Mirapex

Anti-Parkinson Agents, Dopamine Agonists

Oral Administration Oral Solid Formulations

Immediate-release tablets:
May administer with or without food; however, food may minimize the occurrence of nausea.
 
Extended-release tablets:
Take once daily with or without food. Do not crush, chew, or divide tablets; swallow whole. Administration with food may decrease the occurrence of nausea.
Residue in the stool which may resemble a swollen original extended-release tablet or swollen pieces of the original tablet have been reported. Instruct patients to contact their physician if this occurs.

Severe

visual impairment / Early / 3.0-3.0
camptocormia / Delayed / Incidence not known
pleurothotonus / Delayed / Incidence not known
antecollis / Delayed / Incidence not known
rhabdomyolysis / Delayed / Incidence not known
retroperitoneal fibrosis / Delayed / Incidence not known
pulmonary fibrosis / Delayed / Incidence not known
SIADH / Delayed / Incidence not known
heart failure / Delayed / Incidence not known
neuroleptic malignant syndrome-like symptoms / Delayed / Incidence not known

Moderate

orthostatic hypotension / Delayed / 0-53.0
dyskinesia / Delayed / 0-47.0
hallucinations / Early / 5.0-17.0
constipation / Delayed / 4.0-14.0
confusion / Early / 4.0-10.0
dystonic reaction / Delayed / 0-8.0
peripheral edema / Delayed / 2.0-8.0
hypertonia / Delayed / 0-7.0
amnesia / Delayed / 4.0-6.0
sudden sleep onset / Delayed / 3.0-6.0
edema / Delayed / 4.0-5.0
blurred vision / Early / 4.0-4.0
dyspnea / Early / 4.0-4.0
akathisia / Delayed / 0-3.0
chest pain (unspecified) / Early / 3.0-3.0
depression / Delayed / 0-2.0
dysphagia / Delayed / 2.0-2.0
impotence (erectile dysfunction) / Delayed / 2.0-2.0
urinary incontinence / Early / 2.0-2.0
myoclonia / Delayed / 1.0-1.0
myasthenia / Delayed / 1.0-1.0
psychosis / Early / Incidence not known
mania / Early / Incidence not known
impulse control symptoms / Delayed / Incidence not known
hypotension / Rapid / Incidence not known
erythema / Early / Incidence not known
withdrawal / Early / Incidence not known
restless legs syndrome (RLS) augmentation / Delayed / Incidence not known
restless legs syndrome (RLS) rebound / Delayed / Incidence not known

Mild

drowsiness / Early / 6.0-36.0
nausea / Early / 11.0-28.0
insomnia / Early / 4.0-27.0
dizziness / Early / 3.0-26.0
headache / Early / 4.0-16.0
asthenia / Delayed / 1.0-14.0
abnormal dreams / Early / 1.0-11.0
fatigue / Early / 3.0-9.0
xerostomia / Early / 3.0-7.0
diarrhea / Early / 1.0-7.0
influenza / Delayed / 0-7.0
nasal congestion / Early / 0-6.0
increased urinary frequency / Early / 6.0-6.0
anorexia / Delayed / 1.0-5.0
muscle cramps / Delayed / 3.0-5.0
vertigo / Early / 2.0-4.0
abdominal pain / Early / 3.0-4.0
vomiting / Early / 4.0-4.0
dyspepsia / Early / 1.0-4.0
infection / Delayed / 0-4.0
hypoesthesia / Delayed / 3.0-3.0
tremor / Early / 3.0-3.0
appetite stimulation / Delayed / 2.0-3.0
back pain / Delayed / 2.0-3.0
malaise / Early / 2.0-3.0
rhinitis / Early / 3.0-3.0
cough / Delayed / 3.0-3.0
paranoia / Early / 2.0-2.0
hypersalivation / Early / 0-2.0
weight loss / Delayed / 2.0-2.0
rash / Early / 2.0-2.0
libido decrease / Delayed / 1.0-1.0
diplopia / Early / 1.0-1.0
fever / Early / 1.0-1.0
syncope / Early / Incidence not known
agitation / Early / Incidence not known
libido increase / Delayed / Incidence not known
weight gain / Delayed / Incidence not known
myalgia / Early / Incidence not known
musculoskeletal pain / Early / Incidence not known
pruritus / Rapid / Incidence not known
urticaria / Rapid / Incidence not known

Mirapex, Mirapex ER

Rx, OTC

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

For the treatment of moderate to severe primary Restless Legs Syndrome (RLS). Oral dosage (immediate-release tablets) Adults

0.125 mg PO once daily in the evening, given 2 to 3 hours before bedtime. If necessary, may increase after 4 to 7 days to 0.25 mg PO once daily in the evening. If necessary, dosage may be further increased after 4 to 7 days to 0.5 mg PO once daily in the evening 2 to 3 hours before bedtime. Max: 0.5 mg/day PO. Dosages higher than 0.5 mg do not appear to provide additional benefits.

