Kinetica Special Precautions

Sudden Onset of Sleep: Ropinirole has been associated with somnolence and episodes of suddenly falling asleep while engaging in activities of daily living, such as driving or operating machinery, which has sometimes resulted in accidents. Although cases of sudden onset of sleep while engaged in daily living usually occur in a setting of pre-existing somnolence, others may not give such a history. Thus, prescribers should reassess patients for drowsiness or sleepiness, especially since some of the events occur well after treatment initiation. However, some of these adverse events have been reported as late as one year after starting ropinirole therapy. Patients may not be aware of excessive drowsiness or sleepiness, perceived that they had no warning signs (e.g., excessive drowsiness), and that they were alert immediately prior to the event until directly questioned about drowsiness or sleepiness during specific activities.
Many Parkinson's disease patients experience alterations in sleep architecture, resulting to excessive daytime sleepiness or spontaneous dozing; however, the exact cause of these events is not yet known. In addition, dopaminergic agents can also induce sleepiness. There is insufficient information to determine whether this event is associated with ropinirole, all dopaminergic agents or Parkinson's disease itself.
Patients should be advised of the potential occurrence of drowsiness before starting treatment with ropinirole. In addition, the patient should be specifically asked about the factors that may increase the risk of drowsiness, such as concomitant use of sedating medications or alcohol; sleep disorders; or coadministration of drugs that may increase ropinirole plasma levels (see Interactions).
If a patient develops significant daytime sleepiness or episodes of falling asleep during activities that require active participation (e.g., driving, conversation, eating), dose reduction or treatment discontinuation should be considered (see Dosage & Administration). However, there is insufficient information to establish that dose reduction will lessen the risk of falling asleep while engaged in activities of daily living. If a decision is made to continue treatment with ropinirole, patients should be advised to avoid driving and other potentially dangerous activities. Physicians should inform patients of the reported cases of sudden onset of sleep, since these events are not limited to treatment initiation. Patients should also be advised that sudden onset of sleep may occur even without warning signs. Patients should contact their physician immediately if drowsiness or sudden onset of sleep occurs.
Cardiovascular Effects: Patients with pre-existing cardiovascular conditions: Ropinirole has not been studied in patients with a history or evidence of significant cardiovascular disease, such as myocardial infarction, unstable angina, cardiac decompensation, cardiac arrhythmias, vaso-occlusive disease (including cerebral) or cardiomyopathy. Due to its pharmacologic action, ropinirole should be used with caution in patients with these conditions or those with severe cardiovascular disease.
Hypotension/Orthostatic hypotension: Patients with Parkinson's disease may have impaired capacity to respond to hypotension after standing from a seated position or from lying down. In addition, dopamine agonists may impair the systemic regulation of blood pressure with resulting orthostatic symptoms of dizziness or light-headedness, with or without documented hypotension. These symptoms occur particularly during dose initiation and escalation. Significant decrements in blood pressure unrelated to standing were also reported. Therefore, patients treated with ropinirole and other dopamine agonists should be informed of this risk and be carefully monitored for signs and symptoms of orthostatic hypotension, especially during dose initiation/escalation and in patients at risk of hypotension, those receiving antihypertensive and antiarrhythmic drugs (see Interactions), those who poorly tolerate transient hypotensive episodes, and those with severe cardiovascular disease, particularly coronary insufficiency.
Syncope: Syncope, sometimes associated with bradycardia, has been observed in patients with Parkinson's disease during ropinirole therapy.
Elevation of Blood Pressure and Changes in Heart Rate: Increased incidence of elevations of systolic and/or diastolic blood pressure and/or change in pulse occurred in both titration and maintenance phase of ropinirole therapy. In some cases, this effect developed in the titration phase and persisted up to the maintenance period. The elevations of blood pressure and/or changes in heart rate should be considered in patients with cardiovascular disease.
Fibrotic Complications: Ergot-derived dopamine agonists have been associated with cases of retroperitoneal fibrosis, pulmonary infiltrates, pleural effusion, pleural thickening, pericarditis, and cardiac valvulopathy. Although ropinirole is not an ergot, possible fibrotic complications (i.e., pleural effusion, pleural fibrosis, interstitial lung diseases, and cardiac valvulopathy) have been reported with ropinirole in postmarketing studies. Patients should be closely monitored for signs and symptoms of fibrosis.
While discontinuation may resolve these complications, complete resolution does not always occur.
Effects on the Central Nervous System: Withdrawal-Emergent Hyperpyrexia and Confusion: A symptom complex resembling neuroleptic malignant syndrome with no other obvious etiology has been reported with significant dose reduction in, or abrupt withdrawal of antiparkinsonian therapy after long-term use. The syndrome is characterized by elevated temperature, muscular rigidity, altered consciousness, and autonomic instability. It is recommended that the dose must be tapered at the end of treatment.
