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  • CLASSES

    Anti-Parkinson drugs, 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 light
    - Protect from moisture
    - Store at controlled room temperature (between 68 and 77 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.
     
    Ropinirole should be used with caution in patients with pre-existing dyskinesia. Ropinirole may potentiate the dopaminergic adverse effects of L-dopa and may cause and/or exacerbate pre-existing dyskinesia. Decreasing the dose of L-dopa may ameliorate this adverse effect.
     
    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 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 post-marketing trial. If augmentation or early-morning rebound occurs, the use of ropinirole should be reviewed and consider dosage adjustment or discontinuation of treatment.

    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. However, inhibition of lactation is expected because ropinirole inhibits secretion of prolactin in humans. Studies in rats have shown that ropinirole and/or its metabolites are excreted in breast milk. According to the manufacturer, the developmental and health benefits of breast-feeding should be discussed with the mother along with the clinical need for ropinirole and any potential adverse effects on the breast-fed infant or from the underlying maternal condition. If treatment with ropinirole cannot be avoided during breast-feeding, the infant should be monitored for commonly encountered adverse effects of ropinirole therapy including loss of appetite, dyspepsia, sedation, and nausea. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    Children

    The safety and effectiveness of ropinirole in children have not been established.

    Cardiac disease, hypertension, hypotension, orthostatic hypotension, syncope

    The potential for cardiovascular-related adverse effects, including hypertension, hypotension, syncope and changes in heart rate, should be considered during ropinirole therapy. Patients receiving ropinirole should be monitored for signs and symptoms of orthostatic hypotension, particularly during dosage increases, and should be advised of the risk for syncope and hypotension. Dopamine agonists, including ropinirole, may impair the systemic regulation of blood pressure resulting in orthostatic hypotension, especially during dose escalation. In addition, Parkinson's disease patients may have an impaired capacity to respond normally to a fall in blood pressure after standing from lying down or from a seated position. Some cases of orthostatic hypotension have occurred more than 4 weeks after initiation of therapy. Orthostasis has also been observed in patients using ropinirole for restless legs syndrome (RLS). Careful titration may minimize the potential for this adverse effect. Ropinirole has been associated with syncope, sometimes with bradycardia, in both early Parkinson's disease (without L-dopa) patients and advanced Parkinson's disease (with L-dopa) patients. During clinical trials with extended-release ropinirole, severe systolic blood pressure increases (up to 40 mm Hg) and moderate pulse increases or decreases (up to 15 beats/minute) occurred in some patients. It should be noted that patients with significant cardiovascular disease were excluded from study participation. Therefore, caution is advised in those with severe cardiac disease until the safety of ropinirole in this patient population can be established.

    Geriatric, psychosis

    Ropinirole should be used cautiously in patients with preexisting psychosis. Hallucinations have been reported in patients receiving ropinirole alone or in combination with L-dopa. Hallucinations have been reported with ropinirole use in patients with Parkinson's disease but not in patients using ropinirole for Restless Leg Syndrome. The incidence of hallucinations is increased in geriatric patients as well as during concurrent use of ropinirole with other dopaminergic agents, such as entacapone or L-dopa in any patient. Psychotic-like behavior may manifest as hallucinations, confusion, paranoia, aggression, agitation, delusions, and/or disorganized thinking. 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.

    Dialysis, renal failure, renal impairment

    No dosage adjustments are needed in patients with mild to moderate renal impairment (CrCl of 30—50 ml/min). However, initial dose adjustments are recommended in patients with end-stage renal disease (CrCl < 15 ml/min) who are receiving regular dialysis and titration should be based on tolerability and need for efficacy. The use of ropinirole in patients with severe renal impairment (CrCl < 30 ml/min) or renal failure who are not receiving regular dialysis has not been studied.

    Hepatic disease

    The pharmacokinetics of ropinirole have not been studied in patients with hepatic disease. These patients may have higher plasma concentrations and lower clearance of ropinirole than patients with normal hepatic function. Ropinirole should be titrated with caution in patients with hepatic disease.

    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. In a trial in patients with restless leg syndrome (RLS), smokers (n = 7) had lower maximum concentrations and lower overall drug exposure (AUC) than did nonsmokers (n = 11).

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

    Ropinirole commonly causes somnolence. In addition, 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 ropinirole or other 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 one year after the initiation of treatment, and the relation to the medication is not entirely clear. Prior to initiating treatment with ropinirole, patients should be advised of the potential to develop somnolence and specifically asked about factors that may increase the risk of experiencing such an event such as concomitant use of sedating medications (coadministration with other CNS depressants), ethanol ingestion, the presence of sleep disorders (e.g., narcolepsy, sleep apnea), or concomitant use of medications that increase ropinirole plasma levels (e.g., ciprofloxacin). 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. Reassessment for drowsiness or oversedation 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.

