Ropinirole

Restless Legs Syndrome

• Patients with RLS should take ropinirole differently than patients with Parkinson's disease. A lower dose of ropinirole is generally needed for patients with RLS.
• There are known side effects of ropinirole. If you fall asleep or feel very sleepy while doing normal activities such as driving, faint, feel dizzy, nauseated, or sweaty when you stand up from sitting or lying down, you should talk with your doctor.
• Before starting ropinirole, be sure to tell your doctor if you are taking any medicines that make you drowsy.

You should not take ropinirole if you are allergic to the active ingredient ropinirole or to any of the inactive ingredients.

Parkinson's Disease

• Patients with Parkinson's disease should take ropinirole differently than patients with Restless Legs Syndrome. For Parkinson's disease, a higher dose of ropinirole is generally needed.
• There are known side effects of ropinirole.
• If you fall asleep or feel very sleepy while doing normal activities such as driving, faint, feel dizzy, nauseated, or sweaty when you stand up from sitting or lying down, you should talk with your doctor.
• Hallucinations (unreal visions, sounds, or sensations) have been reported in patients taking ropinirole. The risk is greater in patients with Parkinson's disease who are elderly, taking ropinirole with L-dopa or taking higher doses of ropinirole. If these occur, you should discuss them with your doctor.
• Ropinirole may make some of the side effects of L-dopa worse. Ropinirole may cause uncontrolled sudden movements or make such movements you already have worse or more frequent. You should notify your doctor in such a case as dosage adjustments to your anti-Parkinson’s medications may be necessary.
• Before starting ropinirole, be sure to tell your doctor if you are taking any medicines that make you drowsy.
• Studies of people with Parkinson’s disease show that they may be at an increased risk of developing melanoma, a form of skin cancer, when compared to people without Parkinson’s disease. It is not known if this problem is associated with Parkinson’s disease or the medicines used to treat Parkinson’s disease. Ropinirole is one of the medicines used to treat Parkinson’s disease, therefore, patients being treated with ropinirole should have periodic skin examinations.

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

You should not take ropinirole if you are allergic to ropinirole or to any of the inactive ingredients.

• Do not share ropinirole with other people, even if they have the same symptoms you have.
• Keep ropinirole out of the reach of children.
• Store ropinirole at room temperature out of direct sunlight.
• Keep ropinirole in a tightly closed container.

Take ropinirole every day exactly as ordered by your doctor in order to improve your condition as much as possible. Do not take more of it or less of it, and do not take it more or less often than your doctor ordered.

ropinirole comes with a patient information leaflet. Read and follow the instructions carefully. Ask your doctor if you have any questions.

ropinirole may be taken with or without food, or on an empty or full stomach. Taking ropinirole with food may reduce nausea.

The extended-release tablets work differently from the regular tablets, even at the same dose. Do not switch from one form to the other unless your doctor tells you to.

Swallow the extended-release tablet whole. Do not split, crush, or chew it.

Dosing

The dose of ropinirole will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of ropinirole. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For oral dosage form (extended-release tablets):
  • For Parkinson's disease:
    • Adults—At first, 2 milligrams (mg) once a day for 1 to 2 weeks. Your doctor may increase your dose as needed and tolerated. However, the dose is usually not more than 24 mg per day.
    • Children—Use and dose must be determined by your doctor.
• For oral dosage form (tablets):
  • For Parkinson's disease:
    • Adults—At first, 0.25 milligram (mg) three times a day. Your doctor will increase your dose as needed and tolerated. However, the dose is usually not more than 24 mg per day.
    • Children—Use and dose must be determined by your doctor.
  • For Restless Legs Syndrome:
    • Adults—At first, 0.25 milligrams (mg) once a day, 1 to 3 hours before bedtime. Your doctor will increase your dose as needed and tolerated. However, the dose is usually not more than 4 mg per day.
    • Children—Use and dose must be determined by your doctor.

Missed Dose

If you miss a dose of ropinirole, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.

Storage

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Ropinirole tablets are 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)]

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 Ropinirole tablets, patients received Ropinirole tablets 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 Ropinirole tablets (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 Ropinirole tablets 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 Ropinirole tablets (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 Ropinirole tablets participating in the double-blind, placebo-controlled trials and were numerically more common than the incidence for placebo-treated patients. In these trials, either Ropinirole tablets 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 Ropinirole tablets and Numerically More Frequent than the Placebo Group)a

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 Ropinirole tablets (incidence at least 5 % greater than placebo) were dyskinesia, somnolence, nausea, dizziness, confusion, hallucinations, increased sweating, and headache.

