Ropinirole Hcl (ropinirole HCl)

Dosage of ropinirole hydrochloride is expressed in terms of ropinirole.

Therapy should be initiated with a low dosage and titrated slowly until the maximum therapeutic response is achieved.

If ropinirole therapy is interrupted for a substantial period of time, retitration may be warranted.

Because dosage of ropinirole is titrated to clinical response, routine dosage adjustment based solely on age is not necessary in geriatric patients.

Ropinirole is administered orally as conventional (immediate-release) tablets or extended-release tablets. The extended-release tablets are FDA-labeled for use only in the treatment of parkinson disease.

For the management of parkinson disease, ropinirole is administered as immediate-release tablets in 3 equally divided doses daily or as extended-release tablets once daily. For the management of restless legs syndrome (RLS), ropinirole is administered as immediate-release tablets once daily, 1-3 hours before bedtime. Both formulations of the drug may be administered without regard to food.

The extended-release tablets should be swallowed whole, and not chewed, crushed, or divided. The tablet is designed to slowly release ropinirole over a 24-hour period; if rapid GI transit occurs, incomplete release of the drug may occur, causing some tablet residue to appear in the stool.

There is no enhanced messaging for this drug.

There are no contraindication interactions for this drug.

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Selected Dopamine Agonists/Selected Antiemetics

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Selected dopamine agonists are used to treat neurologic conditions such as Parkinson Disease (PD)or restless legs syndrome (RLS), and endocrine disorders such as hyperprolactinemia by directly or indirectly increasing dopamine concentrations at dopamine-2 (D2) receptors in the central nervous system (CNS). Antiemetic agents which block CNS D2 receptors may counteract this effect.(1-5)

CLINICAL EFFECTS: The efficacy of the dopamine agonist may be decreased, leading to exacerbation of the disease being treated. In patients with Parkinson disease motor symptoms may worsen, increasing the risk for falls, dysphagia or aspiration.(5) Patients with other conditions such as restless legs syndrome may also experience symptom exacerbation due to this combination.

PREDISPOSING FACTORS: Patients with Parkinson or Diffuse Lewy Body (DLB) disease are particularly susceptible to adverse effects of dopamine blockade.

PATIENT MANAGEMENT: Reassess antiemetic therapy and use an antiemetic without dopamine (D2) blocking effects if possible. If clinically appropriate and available, consider the use of a 5HT3 blocker (e.g. ondansetron) or domperidone (not available in the US).(4) If concomitant treatment is needed, monitor for loss of efficacy for the disease being treated by the dopamine agonist (e.g. Parkinson disease, restless legs syndrome) and adjust medication(s) or dosage if needed.(1-4) Counsel patients to report symptoms of disease exacerbation.

DISCUSSION: Patients with Parkinson or DLB disease are particularly susceptible to adverse effects of dopamine blockade. The European Academy of Neurology guideline for late Parkinson disease states that metoclopramide, cinnarizine and prochlorperazine must be avoided. Ondansetron or domperidone(not available in the US) may be used for nausea and vomiting.(5) Prescribing information for dopamine agonists warn of the risk for disease exacerbation when dopamine blocking agents are co-prescribed.(1-4)

Selected Dopamine Agonists/Selected Antipsychotics

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Selected dopamine agonists are used to treat neurologic conditions such as Parkinson Disease (PD)or restless legs syndrome, and endocrine disorders such as hyperprolactinemia by directly or indirectly increasing dopamine concentrations at D2 receptors in the central nervous system (CNS). Antipsychotic agents counteract this effect by blocking dopamine activity at CNS D2 receptors.(1-5)

CLINICAL EFFECTS: The efficacy of either agent may be decreased, leading to exacerbation of the disease being treated. In patients with Parkinson disease motor symptoms may worsen, increasing the risk for falls, dysphagia or aspiration.(4,7) Compared with Parkinson patients not receiving antipsychotic therapy, Parkinson patients receiving antipsychotics appear to have an increased mortality risk.(6) Patients with other conditions such as restless legs syndrome or a psychotic disorder may also experience symptom exacerbation due to this combination.

PREDISPOSING FACTORS: Patients with Parkinson or Diffuse Lewy Body (DLB) disease are particularly susceptible to adverse effects of dopamine blockade by antipsychotics.

