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  • CLASSES

    Anti-Parkinson Agents, Dopamine Agonists

    DEA CLASS

    Rx

    DESCRIPTION

    Oral non-ergot-derived dopamine agonist
    Used for Parkinson's disease and moderate to severe restless legs syndrome (RLS) in adults
    Monitor for hallucinations, psychotic-like behavior, impulse control symptoms, and sleep attacks

    COMMON BRAND NAMES

    Requip, Requip XL

    HOW SUPPLIED

    Requip XL/Ropinirole/Ropinirole Hydrochloride Oral Tab ER: 2mg, 4mg, 6mg, 8mg, 12mg
    Requip/Ropinirole/Ropinirole Hydrochloride Oral Tab: 0.25mg, 0.5mg, 1mg, 2mg, 3mg, 4mg, 5mg

    DOSAGE & INDICATIONS

    For the treatment of Parkinson's disease.
    For conversion from immediate-release to extended-release tablets.
    Oral dosage (extended-release tablets)
    Adults

    The initial dose of extended-release tablets should most closely match the current total daily dose of immediate-release tablets. Adjust to response and tolerability. Suggested initial doses are available. Adults currently on 0.75 mg to 2.25 mg/day: Give 2 mg/day PO. Adults currently on 3 to 4.5 mg/day: Give 4 mg/day PO. If taking 6 mg/day PO currently: Give 6 mg/day PO. Adults currently taking 7.5 to 9 mg/day: Give 8 mg/day PO. If taking 12 mg/day PO currently: Give 12 mg/day PO. Adults currently on 15 to 18 mg/day: Give 16 mg/day PO. Adults currently on 21 mg/day: Give 20 mg/day PO. If taking 24 mg/day PO currently: Give 24 mg/day PO.

    Oral dosage (immediate-release tablets)
    Adults

    Initially, 0.25 mg PO 3 times per day for the first week. Gradually titrate at weekly intervals. Week 2: 0.5 mg PO 3 times per day. Week 3: titrate to 0.75 mg PO 3 times per day, and week 4: titrate to 1 mg PO 3 times per day. After week 4, may increase by 1.5 mg/day on a weekly basis up to 9 mg/day total dosage, and then by 3 mg/day at weekly intervals. Max: 24 mg/day (i.e., 8 mg PO 3 times per day). When given as adjunct therapy to levodopa, the concurrent levodopa dose may need to be gradually decreased as tolerated. DISCONTINUATION: Taper gradually over a 7-day period. The frequency of administration should be reduced from 3 times per day to twice daily for 4 days. For the remaining 3 days, the frequency should be reduced to once daily prior to complete withdrawal of the drug.

    Oral dosage (extended-release tablets)
    Adults

    Initially, 2 mg PO once daily for 1 to 2 weeks. Subsequent increases may be made in increments of 2 mg/day at intervals of at least 1 week based upon response and tolerability. Max: 24 mg/day PO. If significant interruption of therapy occurs, retitration may be necessary. When given as adjunct therapy to levodopa, the concurrent levodopa dose may need to be gradually decreased as tolerated. In a clinical trial of ropinirole ER as adjunct therapy to levodopa in patients with advanced Parkinson's disease, the levodopa dose was reduced after 8 mg/day of ropinirole ER was reached. DISCONTINUATION: Taper over a 7-day period.

    For the treatment of restless legs syndrome (RLS).
    Oral dosage (immediate-release tablets; i.e., Requip)
    Adults

    Initially, 0.25 mg PO once daily given 1 to 3 hours before bedtime. During days 3 through 7, the dosage may be increased to 0.5 mg PO once daily. At the beginning of week 2 (day 8) the dose may be increased to 1 mg PO once daily for 7 days. In weeks 3 through 6, the dose may be titrated up by 0.5 mg PO weekly (from 1.5 mg to 3 mg PO over the 5 week period), as needed to achieve desired effect. In week 7, may increase dose to 4 mg PO once daily given 1 to 3 hours before bedtime. Titrate based on clinical response and tolerability. All doses are given 1 to 3 hours before bedtime. In clinical trials, 4 mg/day was the maximum dose evaluated. DISCONTINUATION: When discontinuing ropinirole, the manufacturer recommends a gradual reduction of the daily dose whenever possible.

