Ropinirole is an oral non-ergoline dopamine agonist. The immediate-release formulation is indicated for the treatment of Parkinson's disease and the treatment of moderate to severe restless legs syndrome (RLS) in adults, while the extended-release formulation is indicated only for the treatment of the signs and symptoms of idiopathic Parkinson's disease in adults. Clinical practice guidelines suggest that non-ergot dopamine agonists (including ropinirole) may be used as first-line pharmacologic options for early Parkinson's disease in younger patients (less than 60 years old) who are at high risk for the development of levodopa-induced dyskinesias. Somnolence and dizziness are common side effects associated with ropinirole, and orthostatic hypotension has been reported during initiation and dose titration. Serious adverse effects of ropinirole and other dopamine agonists include hallucinations and psychotic-like behavior, impulse control symptoms, and sleep attacks (falling asleep during activities of daily living). Older patients have an increased risk for cognitive and behavioral adverse effects from dopamine agonists; thus, levodopa therapy generally has a more favorable benefit to risk ratio in this patient population.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
Oral Solid Formulations
Immediate-release tablets:
-May administer with or without food.
Extended-release tablets:
-Administer once daily, with or without food. Taking with food may reduce the occurrence of nausea.
-Swallow whole; do not chew, crush or divide.
Dermatologic adverse reactions have been reported in patients receiving ropinirole alone and in combination with L-dopa. The most commonly observed dermatologic adverse reactions in patients with early Parkinson's disease receiving monotherapy with immediate-release ropinirole and reported at incidences greater than placebo included hyperhidrosis (6%) and flushing (3%). Hyperhidrosis (7%) was the most common dermatologic effect in ropinirole plus L-dopa treated patients with advanced Parkinson's disease. Hyperhidrosis (3%) was also reported more frequently in patients receiving immediate-release ropinirole than placebo during clinical trials for restless legs syndrome. Advise patients about the potential for developing a hypersensitivity reaction which may include symptoms such as urticaria, angioedema, rash (unspecified), and pruritus when taking any ropinirole product.
Adverse reactions affecting the body as a whole have been reported in patients receiving ropinirole alone and in combination with L-dopa. The most commonly observed general adverse reactions reported in patients with early Parkinson's disease receiving monotherapy with immediate-release ropinirole and reported at greater incidences versus placebo included asthenia (16%), chest pain (unspecified) (4%), dependent edema (6%), pain (8%), peripheral ischemia (3%), and peripheral edema (7%). Pain (5%) and peripheral edema (4%) were the most common adverse reactions affecting the body as a whole in patients with advanced Parkinson's disease receiving immediate-release or extended-release ropinirole plus L-dopa versus placebo. Asthenia (9%) and peripheral edema (2%) were reported more frequently in patients receiving immediate-release ropinirole than placebo during clinical trials for restless legs syndrome (RLS).
Cardiovascular adverse reactions have been reported in patients receiving ropinirole alone and in combination with L-dopa. The most commonly observed cardiovascular adverse reactions in patients with early Parkinson's disease receiving monotherapy with immediate-release or extended-release ropinirole occurring at higher incidences versus placebo included atrial fibrillation (2%), extrasystoles (2%), hypertension (up to 15%), hypotension (2%), orthostatic hypotension (6%), palpitations (3%), sinus tachycardia (2%), and syncope (12%, syncope sometimes occurred with bradycardia). In patients with advanced Parkinson's disease receiving immediate-release or extended-release ropinirole plus L-dopa, the following cardiac effects occurred more frequently with active treatment than placebo: hypotension (2%), hypertension (1% to 8%), orthostatic hypotension (5%), and syncope (3%). In patients with restless legs syndrome (RLS) receiving treatment with immediate-release ropinirole, there were reports of syncope in 1% of ropinirole-treated patients. In a fixed-dose trial of extended-release ropinirole in combination with L-dopa in advanced Parkinson's disease, orthostatic hypotension (systolic blood pressure reduction of at least 20 mmHg) was reported more frequently in ropinirole-treated patients (38%) than placebo-treated patients. There was no clear effect of extended-release ropinirole on average heart rate. Most syncope cases occurring with ropinirole monotherapy were reported more than 4 weeks after initiation of ropinirole therapy and were usually associated with a recent increase in dose. Further, ropinirole-induced orthostatic hypotension is thought to be due to dopamine D2-mediated blunting of the noradrenergic response. Hypotension and syncope were the most common cardiovascular adverse reactions reported in patients treated with ropinirole and L-dopa combination therapy. In a clinical trial evaluating extended-release ropinirole in combination with L-dopa for advanced Parkinson's disease, severe systolic blood pressure increases (40 mmHg or more) occurred in 8% of those on active drug in the semi-supine position. While standing, the frequency increased to 9% in the ropinirole group.
Adverse reactions affecting the central and peripheral nervous systems have been reported in patients receiving ropinirole alone and in combination with L-dopa. The most commonly observed adverse reactions affecting the CNS/peripheral nervous systems in patients with early Parkinson's disease receiving monotherapy with immediate-release or extended-release ropinirole and with incidences greater than placebo included dizziness (up to 40%), hyperkinesis (2%), hyperesthesia (4%), yawning (3%), headache (5% to 15%), and vertigo (2%). The most common adverse reactions affecting the CNS/peripheral nervous systems in patients with advanced Parkinson's disease receiving immediate-release or extended-release ropinirole plus L-dopa and more frequently than placebo included dizziness (4% to 26%), dyskinesia (4% to 34%), falls (2% to 10%), headache (17%), hypokinesia (5%), paresis (3%), paresthesias (5%), tremor (6%), vertigo (4%), and insomnia (up to 5%). CNS effects reported more frequently in patients receiving immediate-release ropinirole than placebo for restless legs syndrome (RLS) included dizziness (11%), paresthesias (3%), and vertigo (2%).
Drowsiness is one of the most commonly observed side effects in patients receiving ropinirole, either alone or in combination with other drugs. In placebo-controlled clinical trials of ropinirole monotherapy in patients with early Parkinson's disease, less patients receiving placebo experienced somnolence than patients treated with immediate-release ropinirole (40%) or extended-release ropinirole (8% to 15%). In patients with advanced Parkinson's disease receiving immediate-release or extended-release ropinirole plus L-dopa therapy, somnolence/drowsiness was reported in up to 20% of patients in the active treatment group. Somnolence occurred less frequently during clinical trials of immediate-release ropinirole for restless legs syndrome (12%). Dopamine agonists, including ropinirole, have been associated with sudden sleep onset while driving or performing other normal daytime activities. Excessive and acute lethargy has resulted in auto accidents or other harmful events in the course of daily living, including fatalities resulting from auto accidents. The episodes have occurred as late as 1 year after the initiation of treatment. Some patients have reported feeling completely alert prior to these events. It is not clear whether the medication, the sleep status of the patient, or Parkinson's disease itself is contributing to these episodes; a number of factors may be related to the sudden loss of alertness. During clinical trials of extended-release ropinirole, sudden sleep onset occurred more frequently in patients with advanced Parkinson's disease receiving ropinirole plus L-dopa (up to 8%) and patients with early Parkinson's disease not receiving L-dopa (up to 10%) compared to placebo. The incidence of sudden sleep onset was not dose-related. In a flexible-dose trial of extended-release ropinirole, sudden sleep onset was reported in less than 1% of patients, and less than 1% of patients reported a motor vehicle accident in which it is not known if falling asleep was a contributing factor. Patients should be cautioned against driving or operating machinery, working at heights, or performing other tasks that require alertness while receiving ropinirole. The use of concomitant CNS depressant medications or sleep disorders may increase the risk of falling asleep while taking this medication; patients should be assessed for these risk factors prior to initiation of the drug and be advised of the additive risks for somnolence. Patients should be continually reevaluated for the presence of excessive sedation during treatment and should notify their prescriber if they fall asleep during normal activities. Ropinirole should generally be discontinued in those who experience episodes of falling asleep while engaged in activities of daily living. It is not known if a reduction in dosage will subsequently reduce or eliminate excessive somnolence or sudden episodes of sleep.
Psychiatric adverse reactions have been reported in patients receiving ropinirole alone and in combination with L-dopa. Commonly observed psychiatric adverse reactions reported in patients with early Parkinson's disease receiving monotherapy with immediate-release ropinirole and rated higher than placebo included amnesia (3%), impaired concentration (2%), confusion (5%), and hallucinations (5%). Amnesia (5%), anxiety (2% to 6%), confusion (9%), abnormal dreams (3%), hallucinations (8% to 10%), and nervousness (5%) were the most common psychiatric adverse reactions in ropinirole plus L-dopa treated patients with advanced Parkinson's disease. Discontinuation of treatment due to hallucinations occurred in 2% of patients receiving extended-release ropinirole versus 1% of those taking placebo. Psychotic-like behavior may manifest as hallucinations, confusion, paranoia, aggression, agitation, delusions, and/or disorganized thinking. Hallucinations occur at a higher frequency in the geriatric patient, those being treated for Parkinson's disease, those receiving high doses of ropinirole, and/or those taking concomitant L-dopa.
Impulse control symptoms and compulsive behaviors, such as aggressive behavior, compulsive spending or buying, binge or compulsive eating, have been reported during postmarket use of ropinirole. Some patients receiving medications that increase dopaminergic tone have reported intense and uncontrollable urges to gamble, increased sexual urges, or other intense urges. Causality due to dopaminergic agents has not been established; however, in some cases, the urges stopped after the dose was reduced or the drug 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. Dose reduction or discontinuation should be considered in those who experience these effects.
Gastrointestinal (GI) system adverse reactions have been reported in patients receiving ropinirole alone and in combination with L-dopa. The most commonly observed GI adverse reactions reported in patients with early Parkinson's disease receiving monotherapy with immediate-release or extended-release ropinirole and at rates higher than placebo included abdominal pain (6%), dyspepsia (10%), flatulence (3%), xerostomia (5%), nausea (8% to 60%), and vomiting (up to 12%). Abdominal pain (6% to 9%), constipation (4% to 6%), diarrhea (3% to 5%), dysphagia (2%), flatulence (2%), hypersalivation (2%), xerostomia (2% to 5%), nausea (11% to 30%), and vomiting (7%) were the most common GI system adverse reactions in ropinirole plus L-dopa treated patients with advanced Parkinson's disease. During fixed-dose trials of extended-release ropinirole plus L-dopa in patients with advanced Parkinson's disease, nausea and vomiting were more common in patients greater than 65 years (9% and 5%, respectively) than in patients less than 65 years (7% and 1%, respectively). In clinical trials of immediate-release ropinirole in patients with restless legs syndrome (RLS), the following GI effects occurred in more ropinirole-treated patients than placebo-treated patients: nausea (40%), vomiting (11%), diarrhea (5%), dyspepsia (4%), xerostomia (3%), and upper abdominal pain (3%).
