taking one or more of the medications that increase central dopaminergic tone, that are generally used for the treatment of Parkinson's disease or Restless Legs Syndrome, including ropinirole. In the clinical development program (N = 613), 6 patients treated with REQUIP XL (ropinirole extended release tablets) exhibited compulsive behaviors consisting of pathological gambling and/or hypersexuality. Although it is not proven that the medications caused these events, these urges were reported to have stopped in some cases when the dose was reduced or the medication was stopped. Prescribers should ask patients about the development of new or increased gambling urges, sexual urges or other urges while being treated with REQUIP XL (ropinirole extended release tablets) . Patients should inform their physician if they experience new or increased gambling urges, increased sexual urges or other intense urges while taking REQUIP XL (ropinirole extended release tablets) . Physicians should consider dose reduction or stopping the medication if a patient develops such urges while taking REQUIP XL.

Nursing Mothers

Because of the possibility that ropinirole may be excreted in breast milk, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother [see Use in Specific Populations]. Patients should be advised that ropinirole could inhibit lactation, as ropinirole inhibits prolactin secretion.

Pregnancy

Because ropinirole has been shown to have adverse effects on embryo-fetal development, including teratogenic effects, in animals, and because experience in humans is limited, patients should be advised to notify their physician if they become pregnant or intend to become pregnant during therapy [see Use in Specific Populations].

FDA-Approved Patient Labeling

Patient labeling is reproduced in the PATIENT INFORMATION section.

Physicians should instruct their patients to read the Patient Information leaflet before starting therapy with REQUIP XL (ropinirole extended release tablets) and to reread it upon prescription renewal for new information regarding the use of REQUIP XL (ropinirole extended release tablets) .

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

Two-year carcinogenicity studies were conducted in Charles River CD-1 mice at doses of 5, 15, and 50 mg/kg/day and in Sprague-Dawley rats at doses of 1.5, 15, and 50 mg/kg/day (top doses which, based on mg/m2, are equivalent to 10 and 20 times, respectively, the MRHD of 24 mg/day). In the male rat, there was a significant increase in testicular Leydig cell adenomas at all doses tested, i.e., ≥ 1.5 mg/kg (0.6 times the MRHD on a mg/m2 basis). This finding is of questionable significance because the endocrine mechanisms believed to be involved in the production of Leydig cell hyperplasia and adenomas in rats are not relevant to humans. In the female mouse, there was an increase in benign uterine endometrial polyps at a dose of 50 mg/kg/day (10 times the MRHD on a mg/m2 basis). Ropinirole was not mutagenic or clastogenic in the in vitro Ames test, the in vitrochromosome aberration test in human lymphocytes, the in vitro mouse lymphoma (L1578Y cells) assay, and the in vivo mouse micronucleus test.

When administered to female rats prior to and during mating and throughout pregnancy, ropinirole caused disruption of implantation at doses of 20 mg/kg/day (8 times the MRHD on a mg/m2 basis) or greater. This effect is thought to be due to the prolactin-lowering effect of ropinirole. In humans, chorionic gonadotropin, not prolactin, is essential for implantation. In rat studies using low doses (5 mg/kg) during the prolactin-dependent phase of early pregnancy (gestation days 0 to 8), ropinirole did not affect female fertility at dosages up to 100 mg/kg/day (40 times the MRHD on a mg/m2 basis). No effect on male fertility was observed in rats at dosages up to 125 mg/kg/day (50 times the MRHD on a mg/m2 basis).

Use In Specific Populations

Pregnancy

Pregnancy Category C. There are no adequate and well-controlled studies using ropinirole in pregnant women. REQUIP XL (ropinirole extended release tablets) should be used during pregnancy only if the potential benefit outweighs the potential risk to the fetus.

In animal reproduction studies, ropinirole has been shown to have adverse effects on embryo-fetal development, including teratogenic effects. Treatment of pregnant rats with ropinirole during organogenesis resulted in decreased fetal body weight, increased fetal death, and digital malformations at 24, 36, and 60 times the MRHD, respectively. The combined administration of ropinirole at 8 times the MRHD and a clinically relevant dose of L-dopa to pregnant rabbits during organogenesis produced a greater incidence and severity of fetal malformations (primarily digit defects) than were seen in the offspring of rabbits treated with L-dopa alone. In a perinatal-postnatal study in rats, impaired growth and development of nursing offspring and altered neurological development of female offspring were observed when dams were treated with 4 times the MRHD.

Nursing Mothers

Ropinirole inhibits prolactin secretion in humans and could potentially inhibit lactation.

Ropinirole has been detected in the milk of lactating rats. Although many drugs are excreted in human milk, transfer of ropinirole into human milk has not been demonstrated. Due to the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of ropinirole to the mother.

Pediatric Use

Safety and effectiveness in the pediatric population have not been established.

Geriatric use

Dosage adjustment is not necessary in the elderly (above 65 years), as the dose of REQUIP XL (ropinirole extended release tablets) is to be individually titrated to clinical response [see CLINICAL PHARMACOLOGY]. Pharmacokinetic studies conducted in patients demonstrated that oral clearance of ropinirole is reduced by 15% in patients above 65 years of age compared to younger patients.

Of the total number of patients who participated in clinical trials of REQUIP XL (ropinirole extended release tablets) for Parkinson's disease, 387 patients were 65 and over and 107 patients were 75 and over. Among patients receiving REQUIP XL (ropinirole extended release tablets) , hallucination was more common in elderly subjects (10%) compared with non-elderly subjects (2%). The incidence of overall adverse events increased with increasing age for both patients receiving REQUIP XL and placebo.

Renal Impairment

No dosage adjustment of ropinirole is needed in patients with moderate renal impairment (creatinine clearance of 30 to 50 mL/min). The use of ropinirole 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 should be titrated with caution in these patients.

This monograph has been modified to include the generic and brand name in many instances.

OverDose

Human Overdose Experience

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 with immediate-release ropinirole in 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 hallucination, 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

The symptoms of overdose with ropinirole are generally related to its dopaminergic activity; these symptoms may be alleviated by appropriate treatment with dopamine antagonists such as neuroleptics or metoclopramide. General supportive measures are recommended. Vital signs should be maintained, if necessary. Removal of any unabsorbed material (e.g., by gastric lavage) may be considered.

ContrainDications

None.

This monograph has been modified to include the generic and brand name in many instances.

Clinical Pharamacology

Mechanism Of Action

Ropinirole is a non-ergoline dopamine agonist with high relative in vitro specificity and full intrinsic activity at the D2 and D3 dopamine receptor subtypes, binding with higher affinity to D3 than to D2 or D4 receptor subtypes.

Ropinirole has moderate in vitro affinity for opioid receptors. Ropinirole and its metabolites have negligible in vitro affinity for dopamine D1, 5-HT1, 5-HT2, benzodiazepine, GABA, muscarinic, alpha1-, alpha2-, and beta-adrenoreceptors.

