Ropinirole is an active pharmaceutical ingredient in the Dopamine Agonists group (N04BC). The information below is compiled per regulator from the product labels on record, with direct links to the original documents.
GBOfficial regulatory label· revised October 3, 2025[1]
Treatment of Parkinson's Disease under the following conditions: - Initial treatment as monotherapy, in order to delay the introduction of levodopa. - In combination with levodopa, over the course of the disease, when the effect of levodopa wears off or becomes inconsistent and fluctuations in the therapeutic effect occur (“end of dose” or “on-off” type fluctuations).
How to take
CACanada· Health Canada
21 products
Uses
CAOfficial regulatory label· revised March 22, 2025[2]
AND CLINICAL USE.............................................................................. 4 CONTRAINDICATIONS ................................................................................................... 4 WARNINGS AND PRECAUTIONS .................................................................................
5 ADVERSE REACTIONS ................................................................................................. 10 DRUG INTERACTIONS ..................................................................................................
21 DOSAGE AND ADMINISTRATION .............................................................................. 23 OVERDOSAGE ................................................................................................................
24 ACTION AND CLINICAL PHARMACOLOGY ............................................................ 25 STORAGE AND STABILITY ......................................................................................... 28 DOSAGE FORMS, COMPOSITION AND PACKAGING .............................................
USUnited States· FDA
2 products
Uses
USOfficial regulatory label· revised October 7, 2024[3]
1 INDICATIONS AND USAGE Ropinirole Tablets are a non-ergoline dopamine agonist indicated for the treatment of Parkinson’s disease (PD) and moderate-to-severe primary Restless Legs Syndrome (RLS). 2). 1 Parkinson's Disease Ropinirole tablets are indicated for the treatment of Parkinson’s disease.
2 Restless Legs Syndrome Ropinirole tablets are indicated for the treatment of moderate-to-severe primary Restless Legs Syndrome (RLS).
How to take
Drug interactions
Known interactions involving Ropinirole. Select one for details. This list is informational and not a complete interaction checker.
Showing 240 of 465. Type above to find a specific drug.
Interaction data compiled from DDInter (academic, CC-BY). Severity classification only - this is not a complete interaction checker and not medical advice.
[1]MHRA (UK) · PL537970088 · revised October 3, 2025
[2]Health Canada (DPD) · 02326604 · revised March 22, 2025
[3]FDA DailyMed · 00c0ab77-914a-4e… · revised October 7, 2024 [PDF]
[4]OpenFDA adverse-event reports (US), 12 months ending June 4, 2026.
Information on this page is compiled from public regulatory records. Drugvu is not affiliated with any regulator or pharmaceutical manufacturer. This is not medical advice. Always consult a qualified healthcare professional.
Posology Adults Individual dose titration against efficacy and tolerability is recommended. Ropinirole should be taken three times a day, preferably with meals to improve gastrointestinal tolerance. 25 mg three times daily for one week.
25mg three times daily increments, according to the following regimen: Week 3 Unit dose (mg) of ropinirole 0. 7 5 Total daily dose (mg) of ropinirole 2. 5 to 3mg/day) of ropinirole may be given. A therapeutic response may be seen between 3 and 9 mg/day of ropinirole.
If sufficient symptomatic control is not achieved, or maintained after the initial titration as described above, the dose of ropinirole may be increased up to 24mg/day. Doses of ropinirole above 24 mg/day have not been studied. If treatment is interrupted for one day or more, re-initiation by dose titration should be considered (see above).
When ropinirole is administered as adjunct therapy to L-dopa, the concurrent dose of L-dopa may be reduced gradually according to the symptomatic response. In clinical trials, the levodopa dose was reduced gradually by around 20% in patients treated with ropinirole as adjunct therapy.
In patients with advanced Parkinson’s disease receiving ropinirole in combination with L- dopa, dyskinesias can occur during the initial titration of ropinirole. 8). When switching treatment from another dopamine agonist to ropinirole, the manufacturer's guidance on discontinuation should be followed before initiating ropinirole.
4). Renal impairment In patients with mild to moderate renal impairment (creatinine clearance 30-50 ml/min) no change in the clearance of ropinirole was observed, indicating that no dosage adjustment is necessary in this population.
