Pramipexole Dihydrochloride 1.5 mg Tablet, Extended Release, 30-count
🆔 Identity & classification
Where does this data come from?
🏷️ RxNorm drug class
This medicine belongs to the Nonergot Dopamine Agonist class.
Where does this data come from?
🏭 Manufacturer & labeler
Where does this data come from?
🩺 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...
Patient education
Supplement & herbal interactions
Where does this data come from?
Ask a licensed pharmacist directly — free, answered by our team.
💊 What it looks like
Where does this data come from?
🧪 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.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
-
UNII 4Q93RCW27E
A synthetic polymer made from acrylic acid that's crosslinked for stability. It acts as a thickener and gelling agent in creams and gels, helping the medicine spread evenly and maintain its texture.
-
UNII 3NXW29V3WO
Hypromellose is a plant-based thickener made from cellulose. It's used in medicines as a binder to hold ingredients together, a coating for tablets, and a thickener for liquids.
-
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.
-
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.
-
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.
-
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.
6 inactive ingredients listed in the exact product block matched to this NDC.
Where does this data come from?
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
Are inactive ingredients the same for every manufacturer?
Why might an inactive ingredient be missing?
Can inactive ingredients matter?
💲 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 | $1.718 | $51.55 / 30 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 | $3.78 | $113.47 / 30 tablets |
Where does this data come from?
🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Pramipexole Dihydrochloride 1.5 mgthis 16714-0918-01 | NorthStar | 30 tablets | $1.718 | AB | Availability likely | — |
| Pramipexole Dihydrochloride 1.5 mg 33342-0210-07 | Macleods | 30 tablets | $1.718 | AB | Availability likely | — |
| Pramipexole dihydrochloride 1.5 mg 50742-0333-30 | Ingenus | 30 tablets | $1.718 | AB | Availability likely | — |
| Pramipexole dihydrochloride 1.5 mg 55111-0613-30 | Dr. | 30 tablets | $1.718 | AB | Availability likely | — |
| Pramipexole Dihydrochloride 1.5 mg 62332-0156-30 | Alembic | 30 tablets | $1.718 | AB | Availability likely | — |
| Pramipexole Dihydrochloride 1.5 mg 46708-0576-30 | Alembic | 30 tablets | — | AB | FDA listed | — |
Where does this data come from?
⏳ Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
Where does this data come from?
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
🔬 Reported adverse events (FAERS)
Top reported reactions
Age at onset
Reporter sex
Where does this data come from?
📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 16714-0918-01 You're viewing this | 30 TABLET, EXTENDED RELEASE in 1 BOTTLE (16714-918-01) | 2019-03-06 | Active |
📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Pramipexole dihydrochloride extended-release tablets are indicated for the treatment of Parkinson's disease. Pramipexole dihydrochloride extended-release tablets are a non-ergot dopamine agonist indicated for the treatment of Parkinson's disease (PD) ( 1 )
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION • Pramipexole dihydrochloride extended-release tablets are taken once daily, with or without food ( 2.1 ) • Tablets must be swallowed whole and must not be chewed, crushed, or divided ( 2.1 ) • Starting dose is 0.375 mg given once daily ( 2.2 ) • 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 ( 2.2 ) • 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 ( 2.3 ) • Pramipexole dihydrochloride extended-release tablets should be discontinued gradually ( 2.2 )
2.1General Dosing Considerations 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.
2.2Recommended Dosage 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 [see Clinical Studies ( 14 )]. Due to the flexible dose design used in clinical trials, specific dose-response information could not be determined [see Clinical Studies ( 14 )].
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 [ see Warnings and Precautions ( 5.10 , 5.11 )]. Recommended Dosage in Patients with Renal Impairment In patients with moderate renal impairment (creatinine clearance between 30 and 50 mL/min), pramipexole dihydrochloride extended-release tablets should initially be taken every other day.
Caution should be exercised and careful assessment of therapeutic response and tolerability should be made before increasing to daily dosing after one week, and before any additional titration in 0.375 mg increments up to 2.25 mg per day. Dose adjustment should occur no more frequently than at weekly intervals. 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.
2.3Switching from Immediate-Release Pramipexole Tablets to Pramipexole Dihydrochloride Extended-Release Tablets 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.
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS • 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. • 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. Extended-release tablets: 0.375 mg, 0.75 mg, 1.5 mg, 2.25 mg, 3 mg and 4.5 mg ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS None. None ( 4 )
⚠️ 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 closely especially 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 extended-release tablets ( 5.5 ) • Postural Deformity: Consider reducing the dose or discontinuing pramipexole dihydrochloride extended-release 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.
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) [ 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 extended-release tablets should ordinarily be discontinued.
If a decision is made to continue pramipexole dihydrochloride extended-release 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 r…
🤒 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: somnolence, nausea, constipation, dizziness, fatigue, hallucinations, dry mouth, muscle spasms, and peripheral edema ( 6.1 ) • Advanced PD with levodopa: dyskinesia, nausea, constipation, hallucinations, headache, and anorexia ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact NorthStar RxLLC at 1-800-206-7821 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 (or of another development program of a different formulation of the same drug) and may not reflect the rates observed in practice. During the premarketing development of pramipexole dihydrochloride extended-release tablets, patients with early Parkinson's disease were treated with pramipexole dihydrochloride extended-release tablets, placebo, or immediate-release pramipexole tablets.