The precise mechanism of action of ropinirole as a treatment for Parkinson's disease is unknown, although it is believed to be due to stimulation of postsynaptic dopamine D2-type receptors within the caudate-putamen in the brain. This conclusion is supported by studies that show that ropinirole improves motor function in various animal models of Parkinson's disease. In particular, ropinirole attenuates the motor deficits induced by lesioning the ascending nigrostriatal dopaminergic pathway with the neurotoxin 1-methyl-4 phenyl-1,2,3,6-tetrahydropyridine (MPTP) in primates. The relevance of D3 receptor binding in Parkinson's disease is unknown.

Pharmacodynamics

Clinical experience with dopamine agonists, including ropinirole, suggests an association with impaired ability to regulate blood pressure with resulting postural hypotension, especially during dose escalation. In some subjects in clinical trials, blood pressure changes were associated with the emergence of orthostatic symptoms, bradycardia, and, in one case in a healthy volunteer, transient sinus arrest with syncope.

The mechanism of postural hypotension induced by ropinirole is presumed to be due to a D2-mediated blunting of the noradrenergic response to standing and subsequent decrease in peripheral vascular resistance. Nausea is a common concomitant symptom of orthostatic signs and symptoms.

At oral doses as low as 0.2 mg, ropinirole suppressed serum prolactin concentrations in healthy male volunteers.

Immediate-release ropinirole had no dose-related effect on ECG wave form and rhythm in young, healthy, male volunteers in the range of 0.01 to 2.5 mg. Immediate-release ropinirole had no dose- or exposure-related effect on mean QT intervals in healthy male and female volunteers titrated to doses up to 4 mg/day. The effect of ropinirole on QT intervals at higher exposures achieved either due to drug interactions, hepatic impairment, or at higher doses has not been systematically evaluated.

Pharmacokinetics

Absorption

In clinical studies with immediate-release ropinirole, over 88% of a radiolabeled dose was recovered in urine, and the absolute bioavailability was 45% to 55%, indicating approximately 50% first-pass effect.

Ropinirole displayed linear kinetics up to doses of 24 mg/day (8 mg immediate-release, 3 times a day). Increase in systemic exposure of ropinirole following oral administration of 2 to 12 mg of REQUIP XL (ropinirole extended release tablets) was approximately dose-proportional. For REQUIP XL, steady-state concentrations of ropinirole are expected to be achieved within 4 days of dosing.

Relative bioavailability of REQUIP XL (ropinirole extended release tablets) Extended-Release Tablets compared with immediate-release tablets was approximately 100%. In a repeat-dose study in patients with Parkinson's disease using REQUIP XL (ropinirole extended release tablets) 8 mg, the dose-normalized AUC(0-24) and Cmin for REQUIP XL and immediate-release ropinirole were similar. Dose-normalized Cmax was, on average, 12% lower for REQUIP XL (ropinirole extended release tablets) than for the immediate-release formulation and the median time-to-peak concentration was 6 to 10 hours. In a single-dose study, administration of REQUIP XL (ropinirole extended release tablets) to healthy volunteers with food (i.e., high-fat meal) increased AUC by approximately 30% and Cmax by approximately 44%, compared with dosing under fasted conditions. In a repeat-dose study in patients with Parkinson's disease, food (i.e., high-fat meal) increased AUC by approximately 20% and Cmax by approximately 44%; Tmax was prolonged by 3 hours (median prolongation) compared with dosing under fasted conditions [see DOSAGE AND ADMINISTRATION].

Distribution

Ropinirole is widely distributed throughout the body, with an apparent volume of distribution of 7.5 L/kg (cv = 32%). It is up to 40% bound to plasma proteins and has a blood-to-plasma ratio of 1:1.

Metabolism

Ropinirole is extensively metabolized by the liver. The major metabolic pathways are N-despropylation and hydroxylation to form the inactive N-despropyl metabolite and hydroxy metabolites. The N-despropyl metabolite is converted to carbamyl glucuronide, carboxylic acid, and N-despropyl hydroxy metabolites. The hydroxy metabolite of ropinirole is rapidly glucuronidated.

In vitro studies indicate that the major cytochrome P450 isozyme involved in the metabolism of ropinirole is CYP1A2, an enzyme known to be induced by smoking and omeprazole, and inhibited by, for example, fluvoxamine, mexiletine, and the older fluoroquinolones such as ciprofloxacin and norfloxacin.

Elimination

The clearance of ropinirole after oral administration to patients is 47 L/hr (cv = 45%) and its elimination half-life is approximately 6 hours. Less than 10% of the administered dose is excreted as unchanged drug in urine. N-despropyl ropinirole is the predominant metabolite found in urine (40%), followed by the carboxylic acid metabolite (10%), and the glucuronide of the hydroxy metabolite (10%).

Drug Interactions

Ciprofloxacin

Coadministration of ciprofloxacin (500 mg twice daily), an inhibitor of CYP1A2, with immediate-release ropinirole (2 mg 3 times daily) increased ropinirole AUC by 84% on average and Cmax by 60% (n = 12 patients).

Digoxin

Coadministration of immediate-release ropinirole (2 mg 3 times daily) with digoxin (0.125 to 0.25 mg once daily) did not alter the steady-state pharmacokinetics of digoxin in 10 patients.

Theophylline

Administration of theophylline (300 mg twice daily, a substrate of CYP1A2) did not alter the steady-state pharmacokinetics of immediate-release ropinirole (2 mg 3 times daily) in 12 patients with Parkinson's disease. Immediate-release ropinirole (2 mg 3 times daily) did not alter the pharmacokinetics of theophylline (5 mg/kg IV) in 12 patients with Parkinson's disease.

L-dopa

Coadministration of carbidopa + L-dopa (SINEMET 10/100 mg twice daily) with immediate-release ropinirole (2 mg 3 times daily) had no effect on the steady-state pharmacokinetics of ropinirole (n = 28 patients). Oral administration of immediate-release ropinirole 2 mg 3 times daily increased mean steady-state Cmax of L-dopa by 20%, but its AUC was unaffected (n = 23 patients).

Estrogens

Population pharmacokinetic analysis revealed that higher doses of estrogens (usually associated with hormone replacement therapy [HRT]) reduced the oral clearance of ropinirole by approximately 35%.

Commonly Administered Drugs

Population analysis showed that commonly administered drugs, e.g., selegiline, amantadine, tricyclic antidepressants, benzodiazepines, ibuprofen, thiazides, antihistamines, and anticholinergics, did not affect the oral clearance of ropinirole.

Population Subgroups

Because therapy with REQUIP XL (ropinirole extended release tablets) is initiated at a low dose and gradually titrated upward according to clinical tolerability to obtain the optimum therapeutic effect, adjustment of the initial dose based on gender, weight, or age is not necessary.

Age

Oral clearance of ropinirole is reduced by approximately 15% in patients above 65 years of age compared with younger patients. Dosage adjustment is not necessary in the elderly (above 65 years), as the dose of ropinirole is individually titrated to clinical response.

Gender

Female and male patients showed similar oral clearance.