    Abrupt discontinuation

    Avoid abrupt discontinuation or rapid dose reduction of immediate-release and extended-release ropinirole if possible. Adverse events resembling neuroleptic malignant syndrome (e.g., withdrawal-emergent hyperpyrexia, confusion, muscular rigidity, altered consciousness, autonomic instability) have been reported in association with rapid dose reduction of, withdrawal from, or changes in dopaminergic therapy. 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 three 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. When discontinuing immediate-release ropinirole in patients with Restless Legs Syndrome (RLS), the manufacturer recommends a gradual unspecified taper of the daily dose. Rebound symptoms have been reported following abrupt discontinuation of some dopaminergic medications in patients with RLS.

    Melanoma

    Epidemiological studies have shown that patients with Parkinson's disease have a 2- to 6-fold higher risk of developing melanoma than the general population. It is unclear if this increased risk is disease-related or associated with other factors such as the medications used to treat Parkinson's disease. Therefore, it is recommended that a qualified practitioner (e.g., dermatologist) monitor for melanomas on a regular basis during ropinirole use for any indication. In addition, patients should be instructed to regularly monitor for skin changes that may indicate the presence of melanoma and to promptly report these changes to their provider.

    Impulse control symptoms

    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. Practitioners should inquire periodically about new or worsening impulse control symptoms in patients receiving ropinirole. 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.

    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
    new primary malignancy / 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
    xerophthalmia / Early / 2.0-2.0
    diplopia / 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