For the treatment of the signs and symptoms of idiopathic Parkinson's disease. Oral dosage (immediate-release tablets) Adults

Initially, 0.125 mg PO 3 times per day. Gradually increase by 0.125 to 0.25 mg/dose (0.375 to 0.75 mg/day) every 5 to 7 days. Max: 1.5 mg PO 3 times per day  (4.5 mg/day PO). Use with or without concomitant levodopa up to 800 mg/day. When used in combination with levodopa, consider reducing the levodopa dosage. In a controlled study in advanced Parkinson disease, the dosage of levodopa was reduced an average of 27% from baseline. DISCONTINUATION: Avoid abrupt discontinuation. If discontinuation of treatment becomes necessary, gradually taper the dose over a 1 week period, if possible.

Oral dosage (extended-release tablets) Adults

Initially, 0.375 mg PO once daily. May increase based on efficacy and tolerability up to 0.75 mg PO once daily after a minimum of 5 days. May then increase by 0.75 mg/day no more frequently than every 5 to 7 days. Titration as directed helps limit common side effects, including blood pressure increases. Max: 4.5 mg PO once daily. DISCONTINUATION: If discontinuation becomes necessary, gradually taper in increments of 0.75 mg/day until the daily dose has been reduced to 0.75 mg/day. Thereafter, the dose may be reduced by 0.375 mg/day.

Hepatic Impairment

Hepatic impairment is not expected to have a significant effect on pramipexole clearance; therefore, no dosage adjustments are necessary.

Renal Impairment

Immediate-release tablets in patients with Parkinson's disease:
Normal to mild renal impairment (CrCl greater than 50 mL/minute): No dosage adjustment needed.
Moderate renal impairment (CrCl 30 to 50 mL/minute): Initially, 0.125 mg PO twice daily; max, 1.5 mg PO twice daily.
Severe renal impairment (CrCl 15 to 29 mL/minute): Initially, 0.125 mg PO once daily; max, 1.5 mg PO once daily.
Very severe renal impairment (CrCl less than 15 mL/minute): Use of pramipexole has not been adequately studied.
 
Immediate-release tablets in patients with restless legs syndrome (RLS):
Moderate to severe renal impairment (CrCl 20 to 60 mL/minute): Dosages for RLS remain the same, but use slower titration between dose increases. The duration between titration steps should be increased to 14 days.
 
Extended-release tablets:
Normal to mild renal impairment (CrCl greater than 50 mL/minute): No dosage adjustment needed.
Moderate renal impairment: (CrCl 30 to 50 mL/minute): Initially, 0.375 mg PO every other day; carefully assess response and tolerability before increasing dose. Titrate the dose in 0.375 mg increments at a minimum of weekly intervals; do not exceed 2.25 mg/day PO.
Severe renal impairment (CrCl less than 30 mL/minute): Use of extended-release pramipexole is not recommended.
 
Hemodialysis
Pramipexole clearance is very low and a negligible amount of the drug is removed by dialysis. Immediate-release tablets have not been adequately studied in hemodialysis patients; use of the extended-release tablets in hemodialysis patients has not been studied and is not recommended.

Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Concomitant use of pramipexole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of pramipexole.
Acetaminophen; Caffeine; Dihydrocodeine: (Major) Concomitant use of opioid agonists with pramipexole may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking pramipexole. Limit the use of opioid pain medications with pramipexole 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. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like pramipexole 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.
Acetaminophen; Caffeine; Pyrilamine: (Moderate) Concomitant use of pramipexole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of pramipexole.
Acetaminophen; Chlorpheniramine: (Moderate) Concomitant use of pramipexole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of pramipexole.
Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) Concomitant use of pramipexole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of pramipexole.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Concomitant use of pramipexole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of pramipexole.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Concomitant use of pramipexole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of pramipexole.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Concomitant use of pramipexole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of pramipexole.
Acetaminophen; Codeine: (Major) Concomitant use of opioid agonists with pramipexole may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking pramipexole. Limit the use of opioid pain medications with pramipexole 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. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like pramipexole 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.
Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Concomitant use of pramipexole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of pramipexole.
Acetaminophen; Dichloralphenazone; Isometheptene: (Major) The use of sedatives in combination with pramipexole may increase the risk of clinically significant sedation via a pharmacodynamic interaction.
Acetaminophen; Diphenhydramine: (Moderate) Concomitant use of pramipexole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of pramipexole.
Acetaminophen; Hydrocodone: (Major) Concomitant use of opioid agonists with pramipexole may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking pramipexole. Limit the use of opioid pain medications with pramipexole 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. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like pramipexole 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.
Acetaminophen; Oxycodone: (Major) Concomitant use of opioid agonists with pramipexole may cause excessive sedation and somnolence. Limit the use of opioid pain medications with pramipexole 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. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like pramipexole 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.
Acetaminophen; Pamabrom; Pyrilamine: (Moderate) Concomitant use of pramipexole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of pramipexole.
Acrivastine; Pseudoephedrine: (Moderate) Concomitant use of pramipexole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of pramipexole.
Alfentanil: (Major) Concomitant use of opioid agonists with pramipexole may cause excessive sedation and somnolence. Limit the use of opioid pain medications with pramipexole 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. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like pramipexole 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.
Alprazolam: (Major) Concomitant administration of benzodiazepines with CNS-depressant drugs, including pramipexole, can potentiate the CNS effects.
Amoxapine: (Moderate) Pramipexole may cause additive drowsiness when combined with amoxapine.
Apomorphine: (Moderate) Concomitant administration of apomorphine and CNS depressants, such as pramipexole, could result in additive depressant effects. Careful monitoring is recommended during combined use of pramipexolet 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 pramipexole during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and pramipexole may interfere with the effectiveness of each other. Additive CNS depressant effects are also possible. In general, atypical antipsychotics are less likely to interfere with pramipexole 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 pramipexole during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and pramipexole may interfere with the effectiveness of each other. Additive CNS depressant effects are also possible. In general, atypical antipsychotics are less likely to interfere with pramipexole 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; Carisoprodol; Codeine: (Major) Concomitant use of opioid agonists with pramipexole may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking pramipexole. Limit the use of opioid pain medications with pramipexole 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. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like pramipexole 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.
Aspirin, ASA; Oxycodone: (Major) Concomitant use of opioid agonists with pramipexole may cause excessive sedation and somnolence. Limit the use of opioid pain medications with pramipexole 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. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like pramipexole 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.
Atropine; Difenoxin: (Moderate) The use of opiate agonists in combination with pramipexole may increase the risk of clinically significant sedation via a pharmacodynamic interaction.
atypical antipsychotic: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or pramipexole during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and pramipexole may interfere with the effectiveness of each other. Additive CNS depressant effects are also possible. In general, atypical antipsychotics are less likely to interfere with pramipexole 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 pramipexole.
Azelastine; Fluticasone: (Moderate) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including pramipexole.
Barbiturates: (Major) The use of barbiturates in combination with pramipexole may increase the risk of clinically significant sedation via a pharmacodynamic interaction.
Belladonna; Opium: (Major) Concomitant use of opioid agonists with pramipexole may cause excessive sedation and somnolence. Limit the use of opioid pain medications with pramipexole 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. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like pramipexole 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.
Benzhydrocodone; Acetaminophen: (Major) Concomitant use of opioid agonists with pramipexole may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with pramipexole 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. If benzhydrocodone is initiated in a patient taking pramipexole, reduce initial dosage and titrate to clinical response. If pramipexole is initiated in a patient taking an opioid agonist, use a lower initial dose of pramipexole and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Benzodiazepines: (Major) Concomitant administration of benzodiazepines with CNS-depressant drugs, including pramipexole, can potentiate the CNS effects.
Brexpiprazole: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or pramipexole during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and pramipexole may interfere with the effectiveness of each other. Additive CNS depressant effects are also possible. In general, atypical antipsychotics are less likely to interfere with pramipexole than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Brompheniramine: (Moderate) Concomitant use of pramipexole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of pramipexole.
Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Concomitant use of pramipexole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of pramipexole.
Brompheniramine; Phenylephrine: (Moderate) Concomitant use of pramipexole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of pramipexole.
Brompheniramine; Pseudoephedrine: (Moderate) Concomitant use of pramipexole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of pramipexole.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Concomitant use of pramipexole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of pramipexole.
Buprenorphine: (Moderate) Concomitant use of buprenorphine with other CNS depressants can lead to additive CNS depressive effects. Hypotension, profound sedation, coma, respiratory depression, or death may occur; examples of other CNS depressants can include pramipexole. Prior to concurrent use of buprenorphine 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. 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 can lead to additive CNS depressive effects. Hypotension, profound sedation, coma, respiratory depression, or death may occur; examples of other CNS depressants can include pramipexole. Prior to concurrent use of buprenorphine 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. 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.