Race

The influence of race on the pharmacokinetics of ropinirole has not been evaluated.

Renal Impairment

Based on population pharmacokinetic analysis, no difference was observed in the pharmacokinetics of ropinirole in patients with moderate renal impairment (creatinine clearance between 30 to 50 mL/min) compared with an age-matched population with creatinine clearance above 50 mL/min. 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 effect of hemodialysis on ropinirole clearance is not known, but because of the relatively high apparent volume of distribution of ropinirole (7.5 L/kg), significant removal of ropinirole by hemodialysis is unlikely.

Hepatic Impairment

The pharmacokinetics of ropinirole have not been studied in patients with hepatic impairment. These patients may have higher plasma levels and lower clearance of ropinirole than patients with normal hepatic function. REQUIP XL (ropinirole extended release tablets) should be titrated with caution in this population.

Other Diseases

Population pharmacokinetic analysis revealed no change in the oral clearance of ropinirole in patients with concomitant diseases such as hypertension, depression, osteoporosis/arthritis, and insomnia compared with patients who had Parkinson's disease only.

Clinical Studies

The effectiveness of the immediate-release formulation of ropinirole (REQUIP Tablets) in the treatment of early and advanced Parkinson's disease was initially established in 3 randomized, double-blind, placebo-controlled trials.

The effectiveness of REQUIP XL (ropinirole extended release tablets) in the treatment of Parkinson's disease was supported by 2 randomized, double-blind, multicenter clinical trials and clinical pharmacokinetic considerations. One trial conducted in advanced Parkinson's disease patients compared REQUIP XL (ropinirole extended release tablets) with placebo as adjunctive therapy to L-dopa. A second trial compared REQUIP XL (ropinirole extended release tablets) with REQUIP Tablets in early phase Parkinson's disease patients not receiving L-dopa.

In these studies a variety of measures were used to assess the effects of treatment (e.g., patient diaries recording time “on” and “off,” tolerability of L-dopa dose reductions, and the Unified Parkinson's Disease Rating Scale [UPDRS] scores). The UPDRS is a multi-item rating scale evaluating mentation (Part I), activities of daily living (Part II), motor performance (Part III), and complications of therapy (Part IV). Part III of the UPDRS contains 14 items designed to assess the severity of the cardinal motor findings in patients with Parkinson's disease (e.g., tremor, rigidity, bradykinesia, postural instability, etc.) scored for different body regions and has a maximum (worst) score of 108.

Study in Patients With Advanced Parkinson's Disease (With L-dopa)

The effectiveness of REQUIP XL (ropinirole extended release tablets) as adjunctive therapy to L-dopa in patients with Parkinson's disease was established in a randomized, double-blind, placebo-controlled, parallel group, 24-week clinical trial in 393 patients (Hoehn & Yahr criteria Stages II-IV) who were not adequately controlled by L-dopa therapy. Patients were allowed to be on concomitant selegiline, amantadine, anticholinergics, and catechol-O-methyltransferase (COMT) inhibitors provided the doses were stable for at least 4 weeks prior to screening and throughout the trial. The primary efficacy endpoint evaluated was the mean change from baseline in total awake time spent “off”.

Patients in this study had a mean disease duration of 8.6 years, a mean duration of exposure to L-dopa of 6.5 years, had experienced a minimum of 3 hours awake time “off” with a baseline average of approximately 7 hours awake time “off”, and had a mean baseline UPDRS motor score of approximately 30 points with similar mean data in each treatment group. The mean baseline dose of L-dopa in the group receiving REQUIP XL (ropinirole extended release tablets) was 824 mg/day and 776 mg/day for the placebo group. Patients initiated treatment at 2 mg/day for 1 week followed by increases of 2 mg/day at weekly intervals to a minimum dose of 6 mg/day. The following week, the REQUIP XL total daily dose could be further increased (based upon therapeutic response and tolerability ) to 8 mg/day. Once a daily dose of 8 mg/day was reached, the background L-dopa dosage was reduced. Thereafter, the daily dose could be increased by up to 4 mg/day approximately every 2 weeks until an optimal dose was achieved (based upon therapeutic response and tolerability). The mean dose of REQUIP XL at the end of Week 24 was 18.8 mg/day. Dose titrations were based upon the degree of symptom control, planned L-dopa dosage reduction, and/or tolerability. The maximal allowed daily dosage for REQUIP XL (ropinirole extended release tablets) was 24 mg/day.

The primary efficacy endpoint was mean change from baseline in total awake time spent “off” at Week 24. At baseline the mean total awake time spent “off” was approximately 7 hours in each treatment group. At Week 24, the total awake time spent “off”, on average, had decreased by approximately 2 hours in the group receiving REQUIP XL (ropinirole extended release tablets) and by approximately half an hour in the placebo group. The adjusted mean difference in total awake time spent “off” between REQUIP XL and placebo was -1.7 hours, which was statistically significant (ANCOVA, p < 0.0001). Results for this endpoint showing the statistical superiority of REQUIP XL (ropinirole extended release tablets) over Placebo are presented in Table 3.

Table 3. Change from Baseline in Total Awake Time Spent "Off" at Week 24

  REQUIP XL
(n = 201)
Placebo
(n = 190)
Mean “Off” time at Baseline (hours) 7.0 7.0
Mean Change from Baseline in “Off “ time (hours) -2.1 -0.4

The difference between groups in favor of REQUIP XL (ropinirole extended release tablets) , with regard to a decrease in total “off” hours, was primarily related to an increase in total “on” hours without troublesome dyskinesia. Patients treated with REQUIP XL (ropinirole extended release tablets) had a mean reduction in L-dopa dose of 278 mg/day (34%) while patients treated with placebo had a mean reduction of 164 mg/day (21%). In patients who reduced their L-dopa dose, reduction was sustained in 93% of patients treated with REQUIP XL (ropinirole extended release tablets) and in 72% of patients treated with placebo (p < 0.001).

Study in Patients With Early Parkinson's Disease (Without L-dopa)

A 36-week multicenter, double-blind, titration/3-period maintenance, cross-over study compared the efficacy of REQUIP XL (ropinirole extended release tablets) with the immediate-release formulation of REQUIP (IR) in 161 patients with early phase Parkinson's disease (Hoehn & Yahr Stages I-III) with limited prior exposure to L-dopa or dopamine agonists. Eligible subjects were randomized (1:1:1:1) to 4 treatment sequences (2 were titrated on REQUIP IR and 2 on REQUIP XL (ropinirole extended release tablets) ). The REQUIP IR titration was slower in rate than that of the REQUIP XL (ropinirole extended release tablets) . Patients were titrated, during the 12-week titration period, to their optimal dosage, based upon tolerance and therapeutic response. This was followed by 3 consecutive 8-week maintenance periods, during which patients were either maintained on the prior formulation or switched to the alternative formulation. All switches were performed overnight by using the approximately equivalent doses of ropinirole. The primary efficacy endpoint was the change of UPDRS motor score within each maintenance period.