    Acetaminophen; Butalbital: (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.
    Acetaminophen; 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.
    Acetaminophen; 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.
    Acetaminophen; Tramadol: (Moderate) Ropinirole can cause CNS depression. Tramadol use increases the risk of CNS depression and respiratory depression when used with other agents that are CNS depressants. Extreme caution is needed in using tramadol at the same time as other CNS depressants. A reduced dose of tramadol is recommended when used with another CNS depressant.
    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.
    Amitriptyline; Chlordiazepoxide: (Moderate) Concomitant use of ropinirole with other CNS depressants can potentiate the sedation effects of 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: (Major) Ropinirole is a potent dopamine-receptor agonist. Dopamine-receptor antagonists, including antipsychotics may antagonize the effects of ropinirole. In general, the atypical antipsychotics are less likely to interfere with antiparkinson treatments than traditional antipsychotic agents. However, antipsychotics should be avoided during therapy for Parkinson's disease unless the benefit of the drug outweighs the risk of decreased therapeutic response to levodopa or other treatments.
    Asenapine: (Major) Ropinirole is a potent dopamine-receptor agonist. Dopamine-receptor antagonists, including antipsychotics may antagonize the effects of ropinirole. In general, the atypical antipsychotics are less likely to interfere with antiparkinson treatments than traditional antipsychotic agents. However, antipsychotics should be avoided during therapy for Parkinson's disease unless the benefit of the drug outweighs the risk of decreased therapeutic response to levodopa or other treatments.
    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.
    Atropine; Hyoscyamine; Phenobarbital; 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.
    atypical antipsychotic: (Major) Ropinirole is a potent dopamine-receptor agonist. Dopamine-receptor antagonists, including antipsychotics may antagonize the effects of ropinirole. In general, the atypical antipsychotics are less likely to interfere with antiparkinson treatments than traditional antipsychotic agents. However, antipsychotics should be avoided during therapy for Parkinson's disease unless the benefit of the drug outweighs the risk of decreased therapeutic response to levodopa or other treatments.
    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: (Major) Ropinirole is a potent dopamine-receptor agonist. Dopamine-receptor antagonists, including antipsychotics may antagonize the effects of ropinirole. In general, the atypical antipsychotics are less likely to interfere with antiparkinson treatments than traditional antipsychotic agents. However, antipsychotics should be avoided during therapy for Parkinson's disease unless the benefit of the drug outweighs the risk of decreased therapeutic response to levodopa or other treatments.
    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.
    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: (Major) Ropinirole is a potent dopamine-receptor agonist. Dopamine-receptor antagonists, including antipsychotics may antagonize the effects of ropinirole. In general, the atypical antipsychotics are less likely to interfere with antiparkinson treatments than traditional antipsychotic agents. However, antipsychotics should be avoided during therapy for Parkinson's disease unless the benefit of the drug outweighs the risk of decreased therapeutic response to levodopa or other treatments.
    Cetirizine: (Moderate) Additive drowsiness may occur if cetirizine or levocetirizine is administered with other drugs that depress the CNS, such as ropinirole. Coadminister these drugs with caution.
    Cetirizine; Pseudoephedrine: (Moderate) Additive drowsiness may occur if cetirizine or levocetirizine is administered with other drugs that depress the CNS, such as ropinirole. Coadminister these drugs with caution.
    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; Clidinium: (Moderate) Concomitant use of ropinirole with other CNS depressants can potentiate the sedation effects of ropinirole.
    Chlorpromazine: (Major) Ropinirole is a potent dopamine-receptor agonist. Dopamine-receptor antagonists, including antipsychotics (e.g., phenothiazines) should be avoided concurrently because they may antagonize the effects of ropinirole. Antipsychotics should be avoided during therapy for Parkinson's disease unless the benefit of the drug outweighs the risk of decreased therapeutic response to levodopa or other treatments.
    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: (Major) Ropinirole is a potent dopamine-receptor agonist. Dopamine-receptor antagonists, including antipsychotics may antagonize the effects of ropinirole. In general, the atypical antipsychotics are less likely to interfere with antiparkinson treatments than traditional antipsychotic agents. However, antipsychotics should be avoided during therapy for Parkinson's disease unless the benefit of the drug outweighs the risk of decreased therapeutic response to levodopa or other treatments.
    Codeine; Phenylephrine; Promethazine: (Major) Promethazine may inhibit the clinical antiparkinsonian response to ropinirole therapy by blocking dopamine receptors in the brain. Ropinirole may also cause additive drowsiness when combined with promethazine. In general, the use of a phenothiazine-type drug should be avoided in patients requiring therapy for Parkinson's disease.
    Codeine; Promethazine: (Major) Promethazine may inhibit the clinical antiparkinsonian response to ropinirole therapy by blocking dopamine receptors in the brain. Ropinirole may also cause additive drowsiness when combined with promethazine. In general, the use of a phenothiazine-type drug should be avoided in patients requiring therapy for Parkinson's disease.
