24 Hr Ropinirole 6 Mg Extended Release Oral Tablet

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 (14.2)]. Due to the flexible dosing design used in clinical studies, specific dose response information could not be determined.   

When Ropinirole Extended-release Tablets are 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 Ropinirole Extended-release Tablets of 8 mg/day. Overall, L-dopa dose reduction was sustained in 93% of patients treated with 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 Ropinirole Extended-release Tablets [see Clinical Studies (14)].

Ropinirole Extended-release Tablets should be discontinued gradually over a 7-day period.   

                                                                                                                                 771

      one side and plain on other side.

●    4 mg Light brown, coated, circular shaped tablets with beveled edge, debossed with  

      ‘W’   on one side and plain on other side.

     773

●    6 mg White, coated, circular shaped tablets with beveled edge, debossed with ‘W’ on

                                                                                                                                    776

     one side and plain on other side.

●    8 mg Brown, coated, circular shaped tablets with beveled edge, debossed with ‘W’ on

                                                                                                                                     774

     one side and plain on other side.

●    12 mg Green, coated, circular shaped tablets with beveled edge, debossed with ‘W’

                                                                                                                                     775

     on one side and plain on other side.

Among the 613 patients who received 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 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 Ropinirole Extended-release Tablets compared with 15% (22 of 149) of patients receiving the immediate-release formulation of ropinirole tablets [see Adverse Reactions (6)]. However, because dose-response was not systematically studied with Ropinirole Extended-release Tablets, the occurrence of somnolence at the highest recommended doses may be higher than these reported frequencies [see Adverse Reactions (6)].   

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 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 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 (7.1)]. If a patient develops significant daytime sleepiness or episodes of falling asleep during activities that require active participation (e.g., driving a motor vehicle, conversations, eating, etc.), Ropinirole Extended-release Tablets should ordinarily be discontinued [see Dosage and Administration for guidance in discontinuing Ropinirole Extended-release Tablets (2.2)]. If a decision is made to continue 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.  

In a placebo-controlled study involving patients with advanced Parkinson’s disease, syncope occurred in 2 of the 202 patients (1%) who received Ropinirole Extended-release Tablets and in none of the 191 patients who received placebo.  

Because the study of 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.

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 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 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 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 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 Ropinirole Extended-release Tablets vs. 31% for placebo for mild to moderate systolic blood pressure decrements (≥20 mm Hg), 63% for Ropinirole Extended-release Tablets vs. 58% for  placebo for mild to moderate diastolic blood pressure decrements (≥10 mm Hg), 10% for Ropinirole Extended-release Tablets vs. 7% for placebo for severe diastolic blood pressure decrements (≥20 mm Hg), and 23% for 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 Ropinirole Extended-release Tablets. In the semi-supine position, the frequency was 10% for Ropinirole Extended-release Tablets vs. 8% for placebo for severe systolic blood pressure decrease (≥40 mm Hg), and was 25% for 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.  

In the semi-supine position, the frequency was 8% for 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 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 Ropinirole Extended-release Tablets vs. 18% for placebo for moderate pulse increase (≥15 beats/minute), and 19% for Ropinirole Extended-release Tablets vs. 17% for placebo for moderate pulse decrease (≥15 beats/minute). In the standing position, the frequency was 2% for Ropinirole Extended-release Tablets vs. <1% for placebo for severe pulse increase (≥30 beats/minute), and 24% for 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 Ropinirole Extended-release Tablets should be considered when treating patients with cardiovascular disease.

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 Ropinirole Extended-release Tablets plus L-dopa (6%), and in 7 of 47 patients taking entacapone with Ropinirole Extended-release Tablets plus L-dopa (15%).   

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 Ropinirole Extended-release Tablets as a prophylactic measure [see Dosage and Administration (2.2)].

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 ropinirole tablets or 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 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 Ropinirole Extended-release Tablets and also levodopa/carbidopa developed melanoma. Patients using Ropinirole Extended-release Tablets should be made aware of these results and undergo periodic dermatologic screening.  

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.

During the premarketing development of Ropinirole Extended-release Tablets patients with advanced Parkinson’s disease received 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 Ropinirole Extended-release Tablets or the immediate-release formulation of ropinirole tablets 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 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 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 Ropinirole Extended-release Tablet 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 Ropinirole Extended-release Tablets who participated in the 26-week, double-blind, placebo-controlled study. In this study, either Ropinirole Extended-release Tablets or placebo was used as an adjunct to L-dopa. Adverse reactions were generally mild or moderate in intensity.  