Adverse reactions affecting the metabolic and nutritional systems have been reported in patients receiving ropinirole alone and in combination with L-dopa. The most commonly observed adverse reactions affecting the metabolic and nutritional systems in patients with early Parkinson's disease receiving monotherapy with immediate-release ropinirole and at rates higher than placebo were increased alkaline phosphatase (3%) and anorexia (4%). Weight loss (2%) was the most common adverse reaction affecting the metabolic and nutritional systems in ropinirole plus L-dopa treated patients with advanced Parkinson's disease.
Genitourinary and reproductive adverse reactions have been reported in patients receiving ropinirole alone and in combination with L-dopa. The most common reproductive system adverse reaction reported in patients with early Parkinson's disease receiving immediate-release ropinirole monotherapy was impotence (erectile dysfunction) (3%). Pyuria (2%) and urinary incontinence (2%) were the most common urinary system adverse reactions in ropinirole plus L-dopa treated patients with advanced Parkinson's disease.
Musculoskeletal system adverse reactions have been reported in patients receiving ropinirole with or without L-dopa. Back pain (up to 15%) was reported more frequently in patients with early Parkinson's disease receiving monotherapy with ropinirole than in those receiving placebo. The most commonly observed musculoskeletal system adverse reactions in patients with advanced Parkinson's disease receiving immediate-release or extended-release ropinirole in combination with L-dopa were arthralgia (up to 8%), back pain (3%), and arthritis (3%). Musculoskeletal effects that were reported more frequently in patients receiving immediate-release ropinirole than placebo during clinical trials for restless legs syndrome (RLS) included arthralgia (4%), muscle cramps (3%), and extremity pain (3%).
Restless legs syndrome (RLS) augmentation occurs when dopamine agonists, such as ropinirole, cause a worsening of RLS symptom severity above and beyond the level at the time the medication was started or may involve an earlier time of symptom onset each day compared to pre-treatment levels. Augmentation symptoms may include the earlier onset of symptoms in the evening or afternoon, increase in symptoms, or spread of symptoms to involve other extremities. Restless legs syndrome (RLS) rebound is an exacerbation of RLS symptoms and is considered to be an end-of-dose effect related to the half-life of the drug. Rebound has been observed during discontinuation of the dopaminergic agent, and in the early morning hours during ongoing treatment (also known as early-morning rebound). If augmentation or early-morning rebound occurs, the use of ropinirole should be re-assessed, and a dosage adjustment or discontinuation of treatment should be considered. When discontinuing ropinirole, a gradual taper is recommended to minimize rebound effects.
The most commonly observed infections or respiratory adverse reactions reported in patients with early Parkinson's disease receiving monotherapy with immediate-release ropinirole at rates higher than placebo included viral infection (11%), bronchitis (3%), dyspnea (3%), pharyngitis (6%), rhinitis (4%), sinusitis (4%), and urinary tract infection (5%). In patients with advanced Parkinson's disease receiving ropinirole plus L-dopa, the following infections or respiratory system effects were reported more frequently in patients receiving immediate-release or extended-release ropinirole than placebo: upper respiratory tract infection (9%), naso-pharyngitis (up to 8%), urinary tract infection (6%), and dyspnea (3%). In clinical trials of patients with restless legs syndrome (RLS), the following effects occurred in more immediate-release ropinirole-treated patients than placebo-treated patients: naso-pharyngitis (9%), influenza (3%), cough (3%), and nasal congestion (2%). Fibrotic complications have been reported in some patients treated with ergot-derived dopaminergic agents. Although these adverse reactions are believed to be related to the ergoline structure of these compounds, it is not known if other non-ergot derived dopamine agonists (e.g., ropinirole) can cause them.
Adverse reactions affecting vision have been reported in patients receiving ropinirole alone and in combination with L-dopa. The most commonly observed adverse reactions affecting vision in patients with early Parkinson's disease receiving monotherapy with immediate-release ropinirole at rates greater than with placebo were unspecified eye abnormality (3%), visual impairment (6%), and xerophthalmia (2%). Diplopia (2%) was the most common adverse reaction affecting the ocular system in ropinirole plus L-dopa treated patients with advanced Parkinson's disease. Animal data have shown that ropinirole binds to melanin-containing tissues (i.e., eyes, skin); these data indicate long-term retention of ropinirole with an ocular half-life of 20 days. It is not known if ropinirole accumulates in these tissues over time. In a 2-year safety study of retinal deterioration and vision, 234 patients with Parkinson's disease were randomized to pramipexole (n = 115; mean dose 3 mg/day PO) or ropinirole (n = 119; mean dose 9.5 mg/day PO). Clinical abnormalities that were considered meaningful developed in 29/196 patients who had been treated for 2 years (19 patients in each treatment arm had received treatment for less than 2 years). There was no statistically significant difference in retinal deterioration between the treatment arms; however, the study was only capable of detecting a very large difference between treatments. Because the study did not include a placebo group, a causal relationship to either drug cannot be established. It is unknown whether the findings reported in patients treated with either drug are greater than the background rate in an aging population.
During clinical trials in patients with advanced Parkinson's disease, anemia (2%) was reported more frequently in ropinirole immediate-release plus L-dopa treated patients than with placebo-treated patients.
A withdrawal or discontinuation syndrome has been associated with the abrupt stoppage of dopamine agonist therapy, such as ropinirole, in patients with Parkinson's disease. Discontinuation symptoms of apathy, anxiety, depression, fatigue, insomnia, sweating, and pain have been reported in patients with Parkinson's disease during dosage tapering or treatment discontinuation; these symptoms generally do not respond to treatment with levodopa. Closely monitor these patients during and after treatment discontinuation. Re-administration at the lowest effective ropinirole dose may be considered if severe withdrawal symptoms develop. Rarely, neuroleptic malignant syndrome-like symptoms (e.g., hyperpyrexia, confusion, muscular rigidity, altered consciousness, autonomic instability), with no other obvious etiology, have been reported in association with rapid dose reductions of, withdrawal from, or changes in dopaminergic therapy. If discontinuation of ropinirole becomes necessary, a gradual reduction in dose is recommended for both the immediate-release and extended-release formulations in patients with Parkinson's disease or restless legs syndrome (RLS).
Ropinirole is contraindicated in patients with a known hypersensitivity (including urticaria, angioedema, rash, pruritus) to ropinirole or its excipients.
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.
Treatment of Restless Legs syndrome (RLS) with dopaminergic medications can result in a worsening of symptoms in the early morning hours, referred to as rebound. Augmentation, which may also occur during treatment with dopaminergic agents, refers to the earlier onset of RLS symptoms in the afternoon or evening, increase in symptoms, and spread of symptoms to involve other extremities. Augmentation and/or early-morning rebound have been observed in a postmarketing trial. If augmentation or early-morning rebound occurs, the use of ropinirole should be reviewed; consider dosage adjustment or discontinuation of treatment.
Syncope, sometimes associated with bradycardia, was observed in association with treatment with ropinirole in both patients with Parkinson's disease and patients with restless legs syndrome (RLS). Most cases occurred more than 4 weeks after initiation of therapy and were usually associated with a recent increase in dose. 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 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. Patients with significant cardiac disease should be treated with ropinirole with caution.
Ropinirole commonly causes somnolence. Sudden sleep onset has been reported during the use of dopamine agonists, including ropinirole. Some incidents have occurred while the patient was driving or performing other potentially hazardous activities. In some cases, excessive drowsiness due to dopamine agonists has resulted in auto accidents or other harmful events in the course of daily living. Sudden sleep onset has occurred as late as 1 year after the initiation of treatment. Prior to initiating treatment with ropinirole, patients should be advised of the potential for somnolence and assessed for factors that may increase the risk of experiencing such an event including the presence of sleep disorders (e.g., narcolepsy, sleep apnea), ethanol ingestion, or coadministration with other CNS depressants or other interacting medications that increase ropinirole concentrations. Patients should be cautioned against driving or operating machinery or performing other tasks that require alertness until they gauge how ropinirole affects their motor performance. Assessment for somnolence is necessary throughout ropinirole therapy because patients may not acknowledge drowsiness or sleepiness until directly questioned about drowsiness or sleepiness during specific activities. If a patient develops significant daytime sleepiness or episodes of falling asleep during activities that require active participation (e.g., conversations, eating, etc.), ropinirole should ordinarily be discontinued. If a decision is made to continue the drug, 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.
Some patients receiving medications that increase dopaminergic tone, such as medications used to treat Parkinson's disease, have reported intense and uncontrollable urges to gamble, increased sexual urges, or other intense urges. Causality due to dopaminergic agents has not been established; however, in some cases, the urges stopped after the dose was reduced or the drug was discontinued. Practitioners should inquire periodically about new or worsening impulse control symptoms in patients receiving ropinirole because patients may not recognize these behaviors as abnormal. Likewise, patients should be instructed to report such changes while receiving ropinirole. Dose reduction or discontinuation should be considered in those who experience these effects.
Due to the risk of psychosis exacerbation, patients with psychotic disorders (e.g., schizophrenia) should generally not receive treatment with dopamine agonists, including ropinirole. New or worsening mental status and behavioral changes, including hallucinations, psychotic-like behavior, symptoms of mania (e.g., insomnia, psychomotor agitation), paranoid ideation, delusions, confusion, disorientation, aggressive behavior, agitation, and delirium, have been reported in patients treated with ropinirole and other dopamine agonists. Age appears to increase the risk of hallucinations related to ropinirole administration; the elderly may be more at risk. Additionally, certain medications used to treat psychosis may exacerbate the symptoms of Parkinson's disease and may decrease the efficacy of ropinirole.
