Requip

Ropinirole, sold under the brand name Requip, is used to treat Parkinson's disease and restless legs syndrome (RLS).

The medication is in a class of drugs called dopamine agonists, which work by replacing dopamine, a natural substance in the brain that helps control movement (among other functions).

Ropinirole comes in an oral standard tablet and an extended-release tablet (Requip XL). It was approved by the Food and Drug Administration (FDA) in 2008 and is manufactured by GlaxoSmithKline.

Ropinirole Warnings

Some medications have names that are similar to the brand name of this drug. Be sure that you receive ropinirole, Requip, or Requip XL — not a different drug with a similar name.

Your doctor will probably start you on a low dose of ropinirole and gradually increase your dose. It may take several weeks before you achieve a dose that works for you.

You should continue to take ropinirole even if you feel well.

Don't stop taking this drug without talking to your doctor, as abruptly stopping ropinirole may cause fever, fast heartbeat, muscle stiffness, sweating, confusion, or other symptoms.

Your doctor will likely decrease your dose gradually if you stop taking ropinirole.

This medicine may make you feel drowsy or sleepy. You should not drive a car, operate machinery, or participate in activities that require alertness until you know how ropinirole will affect you.

If you have Parkinson's disease, you may have a greater risk of developing melanoma, a type of skin cancer. There's not enough research to know whether medications used to treat Parkinson's, such as ropinirole, contribute to this risk.

You should have regular skin examinations to check for melanoma while taking ropinirole.

Some people who take medications such as ropinirole develop gambling problems, sexually compulsive behaviors, or other urges or unusual behaviors. Call your doctor if you experience any intense or unusual urges.

Pregnancy and Ropinirole

There are no adequate studies to show ropinirole is safe in pregnant or breastfeeding women.

If you're pregnant, might become pregnant, or are breastfeeding, talk with your doctor before taking ropinirole.

An average dosing schedule of ropinirole may look like this:

Oral dosage extended-release tablets:

For Parkinson's disease:

Adults: Start with 2 milligrams (mg) once a day for one to two weeks. Your doctor may increase your dose. However, the dose is usually not more than 24 mg per day.

You should swallow the extended-release tablets (Requip XL) whole. Do not split, chew, or crush them.

Oral dosage regular tablets:

For Parkinson's disease:

• Adults: Start with 0.25 mg, three times a day. Your doctor may increase your dose. However, the dose is usually not more than 24 mg a day.

For Restless Leg Syndrome (RLS):

• Adults: Start with 0.25 mg, once a day, one to three hours before bedtime. Your doctor will increase your dose as needed. However, the dose is usually not more than 4 mga day.

Ropinirole Overdose

If you suspect an overdose, immediately contact an emergency room or a poison control center at (800) 222-1222.

Missed Dose of Ropinirole

If you forget to take a dose of ropinirole regular or extended-release tablets to treat Parkinson’s disease, take it as soon as you remember.

However, if it's almost time for the next dose, skip the missed dose and continue on your regular dosing schedule.

If you forget to take a dose of ropinirole regular tablets to treat restless leg syndrome (RLS), skip the missed dose.

Take your regular dose one to three hours before your next bedtime.

Don't “double dose” to make up for the missed dose.

Parkinsonian Syndrome

Symptomatic management of idiopathic parkinsonian syndrome.1 2 3 4 5 7 8 11 13 14 15

Used as an adjunct to levodopa for the symptomatic management of parkinsonian syndrome in patients with advanced disease.18 19

Also used as monotherapy for the initial symptomatic management of parkinsonian syndrome.18 Most clinicians would use levodopa for initial therapy in individuals >70 years of age (less likely than younger individuals to develop levodopa-related motor complications and because of concerns about cognitive dysfunction), in patients with cognitive impairment, and in those with severe disease.18 A dopamine receptor agonist may be preferred for initial therapy in patients ≤70 years of age.18

Restless Legs Syndrome

Symptomatic management of moderate-to-severe primary restless legs syndrome (Ekbom syndrome).1 21 22 23 24 25 26 27

Metabolized principally by CYP1A2.1

Drugs Affecting Hepatic Microsomal Enzymes

Potential for pharmacokinetic interactions with drugs that are inhibitors or inducers of CYP1A2, with possible alteration in metabolism of ropinirole.1 If a potent CYP1A2 inhibitor is initiated or discontinued during treatment with ropinirole, adjustment of the ropinirole dosage may be required.1

Dopamine Antagonists

Possible pharmacodynamic interaction, resulting in diminished effectiveness of ropinirole.1

Specific Drugs

Drug	Interaction	Comments
Amantadine	Alteration of oral clearance of ropinirole is unlikely1
Anticholinergic agents	Alteration of oral clearance of ropinirole is unlikely1
Antidepressants, tricyclics	Alteration of oral clearance of ropinirole is unlikely1
Antihistamines	Alteration of oral clearance of ropinirole is unlikely1
Antipsychotic agents (e.g., phenothiazines, butyrophenones, thioxanthenes)	Dopamine antagonist activity of the antipsychotic agent may diminish effectiveness of ropinirole1	Use concomitantly in patients with major psychotic disorders only if the potential benefits outweigh the risks1
Benzodiazepines	Alteration of oral clearance of ropinirole is unlikely1
Ciprofloxacin	Increased peak plasma concentration and AUC of ropinirole1	Use with caution1
CNS depressants (e.g., alcohol, antidepressants, antipsychotics, benzodiazepines)	Possible additive sedative effects1	Use with caution1
Digoxin	Pharmacokinetic interaction unlikely1
Diuretics, thiazides	Alteration of oral clearance of ropinirole is unlikely1
Estrogens (e.g., ethinyl estradiol)	Reduced oral clearance of ropinirole1	If estrogen therapy is initiated or discontinued during treatment with ropinirole, adjustment of the ropinirole dosage may be required1
Ibuprofen	Alteration of oral clearance of ropinirole is unlikely1
Levodopa	Parkinsonian syndrome: Additive therapeutic and/or adverse (e.g., dyskinesia) effects1 17	Parkinsonian syndrome: Consider a reduction in levodopa dosage when ropinirole is added to levodopa therapy1 17
Metoclopramide	Dopamine antagonist activity of metoclopramide may diminish effectiveness of ropinirole1
Selegiline	Alteration of oral clearance of ropinirole is unlikely1
Smoking	Smoking is expected to increase the clearance of ropinirole, since CYP1A2 is induced by smoking1
Theophylline	Pharmacokinetic interaction unlikely1

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

rOPINIRole Hydrochloride

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets, film-coated	0.25 mg (of ropinirole)*	Requip Tiltab	GlaxoSmithKline
			Ropinirole Hydrochloride Tablets
		0.5 mg (of ropinirole)*	Requip Tiltab	GlaxoSmithKline
			Ropinirole Hydrochloride Tablets
		1 mg (of ropinirole)*	Requip Tiltab	GlaxoSmithKline
			Ropinirole Hydrochloride Tablets
		2 mg (of ropinirole)*	Requip Tiltab	GlaxoSmithKline
			Ropinirole Hydrochloride Tablets
		3 mg (of ropinirole)*	Requip Tiltab	GlaxoSmithKline
			Ropinirole Hydrochloride Tablets
		4 mg (of ropinirole)*	Requip Tiltab	GlaxoSmithKline
			Ropinirole Hydrochloride Tablets
		5 mg (of ropinirole)*	Requip Tiltab	GlaxoSmithKline
			Ropinirole Hydrochloride Tablets

• Tell all of your health care providers that you take Requip. This includes your doctors, nurses, pharmacists, and dentists.
• Avoid driving and doing other tasks or actions that call for you to be alert until you see how this medicine affects you.
• To lower the chance of feeling dizzy or passing out, rise slowly if you have been sitting or lying down. Be careful going up and down stairs.
• Do not stop taking Requip all of a sudden without calling your doctor. You may have a greater risk of side effects. If you need to stop this medicine, you will want to slowly stop it as ordered by your doctor.
• If you start or stop smoking, talk with your doctor. How much drug you take may need to be changed.
• Talk with your doctor before you drink alcohol or use other drugs and natural products that slow your actions.
• Check blood pressure and heart rate as the doctor has told you. Talk with the doctor.
• Do not switch between different forms of Requip without first talking with the doctor.
• If you are 65 or older, use this medicine with care. You could have more side effects.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using Requip while you are pregnant.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

Parkinson's disease:

• The chance of a type of skin cancer called melanoma may be raised in people with Parkinson's disease. It is not known if this medicine may also raise the chance. Have skin exams while you take Requip. Talk with your doctor.