25 mg three times a day. Further dose escalations should be based on tolerability and efficacy. The recommended maximum dose of Ropinirole Tablets is 18 mg/day in patients receiving regular haemodialysis. 2). The use of ropinirole in patients with severe renal impairment (creatinine clearance <30ml/min) without regular haemodialysis has not been studied.
Elderly The clearance of ropinirole is decreased by approximately 15% in patients aged 65 years or above. Although a dose adjustment is not required, ropinirole dose should be individually titrated, with careful monitoring of tolerability, to the optimal clinical response.
Paediatric population Ropinirole is not recommended for use in children below 18 years of age due to a lack of data on safety and efficacy. Method of Administration Ropinirole Film-coated Tablets are for oral use. The tablets should be swallowed whole with a glass of water, preferably with food.
This is not medical advice. Consult a qualified healthcare professional.
Side effects & warnings
GBOfficial regulatory label· Adverse reactions· revised October 3, 2025[1]
Undesirable effects are listed below by system organ class and frequency. It is noted if these undesirable effects were reported in clinical trials as monotherapy or adjunct therapy to levodopa Frequencies are defined as: very common (>1/10), common (>1/100, <1/10), uncommon (>1/1,000, <1/100), rare (>1/10,000, <1/1,000) very rare (<1/10,000), not known (cannot be estimated from the available data).
Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
Immune system disorders Not known:
Hypersensitivity reactions (including urticaria, angioedema, rash, pruritus Psychiatric disorders Common: hallucinations. Uncommon: psychotic reactions (other than hallucinations) including delirium, delusio paranoia. Not known: aggression*, dopamine dysregulation syndrome *aggression has been associated with psychotic reactions as well as compulsive symptoms.
Impulse control disorders Pathological gambling, increased libido, hypersexuality, compulsive spending or buying, binge eating and compulsive eating can occur in patients treated with dopamine agonists including ropinirole. 4. 'Special warnings and precautions for use').
Use in adjunct therapy studies:
Common: confusion. Nervous system disorders Very common: somnolence. Common: dizziness (including vertigo). Uncommon: sudden onset of sleep, excessive daytime somnolence. Ropinirole is associated with somnolence and has been associated uncommonly with excessive daytime somnolence and sudden sleep onset episodes.
Use in monotherapy studies:
Very common: syncope.
Use in adjunct therapy studies:
Very common: dyskinesia. In patients with advanced Parkinson's disease, dyskinesias can occur during the initial titration of ropinirole. 2) Vascular disorders Uncommon: postural hypotension, hypotension. Postural hypotension or hypotension is rarely severe.
Gastrointestinal disorders Very Common: nausea. Common: heartburn. Use in monotherapy studies Common: vomiting, abdominal pain. Hepatobiliary disorders Not known: hepatic reactions, mainly increased liver enzymes.
General disorders Use in monotherapy studies:
Common: oedema peripheral (including leg oedema).
Not known:
Dopamine agonist withdrawal syndrome including apathy, anxiety, depression, fatigue, sweating and pain. 4). Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important.
It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
GBOfficial regulatory label· Warnings and precautions· revised October 3, 2025[1]
Patients with major psychiatric or psychotic disorders, or a history of these disorders, should only be treated with dopamine agonists if the potential benefits outweigh the risks. Ropinirole has been associated with somnolence and episodes of sudden sleep onset, particularly in patients with Parkinson's Disease.
Sudden onset of sleep during daily activities, in some cases without awareness or warning signs, has been reported uncommonly. Patients must be informed of this and advised to exercise caution while driving or operating machines during treatment with ropinirole.
Patients who have experienced somnolence and/or an episode of sudden sleep onset must refrain from driving or operating machines. Furthermore, a reduction of dosage or termination of therapy may be considered. Impulse control disorders Patients should be regularly monitored for the development of impulse control disorders.
Patients and carers should be made aware that behavioural symptoms of impulse control disorders including pathological gambling, increased libido, hypersexuality, compulsive spending or buying, binge eating and compulsive eating can occur in patients treated with dopamine agonists, including ropinirole.
Dose reduction/tapered discontinuation should be considered if such symptoms develop. Impulse control disorders were reported especially at high doses and were generally reversible upon reduction of the dose or treatment discontinuation.
8). Dopamine Dysregulation Syndrome Dopamine Dysregulation Syndrome (DDS) has been reported. Neuroleptic malignant syndrome Symptoms suggestive of neuroleptic malignant syndrome have been reported with abrupt withdrawal of dopaminergic therapy.
