Pramipexole is an oral non-ergot dopamine agonist. Immediate-release pramipexole is indicated for use in adults for the treatment of Parkinson's disease and the treatment of moderate to severe primary restless legs syndrome (RLS). An extended-release formulation is indicated only for the treatment of Parkinson's disease. Clinical practice guidelines suggest that non-ergot dopamine agonists (including pramipexole) may be used as first-line pharmacologic options for early Parkinson's disease in younger patients (less than 60 years old) who are at high risk for the development of levodopa-induced dyskinesias. Nausea, dizziness, and somnolence are common side effects associated with pramipexole, and orthostatic hypotension has been reported during initiation and dose titration. Serious adverse effects of pramipexole and other dopamine agonists include hallucinations and psychotic-like behavior, impulse control symptoms, and sleep attacks (falling asleep during activities of daily living). Older patients have an increased risk for cognitive and behavioral adverse effects from dopamine agonists; thus, levodopa therapy generally has a more favorable benefit to risk ratio in this patient population.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
Oral Solid Formulations
Immediate-release tablets:
-May administer with or without food; 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.
During clinical trials of immediate-release pramipexole in the treatment of early or advanced Parkinson's disease (PD), the following centrally-mediated effects were reported more frequently in patients receiving pramipexole than placebo: drowsiness (9% to 36%), dizziness (25% to 26%), insomnia (17% to 27%), hypoesthesia (3%), asthenia (10% to 14%), gait abnormalities (7%), and myoclonia (1%). In a double-blind, placebo controlled trial of patients with early PD (without concomitant levodopa), the frequencies of adverse effects reported with immediate-release pramipexole and extended-release pramipexole were as follows: dizziness (12%, 12%), tremor (3%, 3%), asthenia (1%, 3%), vertigo (2%, 4%), insomnia (4%, 4%), and balance disorder (0%, 2%). In a double-blind, placebo controlled trial of patients with advanced PD receiving levodopa, adverse effects reported with immediate-release pramipexole and extended-release pramipexole, respectively, were as follows: headache (4%, 7%), postural dizziness (3%, 2%), and insomnia (4%, 4%). In clinical trials for restless legs syndrome (RLS), the following CNS effects occurred more frequently in patients receiving pramipexole than placebo: drowsiness (6%), headache (16%), and insomnia (9% to 13%). Syncope has also been reported during postmarketing use of pramipexole.
During clinical trials of immediate-release pramipexole in the treatment of early or advanced Parkinson's disease, the following psychiatric effects were reported more frequently with pramipexole than placebo: confusion (4% to 10%), amnesia (4% to 6%), abnormal dreams (11%), abnormal thinking (2% to 3%), libido decrease (1%), paranoia (2%), delusions (1%), and hallucinations (9% to 17%). In a double-blind, placebo-controlled trial of patients with early Parkinson's disease (without concomitant levodopa), the following psychiatric adverse effects were reported more frequently with immediate-release pramipexole and extended-release pramipexole than placebo: depression (0%, 2%) and auditory/visual hallucinations (6%, 5%). In a double-blind, placebo-controlled trial of patients with advanced Parkinson's disease receiving levodopa, auditory and/or visual hallucinations were reported more frequently with immediate-release pramipexole/levodopa and extended-release pramipexole/levodopa than levodopa monotherapy (7%, 9%, 2%). The relative risk of hallucinations is increased in elderly patients with PD. In patients with early PD receiving immediate-release pramipexole, the risk of hallucinations was 1.9 times greater than placebo in adults less than 65 years and 6.8 times greater than placebo in patients older than 65 years. In advanced PD patients, the risk of hallucinations was 3.5 times greater than placebo in patients younger than 65 years and 5.2 times greater than placebo in patients older than 65 years. During a clinical trial of extended-release pramipexole, hallucinations occurred in 8% of those 65 years and older compared to 3% of those under 65 years. In clinical trials of immediate-release pramipexole for restless legs syndrome (RLS), abnormal dreams were reported in 1% to 8% of patients receiving pramipexole and more frequently than in those receiving placebo. One patient with RLS experienced hallucinations, which resolved following treatment discontinuation. Other mental status and behavioral changes, including psychotic-like behavior, symptoms of mania (e.g., insomnia, psychomotor agitation), disorientation, aggressive behavior, agitation, psychosis, and delirium have been reported in patients treated with pramipexole.
Some patients receiving medications that increase dopaminergic tone have reported intense and uncontrollable urges to gamble, increased sexual urges, other intense impulse control symptoms, as well as the inability to control the urges. Binge eating, compulsive eating, compulsive shopping, hypersexuality (excessive libido increase), and pathological gambling were detected in a cross-sectional study and in case reports. Practitioners should inquire periodically about new or worsening impulse control symptoms in patients receiving pramipexole and instruct patients to report these types of events. Dose reduction or discontinuation should be considered in those who experience these effects; in some cases (but not all), urges have stopped after these adjustments.