    COMT inhibitors: (Moderate) COMT inhibitors should be given cautiously with other agents that cause CNS depression due to the possibility of additive sedation.
    Conjugated Estrogens: (Minor) Estrogens reduce the oral clearance of ropinirole by 36 percent. Dosage adjustment may not be needed for ropinirole in patients on estrogen therapy because patients must be carefully titrated with ropinirole to tolerance or adequate effect. However, if estrogen therapy is stopped or started during treatment with ropinirole, then adjustment of the ropinirole dose may be required.
    Conjugated Estrogens; Bazedoxifene: (Minor) Estrogens reduce the oral clearance of ropinirole by 36 percent. Dosage adjustment may not be needed for ropinirole in patients on estrogen therapy because patients must be carefully titrated with ropinirole to tolerance or adequate effect. However, if estrogen therapy is stopped or started during treatment with ropinirole, then adjustment of the ropinirole dose may be required.
    Conjugated Estrogens; Medroxyprogesterone: (Minor) Estrogens reduce the oral clearance of ropinirole by 36 percent. Dosage adjustment may not be needed for ropinirole in patients on estrogen therapy because patients must be carefully titrated with ropinirole to tolerance or adequate effect. However, if estrogen therapy is stopped or started during treatment with ropinirole, then adjustment of the ropinirole dose may be required.
    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.
    Dexmethylphenidate: (Moderate) Increased dopaminergic effects may occur during coadministration of dexmethylphenidate, an inhibitor 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; Promethazine: (Major) Promethazine may inhibit the clinical antiparkinsonian response to ropinirole therapy by blocking dopamine receptors in the brain. Ropinirole may also cause additive drowsiness when combined with promethazine. In general, the use of a phenothiazine-type drug should be avoided in patients requiring therapy for Parkinson's disease.
    Diazepam: (Moderate) Concomitant use of ropinirole with other CNS depressants can potentiate the sedation effects of ropinirole.
    Dienogest; Estradiol valerate: (Minor) Estrogens reduce the oral clearance of ropinirole by 36 percent. Dosage adjustment may not be needed for ropinirole in patients on estrogen therapy because patients must be carefully titrated with ropinirole to tolerance or adequate effect. However, if estrogen therapy is stopped or started during treatment with ropinirole, then adjustment of the ropinirole dose may be required.
    Diethylstilbestrol, DES: (Minor) Estrogens reduce the oral clearance of ropinirole by 36 percent. Dosage adjustment may not be needed for ropinirole in patients on estrogen therapy because patients must be carefully titrated with ropinirole to tolerance or adequate effect. However, if estrogen therapy is stopped or started during treatment with ropinirole, then adjustment of the ropinirole dose may be required.
    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; Estradiol: (Minor) Estrogens reduce the oral clearance of ropinirole by 36 percent. Dosage adjustment may not be needed for ropinirole in patients on estrogen therapy because patients must be carefully titrated with ropinirole to tolerance or adequate effect. However, if estrogen therapy is stopped or started during treatment with ropinirole, then adjustment of the ropinirole dose may be required.
    Drospirenone; Ethinyl Estradiol: (Minor) Estrogens reduce the oral clearance of ropinirole by 36 percent. Dosage adjustment may not be needed for ropinirole in patients on estrogen therapy because patients must be carefully titrated with ropinirole to tolerance or adequate effect. However, if estrogen therapy is stopped or started during treatment with ropinirole, then adjustment of the ropinirole dose may be required.
    Drospirenone; Ethinyl Estradiol; Levomefolate: (Minor) Estrogens reduce the oral clearance of ropinirole by 36 percent. Dosage adjustment may not be needed for ropinirole in patients on estrogen therapy because patients must be carefully titrated with ropinirole to tolerance or adequate effect. However, if estrogen therapy is stopped or started during treatment with ropinirole, then adjustment of the ropinirole dose may be required.
    Estazolam: (Moderate) Concomitant use of ropinirole with other CNS depressants can potentiate the sedation effects of ropinirole.
    Esterified Estrogens: (Minor) Estrogens reduce the oral clearance of ropinirole by 36 percent. Dosage adjustment may not be needed for ropinirole in patients on estrogen therapy because patients must be carefully titrated with ropinirole to tolerance or adequate effect. However, if estrogen therapy is stopped or started during treatment with ropinirole, then adjustment of the ropinirole dose may be required.
    Esterified Estrogens; Methyltestosterone: (Minor) Estrogens reduce the oral clearance of ropinirole by 36 percent. Dosage adjustment may not be needed for ropinirole in patients on estrogen therapy because patients must be carefully titrated with ropinirole to tolerance or adequate effect. However, if estrogen therapy is stopped or started during treatment with ropinirole, then adjustment of the ropinirole dose may be required.
    Estradiol Cypionate; Medroxyprogesterone: (Minor) Estrogens reduce the oral clearance of ropinirole by 36 percent. Dosage adjustment may not be needed for ropinirole in patients on estrogen therapy because patients must be carefully titrated with ropinirole to tolerance or adequate effect. However, if estrogen therapy is stopped or started during treatment with ropinirole, then adjustment of the ropinirole dose may be required.
    Estradiol: (Minor) Estrogens reduce the oral clearance of ropinirole by 36 percent. Dosage adjustment may not be needed for ropinirole in patients on estrogen therapy because patients must be carefully titrated with ropinirole to tolerance or adequate effect. However, if estrogen therapy is stopped or started during treatment with ropinirole, then adjustment of the ropinirole dose may be required.