2). Due to the risk of hypotension, blood pressure monitoring is recommended, particularly at the start of treatment, in patients with severe cardiovascular disease (in particular coronary insufficiency). Co-administration of ropinirole with anti-hypertensive and anti-arrhythmic agents has not been studied.
Caution should be exercised when these compounds are given concomitantly with ropinirole because of the unknown potential for the occurrence of hypotension, bradycardias or other arrhythmias. 2). Non-motor adverse effects may occur when tapering or discontinuing dopamine agonists including ropinirole.
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
GBOfficial regulatory label· Contraindications· revised October 3, 2025[1]
1. Severe renal impairment (creatinine clearance <30ml/min) without regular haemodialysis. Hepatic impairment.
This is not medical advice. Consult a qualified healthcare professional.
28 PART II: SCIENTIFIC INFORMATION ................................................................................ 30 PHARMACEUTICAL INFORMATION ......................................................................... 30 CLINICAL TRIALS..........................................................................................................
38 REFERENCES .................................................................................................................. 44 PART III: CONSUMER INFORMATION ..............................................................................
0 mg Colloidal Silicon Dioxide, Croscarmellose Sodium, DL-Methionine, FD & C Blue # 2 / Indigo Carmine Aluminum Lake, Hydroxypropyl Methylcellulose, Hypromellose, Iron Oxide Yellow, Lactose, Macrogol, Magnesium Stearate, Microcelac, Microcrystalline Cellulose, Polyethylene Glycol, and Titanium Dioxide.
0 mg Colloidal Silicon Dioxide, Croscarmellose Sodium, DL-Methionine, FD & C Blue #2 / Indigo Carmine Aluminum Lake, FD & C Yellow # 6 / Sunset Yellow aluminum lake, Hypromellose, Hydroxypropyl Methylcellulose, Iron Oxide Red, Lactose, Macrogol, Magnesium Stearate, Microcelac, Microcrystalline Cellulose, Polyethylene Glycol, and Titanium Dioxide.
0 mg Colloidal Silicon Dioxide, Croscarmellose Sodium, DL-Methionine, FD & C Blue # 2 Aluminum Lake, Hypromellose, Hydroxypropyl Methylcellulose, Lactose, Macrogol, Magnesium Stearate, Microcelac, Microcrystalline Cellulose, Polyethylene Glycol, Polysorbate 80, and Titanium Dioxide.
pms-ROPINIROLE Product Monograph Page 4 of 52 INDICATIONS AND CLINICAL USE Adults pms-ROPINIROLE (ropinirole hydrochloride) is indicated in the treatment of the signs and symptoms of idiopathic Parkinson's disease. pms-ROPINIROLE can be used both as early therapy without concomitant levodopa and as an adjunct to levodopa.
Geriatrics (> 65 years of age) Oral clearance of ropinirole is reduced in patients older than 65 years of age, however the dosing of ropinirole for elderly patients can be titrated in the normal manner. (see ACTION AND CLINICAL PHARMACOLOGY, Special Populations and Conditions, Geriatrics) Pediatrics (≤ 18 years of age) The safety and efficacy of pms-ROPINIROLE have not been established in children under 18 years of age, therefore pms-ROPINIROLE is not recommended in this patient population.
CONTRAINDICATIONS pms-ROPINIROLE is contraindicated in patients with a known hypersensitivity to ropinirole hydrochloride or the excipients of the drug product. For a complete listing of excipients, see DOSAGE FORMS, COMPOSITION AND PACKAGING.
pms-ROPINIROLE Product Monograph Page 5 of 52 WARNINGS AND PRECAUTIONS The following Warnings and Precautions are listed in alphabetical order.
Carcinogenesis and Mutagenesis See PART II:
TOXICOLOGY, Carcinogenicity and Mutagenicity for discussion on animal data. Cardiovascular Patients with pre-existing cardiovascular conditions Since ropinirole has not been studied in patients with a history or evidence of significant cardiovascular disease including myocardial infarction, unstable angina, cardiac decompensation, cardiac arrhythmias, vaso-occlusive disease (including cerebral) or cardiomyopathy, it should be used with caution in such patients.