Restless leg syndrome:

• Tell your doctor if your signs become worse or start earlier in the day.
• Have your skin checked as you have been told by your doctor. Talk with your doctor.

• Store at room temperature.
• Protect from light.
• Store in a dry place. Do not store in a bathroom.
• Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
• Check with your pharmacist about how to throw out unused drugs.

Requip is contraindicated in patients known to have a hypersensitivity/allergic reaction (including urticaria, angioedema, rash, pruritus) to ropinirole or to any of the excipients.

The following adverse reactions are described in more detail in other sections of the label:

• Hypersensitivity [see Contraindications (4)] • Falling Asleep during Activities of Daily Living and Somnolence [see Warnings and Precautions (5.1)] • Syncope [see Warnings and Precautions (5.2)] • Hypotension/Orthostatic Hypotension [see Warnings and Precautions (5.3)] • Hallucinations/Psychotic-like Behavior [see Warnings and Precautions (5.4)] • Dyskinesia [see Warnings and Precautions (5.5)] • Impulse Control/Compulsive Behaviors [see Warnings and Precautions (5.6)] • Withdrawal-Emergent Hyperpyrexia and Confusion [see Warnings and Precautions (5.7)] • Melanoma [see Warnings and Precautions (5.8)] • Augmentation and Early-Morning Rebound in RLS [see Warnings and Precautions (5.9)] • Fibrotic Complications [see Warnings and Precautions (5.10)] • Retinal Pathology [see Warnings and Precautions (5.11)]

Clinical Trials 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.

Parkinson’s Disease

During the premarketing development of Requip, patients received Requip either without L-dopa (early Parkinson’s disease trials) or as concomitant therapy with L-dopa (advanced Parkinson’s disease trials). Because these two populations may have differential risks for various adverse reactions, this section will in general present adverse reaction data for these two populations separately.

Early Parkinson’s Disease (without L-dopa)

In the double-blind, placebo-controlled trials in patients with early-stage Parkinson’s disease, the most commonly observed adverse reactions in patients treated with Requip (incidence at least 5% greater than placebo) were nausea, somnolence, dizziness, syncope, asthenic condition (i.e., asthenia, fatigue, and/or malaise), viral infection, leg edema, vomiting, and dyspepsia.

Approximately 24% of patients treated with Requip who participated in the double-blind, placebo-controlled early Parkinson’s disease (without L-dopa) trials discontinued treatment due to adverse reactions compared with 13% of patients who received placebo. The most common adverse reactions in patients treated with Requip (incidence at least 2% greater than placebo) of sufficient severity to cause discontinuation were nausea and dizziness.

Table 3 lists treatment-emergent adverse reactions that occurred in at least 2% of patients with early Parkinson’s disease (without L-dopa) treated with Requip participating in the double-blind, placebo-controlled trials and were numerically more common than the incidence for placebo-treated patients. In these trials, either Requip or placebo was used as early therapy (i.e., without L-dopa).

Table 3. Treatment-Emergent Adverse Reaction Incidence in Double-blind, Placebo-Controlled Early Parkinson’s Disease (without L-dopa) Trials (Events ≥2% of Patients Treated with Requip and Numerically More Frequent than the Placebo Group)a

Body System/Adverse Reaction	Requip (n = 157) (%)	Placebo (n = 147) (%)
Autonomic nervous system
Flushing	3	1
Dry mouth	5	3
Increased sweating	6	4
Body as a whole
Asthenic conditionb	16	5
Chest pain	4	2
Dependent edema	6	3
Leg edema	7	1
Pain	8	4
Cardiovascular general
Hypertension	5	3
Hypotension	2	0
Orthostatic symptoms	6	5
Syncope	12	1
Central/peripheral nervous system
Dizziness	40	22
Hyperkinesia	2	1
Hypesthesia	4	2
Vertigo	2	0
Gastrointestinal
Abdominal pain	6	3
Anorexia	4	1
Dyspepsia	10	5
Flatulence	3	1
Nausea	60	22
Vomiting	12	7
Heart rate/rhythm
Extrasystoles	2	1
Atrial fibrillation	2	0
Palpitation	3	2
Tachycardia	2	0
Metabolic/nutritional
Increased alkaline phosphatase	3	1
Psychiatric
Amnesia	3	1
Impaired concentration	2	0
Confusion	5	1
Hallucination	5	1
Somnolence	40	6
Yawning	3	0
Reproductive male
Impotence	3	1
Resistance mechanism
Viral infection	11	3
Respiratory
Bronchitis	3	1
Dyspnea	3	0
Pharyngitis	6	4
Rhinitis	4	3
Sinusitis	4	3
Urinary
Urinary tract infection	5	4
Vascular extracardiac
Peripheral ischemia	3	0
Vision
Eye abnormality	3	1
Abnormal vision	6	3
Xerophthalmia	2	0

  a Patients may have reported multiple adverse reactions during the trial or at discontinuation; thus, patients may be included in more than one category.   b Asthenic condition (i.e., asthenia, fatigue, and/or malaise).

Advanced Parkinson’s Disease (with L-dopa)

In the double-blind, placebo-controlled trials in patients with advanced-stage Parkinson’s disease, the most commonly observed adverse reactions in patients treated with Requip (incidence at least 5% greater than placebo) were dyskinesia, somnolence, nausea, dizziness, confusion, hallucinations, increased sweating, and headache.

Approximately 24% of patients who received Requip in the double-blind, placebo-controlled advanced Parkinson’s disease (with L-dopa) trials discontinued treatment due to adverse reactions compared with 18% of patients who received placebo. The most common adverse reaction in patients treated with Requip (incidence at least 2% greater than placebo) of sufficient severity to cause discontinuation was dizziness.

Table 4 lists treatment-emergent adverse reactions that occurred in at least 2% of patients with advanced Parkinson’s disease (with L-dopa) treated with Requip who participated in the double-blind, placebo-controlled trials and were numerically more common than the incidence for placebo-treated patients. In these trials, either Requip or placebo was used as an adjunct to L-dopa.