There have been reports of patients who have fallen asleep while performing activities of daily living, including driving, while receiving pramipexole. Excessive drowsiness has, in some cases, occurred as late as 1 year after the initiation of treatment. In some cases, sudden sleep onset due to pramipexole has resulted in auto accidents. During a clinical trial of early Parkinson's disease patients, sudden sleep onset or sleep attacks were reported more frequently in those receiving pramipexole immediate-release tablets (6%) and extended-release tablets (3%) than with placebo. Unspecified sleep disorders were reported in clinical trials of immediate-release pramipexole (1% to 3%). Symptoms of excessive drowsiness may not be preceded by warning signs. The use of concomitant CNS depressant medications or the presence of sleep disorders may increase the risks of these events. Those who have experienced somnolence or a sudden episode of sleep while taking the drug should avoid activities such as driving or operating machinery, working at heights, or performing other tasks that require alertness. Assess for oversedation throughout pramipexole therapy; patients should report if they fall asleep during normal activities. Pramipexole should generally be discontinued in patients who experience episodes of falling asleep while engaged in activities of daily living. It is not known if a reduction in dosage will subsequently reduce or eliminate excessive somnolence or sudden episodes of sleep.
During clinical trials of immediate-release pramipexole in the treatment of early or advanced Parkinson's disease (PD), the following extrapyramidal effects were reported more frequently with pramipexole than placebo: dystonic reaction (2% to 8%), akathisia (2% to 3%), dyskinesia (47%), extrapyramidal syndrome (unspecified) (28%), and hypertonia (7%). In a double-blind, placebo controlled trial of patients with advanced PD receiving levodopa, dyskinesia was reported with immediate-release pramipexole/levodopa (18%), extended-release pramipexole/levodopa (17%), and levodopa monotherapy (8%). The incidence of these side effects may be influenced by indication for use; in clinical trials of immediate-release pramipexole for restless legs syndrome (RLS), no extrapyramidal effects were reported. Postural deformities, including antecollis, camptocormia (Bent Spine Syndrome), and pleurothotonus (Pisa Syndrome) have been reported in patients after starting or increasing the dose of pramipexole. Postural deformities may occur several months after initiation of treatment or a dose increase. The drug might worsen a pre-existing deformity. Reducing the dose or discontinuing pramipexole has been associated with an improvement in postural deformities in some patients, and should be considered if a postural deformity occurs.
Gastrointestinal (GI) effects are among the most common adverse events associated with pramipexole therapy. During clinical trials of immediate-release pramipexole in the treatment of early or advanced Parkinson's disease (PD), the following GI effects were reported more frequently with pramipexole than placebo: nausea (28%), constipation (10% to 14%), anorexia (4%), dysphagia (2%), xerostomia (7%), and weight loss (2%). The adverse event that most commonly resulted in treatment discontinuation was nausea (1%). In a double-blind, placebo controlled trial of patients with early PD (without concomitant levodopa), the frequencies of GI adverse effects reported with immediate-release pramipexole and extended-release pramipexole were as follows: nausea (24%; 22%), vomiting (4%; 4%), xerostomia (4%; 5%), upper abdominal pain (4%; 3%), dyspepsia (3%; 3%), abdominal discomfort (1%; 2%), appetite stimulation (2%; 3%) and constipation (12%; 14%). In a double-blind, placebo controlled trial of patients with advanced PD receiving levodopa, the frequencies of adverse effects reported with immediate-release pramipexole/levodopa, extended-release pramipexole/levodopa, and levodopa monotherapy, respectively, were as follows: anorexia (1%; 5%; 2%), nausea (11%; 11%; 10%), constipation (6%; 7%; 5%), hypersalivation (0%; 2%; 0%), and diarrhea (1%; 2%; 1%). In clinical trials of immediate-release pramipexole for restless legs syndrome (RLS), the following GI effects were reported in the pramipexole group at higher rates than with placebo: nausea (11% to 27%), constipation (4%), diarrhea (1% to 7%), dyspepsia (1% to 4%), and xerostomia (3%). Vomiting and weight gain have been reported during postmarketing use of pramipexole. There are also postmarketing reports of tablet residue from pramipexole ER tablets appearing in the stool and resembling a swollen whole tablet or swollen pieces of the tablet. Some patients have reported a worsening of their PD symptoms in conjunction with the appearance of tablet residue. A re-evaluation of the use of ER pramipexole may be needed if this occurs. Have patients contact their provider if they observe tablet residue in their stool.
