Pramipexole dihydrochloride .25 mg Tablet, 500-count
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Nonergot Dopamine Agonist class.
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🏭 Manufacturer & labeler
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🩺 Clinical
Pramipexole is used alone or with other medications to treat the symptoms of Parkinson's disease (PD; a disorder of the nervous system that causes difficulties with movement, muscle control, and balance), including shaking of parts of the body, stiffness, slowed movements, and problems with balance. Pramipexole is also used to treat restless legs syndrome (RLS; a condition that causes discomfort in the legs and a strong urge to move the legs, especially at night and when sitting or lying down). Pramipexole is in a class of medications called dopamine agonists. It works by acting in place of do...
Read the full MedlinePlus article ↗- Pramipexole is mainly used to treat Parkinson's disease — it helps manage the motor symptoms like tremor and stiffness by mimicking a brain chemical called dopamine. The immediate-...
- It can, yes — drowsiness is one of the most common side effects. But the bigger concern is something called a 'sleep attack,' where you fall asleep suddenly during everyday activit...
- Will this medication make me really drowsy?
- This is a real and important risk. Some people develop strong, hard-to-control urges while taking pramipexole — things like gambling, spending money compulsively, binge eating, or...
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💊 What it looks like
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
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UNII 70097M6I30
Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
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UNII 3OWL53L36A
A natural sugar alcohol derived from seaweed or synthesized in the lab. It's used as a filler to add bulk, a sweetener in sugar-free formulas, and a disintegrant to help tablets break apart in the stomach.
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UNII K0KQV10C35
Povidone K25 is a synthetic polymer made from vinyl pyrrolidone. It acts as a binder to hold tablet ingredients together and as a disintegrant to help the tablet break apart in the stomach for better absorption.
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UNII ETJ7Z6XBU4
Silicon dioxide is a naturally occurring mineral used as a glidant and anti-caking agent. It helps powder ingredients flow smoothly and prevents clumping during manufacturing and storage.
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UNII O8232NY3SJ
A plant-based carbohydrate derived from corn kernels. It acts as a filler to add bulk, a binder to hold ingredients together, and a disintegrant to help the tablet break apart in your stomach for absorption.
5 inactive ingredients listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per ea | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $0.050 | $25.00 / 500 tablets |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · Q2 2026 | $0.1159 | $57.95 / 500 tablets |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Pramipexole Dihydrochloride .25 mg 00904-6704-61 | Major | 100 tablets | $0.047 | AB | Availability likely | save 6% |
| Pramipexole Dihydrochloride .25 mg 13668-0092-05 | Torrent | 500 tablets | $0.047 | AB | Availability likely | save 6% |
| Pramipexole Dihydrochloride .25 mg 50228-0127-10 | ScieGen | 1000 tablets | $0.047 | AB | Availability likely | save 6% |
| Pramipexole Dihydrochloride .25 mg 57237-0181-90 | Rising | 90 tablets | $0.047 | AB | Availability likely | save 6% |
| Pramipexole Dihydrochloride .25 mg 60687-0570-01 | American | 100 tablets | $0.047 | AB | Availability likely | save 6% |
| Pramipexole dihydrochloride .25 mgthis 33342-0032-15 | Macleods | 500 tablets | $0.050 | — | FDA listed | — |