Butalbital; Acetaminophen; Caffeine; Codeine: (Major) Concomitant use of opioid agonists with pramipexole may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking pramipexole. Limit the use of opioid pain medications with pramipexole 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. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like pramipexole 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.
Butalbital; Aspirin; Caffeine; Codeine: (Major) Concomitant use of opioid agonists with pramipexole may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking pramipexole. Limit the use of opioid pain medications with pramipexole 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. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like pramipexole 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.
Butorphanol: (Moderate) Concomitant use of butorphanol with other CNS depressants, such as pramipexole, can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation.
Cannabidiol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and pramipexole. CNS depressants can potentiate the effects of cannabidiol.
Carbidopa; Levodopa: (Minor) Pramipexole increases the Cmax of levodopa and decreases Tmax from 2.5 to 0.5 hrs.
Carbidopa; Levodopa; Entacapone: (Moderate) Coadministration of COMT inhibitors and pramipexole may cause additive sedation. 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 should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them. (Minor) Pramipexole increases the Cmax of levodopa and decreases Tmax from 2.5 to 0.5 hrs.
Carbinoxamine: (Moderate) Concomitant use of pramipexole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of pramipexole.
Cariprazine: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or pramipexole during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and pramipexole may interfere with the effectiveness of each other. Additive CNS depressant effects are also possible. In general, atypical antipsychotics are less likely to interfere with pramipexole than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Celecoxib; Tramadol: (Major) Concomitant use of opioid agonists with pramipexole may cause excessive sedation and somnolence. Limit the use of opioid pain medications with pramipexole 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. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like pramipexole 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.
Cenobamate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cenobamate and pramipexole. Concurrent use may result in additive CNS depression. Dopaminergic agents, such as pramipexole, 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 pramipexole 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 pramipexole should generally be avoided because of the possibility of additive sedative effects. Dopaminergic agents have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Chlophedianol; Dexbrompheniramine: (Moderate) Concomitant use of pramipexole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of pramipexole.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Concomitant use of pramipexole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of pramipexole.
Chlorcyclizine: (Moderate) Concomitant use of pramipexole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of pramipexole.
Chlordiazepoxide: (Major) Concomitant administration of benzodiazepines with CNS-depressant drugs, including pramipexole, can potentiate the CNS effects.
Chlordiazepoxide; Amitriptyline: (Major) Concomitant administration of benzodiazepines with CNS-depressant drugs, including pramipexole, can potentiate the CNS effects.
Chlordiazepoxide; Clidinium: (Major) Concomitant administration of benzodiazepines with CNS-depressant drugs, including pramipexole, can potentiate the CNS effects.
Chlorpheniramine: (Moderate) Concomitant use of pramipexole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of pramipexole.
Chlorpheniramine; Codeine: (Major) Concomitant use of opioid agonists with pramipexole may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking pramipexole. Limit the use of opioid pain medications with pramipexole 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. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like pramipexole 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. (Moderate) Concomitant use of pramipexole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of pramipexole.
Chlorpheniramine; Dextromethorphan: (Moderate) Concomitant use of pramipexole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of pramipexole.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Concomitant use of pramipexole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of pramipexole.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Concomitant use of pramipexole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of pramipexole.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Major) Concomitant use of opioid agonists with pramipexole may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking pramipexole. Limit the use of opioid pain medications with pramipexole 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. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like pramipexole 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. (Moderate) Concomitant use of pramipexole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of pramipexole.
Chlorpheniramine; Hydrocodone: (Major) Concomitant use of opioid agonists with pramipexole may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking pramipexole. Limit the use of opioid pain medications with pramipexole 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. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like pramipexole 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. (Moderate) Concomitant use of pramipexole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of pramipexole.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Concomitant use of pramipexole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of pramipexole.
Chlorpheniramine; Phenylephrine: (Moderate) Concomitant use of pramipexole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of pramipexole.
Chlorpheniramine; Pseudoephedrine: (Moderate) Concomitant use of pramipexole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of pramipexole.
Chlorpromazine: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and pramipexole 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. In addition, coadministration may result in additive sedation.
Clemastine: (Moderate) Concomitant use of pramipexole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of pramipexole.
Clobazam: (Moderate) Clobazam, a benzodiazepine, may cause drowsiness or other CNS effects. Potentiation of CNS effects (i.e., increased sedation or respiratory depression) may occur when clobazam is combined with other CNS depressants such as pramipexole.
Clonazepam: (Major) Concomitant administration of benzodiazepines with CNS-depressant drugs, including pramipexole, can potentiate the CNS effects.
Clorazepate: (Major) Concomitant administration of benzodiazepines with CNS-depressant drugs, including pramipexole, can potentiate the CNS effects.
Clozapine: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or pramipexole during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and pramipexole may interfere with the effectiveness of each other. Additive CNS depressant effects are also possible. In general, atypical antipsychotics are less likely to interfere with pramipexole than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Codeine: (Major) Concomitant use of opioid agonists with pramipexole may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking pramipexole. Limit the use of opioid pain medications with pramipexole 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. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like pramipexole 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.
Codeine; Guaifenesin: (Major) Concomitant use of opioid agonists with pramipexole may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking pramipexole. Limit the use of opioid pain medications with pramipexole 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. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like pramipexole 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.
Codeine; Guaifenesin; Pseudoephedrine: (Major) Concomitant use of opioid agonists with pramipexole may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking pramipexole. Limit the use of opioid pain medications with pramipexole 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. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like pramipexole 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.