Dopamine agonists can cause hypotension or orthostatic hypotension (OH). During a clinical trial in patients with early Parkinson's disease (PD), immediate-release pramipexole did not cause OH to a greater extent than placebo at dosages of 1.5 mg per day PO or less. The incidence of OH increases as the dosage of pramipexole is increased from 1.5 mg to 6 mg per day. The frequency of OH was generally 2-fold higher than placebo in those patients taking more than 3 mg per day of pramipexole. In a study of patients with advanced PD, OH occurred in 53% of patients receiving pramipexole and 48% of patients receiving placebo. In a double-blind, placebo controlled trial of patients with early PD (without concomitant levodopa), the frequency of OH with immediate-release pramipexole was 0% and 3% with extended-release pramipexole. Careful titration of dose increases may minimize the potential for OH.
During clinical trials of immediate-release pramipexole in the treatment of early or advanced Parkinson's disease (PD), the following musculoskeletal-related effects were reported more frequently in patients receiving pramipexole than placebo: accidental injury (17%), arthritis (3%), twitching (2%), bursitis (2%), and myasthenia (1%). In a double-blind, placebo controlled trial of patients with early PD (without concomitant levodopa), muscle spasms or muscle cramps were reported with immediate-release pramipexole (3%) and extended-release pramipexole (5%). In a double-blind, placebo controlled trial of patients with advanced PD receiving levodopa, back pain was reported with immediate-release pramipexole/levodopa (3%), extended-release pramipexole/levodopa (2%), and levodopa monotherapy (1%). A case of rhabdomyolysis with myalgia in a patient with advanced PD treated with pramipexole has been reported; the symptoms resolved after discontinuation of the drug. Increased creatine phosphokinase (1%) was reported more frequently in PD patients receiving pramipexole than placebo. In clinical trials for restless legs syndrome (RLS), pain in an extremity (musculoskeletal pain) occurred more frequently in patients receiving pramipexole (3% to 7%) than placebo.
During clinical trials of immediate-release pramipexole in the treatment of early or advanced Parkinson's disease (PD), the following ophthalmic effects were reported more frequently in patients receiving pramipexole than placebo: visual impairment (3%), accomodation abnormalities (blurred vision) (4%), and diplopia (1%). Unspecified vision abnormalities were reported during other clinical trial evaluations of pramipexole. In a 2-year safety study of retinal deterioration and vision, 234 patients with PD were randomized to pramipexole (n = 115; mean dose 3 mg per day PO) or comparator (ropinirole). Clinically meaningful abnormalities developed in 29/196 PD patients treated for 2 years (19 patients in each treatment arm had received treatment for less than 2 years). There was no statistically significant difference in retinal deterioration between the treatment arms; however, the study was only capable of detecting a very large difference between treatments. Because the study did not include a placebo group, a causal relationship to either drug cannot be established. It is nor known if the findings reported are greater than the usual background rate in older adults.
During clinical trials of immediate-release pramipexole in the treatment of early or advanced Parkinson's disease, the following general effects were reported more frequently in patients receiving pramipexole than placebo: general edema (4% to 5%), malaise (2% to 3%), and peripheral edema (2% to 5%). In clinical trials for restless legs syndrome (RLS), fatigue (3% to 9%) occurred more frequently in patients receiving pramipexole than placebo. In a double-blind, placebo controlled trial of patients with early Parkinson's disease (without concomitant levodopa), the frequencies of adverse effects reported with immediate-release pramipexole and extended-release pramipexole, respectively, were as follows: fatigue (6%, 6%), fall (4%, 4%), and peripheral edema (8%, 5%).
During clinical trials of immediate-release pramipexole in the treatment of advanced Parkinson's disease, rash (unspecified), described as unspecified skin disorders, was reported more frequently in patients receiving pramipexole (2%) than placebo. Other skin reactions, including erythema, pruritus, and urticaria, have been reported during postmarketing use of pramipexole for various indications.
During clinical trials of immediate-release pramipexole in the treatment of early or advanced Parkinson's disease, the following infections or related symptoms were reported more frequently in patients receiving pramipexole than placebo: fever (1%) urinary tract infection (4%), and pneumonia (2%). In clinical trials for restless legs syndrome (RLS), influenza was reported in 1% to 7% of patients receiving pramipexole and at rates higher than with placebo.