Ropinirole may cause or exacerbate pre-existing dyskinesia in patients treated with levodopa for Parkinson's disease (PD). In double-blind, placebo-controlled trials in advanced PD, dyskinesia was much more common in patients treated with ropinirole than in those treated with placebo. Decreasing the dose of dopaminergic medications may ameliorate this adverse reaction.
No dosage adjustments are needed in patients with mild to moderate renal impairment (CrCl of 30 to 50 mL/minute or more). Initial dose adjustments are recommended in patients with end-stage renal disease (CrCl less than 15 mL/minute) who are receiving regular dialysis; titration should be based on tolerability and response. The use of ropinirole in patients with severe renal impairment (CrCl less than 30 mL/minute) or renal failure who are not receiving regular dialysis has not been studied.
Ropinirole should be titrated with caution in patients with hepatic disease, as studies in these patients have not been performed. These patients may have higher plasma concentrations and lower clearance of ropinirole than patients with normal hepatic function.
Avoid abrupt discontinuation or rapid dose reduction of immediate-release and extended-release ropinirole if possible. If discontinuation of ropinirole becomes necessary in patients with Parkinson's disease, the manufacturer of the immediate-release formulation recommends a gradual reduction of the daily dose over a 7-day period beginning with a frequency reduction from 3-times per day to twice per day for 4 days followed by once daily administration for the remaining 3 days. The manufacturer of the extended-release formulation recommends an unspecified taper over 7 days. Adverse events resembling neuroleptic malignant syndrome (e.g., hyperpyrexia, confusion, muscular rigidity, altered consciousness, autonomic instability) have been reported in association with rapid dose reductions of, withdrawal from, or changes in dopaminergic therapy. Further, symptoms of apathy, anxiety, depression, fatigue, insomnia, sweating, and pain have been reported during dosage tapering or after discontinuation of dopamine agonists, such as ropinirole. These symptoms generally do not respond to treatment with levodopa. Inform drug recipients about the potential for withdrawal symptoms prior to stopping ropinirole, and closely monitor these patients during and after treatment discontinuation. Re-administration at the lowest effective dose may be considered if severe withdrawal symptoms develop. In patients with restless legs syndrome (RLS), rebound symptoms have been reported following abrupt discontinuation of some dopaminergic medications. When discontinuing immediate-release ropinirole in patients with RLS, a gradual unspecified taper of the daily dose is recommended.
The relative risk of hallucinations during ropinirole administration is increased in geriatric adults with Parkinson's disease compared to younger adults. Despite some pharmacokinetic differences compared to younger adults, dosage adjustment is not necessary in older adults more than 65 years of age, as the dose of ropinirole is to be individually titrated to clinical response.
There are no adequate or well-controlled studies of ropinirole in human pregnancy; therefore, ropinirole should be used in pregnancy only if the potential benefit to the mother outweighs the potential risk to the fetus. The low molecular weight and pharmacokinetic profile of the drug suggest that placental transfer is likely. In animal studies, ropinirole was teratogenic (e.g., digital malformations) and also produced other adverse effects on embryo-fetal development (e.g., decreased fetal weight, increased fetal deaths). Combined use of ropinirole and L-dopa in pregnant rabbits produced a greater incidence and severity of fetal malformations (primarily digit defects) than were seen in the offspring of rabbits treated with L-dopa alone. In a perinatal-postnatal study in rats, growth and development of nursing offspring were impaired and female offspring experienced altered neurological development. The effects of ropinirole during labor and delivery are unknown.
The use of ropinirole during breast-feeding is generally not recommended; consider alternate treatments. There are no data on the presence of ropinirole in human milk, the effects of ropinirole on the breastfed infant, or the effects of ropinirole on milk production. However, inhibition of lactation is expected because ropinirole inhibits secretion of prolactin in humans. Ropinirole has been detected in the milk of lactating rats. The benefits of breast-feeding should be considered along with the clinical need for ropinirole therapy and any potential adverse effects on the breastfed infant from ropinirole or from the underlying maternal condition.
Safe and effective use of ropinirole has not been established in pediatric patients less than 18 years of age. Juvenille Parkinson's disease is rare in children and adolescents, and the drug has not been systematically evaluated in pediatric restless leg syndrome. There is no identified potential use of ropinirole in infants.
Tobacco smoking is expected to increase the clearance of ropinirole since CYP1A2 is known to be induced by smoking and is the main enzyme responsible for ropinirole metabolism. Patients should inform their prescriber if they start or stop smoking during treatment.
For the treatment of Parkinson's disease:
Oral dosage (immediate-release):
Adults: 0.25 mg PO 3 times daily, initially. May increase the dose by 0.25 mg/dose weekly based on clinical response and tolerability. After week 4, may increase the dose by 1.5 mg/day weekly up to 9 mg day, and then by 3 mg/day weekly. Max: 24 mg/day. To discontinue, reduce dose from 3 times daily to twice daily for 4 days, then once daily for 3 days, and then discontinue.
Oral dosage (extended-release):
Adults: 2 mg PO once daily for 1 to 2 weeks, initially. May increase the dose by 2 mg/day weekly based on clinical response and tolerability. Usual dose 12 mg/day or less. Max: 24 mg/day. To discontinue, taper dose gradually over 1 week.
Oral dosage (extended-release conversion from immediate-release ropinirole):
Adults: 2 mg PO once daily for 0.75 to 2.25 mg/day immediate-release; 4 mg PO once daily for 3 to 4.5 mg/day immediate-release; 6 mg PO once daily for 6 mg/day immediate-release; 8 mg PO once daily for 7.5 to 9 mg/day immediate-release; 12 mg PO once daily for 12 mg/day immediate-release; 16 mg PO once daily for 15 mg/day immediate-release; 18 mg PO once daily for 18 mg/day immediate-release; 20 mg PO once daily for 21 mg/day immediate-release; 24 mg PO once daily for 24 mg/day immediate-release. May increase the dose by 2 mg/day weekly based on clinical response and tolerability. Usual dose: 12 mg/day or less. Max: 24 mg/day. To discontinue, taper dose gradually over 1 week.
For the treatment of restless legs syndrome (RLS):
Oral dosage (immediate-release tablets; i.e., Requip):
Adults: 0.25 mg PO once daily given 1 to 3 hours before bedtime, initially. During days 3 through 7, may increase to 0.5 mg/day. At week 2 (day 8), may increase to 1 mg/day for 7 days. In weeks 3 through 6, may titrate further by 0.5 mg/week (from 1.5 mg to 3 mg/day over the 5-week period), as needed to achieve the desired effect. In week 7, may increase dose to 4 mg/day, based on clinical response and tolerability. All daily doses are given 1 to 3 hours before bedtime. Max: 4 mg/day PO. DISCONTINUATION: When discontinuing a gradual reduction of the daily dose is recommended.
Maximum Dosage Limits:
-Adults
24 mg/day PO.
-Geriatric
24 mg/day PO.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Specific dose adjustment recommendations are not available due to lack of studies in patients with hepatic impairment. Because ropinirole is extensively metabolized by the liver, these patients may have higher plasma levels and lower clearance of ropinirole than patients with normal hepatic function. Titrate initial dose with caution if ropinirole immediate-release tablets are prescribed. No information is available for extended-release tablets.
Patients with Renal Impairment Dosing
CrCl 30 to 50 mL/min, or above: No dose adjustment is needed.
CrCl less than 30 mL/min: Use in patients with severe renal impairment who are not receiving regular dialysis has not been studied.
Intermittent hemodialysis
For patients with end-stage renal disease (CrCl less than 15 mL/min) receiving regular hemodialysis sessions, the recommended initial dose for Parkinson's disease for the immediate-release tablets is 0.25 mg PO three times a day. Further dose escalations should be based on tolerability and need for efficacy. A reduced maximum dose is recommended for the immediate-release tablets. Max: 18 mg/day PO. The recommended initial dose of ropinirole for Restless-Leg Syndrome patients with end-stage renal disease on hemodialysis is 0.25 mg PO once daily. Max: 3 mg/day PO in patients receiving regular dialysis. Information regarding dose adjustment for the extended-release product is not available.
*non-FDA-approved indication
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Concomitant use of ropinirole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of ropinirole.
Acetaminophen; Caffeine; Dihydrocodeine: (Major) Concomitant use of opioid agonists with ropinirole may cause excessive sedation and somnolence. Limit the use of opioid pain medication with ropinirole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Acetaminophen; Caffeine; Pyrilamine: (Moderate) Concomitant use of ropinirole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of ropinirole.
Acetaminophen; Chlorpheniramine: (Moderate) Concomitant use of ropinirole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of ropinirole.
Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) Concomitant use of ropinirole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of ropinirole.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Concomitant use of ropinirole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of ropinirole.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Concomitant use of ropinirole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of ropinirole.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Concomitant use of ropinirole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of ropinirole.
Acetaminophen; Codeine: (Major) Concomitant use of opioid agonists with ropinirole may cause excessive sedation and somnolence. Limit the use of opioid pain medication with ropinirole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Concomitant use of ropinirole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of ropinirole.
Acetaminophen; Diphenhydramine: (Moderate) Concomitant use of ropinirole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of ropinirole.
Acetaminophen; Hydrocodone: (Major) Concomitant use of opioid agonists with ropinirole may cause excessive sedation and somnolence. Limit the use of opioid pain medication with ropinirole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Acetaminophen; Oxycodone: (Major) Concomitant use of opioid agonists with ropinirole may cause excessive sedation and somnolence. Limit the use of opioid pain medication with ropinirole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Acetaminophen; Pamabrom; Pyrilamine: (Moderate) Concomitant use of ropinirole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of ropinirole.
Acrivastine; Pseudoephedrine: (Moderate) Concomitant use of ropinirole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of ropinirole.
Alfentanil: (Major) Concomitant use of opioid agonists with ropinirole may cause excessive sedation and somnolence. Limit the use of opioid pain medication with ropinirole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Alprazolam: (Moderate) Concomitant use of ropinirole with other CNS depressants, such as alprazolam, can potentiate the sedation effects of ropinirole.
Amitriptyline: (Moderate) Ropinirole may cause additive drowsiness when combined with tricyclic antidepressants.