Codeine; Phenylephrine; Promethazine: (Major) Concomitant use of opioid agonists with pramipexole may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking pramipexole. Limit the use of opioid pain medications with pramipexole 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. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like pramipexole 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. (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and pramipexole 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. In addition, coadministration may result in additive sedation.
Codeine; Promethazine: (Major) Concomitant use of opioid agonists with pramipexole may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking pramipexole. Limit the use of opioid pain medications with pramipexole 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. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like pramipexole 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. (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and pramipexole 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. In addition, coadministration may result in additive sedation.
COMT inhibitors: (Moderate) Coadministration of COMT inhibitors and pramipexole may cause additive sedation. 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 should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
Cyclizine: (Moderate) Concomitant use of pramipexole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of pramipexole.
Cyproheptadine: (Moderate) Concomitant use of pramipexole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of pramipexole.
Deutetrabenazine: (Moderate) Concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as pramipexole, may have additive effects and worsen drowsiness or sedation. Advise patients about worsened somnolence and not to drive or perform other tasks requiring mental alertness until they know how deutetrabenazine affects them.
Dexbrompheniramine: (Moderate) Concomitant use of pramipexole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of pramipexole.
Dexbrompheniramine; Pseudoephedrine: (Moderate) Concomitant use of pramipexole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of pramipexole.
Dexchlorpheniramine: (Moderate) Concomitant use of pramipexole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of pramipexole.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Concomitant use of pramipexole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of pramipexole.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Concomitant use of pramipexole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of pramipexole.
Diazepam: (Major) Concomitant administration of benzodiazepines with CNS-depressant drugs, including pramipexole, can potentiate the CNS effects.
Difelikefalin: (Moderate) Monitor for dizziness, somnolence, mental status changes, and gait disturbances if concomitant use of difelikefalin with CNS depressants is necessary. Concomitant use may increase the risk for these adverse reactions.
Dimenhydrinate: (Moderate) Concomitant use of pramipexole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of pramipexole.
Diphenhydramine: (Moderate) Concomitant use of pramipexole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of pramipexole.
Diphenhydramine; Ibuprofen: (Moderate) Concomitant use of pramipexole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of pramipexole.
Diphenhydramine; Naproxen: (Moderate) Concomitant use of pramipexole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of pramipexole.
Diphenhydramine; Phenylephrine: (Moderate) Concomitant use of pramipexole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of pramipexole.
Diphenoxylate; Atropine: (Moderate) The use of opiate agonists in combination with pramipexole may increase the risk of clinically significant sedation via a pharmacodynamic interaction.
Doxylamine: (Moderate) Concomitant use of pramipexole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of pramipexole.
Doxylamine; Pyridoxine: (Moderate) Concomitant use of pramipexole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of pramipexole.
Dronabinol: (Moderate) Concomitant use of dronabinol with other CNS depressants, such as pramipexole, can potentiate the effects of dronabinol on respiratory depression.
Droperidol: (Major) Droperidol, a butyrophenone derivative, is a dopamine D2 receptor antagonist and thus, may reduce the therapeutic effects of dopamine agonists. Avoidance of droperidol use in a patient with Parkinson's disease may be advisable unless the benefit of droperidol outweighs the risk of CNS depressive effects and decreased therapeutic response to dopamine agonists.
Entacapone: (Moderate) Coadministration of COMT inhibitors and pramipexole may cause additive sedation. 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 should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
Esketamine: (Major) Because of the possibility of additive sedative effects, caution is advisable during concurrent use of dopaminergic agents, such as pramipexole, 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: (Major) Concomitant administration of benzodiazepines with CNS-depressant drugs, including pramipexole, can potentiate the CNS effects.
Eszopiclone: (Moderate) A reduction in the dose of eszopiclone and concomitantly administered dopamine agonists with sedative properties (e.g., ropinirole, pramipexole, rotigotine, apomorphine) should be considered to minimize additive sedative effects. In addition, the risk of next-day psychomotor impairment is increased during co-administration of eszopiclone and other CNS depressants, which may decrease the ability to perform tasks requiring full mental alertness such as driving.
Ethanol: (Major) Advise patients to avoid the ingestion of alcohol-containing beverages while taking pramipexole. The use of alcohol in combination with pramipexole may increase the risk of clinically significant sedation and falling asleep during activities of daily living.
Fenfluramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of fenfluramine and pramipexole. Concurrent use may result in additive CNS depression. Dopaminergic agents, such as pramipexole, have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should reassess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment.
Fentanyl: (Major) Concomitant use of opioid agonists with pramipexole may cause excessive sedation and somnolence. Limit the use of opioid pain medications with pramipexole 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. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like pramipexole 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.
Fluphenazine: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and pramipexole 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. In addition, coadministration may result in additive sedation.
Flurazepam: (Major) Concomitant administration of benzodiazepines with CNS-depressant drugs, including pramipexole, can potentiate the CNS effects.
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 pramipexole. Concomitant use of gabapentin with pramipexole may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents, such as pramipexole, 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.
Guaifenesin; Hydrocodone: (Major) Concomitant use of opioid agonists with pramipexole may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking pramipexole. Limit the use of opioid pain medications with pramipexole 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. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like pramipexole 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.
Haloperidol: (Major) Due to opposing effects on central dopaminergic activity, haloperidol and pramipexole 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. Additive sedation is also possible.
Homatropine; Hydrocodone: (Major) Concomitant use of opioid agonists with pramipexole may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking pramipexole. Limit the use of opioid pain medications with pramipexole 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. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like pramipexole 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.
Hydrocodone: (Major) Concomitant use of opioid agonists with pramipexole may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking pramipexole. Limit the use of opioid pain medications with pramipexole 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. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like pramipexole 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.
Hydrocodone; Ibuprofen: (Major) Concomitant use of opioid agonists with pramipexole may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking pramipexole. Limit the use of opioid pain medications with pramipexole 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. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like pramipexole 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.