Patients in all 4 groups started out with similar UPDRS motor scores (about 21) at baseline. All 4 groups exhibited similar improvement in UPDRS total motor scores from baseline until the completion of the titration phase, with a change in score of about -9 observed for the groups started on REQUIP IR and of about -10 for the groups started on REQUIP XL (ropinirole extended release tablets) . No difference was observed between groups when switches were made between identical formulations or between different formulations. This suggests therapeutic dosage equivalence between REQUIP IR and REQUIP XL (ropinirole extended release tablets) formulations.

The optimal daily dose at the end of the titration period for patients on REQUIP IR was substantially lower (mean 7 mg) compared to the dose at the end of the titration period for patients on REQUIP XL (ropinirole extended release tablets) (mean 18 mg). In this study, the marked difference in the final optimal dosages suggests that the higher doses afforded no additional benefit when compared to the lower doses [see DOSAGE AND ADMINISTRATION].

This monograph has been modified to include the generic and brand name in many instances.

Patient Information

REQUIP®
(RE-qwip)
(ropinirole) Tablets

REQUIP® XL ™
(RE-qwip)
(ropinirole extended-release tablets)

IF YOU HAVE PARKINSON'S DISEASE, READ THIS SIDE

IF YOU HAVE RESTLESS LEGS SYNDROME, READ THE SECOND HALF OF THIS SECTION

IMPORTANT NOTE: REQUIP XL (ropinirole extended release tablets) has not been studied in Restless Legs Syndrome (RLS) and is not approved for the treatment of RLS. However, an immediate-release form of ropinirole (REQUIP) is approved for the treatment of RLS (see second half of this section).

Read this information completely before you start taking REQUIP or REQUIP XL. Read the information each time you get more medicine. There may be new information. This leaflet provides a summary about REQUIP and REQUIP XL (ropinirole extended release tablets) . It does not include everything there is to know about your medicine. This information should not take the place of discussions with your healthcare provider about your medical condition or treatment with REQUIP or REQUIP XL (ropinirole extended release tablets) .

What are REQUIP and REQUIP XL (ropinirole extended release tablets) ?

REQUIP is a short-acting prescription medicine containing ropinirole (usually taken 3 times a day) used to treat Parkinson's disease. It is also used to treat a condition called Restless Legs Syndrome.

REQUIP XL is a long-acting prescription medicine containing ropinirole (taken once a day) used to treat Parkinson's disease.

You should not be taking more than one medicine containing ropinirole. Inform your physician if you are taking any other medicine containing ropinirole.

REQUIP and REQUIP XL (ropinirole extended release tablets) have not been studied in children.

What is the most important information I should know about REQUIP and REQUIP XL?

REQUIP and REQUIP XL (ropinirole extended release tablets) can cause serious side effects including:

  • Falling asleep during normal activities. You may fall asleep while doing normal activities such as driving a car, doing physical tasks, or using hazardous machinery while taking REQUIP or REQUIP XL (ropinirole extended release tablets) . You may suddenly fall asleep without being drowsy or without warning. This may result in having accidents. Your chances of falling asleep while doing normal activities while taking REQUIP or REQUIP XL (ropinirole extended release tablets) are greater if you take other medicines that cause drowsiness. Tell your healthcare provider right away if this happens. Before starting REQUIP or REQUIP XL (ropinirole extended release tablets) , be sure to tell your healthcare provider if you take any medicines that make you drowsy.
  • Changes in blood pressure. REQUIP and REQUIP XL (ropinirole extended release tablets) can decrease or increase your blood pressure. Lowering of your blood pressure is of special concern. If you faint, feel dizzy, nauseated, or sweaty when you stand up from sitting or lying down, this may mean that your blood pressure is decreased. If you notice this, you should contact your healthcare provider. Also, when changing position from lying down or sitting to standing up, you should do it carefully and slowly. Lowering of your blood pressure can happen especially when you start taking REQUIP or REQUIP XL (ropinirole extended release tablets) or when your dose is increased.
  • Fainting. Fainting can occur, and sometimes your heart rate may be decreased. This can happen especially when you start taking REQUIP or REQUIP XL or your dose is increased. Tell your healthcare provider if you faint or feel dizzy.
  • Hallucinations (unreal visions, sounds, or sensations) can occur in patients taking REQUIP or REQUIP XL (ropinirole extended release tablets) . The chances of having hallucinations are higher in patients with Parkinson's disease who are elderly, taking REQUIP or REQUIP XL (ropinirole extended release tablets) with other Parkinson's disease drugs, or taking higher doses of REQUIP or REQUIP XL (ropinirole extended release tablets) . If you have hallucinations, talk with your healthcare provider
  • Uncontrolled sudden movements. REQUIP or REQUIP XL (ropinirole extended release tablets) may cause uncontrolled sudden movements or make such movements you already have worse or more frequent. Tell your healthcare provider if this happens. The doses of your anti Parkinson's medicines may need to be changed.

Unusual urges. Some patients taking REQUIP or REQUIP XL (ropinirole extended release tablets) get urges to behave in a way unusual for them. Examples of this are an unusual urge to gamble or increased sexual urges and behaviors. If you notice or your family notices that you are developing any unusual behaviors, talk to your healthcare provider.

See “What are the possible side effects of REQUIP and REQUIP XL (ropinirole extended release tablets) ?”

What should I tell my healthcare provider before taking REQUIP or REQUIP XL?

Be sure to tell your healthcare provider if you:

  • have daytime sleepiness from a sleep disorder or have unexpected or unpredictable sleepiness or periods of sleep.
  • are taking any other prescription or over-the-counter medicines. Some of these medicines may increase your chances of getting side effects while taking REQUIP or REQUIP XL (ropinirole extended release tablets) .
  • start or stop taking other medicines while you are taking REQUIP or REQUIP XL. This may increase your chances of getting side effects.
  • start or stop smoking while you are taking REQUIP or REQUIP XL (ropinirole extended release tablets) . Smoking may decrease the treatment effect of REQUIP or REQUIP XL (ropinirole extended release tablets) .
  • feel dizzy, nauseated, sweaty, or faint when you first stand up from sitting or lying down.
  • drink alcoholic beverages. This may increase your chances of becoming drowsy or sleepy while taking REQUIP or REQUIP XL (ropinirole extended release tablets) .
  • have high or low blood pressure.
  • are pregnant or plan to become pregnant. REQUIP and REQUIP XL (ropinirole extended release tablets) should only be used during pregnancy if needed.
  • are breastfeeding. It is not known if REQUIP or REQUIP XL (ropinirole extended release tablets) passes into your breast milk. Talk to your healthcare provider to decide whether you will breastfeed or take REQUIP or REQUIP XL (ropinirole extended release tablets) .
  • are allergic to any of the ingredients in REQUIP or REQUIP XL (ropinirole extended release tablets) . See the end of this Patient Information leaflet for a complete list of the ingredients in REQUIP and REQUIP XL (ropinirole extended release tablets) .

How should I take REQUIP or REQUIP XL (ropinirole extended release tablets) for Parkinson's disease?

