Pramipexole
Tablet · Oral
Uses
1 INDICATIONS & USAGE PRAMIPEXOLE DIHYDROCHLORIDE tablets is a non-ergot dopamine agonist indicated for the treatment of
• the signs and symptoms of idiopathic Parkinson's disease (PD) ( 1.1 ) 1.1 Parkinson's Disease Pramipexole dihydrochloride tablets are indicated for the treatment of the signs and symptoms of idiopathic Parkinson's disease.
Dosage and administration
Parkinson's Disease-Normal Renal Function* ( 2.2 ) Week Dosage (mg) Total Daily Dose (mg) 1 0.125 TID 0.375 2 0.25 TID 0.75 3 0.5 TID 1.5 4 0.75 TID 2.25 5 1 TID 3 6 1.25 TID 3.75 7 1.5 TID 4.5 * Doses should not be increased more frequently than every 5-7 days. Titrate to effective dose. If used with levodopa, may need to reduce levodopa dose. Parkinson's Disease-Impaired Renal Function ( 2.2 ) Creatinine Clearance Starting Dose (mg) Maximum Dose (mg) > 50 mL/min 0.125 TID 1.5 TID 30 to 50 mL/min 0.125 BID 0.75 TID 15 to 30 mL/min 0.125 QD 1.5 QD < 15 mL/min and hemodialysis patients Data not available 2.1 General Dosing Considerations Pramipexole dihydrochloride tablets are taken orally, with or without food. If a significant interruption in therapy with pramipexole dihydrochloride tablets has occurred, re-titration of therapy may be warranted. 2.2 Parkinson's Disease In all clinical studies, dosage was initiated at a subtherapeutic level to avoid intolerable adverse effects and orthostatic hypotension. Pramipexole dihydrochloride tablets should be titrated gradually in all patients. The dose should be increased to achieve a maximum therapeutic effect, balanced against the principal side effects of dyskinesia, hallucinations, somnolence, and dry mouth. Dosing in Patients with Normal Renal Function Initial Treatment Doses should be increased gradually from a starting dose of 0.375 mg/day given in three divided doses and should not be increased more frequently than every 5 to 7 days. A suggested ascending dosage schedule that was used in clinical studies is shown in the following table: Table 1 Ascending Dosage Schedule of pramipexole dihydrochloride tablets for Parkinson's Disease Parkinson's Disease-Normal Renal Function*(2.2) Week Dosage (mg) Total Daily Dose (mg) 1 0.125 TID 0.375 2 0.25 TID 0.75 3 0.5 TID 1.5 4 0.75 TID 2.25 5 1 TID 3 6 1.25 TID 3.75 7 1.5 TID 4.5 *Doses should not be increased more frequently than every 5-7 days. Titrate to effective dose. If used with levodopa, may need to reduce levodopa dose. Maintenance Treatment Pramipexole dihydrochloride tablets were effective and well tolerated over a dosage range of 1.5 to 4.5 mg/day administered in equally divided doses three times per day with or without concomitant levodopa (approximately 800 mg/day). In a fixed-dose study in early Parkinson's disease patients, doses of 3 mg, 4.5 mg, and 6 mg per day of pramipexole dihydrochloride tablets were not shown to provide any significant benefit beyond that achieved at a daily dose of 1.5 mg/day. However, in the same fixed-dose study, the following adverse events were dose related: postural hypotension, nausea, constipation, somnolence, and amnesia. The frequency of these events was generally 2-fold greater than placebo for pramipexole doses greater than 3 mg/day. The incidence of somnolence reported with pramipexole at a dose of 1.5 mg/day was comparable to placebo. When pramipexole dihydrochloride tablets are used in combination with levodopa, a reduction of the levodopa dosage should be considered. In a controlled study in advanced Parkinson's disease, the dosage of levodopa was reduced by an average of 27% from baseline. Dosing in Patients with Renal Impairment Table 2 Dosing of pramipexole dihydrochloride tablets in Parkinson's Disease Patients with Renal Impairment Renal Status Starting Dose (mg) Maximum Dose (mg) Normal to mild impairment (creatinine Cl >50 mL/min) 0.125 TID 1.5 TID Moderate impairment (creatinine Cl =30 to 50 mL/min) 0.125 BID 0.75 TID Severe impairment (creatinine Cl =15 to <30 mL/min) 0.125 QD 1.5 QD Very severe impairment (creatinine Cl <15 mL/min and hemodialysis patients) The use of pramipexole dihydrochloride tablets has not been adequately studied in this group of patients Discontinuation of Treatment Pramipexole dihydrochloride tablets should 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 should be reduced by 0.375 mg per day. [see Warnings and Precautions(5.9)].