Table 4. Treatment-Emergent Adverse Reaction Incidence in Double-blind, Placebo-Controlled Advanced Parkinson’s Disease (with L-dopa) Trials (Events ≥2% of Patients Treated with Requip and Numerically More Frequent than the Placebo Group)a

Body System/Adverse Reaction	Requip (n = 208) (%)	Placebo (n = 120) (%)
Autonomic nervous system
Dry mouth	5	1
Increased sweating	7	2
Body as a whole
Increased drug level	7	3
Pain	5	3
Cardiovascular general
Hypotension	2	1
Syncope	3	2
Central/peripheral nervous system
Dizziness	26	16
Dyskinesia	34	13
Falls	10	7
Headache	17	12
Hypokinesia	5	4
Paresis	3	0
Paresthesia	5	3
Tremor	6	3
Gastrointestinal
Abdominal pain	9	8
Constipation	6	3
Diarrhea	5	3
Dysphagia	2	1
Flatulence	2	1
Nausea	30	18
Increased saliva	2	1
Vomiting	7	4
Metabolic/nutritional
Weight decrease	2	1
Musculoskeletal
Arthralgia	7	5
Arthritis	3	1
Psychiatric
Amnesia	5	1
Anxiety	6	3
Confusion	9	2
Abnormal dreaming	3	2
Hallucination	10	4
Nervousness	5	3
Somnolence	20	8
Red blood cell
Anemia	2	0
Resistance mechanism
Upper respiratory tract infection	9	8
Respiratory
Dyspnea	3	2
Urinary
Pyuria	2	1
Urinary incontinence	2	1
Urinary tract infection	6	3
Vision
Diplopia	2	1

  a Patients may have reported multiple adverse reactions during the trial or at discontinuation; thus, patients may be included in more than one category.

Restless Legs Syndrome

In the double-blind, placebo-controlled trials in patients with RLS, the most commonly observed adverse reactions in patients treated with Requip (incidence at least 5% greater than placebo) were nausea, vomiting, somnolence, dizziness, and asthenic condition (i.e., asthenia, fatigue, and/or malaise).

Approximately 5% of patients treated with Requip who participated in the double-blind, placebo-controlled trials in the treatment of RLS discontinued treatment due to adverse reactions compared with 4% of patients who received placebo. The most common adverse reaction in patients treated with Requip (incidence at least 2% greater than placebo) of sufficient severity to cause discontinuation was nausea.

Table 5 lists treatment-emergent adverse reactions that occurred in at least 2% of patients with RLS treated with Requip participating in the 12-week, double-blind, placebo-controlled trials and were numerically more common than the incidence for placebo-treated patients.

Table 5. Treatment-Emergent Adverse Reaction Incidence in Double-blind, Placebo-Controlled RLS Trials (Events ≥2% of Patients Treated with Requip and Numerically More Frequent than the Placebo Group)a

Body System/Adverse Reaction	Requip (n = 496) (%)	Placebo (n =500) (%)
Ear and labyrinth
Vertigo	2	1
Gastrointestinal
Nausea	40	8
Vomiting	11	2
Diarrhea	5	3
Dyspepsia	4	3
Dry mouth	3	2
Abdominal pain upper	3	1
General disorders and administration site conditions
Asthenic conditionb	9	4
Edema peripheral	2	1
Infections and infestations
Nasopharyngitis	9	8
Influenza	3	2
Musculoskeletal and connective tissue
Arthralgia	4	3
Muscle cramps	3	2
Pain in extremity	3	2
Nervous system
Somnolence	12	6
Dizziness	11	5
Paresthesia	3	1
Respiratory, thoracic, and mediastinal
Cough	3	2
Nasal congestion	2	1
Skin and subcutaneous tissue
Hyperhidrosis	3	1

  a Patients may have reported multiple adverse reactions during the trial or at discontinuation; thus, patients may be included in more than one category.   b Asthenic condition (i.e., asthenia, fatigue, and/or malaise).

CYP1A2 Inhibitors and Inducers

In vitro metabolism 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 Requip, adjustment of the dose of Requip may be required. Coadministration of ciprofloxacin, an inhibitor of CYP1A2, increases the AUC and Cmax of ropinirole [see Clinical Pharmacology (12.3)]. Cigarette smoking is expected to increase the clearance of ropinirole since CYP1A2 is known to be induced by smoking [see Clinical Pharmacology (12.3)].

Estrogens

Population pharmacokinetic analysis revealed that higher doses of estrogens (usually associated with hormone replacement therapy [HRT]) reduced the clearance of ropinirole. Starting or stopping HRT may require adjustment of dosage of Requip [see Clinical Pharmacology (12.3)].

Dopamine Antagonists

Because ropinirole is a dopamine agonist, it is possible that dopamine antagonists such as neuroleptics (e.g., phenothiazines, butyrophenones, thioxanthenes) or metoclopramide may reduce the efficacy of Requip.

The symptoms of overdose with Requip are related to its dopaminergic activity. General supportive measures are recommended. Vital signs should be maintained, if necessary.

In clinical trials, there have been patients who accidentally or intentionally took more than their prescribed dose of ropinirole. The largest overdose reported with 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 hallucinations, hyperhidrosis, claustrophobia, chorea, palpitations, asthenia, and nightmares. Additional symptoms reported in cases of overdose included vomiting, increased coughing, fatigue, syncope, vasovagal syncope, dyskinesia, agitation, chest pain, orthostatic hypotension, somnolence, and confusional state.

Parkinson’s Disease

The effectiveness of Requip in the treatment of Parkinson’s disease was evaluated in a multinational drug development program consisting of 11 randomized, controlled trials. Four trials were conducted in patients with early Parkinson’s disease and no concomitant L-dopa and seven trials were conducted in patients with advanced Parkinson’s disease with concomitant L-dopa.

Three placebo-controlled trials provide evidence of effectiveness of Requip in the management of patients with Parkinson’s disease who were and were not receiving concomitant L-dopa. Two of these three trials enrolled patients with early Parkinson’s disease (without L-dopa) and one enrolled patients receiving L-dopa.

In these trials a variety of measures were used to assess the effects of treatment (e.g., the Unified Parkinson’s Disease Rating Scale [UPDRS], Clinical Global Impression [CGI] scores, patient diaries recording time “on” and “off,” tolerability of L-dopa dose reductions).

In both trials of patients with early Parkinson’s disease (without L-dopa), the motor component (Part III) of the UPDRS was the primary outcome assessment. The UPDRS is a multi-item rating scale intended to evaluate 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) scored for different body regions and has a maximum (worst) score of 108. In the trial of patients with advanced Parkinson’s disease (with L-dopa), both reduction in percent awake time spent “off” and the ability to reduce the daily use of L-dopa were assessed as a combined endpoint and individually.

Trials in Patients with Early Parkinson’s Disease (without L-dopa)

Trial 1 was a 12-week multicenter trial in which 63 patients with idiopathic Parkinson’s disease receiving concomitant anti-Parkinson medication (but not L-dopa) were enrolled and 41 were randomized to Requip and 22 to placebo. Patients had a mean disease duration of approximately 2 years. Patients were eligible for enrollment if they presented with bradykinesia and at least tremor, rigidity, or postural instability. In addition, they must have been classified as Hoehn & Yahr Stage I-IV. This scale, ranging from I = unilateral involvement with minimal impairment to V = confined to wheelchair or bed, is a standard instrument used for staging patients with Parkinson’s disease. The primary outcome measure in this trial was the proportion of patients experiencing a decrease (compared with baseline) of at least 30% in the UPDRS motor score.

Patients were titrated for up to 10 weeks, starting at 0.5 mg twice daily, with weekly increments of 0.5 mg twice daily to a maximum of 5 mg twice daily. Once patients reached their maximally tolerated dose (or 5 mg twice daily), they were maintained on that dose through 12 weeks. The mean dose achieved by patients at trial endpoint was 7.4 mg/day. Mean baseline UPDRS motor score was 18.6 for patients treated with Requip and 19.9 for patients treated with placebo. At the end of 12 weeks, the percentage of responders was greater on Requip than on placebo and the difference was statistically significant (Table 6).

