Requip

Anti-Parkinson Agents, Dopamine Agonists

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

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

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

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

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

Requip, Requip XL

Rx

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

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.

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.

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.

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.

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.

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.

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.
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.
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.
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.
Butalbital; Aspirin; 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.
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.
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%.
Difelikefalin: (Moderate) Monitor for dizziness, somnolence, mental status changes, and gait disturbances if concomitant use of difelikefalin with CNS depressants is necessary. Concomitant use may increase the risk for these adverse reactions.
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: (Moderate) Concomitant use of ropinirole and higher doses of estrogens may increase the exposure of ropinirole. A dose adjustment of ropinirole may be needed when estrogen therapy is initiated or discontinued. Some estrogens have reduced ropinirole oral clearance by 36%.
Estradiol; Levonorgestrel: (Moderate) Concomitant use of ropinirole and higher doses of estrogens may increase the exposure of ropinirole. A dose adjustment of ropinirole may be needed when estrogen therapy is initiated or discontinued. Some estrogens have reduced ropinirole oral clearance by 36%.
Estradiol; Norethindrone: (Moderate) Concomitant use of ropinirole and higher doses of estrogens may increase the exposure of ropinirole. A dose adjustment of ropinirole may be needed when estrogen therapy is initiated or discontinued. Some estrogens have reduced ropinirole oral clearance by 36%.
Estradiol; Norgestimate: (Moderate) Concomitant use of ropinirole and higher doses of estrogens may increase the exposure of ropinirole. A dose adjustment of ropinirole may be needed when estrogen therapy is initiated or discontinued. Some estrogens have reduced ropinirole oral clearance by 36%.
Estradiol; Progesterone: (Moderate) Concomitant use of ropinirole and higher doses of estrogens may increase the exposure of ropinirole. A dose adjustment of ropinirole may be needed when estrogen therapy is initiated or discontinued. Some estrogens have reduced ropinirole oral clearance by 36%.
Estrogens: (Moderate) Concomitant use of ropinirole and higher doses of estrogens may increase the exposure of ropinirole. A dose adjustment of ropinirole may be needed when estrogen therapy is initiated or discontinued. Some estrogens have reduced ropinirole oral clearance by 36%.
Estropipate: (Moderate) Concomitant use of ropinirole and higher doses of estrogens may increase the exposure of ropinirole. A dose adjustment of ropinirole may be needed when estrogen therapy is initiated or discontinued. Some estrogens have reduced ropinirole oral clearance by 36%.
Eszopiclone: (Moderate) Using eszopiclone with ropinirole or other CNS depressants may have cumulative effects and can increase the risk for sedation. A dose reduction may be necessary if eszopiclone is coadministered with other CNS depressants, such as ropinirole.
Ethanol: (Major) Patients should be advised that alcohol use may increase the risk of somnolence during treatment with ropinirole. In addition, the sudden onset of sleep during activities that require active participation (e.g., driving a vehicle, conversations, eating) has occurred during treatment with dopamine agonists, including ropinirole. In some cases, excessive drowsiness due to ropinirole or other dopamine agonists has resulted in auto accidents or other harmful events in the course of daily living. Advise patients to avoid alcohol and notify their healthcare provider if they experience excess sedation or sudden sleep onset while receiving ropinirole.
Ethinyl Estradiol; Norelgestromin: (Moderate) Concomitant use of ropinirole and higher doses of estrogens may increase the exposure of ropinirole. A dose adjustment of ropinirole may be needed when estrogen therapy is initiated or discontinued. Some estrogens have reduced ropinirole oral clearance by 36%.
Ethinyl Estradiol; Norethindrone Acetate: (Moderate) Concomitant use of ropinirole and higher doses of estrogens may increase the exposure of ropinirole. A dose adjustment of ropinirole may be needed when estrogen therapy is initiated or discontinued. Some estrogens have reduced ropinirole oral clearance by 36%.
Ethinyl Estradiol; Norgestrel: (Moderate) Concomitant use of ropinirole and higher doses of estrogens may increase the exposure of ropinirole. A dose adjustment of ropinirole may be needed when estrogen therapy is initiated or discontinued. Some estrogens have reduced ropinirole oral clearance by 36%.
Ethynodiol Diacetate; Ethinyl Estradiol: (Moderate) Concomitant use of ropinirole and higher doses of estrogens may increase the exposure of ropinirole. A dose adjustment of ropinirole may be needed when estrogen therapy is initiated or discontinued. Some estrogens have reduced ropinirole oral clearance by 36%.