During clinical trials of immediate-release pramipexole in the treatment of advanced Parkinson's disease (PD), the following respiratory effects were reported more frequently in patients receiving pramipexole than placebo: dyspnea (4%) and rhinitis (3%). In a double-blind, placebo controlled trial of patients with early PD (without concomitant levodopa), cough was reported with immediate-release pramipexole (3%) and extended-release pramipexole (3%) at higher rates than with placebo. In clinical trials for restless legs syndrome (RLS), nasal congestion occurred more frequently in patients receiving pramipexole (6% or less) than placebo. Cases of retroperitoneal fibrosis, pulmonary infiltrates, pleural effusion, pleural thickening, pericarditis, and cardiac valvulopathy have been reported with ergot-derived dopamine agonists (e.g., bromocriptine, pergolide), and these adverse events are believed to be related to the ergoline structure of these compounds. Pramipexole, a non-ergot derived dopamine agonist, has been associated with cases of possible fibrotic complications, including retroperitoneal fibrosis, pleural fibrosis, and pulmonary fibrosis; the evidence is not sufficient to establish a causal relationship between pramipexole and these fibrotic complications, a contribution of pramipexole cannot be completely ruled out.
During clinical trials of immediate-release pramipexole in the treatment of early Parkinson's disease, impotence (erectile dysfunction) was reported more frequently in male patients receiving pramipexole (2%) than with placebo. Impotence has not been reported with extended-release tablets.
During clinical trials of immediate-release pramipexole in the treatment of advanced Parkinson's disease, the following urogenital effects were reported more frequently with pramipexole than placebo: increased urinary frequency (6%) and urinary incontinence (2%).
The syndrome of inappropriate antidiuretic hormone secretion (SIADH) has been reported during postmarketing use of pramipexole. The frequency is unknown and causality to the drug has not been established.
Chest pain (unspecified) was reported in 3% of patients with advanced Parkinson's disease receiving immediate-release pramipexole and at a higher rate than with placebo. Increases in blood pressure (systolic and diastolic increases of 10 mmHg and 7 mmHg, respectively) and heart rate (10 bpm more than placebo) were seen in a study of healthyt volunteers who were up-titrated from 0.375 mg to 4.5 mg of pramipexole daily over 6 days. Mean values remained in normal reference ranges throughout the study; these effects have not been demonstrated in clinical trials involving Parkinson's disease patients who were titrated according to clinical recommendations. Additionally, no dose- or exposure-related effects on mean QT intervals were detected among the healthy volunteers.
Heart failure has been reported during postmarketing use of pramipexole. In September 2012, the FDA warned patients and health care providers that pramipexole may be associated with an increased risk of heart failure. Analyses of clinical trials found that heart failure occurred more often in patients taking pramipexole vs. placebo; however, study limitations and confounding factors prevented definitive conclusions regarding risk. Pramipexole is associated with peripheral edema, which may have led to increased testing and detection of heart failure in those taking pramipexole, despite sensitivity analyses that were performed. The FDA continues to work with the manufacturer to determine the risk of heart failure and will communicate information as it becomes available. Counsel patients on the risks and benefits of pramipexole therapy, as well as symptoms of heart failure that should be reported to their health care provider. Adverse effects should be reported to the FDA MedWatch program.
A withdrawal or discontinuation syndrome has been associated with the abrupt stoppage of dopamine agonist therapy, such as pramipexole, in Parkinson's disease patients. Discontinuation symptoms of apathy, anxiety, depression, fatigue, insomnia, sweating, and pain have been reported in patients with Parkinson's disease during dosage tapering or treatment discontinuation; these symptoms generally do not respond to treatment with levodopa. Closely monitor these patients during and after treatment discontinuation. Re-administration at the lowest effective pramipexole dose may be considered if severe withdrawal symptoms develop. Rarely, neuroleptic malignant syndrome-like symptoms (e.g. hyperpyrexia, muscular rigidity, altered consciousness, autonomic instability) have been reported in association with rapid dose reduction or rapid withdrawal of antiparkinson therapy. Although not reported with pramipexole in initial clinical trials, it is recommended that pramipexole be discontinued over a period of 1 week in Parkinson's disease patients to avoid this potential withdrawal reaction.
Restless legs syndrome (RLS) augmentation occurs when dopamine agonists, such as pramipexole, cause a worsening of RLS symptom severity above and beyond the level at the time the medication was started or may involve an earlier time of symptom onset each day compared to pre-treatment levels. Augmentation symptoms may include the earlier onset of symptoms in the evening or afternoon, increase in symptoms, or spread of symptoms to involve other extremities. Restless legs syndrome (RLS) rebound is an exacerbation of RLS symptoms and is considered to be an end-of-dose effect related to the half-life of the drug. Rebound has been observed during discontinuation of the dopaminergic agent, and in the early morning hours during ongoing treatment (also known as early-morning rebound). If augmentation or early-morning rebound occurs, the use of pramipexole should be re-assessed, and a dosage adjustment or discontinuation of treatment should be considered. When discontinuing pramipexole, a gradual taper is recommended to minimize rebound effects.