Table 6. Percent Responders for UPDRS Motor Score in Trial 1 (Intent-to-Treat Population)

	% Responders	Difference from Placebo
Placebo	41%	NA
Requip	71%	30%

Trial 2 in patients with early Parkinson’s disease (without L-dopa) was a double-blind, randomized, placebo-controlled, 6-month trial. In this trial, 241 patients were enrolled and 116 were randomized to Requip and 125 to placebo. Patients were essentially similar to those in the trial described above; concomitant use of selegiline was allowed, but patients were not permitted to use anticholinergics or amantadine during the trial. Patients had a mean disease duration of 2 years and limited (not more than a 6-week period) or no prior exposure to L-dopa. The starting dosage of Requip in this trial was 0.25 mg three times daily. The dosage was titrated at weekly intervals by increments of 0.25 mg three times daily to a dosage of 1 mg three times daily. Further titrations at weekly intervals were at increments of 0.5 mg three times daily up to a dosage of 3 mg three times daily, and then weekly at increments of 1 mg three times daily. Patients were to be titrated to a dosage of at least 1.5 mg three times daily and then to their maximally tolerated dosage, up to a maximum of 8 mg three times daily. The mean dose attained in patients at trial endpoint was 15.7 mg/day.

The primary measure of effectiveness was the mean percent reduction (improvement) from baseline in the UPDRS motor score. At the end of the 6-month trial, patients treated with Requip showed improvement in motor score compared with placebo and the difference was statistically significant (Table 7).

Table 7. Mean Percentage Change from Baseline in UPDRS Motor Score at End of Treatment in Trial 2 (Intent-to-Treat Population)

Treatment	Baseline UPDRS Motor Score	Mean Change from Baseline	Difference from Placebo
Placebo	17.7	+4%	NA
Requip	17.9	-22%	-26%

Trial in Patients with Advanced Parkinson’s Disease (with L-dopa)

Trial 3 was a double-blind, randomized, placebo-controlled, 6-month trial that randomized 149 patients (Hoehn & Yahr II-IV) who were not adequately controlled on L-dopa. Ninety-five patients were randomized to Requip and 54 were randomized to placebo. Patients in this trial had a mean disease duration of approximately 9 years, had been exposed to L-dopa for approximately 7 years, and had experienced “on-off” periods with L-dopa therapy. Patients previously receiving stable doses of selegiline, amantadine, and/or anticholinergic agents could continue on these agents during the trial. Patients were started at a dosage of 0.25 mg three times daily of Requip and titrated upward by weekly intervals until an optimal therapeutic response was achieved. The maximum dosage of trial medication was 8 mg three times daily. All patients had to be titrated to at least a dosage of 2.5 mg three times daily. Patients could then be maintained on this dosage level or higher for the remainder of the trial. Once a dosage of 2.5 mg three times daily was achieved, patients underwent a mandatory reduction in their L-dopa dosage, to be followed by additional mandatory reductions with continued escalation of the dosage of Requip. Reductions in the dosage of l-dopa were also allowed if patients experienced adverse reactions that the investigator considered related to dopaminergic therapy. The mean dose attained at trial endpoint was 16.3 mg/day. The primary outcome was the proportion of responders, defined as patients who were able both to achieve a decrease (compared with baseline) of at least 20% in their L-dopa dosage and a decrease of at least 20% in the proportion of the time awake in the “off” condition (a period of time during the day when patients are particularly immobile), as determined by subject diary. In addition, the mean change in “off” time from baseline and the percent change from baseline in daily L-dopa dosage were examined.

At the end of 6 months, the percentage of responders was greater on Requip than on placebo and the difference was statistically significant (Table 8).

Based on the protocol-mandated reductions in L-dopa dosage with escalating doses of Requip, patients treated with Requip had a 19.4% mean reduction in L-dopa dosage while patients treated with placebo had a 3% reduction. Mean daily L-dopa dosage at baseline was 759 mg for patients treated with Requip and 843 mg for patients treated with placebo.

The mean number of daily “off” hours at baseline was 6.4 hours for patients treated with Requip and 7.3 hours for patients treated with placebo. At the end of the 6-month trial, there was a mean reduction of 1.5 hours of “off” time in patients treated with Requip and a mean reduction of 0.9 hours of “off” time in patients treated with placebo, resulting in a treatment difference of 0.6 hours of “off” time.

Table 8. Mean Responder Percentage of Patients Reducing Daily L-Dopa Dosage by at Least 20% and Daily Proportion of “Off” Time by at Least 20% at End of Treatment in Trial 3 (Intent-to-Treat Population)

Treatment	% Responders	Difference from Placebo
Placebo	11%	NA
Requip	28%	17%

Restless Legs Syndrome

The effectiveness of Requip in the treatment of RLS was demonstrated in randomized, double-blind, placebo-controlled trials in adults diagnosed with RLS using the International Restless Legs Syndrome Study Group diagnostic criteria. Patients were required to have a history of a minimum of 15 RLS episodes/month during the previous month and a total score of ≥15 on the International RLS Rating Scale (IRLS scale) at baseline. Patients with RLS secondary to other conditions (e.g., pregnancy, renal failure, anemia) were excluded. All trials employed flexible dosing, with patients initiating therapy at 0.25 mg Requip once daily. Patients were titrated based on clinical response and tolerability over 7 weeks to a maximum of 4 mg once daily. All doses were taken between 1 and 3 hours before bedtime.

A variety of measures were used to assess the effects of treatment, including the IRLS scale and Clinical Global Impression-Global Improvement (CGI-I) scores. The IRLS scale contains 10 items designed to assess the severity of sensory and motor symptoms, sleep disturbance, daytime somnolence, and impact on activities of daily living and mood associated with RLS. The range of scores is 0 to 40, with 0 being absence of RLS symptoms and 40 the most severe symptoms. Three of the controlled trials utilized the change from baseline in the IRLS scale at the Week 12 endpoint as the primary efficacy outcome.

Three hundred eighty patients were randomized to receive Requip (n = 187) or placebo (n = 193) in a US trial (RLS-1); 284 were randomized to receive either Requip (n = 146) or placebo (n = 138) in a multinational trial (excluding US) (RLS-2); and 267 patients were randomized to Requip (n = 131) or placebo (n = 136) in a multinational trial (including US) (RLS-3). Across the three trials, the mean duration of RLS was 16 to 22 years (range: 0 to 65 years), mean age was approximately 54 years (range: 18 to 79 years), and approximately 61% were women. The mean dose at Week 12 was approximately 2 mg/day for the three trials.

At baseline, mean total IRLS score was 22.0 for Requip and 21.6 for placebo in RLS-1, was 24.4 for Requip and 25.2 for placebo in RLS-2, and was 23.6 for Requip and 24.8 for placebo in RLS-3. In all three trials, a statistically significant difference between the treatment group receiving Requip and the treatment group receiving placebo was observed at Week 12 for both the mean change from baseline in the IRLS scale total score and the percentage of patients rated as responders (much improved or very much improved) on the CGI-I (see Table 9).