Serious Warnings and Precautions Sudden Onset of Sleep Patients receiving treatment with ropinirole hydrochloride and other dopaminergic agents have reported suddenly falling asleep while engaged in activities of daily living, including operating a motor vehicle, which has sometimes resulted in accidents.
Although some of the patients reported somnolence while on ropinirole hydrochloride, others perceived that they had no warning signs, such as excessive drowsiness, and believed that they were alert immediately prior to the event. Physicians should alert patients of the reported cases of sudden onset of sleep, […]
Side effects & warnings
CAOfficial regulatory label· Adverse reactions· revised March 22, 2025[2]
Adverse Drug Reaction Overview Most Frequent Adverse Events Adverse events occurring with an incidence of greater than, or equal to, 10% were as follows: Early therapy: nausea, dizziness, somnolence, headache, peripheral oedema, vomiting, syncope, fatigue and viral infection.
Adjunct therapy: dyskinesia, nausea, dizziness, somnolence and headache. 3% in adjunct-therapy studies discontinued treatment due to adverse reactions. 3%). 4%). Patients over 75 years of age (n=130) showed slightly higher incidences of withdrawal due to hallucination, confusion and dizziness than patients less than 75 years of age.
Clinical Trial Adverse Drug Reactions Because clinical trials are conducted under very specific conditions the adverse reaction rates observed in the clinical trials may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.
Adverse drug reaction information from clinical trials is useful for identifying drug-related adverse events and for approximating rates. Incidence of Adverse Events in Placebo Controlled Trials The incidence of postural hypotension, an event commonly associated with initiation of dopamine agonist therapy, was not notably different from placebo in clinical trials.
6% (> 75 years) of patients treated with ropinirole. The following table lists adverse events that occurred at an incidence of 1% or more among ropinirole-treated patients who participated in placebo-controlled trials for up to one year.
75 mg to 24 mg/day. Reported adverse events were classified using a standard World Health Organization Reaction Term Thesaurus (WHO-ART). 4 […]
CAOfficial regulatory label· Warnings and precautions· revised March 22, 2025[2]
The following Warnings and Precautions are listed in alphabetical order.
Carcinogenesis and Mutagenesis See PART II:
TOXICOLOGY, Carcinogenicity and Mutagenicity for discussion on animal data. Cardiovascular Patients with pre-existing cardiovascular conditions Since ropinirole has not been studied in patients with a history or evidence of significant cardiovascular disease including myocardial infarction, unstable angina, cardiac decompensation, cardiac arrhythmias, vaso-occlusive disease (including cerebral) or cardiomyopathy, it should be used with caution in such patients.
Serious Warnings and Precautions Sudden Onset of Sleep Patients receiving treatment with ropinirole hydrochloride and other dopaminergic agents have reported suddenly falling asleep while engaged in activities of daily living, including operating a motor vehicle, which has sometimes resulted in accidents.
Although some of the patients reported somnolence while on ropinirole hydrochloride, others perceived that they had no warning signs, such as excessive drowsiness, and believed that they were alert immediately prior to the event. Physicians should alert patients of the reported cases of sudden onset of sleep, bearing in mind that these events are NOT limited to initiation of therapy.
Patients should also be advised that sudden onset of sleep has occurred without warning signs. If drowsiness or sudden onset of sleep should occur, patients should immediately contact their physician. , operating machines). Episodes of falling asleep while engaged in activities of daily living have also been reported in patients taking other dopaminergic agents, therefore, symptoms may not be alleviated by substituting these products.
Presently, the precise cause of this event is unknown. It is known that many Parkinson's disease patients experience alterations in sleep architecture, which results in excessive daytime sleepiness or spontaneous dozing, and that dopaminergic agents can also induce sleepiness.
There is insufficient information to determine whether this event is associated with ropinirole hydrochloride, all dopaminergic agents or Parkinson's disease itself. pms-ROPINIROLE Product Monograph Page 6 of 52 There is limited experience with ropinirole in patients treated with antihypertensive and antiarrhythmic agents.
Consequently, in such patients, the dose of ropinirole should be titrated with caution. Orthostatic hypotension Dopamine agonists appear to impair the systemic regulation of blood pressure with resulting orthostatic symptoms of dizziness or light headedness, with or without documented hypotension.