PATIENT MANAGEMENT: Reassess the need for antipsychotic therapy. If psychosis or hallucinations are due to an antiparkinson agent, when possible consider reducing the dose or changing the antiparkinson agent before initiating antipsychotic therapy. In patients with PD and dementia, addition of a cholinesterase inhibitor (e.g. rivastigmine) may improve psychosis. If an antipsychotic is required, then an atypical antipsychotic should be used.(6,7) In patients with major psychotic disorders, consider reducing the dose, changing or stopping the dopamine agonist. The US manufacturer of ropinirole recommends treatment with dopamine agonists only if potential benefits outweigh risks.(1) The US manufacturer of entacapone states it should not ordinarily be used in patients with major psychotic disorders as entacapone may lead to an exacerbation of psychosis.(4)

DISCUSSION: An epidemiologic study evaluated 21,043 elderly patients with Parkinson disease to determine if recent initiation of a typical or atypical antipsychotic was associated with increased mortality. They found an adjusted odds ratio of 2.0 for death associated with atypical antipsychotics versus no antipsychotic They found an adjusted odds ratio of 2.4 for death associated with typical versus atypical antipsychotics. The authors noted the increased mortality found with typical antipsychotics supports current treatment recommendations to use atypical antipsychotic agents in patients with Parkinson disease.(6,7)

Selected Dopaminergic Agents/Slt Antipsychotics

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Selected dopaminergic agents are used to treat neurologic conditions such as Parkinson Disease (PD) or restless legs syndrome, and endocrine disorders such as hyperprolactinemia by directly or indirectly increasing dopamine concentrations at D2 receptors in the central nervous system (CNS). Antipsychotic agents counteract this effect by blocking dopamine activity at CNS D2 receptors.(1-5)

CLINICAL EFFECTS: The efficacy of either agent may be decreased, leading to exacerbation of the disease being treated. In patients with Parkinson disease motor symptoms may worsen, increasing the risk for falls, dysphagia or aspiration.(4,7) Compared with Parkinson patients not receiving antipsychotic therapy, Parkinson patients receiving antipsychotics appear to have an increased mortality risk.(6) Patients with other conditions such as restless legs syndrome or a psychotic disorder may also experience symptom exacerbation due to this combination.

PREDISPOSING FACTORS: Patients with Parkinson or Diffuse Lewy Body (DLB) disease are particularly susceptible to adverse effects of dopamine blockade by antipsychotics.

PATIENT MANAGEMENT: Reassess the need for antipsychotic therapy. If psychosis or hallucinations are due to an antiparkinson agent, when possible consider reducing the dose or changing the antiparkinson agent before initiating antipsychotic therapy. In patients with PD and dementia, addition of a cholinesterase inhibitor (e.g. rivastigmine) may improve psychosis. If an antipsychotic is required, then an atypical antipsychotic should be used.(6,7) In patients with major psychotic disorders, consider reducing the dose, changing or stopping the dopaminergic agent. The US manufacturer of ropinirole recommends treatment with dopaminergic agents only if potential benefits outweigh risks.(1) The US manufacturer of entacapone states it should not ordinarily be used in patients with major psychotic disorders as entacapone may lead to an exacerbation of psychosis.(4)

DISCUSSION: An epidemiologic study evaluated 21,043 elderly patients with Parkinson disease to determine if recent initiation of a typical or atypical antipsychotic was associated with increased mortality. They found an adjusted odds ratio of 2.0 for death associated with atypical antipsychotics versus no antipsychotic They found an adjusted odds ratio of 2.4 for death associated with typical versus atypical antipsychotics. The authors noted the increased mortality found with typical antipsychotics supports current treatment recommendations to use atypical antipsychotic agents in patients with Parkinson disease.(6,7)

Moderate Interaction: Assess the risk to the patient and take action as needed.

