Pramipexole Dihydrochloride
Pramipexole Dihydrochloride Prescribing Information
Pramipexole dihydrochloride extended-release tablets are indicated for the treatment of Parkinson's disease.
• Pramipexole dihydrochloride extended-release tablets are taken once daily, with or without food (
Pramipexole dihydrochloride extended-release tablets are taken orally once daily, with or without food.
Pramipexole dihydrochloride extended-release tablets must be swallowed whole and must not be chewed, crushed, or divided.
If a significant interruption in therapy with pramipexole dihydrochloride extended-release tablets has occurred, re-titration of therapy may be warranted.
• Tablets must be swallowed whole and must not be chewed, crushed, or divided (
Pramipexole dihydrochloride extended-release tablets are taken orally once daily, with or without food.
Pramipexole dihydrochloride extended-release tablets must be swallowed whole and must not be chewed, crushed, or divided.
If a significant interruption in therapy with pramipexole dihydrochloride extended-release tablets has occurred, re-titration of therapy may be warranted.
• Starting dose is 0.375 mg given once daily (
The starting dose is 0.375 mg given once per day. Based on efficacy and tolerability, dosages may be increased gradually, not more frequently than every 5 to 7 days, first to 0.75 mg per day and then by 0.75 mg increments up to a maximum recommended dose of 4.5 mg per day.
In clinical trials, dosage was initiated at 0.375 mg/day and gradually titrated based on individual therapeutic response and tolerability. Doses greater than 4.5 mg/day have not been studied in clinical trials. Patients should be assessed for therapeutic response and tolerability at a minimal interval of 5 days or longer after each dose increment
Due to the flexible dose design used in clinical trials, specific dose-response information could not be determined
Pramipexole dihydrochloride extended-release tablets may be tapered off at a rate of 0.75 mg per day until the daily dose has been reduced to 0.75 mg. Thereafter, the dose may be reduced by 0.375 mg per day [
Pramipexole dihydrochloride extended-release tablets have not been studied in patients with severe renal impairment (creatinine clearance <30 mL/min) or patients on hemodialysis, and are not recommended in these patients.
• Dose may be increased gradually, not more frequently than every 5 to 7 days, first to 0.75 mg per day and then by 0.75 mg increments up to a maximum recommended dose of 4.5 mg per day. Assess therapeutic response and tolerability at a minimal interval of 5 days or longer after each dose increment (
The starting dose is 0.375 mg given once per day. Based on efficacy and tolerability, dosages may be increased gradually, not more frequently than every 5 to 7 days, first to 0.75 mg per day and then by 0.75 mg increments up to a maximum recommended dose of 4.5 mg per day.
In clinical trials, dosage was initiated at 0.375 mg/day and gradually titrated based on individual therapeutic response and tolerability. Doses greater than 4.5 mg/day have not been studied in clinical trials. Patients should be assessed for therapeutic response and tolerability at a minimal interval of 5 days or longer after each dose increment
Due to the flexible dose design used in clinical trials, specific dose-response information could not be determined
Pramipexole dihydrochloride extended-release tablets may be tapered off at a rate of 0.75 mg per day until the daily dose has been reduced to 0.75 mg. Thereafter, the dose may be reduced by 0.375 mg per day [
Pramipexole dihydrochloride extended-release tablets have not been studied in patients with severe renal impairment (creatinine clearance <30 mL/min) or patients on hemodialysis, and are not recommended in these patients.
• Patients may be switched overnight from immediate-release pramipexole tablets to pramipexole dihydrochloride extended-release tablets at the same daily dose. Dose adjustment may be needed in some patients (
Patients with Parkinson's disease may be switched overnight from immediate-release pramipexole tablets to pramipexole dihydrochloride extended-release tablets at the same daily dose. When switching between immediate-release pramipexole tablets and pramipexole dihydrochloride extended-release tablets, patients should be monitored to determine if dosage adjustment is necessary.
• Pramipexole dihydrochloride extended-release tablets should be discontinued gradually (
The starting dose is 0.375 mg given once per day. Based on efficacy and tolerability, dosages may be increased gradually, not more frequently than every 5 to 7 days, first to 0.75 mg per day and then by 0.75 mg increments up to a maximum recommended dose of 4.5 mg per day.
In clinical trials, dosage was initiated at 0.375 mg/day and gradually titrated based on individual therapeutic response and tolerability. Doses greater than 4.5 mg/day have not been studied in clinical trials. Patients should be assessed for therapeutic response and tolerability at a minimal interval of 5 days or longer after each dose increment
Due to the flexible dose design used in clinical trials, specific dose-response information could not be determined
Pramipexole dihydrochloride extended-release tablets may be tapered off at a rate of 0.75 mg per day until the daily dose has been reduced to 0.75 mg. Thereafter, the dose may be reduced by 0.375 mg per day [
Pramipexole dihydrochloride extended-release tablets have not been studied in patients with severe renal impairment (creatinine clearance <30 mL/min) or patients on hemodialysis, and are not recommended in these patients.