These symptoms appear to occur especially during dose initiation and escalation. Therefore, patients treated with ropinirole and other dopamine agonists should be carefully monitored for signs and symptoms of orthostatic hypotension, especially during dose initiation and escalation (see DOSAGE AND ADMINISTRATION) and should be informed of this risk (see PART III: CONSUMER INFORMATION).
This is not medical advice. Consult a qualified healthcare professional.
USOfficial regulatory label· revised October 7, 2024[3]
2 DOSAGE AND ADMINISTRATION · Ropinirole tablets can be taken with or without food. 1) · Retitration of ropinirole tablets may be warranted if therapy is interrupted. 25 mg taken three times daily; titrate to a maximum daily dose of 24 mg.
2) · Renal Impairment: The maximum recommended dose is 18 mg/day in patients with end-stage renal disease on hemodialysis. 25 mg once daily, 1 to 3 hours before bedtime, titrate to a maximum recommended dose of 4 mg daily. 3) · Renal Impairment: The maximum recommended dose is 3 mg/day in patients with end-stage renal disease on hemodialysis.
3)] . If a significant interruption in therapy with ropinirole tablets have occurred, retitration of therapy may be warranted. 8)]. The frequency of administration should be reduced from three times daily to twice daily for 4 days. For the remaining 3 days, the frequency should be reduced to once daily prior to complete withdrawal of ropinirole tablets.
Renal Impairment No dose adjustment is necessary in patients with moderate renal impairment (creatinine clearance of 30 to 50 mL/min). 25 mg three times a day. Further dose escalations should be based on tolerability and need for efficacy.
The recommended maximum total daily dose is 18 mg/day in patients receiving regular dialysis. Supplemental doses after dialysis are not required. The use of ropinirole tablets in patients with severe renal impairment without regular dialysis has not been studied.
25 mg once daily 1 to 3 hours before bedtime. 5 mg once daily, and to 1 mg once daily at the end of the first week of dosing, then as shown in Table 2 as needed to achieve efficacy. Titration should be based on individual patient therapeutic response and tolerability, up to a maximum recommended dose of 4 mg daily.
For RLS, the safety and effectiveness of doses greater than 4 mg once daily have not been established. Table 2. 9)]. Renal Impairment No dose adjustment is necessary in patients with moderate renal impairment (creatinine clearance of 30 to 50 mL/min).
25 mg once daily. Further dose escalations should be based on tolerability and need for efficacy. The recommended maximum total daily dose is 3 mg/day in patients receiving regular dialysis. Supplemental doses after dialysis are not required.
The use of ropinirole tablets in patients with severe renal impairment without regular dialysis has not been studied.
This is not medical advice. Consult a qualified healthcare professional.
Most-reported reactions to the US regulator (12 mo to June 4, 2026): 1,243 reports total. [4]
Fatigue 94
Nausea 87
Drug Ineffective 79
Fall 75
Death 70
Hallucination 69
Product Dose Omission Issue 65
Dyspnoea 57
Headache 55
Dizziness 52
Off Label Use 51
Diarrhoea 47
Side effects & warnings
USOfficial regulatory label· Adverse reactions· revised October 7, 2024[3]
11)] Most common adverse reactions (incidence with ropinirole tablets at least 5% greater than placebo) in the respective indications were: Early PD: Nausea, somnolence, dizziness, syncope, asthenic condition, viral infection, leg edema, vomiting, and dyspepsia.
1) Advanced PD: Dyskinesia, somnolence, nausea, dizziness, confusion, hallucinations, sweating, and headache. 1) RLS: Nausea, vomiting, somnolence, dizziness, and asthenic condition. gov/medwatch. 1 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. , 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.
, 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 Body System/ Adverse Reaction Ropinirole Tablets (n = 157) (%) Placebo (n = 147) (%) Autonomic nervous system Flushing 3 1 Dry mouth 5 3 Increased sweating 6 4 Body as a whole Asthenic condition b 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.