Dosage forms and strengths
0.125 mg: white to off-white, round, flat, beveled edge uncoated tablets, debossed with 'SG' on one side '126' on other side. 0.25 mg: white to off white, oval, flat, beveled edge uncoated functional scored tablets debossed on one side with 'S' on the left side of bisect and 'G'on the right side of bisect and other side '1' on the left side and '27' on the right side of the bisect. 0.5 mg: white to off white, oval, flat, beveled edge uncoated functional scored tablets debossed on one side with'S' on the left side of bisect and'G'on the right side of bisect and other side'1'on the left side and '28' on the right side of the bisect. 0.75 mg: white to off white, oval, flat, beveled edge uncoated tablets, debossed with 'SG' on one side '129'on other side. 1.0 mg: white to off white, oval, flat, beveled edge uncoated functional scored tablets debossed on one side with 'S' on the left side of bisect and 'G' on the right side of bisect and other side '1' on the left side and '30' on the right side of the bisect. 1.5 mg: white to off white, oval, flat, beveled edge uncoated functional scored tablets debossed on one side with 'S' on the left side of bisect and 'G' on the right side of bisect and other side '1' on the left side and '31' on the right side of the bisect. Tablets: 0.125 mg, 0.25 mg (functional scored tablets), 0.5 mg (functional scored tablets), 0.75 mg, 1 mg (functional scored tablets), and 1.5 mg (functional scored tablets) ( 3 ).
Contraindications
None. None (4)
Warnings and precautions
• Falling asleep during activities of daily living: Sudden onset of sleep may occur without warning. Advise patients to report symptoms to the prescriber. ( 5.1 )
• Symptomatic orthostatic hypotension. Monitor during dose escalation ( 5.2 )
• Impulse control/Compulsive behaviors: Patients may experience compulsive behaviors and other intense urges ( 5.3 )
• Hallucinations: May occur. Risk increases with age. ( 5.4 )
• Dyskinesia: May be caused or exacerbated by PRAMIPEXOLE DIHYDROCHLORIDE tablets ( 5.5 )
• Renal Impairment: Requires dose reduction ( 2.2 , 12.3 )
• Events reported with dopaminergic therapy: Include withdrawal-emergent hyperpyrexia and confusion, fibrotic complications, and melanoma ( 5.9 ) 5.1 Falling Asleep During Activities of Daily Living 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 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. Somnolence is a common occurrence in patients receiving pramipexole at doses above 1.5 mg/day (0.5 mg TID) for Parkinson's disease. Many clinical experts believe that falling asleep while engaged in activities of daily living always occurs in a setting of pre-existing somnolence, although patients may not give such a history. For this reason, prescribers should continually 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 tablets, advise patients of the potential to develop drowsiness and specifically asked about factors that may increase the risk with pramipexole dihydrochloride tablets 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) [see Clinical Pharmacology (12.3)]. If a patient develops significant daytime sleepiness or episodes of falling asleep during activities that require active participation (e.g., conversations, eating, etc.), pramipexole dihydrochloride tablets should ordinarily be discontinued. If a decision is made to continue pramipexole dihydrochloride tablets, advise patients not to drive and to avoid other potentially dangerous activities. While dose reduction reduces the degree of somnolence, there is insufficient information to establish that dose reduction will eliminate episodes of falling asleep while engaged in activities of daily living. 