  • Take REQUIP or REQUIP XL (ropinirole extended release tablets) exactly as directed by your healthcare provider.
  • Do not suddenly stop taking REQUIP or REQUIP XL (ropinirole extended release tablets) without talking to your healthcare provider. If you stop this medicine suddenly, you may develop fever, confusion, or severe muscle stiffness.
  • Before starting REQUIP or REQUIP XL (ropinirole extended release tablets) , you should talk to your healthcare provider about what to do if you miss a dose. If you have missed the previous dose and it is time for your next dose, do not double the dose
  • Your healthcare provider will start you on a low dose of REQUIP or REQUIP XL. Your healthcare provider will change the dose until you are taking the right amount of medicine to control your symptoms. It may take several weeks before you reach a dose that controls your symptoms.

If you are taking REQUIP:

  • REQUIP Tablets are usually taken 3 times each day for Parkinson's disease.

If you are taking REQUIP XL (ropinirole extended release tablets) :

  • Take REQUIP XL (ropinirole extended release tablets) Tablets 1 time each day for Parkinson's disease, preferably at or around the same time of day
  • Swallow REQUIP XL (ropinirole extended release tablets) Tablets whole. Do not chew, crush, or split REQUIP XL (ropinirole extended release tablets) Tablets.

If you are taking either REQUIP or REQUIP XL (ropinirole extended release tablets) :

  • Contact your healthcare provider if you stop taking REQUIP or REQUIP XL (ropinirole extended release tablets) for any reason. Do not restart without talking with your healthcare provider.
  • Your healthcare provider may prescribe REQUIP or REQUIP XL (ropinirole extended release tablets) alone, or add REQUIP or REQUIP XL (ropinirole extended release tablets) to medicine that you are already taking for Parkinson's disease.
  • You should not substitute REQUIP for REQUIP XL (ropinirole extended release tablets) or REQUIP XL (ropinirole extended release tablets) for REQUIP without talking with your healthcare provider.
  • You can take REQUIP or REQUIP XL (ropinirole extended release tablets) with or without food. If you experience nausea you may try taking REQUIP or REQUIP XL (ropinirole extended release tablets) with food.

What are the possible side effects of REQUIP and REQUIP XL (ropinirole extended release tablets) ?

Serious side effects in people taking REQUIP and REQUIP XL (ropinirole extended release tablets) are described in the section “REQUIP and REQUIP XL (ropinirole extended release tablets) can cause serious side effects including” and include:

  • Falling asleep during normal activities
  • Changes in blood pressure
  • Fainting
  • Hallucinations
  • Uncontrolled sudden movements

Some patients taking REQUIP or REQUIP XL (ropinirole extended release tablets) get urges to behave in a way unusual for them. Examples of this are an unusual urge to gamble or increased sexual urges and behaviors. If you notice or your family notices that you are developing any unusual behaviors, talk to your healthcare provider.

You should be careful until you know if REQUIP or REQUIP XL (ropinirole extended release tablets) affects your ability to remain alert while doing normal daily activities, driving a car, operating machinery, or working at heights. You should also watch for the development of significant daytime sleepiness or episodes of falling asleep.

Common side effects in people taking REQUIP and REQUIP XL (ropinirole extended release tablets) include:

  • Fainting
  • Sleepiness
  • Hallucinations
  • Dizziness
  • Nausea or vomiting
  • Uncontrolled sudden movements
  • Leg swelling
  • Fatigue
  • Headache
  • Upset stomach
  • Increased sweating

This is not a complete list of side effects and should not take the place of discussions with your healthcare providers. Your healthcare provider or pharmacist can give you a more complete list of possible side effects.

Call your healthcare provider for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store REQUIP and REQUIP XL (ropinirole extended release tablets) ?

  • Store REQUIP Tablets between 68°-77°F (20°-25°C).
  • Store REQUIP XL (ropinirole extended release tablets) Tablets between 59°-86°F (15°-30°C).
  • Store REQUIP or REQUIP XL (ropinirole extended release tablets) at room temperature out of direct sunlight.
  • Keep REQUIP or REQUIP XL (ropinirole extended release tablets) in a tightly closed container.
  • Keep REQUIP or REQUIP XL (ropinirole extended release tablets) out of the reach of children.

Other Information about REQUIP and REQUIP XL (ropinirole extended release tablets) :

  • Do not share REQUIP or REQUIP XL (ropinirole extended release tablets) with other people, even if they have the same symptoms you have.
  • Studies of people with Parkinson's disease show that they may be at an increased risk of developing melanoma, a form of skin cancer, when compared to people without Parkinson's disease. It is not known if this problem is associated with Parkinson's disease or the medicines used to treat Parkinson's disease. REQUIP and REQUIP XL (ropinirole extended release tablets) are two of the medicines used to treat Parkinson's disease, therefore, patients being treated with REQUIP or REQUIP XL (ropinirole extended release tablets) should have periodic skin examinations.

This patient information leaflet summarizes the most important information about REQUIP and REQUIP XL (ropinirole extended release tablets) for Parkinson's disease. Medicines are sometimes prescribed for purposes other than those listed in this leaflet. Do not take REQUIP or REQUIP XL (ropinirole extended release tablets) for a condition for which it was not prescribed. For more information, talk with your healthcare provider or pharmacist. They can give you information about REQUIP and REQUIP XL (ropinirole extended release tablets) that is written for healthcare professionals. For more information call 1-888-825-5249 (toll-free) or visit www.requipxl.com.

What are the ingredients in REQUIP and REQUIP XL (ropinirole extended release tablets) ?

The following ingredients are in REQUIP:

Active ingredient: ropinirole (as ropinirole hydrochloride)

Inactive ingredients: croscarmellose sodium, hydrous lactose, magnesium stearate, microcrystalline cellulose, and one or more of the following: carmine, FD&C Blue No. 2 aluminum lake, FD&C Yellow No. 6 aluminum lake, hypromellose, iron oxides, polyethylene glycol, polysorbate 80, titanium dioxide.

The following ingredients are in REQUIP XL:

Active ingredient: ropinirole (as ropinirole hydrochloride)

Inactive ingredients: carboxymethylcellulose sodium, colloidal silicon dioxide, glycerol behenate, hydrogenated castor oil, hypromellose, lactose monohydrate, magnesium stearate, maltodextrin, mannitol, povidone, and one or more of the following: FD&C Yellow No. 6 aluminum lake, FD&C Blue No. 2 aluminum lake, ferric oxides (black, red, yellow), polyethylene glycol 400, titanium dioxide.

REQUIP®
(RE-qwip)
(ropinirole) Tablets

IF YOU HAVE RESTLESS LEGS SYNDROME (RLS), READ THIS SECTION

IF YOU HAVE PARKINSON'S DISEASE, READ THE EARLIER SECTION

Read this information completely before you start taking REQUIP. Read the information each time you get more medicine. There may be new information. This leaflet provides a summary about REQUIP. It does not include everything there is to know about your medicine. This information should not take the place of discussions with your healthcare provider about your medical condition or treatment with REQUIP.