Table 9. Mean Change in Total IRLS Score and Percent Responders on CGI-I

	Requip	Placebo	Difference from Placebo
Mean change in total IRLS score at Week 12
RLS-1	-13.5	-9.8	-3.7
RLS-2	-11.0	-8.0	-3.0
RLS-3	-11.2	-8.7	-2.5
Percent responders on CGI-I at Week 12
RLS-1	73.3%	56.5%	16.8%
RLS-2	53.4%	40.9%	12.5%
RLS-3	59.5%	39.6%	19.9%

Long-term maintenance of efficacy in the treatment of RLS was demonstrated in a 36-week trial. Following a 24-week, single-blind treatment phase (flexible dosages of Requip of 0.25 to 4 mg once daily), patients who were responders (defined as a decrease of >6 points on the IRLS scale total score relative to baseline) were randomized in double-blind fashion to placebo or continuation of Requip for an additional 12 weeks. Relapse was defined as an increase of at least 6 points on the IRLS scale total score to a total score of at least 15, or withdrawal due to lack of efficacy. For patients who were responders at Week 24, the mean dose of Requip was 2 mg (range: 0.25 to 4 mg). Patients continued on Requip demonstrated a significantly lower relapse rate compared with patients randomized to placebo (32.6% versus 57.8%, P = 0.0156).

Advise the patient to read the FDA-approved patient labeling (Patient Information).

Dosing Instructions

Instruct patients to take Requip only as prescribed. If a dose is missed, advise patients not to double their next dose. Requip can be taken with or without food [see Dosage and Administration (2.1)].

Ropinirole is the active ingredient in both Requip XL and Requip tablets (the immediate-release formulation). Ask your patients if they are taking another medication containing ropinirole.

Hypersensitivity/Allergic Reactions

Advise patients about the potential for developing a hypersensitivity/allergic reaction including manifestations such as urticaria, angioedema, rash, and pruritus when taking any ropinirole product. Inform patients who experience these or similar reactions to immediately contact their healthcare professional [see Contraindications (4)].

Falling Asleep during Activities of Daily Living and Somnolence

Alert patients to the potential sedating effects caused by Requip, including somnolence and the possibility of falling asleep while engaged in activities of daily living. Because somnolence is a frequent adverse reaction with potentially serious consequences, patients should not drive a car, operate machinery, or engage in other potentially dangerous activities until they have gained sufficient experience with Requip to gauge whether or not it adversely affects their mental and/or motor performance. Advise patients 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.

Advise patients of possible additive effects when patients are taking other sedating medications, alcohol, or other central nervous system depressants (e.g., benzodiazepines, antipsychotics, antidepressants, etc.) in combination with Requip or when taking a concomitant medication (e.g., ciprofloxacin) that increases plasma levels of ropinirole [see Warnings and Precautions (5.1)].

Syncope and Hypotension/Orthostatic Hypotension

Advise patients that they may experience syncope and may develop hypotension with or without symptoms such as dizziness, nausea, syncope, and sometimes sweating while taking Requip, especially if they are elderly. 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). Postural/orthostatic symptoms may be related to sitting up or standing. Accordingly, caution patients against standing 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 [see Warnings and Precautions (5.2, 5.3)].

Hallucinations/Psychotic-like Behavior

Inform patients that they may experience hallucinations (unreal visions, sounds, or sensations), and that other psychotic-like behavior can occur while taking Requip. The elderly are at greater risk than younger patients with Parkinson’s disease. This risk is greater in patients who are taking Requip with L-dopa or taking higher doses of Requip and may also be further increased in patients taking any other drugs that increase dopaminergic tone. Tell patients to report hallucinations or psychotic-like behavior to their healthcare provider promptly should they develop [see Warnings and Precautions (5.4)].

Dyskinesia

Inform patients that Requip may cause and/or exacerbate pre-existing dyskinesias [see Warnings and Precautions (5.5)].

Impulse Control/Compulsive Behaviors

Advise patients that they may experience impulse control and/or compulsive behaviors while taking 1 or more of the medications (including Requip) that increase central dopaminergic tone, that are generally used for the treatment of Parkinson’s disease. Advise patients to inform their physician or healthcare provider if they develop new or increased gambling urges, sexual urges, uncontrolled spending, binge or compulsive eating, or other urges while being treated with Requip. Physicians should consider dose reduction or stopping the medication if a patient develops such urges while taking Requip [see Warnings and Precautions (5.6)].

Withdrawal-Emergent Hyperpyrexia and Confusion

Advise patients to contact their healthcare provider if they wish to discontinue Requip or decrease the dose of Requip [see Warnings and Precautions (5.7)].

Melanoma

Advise patients with Parkinson’s disease that they have a higher risk of developing melanoma. Advise patients to have their skin examined on a regular basis by a qualified healthcare provider (e.g., dermatologist) when using Requip for any indication [see Warnings and Precautions (5.8)].

Augmentation and Rebound

Inform patients with RLS that augmentation and/or rebound may occur after starting treatment with Requip [see Warnings and Precautions (5.9)].

Nursing Mothers

Because of the possibility that ropinirole may be excreted in breast milk, discuss the developmental and health benefits of breastfeeding along with the mother’s clinical need for Requip and any potential adverse effects on the breastfed child from ropinirole or from the underlying maternal condition [see Use in Specific Populations (8.2)]. Advise patients that Requip could inhibit lactation because ropinirole inhibits prolactin secretion.

Pregnancy

Because experience with ropinirole in pregnant women is limited and ropinirole has been shown to have adverse effects on embryofetal development in animals, including teratogenic effects, advise patients of this potential risk. Advise patients to notify their physician if they become pregnant or intend to become pregnant during therapy [see Use in Specific Populations (8.1)].

Requip and TILTAB are registered trademarks of the GSK group of companies.

GlaxoSmithKline

Research Triangle Park, NC 27709

©2017 the GSK group of companies. All rights reserved.