    Estradiol; Levonorgestrel: (Minor) Estrogens reduce the oral clearance of ropinirole by 36 percent. Dosage adjustment may not be needed for ropinirole in patients on estrogen therapy because patients must be carefully titrated with ropinirole to tolerance or adequate effect. However, if estrogen therapy is stopped or started during treatment with ropinirole, then adjustment of the ropinirole dose may be required.
    Estradiol; Norethindrone: (Minor) Estrogens reduce the oral clearance of ropinirole by 36 percent. Dosage adjustment may not be needed for ropinirole in patients on estrogen therapy because patients must be carefully titrated with ropinirole to tolerance or adequate effect. However, if estrogen therapy is stopped or started during treatment with ropinirole, then adjustment of the ropinirole dose may be required.
    Estradiol; Norgestimate: (Minor) Estrogens reduce the oral clearance of ropinirole by 36 percent. Dosage adjustment may not be needed for ropinirole in patients on estrogen therapy because patients must be carefully titrated with ropinirole to tolerance or adequate effect. However, if estrogen therapy is stopped or started during treatment with ropinirole, then adjustment of the ropinirole dose may be required.
    Estrogens: (Minor) Estrogens reduce the oral clearance of ropinirole by 36 percent. Dosage adjustment may not be needed for ropinirole in patients on estrogen therapy because patients must be carefully titrated with ropinirole to tolerance or adequate effect. However, if estrogen therapy is stopped or started during treatment with ropinirole, then adjustment of the ropinirole dose may be required.
    Estropipate: (Minor) Estrogens reduce the oral clearance of ropinirole by 36 percent. Dosage adjustment may not be needed for ropinirole in patients on estrogen therapy because patients must be carefully titrated with ropinirole to tolerance or adequate effect. However, if estrogen therapy is stopped or started during treatment with ropinirole, then adjustment of the ropinirole dose may be required.
    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: (Minor) Estrogens reduce the oral clearance of ropinirole by 36 percent. Dosage adjustment may not be needed for ropinirole in patients on estrogen therapy because patients must be carefully titrated with ropinirole to tolerance or adequate effect. However, if estrogen therapy is stopped or started during treatment with ropinirole, then adjustment of the ropinirole dose may be required.
    Ethinyl Estradiol; Desogestrel: (Minor) Estrogens reduce the oral clearance of ropinirole by 36 percent. Dosage adjustment may not be needed for ropinirole in patients on estrogen therapy because patients must be carefully titrated with ropinirole to tolerance or adequate effect. However, if estrogen therapy is stopped or started during treatment with ropinirole, then adjustment of the ropinirole dose may be required.
    Ethinyl Estradiol; Ethynodiol Diacetate: (Minor) Estrogens reduce the oral clearance of ropinirole by 36 percent. Dosage adjustment may not be needed for ropinirole in patients on estrogen therapy because patients must be carefully titrated with ropinirole to tolerance or adequate effect. However, if estrogen therapy is stopped or started during treatment with ropinirole, then adjustment of the ropinirole dose may be required.
    Ethinyl Estradiol; Etonogestrel: (Minor) Estrogens reduce the oral clearance of ropinirole by 36 percent. Dosage adjustment may not be needed for ropinirole in patients on estrogen therapy because patients must be carefully titrated with ropinirole to tolerance or adequate effect. However, if estrogen therapy is stopped or started during treatment with ropinirole, then adjustment of the ropinirole dose may be required.
    Ethinyl Estradiol; Levonorgestrel: (Minor) Estrogens reduce the oral clearance of ropinirole by 36 percent. Dosage adjustment may not be needed for ropinirole in patients on estrogen therapy because patients must be carefully titrated with ropinirole to tolerance or adequate effect. However, if estrogen therapy is stopped or started during treatment with ropinirole, then adjustment of the ropinirole dose may be required.
    Ethinyl Estradiol; Levonorgestrel; Ferrous bisglycinate: (Minor) Estrogens reduce the oral clearance of ropinirole by 36 percent. Dosage adjustment may not be needed for ropinirole in patients on estrogen therapy because patients must be carefully titrated with ropinirole to tolerance or adequate effect. However, if estrogen therapy is stopped or started during treatment with ropinirole, then adjustment of the ropinirole dose may be required.
    Ethinyl Estradiol; Levonorgestrel; Folic Acid; Levomefolate: (Minor) Estrogens reduce the oral clearance of ropinirole by 36 percent. Dosage adjustment may not be needed for ropinirole in patients on estrogen therapy because patients must be carefully titrated with ropinirole to tolerance or adequate effect. However, if estrogen therapy is stopped or started during treatment with ropinirole, then adjustment of the ropinirole dose may be required.
    Ethinyl Estradiol; Norelgestromin: (Minor) Estrogens reduce the oral clearance of ropinirole by 36 percent. Dosage adjustment may not be needed for ropinirole in patients on estrogen therapy because patients must be carefully titrated with ropinirole to tolerance or adequate effect. However, if estrogen therapy is stopped or started during treatment with ropinirole, then adjustment of the ropinirole dose may be required.
    Ethinyl Estradiol; Norethindrone Acetate: (Minor) Estrogens reduce the oral clearance of ropinirole by 36 percent. Dosage adjustment may not be needed for ropinirole in patients on estrogen therapy because patients must be carefully titrated with ropinirole to tolerance or adequate effect. However, if estrogen therapy is stopped or started during treatment with ropinirole, then adjustment of the ropinirole dose may be required.
