Ropinirole
Generic: ROPINIROLE
Basic Information
Manufacturer
Marlex Pharmaceuticals Inc
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
ORAL
FDA Set ID
35d90f6f-3116-4afa-be2d-b65c160e8ab3
Indications & Usage
1 INDICATIONS AND USAGE Ropinirole tablet is a non-ergoline dopamine agonist indicated for the treatment of Parkinson’s disease (PD) and moderate- to-severe primary Restless Legs Syndrome (RLS).
( 1.1, 1.2 ) 1.1 Parkinson's Disease Ropinirole tablets are indicated for the treatment of Parkinson’s disease.
1.2 Restless Legs Syndrome Ropinirole tablets are indicated for the treatment of moderate-to-severe primary Restless Legs Syndrome (RLS).
( 1.1, 1.2 ) 1.1 Parkinson's Disease Ropinirole tablets are indicated for the treatment of Parkinson’s disease.
1.2 Restless Legs Syndrome Ropinirole tablets are indicated for the treatment of moderate-to-severe primary Restless Legs Syndrome (RLS).
Adverse Reactions
6 ADVERSE REACTIONS 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 a nd 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 )] Withdrawal Symptoms [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 )] Most common adverse reactions (incidence with ropinirole hydrochloride 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.
( 6.1 ) Advanced PD: Dyskinesia, somnolence, nausea, dizziness, confusion, hallucinations, sweating, and headache.
( 6.1 ) RLS: Nausea, vomiting, somnolence, dizziness, and asthenic condition.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Marlex Pharmaceuticals at 1-888-582-1953 or drugsafety@marlexpharm.com or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 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 hydrochloride, patients received ropinirole hydrochloride 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 hydrochloride (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 hydrochloride 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 hydrochloride (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 hydrochloride 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 hydrochloride 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 Hydrochloride and Numerically More Frequent than the Placebo Group) a Body System/Adverse Reaction Ropinirole Hydrochloride (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.
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 hydrochloride (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 hydrochloride 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 hydrochloride (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 hydrochloride 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 hydrochloride 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 Hydrochloride and Numerically More Frequent than the Placebo Group) a Body System/Adverse Reaction Ropinirole Hydrochloride Placebo (n = 208) (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 Hypotension 2 1 Syncope 3 2 Central/peripheral nervous system Dizziness 26 16 Dyskinesia 34 13 Falls 10 7 Headache 17 12 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 Increase 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 Hallucinations 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 ropinirole hydrochloride (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 hydrochloride 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 hydrochloride (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 hydrochloride 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 Hydrochloride and Numerically More Frequent than the Placebo Group) a Body System/Adverse Reaction Ropinirole Hydrochloride (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 conditions b 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).
6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of ropinirole hydrochloride.
Because these reactions are not 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.
General Disorders and Administration Site Conditions Withdrawal symptoms [see Warnings and Precautions ( 5.8 )]
( 6.1 ) Advanced PD: Dyskinesia, somnolence, nausea, dizziness, confusion, hallucinations, sweating, and headache.
( 6.1 ) RLS: Nausea, vomiting, somnolence, dizziness, and asthenic condition.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Marlex Pharmaceuticals at 1-888-582-1953 or drugsafety@marlexpharm.com or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 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 hydrochloride, patients received ropinirole hydrochloride 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 hydrochloride (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 hydrochloride 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 hydrochloride (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 hydrochloride 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 hydrochloride 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 Hydrochloride and Numerically More Frequent than the Placebo Group) a Body System/Adverse Reaction Ropinirole Hydrochloride (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.
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 hydrochloride (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 hydrochloride 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 hydrochloride (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 hydrochloride 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 hydrochloride 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 Hydrochloride and Numerically More Frequent than the Placebo Group) a Body System/Adverse Reaction Ropinirole Hydrochloride Placebo (n = 208) (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 Hypotension 2 1 Syncope 3 2 Central/peripheral nervous system Dizziness 26 16 Dyskinesia 34 13 Falls 10 7 Headache 17 12 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 Increase 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 Hallucinations 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 ropinirole hydrochloride (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 hydrochloride 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 hydrochloride (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 hydrochloride 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 Hydrochloride and Numerically More Frequent than the Placebo Group) a Body System/Adverse Reaction Ropinirole Hydrochloride (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 conditions b 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).
6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of ropinirole hydrochloride.
Because these reactions are not 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.
General Disorders and Administration Site Conditions Withdrawal symptoms [see Warnings and Precautions ( 5.8 )]