• 0.375 mg: White colored, circular, flat, beveled edged, uncoated tablet debossed ‘ER 1’ on one side of the tablet and ‘0.375’ on other side. Each extended-release tablet contains 0.375 mg pramipexole dihydrochloride monohydrate equivalent to 0.352 mg pramipexole dihydrochloride, USP.
• 0.75 mg: White colored, circular, flat, beveled edged, uncoated tablet debossed ‘ER 2’ on one side of the tablet and ‘0.75’ on other side. Each extended-release tablet contains 0.75 mg pramipexole dihydrochloride monohydrate equivalent to 0.705 mg pramipexole dihydrochloride, USP.
• 1.5 mg: White colored, oval shaped, biconvex, uncoated tablet debossed ‘ER 3’ on one side of the tablet and ‘1.5’ on other side. Each extended-release tablet contains 1.5 mg pramipexole dihydrochloride monohydrate equivalent to 1.41 mg pramipexole dihydrochloride, USP.
• 2.25 mg: White colored, oval shaped, biconvex, uncoated tablet debossed ‘ER 4’ on one side of the tablet and ‘2.25’ on other side. Each extended-release tablet contains 2.25 mg pramipexole dihydrochloride monohydrate equivalent to 2.12 mg pramipexole dihydrochloride, USP.
• 3 mg: White colored, oval shaped, biconvex, uncoated tablet debossed ‘ER 5’ on one side of the tablet and ‘3.0’ on other side. Each extended-release tablet contains 3 mg pramipexole dihydrochloride monohydrate equivalent to 2.82 mg pramipexole dihydrochloride, USP.
• 3.75 mg: White colored, oval shaped, biconvex, uncoated tablet debossed ‘ER 6’ on one side of the tablet and ‘3.75’ on other side. Each extended-release tablet contains 3.75 mg pramipexole dihydrochloride monohydrate equivalent to 3.53 mg pramipexole dihydrochloride, USP.
• 4.5 mg: White colored, oval shaped, biconvex, uncoated tablet debossed ‘ER 7’ on one side of the tablet and ‘4.5’ on other side. Each extended-release tablet contains 4.5 mg pramipexole dihydrochloride monohydrate equivalent to 4.23 mg pramipexole dihydrochloride, USP.
Pregnancy: Based on animal data, may cause fetal harm (
There are no adequate data on the developmental risk associated with the use of pramipexole dihydrochloride extended-release tablets in pregnant women. No adverse developmental effects were observed in animal studies in which pramipexole was administered to rabbits during pregnancy. Effects on embryofetal development could not be adequately assessed in pregnant rats; however, postnatal growth was inhibited at clinically relevant exposures
In the U.S. general population, the estimated background risk of major birth defects and of miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown.
None.
• Falling Asleep During Activities of Daily Living: Sudden onset of sleep may occur without warning; advise patients to report symptoms (
Patients treated with pramipexole have reported falling asleep while engaged in activities of daily living, including the operation of motor vehicles, which sometimes resulted in accidents. Although many of these patients reported somnolence while on pramipexole tablets, some perceived that they had no warning signs (sleep attack) such as excessive drowsiness, and believed that they were alert immediately prior to the event. Some of these events had been reported as late as one year after the initiation of treatment. In placebo-controlled clinical trials in Parkinson's disease, the sudden onset of sleep or sleep attacks were reported in 8 of 387 (2%) patients treated with pramipexole dihydrochloride extended-release tablets compared to 2 of 281 (1%) patients on placebo.
In early Parkinson’s disease, somnolence was reported in 36% of 223 patients treated with pramipexole dihydrochloride extended-release tablets, median dose 3.0 mg/day, compared to 15% of 103 patients on placebo. In advanced Parkinson’s disease, somnolence was reported in 15% of 164 patients treated with pramipexole dihydrochloride extended-release tablets, median dose 3 mg/day, compared to 16% of 178 patients on placebo. It has been reported that falling asleep while engaged in activities of daily living usually occurs in a setting of preexisting somnolence, although patients may not give such a history. For this reason, prescribers should reassess patients for drowsiness or sleepiness, especially since some of the events occur well after the start of treatment. Prescribers should also be aware that patients may not acknowledge drowsiness or sleepiness until directly questioned about drowsiness or sleepiness during specific activities.