, 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 Body System/Adverse Reaction Ropinirole Tablets (n = 208) (%) Placebo (n = 120) (%) Autonomic nervous system Dry mouth Increased sweating 5 7 1 2 Body as a whole Increased drug level Pain 7 5 3 3 Cardiovascular general Hypotension Syncope 2 3 1 2 Central/peripheral nervous system Dizziness Dyskinesia Falls Headache Hypokinesia Paresis Paresthesia Tremor 26 34 10 17 5 3 5 6 16 13 7 12 4 0 3 3 Gastrointestinal Abdominal pain Constipation Diarrhea Dysphagia Flatulence Nausea Increased saliva Vomiting 9 6 5 2 2 30 2 7 8 3 3 1 1 18 1 4 Metabolic/nutritional Weight decrease 2 1 Musculoskeletal Arthralgia Arthritis 7 3 5 1 Psychiatric Amnesia Anxiety Confusion Abnormal dreaming Hallucination Nervousness Somnolence 5 6 9 3 10 5 20 1 3 2 2 4 3 8 Red blood cell Anemia 2 0 Resistance mechanism Upper respiratory tract infection 9 8 Respiratory Dyspnea 3 2 Urinary Pyuria Urinary incontinence Urinary tract infection 2 2 6 1 1 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.
, 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 Body System/Adverse Reaction Ropinirole Tablets (n = 496) (%) Placebo (n =500) (%) Ear and labyrinth Vertigo 2 1 Gastrointestinal Nausea Vomiting Diarrhea Dyspepsia Dry mouth Abdominal pain upper 40 11 5 4 3 3 8 2 3 3 2 1 General disorders and administration site conditions Asthenic condition b Edema peripheral 9 2 4 1 Infections and infestations Nasopharyngitis Influenza 9 3 8 2 Musculoskeletal and connective tissue Arthralgia Muscle cramps Pain in extremity 4 3 3 3 2 2 Nervous system Somnolence Dizziness Paresthesia 12 11 3 6 5 1 Respiratory, thoracic, and mediastinal Cough Nasal congestion 3 2 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.
, asthenia, fatigue, and/or malaise). 2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of ropinirole. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
8)]
USOfficial regulatory label· Warnings and precautions· revised October 7, 2024[3]
1 Falling Asleep during Activities of Daily Living and Somnolence Patients treated with ropinirole tablets have reported falling asleep while engaged in activities of daily living, including driving or operating machinery, which sometimes resulted in accidents.
Although many of these patients reported somnolence while on ropinirole tablets, some perceived that they had no warning signs, such as excessive drowsiness, and believed that they were alert immediately prior to the event. Some have reported these events more than 1 year after initiation of treatment.
1)] . It has been reported that falling asleep while engaged in activities of daily living usually occurs in a setting of pre-existing somnolence, although patients may not give such a history. For this reason, prescribers should 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. 1)] . 3)] . If a decision is made to continue ropinirole 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 . 2 Syncope Syncope, sometimes associated with bradycardia, was observed in association with treatment with ropinirole in both patients with Parkinson’s disease and patients with RLS.
In controlled clinical trials in patients with Parkinson’s disease, syncope was observed more frequently in patients receiving ropinirole tablets than in patients receiving placebo (early Parkinson’s disease without levodopa [L-dopa]: ropinirole tablets 12%, placebo 1%; advanced Parkinson’s disease: ropinirole tablets 3%, placebo 2%).
1)] . Most cases occurred more than 4 weeks after initiation of therapy with ropinirole tablets, and were usually associated with a recent increase in dose. Because the trials conducted with ropinirole tablets excluded patients with significant cardiovascular disease, patients with significant cardiovascular disease should be treated with caution.
This is not medical advice. Consult a qualified healthcare professional.
Who should not take it
USOfficial regulatory label· Contraindications· revised October 7, 2024[3]
4 CONTRAINDICATIONS 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. History of hypersensitivity/allergic reaction (including urticaria, angioedema, rash, pruritus) to ropinirole or to any of the excipients (4)
This is not medical advice. Consult a qualified healthcare professional.
Symptoms include apathy, anxiety, depression, fatigue, sweating and pain which may be severe. Patients should be informed about this before tapering the dopamine agonist, and monitored regularly thereafter. 8).
Hallucinations:
Hallucinations are known as a side effect of treatment with dopamine agonists and levodopa. Patients should be informed that hallucinations can occur. This medicinal product also contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Connective tissue 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 events are believed to be related to the ergoline structure of these compounds, whether other, nonergot-derived dopamine agonists can cause them is unknown.
A small number of reports have been received of possible fibrotic complications, including pleural effusion, pleural fibrosis, interstitial lung diseases, and cardiac valvulopathy, in the development program and postmarketing experience for ropinirole.