Caution is advised in using pramipexole in patients with cardiac disease or predisposed to hypotension. Dopamine agonists, including pramipexole, can cause orthostatic hypotension especially during dose escalation. In clinical trials for pramipexole, patients were carefully titrated and those with active cardiovascular disease or significant orthostatic hypotension at baseline were excluded. In addition, Parkinson's disease patients appear to have an impaired capacity to respond to an orthostatic challenge. Clinical trials in patients with restless legs syndrome (RLS) did not incorporate orthostatic challenges with extensive blood pressure monitoring in close temporal proximity to dosing. Therefore, patients with either Parkinson's disease or RLS should be monitored closely for symptoms of orthostatic hypotension; careful titration may minimize the potential for this adverse effect.
Pramipexole commonly causes somnolence. Sudden sleep onset has been reported during the use of dopamine agonists, including pramipexole. Some incidents have occurred while the patient was driving or performing other potentially hazardous activities. In some cases, excessive drowsiness due to dopamine agonists has resulted in auto accidents or other harmful events in the course of daily living. Sudden sleep onset has occurred as late as 1 year after the initiation of treatment. Prior to initiating treatment with pramipexole, patients should be advised of the potential for somnolence and assessed for factors that may increase the risk of experiencing such an event including the presence of sleep disorders (e.g., narcolepsy, sleep apnea), ethanol ingestion, or coadministration with other CNS depressants or other interacting medications that increase pramipexole concentrations. Patients should be cautioned against driving or operating machinery or performing other tasks that require alertness until they gauge how pramipexole affects their motor performance. Assessment for somnolence is necessary throughout pramipexole therapy because patients may not acknowledge drowsiness or sleepiness until directly questioned about drowsiness or sleepiness during specific activities. If a patient develops significant daytime sleepiness or episodes of falling asleep during activities that require active participation (e.g., conversations, eating, etc.), pramipexole should ordinarily be discontinued. If a decision is made to continue the drug, patients should be advised to not drive and to avoid other potentially dangerous activities. There is insufficient information to establish that dose reduction will eliminate episodes of falling asleep while engaged in activities of daily living.
Some patients receiving medications that increase dopaminergic tone, such as medications used to treat Parkinson's disease, have reported intense and uncontrollable urges to gamble, increased sexual urges, or other intense urges. Causality due to dopaminergic agents has not been established; however, in some cases, the urges stopped after the dose was reduced or the drug was discontinued. Practitioners should inquire periodically about new or worsening impulse control symptoms in patients receiving pramipexole because patients may not recognize these behaviors as abnormal. Likewise, patients should be instructed to report such changes while receiving pramipexole. Dose reduction or discontinuation should be considered in those who experience these effects.
Due to the risk of psychosis exacerbation, patients with psychotic disorders (e.g., schizophrenia) should generally not receive treatment with dopamine agonists, including pramipexole. New or worsening mental status and behavioral changes, including hallucinations, psychotic-like behavior, symptoms of mania (e.g., insomnia, psychomotor agitation), paranoid ideation, delusions, confusion, disorientation, aggressive behavior, agitation, and delirium, have been reported in patients treated with pramipexole. Age appears to increase the risk of hallucinations related to pramipexole administration; the elderly may be more at risk. Additionally, certain medications used to treat psychosis may exacerbate the symptoms of Parkinson's disease and may decrease the efficacy of pramipexole.
Pramipexole is primarily (more than 90%) excreted in the urine unchanged. Dosage adjustments are recommended in patients with moderate to severe renal impairment receiving immediate-release pramipexole and in patients with moderate renal impairment receiving extended-release (ER) pramipexole. Immediate-release pramipexole has not been studied in patients with very severe renal impairment (CrCl less than 15 mL/minute) or in those with renal failure or receiving dialysis. The ER formulation has not been studied in patients with severe renal impairment or renal failure (CrCl less than 30 mL/minute), or in patients receiving hemodialysis, and is not recommended in these populations.
Dopamine agonists, including pramipexole, may cause or exacerbate preexisting dyskinesia. Postural deformities, including antecollis, camptocormia (Bent Spine Syndrome), and pleurothotonus (Pisa Syndrome), have been reported in patients after starting or increasing the dose of pramipexole. Postural deformities may occur several months after initiation of treatment or a dose increase. Monitor patients closely for new or worsening symptoms if the patient already has signs of deformity present. Reducing the dose or discontinuing pramipexole has been associated with an improvement in postural deformities in some patients, and should be considered if a postural deformity occurs. Postural deformities can be frequent and disabling complications of Parkinson's disease and atypical parkinsonism. Early detection, whether from drug therapy or factors associated with the disease process, could help minimize the development of irreversible deformities and their associated complications (e.g., pain, radiculopathy, dysphagia, shortness of breath, visual disruption, unsteadiness leading to falls).