5.2 Symptomatic Orthostatic Hypotension 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 ordinarily require careful monitoring for signs and symptoms of orthostatic hypotension, especially during dose escalation, and should be informed of this risk. In clinical trials of pramipexole, however, and despite clear orthostatic effects in normal volunteers, the reported incidence of clinically significant orthostatic hypotension was not greater among those assigned to pramipexole tablets than among those assigned to placebo. This result, especially with the higher doses used in Parkinson's disease, is clearly unexpected in light of the previous experience with the risks of dopamine agonist therapy. While this finding could reflect a unique property of pramipexole, it might also be explained by the conditions of the study and the nature of the population enrolled in the clinical trials. Patients were very carefully titrated, and patients with active cardiovascular disease or significant orthostatic hypotension at baseline were excluded. 5.3 Impulse Control/Compulsive Behaviors Case reports and the results of a cross-sectional study suggest that patients can experience intense urges to gamble, increased sexual urges, intense urges to spend money uncontrollably, 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 tablets, that increase central dopaminergic tone and that are generally used for the treatment of Parkinson’s disease. 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 tablets. Physicians should consider dose reduction or stopping the medication if a patient develops such urges while taking pramipexole dihydrochloride tablets. 5.4 Hallucinations and Psychotic-like Behavior In the three double-blind, placebo-controlled trials in early Parkinson's disease, hallucinations were observed in 9% (35 of 388) of patients receiving pramipexole dihydrochloride tablets, compared with 2.6% (6 of 235) of patients receiving placebo.
Side effects
The following adverse reactions are discussed in greater detail in other sections of the labeling:
• Falling Asleep During Activities of Daily Living [see Warnings and Precautions (5.1)].
• Symptomatic Orthostatic Hypotension [see Warnings and Precautions (5.2)].
• Impulse Control/Compulsive Behaviors [see Warnings and Precautions (5.3)].
• Hallucinations [see Warnings and Precautions ( 5.4 )].
• Dyskinesia [see Warnings and Precautions ( 5.5)].
• Renal Impairment [see Warnings and Precautions (5.6)].
• Rhabdomyolysis [see Warnings and Precautions (5.7)].
• Retinal Pathology [see Warnings and Precautions ( 5.8)].
• Events Reported with Dopaminergic Therapy [see Warnings and Precautions (5.9)]. Most common adverse events (incidence >5% and greater than placebo):
• Early PD without levodopa: nausea, dizziness, somnolence, insomnia, constipation, asthenia, and hallucinations ( 6.1 ).
• Advanced PD with levodopa: postural (orthostatic) hypotension, dyskinesia, extrapyramidal syndrome, insomnia, dizziness, hallucinations, accidental injury, dream abnormalities, confusion, constipation, asthenia, somnolence, dystonia, gait abnormality, hypertonia, dry mouth, amnesia, and urinary frequency ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Hetero Labs Limited at 866-495-1995 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse event rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Parkinson's Disease During the premarketing development of pramipexole, patients with either early or advanced Parkinson's disease were enrolled in clinical trials. Apart from the severity and duration of their disease, the two populations differed in their use of concomitant levodopa therapy. Patients with early disease did not receive concomitant levodopa therapy during treatment with pramipexole; those with advanced Parkinson's disease all received concomitant levodopa treatment. Because these two populations may have differential risks for various adverse events, this section will, in general, present adverse-event data for these two populations separately. Because the controlled trials performed during premarketing development all used a titration design, with a resultant confounding of time and dose, it was impossible to adequately