    MAXIMUM DOSAGE

    Adults

    24 mg/day PO.

    Elderly

    24 mg/day PO.

    Adolescents

    Safety and efficacy have not been established.

    Children

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    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.

    Renal Impairment

    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.

    ADMINISTRATION

    Oral Administration

    Ropinirole may be administered without regard to meals; however, administration with food may decrease the likelihood of nausea.

    Oral Solid Formulations

    Extended-release tablets: Swallow whole; do not chew, crush or divide the ropinirole tablets.

    STORAGE

    Requip:
    - Protect from moisture
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Requip XL:
    - Store at 77 degrees F; excursions permitted to 59-86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    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.

    Cardiac disease, orthostatic hypotension, syncope

    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.

    Coadministration with other CNS depressants, driving or operating machinery, ethanol ingestion, narcolepsy, sleep apnea, sudden sleep onset

    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.

    Impulse control symptoms

    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.

    Behavioral changes, psychosis, schizophrenia

    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.

    Dyskinesia

    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.

    Dialysis, renal failure, renal impairment

    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.

    Hepatic disease

    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.

    Abrupt discontinuation

    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.

    Geriatric

    The relative risk of hallucinations during ropinirole administration is increased in geriatric patients with Parkinson's disease compared to younger adults. Despite some pharmacokinetic differences compared to younger adults, dosage adjustment is not necessary in the older adults (older than 65 years), as the dose of ropinirole is to be individually titrated to clinical response. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs). According to OBRA, antiparkinson medications may cause significant confusion, restlessness, delirium, dyskinesia, nausea, dizziness, hallucinations, and agitation. In addition, there is an increased risk of postural hypotension and falls, particularly during concurrent use of antihypertensive medications.

    Pregnancy

    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.

    Breast-feeding

    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 or metabolites, or both, are present in rat milk. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition.

    Children, infants

    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

    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.

    ADVERSE REACTIONS

    Severe

    visual impairment / Early / 6.0-6.0
    atrial fibrillation / Early / 2.0-2.0
    angioedema / Rapid / Incidence not known
    bradycardia / Rapid / Incidence not known
    neuroleptic malignant syndrome-like symptoms / Delayed / Incidence not known

    Moderate

    orthostatic hypotension / Delayed / 5.0-38.0
    dyskinesia / Delayed / 4.0-34.0
    hypertension / Early / 1.0-15.0
    sudden sleep onset / Delayed / 0-10.0
    hallucinations / Early / 5.0-10.0
    confusion / Early / 5.0-9.0
    peripheral edema / Delayed / 2.0-7.0
    edema / Delayed / 6.0-6.0
    constipation / Delayed / 4.0-6.0
    amnesia / Delayed / 3.0-5.0
    chest pain (unspecified) / Early / 4.0-4.0
    hyperesthesia / Delayed / 4.0-4.0
    palpitations / Early / 3.0-3.0
    paresis / Delayed / 3.0-3.0
    impotence (erectile dysfunction) / Delayed / 3.0-3.0
    dyspnea / Early / 3.0-3.0
    sinus tachycardia / Rapid / 2.0-2.0
    hypotension / Rapid / 2.0-2.0
    dysphagia / Delayed / 2.0-2.0
    urinary incontinence / Early / 2.0-2.0
    pyuria / Delayed / 2.0-2.0
    anemia / Delayed / 0-2.0
    impulse control symptoms / Delayed / Incidence not known
    restless legs syndrome (RLS) rebound / Delayed / Incidence not known
    restless legs syndrome (RLS) augmentation / Delayed / Incidence not known
    withdrawal / Early / Incidence not known