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. Neurologic Neuroleptic Malignant Syndrome A symptom complex resembling the neuroleptic malignant syndrome (characterized by elevated temperature, muscular rigidity, altered consciousness, and autonomic instability), with no other obvious aetiology, has been reported in association with rapid dose reduction, withdrawal of, or changes in antiparkinsonian therapy.
A single spontaneous report of a symptom complex resembling the neuroleptic malignant syndrome has been observed in a 66 year old diabetic male patient with Parkinson's disease, who developed fever, muscle stiffness, and drowsiness 8 days after beginning ropinirole treatment.
The patient also experienced acute bronchitis, which did not respond to antibiotic treatment. Ropinirole was discontinued three days before the patient died. The reporting physician considered these events to be possibly related to ropinirole treatment (see DOSAGE AND ADMINISTRATION).
A single spontaneous report of severe muscle pain has been reported in a 66 year old male patient around his thigh. The reporting physician considered the event to be probably related to ropinirole pms-ROPINIROLE Product Monograph Page 7 of 52 treatment.
Dyskinesia with Adjunctive Levodopa Ropinirole may potentiate the dopaminergic side effects of levodopa and may cause or exacerbate pre-existing dyskinesia. Decreasing the dose of levodopa may ameliorate this side effect. 5, 15 and 50 mg/kg/day respectively.
The incidence was […]
Approximately 4% of patients with Parkinson’s disease enrolled in Phase 1 trials had syncope following a 1-mg dose of ropinirole tablets. In two trials in patients with RLS that used a forced-titration regimen and orthostatic challenge with intensive blood pressure monitoring, 2% of RLS patients treated with ropinirole tablets compared with 0% of patients receiving placebo reported syncope.
In Phase 1 trials including healthy volunteers, the incidence of syncope was 2%. Of note, 1 subject with syncope developed hypotension, bradycardia, and sinus arrest; the subject recovered spontaneously without intervention. 3 Hypotension/Orthostatic Hypotension Patients with Parkinson’s disease may have impaired ability to respond normally to a fall in blood pressure after standing from lying down or seated position.
Patients on ropinirole tablets should be monitored for signs and symptoms of orthostatic hypotension, especially during dose escalation, and should be informed of the risk for syncope and hypotension [see Patient Counseling Information (17)] .
Although the clinical trials were not designed to systematically monitor blood pressure, there were individual reported cases of orthostatic hypotension in early Parkinson’s disease (without L-dopa) in patients treated with ropinirole tablets.
Most of these cases occurred more than 4 weeks after initiation of therapy with ropinirole tablets and were usually associated with a recent increase in dose. 4%) receiving placebo. In two Phase 2 studies in patients with RLS, 14 of 55 patients (25%) receiving ropinirole tablets experienced an adverse event of hypotension or orthostatic hypotension compared with none of the 27 patients receiving placebo.
In these studies, 11 of the 55 patients (20%) receiving ropinirole tablets and 3 of the 26 patients (12%) who had post-dose blood pressure assessments following placebo, experienced an orthostatic blood pressure decrease of at least 40 mm Hg systolic and/or at least 20 mm Hg diastolic.
In Phase 1 trials of ropinirole tablets with healthy volunteers who received single doses on more than one occasion without titration, 7% had documented symptomatic orthostatic hypotension. 8 mg and these doses are higher than the starting doses recommended for patients with either Parkinson’s disease or with RLS.
2)] . Although dizziness is not a specific manifestation of hypotension or orthostatic hypotension, patients with hypotension or orthostatic hypotension frequently reported dizziness. In controlled clinical trials, dizziness was a common adverse reaction in patients receiving ropinirole tablets and was more frequent in patients with Parkinson’s disease or with RLS receiving ropinirole tablets than in patients receiving placebo (early Parkinson’s disease without L-dopa: ropinirole tablets 40%, placebo 22%; advanced Parkinson’s disease: ropinirole tablets 26%, placebo 16%; RLS: ropinirole tablets 11%, placebo 5%).
1)]. 4% of patients on placebo (2 of 147). 2% (5 of 120) of patients treated with placebo and L-dopa. 5)] . Postmarketing reports indicate that patients with Parkinson’s disease or RLS may experience new or worsening mental status and behavioral changes, which may be severe, including psychotic-like behavior during treatment with ropinirole tablets or after starting or increasing the dose of ropinirole tablets.