Ropinirole/Strong And Moderate Cyp1a2 Inhibitors

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Ropinirole is a CYP1A2 substrate. Strong and moderate CYP1A2 inhibitors may decrease the metabolism of ropinirole.(1-3)

CLINICAL EFFECTS: The concurrent administration of strong or moderate CYP1A2 inhibitors and ropinirole may result in elevated levels of ropinirole, increased clinical effects, and signs of toxicity.(1-3)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: In patients receiving strong or moderate CYP1A2 inhibitors who are started on ropinirole, ropinirole may be titrated to effect according to the manufacturer's dosage instructions. If the strong or moderate CYP1A2 inhibitor is started or discontinued in a patient receiving ropinirole, the dosage of ropinirole may need to be adjusted.(1-2)

DISCUSSION: In a study in 12 subjects, the concurrent administration of ropinirole with ciprofloxacin resulted in increases in the maximum concentration (Cmax) and area-under-curve (AUC) of ropinirole by 84% and 60%, respectively. The major pathway for ropinirole metabolism has been shown to be CYP1A2.(1-3) Strong CYP1A2 inhibitors linked to this monograph include: Angelica dahurica, enasidenib, enoxacin, and fluvoxamine. Moderate CYP1A2 inhibitors linked to this monograph include: capmatinib, centanafadine, ciprofloxacin, dipyrone, fexinidazole, genistein, estrogen-containing contraceptives, methoxsalen, mexiletine, osilodrostat, phenylpropanolamine, pipemidic acid, rucaparib, troleandomycin, vemurafenib, and viloxazine.(4)

Selected Dopamine Agonists/Select Atypical Antipsychotics

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Selected dopamine agonists are used to treat neurologic conditions such as Parkinson Disease (PD) or restless legs syndrome, and endocrine disorders such as hyperprolactinemia by directly or indirectly increasing dopamine concentrations at D2 receptors in the central nervous system (CNS). Antipsychotic agents counteract this effect by blocking dopamine activity at CNS D2 receptors.(1-5)

CLINICAL EFFECTS: The efficacy of either agent may be decreased, leading to exacerbation of the disease being treated, e.g. Parkinson disease or a psychotic disorder. Dopamine agonists linked to this monograph are: bromocriptine, entacapone, levodopa, pergolide, pramipexole, ropinirole and rotigotine. Atypical antipsychotics linked to this monograph are: aripiprazole, asenapine, iloperidone, lumateperone, lurasidone, paliperidone, quetiapine, risperidone, ziprasidone and zotepine.

PREDISPOSING FACTORS: Patients with Parkinson or Diffuse Lewy Body (DLB) disease are particularly susceptible to adverse effects of dopamine blockade by antipsychotics.

PATIENT MANAGEMENT: Reassess the need for antipsychotic therapy. If psychosis or hallucinations are due to an antiparkinson agent, when possible consider reducing the dose or changing the antiparkinson agent before initiating antipsychotic therapy. In patients with PD and dementia, addition of a cholinesterase inhibitor (e.g. rivastigmine) may improve psychosis. If an antipsychotic is required, then an atypical antipsychotic should be used.(6,7) In patients with major psychotic disorders, consider reducing the dose, changing, or stopping the dopamine agonist. The US manufacturer of ropinirole recommends treatment with dopamine agonists only if potential benefits outweigh risks.(1) The US manufacturer of entacapone states it should not ordinarily be used in patients with major psychotic disorders as entacapone may lead to an exacerbation of psychosis.(4)

DISCUSSION: An epidemiologic study evaluated 21,043 elderly patients with Parkinson disease to determine if recent initiation of a typical or atypical antipsychotic was associated with increased mortality. They found an adjusted odds ratio of 2.0 for death associated with atypical antipsychotics versus no antipsychotic. They found an adjusted odds ratio of 2.4 for death associated with typical versus atypical antipsychotics. The authors noted the increased mortality found with typical antipsychotics supports current treatment recommendations to use atypical antipsychotic agents in patients with Parkinson disease.(6,7) Two clozapine trials showed significant improvement in psychosis without worsening of motor symptoms. In contrast, two olanzapine trials were associated with unacceptable worsening of motor symptoms. Risperidone has also been associated with motor worsening in case reports. Quetiapine evaluations have been conflicting with several small studies showing improvement in psychotic symptoms while a more rigorous trial showed no improvement.(6)

*Known hypersensitivity to ropinirole hydrochloride or any ingredient in the formulation.

There are no contraindication contraindications for this drug.