Hydrocodone; Pseudoephedrine: (Major) Concomitant use of opioid agonists with pramipexole may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking pramipexole. Limit the use of opioid pain medications with pramipexole 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. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like pramipexole 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.
Hydromorphone: (Major) Concomitant use of opioid agonists with pramipexole may cause excessive sedation and somnolence. Limit the use of opioid pain medications with pramipexole 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. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like pramipexole 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.
Hydroxyzine: (Moderate) Concomitant use of pramipexole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of pramipexole.
Ibuprofen; Oxycodone: (Major) Concomitant use of opioid agonists with pramipexole may cause excessive sedation and somnolence. Limit the use of opioid pain medications with pramipexole 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. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like pramipexole 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.
Iloperidone: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or pramipexole during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and pramipexole may interfere with the effectiveness of each other. Additive CNS depressant effects are also possible. In general, atypical antipsychotics are less likely to interfere with pramipexole 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.
Lasmiditan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and pramipexole. Concurrent use may result in additive CNS depression. Dopaminergic agents, such as pramipexole, 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 pramipexole. Dosage adjustments of lemborexant and pramipexole 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 pramipexole 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.
Levodopa: (Minor) Pramipexole increases the Cmax of levodopa and decreases Tmax from 2.5 to 0.5 hrs.
Levorphanol: (Major) Concomitant use of opioid agonists with pramipexole may cause excessive sedation and somnolence. Limit the use of opioid pain medications with pramipexole 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. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like levorphanol 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.
Lofexidine: (Major) Monitor for excessive hypotension and sedation during coadministration of lofexidine and pramipexole. Lofexidine can potentiate the effects of CNS depressants.
Lorazepam: (Major) Concomitant administration of benzodiazepines with CNS-depressant drugs, including pramipexole, can potentiate the CNS effects.
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 pramipexole during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and pramipexole may interfere with the effectiveness of each other. Additive CNS depressant effects are also possible. In general, atypical antipsychotics are less likely to interfere with pramipexole 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 pramipexole during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and pramipexole may interfere with the effectiveness of each other. Additive CNS depressant effects are also possible. In general, atypical antipsychotics are less likely to interfere with pramipexole 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) Pramipexole may cause additive drowsiness when combined with maprotiline.
Meclizine: (Moderate) Concomitant use of pramipexole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of pramipexole.
Meperidine: (Major) Concomitant use of opioid agonists with pramipexole may cause excessive sedation and somnolence. Limit the use of opioid pain medications with pramipexole 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. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like pramipexole 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.
Methadone: (Major) Concomitant use of opioid agonists with pramipexole may cause excessive sedation and somnolence. Limit the use of opioid pain medications with pramipexole 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. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like pramipexole 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.
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 pramipexole, should be used with caution. Additive drowsiness and/or dizziness is possible.
Midazolam: (Major) Concomitant administration of benzodiazepines with CNS-depressant drugs, including pramipexole, can potentiate the CNS effects.
Mirtazapine: (Moderate) Some medicines used for treatment of Parkinson's disease, like pramipexole, could potentially cause additive drowsiness when coadministered with mirtazapine.
Molindone: (Major) Due to opposing effects on central dopaminergic activity, molindone and dopamine agonists may interfere with the effectiveness of each other. Avoid concurrent use if possible and consider an atypical antipsychotic as an alternative to molindone. If coadministration cannot be avoided, monitor for changes in movement, moods, or behaviors.
Morphine: (Major) Concomitant use of opioid agonists with pramipexole may cause excessive sedation and somnolence. Limit the use of opioid pain medications with pramipexole 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. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like pramipexole 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.
Morphine; Naltrexone: (Major) Concomitant use of opioid agonists with pramipexole may cause excessive sedation and somnolence. Limit the use of opioid pain medications with pramipexole 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. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like pramipexole 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.
Nabilone: (Moderate) Concomitant use of nabilone with other CNS depressants, like pramipexole, can potentiate the effects of nabilone on respiratory depression.
Nalbuphine: (Moderate) Concomitant use of nalbuphine with other CNS depressants, like pramipexole, can potentiate the effects of nalbuphine on respiratory depression, CNS depression, and sedation.
Olanzapine: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or pramipexole during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and pramipexole may interfere with the effectiveness of each other. Additive CNS depressant effects are also possible. In general, atypical antipsychotics are less likely to interfere with pramipexole 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 pramipexole during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and pramipexole may interfere with the effectiveness of each other. Additive CNS depressant effects are also possible. In general, atypical antipsychotics are less likely to interfere with pramipexole 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 pramipexole during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and pramipexole may interfere with the effectiveness of each other. Additive CNS depressant effects are also possible. In general, atypical antipsychotics are less likely to interfere with pramipexole than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Oliceridine: (Major) Concomitant use of oliceridine with pramipexole may cause excessive sedation and somnolence. Limit the use of oliceridine with pramipexole 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.
Opicapone: (Moderate) Coadministration of COMT inhibitors and pramipexole may cause additive sedation. 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 should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
Oxazepam: (Major) Concomitant administration of benzodiazepines with CNS-depressant drugs, including pramipexole, can potentiate the CNS effects.
Oxycodone: (Major) Concomitant use of opioid agonists with pramipexole may cause excessive sedation and somnolence. Limit the use of opioid pain medications with pramipexole 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. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like pramipexole 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.
Oxymorphone: (Major) Concomitant use of opioid agonists with pramipexole may cause excessive sedation and somnolence. Limit the use of opioid pain medications with pramipexole 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. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like pramipexole 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.
Paliperidone: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or pramipexole during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and pramipexole may interfere with the effectiveness of each other. Additive CNS depressant effects are also possible. In general, atypical antipsychotics are less likely to interfere with pramipexole 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.