REP:6PI

PHARMACISTDETACH HERE AND GIVE INSTRUCTIONS TO PATIENT

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 (RLS), read the other side. Important Note: Requip XL 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 moderate to severe primary RLS (see other side of this leaflet).
What is the most important information I should know about Requip and Requip XL? Requip and Requip XL 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. 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 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, be sure to tell your healthcare provider if you take any medicines that make you drowsy. • Fainting. Fainting can happen, 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, feel dizzy, or feel light-headed. • Decrease in blood pressure. Requip and Requip XL can decrease your blood pressure (hypotension), especially when you start taking Requip or Requip XL or when your dose is changed. If you faint or feel dizzy, nauseated, or sweaty when you stand up from sitting or lying down (orthostatic hypotension), this may mean that your blood pressure is decreased. When you change position from lying down or sitting to standing up, you should do it carefully and slowly. Call your healthcare provider if you have any of the symptoms of decreased blood pressure listed above. • Increase in blood pressure. Requip XL may increase your blood pressure. • Changes in heart rate (decrease or increase). Requip and Requip XL can decrease or increase your heart rate. • Hallucinations and other psychotic-like behavior. Requip and Requip XL can cause or worsen psychotic-like behavior including hallucinations (seeing or hearing things that are not real), confusion, excessive suspicion, aggressive behavior, agitation, delusional beliefs (believing things that are not real), and disorganized thinking. The chances of having hallucinations or these other psychotic-like changes are higher in people with Parkinson’s disease who are taking Requip or Requip XL or taking higher doses of these drugs. If you have hallucinations or any of these other psychotic-like changes, talk with your healthcare provider. • Uncontrolled sudden movements. Requip and Requip XL 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 medicine may need to be changed. • Unusual urges. Some patients taking Requip or Requip XL get urges to behave in a way unusual for them. Examples of this are an unusual urge to gamble, increased sexual urges and behaviors, or an uncontrollable urge to shop, spend money, or eat. If you notice or your family notices that you are developing any unusual behaviors, talk to your healthcare provider. • Increased chance of skin cancer (melanoma). People with Parkinson’s disease may have a higher chance of getting melanoma. It is not known if Requip and Requip XL increase your chances of getting melanoma. You and your healthcare provider should check your skin on a regular basis. Tell your healthcare provider right away if you notice any changes in your skin such as a change in the size, shape, or color of moles on your skin.
What are Requip and Requip XL? • Requip is a short-acting prescription medicine containing ropinirole (usually taken 3 times a day) that is used to treat Parkinson’s disease. It is also used to treat a condition called Restless Legs Syndrome (RLS). • Requip XL is a long-acting prescription medicine containing ropinirole (taken 1 time a day) that is used only to treat Parkinson’s disease but not to treat RLS. Having one of these conditions does not mean you have or will develop the other condition. You should not be taking more than 1 medicine containing ropinirole. Tell your healthcare provider if you are taking any other medicine containing ropinirole. It is not known if Requip and Requip XL are safe and effective for use in children younger than 18 years of age.
Do not take Requip or Requip XL if you: • are allergic to ropinirole or any of the ingredients in Requip or Requip XL. See the end of this page for a complete list of the ingredients in Requip and Requip XL.   Get help right away if any of the symptoms of an allergic reaction cause problems swallowing or breathing. Call your healthcare provider if you have any of the symptoms of an allergic reaction. Symptoms of an allergic reaction may include:         •  hives                                                                                     •  rash         •  swelling of the face, lips, mouth, tongue, or throat              •  itching
Before taking Requip or Requip XL, tell your healthcare provider about all of your medical conditions, including if you: • have daytime sleepiness from a sleep disorder or have unexpected or unpredictable sleepiness or periods of sleep. • 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. Smoking may decrease the treatment effect of Requip or Requip XL. • feel dizzy, nauseated, sweaty, or faint when you 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. • have high or low blood pressure. • have or have had heart problems. • are pregnant or plan to become pregnant. It is not known if Requip or Requip XL can harm your unborn baby. • are breastfeeding or plan to breastfeed. It is not known if Requip or Requip XL passes into your breast milk. The amount of breast milk you make may be decreased while taking Requip or Requip XL. Talk to your healthcare provider to decide if you should breastfeed while taking Requip or Requip XL. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Some of these medicines may increase your chances of getting side effects while taking Requip or Requip XL.
How should I take Requip or Requip XL? • Take Requip or Requip XL exactly as directed by your healthcare provider. • Take Requip or Requip XL with or without food. • Do not suddenly stop taking Requip or Requip XL 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, 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. • Contact your healthcare provider if you stop taking Requip or Requip XL for any reason. Do not restart without talking with your healthcare provider. • Your healthcare provider may prescribe Requip or Requip XL alone, or add Requip or Requip XL to medicine that you are already taking for Parkinson’s disease. • You should not substitute Requip for Requip XL or Requip XL for Requip without talking with your healthcare provider. If you are taking Requip: • Requip tablets are usually taken 3 times a day for Parkinson’s disease. If you are taking Requip XL: • Take Requip XL extended-release tablets 1 time each day for Parkinson’s disease, preferably at or around the same time of day. • Swallow Requip XL extended-release tablets whole. Do not chew, crush, or split Requip XL extended-release tablets. • Requip XL extended-release tablets release drug over a 24-hour period. If you have a condition where medicine passes through your body too quickly, such as diarrhea, the tablet(s) may not dissolve completely and you may see tablet residue in your stool. If this happens, let your healthcare provider know as soon as possible.
What are the possible side effects of Requip and Requip XL? Requip and Requip XL can cause serious side effects, including: • See “What is the most important information I should know about Requip and Requip XL?” The most common side effects of Requip and Requip XL include:       •  fainting             •  sleepiness or                •  hallucinations (seeing or hearing              •  dizziness                                        or drowsiness                  things that are not real)       •  nausea or           •  uncontrolled                 •  upset stomach, abdominal pain       •  fatigue, tiredness,         vomiting                 sudden movements           or discomfort                                      or weakness       •  confusion               •  headache               •  leg swelling              •  increased sweating       •  constipation               •  suddenly falling               •  high blood pressure                                                 asleep                               •  (hypertension) Tell your healthcare provider about any side effect that bothers you or that does not go away. These are not all of the possible side effects with Requip and Requip XL. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
How should I store Requip or Requip XL? • Store Requip or Requip XL at room temperature between 68°F and 77°F (20°C to 25°C). • Keep Requip or Requip XL in a tightly closed container and out of direct sunlight. Keep Requip or Requip XL and all medicines out of the reach of children.
General information about the safe and effective use of Requip or Requip XL: Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use Requip or Requip XL for a condition for which it was not prescribed. Do not give Requip or Requip XL to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about Requip or Requip XL that is written for health professionals.
What are the ingredients in Requip and Requip XL? 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.

_ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _ _

PATIENT INFORMATION
Requip® (RE-qwip) (ropinirole) tablets
If you have Restless Legs Syndrome (RLS), read this side. If you have Parkinson’s disease, read the other side. Important Note: Requip XL has not been studied in Restless Legs Syndrome (RLS) and is not approved for the treatment of RLS.
People with RLS should take Requip differently than people 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 people 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. • Fainting. Fainting can happen, 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, feel dizzy, or feel light-headed. • Decrease in blood pressure. Requip can decrease your blood pressure (hypotension), especially when you start taking Requip or when your dose is changed. If you faint or feel dizzy, nauseated, or sweaty when you stand up from sitting or lying down (orthostatic hypotension), this may mean that your blood pressure is decreased. When you change position from lying down or sitting to standing up, you should do it carefully and slowly. Call your healthcare provider if you have any of the symptoms of decreased blood pressure listed above. • Hallucinations and other psychotic-like behavior. Requip can cause or worsen psychotic-like behavior including hallucinations (seeing or hearing things that are not real), confusion, excessive suspicion, aggressive behavior, agitation, delusional beliefs (believing things that are not real), and disorganized thinking. If you have hallucinations or any of these other psychotic-like changes, 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, increased sexual urges and behaviors, or an uncontrollable urge to shop, spend money, or eat. If you notice or your family notices that you are developing any unusual behaviors, talk to your healthcare provider. • Increased chance of skin cancer (melanoma). It is not known if Requip increases your chance of getting melanoma. You and your healthcare provider should check your skin on a regular basis. Tell your healthcare provider right away if you notice any changes in your skin such as a change in the size, shape, or color of moles on your skin. • Changes in Restless Legs Syndrome symptoms. Requip may cause Restless Legs symptoms to come back in the morning (rebound), happen earlier in the evening, or even happen in the afternoon.
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 condition. You should not be taking more than 1 medicine containing ropinirole. Tell your healthcare provider if you are taking any other medicine containing ropinirole. It is not known if Requip is safe and effective for use in children younger than 18 years of age.
Do not take Requip if you: • are allergic to ropinirole or any of the ingredients in Requip. See the end of this page for a complete list of the ingredients in Requip.   Get help right away if any of the symptoms of an allergic reaction cause problems swallowing or breathing. Call your healthcare provider if you have any of the symptoms of an allergic reaction. Symptoms of an allergic reaction may include:         •  hives                                                                                     •  rash         •  swelling of the face, lips, mouth, tongue, or throat              •  itching
Before taking Requip, tell your healthcare provider about all of your medical conditions, including if you: • have daytime sleepiness from a sleep disorder or have unexpected or unpredictable sleepiness or periods of sleep. • 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 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. • have or have had heart problems. • are pregnant or plan to become pregnant. It is not known if Requip can harm your unborn baby. • are breastfeeding or plan to breastfeed. It is not known if Requip passes into your breast milk. The amount of breast milk you make may be decreased while taking Requip. Talk to your healthcare provider to decide if you should breastfeed while taking Requip. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Some of these medicines may increase your chances of getting side effects while taking Requip.
How should I take Requip? • Take Requip exactly as directed by your healthcare provider. • Requip tablets are usually taken once in the evening, 1 to 3 hours before bedtime. • Take Requip with or without food. • Do not suddenly stop taking Requip without talking to your healthcare provider. If you stop this medicine suddenly, you may develop fever, confusion, or severe muscle stiffness. • 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 talking with your healthcare provider.
What are the possible side effects of Requip? Requip can cause serious side effects, including: • See “What is the most important information I should know about Requip?” The most common side effects of Requip include:       •  nausea or vomiting                                          •  drowsiness or sleepiness       •  dizziness                                                          •  fatigue, tiredness, or weakness Tell your healthcare provider about any side effect that bothers you or that does not go away. These are not all of the possible side effects with Requip. Call your doctor 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 at room temperature between 68°F and 77°F (20°C to 25°C). • Keep Requip in a tightly closed container and out of direct sunlight. Keep Requip and all medicines out of the reach of children.
General information about the safe and effective use of Requip: Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use Requip for a condition for which it was not prescribed. Do not give Requip to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or healthcare provider for information about Requip that is written for health professionals.
What are the ingredients 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.
Requip and Requip XL are registered trademarks of the GSK group of companies. GlaxoSmithKline: Research Triangle Park, NC 27709; ©2017 the GSK group of companies. All rights reserved. REP:5PIL For more information go to www.gsk.com or call 1-888-825-5249 (toll-free).
This Patient Information has been approved by the U.S. Food and Drug Administration.	Revised: 05/2017