evaluate the effects of dose on the incidence of adverse events. Early Parkinson's Disease In the three double-blind, placebo-controlled trials of patients with early Parkinson's disease, the most commonly observed adverse events (>5%) that were numerically more frequent in the group treated with pramipexole dihydrochloride tablets were nausea, dizziness, somnolence, insomnia, constipation, asthenia, and hallucinations. Approximately 12% of 388 patients with early Parkinson's disease and treated with pramipexole dihydrochloride tablets who participated in the double-blind, placebo-controlled trials discontinued treatment due to adverse events compared with 11% of 235 patients who received placebo. The adverse events most commonly causing discontinuation of treatment were related to the nervous system (hallucinations [3.1% on pramipexole dihydrochloride tablets vs 0.4% on placebo]; dizziness [2.1% on pramipexole dihydrochloride tablets vs 1% on placebo]; somnolence [1.6% on pramipexole dihydrochloride tablets vs 0% on placebo]; extrapyramidal syndrome [1.6% on pramipexole dihydrochloride tablets vs 6.4% on placebo]; headache and confusion [1.3% and 1.0%, respectively, on pramipexole dihydrochloride tablets vs 0% on placebo]); and gastrointestinal system (nausea [2.1% on pramipexole dihydrochloride tablets vs 0.4% on placebo]). Adverse-event Incidence in Controlled Clinical Studies in Early Parkinson's Disease: Table 4 lists treatment-emergent adverse events that occurred in the double-blind, placebo-controlled studies in early Parkinson's disease that were reported by ≥1% of patients treated with pramipexole dihydrochloride tablets and were numerically more frequent than in the placebo group. In these studies, patients did not receive concomitant levodopa. Adverse events were usually mild or moderate in intensity. The prescriber should be aware that these figures cannot be used to predict the incidence of adverse events in the course of usual medical practice where patient characteristics and other factors differ from those that prevailed in the clinical studies. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses, and investigators. However, the cited figures do provide the prescribing physician with some basis for estimating the relative contribution of drug and nondrug factors to the adverse-event incidence rate in the population studied. Table 4 Treatment-Emergent Adverse-Event* Incidence in Double-Blind, Placebo-Controlled Trials in Early Parkinson's Disease (Events ≥1% of Patients Treated with pramipexole dihydrochloride tablets and Numerically More Frequent than in the Placebo Group) Body System/ Adverse Event Pramipexole dihydrochloride tablets (N=388) % Placebo (N=235) % Body as a Whole Asthenia 14 12 General edema 5 3 Malaise 2 1 Reaction unevaluable 2 1 Fever 1 0 Digestive System Nausea 28 18 Constipation 14 6 Anorexia 4 2 Dysphagia 2 0 Metabolic & Nutritional System Peripheral edema 5 4 Decreased weight 2 0 Nervous System Dizziness 25 24 Somnolence 22 9 Insomnia 17 12 Hallucinations 9 3 Confusion 4 1 Amnesia 4 2 Hypesthesia 3 1 Dystonia 2 1 Akathisia 2 0 Thinking abnormalities 2 0 Decreased libido 1 0 Myoclonus 1 0 Special Senses Vision abnormalities 3 0 Urogenital System Impotence 2 1 *Patients may have reported multiple adverse experiences during the study or at discontinuation; thus, patients may be included in more than one category.
Drug interactions
See also Dosage and Administration (2.2) and Clinical Pharmacology ( 12.3 ) Dopamine antagonists may diminish the effectiveness of pramipexole ( 7.1 ). 7.1 Dopamine Antagonists Since pramipexole is a dopamine agonist, it is possible that dopamine antagonists, such as the neuroleptics (phenothiazines, butyrophenones, thioxanthenes) or metoclopramide, may diminish the effectiveness of pramipexole dihydrochloride tablets. 7.2 Drug/Laboratory Test Interactions There are no known interactions between pramipexole and laboratory tests.