Other drugs prescribed to improve the symptoms of Parkinson’s disease or RLS can have similar effects on thinking and behavior. This abnormal thinking and behavior can consist of one or more of a variety of manifestations including paranoid ideation, delusions, hallucinations, confusion, psychotic-like behavior, mania, disorientation, aggressive behavior, agitation, and delirium.
Patients with a major psychotic disorder should ordinarily not be treated with ropinirole tablets because of the risk of exacerbating the psychosis. 3)]. 5 Dyskinesia Ropinirole tablets may cause or exacerbate pre-existing dyskinesia in patients treated with L-dopa for Parkinson’s disease.
In double-blind, placebo-controlled trials in advanced Parkinson’s disease, dyskinesia was much more common in patients treated with ropinirole tablets than in those treated with placebo. 1)]. Decreasing the dose of dopaminergic medications may ameliorate this adverse reaction.
6 Impulse Control/Compulsive Behaviors Reports suggest that patients can experience intense urges to gamble, increased sexual urges, intense urges to spend money, binge or compulsive eating, and/or other intense urges, and the inability to control these urges while taking one or more of the medications, including ropinirole tablets, that increase central dopaminergic tone.
In some cases, although not all, these urges were reported to have stopped when the dose was reduced or the medication was discontinued. Because patients may not recognize these behaviors as abnormal, it is important for prescribers to specifically ask patients or their caregivers about the development of new or increased gambling urges, sexual urges, uncontrolled spending, binge or compulsive eating, or other urges while being treated with ropinirole tablets for Parkinson’s disease and RLS.
Physicians should consider dose reduction or stopping the medication if a patient develops such urges while taking ropinirole tablets. 7 Withdrawal-Emergent Hyperpyrexia and Confusion 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 of, withdrawal of, or changes in, dopaminergic therapy.
3)] . 8 Withdrawal Symptoms Symptoms including insomnia, apathy, anxiety, depression, fatigue, sweating, and pain have been reported during taper or after discontinuation of dopamine agonists, including ropinirole tablets. These symptoms generally do not respond to levodopa.
Prior to discontinuation of ropinirole tablets, patients should be informed about potential withdrawal symptoms, and monitored during and after discontinuation. In case of severe withdrawal symptoms, a trial re-administration of a dopamine agonist at the lowest effective dose may be considered.
9 Augmentation and Early-Morning Rebound in Restless Legs Syndrome Augmentation is a phenomenon in which dopaminergic medication causes a worsening of symptom severity above and beyond the level at the time the medication was started.
The symptoms of augmentation may include the earlier onset of symptoms in the evening (or even the afternoon), increase in symptoms, and spread of symptoms to involve other extremities. Augmentation has been described during therapy for RLS.
Rebound refers to new onset of symptoms in the early morning hours. Augmentation and/or early-morning rebound have been observed in a postmarketing trial of ropinirole tablets. If augmentation or early-morning rebound occurs, the use of ropinirole tablets should be reviewed and dosage adjustment or discontinuation of treatment should be considered.
3] . 10 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, non-ergot-derived dopamine agonists such as ropinirole can cause them is unknown.
Cases of possible fibrotic complications, including pleural effusion, pleural fibrosis, interstitial lung disease, and cardiac valvulopathy have been reported in the development program and postmarketing experience for ropinirole. While the evidence is not sufficient to establish a causal relationship between ropinirole and these fibrotic complications, a contribution of ropinirole cannot be excluded.
11 Retinal Pathology Retinal degeneration was observed in albino rats in the 2-year carcinogenicity study at all doses tested. 5 mg/kg/day the maximum recommended human dose (MRHD) for Parkinson’s disease (24 mg/day) on a mg/m 2 basis.
Retinal degeneration was not observed in a 3-month study in pigmented rats, in a 2-year carcinogenicity study in albino mice, or in 1-year studies in monkeys or albino rats. , disk shedding). 2 mg/day) were evaluated for evidence of retinal dysfunction through electroretinograms.
There was no clinically meaningful difference between the treatment groups in retinal function over the duration of the trial. , eyes, skin) in pigmented rats. After a single dose, long-term retention of drug was demonstrated, with a half-life in the eye of 20 days.