Avoid abrupt discontinuation or rapid dose reduction of pramipexole and follow recommended tapering as described in the product labels. Adverse events resembling neuroleptic malignant syndrome have been reported in association with rapid dose reductions, changes in, or withdrawal of dopaminergic therapy in patients with Parkinson's disease. Further, symptoms of apathy, anxiety, depression, fatigue, insomnia, sweating, and pain have been reported during dosage tapering or after discontinuation of dopamine agonists, such as pramipexole. These symptoms generally do not respond to treatment with levodopa. Inform patients about the potential for withdrawal symptoms prior to stopping pramipexole, and closely monitor these patients during and after treatment discontinuation. Re-administration at the lowest effective dose may be considered if severe withdrawal symptoms develop. Rebound, defined as a worsening of symptoms following treatment discontinuation with greater intensity than described before starting treatment, has been reported following abrupt discontinuation of dopaminergic medications in patients with restless legs syndrome (RLS). Although pramipexole was discontinued without a taper during RLS trials, results from 1 study indicated that RLS patients suddenly withdrawn from pramipexole experienced a worsening of RLS symptom severity beyond their untreated baseline. Therefore, consideration of a gradual taper may be advisable when discontinuing pramipexole in RLS patients.
The relative risk of hallucinations during pramipexole administration is increased in geriatric adults with Parkinson's disease compared to younger adults. Pharmacokinetic changes also occur, the clearance of pramipexole is decreased in geriatric adults, likely due to an age-related decline in renal function. It is advisable to carefully monitor older adults receiving pramipexole, particularly during initiation of treatment and following dosage changes.
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 caesarean 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.
There are no data on the presence of pramipexole in human breast milk, the effects of pramipexole exposure on the breastfed infant, or the effects of pramipexole on milk production. However, inhibition of lactation is expected because pramipexole inhibits secretion of prolactin in humans. Pramipexole and/or metabolites are excreted into the breast milk of lactating rats at concentrations 3 to 6 times those in the maternal plasma. The developmental and health benefits of breast-feeding should be considered along with the clinical need for pramipexole treatment and any potential adverse effects on the breastfed infant or from the underlying maternal condition being treated. Due to the possible reduction in milk production, the use of pramipexole during breast-feeding is generally not recommended.
Safe and effective use of pramipexole has not been established in pediatric patients less than 18 years of age. Juvenille Parkinson's disease is rare in children and adolescents, and the drug has not been systematically evaluated in pediatric restless leg syndrome. There is no identified potential use of pramipexole in infants.
General Dosage Information
-Conversion from immediate-release to extended-release pramipexole: For persons with Parkinsons disease, may switch overnight from immediate-release pramipexole to extended-release pramipexole at the same daily dose. When switching between immediate-release and extended-release pramipexole, monitor to determine if dosage adjustment is necessary.
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 Parkinson's disease:
Oral dosage (immediate-release):
Adults: 0.125 mg PO 3 times daily, initially. May increase the dose to 0.25 mg PO 3 times daily after 5 to 7 days, and then by 0.25 mg/dose every 5 to 7 days based on clinical response and tolerability. Max: 4.5 mg/day. To discontinue, taper dose by 0.75 mg/day until the daily dose has been reduced to 0.75 mg/day, then may reduce dose by 0.375 mg/day.
Oral dosage (extended-release):
Adults: 0.375 mg PO once daily, initially. May increase the dose to 0.75 mg PO once daily after 5 to 7 days, and then by 0.75 mg/day every 5 to 7 days based on clinical response and tolerability. Max: 4.5 mg/day. To discontinue, taper dose by 0.75 mg/day until the daily dose has been reduced to 0.75 mg/day, then may reduce dose by 0.375 mg/day.
Maximum Dosage Limits:
-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.
Patients with Hepatic Impairment Dosing
Hepatic impairment is not expected to have a significant effect on pramipexole clearance; therefore, no dosage adjustments are necessary.
Patients with Renal Impairment Dosing
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.
*non-FDA-approved indication
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; 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.
Amitriptyline: (Moderate) Pramipexole may cause additive drowsiness when combined with tricyclic antidepressants.
Amobarbital: (Major) The use of barbiturates in combination with pramipexole may increase the risk of clinically significant sedation via a pharmacodynamic interaction.
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; Butalbital; Caffeine: (Major) The use of barbiturates in combination with pramipexole may increase the risk of clinically significant sedation via a pharmacodynamic interaction.
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: (Major) The use of barbiturates in combination with pramipexole may increase the risk of clinically significant sedation via a pharmacodynamic interaction.