    Mild

    nausea / Early / 8.0-60.0
    dizziness / Early / 0-40.0
    drowsiness / Early / 0-40.0
    headache / Early / 5.0-17.0
    asthenia / Delayed / 9.0-16.0
    back pain / Delayed / 0-15.0
    syncope / Early / 1.0-12.0
    vomiting / Early / 0-12.0
    dyspepsia / Early / 4.0-10.0
    abdominal pain / Early / 3.0-9.0
    pharyngitis / Delayed / 0-9.0
    arthralgia / Delayed / 0-8.0
    hyperhidrosis / Delayed / 3.0-7.0
    tremor / Early / 6.0-6.0
    anxiety / Delayed / 2.0-6.0
    paresthesias / Delayed / 3.0-5.0
    insomnia / Early / 0-5.0
    xerostomia / Early / 2.0-5.0
    diarrhea / Early / 3.0-5.0
    vertigo / Early / 2.0-4.0
    anorexia / Delayed / 4.0-4.0
    rhinitis / Early / 4.0-4.0
    sinusitis / Delayed / 4.0-4.0
    flushing / Rapid / 0-3.0
    yawning / Early / 3.0-3.0
    abnormal dreams / Early / 3.0-3.0
    flatulence / Early / 2.0-3.0
    muscle cramps / Delayed / 3.0-3.0
    influenza / Delayed / 3.0-3.0
    cough / Delayed / 3.0-3.0
    hyperkinesis / Delayed / 2.0-2.0
    hypersalivation / Early / 2.0-2.0
    weight loss / Delayed / 2.0-2.0
    nasal congestion / Early / 2.0-2.0
    diplopia / Early / 2.0-2.0
    xerophthalmia / Early / 2.0-2.0
    urticaria / Rapid / Incidence not known
    pruritus / Rapid / Incidence not known
    rash / Early / Incidence not known
    lethargy / Early / Incidence not known

    DRUG INTERACTIONS

    Albendazole: (Moderate) Albendazole induces CYP1A and may induce the metabolism of ropinirole. Patients receiving this combination should be closely monitored when albendazole is prescribed, as albendazole may increase the clearance of ropinirole. Conversely, the discontinuation of albendazole therapy may result in a reduced clearance of ropinirole, leading to an increase in serum concentrations. The patient's clinical status should be monitored carefully when albendazole is prescribed and on discontinuation of albendazole therapy.
    Alprazolam: (Moderate) Concomitant use of ropinirole with other CNS depressants, such as alprazolam, can potentiate the sedation effects of ropinirole.
    Amiodarone: (Moderate) Amiodarone inhibits cytochrome P450 CYP1A2 isoenzymes, which can potentially lead to increased plasma concentrations of CYP1A2 substrates like ropinirole.
    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; Butalbital; Caffeine; Codeine: (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.
    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 Alkaloids; Ergotamine; 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.
    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; Carbetapentane; Phenylephrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane with other CNS depressants including atypical antipsychotics.
    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.
    Butabarbital: (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: (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: (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.
    Carbetapentane; Chlorpheniramine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane with other CNS depressants including atypical antipsychotics.
    Carbetapentane; Chlorpheniramine; Phenylephrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane with other CNS depressants including atypical antipsychotics.
    Carbetapentane; Diphenhydramine; Phenylephrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane with other CNS depressants including atypical antipsychotics.
    Carbetapentane; Guaifenesin: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane with other CNS depressants including atypical antipsychotics.
    Carbetapentane; Guaifenesin; Phenylephrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane with other CNS depressants including atypical antipsychotics.
    Carbetapentane; Phenylephrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane with other CNS depressants including atypical antipsychotics.
    Carbetapentane; Phenylephrine; Pyrilamine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane with other CNS depressants including atypical antipsychotics.
    Carbetapentane; Pseudoephedrine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane with other CNS depressants including atypical antipsychotics.
    Carbetapentane; Pyrilamine: (Moderate) Drowsiness has been reported during administration of carbetapentane. An enhanced CNS depressant effect may occur when carbetapentane with other CNS depressants including atypical antipsychotics.
    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.
    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.
    Chloral Hydrate: (Major) The central nervous system-depressant effects of chloral hydrate can be potentiated by CNS depressants including ropinirole. Use caution to avoid overdosage if chloral hydrate is used concomitantly with other depressant drugs. CNS depressants are additive in effect, and the dosage should be reduced when such combinations are used concurrently.
    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.
    Chlordiazepoxide; Clidinium: (Moderate) Concomitant use of ropinirole with other CNS depressants 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%.
    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.
    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; Phenylephrine; 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.
    Codeine; 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.
    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%.
    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.
    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%.
    Diethylstilbestrol, DES: (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%.
    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.
    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%.
    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 Cypionate; 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%.
    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: (Moderate) 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 notify their healthcare provider if they experience excess sedation or sudden sleep onset while receiving Ropinirole.
    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%.
    Ethinyl Estradiol; Levonorgestrel; Folic Acid; 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%.
    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.
    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.
    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.
    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.
    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%.
    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.
    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; 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.
    Mephobarbital: (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.
    Meprobamate: (Moderate) Concomitant use of ropinirole with other CNS depressants can potentiate the sedation effects of ropinirole.
    Mesoridazine: (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.
    Mestranol; 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%.
    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.
    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.
    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%.
    Norfloxacin: (Moderate) Ropinirole is primarily metabolized by CYP1A2. Ropinirole clearance may be altered by coadministration of norfloxacin, an inhibitor of CYP1A2.
    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%.
    Obeticholic Acid: (Moderate) Obeticholic acid may increase the exposure to concomitant drugs that are CYP1A2 substrates, such as ropinirole. If these drugs are coadministered, adjustment of ropinirole dose may be required. Therapeutic monitoring is recommended with coadministration.
    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.
    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.
    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.
    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.
    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%.
    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.
    Rucaparib: (Moderate) Monitor for an increase in ropinirole-related adverse reactions if coadministration with rucaparib is necessary. Ropinirole is a CYP1A2 substrate and rucaparib is a moderate CYP1A2 inhibitor. Coadministration with another moderate CYP1A2 inhibitor increased ropinirole exposure by 84%.
    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%.
    Simeprevir: (Moderate) Simeprevir mildly inhibits CYP1A2, which can potentially lead to increased plasma concentrations of ropinirole. If these drugs are coadministered, adjustment of ropinirole dose may be required.
    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.
    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.
    Tacrine: (Moderate) Tacrine is a substrate and inhibitor of CYP1A2, the primary isoenzyme responsible for the metabolism of ropinirole. Therefore, addition of tacrine to a stable ropinirole regimen may lead to ropinirole-related adverse effects. Close monitoring for adverse effects is recommended during concomitant therapy.
    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.
    Thiabendazole: (Moderate) Thiabendazole is a potent CYP1A2 inhibitor. Ropinirole is primarily metabolized by CYP1A2. Ropinirole clearance has been shown to be reduced by coadministration with other CYP1A2 inhibitors. Therefore, if coadministration is necessary, monitor patient and adjust ropinirole dose as needed.
    Thiethylperazine: (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.
    Thiopental: (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.
    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: (Minor) Tobacco smokers might eliminate ropinirole more quickly than nonsmokers; the significance of this interaction has not been assessed. Sudden cessation of tobacco smoking may result in a reduced clearance of ropinirole, despite the initiation of a nicotine replacement product. Patients taking ropinirole should be monitored carefully when changes in smoking status occur.
    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.
    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.