Amobarbital: (Moderate) Coadministration of ropinirole and barbiturates may result in decreased concentrations of ropinirole. If therapy with barbiturates is initiated or discontinued during treatment with ropinirole, adjustment of ropinirole dose may be required. Ropinirole is primarily metabolized by CYP1A2; barbiturates are inducers of CYP1A2. Also, somnolence is a commonly reported adverse effect of ropinirole; coadministration of ropinirole with barbiturates may result in additive sedative effects.
Amoxapine: (Moderate) Ropinirole may cause additive drowsiness when combined with amoxapine.
Anagrelide: (Moderate) Anagrelide has been shown to inhibit CYP1A2. In theory, coadministration of anagrelide with substrates of CYP1A2, including ropinirole, could lead to increases in the serum concentrations of ropinirole and, thus, adverse effects. Patients receiving anagrelide and ropinirole concomitantly should be monitored for increased toxicity of ropinirole.
Apomorphine: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and CNS depressants, such as ropinirole, could result in additive depressant effects. Careful monitoring is recommended during combined use of a CNS depressant and apomorphine. A dose reduction of one or both drugs may be warranted.
Aripiprazole: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or ropinirole during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and ropinirole may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with ropinirole than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Asenapine: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or ropinirole during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and ropinirole may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with ropinirole than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Coadministration of ropinirole and barbiturates may result in decreased concentrations of ropinirole. If therapy with barbiturates is initiated or discontinued during treatment with ropinirole, adjustment of ropinirole dose may be required. Ropinirole is primarily metabolized by CYP1A2; barbiturates are inducers of CYP1A2. Also, somnolence is a commonly reported adverse effect of ropinirole; coadministration of ropinirole with barbiturates may result in additive sedative effects.
Aspirin, ASA; Carisoprodol; Codeine: (Major) Concomitant use of opioid agonists with ropinirole may cause excessive sedation and somnolence. Limit the use of opioid pain medication with ropinirole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Aspirin, ASA; Oxycodone: (Major) Concomitant use of opioid agonists with ropinirole may cause excessive sedation and somnolence. Limit the use of opioid pain medication with ropinirole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
atypical antipsychotic: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or ropinirole during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and ropinirole may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with ropinirole than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Azelastine: (Moderate) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including ropinirole.
Azelastine; Fluticasone: (Moderate) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including ropinirole.
Barbiturates: (Moderate) Coadministration of ropinirole and barbiturates may result in decreased concentrations of ropinirole. If therapy with barbiturates is initiated or discontinued during treatment with ropinirole, adjustment of ropinirole dose may be required. Ropinirole is primarily metabolized by CYP1A2; barbiturates are inducers of CYP1A2. Also, somnolence is a commonly reported adverse effect of ropinirole; coadministration of ropinirole with barbiturates may result in additive sedative effects.
Belladonna; Opium: (Major) Concomitant use of opioid agonists with ropinirole may cause excessive sedation and somnolence. Limit the use of opioid pain medication with ropinirole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Benzhydrocodone; Acetaminophen: (Major) Concomitant use of opioid agonists with ropinirole may cause excessive sedation and somnolence. Limit the use of opioid pain medication with ropinirole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Brexpiprazole: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or ropinirole during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and ropinirole may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with ropinirole than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Brompheniramine: (Moderate) Concomitant use of ropinirole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of ropinirole.
Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Concomitant use of ropinirole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of ropinirole.
Brompheniramine; Phenylephrine: (Moderate) Concomitant use of ropinirole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of ropinirole.
Brompheniramine; Pseudoephedrine: (Moderate) Concomitant use of ropinirole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of ropinirole.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Concomitant use of ropinirole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of ropinirole.
Buprenorphine: (Moderate) Concomitant use of buprenorphine with other CNS depressants, such as ropinirole, can lead to additive CNS depressive effects. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. A dose reduction of one or both drugs may be warranted. It is recommended that the injectable buprenorphine dose be halved for patients who receive other drugs with CNS depressant effects; for the buprenorphine transdermal patch, start with the 5 mcg/hour patch. Monitor patients for sedation or respiratory depression.
Buprenorphine; Naloxone: (Moderate) Concomitant use of buprenorphine with other CNS depressants, such as ropinirole, can lead to additive CNS depressive effects. Hypotension, profound sedation, coma, respiratory depression, or death may occur. Prior to concurrent use, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. A dose reduction of one or both drugs may be warranted. It is recommended that the injectable buprenorphine dose be halved for patients who receive other drugs with CNS depressant effects; for the buprenorphine transdermal patch, start with the 5 mcg/hour patch. Monitor patients for sedation or respiratory depression.
Buspirone: (Moderate) The combination of buspirone and other CNS depressants, such as ropinirole, can increase the risk for sedation.
Butalbital; Acetaminophen: (Moderate) Coadministration of ropinirole and barbiturates may result in decreased concentrations of ropinirole. If therapy with barbiturates is initiated or discontinued during treatment with ropinirole, adjustment of ropinirole dose may be required. Ropinirole is primarily metabolized by CYP1A2; barbiturates are inducers of CYP1A2. Also, somnolence is a commonly reported adverse effect of ropinirole; coadministration of ropinirole with barbiturates may result in additive sedative effects.
Butalbital; Acetaminophen; Caffeine: (Moderate) Coadministration of ropinirole and barbiturates may result in decreased concentrations of ropinirole. If therapy with barbiturates is initiated or discontinued during treatment with ropinirole, adjustment of ropinirole dose may be required. Ropinirole is primarily metabolized by CYP1A2; barbiturates are inducers of CYP1A2. Also, somnolence is a commonly reported adverse effect of ropinirole; coadministration of ropinirole with barbiturates may result in additive sedative effects.
Butalbital; Acetaminophen; Caffeine; Codeine: (Major) Concomitant use of opioid agonists with ropinirole may cause excessive sedation and somnolence. Limit the use of opioid pain medication with ropinirole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. (Moderate) Coadministration of ropinirole and barbiturates may result in decreased concentrations of ropinirole. If therapy with barbiturates is initiated or discontinued during treatment with ropinirole, adjustment of ropinirole dose may be required. Ropinirole is primarily metabolized by CYP1A2; barbiturates are inducers of CYP1A2. Also, somnolence is a commonly reported adverse effect of ropinirole; coadministration of ropinirole with barbiturates may result in additive sedative effects.
Butalbital; Aspirin; Caffeine; Codeine: (Major) Concomitant use of opioid agonists with ropinirole may cause excessive sedation and somnolence. Limit the use of opioid pain medication with ropinirole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. (Moderate) Coadministration of ropinirole and barbiturates may result in decreased concentrations of ropinirole. If therapy with barbiturates is initiated or discontinued during treatment with ropinirole, adjustment of ropinirole dose may be required. Ropinirole is primarily metabolized by CYP1A2; barbiturates are inducers of CYP1A2. Also, somnolence is a commonly reported adverse effect of ropinirole; coadministration of ropinirole with barbiturates may result in additive sedative effects.
Butorphanol: (Moderate) Concomitant use of butorphanol with ropinirole can potentiate the effects of butorphanol on respiratory depression, CNS depression (e.g., dizziness, impaired mental function), and sedation. Use together with caution. If a centrally acting medication needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol.
Cannabidiol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and ropinirole. CNS depressants can potentiate the effects of cannabidiol.
Carbamazepine: (Moderate) Carbamazepine induces cytochrome P450 CYP1A2 isoenzymes, which can potentially lead to decreased plasma concentrations of CYP1A2 substrates, such as ropinirole. If these drugs are coadministered, adjustment of ropinirole dose may be required. Decreased anticonvulsant efficacy is a possibility when some antipsychotic or antidepressant agents are administered to patients with a seizure disorder, because some of these drugs lower the seizure threshold. Clinical documentation of interactions is not always available. Clinicians should be alert to altered effects of any of these agents. Dosage adjustments may be necessary, and closer monitoring of clinical and/or adverse effects is warranted.
Carbinoxamine: (Moderate) Concomitant use of ropinirole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of ropinirole.
Cariprazine: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or ropinirole during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and ropinirole may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with ropinirole than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Celecoxib; Tramadol: (Major) Concomitant use of opioid agonists with ropinirole may cause excessive sedation and somnolence. Limit the use of opioid pain medication with ropinirole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Cenobamate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cenobamate and ropinirole. Concurrent use may result in additive CNS depression. Dopaminergic agents, such as ropinirole, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Cetirizine: (Moderate) Concurrent use of cetirizine/levocetirizine with ropinirole should generally be avoided because of the possibility of additive sedative effects. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Cetirizine; Pseudoephedrine: (Moderate) Concurrent use of cetirizine/levocetirizine with ropinirole should generally be avoided because of the possibility of additive sedative effects. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Chlophedianol; Dexbrompheniramine: (Moderate) Concomitant use of ropinirole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of ropinirole.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Concomitant use of ropinirole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of ropinirole.
Chlorcyclizine: (Moderate) Concomitant use of ropinirole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of ropinirole.
Chlordiazepoxide: (Moderate) Concomitant use of ropinirole with other CNS depressants can potentiate the sedation effects of ropinirole.
Chlordiazepoxide; Amitriptyline: (Moderate) Concomitant use of ropinirole with other CNS depressants can potentiate the sedation effects of ropinirole. (Moderate) Ropinirole may cause additive drowsiness when combined with tricyclic antidepressants.
Chlordiazepoxide; Clidinium: (Moderate) Concomitant use of ropinirole with other CNS depressants can potentiate the sedation effects of ropinirole.
Chlorpheniramine: (Moderate) Concomitant use of ropinirole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of ropinirole.
Chlorpheniramine; Codeine: (Major) Concomitant use of opioid agonists with ropinirole may cause excessive sedation and somnolence. Limit the use of opioid pain medication with ropinirole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. (Moderate) Concomitant use of ropinirole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of ropinirole.
Chlorpheniramine; Dextromethorphan: (Moderate) Concomitant use of ropinirole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of ropinirole.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Concomitant use of ropinirole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of ropinirole.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Concomitant use of ropinirole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of ropinirole.
Chlorpheniramine; Hydrocodone: (Major) Concomitant use of opioid agonists with ropinirole may cause excessive sedation and somnolence. Limit the use of opioid pain medication with ropinirole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. (Moderate) Concomitant use of ropinirole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of ropinirole.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Concomitant use of ropinirole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of ropinirole.