Patients with RLS should take REQUIP differently than patients with Parkinson's disease (see How should I take REQUIP for RLS? for the recommended dosing for RLS). A lower dose of REQUIP is generally needed for patients with RLS, and is taken once daily before bedtime.

What is the most important information I should know about REQUIP?

REQUIP can cause serious side effects including:

  • Falling asleep during normal activities. You may fall asleep while doing normal activities such as driving a car, doing physical tasks, or using hazardous machinery while taking REQUIP. You may suddenly fall asleep without being drowsy or without warning. This may result in having accidents. Your chances of falling asleep while doing normal activities while taking REQUIP are greater if you take other medicines that cause drowsiness. Tell your healthcare provider right away if this happens. Before starting REQUIP, be sure to tell your healthcare provider if you take any medicines that make you drowsy.
  • Decrease in blood pressure. REQUIP can decrease your blood pressure. Lowering of your blood pressure is of special concern. If you faint, feel dizzy, nauseated, or sweaty when you stand up from sitting or lying down, this may mean that your blood pressure is decreased. If you notice this, you should contact your healthcare provider. Also, when changing position from lying down or sitting to standing up, you should do it carefully and slowly. Lowering of your blood pressure can happen especially when you start taking REQUIP or when your dose is increased.
  • Fainting. Fainting can occur, and sometimes your heart rate may be decreased. This can happen especially when you start taking REQUIP or your dose is increased. Tell your healthcare provider if you faint or feel dizzy
  • Hallucinations (unreal visions, sounds, or sensations) can occur in patients taking REQUIP. If you have hallucinations, talk with your healthcare provider.

Unusual urges. Some patients taking REQUIP get urges to behave in a way unusual for them. Examples of this are an unusual urge to gamble or increased sexual urges and behaviors. If you notice or your family notices that you are developing any unusual behaviors, talk to your healthcare provider.

See “What are the possible side effects of REQUIP?”

What is REQUIP?

REQUIP is a prescription medicine containing ropinirole used to treat moderate-to-severe primary Restless Legs Syndrome. It is also used to treat Parkinson's disease. Having one of these conditions does not mean you have or will develop the other.

REQUIP has not been studied in children.

What should I tell my healthcare provider before taking REQUIP?

Be sure to tell your healthcare provider if you:

  • have daytime sleepiness from a sleep disorder or have unexpected or unpredictable sleepiness or periods of sleep.
  • are taking any other prescription or over-the-counter medicines. Some of these medicines may increase your chances of getting side effects while taking REQUIP.
  • start or stop taking other medicines while you are taking REQUIP. This may increase your chances of getting side effects.
  • start or stop smoking while you are taking REQUIP. Smoking may decrease the treatment effect of REQUIP.
  • feel dizzy, nauseated, sweaty, or faint when you first stand up from sitting or lying down.
  • drink alcoholic beverages. This may increase your chances of becoming drowsy or sleepy while taking REQUIP.
  • have high or low blood pressure.
  • are pregnant or plan to become pregnant. REQUIP should only be used during pregnancy if needed.
  • are breastfeeding. It is not known if REQUIP passes into your breast milk. Talk to your healthcare provider to decide whether you will breastfeed or take REQUIP.
  • are allergic to any of the ingredients in REQUIP. See the end of this Patient Information leaflet for a complete list of the ingredients in REQUIP.

How should I take REQUIP for RLS?

  • Take REQUIP exactly as directed by your healthcare provider.
  • The usual way to take REQUIP is once in the evening, 1 to 3 hours before bedtime.
  • Your healthcare provider will start you on a low dose of REQUIP. Your healthcare provider may change the dose until you are taking the right amount of medicine to control your symptoms.
  • If you miss your dose, do not double your next dose. Take only your usual dose 1 to 3 hours before your next bedtime.
  • Contact your healthcare provider if you stop taking REQUIP for any reason. Do not restart without consulting your healthcare provider.
  • You can take REQUIP with or without food. Taking REQUIP with food may decrease the chances of feeling nauseated.

What are the possible side effects of REQUIP?

Serious side effects in people taking REQUIP are described in the section “REQUIP can cause serious side effects including” and include:

  • Falling asleep during normal activities
  • Decrease in blood pressure
  • Fainting
  • Hallucinations

Some patients taking REQUIP get urges to behave in a way unusual for them. Examples of this are an unusual urge to gamble or increased sexual urges and behaviors. If you notice or your family notices that you are developing any unusual behaviors, talk to your healthcare provider.

You should be careful until you know if REQUIP affects your ability to remain alert while doing normal daily activities, driving a car, operating machinery, or working at heights. You should also watch for the development of significant daytime sleepiness or episodes of falling asleep.

Common side effects in people taking REQUIP include:

  • Nausea or vomiting
  • Sleepiness or drowsiness
  • Dizziness
  • Fatigue

This is not a complete list of side effects and should not take the place of discussions with your healthcare providers. Your healthcare provider or pharmacist can give you a more complete list of possible side effects.

Call your healthcare provider for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store REQUIP?

  • Store REQUIP Tablets between 68°-77°F (20°-25°C).
  • Store REQUIP at room temperature out of direct sunlight.
  • Keep REQUIP in a tightly closed container.
  • Keep REQUIP out of the reach of children

Other Information about REQUIP

  • Do not share REQUIP with other people, even if they have the same symptoms you have.
  • Studies of people with Parkinson's disease show that they may be at an increased risk of developing melanoma, a form of skin cancer, when compared to people without Parkinson's disease. It is not known if this problem is associated with Parkinson's disease or the medicines used to treat Parkinson's disease. REQUIP is one of the medicines used to treat Parkinson's disease, therefore, patients being treated with REQUIP should have periodic skin examinations.

This patient information leaflet summarizes important information about REQUIP for Restless Legs Syndrome. Medicines are sometimes prescribed for purposes other than those listed in this leaflet. Do not take REQUIP for a condition for which it was not prescribed. For more information, talk with your healthcare provider or pharmacist. They can give you information about REQUIP that is written for healthcare professionals. For more information call 1-888-825-5249 (toll-free) or visit www.requip.com.

What are the ingredients in REQUIP?

The following ingredients are in REQUIP:

Active ingredient: ropinirole (as ropinirole hydrochloride)

Inactive ingredients: croscarmellose sodium, hydrous lactose, magnesium stearate, microcrystalline cellulose, and one or more of the following: carmine, FD&C Blue No. 2 aluminum lake, FD&C Yellow No. 6 aluminum lake, hypromellose, iron oxides, polyethylene glycol, polysorbate 80, titanium dioxide.

This monograph has been modified to include the generic and brand name in many instances.

Consumer Overview Uses

IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

 

ROPINIROLE EXTENDED-RELEASE - ORAL

 

(row-PIN-uh-roll)

 

COMMON BRAND NAME(S): Requip XL

 

USES: This medication is used alone or with other medications to treat Parkinson's disease. It can improve your ability to move and decrease shakiness (tremor), stiffness, slowed movement, and unsteadiness. It may also decrease the number of episodes of not being able to move ("on-off syndrome").