Dyskinesia with Adjunctive Levodopa: Ropinirole may cause or exacerbate pre-existing dyskinesia due to its potentiation of the dopaminergic adverse effects of levodopa. Decreasing the dose of levodopa may ameliorate this effect.
Psychiatric Effects: Impulse Control/Compulsive Behaviors: Impulse control symptoms, including compulsive behaviors (e.g., pathological gambling, increased libido, hypersexuality, compulsive shopping, and binge eating), have been reported in patients treated with ropinirole or other dopamine agonists, especially at high doses. In some cases, these symptoms were generally reversible upon dose reduction or treatment discontinuation. Other factors that may increase these urges, such as a history of compulsive behaviors or concurrent dopaminergic treatment, may also be present.
Since patients may not recognize that these behaviors were abnormal, patients should be regularly monitored for the development of impulse control disorders. It is also important for prescribers to specifically ask patients or their caregivers about the development of new or increased incidences of compulsive behaviors while being treated with ropinirole. Dose reduction or tapered discontinuation should be considered if the patient develops such compulsive behaviors.
Aggression has been associated with psychotic reactions as well as compulsive symptoms.
Hallucinations/Psychotic-like Behavior: Patients may experience new or worsening mental status and behavioral changes, which may be severe, including psychotic-like behavior, during initiation of treatment with ropinirole or after increasing the dose. Other drugs prescribed to improve the symptoms of Parkinson's disease can have similar effects on thinking and behavior. The manifestations of abnormal thinking and behavior include paranoid ideation, delusions, hallucinations, confusion, psychotic-like behavior, disorientation, aggressive behavior, agitation, and delirium.
Since ropinirole may exacerbate psychosis, it should only be used in patients with a history or presence of major psychotic disorder if the potential benefits outweigh the risks of treatment. In addition, certain medications used to treat psychosis may aggravate the symptoms of Parkinson's disease and may decrease the effectiveness of ropinirole (see Interactions).
Hallucination is a known adverse effect of treatment with dopamine agonist and levodopa. Patients and caregivers should be informed that hallucinations may occur during ropinirole treatment.
Dermatologic Effects: Epidemiological studies demonstrated that patients with Parkinson's disease have a 2- to 6-fold higher risk of developing melanoma compared with the general population. However, it is unclear if the increased risk observed was due to Parkinson's disease or to the drugs used to manage the disease. Patients and caregivers are advised to monitor for melanomas frequently and regularly during ropinirole treatment. Skin examinations should be performed periodically.
Dopamine Agonist Withdrawal Syndrome: Non-motor adverse effects, such as apathy, anxiety, depression, fatigue, sweating, and pain, may occur when tapering or discontinuing dopamine agonists; these effects may be severe. Treatment with ropinirole should not be abruptly discontinued (see Dosage & Administration). Patients should be informed of this risk before tapering ropinirole therapy, and monitored regularly thereafter. In case of persistent symptoms, it may be necessary to temporarily increase the dose of ropinirole.
Effects on Ability to Drive and Use Machines: Ropinirole may have a significant effect on the ability to drive and use machines since it may cause sudden onset of sleep without any prior warning or apparent daytime somnolence and dizziness, including vertigo. Patients should be informed of this risk and be warned not to drive or engage in other activities where impaired alertness could put themselves and others at risk of serious injury or death (e.g., operating machines), until these episodes and somnolence have been resolved. Since cases of falling asleep while engaged in activities of daily living also occurred in patients taking other dopaminergic agents, symptoms may not be alleviated by substituting these products.
Hepatic Impairment: Since the use of ropinirole in patients with hepatic impairment has not been studied, the use of ropinirole in such patients is not recommended.
Renal Impairment: Dose adjustments are not necessary for patient with mild to moderate renal impairment. Since the use of ropinirole in patients with severe renal impairment (CrCl <30 mL/min without regular dialysis) has not been studied, the use of ropinirole in such patients is not recommended. In patients with end stage renal disease on hemodialysis, a lower maximum dose is recommended which, compared to the maximum exposure evaluated in clinical trials, results in similar exposure to ropinirole, and to a 4.5-fold increased exposure to the N-despropyl inactive metabolite (see Dosage & Administration).
Use in Children: The effectiveness and safety of ropinirole in children below 18 years of age have not been established.
Use in the Elderly: The oral clearance of ropinirole is decreased in patients older than 65 years of age. The dosing of ropinirole for elderly patients should be titrated individually based on clinical therapeutic response and tolerability. For patients 75 years and older, slower titration during treatment initiation is recommended (see Dosage & Administration).