Chlorpheniramine; Phenylephrine: (Moderate) Concomitant use of ropinirole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of ropinirole.
Chlorpheniramine; Pseudoephedrine: (Moderate) Concomitant use of ropinirole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of ropinirole.
Chlorpromazine: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and ropinirole may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Cimetidine: (Moderate) Coadministration of cimetidine and ropinirole may result in increased ropinirole concentrations. Cimetidine is a weak CYP1A2 inhibitor; ropinirole is a CYP1A2 substrate.
Ciprofloxacin: (Moderate) Ropinirole is primarily metabolized by CYP1A2. Ropinirole clearance has been shown to be reduced by coadministration of inhibitors of CYP1A2, such as ciprofloxacin. Therefore, if therapy with a drug known to be a potent inhibitor or inducer of CYP1A2 is initiated or discontinued during treatment with ropinirole, adjustment of ropinirole dose may be required. Coadministration of ciprofloxacin (500 mg twice daily) with ropinirole (2 mg three times per day) significantly increases ropinirole AUC by 84% on average, and Cmax by 60%.
Clemastine: (Moderate) Concomitant use of ropinirole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of ropinirole.
Clobazam: (Moderate) Clobazam, a benzodiazepine, may cause drowsiness or other CNS effects. Potentiation of CNS effects (e.g., increased sedation) may occur when clobazam is combined with other CNS depressants such as ropinirole.
Clomipramine: (Moderate) Ropinirole may cause additive drowsiness when combined with tricyclic antidepressants.
Clorazepate: (Moderate) Concomitant use of ropinirole with other CNS depressants can potentiate the sedation effects of ropinirole.
Clozapine: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or ropinirole during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and ropinirole may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with ropinirole than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Codeine: (Major) Concomitant use of opioid agonists with ropinirole may cause excessive sedation and somnolence. Limit the use of opioid pain medication with ropinirole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Codeine; Guaifenesin: (Major) Concomitant use of opioid agonists with ropinirole may cause excessive sedation and somnolence. Limit the use of opioid pain medication with ropinirole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Codeine; Guaifenesin; Pseudoephedrine: (Major) Concomitant use of opioid agonists with ropinirole may cause excessive sedation and somnolence. Limit the use of opioid pain medication with ropinirole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Codeine; Phenylephrine; Promethazine: (Major) Concomitant use of opioid agonists with ropinirole may cause excessive sedation and somnolence. Limit the use of opioid pain medication with ropinirole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and ropinirole may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Codeine; Promethazine: (Major) Concomitant use of opioid agonists with ropinirole may cause excessive sedation and somnolence. Limit the use of opioid pain medication with ropinirole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and ropinirole may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Conjugated Estrogens: (Moderate) Concomitant use of ropinirole and higher doses of estrogens may increase the exposure of ropinirole. A dose adjustment of ropinirole may be needed when estrogen therapy is initiated or discontinued. Some estrogens have reduced ropinirole oral clearance by 36%.
Conjugated Estrogens; Bazedoxifene: (Moderate) Concomitant use of ropinirole and higher doses of estrogens may increase the exposure of ropinirole. A dose adjustment of ropinirole may be needed when estrogen therapy is initiated or discontinued. Some estrogens have reduced ropinirole oral clearance by 36%.
Conjugated Estrogens; Medroxyprogesterone: (Moderate) Concomitant use of ropinirole and higher doses of estrogens may increase the exposure of ropinirole. A dose adjustment of ropinirole may be needed when estrogen therapy is initiated or discontinued. Some estrogens have reduced ropinirole oral clearance by 36%.
Cyproheptadine: (Moderate) Concomitant use of ropinirole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of ropinirole.
Desipramine: (Moderate) Ropinirole may cause additive drowsiness when combined with tricyclic antidepressants.
Desogestrel; Ethinyl Estradiol: (Moderate) Concomitant use of ropinirole and higher doses of estrogens may increase the exposure of ropinirole. A dose adjustment of ropinirole may be needed when estrogen therapy is initiated or discontinued. Some estrogens have reduced ropinirole oral clearance by 36%.
Deutetrabenazine: (Moderate) Concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as ropinirole, may have additive effects and worsen drowsiness or sedation. Advise patients about worsened somnolence and not to drive or perform other tasks requiring mental alertness until they know how deutetrabenazine affects them.
Dexbrompheniramine: (Moderate) Concomitant use of ropinirole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of ropinirole.
Dexbrompheniramine; Pseudoephedrine: (Moderate) Concomitant use of ropinirole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of ropinirole.
Dexchlorpheniramine: (Moderate) Concomitant use of ropinirole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of ropinirole.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Concomitant use of ropinirole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of ropinirole.
Dexmethylphenidate: (Moderate) Increased dopaminergic effects may occur during coadministration of methylphenidate derivatives, inhibitors of dopamine reuptake, and dopamine agonists such as pergolide, pramipexole, apomorphine, and ropinirole. Dopaminergic side effects, such as nausea, loss of appetite, weight loss, insomnia, tremor, nervousness, or changes in mood or behavior, are possible.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Concomitant use of ropinirole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of ropinirole.
Diazepam: (Moderate) Concomitant use of ropinirole with other CNS depressants can potentiate the sedation effects of ropinirole.
Dienogest; Estradiol valerate: (Moderate) Concomitant use of ropinirole and higher doses of estrogens may increase the exposure of ropinirole. A dose adjustment of ropinirole may be needed when estrogen therapy is initiated or discontinued. Some estrogens have reduced ropinirole oral clearance by 36%.
Difelikefalin: (Moderate) Monitor for dizziness, somnolence, mental status changes, and gait disturbances if concomitant use of difelikefalin with CNS depressants is necessary. Concomitant use may increase the risk for these adverse reactions.
Dimenhydrinate: (Moderate) Concomitant use of ropinirole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of ropinirole.
Diphenhydramine: (Moderate) Concomitant use of ropinirole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of ropinirole.
Diphenhydramine; Ibuprofen: (Moderate) Concomitant use of ropinirole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of ropinirole.
Diphenhydramine; Naproxen: (Moderate) Concomitant use of ropinirole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of ropinirole.
Diphenhydramine; Phenylephrine: (Moderate) Concomitant use of ropinirole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of ropinirole.
Donepezil; Memantine: (Moderate) The pharmacologic effects of dopaminergic agents, including dopamine agonists and certain ergot derivatives may be enhanced with use of memantine; dosage adjustments of dopaminergic agents may be required when memantine is coadministered.
Doxepin: (Moderate) Ropinirole may cause additive drowsiness when combined with tricyclic antidepressants.
Doxylamine: (Moderate) Concomitant use of ropinirole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of ropinirole.
Doxylamine; Pyridoxine: (Moderate) Concomitant use of ropinirole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of ropinirole.
Droperidol: (Major) Droperidol should be avoided, if possible, in patients treated with ropinirole. Droperidol, a butyrophenone derivative, is a dopamine D2 receptor antagonist and thus, may reduce the therapeutic effects of ropinirole, which is an agonist at dopamine D2 receptors. Additive CNS depressant effects may also be seen.
Drospirenone; Estetrol: (Moderate) Concomitant use of ropinirole and higher doses of estrogens may increase the exposure of ropinirole. A dose adjustment of ropinirole may be needed when estrogen therapy is initiated or discontinued. Some estrogens have reduced ropinirole oral clearance by 36%.
Drospirenone; Estradiol: (Moderate) Concomitant use of ropinirole and higher doses of estrogens may increase the exposure of ropinirole. A dose adjustment of ropinirole may be needed when estrogen therapy is initiated or discontinued. Some estrogens have reduced ropinirole oral clearance by 36%.
Drospirenone; Ethinyl Estradiol: (Moderate) Concomitant use of ropinirole and higher doses of estrogens may increase the exposure of ropinirole. A dose adjustment of ropinirole may be needed when estrogen therapy is initiated or discontinued. Some estrogens have reduced ropinirole oral clearance by 36%.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Moderate) Concomitant use of ropinirole and higher doses of estrogens may increase the exposure of ropinirole. A dose adjustment of ropinirole may be needed when estrogen therapy is initiated or discontinued. Some estrogens have reduced ropinirole oral clearance by 36%.
Elagolix; Estradiol; Norethindrone acetate: (Moderate) Concomitant use of ropinirole and higher doses of estrogens may increase the exposure of ropinirole. A dose adjustment of ropinirole may be needed when estrogen therapy is initiated or discontinued. Some estrogens have reduced ropinirole oral clearance by 36%.
Enasidenib: (Moderate) Concomitant use of ropinirole and enasidenib may increase the exposure of ropinirole. A dose adjustment of ropinirole may be needed when therapy with enasidenib is initiated or discontinued. Ropinirole is a CYP1A2 substrate and enasidenib is a strong CYP1A2 inhibitor. Coadministration with another strong CYP1A2 inhibitor increased ropinirole exposure by 84%.
Esketamine: (Major) Because of the possibility of additive sedative effects, caution is advisable during concurrent use of dopaminergic agents, such as ropinirole, and CNS depressants, such as esketamine. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients who have received a dose of esketamine should be instructed not to drive or engage in other activities requiring complete mental alertness until the next day after a restful sleep.
Estazolam: (Moderate) Concomitant use of ropinirole with other CNS depressants can potentiate the sedation effects of ropinirole.
Esterified Estrogens: (Moderate) Concomitant use of ropinirole and higher doses of estrogens may increase the exposure of ropinirole. A dose adjustment of ropinirole may be needed when estrogen therapy is initiated or discontinued. Some estrogens have reduced ropinirole oral clearance by 36%.
Esterified Estrogens; Methyltestosterone: (Moderate) Concomitant use of ropinirole and higher doses of estrogens may increase the exposure of ropinirole. A dose adjustment of ropinirole may be needed when estrogen therapy is initiated or discontinued. Some estrogens have reduced ropinirole oral clearance by 36%.
Estradiol: (Moderate) Concomitant use of ropinirole and higher doses of estrogens may increase the exposure of ropinirole. A dose adjustment of ropinirole may be needed when estrogen therapy is initiated or discontinued. Some estrogens have reduced ropinirole oral clearance by 36%.