    Ethinyl Estradiol; Norethindrone Acetate; Ferrous fumarate: (Minor) Estrogens reduce the oral clearance of ropinirole by 36 percent. Dosage adjustment may not be needed for ropinirole in patients on estrogen therapy because patients must be carefully titrated with ropinirole to tolerance or adequate effect. However, if estrogen therapy is stopped or started during treatment with ropinirole, then adjustment of the ropinirole dose may be required.
    Ethinyl Estradiol; Norethindrone: (Minor) Estrogens reduce the oral clearance of ropinirole by 36 percent. Dosage adjustment may not be needed for ropinirole in patients on estrogen therapy because patients must be carefully titrated with ropinirole to tolerance or adequate effect. However, if estrogen therapy is stopped or started during treatment with ropinirole, then adjustment of the ropinirole dose may be required.
    Ethinyl Estradiol; Norethindrone; Ferrous fumarate: (Minor) Estrogens reduce the oral clearance of ropinirole by 36 percent. Dosage adjustment may not be needed for ropinirole in patients on estrogen therapy because patients must be carefully titrated with ropinirole to tolerance or adequate effect. However, if estrogen therapy is stopped or started during treatment with ropinirole, then adjustment of the ropinirole dose may be required.
    Ethinyl Estradiol; Norgestimate: (Minor) Estrogens reduce the oral clearance of ropinirole by 36 percent. Dosage adjustment may not be needed for ropinirole in patients on estrogen therapy because patients must be carefully titrated with ropinirole to tolerance or adequate effect. However, if estrogen therapy is stopped or started during treatment with ropinirole, then adjustment of the ropinirole dose may be required.
    Ethinyl Estradiol; Norgestrel: (Minor) Estrogens reduce the oral clearance of ropinirole by 36 percent. Dosage adjustment may not be needed for ropinirole in patients on estrogen therapy because patients must be carefully titrated with ropinirole to tolerance or adequate effect. However, if estrogen therapy is stopped or started during treatment with ropinirole, then adjustment of the ropinirole dose may be required.
    Fluoxetine; Olanzapine: (Major) Ropinirole is a potent dopamine-receptor agonist. Dopamine-receptor antagonists, including antipsychotics may antagonize the effects of ropinirole. In general, the atypical antipsychotics are less likely to interfere with antiparkinson treatments than traditional antipsychotic agents. However, antipsychotics should be avoided during therapy for Parkinson's disease unless the benefit of the drug outweighs the risk of decreased therapeutic response to levodopa or other treatments.
    Fluphenazine: (Major) Ropinirole is a potent dopamine-receptor agonist. Dopamine-receptor antagonists, including antipsychotics (e.g., phenothiazines) should be avoided concurrently because they may antagonize the effects of ropinirole. Antipsychotics should be avoided during therapy for Parkinson's disease unless the benefit of the drug outweighs the risk of decreased therapeutic response to levodopa or other treatments.
    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: (Moderate) CNS depressive effects, such as drowsiness or dizziness, may increase when antiparkinsonian agents, such as ropinirole, are given concomitantly with gabapentin. Counsel patients to limit activity until they are aware of how coadministration affects them.
    Haloperidol: (Major) Haloperidol may inhibit the clinical antiparkinsonian response to ropinirole therapy by blocking dopamine receptors in the brain. Haloperidol may also cause additive sedation with ropinirole. Haloperidol should be avoided during therapy for Parkinson's disease unless the benefit of the drug outweighs the risk of decreased therapeutic response to ropinirole.
    Iloperidone: (Major) Ropinirole is a potent dopamine-receptor agonist. Dopamine-receptor antagonists, including antipsychotics may antagonize the effects of ropinirole. In general, the atypical antipsychotics are less likely to interfere with antiparkinson treatments than traditional antipsychotic agents. However, antipsychotics should be avoided during therapy for Parkinson's disease unless the benefit of the drug outweighs the risk of decreased therapeutic response to levodopa or other treatments.
    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.
    Levocetirizine: (Moderate) Additive drowsiness may occur if cetirizine or levocetirizine is administered with other drugs that depress the CNS, such as ropinirole. Coadminister these drugs with caution.
    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) Dopamine-receptor antagonists, including loxapine, should be avoided in combination with dopamine-receptor agonists because loxapine may antagonize the effects of the dopamine-receptor agonists.
    Lurasidone: (Major) Ropinirole is a potent dopamine-receptor agonist. Dopamine-receptor antagonists, including antipsychotics may antagonize the effects of ropinirole. In general, the atypical antipsychotics are less likely to interfere with antiparkinson treatments than traditional antipsychotic agents. However, antipsychotics should be avoided during therapy for Parkinson's disease unless the benefit of the drug outweighs the risk of decreased therapeutic response to levodopa or other treatments.
    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) Promethazine may inhibit the clinical antiparkinsonian response to ropinirole therapy by blocking dopamine receptors in the brain. Ropinirole may also cause additive drowsiness when combined with promethazine. In general, the use of a phenothiazine-type drug should be avoided in patients requiring therapy for Parkinson's disease.
    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) Ropinirole is a potent dopamine-receptor agonist. Dopamine-receptor antagonists, including antipsychotics (e.g., phenothiazines) should be avoided concurrently because they may antagonize the effects of ropinirole. Antipsychotics should be avoided during therapy for Parkinson's disease unless the benefit of the drug outweighs the risk of decreased therapeutic response to levodopa or other treatments.