Use in specific populations
Pregnancy: Based on animal data, may cause fetal harm ( 8.1 ). Pediatric use: Safety and effectiveness in pediatric patients have not been established ( 8.4 ) See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling 8.1 Pregnancy Risk Summary There are no adequate data on the developmental risk associated with the use of pramipexole 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 [see Data]. In the U.S. general population, the estimated background risk of major birth defects and of miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown. Data Animal Data Oral administration of pramipexole (0.1, 0.5, or 1.5 mg/kg/day) to pregnant rats during the period of organogenesis resulted in a high incidence of total resorption of embryos at the highest dose tested. This increase in embryolethality is thought to result from the prolactin-lowering effect of pramipexole; prolactin is necessary for implantation and maintenance of early pregnancy in rats but not rabbits or humans. Because of pregnancy disruption and early embryonic loss in this study, the teratogenic potential of pramipexole could not be adequately assessed in rats. The highest no-effect dose for embryolethality in rats was associated with maternal plasma drug exposures (AUC) approximately equal to those in humans receiving the maximum recommended human dose (MRHD) of 4.5 mg/day. There were no adverse effects on embryo-fetal development following oral administration of pramipexole (0.1, 1, and 10 mg/kg/day) to pregnant rabbits during organogenesis (plasma AUC up to approximately 70 times that in humans at the MRHD). Postnatal growth was inhibited in the offspring of rats treated with pramipexole (0.1, 0.5, or 1.5 mg/kg/day) during the latter part of pregnancy and throughout lactation. The no-effect dose for adverse effects on offspring growth (0.1 mg/kg/day) was associated with maternal plasma drug exposures lower than that in humans at the MRHD 8.2 Lactation Risk Summary There are no data on the presence of pramipexole in human milk, the effects of pramipexole 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 or metabolites, or both, are present in rat milk [see Data]. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for pramipexole and any potential adverse effects on the breastfed infant from pramipexole or from the underlying maternal condition. Data In a study of radio-labeled pramipexole, pramipexole or metabolites, or both, were present in rat milk at concentrations three to six times higher than those in maternal plasma. 8.4 Pediatric Use Safety and effectiveness of pramipexole dihydrochloride tablets in pediatric patients has not been established. 8.5 Geriatric Use Pramipexole total oral clearance is approximately 30% lower in subjects older than 65 years compared with younger subjects, because of a decline in pramipexole renal clearance due to an age-related reduction in renal function. This resulted in an increase in elimination half-life from approximately 8.5 hours to 12 hours. In clinical studies with Parkinson’s disease patients, 38.7% of patients were older than 65 years. There were no apparent differences in efficacy or safety between older and younger patients, except that the relative risk of hallucination associated with the use of pramipexole dihydrochloride tablets was increased in the elderly. 8.6 Patients with Renal Impairment The elimination of pramipexole is dependent on renal function. Pramipexole clearance is extremely low in dialysis patients, as a negligible amount of pramipexole is removed by dialysis. Caution should be exercised when administering pramipexole dihydrochloride tablets to patients with renal disease [see Dosage and Administration (2.2), Warnings and Precautions (5.6), and Clinical Pharmacology ( 12.3)].
Pregnancy
8.1 Pregnancy Risk Summary There are no adequate data on the developmental risk associated with the use of pramipexole 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 [see Data]. In the U.S. general population, the estimated background risk of major birth defects and of miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown. Data Animal Data Oral administration of pramipexole (0.1, 0.5, or 1.5 mg/kg/day) to pregnant rats during the period of organogenesis resulted in a high incidence of total resorption of embryos at the highest dose tested. This increase in embryolethality is thought to result from the prolactin-lowering effect of pramipexole; prolactin is necessary for implantation and maintenance of early pregnancy in rats but not rabbits or humans. Because of pregnancy disruption and early embryonic loss in this study, the teratogenic potential of pramipexole could not be adequately assessed in rats. The highest no-effect dose for embryolethality in rats was associated with maternal plasma drug exposures (AUC) approximately equal to those in humans receiving the maximum recommended human dose (MRHD) of 4.5 mg/day. There were no adverse effects on embryo-fetal development following oral administration of pramipexole (0.1, 1, and 10 mg/kg/day) to pregnant rabbits during organogenesis (plasma AUC up to approximately 70 times that in humans at the MRHD). Postnatal growth was inhibited in the offspring of rats treated with pramipexole (0.1, 0.5, or 1.5 mg/kg/day) during the latter part of pregnancy and throughout lactation. The no-effect dose for adverse effects on offspring growth (0.1 mg/kg/day) was associated with maternal plasma drug exposures lower than that in humans at the MRHD
Pediatric use
8.4 Pediatric Use Safety and effectiveness of pramipexole dihydrochloride tablets in pediatric patients has not been established.