Approximately 24% of patients who received Ropinirole tablets 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 Ropinirole tablets (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 Ropinirole tablets  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 Ropinirole tablets 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 Ropinirole tablets and Numerically More Frequent than the Placebo Group)a

aPatients 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 Ropinirole tablets (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 Ropinirole tablets 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 Ropinirole tablets (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 Ropinirole tablets 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 Ropinirole tablets and Numerically More Frequent than the Placebo Group)a

aPatients may have reported multiple adverse reactions during the trial or at discontinuation;

thus, patients may be included in more than one category.

bAsthenic condition (i.e., asthenia, fatigue, and/or malaise).

Ropinirole Tablets USP, 2 mg (30 Tablets in 1 Bottle)
Each film coated tablet contains Ropinirole Hydrochloride USP equivalent to Ropinirole free base  2 mg.
62332-033-30

Ropinirole Tablets USP, 3 mg (30 Tablets in 1 Bottle)
Each film coated tablet contains Ropinirole Hydrochloride USP equivalent to Ropinirole free base  3 mg.
62332-034-30

• Requip
• Requip XL

• Anti-Parkinson Agent, Dopamine Agonist

Cigarette smoking: Clearance is expected to increase because CYP1A2 is known to be induced by smoking. Cmax was 30% and AUC was 38% lower in smokers compared with nonsmokers.

Parkinson disease: Treatment of Parkinson disease

Restless legs syndrome (immediate release only): Treatment of moderate to severe primary restless legs syndrome (RLS)

Blood pressure (orthostatic); daytime alertness; CNS depression, fall risk, behavior changes (eg, compulsive behaviors); periodic skin examinations

Applies to ropinirole: oral tablet, oral tablet extended release

Along with its needed effects, ropinirole may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking ropinirole:

• Confusion
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• drowsiness
• falling
• nausea
• seeing, hearing, or feeling things that are not there (hallucinations)
• sleepiness or unusual drowsiness
• swelling of the legs
• twisting, twitching, or other unusual body movements
• unusual tiredness or weakness
• worsening of parkinsonism

• Abdominal or stomach pain
• bloating or swelling of the face, arms, hands, lower legs, or feet
• blood in the urine
• blurred vision
• burning, pain, or difficulty in urinating
• chest pain
• chills
• cold sweats
• cough
• double vision or other eye or vision problems
• fainting
• fear or nervousness
• feeling of constant movement of self or surroundings
• high or low blood pressure
• irregular or pounding heartbeat
• loss of memory
• mental depression
• pain
• pain in the arms or legs
• pounding in the ears
• rapid weight gain
• sensation of spinning
• slow or fast heartbeat
• sore throat
• sweating
• tightness in chest
• tingling of the hands or feet
• tingling, numbness, or prickly feelings
• trouble in concentrating
• troubled breathing
• unusual weight gain or loss
• vomiting

• Anxiety
• buzzing or ringing in the ears
• changes in vision
• fever
• headache
• joint pain
• loss of bladder control
• muscle cramps, pain, or spasms
• nasal congestion
• runny nose
• sneezing
• trouble with swallowing
• unusual urges

Get emergency help immediately if any of the following symptoms of overdose occur while taking ropinirole:

• Agitation
• grogginess
• increase in unusual body movements, especially of the face or mouth
• increased coughing
• increased sweating
• lack or loss of strength
• nightmares

Some side effects of ropinirole may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Abnormal dreams
• acid or sour stomach
• back pain
• belching
• decrease in sexual desire or performance
• difficulty having a bowel movement (stool)
• dryness of mouth
• flushing
• general feeling of discomfort or illness
• heartburn or gas
• hot flashes
• indigestion
• loss of appetite
• tremor
• weight loss
• yawning

Parkinson's disease:
Moderate renal impairment (CrCl 30 to 50 mL/mi): No dosage adjustment is necessary
Severe renal impairment without regular dialysis: No data available

Restless Leg Syndrome:
Moderate renal impairment (CrCl 30 to 50 mL/min): No dosage adjustment is necessary
Severe renal impairment without regular dialysis: No data available

Parkinson's disease:
Moderate renal impairment (CrCl 30 to 50 mL/mi): No dosage adjustment is necessary
Severe renal impairment without regular dialysis: No data available

Restless Leg Syndrome:
Moderate renal impairment (CrCl 30 to 50 mL/min): No dosage adjustment is necessary
Severe renal impairment without regular dialysis: No data available