Etonogestrel; Ethinyl Estradiol: (Moderate) Concomitant use of ropinirole and higher doses of estrogens may increase the exposure of ropinirole. A dose adjustment of ropinirole may be needed when estrogen therapy is initiated or discontinued. Some estrogens have reduced ropinirole oral clearance by 36%.
Fenfluramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of fenfluramine and ropinirole. Concurrent use may result in additive CNS depression. Dopaminergic agents, such as ropinirole, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Fluphenazine: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and ropinirole may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Flurazepam: (Moderate) Concomitant use of ropinirole with other CNS depressants can potentiate the sedation effects of ropinirole.
Fluvoxamine: (Moderate) Ropinirole is primarily metabolized by cytochrome P450 1A2. Ropinirole concentrations may increase when coadministered with inhibitors of CYP1A2, such as fluvoxamine. If fluvoxamine is initiated or discontinued during treatment with ropinirole, adjustment of the ropinirole dose may be required.
Food: (Major) Advise patients to avoid cannabis use while taking CNS depressants due to the risk for additive CNS depression and potential for other cognitive adverse reactions.
Gabapentin: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and ropinirole. Concomitant use of gabapentin with ropinirole may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents, such as ropinirole, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Haloperidol: (Major) Due to opposing effects on central dopaminergic activity, haloperidol and ropinirole may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to haloperidol. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
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%.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Moderate) Concomitant use of ropinirole and higher doses of estrogens may increase the exposure of ropinirole. A dose adjustment of ropinirole may be needed when estrogen therapy is initiated or discontinued. Some estrogens have reduced ropinirole oral clearance by 36%.
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.
Meprobamate: (Moderate) Concomitant use of ropinirole with other CNS depressants can potentiate the sedation effects of ropinirole.
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%.
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%.
Olanzapine: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or ropinirole during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and ropinirole may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with ropinirole than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Olanzapine; Fluoxetine: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or ropinirole during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and ropinirole may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with ropinirole than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Olanzapine; Samidorphan: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or ropinirole during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and ropinirole may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with ropinirole than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
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.
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%.
Solriamfetol: (Moderate) Monitor for dopamine-mediated effects including nausea, vomiting, dizziness, tremor, and changes in moods or behaviors if solriamfetol, a central dopamine and norepinephrine reuptake inhibitor, is administered with other dopaminergic drugs, such as ropinirole. Caution is recommended since this combination has not been evaluated.
Stiripentol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and ropinirole. CNS depressants can potentiate the effects of stiripentol.
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.
Teriflunomide: (Moderate) Teriflunomide is a weak inducer of CYP1A2, which may lead to decreased plasma concentrations of ropinirole, a CYP1A2 substrate. If these drugs are coadministered, adjustment of ropinirole dosage may be required.
Thalidomide: (Major) Avoid the concomitant use of thalidomide with other central nervous system depressants such as ropinirole due to the potential for additive sedative effects.
Thioridazine: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and ropinirole may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to the phenothiazine. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Thiothixene: (Major) Due to opposing effects on central dopaminergic activity, thiothixene and dopamine agonists may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic instead of thiothixene, if appropriate. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Tobacco: (Major) Advise patients to avoid smoking tobacco while taking ropinirole. Tobacco smoking may increase the clearance of ropinirole via CYP1A2 induction, leading to reduced efficacy of ropinirole. In one study in patients with restless leg syndrome (RLS), cigarette smokers had an approximately 38% lower ropinirole AUC than did nonsmokers when normalized for dose.
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.

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

24 mg/day PO.

24 mg/day PO.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

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.

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.

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.

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.