Geriatric use
8.5 Geriatric Use Pramipexole total oral clearance is approximately 30% lower in subjects older than 65 years compared with younger subjects, because of a decline in pramipexole renal clearance due to an age-related reduction in renal function. This resulted in an increase in elimination half-life from approximately 8.5 hours to 12 hours. In clinical studies with Parkinson’s disease patients, 38.7% of patients were older than 65 years. There were no apparent differences in efficacy or safety between older and younger patients, except that the relative risk of hallucination associated with the use of pramipexole dihydrochloride tablets was increased in the elderly.
Overdosage
There is no clinical experience with significant overdosage. One patient took 11 mg/day of pramipexole for 2 days in a clinical trial for an investigational use. Blood pressure remained stable although pulse rate increased to between 100 and 120 beats/minute. No other adverse events were reported related to the increased dose. There is no known antidote for overdosage of a dopamine agonist. If signs of central nervous system stimulation are present, a phenothiazine or other butyrophenone neuroleptic agent may be indicated; the efficacy of such drugs in reversing the effects of overdosage has not been assessed. Management of overdose may require general supportive measures along with gastric lavage, intravenous fluids, and electrocardiogram monitoring.
Description
Pramipexole dihydrochloride tablets contain pramipexole dihydrochloride a nonergot dopamine agonist. The chemical name of pramipexole dihydrochloride is (S)-2-amino-4,5,6,7-tetrahydro-6(propylamino)benzothiazole dihydrochloride monohydrate. Its empirical formula is C 10 H 17 N 3 S
• 2HCl
• H2O, and its molecular weight is 302.27. The structural formula is: Pramipexole dihydrochloride is a white to almost white crystalline powder. Melting occurs in the range of 296˚C to 301˚C, with decomposition. Pramipexole Dihydrochloride is freely soluble in water, soluble in methanol, sparingly soluble to slightly soluble in ethanol (96%) and practically insoluble in methylene chloride. Pramipexole dihydrochloride tablets, for oral administration, contain 0.125 mg, 0.25 mg, 0.5 mg, 0.75 mg, 1 mg, or 1.5 mg of pramipexole dihydrochloride, USP. Inactive ingredients consist of mannitol, corn starch, colloidal silicon dioxide, povidone, and magnesium stearate. pramipexolestructure
Mechanism of action
12.1 Mechanism of Action Pramipexole is a non-ergot dopamine agonist with high relative in vitro specificity and full intrinsic activity at the D2 subfamily of dopamine receptors, binding with higher affinity to D3 than to D2 or D4 receptor subtypes. Parkinson's Disease The precise mechanism of action of pramipexole as a treatment for Parkinson's disease is unknown, although it is believed to be related to its ability to stimulate dopamine receptors in the striatum. This conclusion is supported by electrophysiologic studies in animals that have demonstrated that pramipexole influences striatal neuronal firing rates via activation of dopamine receptors in the striatum and the substantia nigra, the site of neurons that send projections to the striatum. The relevance of D3 receptor binding in Parkinson's disease is unknown.