In patients with advanced Parkinson's disease who were treated with the immediate-release formulation of ropinirole tablets 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 ropinirole tablets, 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%).

Coadministration of ciprofloxacin, an inhibitor of CYP1A2, with immediate-release ropinirole increased the AUC of ropinirole by 84% on average and C_max by 60% [see Clinical Pharmacology (12.3)].

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 C_max 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 (12.3)].

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.

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.

Of the total number of patients who participated in clinical trials of Ropinirole Extended-release Tablets for Parkinson’s disease, 387 patients were 65 and over and 107 patients were 75 and over. Among patients receiving 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 Ropinirole Extended-release Tablets and placebo.  

The structural formula is:

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.

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.

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 Ropinirole Extended-release Tablet was approximately dose-proportional. For Ropinirole Extended-release Tablets, steady-state concentrations of ropinirole are expected to be achieved within 4 days of dosing.      

Relative bioavailability of Ropinirole Extended-release Tablets compared with immediate-release tablet was approximately 100%. In a repeat-dose study in patients with Parkinson’s disease using Ropinirole Extended-release Tablets 8 mg, the dose-normalized AUC _(0-24) and C_min for Ropinirole Extended-release Tablets and immediate-release ropinirole were similar. Dose- normalized C_max was, on average, 12% lower for 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 Ropinirole Extended-release Tablets to healthy volunteers with food (i.e., high-fat meal) increased AUC by approximately 30% and C_max 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 C_max by approximately 44%; T_max was prolonged by 3 hours (median prolongation) compared with dosing under fasted conditions [see Dosage and Administration (2.1)].

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 C_max 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 C_max 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 Ropinirole Extended-release Tablets are 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. 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.

Ropinirole was not mutagenic or clastogenic in the in vitro Ames test, the in vitro chromosome 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).

●   2 mg Pink, coated, circular shaped tablets with beveled edge, debossed with ‘W’ on

                                                                                                                                771

     one side and plain on other side, in bottle of 30 (NDC 64679-771-01), 90 (NDC      

      64679-771-02), 100 (NDC 64679-771-05), 500 (NDC 64679-771-03) and Unit dose

      packages of 100 (NDC 64679-771-04).

●   4 mg Light brown, coated, circular shaped tablets with beveled edge, debossed with

      ‘W’  on one side and plain on other side, in bottle of 30 (NDC 64679-773-01),          

773

      90 (NDC 64679-773-02), 100 (NDC 64679-773-05), 500 (NDC 64679-773-03) and

      Unit dose packages of 100 (NDC 64679-773-04).

●     6 mg White, coated, circular shaped tablets with beveled edge, debossed with ‘W’ on

                                                                                                                                    776

     one side and plain on other side, in bottle of 30 (NDC 64679-776-01), 90 (NDC

      64679-776-02), 100 (NDC 64679-776-05), 500 (NDC 64679-776-03) and Unit dose

      packages of 100 (NDC 64679-776-04).

●    8 mg Brown, coated, circular shaped tablets with beveled edge, debossed with ‘W’ on

                                                                                                                                     774

     one side and plain on other side, in bottle of 30 (NDC 64679-774-01), 90 (NDC

      64679-774-02), 100 (NDC 64679-774-05), 500 (NDC 64679-774-03) and Unit dose

      packages of 100 (NDC 64679-774-04).

●   12 mg Green, coated, circular shaped tablets with beveled edge, debossed with ‘W’ on

                                                                                                                                     775

     one side and plain on other side, in bottle of 30 (NDC 64679-775-01), 90 (NDC

      64679-775-02), 100 (NDC 64679-775-05), 500 (NDC 64679-775-03) and Unit dose

      packages of 100 (NDC 64679-775-04).

Storage: Store at 20°-25°C (68°-77°F) [See USP Controlled Room Temperature]. Dispense in a tight, light-resistant container as defined in the USP.

Physicians should instruct their patients to read the Patient Information leaflet before starting therapy with Ropinirole Extended-release Tablets and to reread it upon prescription renewal for new information regarding the use of Ropinirole Extended-release Tablets.   

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 Ropinirole Extended-release Tablets or when taking concomitant medications that increase plasma levels of ropinirole (e.g., ciprofloxacin) [see Warnings and Precautions (5.1)].   

Patients should be advised that ropinirole could inhibit lactation, as ropinirole inhibits prolactin secretion.

Physicians should instruct their patients to read the Patient Information leaflet before starting therapy with Ropinirole Extended-release Tablets and to reread it upon prescription renewal for new information regarding the use of Ropinirole Extended-release Tablets.

*SINEMET is a registered trademark of Merck & co., Inc,

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