• Bradycardia
• Chronic kidney disease stage 5 (failure) GFr<15 ml/min
• Hypotension
• Impulse control disorder
• Orthostatic hypotension
• Psychotic disorder

• Drowsy
• Dyskinesia
• Hallucinations
• Restless leg syndrome
• Tobacco smoker

Common adverse effects of immediate-release ropinirole in patients with early parkinson disease include nausea, somnolence, dizziness, syncope, asthenic condition, viral infection, leg edema, vomiting, and dyspepsia.

Common adverse effects of the extended-release tablets in patients with early parkinson disease include nausea, somnolence, sudden onset of sleep, hypertension, headache, abdominal pain/discomfort, dizziness, and constipation.

Common adverse effects of immediate-release ropinirole in patients with advanced parkinson disease receiving concomitant levodopa include dyskinesia, somnolence, nausea, dizziness, confusion, hallucinations, sweating, and headache.

Common adverse effects with the extended-release ropinirole tablets in patients with advanced parkinson disease include nausea, dyskinesia, dizziness, and hallucinations.

Common adverse effects of immediate-release ropinirole in patients with RLS include nausea, somnolence, vomiting, dizziness, and fatigue.

More Frequent

• Accidental fall
• Dizziness
• Drowsy
• Dyskinesia
• General weakness
• Hallucinations
• Orthostatic hypotension
• Viral infection

Less Frequent

• Anemia
• Arthralgia
• Atrial fibrillation
• Concentration difficulty
• Extrasystoles
• Hypertension
• Hypotension
• Tachycardia
• Visual changes

Rare or Very Rare

• Bradycardia
• Cardiac arrhythmia
• Cramps
• Drug-induced psychosis
• Dysphagia
• Fibrotic drug-induced cardiac valvulopathy
• Hypersensitivity drug reaction
• Impulse control disorder
• Pericarditis
• Peripheral ischemia
• Pleural effusions
• Pleural fibrosis
• Pulmonary infiltrates
• Pyuria
• Retroperitoneal fibrosis
• Sudden onset of sleep

More Frequent

• Dyspepsia
• Headache disorder
• Hyperhidrosis
• Nausea
• Pharyngitis
• Vomiting

Less Frequent

• Acute abdominal pain
• Acute cognitive impairment
• Anorexia
• Arthritis
• Back pain
• Bronchitis
• Chest pain
• Constipation
• Diarrhea
• Diplopia
• Dry eye
• Dyspnea
• Erectile dysfunction
• Flatulence
• Flushing
• Insomnia
• Memory impairment
• Nasal congestion
• Pain
• Paresthesia
• Peripheral edema
• Rhinitis
• Sinusitis
• Syncope
• Tremor
• Urinary incontinence
• Urinary tract infection
• Weight loss
• Xerostomia
• Yawning

Rare or Very Rare

• Aggressive behavior
• Agitation
• Augmentation of restless legs syndrome
• Cough
• Delirium
• Delusional disorder
• Dream disorder
• Fatigue
• Hypoesthesia
• Malaise
• Nervousness
• Paranoid disorder
• Symptoms of anxiety
• Upper respiratory infection
• Vertigo

No enhanced messaging available.

Safety and efficacy of ropinirole have not been established in pediatric patients.

There are no adequate data on the developmental risks associated with the use of ropinirole in pregnant women. In animal studies, adverse developmental effects (e.g., teratogenicity, embyrolethality) were observed when the drug was administered to pregnant rats at dosages similar to or greater than the recommended maximum human dosage; these dosages also were associated with maternal toxicity. In pregnant rabbits, oral administration of ropinirole had no effect on embryofetal development, but when administered in combination with levodopa, an increased incidence of fetal malformations was observed.

It is not known whether ropinirole is distributed into human milk; however, the drug is distributed into milk in rats. The effects of ropinirole on the breast-fed infant or on milk production are not known. The known benefits of breast-feeding should be considered along with the mother's clinical need for ropinirole and any potential adverse effects on the breast-fed infant from the drug or underlying maternal condition.

Because ropinirole inhibits prolactin secretion, the drug is expected to inhibit lactation.

Oral clearance of ropinirole is reduced by 15% in geriatric patients older than 65 years of age compared with younger patients. In clinical studies of ropinirole in patients with parkinson disease, some adverse effects were more frequent in geriatric patients (e.g., hallucinations, vomiting, nausea) than in younger patients receiving the drug.