How supplied
16.1 How Supplied Pramipexole dihydrochloride tablets are available as follows: 0.125 mg, white to off-white, round, flat, beveled edge uncoated tablets, debossed with 'SG' on one side '126' on other side. NDC 31722-906-90: Bottles of 90 tablets NDC 31722-906-05: Bottles of 500 tablets NDC 31722-906-10: Bottles of 1000 tablets 0.25 mg, white to off white, oval, flat, beveled edge uncoated functional scored tablets debossed on one side with 'S' on the left side of bisect and 'G' on the right side of bisect and other side '1' on the left side and '27' on the right side of the bisect. NDC 31722-907-90: Bottles of 90 tablets NDC 31722-907-05: Bottles of 500 tablets NDC 31722-907-10: Bottles of 1000 tablets 0.5 mg, white to off white, oval, flat, beveled edge uncoated functional scored tablets debossed on one side with 'S' on the left side of bisect and 'G' on the right side of bisect and other side '1' on the left side and '28' on the right side of the bisect. NDC 31722-908-90: Bottles of 90 tablets NDC 31722-908-05: Bottles of 500 tablets NDC 31722-908-10: Bottles of 1000 tablets 0.75 mg, white to off white, oval, flat, beveled edge uncoated tablets, debossed with 'SG' on one side '129' on other side. NDC 31722-909-90: Bottles of 90 tablets NDC 31722-909-05: Bottles of 500 tablets NDC 31722-909-10: Bottles of 1000 tablets 1.0 mg, white to off white, oval, flat, beveled edge uncoated functional scored tablets debossed on one side with 'S' on the left side of bisect and 'G' on the right side of bisect and other side '1' on the left side and '30' on the right side of the bisect. NDC 31722-910-90: Bottles of 90 tablets NDC 31722-910-05: Bottles of 500 tablets NDC 31722-910-10: Bottles of 1000 tablets 1.5 mg, white to off white, oval, flat, beveled edge uncoated functional scored tablets debossed on one side with 'S' on the left side of bisect and 'G' on the right side of bisect and other side '1' on the left side and '31' on the right side of the bisect. NDC 31722-911-90: Bottles of 90 tablets NDC 31722-911-05: Bottles of 500 tablets NDC 31722-11-10: Bottles of 1000 tablets 16.2 Storage and Handling Store at 20 ºC to 25ºC (68 ºF to 77ºF); (see USP controlled Room Temperature). Protect from light. Store in a safe place out of the reach of children.
Patient information
Advise the patient to read the FDA-approved patient labeling (Patient Information). Dosing Instructions Instruct patients to take pramipexole dihydrochloride tablets only as prescribed. If a dose is missed, advise patients not to double their next dose. Pramipexole dihydrochloride tablets can be taken with or without food. If patients develop nausea, advise that taking pramipexole dihydrochloride tablets with food may reduce the occurrence of nausea. Pramipexole is the active ingredient that is in both pramipexole dihydrochloride tablets and extended-release pramipexole tablets. Ensure that patients do not take both extended-release pramipexole and pramipexole dihydrochloride tablets. Sedating Effects Alert patients to the potential sedating effects associated with pramipexole dihydrochloride tablets, including somnolence and the possibility of falling asleep while engaged in activities of daily living. Since somnolence is a frequent adverse reaction with potentially serious consequences, patients should neither drive a car nor engage in other potentially dangerous activities until they have gained sufficient experience with pramipexole dihydrochloride tablets to gauge whether or not it affects their mental and/or motor performance adversely. Advise patients that if increased somnolence or new episodes of falling asleep during activities of daily living (e.g., conversations or eating) are experienced at any time during treatment, they should not drive or participate in potentially dangerous activities until they have contacted their physician. Because of possible additive effects, advise caution when patients are taking other sedating medications or alcohol in