    Mestranol; Norethindrone: (Minor) Estrogens reduce the oral clearance of ropinirole by 36 percent. Dosage adjustment may not be needed for ropinirole in patients on estrogen therapy because patients must be carefully titrated with ropinirole to tolerance or adequate effect. However, if estrogen therapy is stopped or started during treatment with ropinirole, then adjustment of the ropinirole dose may be required.
    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: (Moderate) Increased dopaminergic effects may occur during coadministration of methylphenidate, an inhibitor 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) In general, antipsychotics can worsen the motor symptoms of Parkinson's disease thereby decreasing the overall effectiveness of antiparkinsonian agents. Molindone should be avoided in patients receiving medications for Parkinson's disease unless the benefit of molindone therapy outweighs the risk of decreased therapeutic response to levodopa or other treatments.
    Nabilone: (Moderate) Concomitant use of ropinirole with other CNS depressants like nabilone can potentiate the sedation effects of ropinirole.
    Norfloxacin: (Moderate) Ropinirole is primarily metabolized by CYP1A2. Ropinirole clearance may be altered by coadministration of norfloxacin, an inhibitor of CYP1A2.
    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: (Major) Ropinirole is a potent dopamine-receptor agonist. Dopamine-receptor antagonists, including antipsychotics may antagonize the effects of ropinirole. In general, the atypical antipsychotics are less likely to interfere with antiparkinson treatments than traditional antipsychotic agents. However, antipsychotics should be avoided during therapy for Parkinson's disease unless the benefit of the drug outweighs the risk of decreased therapeutic response to levodopa or other treatments.
    Opiate Agonists: (Moderate) Concomitant use of opiate agonists with other central nervous system (CNS) depressants such as ropinirole can potentiate the effects of the opiate and may lead to additive CNS or respiratory depression, profound sedation, or coma. Prior to concurrent use of an opiate in patients taking a CNS depressant, 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. If these agents are used together, a reduced dosage of the opiate and/or the CNS depressant is recommended. Carefully monitor the patient for hypotension, CNS depression, and respiratory depression. Carbon dioxide retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
    Oxazepam: (Moderate) Concomitant use of ropinirole with other CNS depressants can potentiate the sedation effects of ropinirole.
    Paliperidone: (Major) Ropinirole is a potent dopamine-receptor agonist. Dopamine-receptor antagonists, including antipsychotics may antagonize the effects of ropinirole. In general, the atypical antipsychotics are less likely to interfere with antiparkinson treatments than traditional antipsychotic agents. However, antipsychotics should be avoided during therapy for Parkinson's disease unless the benefit of the drug outweighs the risk of decreased therapeutic response to levodopa or other treatments.
    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) Ropinirole is a potent dopamine-receptor agonist. Dopamine-receptor antagonists, including antipsychotics (e.g., phenothiazines) should be avoided concurrently because they may antagonize the effects of ropinirole. Antipsychotics should be avoided during therapy for Parkinson's disease unless the benefit of the drug outweighs the risk of decreased therapeutic response to levodopa or other treatments.
    Perphenazine; Amitriptyline: (Major) Ropinirole is a potent dopamine-receptor agonist. Dopamine-receptor antagonists, including antipsychotics (e.g., phenothiazines) should be avoided concurrently because they may antagonize the effects of ropinirole. Antipsychotics should be avoided during therapy for Parkinson's disease unless the benefit of the drug outweighs the risk of decreased therapeutic response to levodopa or other treatments.
    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.
    Phenothiazines: (Major) Ropinirole is a potent dopamine-receptor agonist. Dopamine-receptor antagonists, including antipsychotics (e.g., phenothiazines) should be avoided concurrently because they may antagonize the effects of ropinirole. Antipsychotics should be avoided during therapy for Parkinson's disease unless the benefit of the drug outweighs the risk of decreased therapeutic response to levodopa or other treatments.
    Phenylephrine; Promethazine: (Major) Promethazine may inhibit the clinical antiparkinsonian response to ropinirole therapy by blocking dopamine receptors in the brain. Ropinirole may also cause additive drowsiness when combined with promethazine. In general, the use of a phenothiazine-type drug should be avoided in patients requiring therapy for Parkinson's disease.
    Pimozide: (Major) Ropinirole is a potent dopamine-receptor agonist. Dopamine-receptor antagonists, including antipsychotics (e.g., pimozide), should be avoided concurrently because they may antagonize the effects of ropinirole. In general, the atypical antipsychotics are less likely to interfere with antiparkinson treatments than traditional antipsychotic agents (e.g., phenothiazines). However, antipsychotics should be avoided during therapy for Parkinson's disease unless the benefit of the drug outweighs the risk of decreased therapeutic response to levodopa or other treatments.
    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) Ropinirole is a potent dopamine-receptor agonist. Dopamine-receptor antagonists, including antipsychotics (e.g., phenothiazines) should be avoided concurrently because they may antagonize the effects of ropinirole. Antipsychotics should be avoided during therapy for Parkinson's disease unless the benefit of the drug outweighs the risk of decreased therapeutic response to levodopa or other treatments.