    PREGNANCY AND LACTATION

    Pregnancy

    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.

    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 or metabolites, or both, are present in rat milk. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition.

    MECHANISM OF ACTION

    Mechanism of Action: Ropinirole is an agonist at both dopamine D2-receptors and D3-receptors (D3 > D2). Although affinity of ropinirole is higher at D3-receptors than at D2-receptors, the relevance of binding at D3-receptors in Parkinson's disease is unknown. It is believed, however, that the efficacy of ropinirole is due to stimulation of post-synaptic D2-receptors within the caudate-putamen in the brain. Ropinirole is also an agonist at peripheral dopamine D2-receptors; domperidone (an antagonist at D2-receptors) prevents the orthostatic response to ropinirole.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.

    PHARMACOKINETICS

    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. Ropinirole is widely distributed throughout the body and protein binding is approximately 40%. It is metabolized via N-despropylation and hydroxylation to form inactive metabolites. 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 hrs.
     
    Affected cytochrome P450 isoenzymes and drug transporters:  CYP1A2
    Ropinirole is primarily metabolized by CYP1A2.

    Oral Route

    Following oral administration, immediate-release ropinirole is rapidly absorbed with peak plasma concentrations occurring in approximately 1—2 hours. The median time-to-peak of extended-release ropinirole is 6—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. The effects of administration with food do not appear clinically significant; therefore, both formulations may be taken without regard to meals. Steady state concentrations of immediate-release and extended-release ropinirole are expected to be achieved within 2 days and 4 days of dosing, respectively.