| Pramipexole dihydrochloride .25 mg 00615-8551-39 | NCS | 30 tablets | — | AB | FDA listed | — |
| pramipexole dihydrochloride .25 mg 29300-0208-10 | Unichem | 1000 tablets | — | — | FDA listed | — |
| Pramipexole .25 mg 31722-0907-05 | Camber | 500 tablets | — | AB | FDA listed | — |
| Pramipexole Dihydrochloride .25 mg 46708-0004-90 | Alembic | 90 tablets | — | — | FDA listed | — |
| Pramipexole Dihydrochloride .25 mg 46708-0612-90 | Alembic | 90 tablets | — | — | FDA listed | — |
| Pramipexole Dihydrochloride .25 mg 50090-3280-00 | A-S | 90 tablets | — | AB | FDA listed | — |
| Pramipexole Dihydrochloride .25 mg 60429-0086-90 | Golden | 90 tablets | — | AB | FDA listed | — |
| Pramipexole Dihydrochloride .25 mg 62332-0004-90 | Alembic | 90 tablets | — | — | FDA listed | — |
| Pramipexole Dihydrochloride .25 mg 63629-5013-01 | Bryant | 90 tablets | — | AB | FDA listed | — |
| pramipexole dihydrochloride .25 mg 64380-0747-01 | Strides | 100 tablets | — | AB | FDA listed | — |
| Pramipexole Dihydrochloride .25 mg 65862-0605-78 | Aurobindo | 100 tablets | — | AB | FDA listed | — |
| Pramipexole dihydrochloride .25 mg 68462-0331-05 | Glenmark | 500 tablets | — | AB | FDA listed | — |
| Pramipexole Dihydrochloride .25 mg 71335-1877-01 | Bryant | 90 tablets | — | AB | FDA listed | — |
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⏳ Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
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📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
🔬 Reported adverse events (FAERS)
Top reported reactions
Age at onset
Reporter sex
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📦 Packaging — all sizes for this product
| Package NDC | Description | Per unit | Per pack | Marketing start | Status |
|---|---|---|---|---|---|
| 33342-0032-06 | 30 BLISTER PACK in 1 CARTON (33342-032-06) / 1 TABLET in 1 BLISTER PACK | — | — | 2012-09-21 | Active |
| 33342-0032-10 | 90 TABLET in 1 BOTTLE (33342-032-10) | $0.0500 / ea | $4.50 | 2012-09-21 | Active |
| 33342-0032-12 | 100 BLISTER PACK in 1 CARTON (33342-032-12) / 1 TABLET in 1 BLISTER PACK | — | — | 2012-09-21 | Active |
| 33342-0032-15 You're viewing this | 500 TABLET in 1 BOTTLE (33342-032-15) | $0.0500 / ea | $25.01 | 2012-09-21 | Active |
This pack effectively ties for the lowest per-ea cost of the 2 priced pack sizes ($0.0500 NADAC).
Pack size FAQ
What quantity is in NDC 33342-0032-15?
What is the difference between NDC 33342-0032-15 and NDC 33342-0032-06?
What NDC number is used to bill for this package of Pramipexole dihydrochloride .25 mg Tablet?
Prices are the latest CMS NADAC pharmacy acquisition cost per NDC; per-pack figures are per-unit × pack quantity, shown only when the pack is denominated in the same measure NADAC prices.
📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS & USAGE Pramipexole dihydrochloride tablets are a non-ergot dopamine agonist indicated for the treatment of: · Parkinson’s disease (PD) ( 1.1 ) • Moderate-to-severe primary Restless Legs Syndrome (RLS) ( 1.2 )
1.1Parkinson's Disease Pramipexole dihydrochloride tablets are indicated for the treatment of Parkinson's disease.
1.2Restless Legs Syndrome Pramipexole dihydrochloride tablets are indicated for the treatment of moderate-to-severe primary Restless Legs Syndrome (RLS).
⏱️ Dosage and Administration ▾
2 DOSAGE & ADMINISTRATION Parkinson’s Disease-Normal Renal Function* ( 2.2 ) Week Dosage (mg) Total Daily Dose (mg) 1 0.125 TID 0.375 2
0.25TID 0.75 3
0.5TID 1.5 4
0.75TID 2.25 5 1 TID 3 6
1.25TID 3.75 7
1.5TID 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
1.5TID 30 to 50 mL/min 0.125 BID
0.75TID 15 to 30 mL/min 0.125 QD
1.5QD < 15 mL/min and hemodialysis patients Data not available Restless Legs Syndrome* ( 2.3 ) Titration Step Dose (mg) 2-3 hours before bedtime 1 0.125 2 (if needed) 0.25 3 (if needed) 0.5 * Dosing interval is 4-7 days (14 days in patients with CrCl 20-60 mL/min)
2.1General 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.