    Promethazine: (Major) Promethazine may inhibit the clinical antiparkinsonian response to ropinirole therapy by blocking dopamine receptors in the brain. Ropinirole may also cause additive drowsiness when combined with promethazine. In general, the use of a phenothiazine-type drug should be avoided in patients requiring therapy for Parkinson's disease.
    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: (Major) Ropinirole is a potent dopamine-receptor agonist. Dopamine-receptor antagonists, including antipsychotics may antagonize the effects of ropinirole. In general, the atypical antipsychotics are less likely to interfere with antiparkinson treatments than traditional antipsychotic agents. However, antipsychotics should be avoided during therapy for Parkinson's disease unless the benefit of the drug outweighs the risk of decreased therapeutic response to levodopa or other treatments.
    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: (Major) Ropinirole is a potent dopamine-receptor agonist. Dopamine-receptor antagonists, including antipsychotics may antagonize the effects of ropinirole. In general, the atypical antipsychotics are less likely to interfere with antiparkinson treatments than traditional antipsychotic agents. However, antipsychotics should be avoided during therapy for Parkinson's disease unless the benefit of the drug outweighs the risk of decreased therapeutic response to levodopa or other treatments.
    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.
    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.
    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.
    Tapentadol: (Moderate) Additive CNS depressive effects are expected if tapentadol is used in conjunction with other CNS depressants. Severe hypotension, profound sedation, coma, or respiratory depression may occur. Prior to concurrent use of tapentadol in patients taking a CNS depressant, 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. If a CNS depressant is used concurrently with tapentadol, a reduced dosage of tapentadol and/or the CNS depressant is recommended. If the extended-release tapentadol tablets are used concurrently with a CNS depressant, it is recommended to use an initial tapentadol dose of 50 mg PO every 12 hours. Monitor patients for sedation and respiratory depression.
    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) Ropinirole is a potent dopamine-receptor agonist. Dopamine-receptor antagonists, including antipsychotics (e.g., phenothiazines) should be avoided concurrently because they may antagonize the effects of ropinirole. Antipsychotics should be avoided during therapy for Parkinson's disease unless the benefit of the drug outweighs the risk of decreased therapeutic response to levodopa or other treatments.
    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) Ropinirole is a potent dopamine-receptor agonist. Dopamine-receptor antagonists, including antipsychotics (e.g., phenothiazines) should be avoided concurrently because they may antagonize the effects of ropinirole. Antipsychotics should be avoided during therapy for Parkinson's disease unless the benefit of the drug outweighs the risk of decreased therapeutic response to levodopa or other treatments.
    Thiothixene: (Major) Concomitant use of thiothixene and dopamine agonists (e.g., pergolide, pramipexole, or ropinirole) is not recommeneded. By blocking dopamine receptors in the brain, thiothixene may inhibit the clinical antiparkinsonian response to dopamine agonists. In addition, concomitant use may cause additive drowsiness. In general, avoid thiothixene in patients requiring therapy for Parkinson's disease unless the benefit of the neuroleptic outweighs the risk of decreased therapeutic response to antiparkinsonian therapy.
    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.
    Tramadol: (Moderate) Ropinirole can cause CNS depression. Tramadol use increases the risk of CNS depression and respiratory depression when used with other agents that are CNS depressants. Extreme caution is needed in using tramadol at the same time as other CNS depressants. A reduced dose of tramadol is recommended when used with another CNS depressant.
    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) Ropinirole is a potent dopamine-receptor agonist. Dopamine-receptor antagonists, including antipsychotics (e.g., phenothiazines) should be avoided concurrently because they may antagonize the effects of ropinirole. Antipsychotics should be avoided during therapy for Parkinson's disease unless the benefit of the drug outweighs the risk of decreased therapeutic response to levodopa or other treatments.
    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.
    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: (Major) Ropinirole is a potent dopamine-receptor agonist. Dopamine-receptor antagonists, including antipsychotics may antagonize the effects of ropinirole. In general, the atypical antipsychotics are less likely to interfere with antiparkinson treatments than traditional antipsychotic agents. However, antipsychotics should be avoided during therapy for Parkinson's disease unless the benefit of the drug outweighs the risk of decreased therapeutic response to levodopa or other treatments.
    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. However, inhibition of lactation is expected because ropinirole inhibits secretion of prolactin in humans. Studies in rats have shown that ropinirole and/or its metabolites are excreted in breast milk. According to the manufacturer, the developmental and health benefits of breast-feeding should be discussed with the mother along with the clinical need for ropinirole and any potential adverse effects on the breast-fed infant or from the underlying maternal condition. If treatment with ropinirole cannot be avoided during breast-feeding, the infant should be monitored for commonly encountered adverse effects of ropinirole therapy including loss of appetite, dyspepsia, sedation, and nausea. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    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.