PRINCIPAL DISPLAY PANEL

NDC 0007-4890-20

Requip®

(rOPINIRole tablets)

0.25 mg

100 Tablets

Rx only

Each tablet contains 0.29 mg ropinirole HCl equivalent to 0.25 mg ropinirole.

Store at controlled room temperature 20o - 25oC (68o - 77oF) [see USP].

Do not accept if seal on bottle opening is missing or broken.

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

Dosage: See Prescribing Information for complete dosing instructions.

GlaxoSmithKline

Research Triangle Park,

NC 27709

Made in Ireland

Rev. 12/16

10000000143764

PRINCIPAL DISPLAY PANEL

NDC 0007-4891-20

Requip®

(rOPINIRole tablets)

0.5 mg

100 Tablets

Rx only

Each tablet contains 0.57 mg ropinirole HCl equivalent to 0.5 mg ropinirole.

Store at controlled room temperature 20o to 25oC (68o to 77oF) [see USP].

Do not accept if seal on bottle opening is missing or broken.

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

Dosage: See Prescribing Information for complete dosing instructions.

GlaxoSmithKline

Research Triangle Park,

NC 27709

Made in Ireland

Rev. 11/16

10000000143765

PRINCIPAL DISPLAY PANEL

NDC 0007-4892-20

Requip®

(rOPINIRole tablets)

1 mg

100 Tablets

Rx only

Each tablet contains 1.14 mg ropinirole HCl equivalent to 1 mg ropinirole.

Store at controlled room temperature 20o - 25oC (68o - 77oF) [see USP].

Do not accept if seal on bottle opening is missing or broken.

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

Dosage: See Prescribing Information for complete dosing instructions.

GlaxoSmithKline

Research Triangle Park,

NC 27709

Made in Ireland

Rev.12/16

10000000143769

PRINCIPAL DISPLAY PANEL

NDC 0007-4893-20

Requip®

(rOPINIRole tablets)

2 mg

100 Tablets

Rx only

Each tablet contains 2.28 mg ropinirole HCl equivalent to 2 mg ropinirole.

Store at controlled room temperature 20o - 25oC (68o - 77oF) [see USP].

Do not accept if seal on bottle opening is missing or broken.

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

Dosage: See Prescribing Information for complete dosing instructions.

GlaxoSmithKline

Research Triangle Park,

NC 27709

Made in Ireland

Rev. 11/16

10000000143770

PRINCIPAL DISPLAY PANEL

NDC 0007-4895-20

Requip®

(rOPINIRole tablets)

3 mg

100 Tablets

Rx only

Each tablet contains 3.42 mg ropinirole HCl equivalent to 3 mg ropinirole.

Store at controlled room temperature 20o - 25oC (68o - 77oF) [see USP].

Do not accept if seal on bottle opening is missing or broken.

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

Dosage: See Prescribing Information for complete dosing instructions.

GlaxoSmithKline

Research Triangle Park,

NC 27709

Made in Ireland

Rev. 12/16

10000000143767

PRINCIPAL DISPLAY PANEL

NDC 0007-4896-20

Requip®

(rOPINIRole tablets)

4 mg

100 Tablets

Rx only

Each tablet contains 4.56 mg ropinirole HCl equivalent to 4 mg ropinirole.

Store at controlled room temperature 20o - 25oC (68o - 77oF) [see USP].

Do not accept if seal on bottle opening is missing or broken.

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

Dosage: See Prescribing Information for complete dosing instructions.

GlaxoSmithKline

Research Triangle Park,

NC 27709

Made in Ireland

Rev. 1/17

10000000143766

PRINCIPAL DISPLAY PANEL

NDC 0007-4894-20

Requip®

(rOPINIRole tablets)

5 mg

100 Tablets

Rx only

Each tablet contains 5.70 mg ropinirole HCl equivalent to 5 mg ropinirole.

Store at controlled room temperature 20o - 25oC (68o - 77oF) [see USP].

Do not accept if seal on bottle opening is missing or broken.

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

Dosage: See Prescribing Information for complete dosing instructions.

GlaxoSmithKline

Research Triangle Park,

NC 27709

Made in Ireland

Rev. 11/16

10000000143768

Requip  ropinirole tablet, film coated

Product Information Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0007-4890 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength ROPINIROLE HYDROCHLORIDE (ROPINIROLE) ROPINIROLE 0.25 mg

Inactive Ingredients Ingredient Name Strength CROSCARMELLOSE SODIUM   LACTOSE MONOHYDRATE   MAGNESIUM STEARATE   CELLULOSE, MICROCRYSTALLINE   HYPROMELLOSE 2910 (3 MPA.S)   POLYETHYLENE GLYCOL 400   POLYSORBATE 80   TITANIUM DIOXIDE   HYPROMELLOSE 2910 (6 MPA.S)

Product Characteristics Color WHITE Score no score Shape FREEFORM (pentagonal (5 sided)) Size 8mm Flavor Imprint Code SB;4890 Contains

Packaging # Item Code Package Description 1 NDC:0007-4890-20 100 TABLET, FILM COATED in 1 BOTTLE

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA020658 10/10/1997

Requip  ropinirole tablet, film coated

Product Information Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0007-4891 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength ROPINIROLE HYDROCHLORIDE (ROPINIROLE) ROPINIROLE 0.5 mg

Inactive Ingredients Ingredient Name Strength CROSCARMELLOSE SODIUM   LACTOSE MONOHYDRATE   MAGNESIUM STEARATE   CELLULOSE, MICROCRYSTALLINE   HYPROMELLOSE 2910 (6 MPA.S)   POLYETHYLENE GLYCOL 400   TITANIUM DIOXIDE   FERRIC OXIDE YELLOW   FERRIC OXIDE RED   INDIGOTINDISULFONATE SODIUM   FD&C BLUE NO. 2   ALUMINUM OXIDE

Product Characteristics Color YELLOW Score no score Shape FREEFORM (pentagonal (5 sided)) Size 8mm Flavor Imprint Code SB;4891 Contains

Packaging # Item Code Package Description 1 NDC:0007-4891-20 100 TABLET, FILM COATED in 1 BOTTLE