2.2Dosing for 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 Table 1: Table 1 Ascending Dosage Schedule of Pramipexole Dihydrochloride Tablets for Parkinson's Disease Week Dosage (mg) Total Daily Dose (mg) 1 0.125 three times a day 0.375 2 0.25 three times a day 0.75 3 0.5 three times a day 1.50 4 0.75 three times a day 2.25 5 1 three times a day 3.0 6 1.25 three times a day 3.75 7 1.5 three times a day
4.50Maintenance 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 The recommended dosing of pramipexole dihydrochloride tablets in Parkinson's disease patients with renal impairment is provided in Table 2. 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 three times a day 1.5 three times a day Moderate impairment (creatinine Cl =30 to 50 mL/min) 0.125 twice a day 0.75 three times a day Severe impairment (creatinine Cl =15 to <30 mL/min) 0.125 once a day 1.5 once a day Very severe impairment (creatinine Cl <15 mL/min and hemod…
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS • 0.125 mg: White coloured, circular, flat, beveled edged uncoated tablet debossed 'CL' on one side of the tablet and '2' on the other side. Each tablet contains 0.125 mg pramipexole dihydrochloride monohydrate equivalent to 0.118 mg pramipexole dihydrochloride. • 0.25 mg: White coloured, oval shaped, uncoated tablet with 'CL' and '3' debossed on one side of the tablet with breakline separating 'CL' and '3' and having a breakline on the other side. Each tablet contains 0.25 mg pramipexole dihydrochloride monohydrate equivalent to 0.235 mg pramipexole dihydrochloride. • 0.5 mg: White coloured, oval shaped, uncoated tablet with 'CL' and '4' debossed on one side of the tablet with breakline separating 'CL' and '4' and having a breakline on the other side.
Each tablet contains 0.5 mg pramipexole dihydrochloride monohydrate equivalent to 0.47 mg pramipexole dihydrochloride. • 1 mg: White coloured, flat, circular, beveled edged uncoated tablet with 'CL' and '5' debossed on one side of the tablet with breakline separating 'CL' and '5' and having a breakline on the other side. Each tablet contains 1 mg pramipexole dihydrochloride monohydrate equivalent to 0.94 mg pramipexole dihydrochloride. • 1.5 mg: White coloured, flat, circular, beveled edged uncoated tablet with 'CL' and '6' debossed on one side of the tablet with breakline separating 'CL' and '6' and having a breakline on the other side.
Each tablet contains 1.5 mg pramipexole dihydrochloride monohydrate equivalent to 1.41 mg pramipexole dihydrochloride. Tablets: 0.125 mg, 0.25 mg, 0.5 mg, 1 mg, and 1.5 mg ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS None. None
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS • Falling Asleep During Activities of Daily Living: Sudden onset of sleep may occur without warning; advise patients to report symptoms ( 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 and Psychotic-like Behavior: May occur; risk increases with age ( 5.4 ) • Dyskinesia: May be caused or exacerbated by pramipexole dihydrochloride tablets ( 5.5 ) • Postural Deformity: Consider reducing the dose or discontinuing pramipexole dihydrochloride tablets if postural deformity occurs ( 5.6 )
5.1Falling Asleep During Activities of Daily Living and Somnolence 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.
Somnolence is a common occurrence in patients receiving pramipexole at doses above 1.5 mg/day (0.5 mg three times a day) for Parkinson's disease. In controlled clinical trials in RLS, patients treated with pramipexole dihydrochloride tablets at doses of 0.25-0.75 mg once a day, the incidence of somnolence was 6% compared to an incidence of 3% for placebo-treated patients [ see Adverse Reactions ( 6.1 ) ]. 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 tablets, advise patients of the potential to develop drowsiness and specifically ask about factors that may increase the risk for somnolence 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 that might result in harm if the patients become somnolent. 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.