Estradiol; Levonorgestrel: (Moderate) Concomitant use of ropinirole and higher doses of estrogens may increase the exposure of ropinirole. A dose adjustment of ropinirole may be needed when estrogen therapy is initiated or discontinued. Some estrogens have reduced ropinirole oral clearance by 36%.
Estradiol; Norethindrone: (Moderate) Concomitant use of ropinirole and higher doses of estrogens may increase the exposure of ropinirole. A dose adjustment of ropinirole may be needed when estrogen therapy is initiated or discontinued. Some estrogens have reduced ropinirole oral clearance by 36%.
Estradiol; Norgestimate: (Moderate) Concomitant use of ropinirole and higher doses of estrogens may increase the exposure of ropinirole. A dose adjustment of ropinirole may be needed when estrogen therapy is initiated or discontinued. Some estrogens have reduced ropinirole oral clearance by 36%.
Estradiol; Progesterone: (Moderate) Concomitant use of ropinirole and higher doses of estrogens may increase the exposure of ropinirole. A dose adjustment of ropinirole may be needed when estrogen therapy is initiated or discontinued. Some estrogens have reduced ropinirole oral clearance by 36%.
Estrogens: (Moderate) Concomitant use of ropinirole and higher doses of estrogens may increase the exposure of ropinirole. A dose adjustment of ropinirole may be needed when estrogen therapy is initiated or discontinued. Some estrogens have reduced ropinirole oral clearance by 36%.
Estropipate: (Moderate) Concomitant use of ropinirole and higher doses of estrogens may increase the exposure of ropinirole. A dose adjustment of ropinirole may be needed when estrogen therapy is initiated or discontinued. Some estrogens have reduced ropinirole oral clearance by 36%.
Eszopiclone: (Moderate) Using eszopiclone with ropinirole or other CNS depressants may have cumulative effects and can increase the risk for sedation. A dose reduction may be necessary if eszopiclone is coadministered with other CNS depressants, such as ropinirole.
Ethanol: (Major) Patients should be advised that alcohol use may increase the risk of somnolence during treatment with ropinirole. In addition, the sudden onset of sleep during activities that require active participation (e.g., driving a vehicle, conversations, eating) has occurred during treatment with dopamine agonists, including ropinirole. In some cases, excessive drowsiness due to ropinirole or other dopamine agonists has resulted in auto accidents or other harmful events in the course of daily living. Advise patients to avoid alcohol and notify their healthcare provider if they experience excess sedation or sudden sleep onset while receiving ropinirole.
Ethinyl Estradiol; Norelgestromin: (Moderate) Concomitant use of ropinirole and higher doses of estrogens may increase the exposure of ropinirole. A dose adjustment of ropinirole may be needed when estrogen therapy is initiated or discontinued. Some estrogens have reduced ropinirole oral clearance by 36%.
Ethinyl Estradiol; Norethindrone Acetate: (Moderate) Concomitant use of ropinirole and higher doses of estrogens may increase the exposure of ropinirole. A dose adjustment of ropinirole may be needed when estrogen therapy is initiated or discontinued. Some estrogens have reduced ropinirole oral clearance by 36%.
Ethinyl Estradiol; Norgestrel: (Moderate) Concomitant use of ropinirole and higher doses of estrogens may increase the exposure of ropinirole. A dose adjustment of ropinirole may be needed when estrogen therapy is initiated or discontinued. Some estrogens have reduced ropinirole oral clearance by 36%.
Ethynodiol Diacetate; Ethinyl Estradiol: (Moderate) Concomitant use of ropinirole and higher doses of estrogens may increase the exposure of ropinirole. A dose adjustment of ropinirole may be needed when estrogen therapy is initiated or discontinued. Some estrogens have reduced ropinirole oral clearance by 36%.
Etonogestrel; Ethinyl Estradiol: (Moderate) Concomitant use of ropinirole and higher doses of estrogens may increase the exposure of ropinirole. A dose adjustment of ropinirole may be needed when estrogen therapy is initiated or discontinued. Some estrogens have reduced ropinirole oral clearance by 36%.
Fenfluramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of fenfluramine and ropinirole. Concurrent use may result in additive CNS depression. Dopaminergic agents, such as ropinirole, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Fentanyl: (Major) Concomitant use of opioid agonists with ropinirole may cause excessive sedation and somnolence. Limit the use of opioid pain medication with ropinirole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Fluphenazine: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and ropinirole may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Flurazepam: (Moderate) Concomitant use of ropinirole with other CNS depressants can potentiate the sedation effects of ropinirole.
Fluvoxamine: (Moderate) Ropinirole is primarily metabolized by cytochrome P450 1A2. Ropinirole concentrations may increase when coadministered with inhibitors of CYP1A2, such as fluvoxamine. If fluvoxamine is initiated or discontinued during treatment with ropinirole, adjustment of the ropinirole dose may be required.
Food: (Major) Advise patients to avoid cannabis use while taking CNS depressants due to the risk for additive CNS depression and potential for other cognitive adverse reactions.
Gabapentin: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and ropinirole. Concomitant use of gabapentin with ropinirole may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents, such as ropinirole, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Haloperidol: (Major) Due to opposing effects on central dopaminergic activity, haloperidol and ropinirole may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to haloperidol. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Homatropine; Hydrocodone: (Major) Concomitant use of opioid agonists with ropinirole may cause excessive sedation and somnolence. Limit the use of opioid pain medication with ropinirole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Hydrocodone: (Major) Concomitant use of opioid agonists with ropinirole may cause excessive sedation and somnolence. Limit the use of opioid pain medication with ropinirole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Hydrocodone; Ibuprofen: (Major) Concomitant use of opioid agonists with ropinirole may cause excessive sedation and somnolence. Limit the use of opioid pain medication with ropinirole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Hydromorphone: (Major) Concomitant use of opioid agonists with ropinirole may cause excessive sedation and somnolence. Limit the use of opioid pain medication with ropinirole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Hydroxyzine: (Moderate) Concomitant use of ropinirole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of ropinirole.
Ibuprofen; Oxycodone: (Major) Concomitant use of opioid agonists with ropinirole may cause excessive sedation and somnolence. Limit the use of opioid pain medication with ropinirole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Iloperidone: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or ropinirole during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and ropinirole may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with ropinirole than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Imipramine: (Moderate) Ropinirole may cause additive drowsiness when combined with tricyclic antidepressants.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Ropinirole is primarily metabolized by cytochrome P450 1A2. Ropinirole clearance may be altered by coadministration of substrates or inhibitors of CYP1A2. Therefore, if therapy with a drug known to be a potent inducer of CYP1A2, such as rifampin, is initiated or discontinued during treatment with ropinirole, adjustment of ropinirole dose may be required.
Isoniazid, INH; Rifampin: (Major) Ropinirole is primarily metabolized by cytochrome P450 1A2. Ropinirole clearance may be altered by coadministration of substrates or inhibitors of CYP1A2. Therefore, if therapy with a drug known to be a potent inducer of CYP1A2, such as rifampin, is initiated or discontinued during treatment with ropinirole, adjustment of ropinirole dose may be required.
Lasmiditan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and ropinirole. Concurrent use may result in additive CNS depression. Dopaminergic agents, such as ropinirole, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Lemborexant: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and ropinirole. Dosage adjustments of lemborexant and ropinirole may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Levocetirizine: (Moderate) Concurrent use of cetirizine/levocetirizine with ropinirole should generally be avoided because of the possibility of additive sedative effects. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Levonorgestrel; Ethinyl Estradiol: (Moderate) Concomitant use of ropinirole and higher doses of estrogens may increase the exposure of ropinirole. A dose adjustment of ropinirole may be needed when estrogen therapy is initiated or discontinued. Some estrogens have reduced ropinirole oral clearance by 36%.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Moderate) Concomitant use of ropinirole and higher doses of estrogens may increase the exposure of ropinirole. A dose adjustment of ropinirole may be needed when estrogen therapy is initiated or discontinued. Some estrogens have reduced ropinirole oral clearance by 36%.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Moderate) Concomitant use of ropinirole and higher doses of estrogens may increase the exposure of ropinirole. A dose adjustment of ropinirole may be needed when estrogen therapy is initiated or discontinued. Some estrogens have reduced ropinirole oral clearance by 36%.
Levorphanol: (Major) Concomitant use of opioid agonists with ropinirole may cause excessive sedation and somnolence. Limit the use of opioid pain medication with ropinirole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Lofexidine: (Major) Monitor for excessive hypotension and sedation during coadministration of lofexidine and ropinirole. Lofexidine can potentiate the effects of CNS depressants.
Lorazepam: (Moderate) Concomitant use of ropinirole with other CNS depressants can potentiate the sedation effects of ropinirole.
Loxapine: (Major) Due to opposing effects on central dopaminergic activity, loxapine and dopamine agonists may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to loxapine, if appropriate. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Lumateperone: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or ropinirole during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and ropinirole may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with ropinirole than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Lurasidone: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or ropinirole during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and ropinirole may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with ropinirole than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Maprotiline: (Moderate) Ropinirole may cause additive drowsiness when combined with maprotiline.
Meclizine: (Moderate) Concomitant use of ropinirole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of ropinirole.
Memantine: (Moderate) The pharmacologic effects of dopaminergic agents, including dopamine agonists and certain ergot derivatives may be enhanced with use of memantine; dosage adjustments of dopaminergic agents may be required when memantine is coadministered.
Meperidine: (Major) Concomitant use of opioid agonists with ropinirole may cause excessive sedation and somnolence. Limit the use of opioid pain medication with ropinirole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Meprobamate: (Moderate) Concomitant use of ropinirole with other CNS depressants can potentiate the sedation effects of ropinirole.
Methadone: (Major) Concomitant use of opioid agonists with ropinirole may cause excessive sedation and somnolence. Limit the use of opioid pain medication with ropinirole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Methohexital: (Moderate) Coadministration of ropinirole and barbiturates may result in decreased concentrations of ropinirole. If therapy with barbiturates is initiated or discontinued during treatment with ropinirole, adjustment of ropinirole dose may be required. Ropinirole is primarily metabolized by CYP1A2; barbiturates are inducers of CYP1A2. Also, somnolence is a commonly reported adverse effect of ropinirole; coadministration of ropinirole with barbiturates may result in additive sedative effects.