Ropinirole works by helping to restore the balance of a certain natural substance (dopamine) in the brain.

 

HOW TO USE: Read the Patient Information Leaflet provided by your pharmacist before you start taking ropinirole and each time you get a refill. If you have any questions, consult your doctor or pharmacist.

Take this medication by mouth, usually once daily with or without food, or as directed by your doctor. Taking this medication with food may decrease the risk of nausea. Do not crush or chew extended-release tablets. Doing so can release all of the drug at once, increasing the risk of side effects. Also, do not split the tablets unless they have a score line and your doctor or pharmacist tells you to do so. Swallow the whole or split tablet without crushing or chewing.

The dosage is based on your medical condition and response to treatment. Your doctor may direct you to start this medication at a low dose and gradually increase your dose to reduce the risk of side effects. Follow your doctor's instructions carefully.

Use this medication regularly to get the most benefit from it. To help you remember, use it at the same time each day. If you stop taking this medication for several days, you may need to slowly increase your dose back to your previous dosage. Talk with your doctor about how to restart this medication.

Do not stop taking this medication without consulting your doctor. If you suddenly stop taking this drug, withdrawal symptoms such as fever, muscle stiffness, and confusion may occur. To prevent these symptoms while you are stopping treatment with this drug, your doctor may reduce your dose gradually. Consult your doctor or pharmacist for more details.

Tell your doctor if your condition does not improve or if it worsens.

Consumer Overview Side Effect

SIDE EFFECTS: Nausea, drowsiness, dizziness, abdominal pain/discomfort, or headache may occur. If these effects persist or worsen, tell your doctor promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

You may develop a sudden drop in blood pressure, which can cause dizziness, nausea, and fainting. This is more likely when you are first starting the medication, when your dose is increased, or when you get up suddenly. To lower your risk, get up slowly from a sitting or lying position.

Tell your doctor immediately if any of these unlikely but serious side effects occur: new or worsening uncontrolled movements (dyskinesia), mental/mood changes (such as hallucinations), unusual urges (such as increased gambling or sexual urges).

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any of the following symptoms of a serious allergic reaction: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

 

Read the Requip XL (ropinirole extended release tablets) Side Effects Center for a complete guide to possible side effects

Learn More »

PRECAUTIONS: Before taking ropinirole, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: heart disease, low blood pressure, sleep disorder (such as sleep apnea, narcolepsy), mental/mood disorder, liver problems.

Some people taking ropinirole have reported falling asleep suddenly during usual daily activities (such as talking on the phone, driving). In some cases, sleep occurred without feelings of drowsiness beforehand. This effect may occur at any time during treatment, including up to 1 year after starting this medication. Therefore, do not drive or take part in other possibly dangerous activities until you are certain that this medication will not cause drowsiness or sudden sleep. This risk is increased with the use of alcohol or other medications that can make you drowsy (see Drug Interactions section). Consult your doctor for more details.

Older adults may be more sensitive to the side effects of this drug, especially mental/mood changes (such as hallucinations).

This drug should be used only when clearly needed during pregnancy. Discuss the risks and benefits with your doctor.

It is unknown if this medication passes into breast milk. Breast-feeding while using this drug is not recommended. Consult your doctor before breast-feeding.

Consumer Overview Missed Dose

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor or pharmacist first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: antipsychotic medications (such as chlorpromazine, haloperidol, thiothixene), metoclopramide.

Other medications can affect the removal of ropinirole from your body, which may affect how ropinirole works. Examples include cimetidine, fluvoxamine, mexiletine, omeprazole, rifampin, drugs to treat seizures (such as carbamazepine, phenobarbital), among others.

Tell your doctor or pharmacist if you are taking other products that can cause drowsiness, including alcohol, antihistamines (such as cetirizine, diphenhydramine), drugs for sleep or anxiety (such as alprazolam, diazepam, zolpidem), muscle relaxants, and narcotic pain relievers (such as codeine).

Check the labels on all your medicines (such as allergy or cough-and-cold products) because they may contain ingredients that cause drowsiness. Ask your pharmacist about using those products safely.

Cigarette smoking decreases blood levels of this medication. Tell your doctor if you smoke or if you have recently stopped smoking.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

 

OVERDOSE: If overdose is suspected, contact a poison control center or emergency room immediately. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.

 

NOTES: Do not share this medication with others.

People with Parkinson's disease may have an increased risk for developing skin cancer (melanoma). If you are taking this drug to treat Parkinson's disease, tell your doctor promptly if you notice a change in the appearance or size of moles or other unusual skin changes. Ask your doctor if you should have regular skin exams.

 

MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

 

STORAGE: Store in a tightly closed container at room temperature between 59-86 degrees F (15-30 degrees C) away from moisture and light.

Do not store in the bathroom. Keep all medications away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

 

Information last revised March 2013. Copyright(c) 2013 First Databank, Inc.

Patient Detailed Side Effect

Brand Names: Requip, Requip XL

Generic Name: ropinirole (oral) (Pronunciation: roe PIN i role)

  • What is ropinirole (Requip XL)?
  • What are the possible side effects of ropinirole (Requip XL)?
  • What is the most important information I should know about ropinirole (Requip XL)?
  • What should I discuss with my healthcare provider before taking ropinirole (Requip XL)?
  • How should I take ropinirole (Requip XL)?
  • What happens if I miss a dose (Requip XL)?
  • What happens if I overdose (Requip XL)?
  • What should I avoid while taking ropinirole (Requip XL)?
  • What other drugs will affect ropinirole (Requip XL)?
  • Where can I get more information?

What is ropinirole (Requip XL)?

Ropinirole has some of the same effects as a chemical called dopamine, which occurs naturally in your body. Low levels of dopamine in the brain are associated with Parkinson's disease.

Ropinirole is used to treat symptoms of Parkinson's disease, such as stiffness, tremors, muscle spasms, and poor muscle control. Ropinirole is also used to treat restless legs syndrome (RLS).

Ropinirole may also be used for other purposes not listed in this medication guide.

Requip 0.25 mg

pentagonal, white, imprinted with 4890, SB

What are the possible side effects of ropinirole (Requip XL)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have any of these serious side effects:

  • feeling like you might pass out;
  • fever, stiff muscles, confusion, sweating, fast or uneven heartbeats (especially if you stop taking ropinirole or use a lower dose);
  • hallucinations;
  • tremors (uncontrolled shaking); or
  • tight feeling in your chest, trouble breathing.

Call your doctor promptly if you fall asleep during a daily activity, if you faint, or if you have hallucinations (hearing or seeing something that is not there). Your doctor may want you to stop taking ropinirole, or take a lower dose.