5.2Symptomatic 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, both Parkinson's disease patients and RLS 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…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the labeling: • Falling Asleep During Activities of Daily Living and Somnolence [ 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 and Psychotic-like Behavior [ see Warnings and Precautions ( 5.4 ) ]. • Dyskinesia [ see Warnings and Precautions ( 5.5 ) ]. • Postural Deformity [ see Warnings and Precautions ( 5.6 ) ] • Rhabdomyolysis [ see Warnings and Precautions ( 5.8 ) ]. • Retinal Pathology [ see Warnings and Precautions ( 5.9 ) ]. • Events Reported with Dopaminergic Therapy [ see Warnings and Precautions ( 5.10 ) ]. • Withdrawal Symptoms [ see Warnings and Precautions ( 5.11 ) ] Most common adverse reactions (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) • RLS: nausea, somnolence, fatigue, and headache (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Macleods Pharma USA, Inc. at 1-888-943-3210 or 1-855-926-3384 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction 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 reactions, this section will, in general, present adverse-reaction 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 reactions.
Early Parkinson's Disease In the three double-blind, placebo-controlled trials of patients with early Parkinson's disease, the most common adverse reactions (>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 reactions compared with 11% of 235 patients who received placebo.
The adverse reactions 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]; 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]…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Dopamine antagonists: May diminish the effectiveness of pramipexole ( 7.1 )
7.1Dopamine 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.
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Pregnancy: Based on animal data, may cause fetal harm ( 8.1 )
8.1Pregnancy Risk Summary There are no adequate data on the developmental risk associated with the use of pramipexole dihydrochloride 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% to 4% and 15% to 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 in 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, or 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.
8.2Lactation 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 dihydrochloride and any potential adverse effects on the breastfed infant from pramipexole dihydrochloride 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.
8.4Pediatric Use Safety and efficacy of pramipexole dihydrochloride in pediatric patients has not been established.
8.5Geriatric 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. In clinical studies with RLS patients, 22% of patients were at least 65 years old. There were no apparent differences in efficacy or safety between olde…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary There are no adequate data on the developmental risk associated with the use of pramipexole dihydrochloride 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% to 4% and 15% to 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 in 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, or 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 ▾
8.4Pediatric Use Safety and efficacy of pramipexole dihydrochloride in pediatric patients has not been established.
🧓 Geriatric Use ▾
8.5Geriatric 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. In clinical studies with RLS patients, 22% of patients were at least 65 years old. There were no apparent differences in efficacy or safety between older and younger patients.
🆘 Overdosage ▾
10 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 reactions 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.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action Pramipexole is a non-ergot dopamine agonist with high relative in vitro specificity and full intrinsic activity at the D 2 subfamily of dopamine receptors, binding with higher affinity to D 3 than to D 2 or D 4 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 D 3 receptor binding in Parkinson’s disease is unknown. Restless Legs Syndrome (RLS) The precise mechanism of action of pramipexole dihydrochloride tablets as a treatment for RLS is unknown. Although the pathophysiology of RLS is largely unknown, neuropharmacological evidence suggests primary dopaminergic system involvement.
Positron Emission Tomographic (PET) studies suggest that a mild striatal presynaptic dopaminergic dysfunction may be involved in the pathogenesis of RLS.
12.2Pharmacodynamics The effect of pramipexole on the QT interval of the ECG was investigated in a clinical study in 60 healthy male and female volunteers. All subjects initiated treatment with 0.375 mg extended release pramipexole tablets administered once daily, and were up-titrated every 3 days to 2.25 mg and 4.5 mg daily, a faster rate of titration than recommended in the label. No dose- or exposure-related effect on mean QT intervals was observed; however, the study did not have a valid assessment of assay sensitivity.