Methylphenidate Derivatives: (Moderate) Increased dopaminergic effects may occur during coadministration of methylphenidate derivatives, inhibitors of dopamine reuptake, and dopamine agonists such as pergolide, pramipexole, apomorphine, and ropinirole. Dopaminergic side effects, such as nausea, loss of appetite, weight loss, insomnia, tremor, nervousness, or changes in mood or behavior, are possible.
Methylphenidate: (Moderate) Increased dopaminergic effects may occur during coadministration of methylphenidate derivatives, inhibitors of dopamine reuptake, and dopamine agonists such as pergolide, pramipexole, apomorphine, and ropinirole. Dopaminergic side effects, such as nausea, loss of appetite, weight loss, insomnia, tremor, nervousness, or changes in mood or behavior, are possible.
Metoclopramide: (Moderate) Agents with dopamine antagonist properties, like metoclopramide, may decrease the effectiveness of dopamine agonists. These agents can cause abrupt and severe worsening of Parkinson's disease or restless leg syndrome (RLS) symptoms. Metoclopramide should be avoided, if possible, in patients treated with dopamine agonists for Parkinson's disease. If not avoidable, monitor for reduced efficacy of the dopamine agonist. Additive somnolence may also be possible.
Metyrapone: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as ropinirole, should be used with caution. Additive drowsiness and/or dizziness is possible.
Mexiletine: (Moderate) Ropinirole and mexiletine are both substrates and inhibitors of CYP1A2. Coadministration may result in increased serum concentrations of either agent.
Mirtazapine: (Moderate) Some medicines used for treatment of Parkinson's disease, like ropinirole, could potentially cause additive drowsiness when coadministered with mirtazapine.
Molindone: (Major) Due to opposing effects on central dopaminergic activity, molindone and dopamine agonists may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to molindone. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Morphine: (Major) Concomitant use of opioid agonists with ropinirole may cause excessive sedation and somnolence. Limit the use of opioid pain medication with ropinirole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Morphine; Naltrexone: (Major) Concomitant use of opioid agonists with ropinirole may cause excessive sedation and somnolence. Limit the use of opioid pain medication with ropinirole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Nabilone: (Moderate) Concomitant use of ropinirole with other CNS depressants like nabilone can potentiate the sedation effects of ropinirole.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Moderate) Concomitant use of ropinirole and higher doses of estrogens may increase the exposure of ropinirole. A dose adjustment of ropinirole may be needed when estrogen therapy is initiated or discontinued. Some estrogens have reduced ropinirole oral clearance by 36%.
Norethindrone; Ethinyl Estradiol: (Moderate) Concomitant use of ropinirole and higher doses of estrogens may increase the exposure of ropinirole. A dose adjustment of ropinirole may be needed when estrogen therapy is initiated or discontinued. Some estrogens have reduced ropinirole oral clearance by 36%.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Moderate) Concomitant use of ropinirole and higher doses of estrogens may increase the exposure of ropinirole. A dose adjustment of ropinirole may be needed when estrogen therapy is initiated or discontinued. Some estrogens have reduced ropinirole oral clearance by 36%.
Norgestimate; Ethinyl Estradiol: (Moderate) Concomitant use of ropinirole and higher doses of estrogens may increase the exposure of ropinirole. A dose adjustment of ropinirole may be needed when estrogen therapy is initiated or discontinued. Some estrogens have reduced ropinirole oral clearance by 36%.
Nortriptyline: (Moderate) Ropinirole may cause additive drowsiness when combined with tricyclic antidepressants.
Olanzapine: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or ropinirole during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and ropinirole may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with ropinirole than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Olanzapine; Fluoxetine: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or ropinirole during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and ropinirole may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with ropinirole than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Olanzapine; Samidorphan: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or ropinirole during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and ropinirole may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with ropinirole than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Oliceridine: (Major) Concomitant use of opioid agonists with ropinirole may cause excessive sedation and somnolence. Limit the use of opioid pain medication with ropinirole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Opiate Agonists: (Major) Concomitant use of opioid agonists with ropinirole may cause excessive sedation and somnolence. Limit the use of opioid pain medication with ropinirole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Oxazepam: (Moderate) Concomitant use of ropinirole with other CNS depressants can potentiate the sedation effects of ropinirole.
Oxycodone: (Major) Concomitant use of opioid agonists with ropinirole may cause excessive sedation and somnolence. Limit the use of opioid pain medication with ropinirole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Oxymorphone: (Major) Concomitant use of opioid agonists with ropinirole may cause excessive sedation and somnolence. Limit the use of opioid pain medication with ropinirole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Paliperidone: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or ropinirole during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and ropinirole may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with ropinirole than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Peginterferon Alfa-2b: (Moderate) If peginterferon alfa-2b and ropinirole are coadministered, a downward adjustment of ropinirole dose may be required. Peginterferon alfa-2b is a CYP1A2 inhibitor, while ropinirole is a CYP1A2 substrate. Drug interaction studies have shown that coadministration of a potent inhibitor of CYP1A2 increases the ropinirole AUC (exposure) by an average of 84% and maximal concentration (Cmax) by an average of 60%. Monitor for excessive side effects of ropinirole, such as sedation, difficulty staying alert, nausea, vomiting, dizziness or feeling faint, hallucinations, or problems with impulse control. Consider a decrease in ropinirole drug dosage if such side effects occur.
Pentobarbital: (Moderate) Coadministration of ropinirole and barbiturates may result in decreased concentrations of ropinirole. If therapy with barbiturates is initiated or discontinued during treatment with ropinirole, adjustment of ropinirole dose may be required. Ropinirole is primarily metabolized by CYP1A2; barbiturates are inducers of CYP1A2. Also, somnolence is a commonly reported adverse effect of ropinirole; coadministration of ropinirole with barbiturates may result in additive sedative effects.
Perampanel: (Moderate) Co-administration of perampanel with CNS depressants, including ethanol, may increase CNS depression. The combination of perampanel (particularly at high doses) with ethanol has led to decreased mental alertness and ability to perform complex tasks (such as driving), as well as increased levels of anger, confusion, and depression; similar reactions should be expected with concomitant use of other CNS depressants, such as ropinirole.
Perphenazine: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and ropinirole may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Perphenazine; Amitriptyline: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and ropinirole may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors. (Moderate) Ropinirole may cause additive drowsiness when combined with tricyclic antidepressants.
Phenobarbital: (Moderate) Coadministration of ropinirole and barbiturates may result in decreased concentrations of ropinirole. If therapy with barbiturates is initiated or discontinued during treatment with ropinirole, adjustment of ropinirole dose may be required. Ropinirole is primarily metabolized by CYP1A2; barbiturates are inducers of CYP1A2. Also, somnolence is a commonly reported adverse effect of ropinirole; coadministration of ropinirole with barbiturates may result in additive sedative effects.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Coadministration of ropinirole and barbiturates may result in decreased concentrations of ropinirole. If therapy with barbiturates is initiated or discontinued during treatment with ropinirole, adjustment of ropinirole dose may be required. Ropinirole is primarily metabolized by CYP1A2; barbiturates are inducers of CYP1A2. Also, somnolence is a commonly reported adverse effect of ropinirole; coadministration of ropinirole with barbiturates may result in additive sedative effects.
Phenothiazines: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and ropinirole may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Pimozide: (Major) Due to opposing effects on central dopaminergic activity, pimozide and ropinirole may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to pimozide. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Pregabalin: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and ropinirole. Concomitant use of pregabalin with ropinirole may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents, such as ropinirole, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Primidone: (Moderate) Coadministration of ropinirole and barbiturates may result in decreased concentrations of ropinirole. If therapy with barbiturates is initiated or discontinued during treatment with ropinirole, adjustment of ropinirole dose may be required. Ropinirole is primarily metabolized by CYP1A2; barbiturates are inducers of CYP1A2. Also, somnolence is a commonly reported adverse effect of ropinirole; coadministration of ropinirole with barbiturates may result in additive sedative effects.
Prochlorperazine: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and ropinirole may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Promethazine: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and ropinirole may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Promethazine; Dextromethorphan: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and ropinirole may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Promethazine; Phenylephrine: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and ropinirole may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Protriptyline: (Moderate) Ropinirole may cause additive drowsiness when combined with tricyclic antidepressants.
Pseudoephedrine; Triprolidine: (Moderate) Concomitant use of ropinirole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of ropinirole.
Quazepam: (Major) Concomitant administration of quazepam with CNS-depressant drugs, such as ropinirole, can potentiate the CNS effects, including increased sedation or respiratory depression, of either agent.
Quetiapine: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or ropinirole during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and ropinirole may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with ropinirole than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Relugolix; Estradiol; Norethindrone acetate: (Moderate) Concomitant use of ropinirole and higher doses of estrogens may increase the exposure of ropinirole. A dose adjustment of ropinirole may be needed when estrogen therapy is initiated or discontinued. Some estrogens have reduced ropinirole oral clearance by 36%.
Remifentanil: (Major) Concomitant use of opioid agonists with ropinirole may cause excessive sedation and somnolence. Limit the use of opioid pain medication with ropinirole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Rifampin: (Major) Ropinirole is primarily metabolized by cytochrome P450 1A2. Ropinirole clearance may be altered by coadministration of substrates or inhibitors of CYP1A2. Therefore, if therapy with a drug known to be a potent inducer of CYP1A2, such as rifampin, is initiated or discontinued during treatment with ropinirole, adjustment of ropinirole dose may be required.
Risperidone: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or ropinirole during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and ropinirole may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with ropinirole than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Secobarbital: (Moderate) Coadministration of ropinirole and barbiturates may result in decreased concentrations of ropinirole. If therapy with barbiturates is initiated or discontinued during treatment with ropinirole, adjustment of ropinirole dose may be required. Ropinirole is primarily metabolized by CYP1A2; barbiturates are inducers of CYP1A2. Also, somnolence is a commonly reported adverse effect of ropinirole; coadministration of ropinirole with barbiturates may result in additive sedative effects.
Sedating H1-blockers: (Moderate) Concomitant use of ropinirole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of ropinirole.