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA020658 10/10/1997

Requip  ropinirole tablet, film coated

Product Information Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0007-4892 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength ROPINIROLE HYDROCHLORIDE (ROPINIROLE) ROPINIROLE 1 mg

Inactive Ingredients Ingredient Name Strength CROSCARMELLOSE SODIUM   LACTOSE MONOHYDRATE   MAGNESIUM STEARATE   CELLULOSE, MICROCRYSTALLINE   HYPROMELLOSE 2910 (6 MPA.S)   POLYETHYLENE GLYCOL 400   TITANIUM DIOXIDE   FERRIC OXIDE YELLOW   FD&C BLUE NO. 2   ALUMINUM OXIDE

Product Characteristics Color GREEN Score no score Shape FREEFORM (pentagonal (5 sided)) Size 8mm Flavor Imprint Code SB;4892 Contains

Packaging # Item Code Package Description 1 NDC:0007-4892-20 100 TABLET, FILM COATED in 1 BOTTLE

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA020658 10/01/1997

Requip  ropinirole tablet, film coated

Product Information Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0007-4893 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength ROPINIROLE HYDROCHLORIDE (ROPINIROLE) ROPINIROLE 2 mg

Inactive Ingredients Ingredient Name Strength CROSCARMELLOSE SODIUM   LACTOSE MONOHYDRATE   MAGNESIUM STEARATE   CELLULOSE, MICROCRYSTALLINE   HYPROMELLOSE 2910 (6 MPA.S)   POLYETHYLENE GLYCOL 400   TITANIUM DIOXIDE   FERRIC OXIDE YELLOW   FERRIC OXIDE RED

Product Characteristics Color YELLOW (pale yellowish-pink) Score no score Shape FREEFORM (pentagonal (5 sided)) Size 8mm Flavor Imprint Code SB;4893 Contains

Packaging # Item Code Package Description 1 NDC:0007-4893-20 100 TABLET, FILM COATED in 1 BOTTLE

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA020658 10/03/1997

Requip  ropinirole tablet, film coated

Product Information Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0007-4895 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength ROPINIROLE HYDROCHLORIDE (ROPINIROLE) ROPINIROLE 3 mg

Inactive Ingredients Ingredient Name Strength CROSCARMELLOSE SODIUM   LACTOSE MONOHYDRATE   MAGNESIUM STEARATE   CELLULOSE, MICROCRYSTALLINE   HYPROMELLOSE 2910 (6 MPA.S)   POLYETHYLENE GLYCOL 400   TITANIUM DIOXIDE   ALUMINUM OXIDE   COCHINEAL   FD&C YELLOW NO. 6   FD&C BLUE NO. 2   INDIGOTINDISULFONATE SODIUM

Product Characteristics Color RED (moderate reddish-purple) Score no score Shape FREEFORM (pentagonal (5 sided)) Size 8mm Flavor Imprint Code SB;4895 Contains

Packaging # Item Code Package Description 1 NDC:0007-4895-20 100 TABLET, FILM COATED in 1 BOTTLE

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA020658 06/19/2001

Requip  ropinirole tablet, film coated

Product Information Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0007-4896 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength ROPINIROLE HYDROCHLORIDE (ROPINIROLE) ROPINIROLE 4 mg

Inactive Ingredients Ingredient Name Strength CROSCARMELLOSE SODIUM   LACTOSE MONOHYDRATE   MAGNESIUM STEARATE   CELLULOSE, MICROCRYSTALLINE   HYPROMELLOSE 2910 (6 MPA.S)   POLYETHYLENE GLYCOL 400   TITANIUM DIOXIDE   FD&C YELLOW NO. 6   FD&C BLUE NO. 2   INDIGOTINDISULFONATE SODIUM   ALUMINUM OXIDE

Product Characteristics Color BROWN (pale brown) Score no score Shape FREEFORM (pentagonal (5 sided)) Size 8mm Flavor Imprint Code SB;4896 Contains

Packaging # Item Code Package Description 1 NDC:0007-4896-20 100 TABLET, FILM COATED in 1 BOTTLE

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA020658 09/21/1999

Requip  ropinirole tablet, film coated

Product Information Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:0007-4894 Route of Administration ORAL DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength ROPINIROLE HYDROCHLORIDE (ROPINIROLE) ROPINIROLE 5 mg

Inactive Ingredients Ingredient Name Strength CROSCARMELLOSE SODIUM   LACTOSE MONOHYDRATE   MAGNESIUM STEARATE   CELLULOSE, MICROCRYSTALLINE   HYPROMELLOSE 2910 (3 MPA.S)   HYPROMELLOSE 2910 (6 MPA.S)   POLYETHYLENE GLYCOL 400   TITANIUM DIOXIDE   INDIGOTINDISULFONATE SODIUM   FD&C BLUE NO. 2   ALUMINUM OXIDE

Product Characteristics Color BLUE Score no score Shape FREEFORM (pentagonal (5 sided)) Size 8mm Flavor Imprint Code SB;4894 Contains

Packaging # Item Code Package Description 1 NDC:0007-4894-20 100 TABLET, FILM COATED in 1 BOTTLE

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA020658 10/10/1997

Labeler - GlaxoSmithKline LLC (167380711)

Revised: 05/2017   GlaxoSmithKline LLC

Take Requip exactly as it was prescribed for you. Follow all directions on your prescription label. Your doctor may occasionally change your dose. Do not take this medicine in larger or smaller amounts or for longer than recommended.

If you are taking immediate-release Requip tablets you should not take the extended-release tablets at the same time.

The dose and timing of Requip in treating Parkinson's disease is different from the dose and timing in treating RLS. Follow the directions on your prescription label. Ask your pharmacist if you have any questions about the kind of ropinirole you receive at the pharmacy.

Requip can be taken with or without food. Take the medicine at the same time each day.

Do not crush, chew, or break an extended-release Requip XL tablet. Swallow the tablet whole.

Call your doctor if you see part of the tablet in your stool. This is a sign that your body may not have absorbed all of the medicine.

If you are taking this medicine for RLS, tell your doctor if your symptoms get worse, if they occur in the morning or earlier than usual in the evening, or if you feel restless symptoms in your hands or arms.

It may take up to several weeks before your symptoms improve. Keep using the medication as directed and tell your doctor if your symptoms do not improve.

Do not stop using Requip suddenly, or you could have unpleasant withdrawal symptoms. Follow your doctor's instructions about tapering your dose.

Store at room temperature away from moisture, heat, and light. Keep the bottle tightly closed when not in use.

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

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

Some people taking Requip have fallen asleep during normal daytime activities such as working, talking, eating, or driving. Tell your doctor if you have any problems with daytime sleepiness or drowsiness.

You may have increased sexual urges, unusual urges to gamble, or other intense urges while taking this medicine. Talk with your doctor if this occurs.

Call your doctor at once if you have:

• extreme drowsiness, falling asleep suddenly (even after feeling alert);

• worsening or no improvement in your symptoms;

• a light-headed feeling, like you might pass out;

• unusual changes in mood or behavior;

• tremors, twitching uncontrollable muscle movements; or

• hallucinations (seeing or hearing things that are not real).

Side effects such as confusion or hallucinations may be more likely in older adults.

Common Requip side effects may include:

• drowsiness, dizziness, weakness;

• headache, confusion, hallucinations;

• increased blood pressure (severe headache, pounding in your neck or ears, nosebleed, irregular heartbeats);

• nausea, vomiting, upset stomach, constipation;

• flu symptoms (fever, chills, body aches);

• sudden muscle movements;

• increased sweating; or

• swelling in your legs or feet.

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.