The effect of pramipexole on QTc intervals at higher exposures achieved either due to drug interactions (e.g., with cimetidine), renal impairment, or at higher doses has not been systematically evaluated. Although mean values remained within normal reference ranges throughout the study, supine systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse rate for subjects treated with pramipexole generally increased during the rapid up-titration phase, by 10 mmHg, 7 mmHg, and 10 bpm higher than placebo, respectively.
Higher SBP, DBP, and pulse rates compared to placebo were maintained until the pramipexole doses were tapered; values on the last day of tapering were generally similar to baseline values. Such effects have not been observed in clinical studies with Parkinson’s disease patients, who were titrated according to labeled recommendations.
12.3Pharmacokinetics Pramipexole displays linear pharmacokinetics over the clinical dosage range. Its terminal half-life is about 8 hours in young healthy volunteers and about 12 hours in elderly volunteers. Steady-state concentrations are achieved within 2 days of dosing.
Absorption Pramipexole is rapidly absorbed, reaching peak concentrations in approximately 2 hours. The absolute bioavailability of pramipexole is greater than 90%, indicating that it is well absorbed and undergoes little presystemic metabolism. Food does not affect the extent of pramipexole absorption, although the time of maximum plasma concentration (T max ) is increased by about 1 hour when the drug is taken with a meal.
Distribution Pramipexole is extensively distributed, having a volume of distribution of about 500 L (coefficient of variation [CV]=20%). It is about 15% bound to plasma proteins. Pramipexole distributes into red blood cells as indicated by an erythrocyte-to-plasma ratio of approximately 2.
Metabolism Pramipexole is metabolized only to a negligible extent (<10%). No specific active metabolite has been identified in human plasma or urine. Elimination Urinary excretion is the major route of pramipexole elimination, with 90% of a pramipexole dose recovered in urine, almost all as unchanged drug.
The renal…
🧬 Mechanism of Action ▾
12.1Mechanism of Action Pramipexole is a non-ergot dopamine agonist with high relative in vitro specificity and full intrinsic activity at the D 2 subfamily of dopamine receptors, binding with higher affinity to D 3 than to D 2 or D 4 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 D 3 receptor binding in Parkinson’s disease is unknown. Restless Legs Syndrome (RLS) The precise mechanism of action of pramipexole dihydrochloride tablets as a treatment for RLS is unknown. Although the pathophysiology of RLS is largely unknown, neuropharmacological evidence suggests primary dopaminergic system involvement.
Positron Emission Tomographic (PET) studies suggest that a mild striatal presynaptic dopaminergic dysfunction may be involved in the pathogenesis of RLS.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1How Supplied Pramipexole dihydrochloride tablets are available as follows: 0.125 mg: White coloured, circular, flat, beveled edged uncoated tablet debossed 'CL' on one side of the tablet and '2' on the other side. Bottles of 90's NDC 33342-031-10 Bottles of 500's NDC 33342-031-15 Unit dose blister Pack of 30's NDC 33342-031-06 Unit dose blister pack of 100's NDC 33342-031-12 0.25 mg: White coloured, oval shaped, uncoated tablet with 'CL' and '3' debossed on one side of the tablet with breakline separating 'CL' and '3' and having a breakline on the other side.
Bottles of 90's NDC 33342-032-10 Bottles of 500's NDC 33342-032-15 Unit dose blister pack of 30's NDC 33342-032-06 Unit dose blister pack of 100's NDC 33342-032-12 0.5 mg: White coloured, oval shaped, uncoated tablet with 'CL' and '4' debossed on one side of the tablet with breakline separating 'CL' and '4' and having a breakline on the other side. Bottles of 90's NDC 33342-033-10 Bottles of 500's NDC 33342-033-15 Unit dose blister pack of 30's NDC 33342-033-06 Unit dose blister pack 100's NDC 33342-033-12 1 mg: White coloured, flat, circular, beveled edged uncoated tablet with 'CL' and '5' debossed on one side of the tablet with breakline separating 'CL' and '5' and having a breakline on the other side.