combination with pramipexole dihydrochloride tablets and when taking concomitant medications that increase plasma levels of pramipexole (e.g., cimetidine) [see Warnings and Precautions ( 5.1 )] . Impulse Control Symptoms Including Compulsive Behaviors Alert patients and their caregivers to the possibility that they may experience intense urges to spend money uncontrollably, intense urges to gamble, increased sexual urges, binge eating and/or other intense urges and the inability to control these urges while taking pramipexole dihydrochloride tablets [see Warnings and Precautions ( 5.3 )]. Hallucinations and Pyschotic-like Behavior Inform patients that hallucinations and other psychotic-like behavior can occur and that the elderly are at a higher risk than younger patients with Parkinson's disease [see Warnings and Precautions ( 5.4 )]. Postural (Orthostatic) Hypotension Advise patients that they may develop postural (orthostatic) hypotension, with or without symptoms such as dizziness, nausea, fainting or blackouts, and sometimes, sweating. Hypotension may occur more frequently during initial therapy. Accordingly, caution patients against rising rapidly after sitting or lying down, especially if they have been doing so for prolonged periods and especially at the initiation of treatment with Pramipexole dihydrochloride tablets [see Warnings and Precautions ( 5.2 )]. Pregnancy Because the teratogenic potential of pramipexole has not been completely established in laboratory animals, and because experience in humans is limited, advise women to notify their physicians if they become pregnant or intend to become pregnant during therapy [see Use in Specific Populations ( 8.1 )]. Lactation Because of the possibility that pramipexole may be excreted in breast milk, advise women to notify their physicians if they intend to breast-feed or are breast-feeding an infant [see Use in Specific Populations ( 8.2 )]. Manufactured for: Camber Pharmaceuticals, Inc. Piscataway, NJ 08854 Manufactured by: ScieGen Pharmaceuticals, Inc. Hauppauge, NY 11788 USA Rev. 08/16 pramopexoleaddress1 pramopexoleaddress1 pramopexoleaddress1
Label text from the FDA structured product label by Camber Pharmaceuticals, Inc. (revised Oct 13, 2016). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Pramipexole Dihydrochloride in 6 products
Pramipexole NDC products (6)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 31722-906 | Pramipexole Dihydrochloride .125 mg/1 Tablet | Camber Pharmaceuticals, Inc. | ANDA |
| 31722-907 | Pramipexole Dihydrochloride .25 mg/1 Tablet | Camber Pharmaceuticals, Inc. | ANDA |
| 31722-908 | Pramipexole Dihydrochloride .5 mg/1 Tablet | Camber Pharmaceuticals, Inc. | ANDA |
| 31722-909 | Pramipexole Dihydrochloride .75 mg/1 Tablet | Camber Pharmaceuticals, Inc. | ANDA |
| 31722-910 | Pramipexole Dihydrochloride 1 mg/1 Tablet | Camber Pharmaceuticals, Inc. | ANDA |
| 31722-911 | Pramipexole Dihydrochloride 1.5 mg/1 Tablet | Camber Pharmaceuticals, Inc. | ANDA |
Frequently asked questions
What is Pramipexole used for?
1 INDICATIONS & USAGE PRAMIPEXOLE DIHYDROCHLORIDE tablets is a non-ergot dopamine agonist indicated for the treatment of • the signs and symptoms of idiopathic Parkinson's disease (PD) ( 1.1 ) 1.1 Parkinson's Disease Pramipexole dihydrochloride tablets are indicated for the treatment of the signs and symptoms of idiopathic Parkinson's disease.
What are the side effects of Pramipexole?
The following adverse reactions are discussed in greater detail in other sections of the labeling: •Falling Asleep During Activities of Daily Living [see Warnings and Precautions (5.1)]. •Symptomatic Orthostatic Hypotension [see Warnings and Precautions (5.2)]. •Impulse Control/Compulsive Behaviors [see Warnings and Precautions (5.3)]. •Hallucinations [see Warnings and Precautions ( 5.4 )].… See the full label for the complete list.
Who makes Pramipexole?
Pramipexole is listed by 1 labeler in the FDA NDC directory, including Camber Pharmaceuticals, Inc..