Pentazocine: (Moderate) Concomitant use of pentazocine with other CNS depressants, such as pramipexole, can potentiate respiratory depression, CNS depression, and sedation.
Pentazocine; Naloxone: (Moderate) Concomitant use of pentazocine with other CNS depressants, such as pramipexole, can potentiate respiratory depression, CNS depression, and sedation.
Perampanel: (Moderate) Use of perampanel with CNS depressants may increase CNS depression. Perampanel (particularly at high doses) 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; these effects may be additive to the concomitant use of other CNS depressants, such as pramipexole.
Perphenazine: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and pramipexole 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. In addition, coadministration may result in additive sedation.
Perphenazine; Amitriptyline: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and pramipexole 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. In addition, coadministration may result in additive sedation.
Phenothiazines: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and pramipexole 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. In addition, coadministration may result in additive sedation.
Pimozide: (Major) Due to opposing effects on central dopaminergic activity, pimozide and pramipexole 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. In addition, coadministration may result in additive sedation.
Pregabalin: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and pramipexole. Concomitant use of pregabalin with pramipexole may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents, such as pramipexole, 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.
Prochlorperazine: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and pramipexole 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. In addition, coadministration may result in additive sedation.
Promethazine: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and pramipexole 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. In addition, coadministration may result in additive sedation.
Promethazine; Dextromethorphan: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and pramipexole 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. In addition, coadministration may result in additive sedation.
Promethazine; Phenylephrine: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and pramipexole 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. In addition, coadministration may result in additive sedation.
Pseudoephedrine; Triprolidine: (Moderate) Concomitant use of pramipexole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of pramipexole.
Pyrilamine: (Moderate) Concomitant use of pramipexole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of pramipexole.
Quazepam: (Major) Concomitant administration of benzodiazepines with CNS-depressant drugs, including pramipexole, can potentiate the CNS effects.
Quetiapine: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or pramipexole during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and pramipexole may interfere with the effectiveness of each other. Additive CNS depressant effects are also possible. In general, atypical antipsychotics are less likely to interfere with pramipexole 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.
Remifentanil: (Major) Concomitant use of opioid agonists with pramipexole may cause excessive sedation and somnolence. Limit the use of opioid pain medications with pramipexole 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. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like pramipexole 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.
Remimazolam: (Major) Concomitant administration of benzodiazepines with CNS-depressant drugs, including pramipexole, can potentiate the CNS effects.
Risperidone: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or pramipexole during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and pramipexole may interfere with the effectiveness of each other. Additive CNS depressant effects are also possible. In general, atypical antipsychotics are less likely to interfere with pramipexole 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.
Sedating H1-blockers: (Moderate) Concomitant use of pramipexole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of pramipexole.
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 pramipexole. Caution is recommended since this combination has not been evaluated.
Stiripentol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and pramipexole. CNS depressants can potentiate the effects of stiripentol.
Sufentanil: (Major) Concomitant use of opioid agonists with pramipexole may cause excessive sedation and somnolence. Limit the use of opioid pain medications with pramipexole 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. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like pramipexole 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.
Suvorexant: (Moderate) CNS depressant drugs may have cumulative effects when administered concurrently and they should be used cautiously with suvorexant. A reduction in dose of the CNS depressant may be needed in some cases.
Tapentadol: (Major) Concomitant use of opioid agonists with pramipexole may cause excessive sedation and somnolence. Limit the use of opioid pain medications with pramipexole 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. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like pramipexole 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.
Temazepam: (Major) Concomitant administration of benzodiazepines with CNS-depressant drugs, including pramipexole, can potentiate the CNS effects.
Thalidomide: (Major) Avoid the concomitant use of thalidomide with other central nervous system depressants such as pramipexole due to the potential for additive sedative effects.
Thioridazine: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and pramipexole 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. In addition, coadministration may result in additive sedation.
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.
Tolcapone: (Moderate) Coadministration of COMT inhibitors and pramipexole may cause additive sedation. 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 should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
Tramadol: (Major) Concomitant use of opioid agonists with pramipexole may cause excessive sedation and somnolence. Limit the use of opioid pain medications with pramipexole 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. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like pramipexole 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.
Tramadol; Acetaminophen: (Major) Concomitant use of opioid agonists with pramipexole may cause excessive sedation and somnolence. Limit the use of opioid pain medications with pramipexole 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. Educate patients about the risks and symptoms of excessive CNS depression. Dopaminergic agents like pramipexole 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.
Triazolam: (Major) Concomitant administration of benzodiazepines with CNS-depressant drugs, including pramipexole, can potentiate the CNS effects.
Tricyclic antidepressants: (Moderate) Pramipexole may cause additive drowsiness when combined with tricyclic antidepressants.
Trifluoperazine: (Major) Due to opposing effects on central dopaminergic activity, phenothiazines and pramipexole 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. In addition, coadministration may result in additive sedation.
Triprolidine: (Moderate) Concomitant use of pramipexole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of pramipexole.
Zaleplon: (Moderate) The use of zaleplon in combination with pramipexole may increase the risk of clinically significant sedation via a pharmacodynamic interaction.
Ziconotide: (Moderate) Pramipexole is a CNS depressant medication that may increase drowsiness, dizziness, and confusion that are associated with ziconotide. Due to potentially additive effects, dosage adjustments may be necessary if ziconotide is used with a drug that has CNS depressant effects.
Ziprasidone: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or pramipexole during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and pramipexole may interfere with the effectiveness of each other. Additive CNS depressant effects are also possible. In general, atypical antipsychotics are less likely to interfere with pramipexole 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) Other CNS depressant drugs, such as pramipexole, may have cumulative effects when administered concurrently with zolpidem and they should be used cautiously with zolpidem. 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. Concurrent use of zolpidem with other sedative-hypnotics, including other zolpidem products, at bedtime or the middle of the night is not recommended.