Bottles of 90's NDC 33342-034-10 Bottles of 500's NDC 33342-034-15 Unit dose blister pack of 30's NDC 33342-034-06 Unit dose blister pack of 100s NDC 33342-034-12 1.5 mg: White coloured, flat, circular, beveled edged uncoated tablet with 'CL' and '6' debossed on one side of the tablet with breakline separating 'CL' and '6' and having a breakline on the other side. Bottles of 90's NDC 33342-035-10 Bottles of 500's NDC 33342-035-15 Unit dose blister pack of 30's NDC 33342-035-06 Unit dose blister pack of 100's NDC 33342-035-12
16.2Storage and Handling Store pramipexole dihydrochloride tablets at 20° to 25°C (68° to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Protect from light. Store in a safe place out of the reach of children.
📋 Description ▾
11 DESCRIPTION Pramipexole dihydrochloride tablets contain pramipexole dihydrochloride (as a monohydrate). Pramipexole is a nonergot dopamine agonist. The chemical name of pramipexole dihydrochloride monohydrate 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•H 2 O, and its molecular weight is 302.26. Pramipexole dihydrochloride is a white to off-white powder substance. Melting occurs in the range of 296°C to 301°C, with decomposition.
Pramipexole dihydrochloride is more than 20% soluble in water, about 8% in methanol, about 0.5% in ethanol, and practically insoluble in dichloromethane. Pramipexole dihydrochloride tablets 0.125 mg: Each tablet contains 0.125 mg pramipexole dihydrochloride monohydrate equivalent to 0.118 mg pramipexole dihydrochloride. Pramipexole dihydrochloride tablets 0.25 mg: Each tablet contains 0.25 mg pramipexole dihydrochloride monohydrate equivalent to 0.235 mg pramipexole dihydrochloride.
Pramipexole dihydrochloride tablets 0.5 mg: Each tablet contains 0.5 mg pramipexole dihydrochloride monohydrate equivalent to 0.47 mg pramipexole dihydrochloride. Pramipexole dihydrochloride 1 mg tablets: Each tablet contains 1 mg pramipexole dihydrochloride monohydrate equivalent to 0.94 mg pramipexole dihydrochloride. Pramipexole dihydrochloride 1.5 mg tablets: Each tablet contains 1.5 mg pramipexole dihydrochloride monohydrate equivalent to 1.41 mg pramipexole dihydrochloride.
Inactive ingredients for all strengths of pramipexole dihydrochloride tablets consist of mannitol, pregelatinized starch, colloidal silicon dioxide, povidone, and magnesium stearate. structure
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information). Dosing Instruction 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 )].
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 ) ].
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 Psychotic-like Behavior Inform patients that hallucinations and other psychotic-like behavior can occur.
In patients with Parkinson’s disease, the elderly are at a higher risk than younger patients [ see Warnings and Precautions ( 5.4 ) ]. Withdrawal-Emergent Hyperpyrexia and Confusion Advise patients who have been prescribed a lower dose or who have been withdrawn from the drug to notify their healthcare provider if they have symptoms such as fever, muscular rigidity, or altered consciousness [ see Warnings and Precautions( 5.10 ) ]. Withdrawal Symptoms Advise patients that withdrawal symptoms may occur during or after discontinuation or dose reduction of pramipexole dihydrochloride tablets.
Advise patients who have been prescribed a lower dose or who have been withdrawn from the drug to notify their healthcare provider if they have withdrawal symptoms such as apathy, anxiety, depression, fatigue, insomnia, sweating, or pain. Notify patients that in case of severe withdrawal symptoms, a trial re-administration of a dopamine agonist at the lowest effective dose may be considered [ see Warnings and Preca…