Less serious side effects may occur, such as:

  • mild nausea, vomiting, stomach pain, or loss of appetite;
  • worsened RLS symptoms early in the morning;
  • diarrhea or constipation;
  • dry mouth, sweating;
  • headache;
  • dizziness, drowsiness;
  • sleep problems (insomnia); or
  • agitation or anxiety.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the Requip XL (ropinirole extended release tablets) Side Effects Center for a complete guide to possible side effects

Learn More »

What is the most important information I should know about ropinirole (Requip XL)?

Ropinirole may cause you to fall asleep during normal daytime activities such as working, talking, eating, or driving. You may fall asleep suddenly, even after feeling alert. Tell your doctor if you have any problems with daytime sleepiness or drowsiness. If you are unsure of how this medicine will affect you, be careful if you drive or do anything that requires you to be awake and alert.

You may have increased sexual urges, unusual urges to gamble, or other intense urges while taking this medication. Talk with your doctor if you believe you have any intense or unusual urges while taking ropinirole.

Do not share this medication with another person, even if they have the same symptoms you do.

Avoid drinking alcohol, which can increase some of the side effects of ropinirole.

Cold or allergy medicine, narcotic pain medicine, sleeping pills, muscle relaxers, and medicine for seizures, depression or anxiety can add to sleepiness caused by ropinirole. Tell your doctor if you regularly use any of these other medicines.

Ropinirole may cause hallucinations (the sensation of hearing or seeing something that is not there), most commonly among elderly people. Call your doctor if you experience hallucinations.

Do not stop using ropinirole or change your dose without first talking to your doctor. You may have side effects such as fever, muscle stiffness, and confusion if you stop the medication suddenly or if you change doses.

Some people taking medicines for Parkinson's disease have developed skin cancer (melanoma). However, people with Parkinson's disease may have a higher risk than most people for developing melanoma. Talk to your doctor about your specific risk and what skin symptoms to watch for. You may need to have regular skin exams.

Side Effects Centers
  • Requip
  • Requip XL

Patient Detailed How Take

What should I discuss with my healthcare provider before taking ropinirole (Requip XL)?

Ropinirole may cause you to fall asleep during normal daytime activities such as working, talking, eating, or driving. You may fall asleep suddenly, even after feeling alert. Tell your doctor if you have any problems with daytime sleepiness or drowsiness. If you are unsure of how this medicine will affect you, be careful if you drive or do anything that requires you to be awake and alert.

You should not use this medication if you are allergic to ropinirole.

If you have certain conditions, you may need a dose adjustment or special tests to safely take this medication. Before you take this medication, tell your doctor if you are allergic to any drugs, or if you have:

  • heart disease;
  • high or low blood pressure;
  • mental illness or compulsive behaviors;
  • kidney disease;
  • liver disease; or
  • if you smoke.

You may have increased sexual urges, unusual urges to gamble, or other intense urges while taking ropinirole. It is not known whether the medicine actually causes this effect. Talk with your doctor if you believe you have any intense or unusual urges while taking ropinirole.

FDA pregnancy category C. It is not known whether ropinirole is harmful to an unborn baby. Before taking this medication, tell your doctor if you are pregnant or plan to become pregnant during treatment.

It is not known whether ropinirole passes into breast milk or if it could harm a nursing baby. Ropinirole may reduce breast milk production. Do not take ropinirole without telling your doctor if you are breast-feeding a baby.

Ropinirole may cause hallucinations (the sensation of hearing or seeing something that is not there), most commonly among elderly people. Call your doctor if you experience hallucinations.

Some people taking medicines for Parkinson's disease have developed skin cancer (melanoma). However, people with Parkinson's disease may have a higher risk than most people for developing melanoma. Talk to your doctor about your specific risk and what skin symptoms to watch for. You may need to have regular skin exams.

How should I take ropinirole (Requip XL)?

Take this medication exactly as it was prescribed for you. Do not take the medication in larger amounts, or take it for longer than recommended by your doctor. Follow the directions on your prescription label.

The dose and timing of ropinirole in treating Parkinson's disease is different from the dose and timing in treating RLS.

You may receive ropinirole in a starting kit that has each pill marked with the day you should take it. Do not mix these pills up because they each contain different amounts of ropinirole. The pills must be taken in order so that you gradually receive higher doses of the medication.

You may have a brief increase in side effects whenever your dose is changed.

Ropinirole can be taken with or without food. Taking the medicine with food may help prevent nausea, which is a common side effect of ropinirole.

It may take several weeks or months of using this medicine before your symptoms improve. For best results, keep using the medication as directed.

Do not stop taking ropinirole suddenly or change your doses, or you could have unpleasant withdrawal symptoms such as fever, muscle stiffness, and confusion. Talk to your doctor about how to avoid withdrawal symptoms when stopping the medication.

Do not share this medication with another person, even if they have the same symptoms you do.

Store ropinirole at room temperature away from moisture and heat.

Side Effects Centers
  • Requip
  • Requip XL

Patient Detailed Avoid Taking

What happens if I miss a dose (Requip XL)?

Take the missed dose as soon as you remember. If it is almost time for your next dose, skip the missed dose and take the medicine at the next regularly scheduled time. Do not take extra medicine to make up the missed dose.

What happens if I overdose (Requip XL)?

Seek emergency medical attention if you think you have used too much of this medicine.

Overdose symptoms may include nausea, vomiting, weakness, fainting, agitation, confusion, hallucinations, muscle twitching, tingly feeling, and chest pain.

What should I avoid while taking ropinirole (Requip XL)?

Ropinirole can cause side effects that may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be awake and alert.

Avoid smoking, which can make ropinirole less effective.

Avoid drinking alcohol. It can increase some of the side effects of ropinirole.

Avoid getting up too fast from a sitting or lying position, or you may feel dizzy. Get up slowly and steady yourself to prevent a fall.

What other drugs will affect ropinirole (Requip XL)?

Cold or allergy medicine, narcotic pain medicine, sleeping pills, muscle relaxers, and medicine for seizures, depression or anxiety can add to sleepiness caused by ropinirole. Tell your doctor if you regularly use any of these other medicines, or any other Parkinson's medications..

Before taking ropinirole, tell your doctor if you are using any of the following drugs:

  • levodopa;
  • ciprofloxacin (Cipro);
  • fluvoxamine (Luvox);
  • metoclopramide (Reglan);
  • omeprazole (Prilosec);
  • a medication used to treat nausea and vomiting or mental illness, such as chlorpromazine (Thorazine), fluphenazine (Prolixin), mesoridazine (Serentil), perphenazine (Trilafon), thioridazine (Mellaril), promazine (Sparine), trifluoperazine (Stelazine), thiothixene (Navane), or haloperidol (Haldol); or
  • an estrogen such as Premarin, Prempro, Estratest, Ogen, Estraderm, Climara, Vivelle, estradiol, and others.

This list is not complete and there may be other drugs that can interact with ropinirole. Tell your doctor about all the prescription and over-the-counter medications you use. This includes vitamins, minerals, herbal products, and drugs prescribed by other doctors. Do not start using a new medication without telling your doctor.

Where can I get more information?

Your pharmacist can provide more information about ropinirole.


Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

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