Butalbital; Acetaminophen; Caffeine: (Major) The use of barbiturates in combination with pramipexole may increase the risk of clinically significant sedation via a pharmacodynamic interaction.
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. (Major) The use of barbiturates in combination with pramipexole may increase the risk of clinically significant sedation via a pharmacodynamic interaction.
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. (Major) The use of barbiturates in combination with pramipexole may increase the risk of clinically significant sedation via a pharmacodynamic interaction.
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. (Moderate) Pramipexole may cause additive drowsiness when combined with tricyclic antidepressants.
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; 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.
Clomipramine: (Moderate) Pramipexole may cause additive drowsiness when combined with tricyclic antidepressants.
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.
Cyproheptadine: (Moderate) Concomitant use of pramipexole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of pramipexole.
Desipramine: (Moderate) Pramipexole may cause additive drowsiness when combined with tricyclic antidepressants.
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.
Dexmethylphenidate: (Moderate) Increased dopaminergic effects may occur during coadministration of methylphenidate derivatives, inhibitors of dopamine reuptake, and dopamine agonists such as pergolide, pramipexole, apomorphine, and ropinirole. Dopaminergic side effects, such as nausea, loss of appetite, weight loss, insomnia, tremor, nervousness, or changes in mood or behavior, are possible.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Concomitant use of 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.
Doxepin: (Moderate) Pramipexole may cause additive drowsiness when combined with tricyclic antidepressants.
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.
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.
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.
Imipramine: (Moderate) Pramipexole may cause additive drowsiness when combined with tricyclic antidepressants.
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.
Methohexital: (Major) The use of barbiturates in combination with pramipexole may increase the risk of clinically significant sedation via a pharmacodynamic interaction.
Methylphenidate Derivatives: (Moderate) Increased dopaminergic effects may occur during coadministration of methylphenidate derivatives, inhibitors of dopamine reuptake, and dopamine agonists such as pergolide, pramipexole, apomorphine, and ropinirole. Dopaminergic side effects, such as nausea, loss of appetite, weight loss, insomnia, tremor, nervousness, or changes in mood or behavior, are possible.
Methylphenidate: (Moderate) Increased dopaminergic effects may occur during coadministration of methylphenidate derivatives, inhibitors of dopamine reuptake, and dopamine agonists such as pergolide, pramipexole, apomorphine, and ropinirole. Dopaminergic side effects, such as nausea, loss of appetite, weight loss, insomnia, tremor, nervousness, or changes in mood or behavior, are possible.
Metoclopramide: (Moderate) Agents with dopamine antagonist properties, like metoclopramide, may decrease the effectiveness of dopamine agonists. These agents can cause abrupt and severe worsening of Parkinson's disease or restless leg syndrome (RLS) symptoms. Metoclopramide should be avoided, if possible, in patients treated with dopamine agonists for Parkinson's disease. If not avoidable, monitor for reduced efficacy of the dopamine agonist. Additive somnolence may also be possible.
Metyrapone: (Moderate) Metyrapone may cause dizziness and/or drowsiness. Other drugs that may also cause drowsiness, such as 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.
Nortriptyline: (Moderate) Pramipexole may cause additive drowsiness when combined with tricyclic antidepressants.
Olanzapine: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or 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; Naloxone: (Moderate) Concomitant use of pentazocine with other CNS depressants, such as pramipexole, can potentiate respiratory depression, CNS depression, and sedation.
Pentobarbital: (Major) The use of barbiturates in combination with pramipexole may increase the risk of clinically significant sedation via a pharmacodynamic interaction.
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. (Moderate) Pramipexole may cause additive drowsiness when combined with tricyclic antidepressants.
Phenobarbital: (Major) The use of barbiturates in combination with pramipexole may increase the risk of clinically significant sedation via a pharmacodynamic interaction.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) The use of barbiturates in combination with pramipexole may increase the risk of clinically significant sedation via a pharmacodynamic interaction.
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.
Primidone: (Major) The use of barbiturates in combination with pramipexole may increase the risk of clinically significant sedation via a pharmacodynamic interaction.
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.
Protriptyline: (Moderate) Pramipexole may cause additive drowsiness when combined with tricyclic antidepressants.
Pseudoephedrine; Triprolidine: (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.
Secobarbital: (Major) The use of barbiturates in combination with pramipexole may increase the risk of clinically significant sedation via a pharmacodynamic interaction.
Sedating H1-blockers: (Moderate) Concomitant use of pramipexole with other CNS depressants, such as sedating H1-blockers, can potentiate the sedation effects of pramipexole.