Before initiating treatment with pramipexole dihydrochloride extended-release tablets, advise patients of the potential to develop drowsiness, and specifically ask about factors that may increase the risk for somnolence such as the use of concomitant sedating medications or alcohol, the presence of sleep disorders, and concomitant medications that increase pramipexole plasma levels (e.g., cimetidine) [
• Symptomatic Orthostatic Hypotension: Monitor closely especially during dose escalation (
Dopamine agonists, in clinical studies and clinical experience, appear to impair the systemic regulation of blood pressure, with resulting orthostatic hypotension, especially during dose escalation. Parkinson's disease patients, in addition, appear to have an impaired capacity to respond to an orthostatic challenge. For these reasons, Parkinson's disease patients being treated with dopaminergic agonists, including pramipexole dihydrochloride extended-release tablets, ordinarily require careful monitoring for signs and symptoms of orthostatic hypotension, especially during dose escalation, and should be informed of this risk. In placebo-controlled clinical trials in Parkinson’s disease, symptomatic orthostatic hypotension was reported in 10 of 387 (3%) patients treated with pramipexole dihydrochloride extended-release tablets compared to 3 of 281 (1%) patients on placebo. One patient of 387 on pramipexole dihydrochloride extended-release tablets discontinued treatment due to hypotension.
• Impulse Control/Compulsive Behaviors: Patients may experience compulsive behaviors and other intense urges (
Case reports and the results of cross-sectional studies suggest that patients can experience intense urges to gamble, increased sexual urges, intense urges to spend money, binge eating, and/or other intense urges, and the inability to control these urges while taking one or more of the medications, including pramipexole dihydrochloride extended-release tablets that increase central dopaminergic tone. In some cases, although not all, these urges were reported to have stopped when the dose was reduced or the medication was discontinued. Because patients may not recognize these behaviors as abnormal, it is important for prescribers to specifically ask patients or their caregivers about the development of new or increased gambling urges, sexual urges, uncontrolled spending or other urges while being treated with pramipexole dihydrochloride extended-release tablets for Parkinson's disease. Physicians should consider dose reduction or stopping the medication if a patient develops such urges while taking pramipexole dihydrochloride extended-release tablets.
A total of 1056 patients with Parkinson’s disease who participated in two pramipexole dihydrochloride extended-release tablets placebo-controlled studies of up to 33 weeks duration were specifically asked at each visit about the occurrence of these symptoms. A total of 14 of 387 (4%) treated with pramipexole dihydrochloride extended-release tablets, 12 of 388 (3%) treated with immediate-release pramipexole tablets, and 4 of 281 (1%) treated with placebo reported compulsive behaviors, including pathological gambling, hypersexuality, and/or compulsive buying.
• Hallucinations and Psychotic-like Behavior: May occur; risk increases with age (
In placebo-controlled clinical trials in Parkinson's disease, hallucinations (visual or auditory or mixed) were reported in 25 of 387 (6%) patients treated with pramipexole dihydrochloride extended-release tablets compared to 5 of 281 (2%) patients receiving placebo. Hallucinations led to discontinuation of treatment in 5 of 387 (1%) patients on pramipexole dihydrochloride extended-release tablets.
Age appears to increase the risk of hallucinations attributable to pramipexole. In placebo-controlled clinical trials in Parkinson’s disease, hallucinations were reported in 15 of 162 (9%) patients ≥65 years of age taking pramipexole dihydrochloride extended-release tablets compared to 10 of 225 (4%) patients <65 years of age taking pramipexole dihydrochloride extended-release tablets.
Postmarketing reports with dopamine agonists, including pramipexole dihydrochloride extended-release tablets, indicate that patients with Parkinson's disease may experience new or worsening mental status and behavioral changes, which may be severe, including psychotic-like behavior during treatment with pramipexole dihydrochloride extended-release tablets or after starting or increasing the dose of pramipexole dihydrochloride extended-release tablets. Other drugs prescribed to improve the symptoms of Parkinson's disease can have similar effects on thinking and behavior. This abnormal thinking and behavior can consist of one or more of a variety of manifestations including paranoid ideation, delusions, hallucinations, confusion, psychotic-like behavior, symptoms of mania (e.g., insomnia, psychomotor agitation), disorientation, aggressive behavior, agitation, and delirium.
Patients with a major psychotic disorder should ordinarily not be treated with dopamine agonists, including pramipexole dihydrochloride extended-release tablets, because of the risk of exacerbating the psychosis. In addition, certain medications used to treat psychosis may exacerbate the symptoms of Parkinson’s disease and may decrease the effectiveness of pramipexole dihydrochloride extended-release tablets
• Dyskinesia: May be caused or exacerbated by pramipexole dihydrochloride extended-release tablets (
Pramipexole dihydrochloride extended-release tablets may cause or exacerbate preexisting dyskinesia.
• Postural Deformity: Consider reducing the dose or discontinuing pramipexole dihydrochloride extended-release tablets if postural deformity occurs (
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 dihydrochloride extended-release tablets. Postural deformity may occur several months after starting treatment or increasing the dose. Reducing the dose or discontinuing pramipexole dihydrochloride extended-release tablets has been reported to improve postural deformity in some patients, and should be considered if postural deformity occurs.