Segesterone Acetate; Ethinyl Estradiol: (Moderate) Concomitant use of ropinirole and higher doses of estrogens may increase the exposure of ropinirole. A dose adjustment of ropinirole may be needed when estrogen therapy is initiated or discontinued. Some estrogens have reduced ropinirole oral clearance by 36%.
Serdexmethylphenidate; Dexmethylphenidate: (Moderate) Increased dopaminergic effects may occur during coadministration of methylphenidate derivatives, inhibitors of dopamine reuptake, and dopamine agonists such as pergolide, pramipexole, apomorphine, and ropinirole. Dopaminergic side effects, such as nausea, loss of appetite, weight loss, insomnia, tremor, nervousness, or changes in mood or behavior, are possible.
Solriamfetol: (Moderate) Monitor for dopamine-mediated effects including nausea, vomiting, dizziness, tremor, and changes in moods or behaviors if solriamfetol, a central dopamine and norepinephrine reuptake inhibitor, is administered with other dopaminergic drugs, such as ropinirole. Caution is recommended since this combination has not been evaluated.
Stiripentol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and ropinirole. CNS depressants can potentiate the effects of stiripentol.
Sufentanil: (Major) Concomitant use of opioid agonists with ropinirole may cause excessive sedation and somnolence. Limit the use of opioid pain medication with ropinirole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Suvorexant: (Moderate) CNS depressant drugs may have cumulative effects when administered concurrently and they should be used cautiously with suvorexant. A reduction in dose of the CNS depressant may be needed in some cases.
Tapentadol: (Major) Concomitant use of opioid agonists with ropinirole may cause excessive sedation and somnolence. Limit the use of opioid pain medication with ropinirole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Teriflunomide: (Moderate) Teriflunomide is a weak inducer of CYP1A2, which may lead to decreased plasma concentrations of ropinirole, a CYP1A2 substrate. If these drugs are coadministered, adjustment of ropinirole dosage may be required.
Thalidomide: (Major) Avoid the concomitant use of thalidomide with other central nervous system depressants such as ropinirole due to the potential for additive sedative effects.
Thioridazine: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and ropinirole may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Thiothixene: (Major) Due to opposing effects on central dopaminergic activity, thiothixene and dopamine agonists may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic instead of thiothixene, if appropriate. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Tobacco: (Major) Advise patients to avoid smoking tobacco while taking ropinirole. Tobacco smoking may increase the clearance of ropinirole via CYP1A2 induction, leading to reduced efficacy of ropinirole. In one study in patients with restless leg syndrome (RLS), cigarette smokers had an approximately 38% lower ropinirole AUC than did nonsmokers when normalized for dose.
Tramadol: (Major) Concomitant use of opioid agonists with ropinirole may cause excessive sedation and somnolence. Limit the use of opioid pain medication with ropinirole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Tramadol; Acetaminophen: (Major) Concomitant use of opioid agonists with ropinirole may cause excessive sedation and somnolence. Limit the use of opioid pain medication with ropinirole to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Triazolam: (Moderate) Concomitant use of ropinirole with other CNS depressants can potentiate the sedation effects of ropinirole.
Tricyclic antidepressants: (Moderate) Ropinirole may cause additive drowsiness when combined with tricyclic antidepressants.
Trifluoperazine: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and ropinirole may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Trimipramine: (Moderate) Ropinirole may cause additive drowsiness when combined with tricyclic antidepressants.
Triprolidine: (Moderate) Concomitant use of ropinirole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of ropinirole.
Vemurafenib: (Moderate) Vemurafenib inhibits CYP1A2, which can potentially lead to increased plasma concentrations of ropinirole, a CYP1A2 substrate. If these drugs are coadministered, adjustment of ropinirole dose may be required.
Viloxazine: (Moderate) A dose adjustment of ropinirole may be needed when therapy with viloxazine is initiated or discontinued. Concomitant use of ropinirole and viloxazine may increase the exposure of ropinirole. Ropinirole is a CYP1A2 substrate and viloxazine is a strong CYP1A2 inhibitor. Coadministration with another strong CYP1A2 inhibitor increased ropinirole exposure by 84%.
Warfarin: (Moderate) A possible drug interaction between ropinirole and warfarin has been reported clinically, with a resultant increase in the INR. While no signs of bleeding occurred in the reported case, the increase in INR necessitated a warfarin dosage adjustment during concurrent treatment. After ropinirole was discontinued, the warfarin dosage had to be adjusted upward. Closely monitor the INR when starting or stopping ropinirole therapy in a patient stabilized on warfarin.
Zaleplon: (Moderate) Concomitant use of ropinirole with other CNS depressants, such as zaleplon, can potentiate the sedation effects of ropinirole.
Ziconotide: (Moderate) Ropinirole is a CNS depressant medication that may increase drowsiness, dizziness, and confusion that are associated with ziconotide.
Zileuton: (Major) Zileuton inhibits cytochrome P450 CYP1A2 isoenzymes, which can potentially lead to increased plasma concentrations of CYP1A2 substrates, such as ropinirole. If these drugs are coadministered, adjustment of ropinirole dose may be required.
Ziprasidone: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or ropinirole during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and ropinirole may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with ropinirole than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Zolpidem: (Moderate) Concomitant use of ropinirole with other CNS depressants, such as zolpidem, can potentiate the sedation effects of ropinirole. If used together, a reduction in the dose of one or both drugs may be needed. For Intermezzo brand of sublingual zolpidem tablets, reduce the dose to 1.75 mg/night.
Zuranolone: (Major) Avoid the use of multiple sedating agents due to the risk for additive CNS depression. If use is necessary, consider a downward dosage adjustment of either or both medications, especially in patients with additional risk factors for sedation-related harm.
Ropinirole is an agonist at both dopamine D2-receptors and D3-receptors, with greater affinity for D3 than D2. While the exact mechanism of action of ropinirole in the treatment of Parkinson's disease is unknown, it is believed to be due to stimulation of the D2-receptors in the caudate-putamen in the brain. Ropinirole is also an agonist at peripheral dopamine D2-receptors, leading to a blunted noradrenergic response to standing and subsequent orthostatic hypotension.The precise mechanism of action of ropinirole as a treatment for restless legs syndrome (RLS) is unknown; however, neuropharmacological evidence suggests primary dopaminergic system involvement. Positron emission tomographic (PET) studies suggest that a mild striatal presynaptic dopaminergic dysfunction may be involved in the pathogenesis of RLS.
Ropinirole is administered orally as an immediate-release or extended-release tablet. Pharmacokinetics are similar for patients with Parkinson's disease or restless legs syndrome, and increases in systemic exposure appear to be dose-proportional. Ropinirole is widely distributed throughout the body and protein binding is approximately 40%. The major metabolic pathways are N-despropylation and hydroxylation to form the inactive N-despropyl metabolite and hydroxy metabolites. The N-despropyl metabolite is converted to carbamyl glucuronide, carboxylic acid, and N-despropyl hydroxy metabolites. The hydroxy metabolite of ropinirole is rapidly glucuronidated. In vitro studies indicate that CYP1A2 is the major isoenzyme involved in the metabolism of ropinirole. Less than 10% of the administered drug is excreted unchanged in the urine; N-despropyl ropinirole is the predominant metabolite found in urine (40%), followed by a carboxylic acid metabolite (10%), and a glucuronide of the hydroxy metabolite (10%). The elimination half-life of ropinirole is roughly 6 hours.
Affected cytochrome P450 isoenzymes and drug transporters: CYP1A2
Since ropinirole is primarily metabolized by CYP1A2, there is the potential for inducers or inhibitors of CYP1A2 to alter the clearance of ropinirole. Therefore, if a potent inducer or inhibitor of CYP1A2 is stopped or started during treatment with ropinirole, dosage adjustment of ropinirole may be required.
-Route-Specific Pharmacokinetics
Oral Route
Following oral administration, immediate-release ropinirole is rapidly absorbed with peak plasma concentrations occurring in approximately 1 to 2 hours. The median time-to-peak of extended-release ropinirole is 6 to 10 hours. Oral bioavailability is 55%. Food does not affect the extent of absorption, however, Tmax of the immediate-release and extended-release formulations is increased by 2.5 hours and 3 hours, respectively, when taken with a high-fat meal. Cmax is decreased by approximately 25% for immediate-release tablets when taken with a high fat meal. In contrast, Cmax increased by approximately 44% and AUC increased by 20% when the extended-release formulation was given with a high fat meal. The manufacturer states that ropinirole may be taken with or without food, and that taking the extended-release formulation with food may reduce the incidence of nausea. Steady-state concentrations of immediate-release and extended-release ropinirole are expected to be achieved within 2 days and 4 days of dosing, respectively.
-Special Populations
Hepatic Impairment
The pharmacokinetics of ropinirole have not been studied in patients with hepatic impairment. Because ropinirole is extensively metabolized by the liver, these patients may have higher plasma levels and lower clearance of ropinirole than patients with normal hepatic function.
Renal Impairment
Based on population pharmacokinetic analysis, no difference was observed in the pharmacokinetics of ropinirole in subjects with moderate renal impairment (CrCl of 30 to 50 mL/minute) compared with an age-matched population with creatinine clearance greater than 50 mL/minute. Therefore, no dosage adjustment is necessary in patients with moderate renal impairment. A trial of immediate-release ropinirole in subjects with end-stage renal disease on hemodialysis has shown that clearance of ropinirole was reduced by approximately 30%; the recommended maximum dose should be reduced in these patients. The use of ropinirole in subjects with severe renal impairment (CrCl less than 30 mL/minute) who are not receiving regular dialysis has not been studied.
Geriatric
In patients more than 65 years of age, the oral clearance of ropinirole is reduced by 15% compared with younger patients. Dosage adjustment is not necessary in this population, as the dose of ropinirole is to be individually titrated to clinical response.
Gender Differences
The clearance of ropinirole was similar in both males and females.
Other
Smoking
Cigarette smoking is expected to increase the clearance of ropinirole since the CYP1A2 isozyme is known to be induced by smoking. In a trial in patients with restless leg syndrome (RLS), smokers (n = 7) had an approximately 30% lower Cmax and a 38% lower AUC than did nonsmokers (n = 11) when those parameters were normalized for dose.