Serdexmethylphenidate; Dexmethylphenidate: (Moderate) Increased dopaminergic effects may occur during coadministration of methylphenidate derivatives, inhibitors of dopamine reuptake, and dopamine agonists such as pergolide, pramipexole, apomorphine, and ropinirole. Dopaminergic side effects, such as nausea, loss of appetite, weight loss, insomnia, tremor, nervousness, or changes in mood or behavior, are possible.
Solriamfetol: (Moderate) Monitor for dopamine-mediated effects including nausea, vomiting, dizziness, tremor, and changes in moods or behaviors if solriamfetol, a central dopamine and norepinephrine reuptake inhibitor, is administered with other dopaminergic drugs, such as 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.
Trimipramine: (Moderate) Pramipexole may cause additive drowsiness when combined with tricyclic antidepressants.
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.
Zuranolone: (Major) Avoid the use of multiple sedating agents due to the risk for additive CNS depression. If use is necessary, consider a downward dosage adjustment of either or both medications, especially in patients with additional risk factors for sedation-related harm.
Pramipexole is a non-ergot dopamine agonist that binds to dopamine D2- and D3-receptors in the striatum, with greater affinity for D3 than D2. While the exact mechanism for treatment of Parkinson's disease is unknown, it is believed to be related to stimulation of dopamine receptors in the striatum. Pramipexole is also an agonist at peripheral dopamine D2-receptors, leading to a blunted noradrenergic response to standing and possible subsequent orthostatic hypotension. The exact mechanism of action of pramipexole in the treatment of restless legs syndrome (RLS) is not known; however, neuropharmacological evidence suggests primary dopaminergic system involvement. Positron emission tomographic (PET) studies suggest mild striatal presynaptic dopaminergic dysfunction may be involved in the pathogenesis of RLS.
Pramipexole is administered orally as immediate-release and extended-release tablets. Pramipexole has an extensive volume of distribution of approximately 500 L. 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: OCT1, OCT2, OCT3
Pramipexole is secreted by the renal tubules, probably by the organic cation transport system (OCT). Population pharmacokinetic analysis suggests that coadministration of drugs that are secreted by the cationic transport system (e.g., cimetidine, ranitidine, diltiazem, triamterene, verapamil, quinidine, and quinine) decreases the oral clearance of pramipexole by about 20%. Other known organic cation transport substrates and/or inhibitors (e.g., cisplatin and procainamide) may also decrease the clearance of pramipexole.
-Route-Specific Pharmacokinetics
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.
-Special Populations
Hepatic Impairment
The effects of hepatic impairment on the pharmacokinetics of pramipexole have not been evaluated. Because about 90% of the drug is excreted as the parent compound in the urine, hepatic impairment is not expected to have a significant effect on pramipexole elimination.
Renal Impairment
In patients with varying degrees of renal impairment, pramipexole clearance correlates well with creatinine clearance (CrCl). The renal clearance of immediate-release pramipexole is about 60% lower in patients with moderate renal impairment (CrCl about 40 mL/minute) and 75% lower in patients with severe renal impairment (CrCl about 20 mL/minute) compared to healthy volunteers. Dose adjustments are recommended in Parkinson's disease patients with a CrCl of 15 to 50 mL/minute and an extended titration interval is recommended in patients with restless legs syndrome who have a CrCl of 20 to 60 mL/minute. Extended-release pramipexole is not recommended in patients with severe renal impairment (CrCl less than 30 mL/minute) or in patients on dialysis. Immediate-release pramipexole has not been studied in patients with renal failure (CrCl less than 15 mL/minute) or in those on dialysis. Only a negligible amount of pramipexole is removed by hemodialysis.
Pediatrics
Pramipexole pharmacokinetic data in pediatric patients are not available.
Geriatric
The total clearance of pramipexole is decreased by 30% in those who are older than 65 years compared to younger adults. The elimination half-life also changes with age, increasing from 8.5 hours in young adults to 12 hours in geriatric patients (an approximate 40% increase). These pharmacokinetic changes are thought to occur secondary to an age-related decline in renal function.
Gender Differences
Pramipexole clearance is about 30% less in women than men; however, this difference can be accounted for by differences in body weight. There is no difference between males and females in the plasma half-life of the drug.
Ethnic Differences
No racial differences in metabolism or elimination have been identified.
Other
Parkinson's Disease
A cross-study comparison of data suggests that Parkinson's disease patients may have a 30% reduction in clearance of pramipexole compared with healthy geriatric adult volunteers. This difference appears to be due to reduced renal function in Parkinson's disease patients, which may be related to their poorer general health. The pharmacokinetics of pramipexole were comparable between early and advanced Parkinson's disease patients.
Restless Legs Syndrome
A cross-study comparison of data suggests that the pharmacokinetics of pramipexole in those with restless legs syndrome are similar to the pharmacokinetic parameters of healthy adult volunteers.