Mirapex ER/Pramipexole/Pramipexole Dihydrochloride Oral Tab ER: 0.375mg, 0.75mg, 1.5mg, 2.25mg, 3mg, 3.75mg, 4.5mg
Mirapex/Pramipexole/Pramipexole Dihydrochloride Oral Tab: 0.125mg, 0.25mg, 0.5mg, 0.75mg, 1mg, 1.5mg

Adults

4.5 mg/day PO.

Geriatric

4.5 mg/day PO.

Adolescents

Safety and efficacy have not been established.

Children

Safety and efficacy have not been established.

Infants

Not indicated.

Pramipexole is a nonergot dopamine agonist; pramipexole is a full dopamine agonist, unlike bromocriptine and pergolide which are partial agonists. Pramipexole binds to D2 and D3 dopamine receptors in the striatum and substantia nigra. It is more selective for the D3 receptor than either bromocriptine or pergolide; bromocriptine is an agonist at D2 dopamine receptors, while pergolide stimulates both type 1 and type 2 dopamine receptors. The relevance of D1 receptor binding in Parkinson's disease is unknown. Pramipexole has no significant effect on other peripheral or central adrenergic or serotonergic receptor families. The exact mechanism of action of pramipexole in the treatment of Restless Legs Syndrome (RLS) is not known. Dopaminergic pathways (e.g., presynaptic dopaminergic dysfunction) are thought to be involved in the pathogenesis of RLS, which presumably explains the benefits of dopamine agonists such as pramipexole in the treatment of the syndrome.

Pramipexole is administered orally as immediate-release and extended-release tablets. Pramipexole has an extensive volume of distribution. Plasma protein binding is negligible (15%). No metabolites of pramipexole have been identified. Renal clearance of pramipexole is approximately 3-times higher than the glomerular filtration rate. Thus, pramipexole is secreted by the renal tubules, probably by the organic cation transport system. About 90% of a dose is eliminated renally as unchanged drug. The elimination half-life is about 8 hours in young healthy adult volunteers and about 12 hours in elderly volunteers.
 
Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: None reported
Pramipexole is secreted by the renal tubules, probably by the organic cation transport system.

Oral Route

The absolute bioavailability of pramipexole is greater than 90%; food does not have a clinically significant effect on absorption. The relative bioavailability of the extended-release (ER) formulation compared to the immediate-release (IR) formulation is 100%. Peak serum concentrations of the IR formulation are achieved approximately 2 hours after an oral dose, while the average time to peak of the ER tablets is 6 hours post-dose. Both the IR and ER formulations display linear kinetics, and their minimum and maximum plasma concentrations after the same total daily dose are equivalent. With continuous dosing, steady-state concentrations of the IR and ER tablets are attained within 2 days and 5 days, respectively.

Pregnancy

There are no adequate data regarding fetal developmental risks associated with the use of pramipexole in human pregnancy. The low molecular weight and pharmacokinetic profile of the drug suggest that placental transfer is likely. In one case report, a woman with Parkinson's disease receiving pramipexole throughout her pregnancy gave birth by caserean section to a healthy infant with an Apgar score of 9. At 6 months, the infant showed normal development. In animal studies, no adverse developmental effects were observed in rabbits due to pramipexole exposure during pregnancy. Pramipexole was associated with impaired implantation and maintenance of early pregnancy in rat studies. These findings were thought to be due to the prolactin lowering effects of pramipexole, since prolactin is necessary for implantation and early maintenance of pregnancy in rats, but not in humans. Postnatal growth was inhibited in the offspring of rats treated with pramipexole during the latter part of pregnancy and throughout lactation. The effects of pramipexole during labor and obstetric delivery in humans are unknown.

The developmental and health benefits of breast-feeding should be considered along with the mother's clinical need for pramipexole and any potential adverse effects on the breast-fed infant or from the underlying maternal condition being treated. It is not known if pramipexole is excreted in human breast milk and the effects of pramipexole exposure on the nursing infant are unknown. However, inhibition of lactation is expected because pramipexole inhibits secretion of prolactin in humans. Pramipexole is excreted into the breast milk of lactating rats at concentrations 3 to 6 times those in the maternal plasma.