In addition, a randomized, double-blind, parallel group trial was conducted in 156 early Parkinson’s disease patients (Hoehn & Yahr Stages I-III) to assess overnight switching of immediate-release pramipexole tablets to pramipexole dihydrochloride extended-release tablets. In this latter study, concomitant treatment with stable doses of levodopa, monoamine oxidase B inhibitor (MAOB-I) drugs, anticholinergics, or amantadine, individually or in combination, was allowed. In a third trial, advanced Parkinson’s disease patients received pramipexole dihydrochloride extended-release tablets, placebo, or immediate-release pramipexole tablets as adjunctive therapy to levodopa.
Early Parkinson's Disease The most common adverse reactions (≥5% and more frequent than placebo) after 33 weeks of treatment with pramipexole dihydrochloride extended-release tablets in the trial of early Parkinson’s disease patients were somnolence, nausea, constipation, dizziness, fatigue, hallucinations, dry mouth, muscle spasms, and peripheral edema. Twenty four of 223 (11%) patients treated with pramipexole dihydrochloride extended-release tablets for 33 weeks discontinued treatment due to adverse reactions compared to 4 of 103 (4%) patients who received placebo and approximately 20 of 213 (9%) patients who received immediate-release pramipexole tablets.
The adverse reaction most commonly causing discontinuation of treatment with pramipexole dihydrochloride extended-release tablets was nausea (2%). Table 1 lists adverse reactions that occurred with a frequency of at least 2% with pramipexole dihydrochloride extended-release tablets and were more frequent than with placebo during 33 weeks of treatment in a double-blind, placebo-controlled study in early Parkinson's disease. In this study, patients did not receive concomitant levodopa; however, levodopa was permitted as rescue medication.
Table 1 Adverse-Reactions in a 33-Week Double-Blind, Placebo-Controlled Trial with Pramipexole Dihydrochloride Extended-Release Tablets in Early Parkinson’s Disease Body System/…
🔄 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 extended-release 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 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 [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 extended-release tablets and any potential adverse effects on the breastfed infant from pramipexole dihydrochloride extended-release tablets 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 effectiveness of pramipexole dihydrochloride extended-release tablets in pediatric patients have not been evaluated.
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 a placebo-controlled clinical trial of pramipexole dihydrochloride extended-release tablets in early Parkinson’s disease, 47% of the 259 patients were ≥65 years of age.
Among patients receiving pramipexole dihydrochloride extended-release tablets, hallucinations were more common in the elderly, occurring in 13% of the patients ≥65 years of age compared to 2% of the patients…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary 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 [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 effectiveness of pramipexole dihydrochloride extended-release tablets in pediatric patients have not been evaluated.
🧓 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 a placebo-controlled clinical trial of pramipexole dihydrochloride extended-release tablets in early Parkinson’s disease, 47% of the 259 patients were ≥65 years of age.
Among patients receiving pramipexole dihydrochloride extended-release tablets, hallucinations were more common in the elderly, occurring in 13% of the patients ≥65 years of age compared to 2% of the patients <65 years of age.
🆘 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. 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.
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 pramipexole dihydrochloride extended-release 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 dihydrochloride extended-release tablets, like immediate-release pramipexole tablets, display linear pharmacokinetics over the entire clinical dosage range. Slow release of pramipexole from pramipexole dihydrochloride extended-release tablets with once-daily administration results in the same daily maximum and minimum pramipexole plasma concentrations (C max , C min ) as three times daily administration of immediate-release pramipexole tablets. Absorption The absolute bioavailability of pramipexole is greater than 90%, indicating that it is well absorbed and undergoes little presystemic metabolism.
Increase in systemic exposure of pramipexole following oral administration of 0.375 mg to 4.5 mg of pramipexole dihydrochloride extended-release tablets was dose-proportional. For pramipexole dihydrochloride extended-release tablets, steady state of exposure is reached within 5 days of continuous dosing. Relative bioavailability of pramipexole dihydrochloride extended-release tablets compared with immediate-release tablets was approximately 100%.
In a repeat-dose study in healthy, normal volunteers, pramipexole dihydrochloride extended-release tablets 4.5 mg administered once daily was bioequivalent with regard to C max and AUC over 24 hours to immediate-release pramipexole tablets 1.5 mg administered three times daily. The average time-to-peak concentration for pramipexole dihydrochloride extended-release tablets is 6 hours. Administration of pramipexole dihydrochloride extended-release tablets with food (i.e., high-fat meal) did not affect AUC but increased C max by approximately 20% and delayed T max by approximately 2 hours compared with dosing under fasted conditions; these diffe…
🧬 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. 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.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING
16.1How Supplied Pramipexole dihydrochloride extended-release tablets are available as follows: 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. Unit of Use Bottles of 30 NDC 16714-916-01 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.
Unit of Use Bottles of 30 NDC 16714-917-01 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. Unit of Use Bottles of 30 NDC 16714-918-01 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. Unit of Use Bottles of 30 NDC 16714-919-01 3.0 mg: White colored, oval shaped, biconvex, uncoated tablet debossed ‘ER 5’ on one side of the tablet and ‘3.0’ on other side.
Unit of Use Bottles of 30 NDC 16714-920-01 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. Unit of Use Bottles of 30 NDC 16714-922-01
16.2Storage and Handling Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Protect from exposure to high humidity. Store in a safe place out of the reach of children.
📋 Description ▾
11 DESCRIPTION Pramipexole dihydrochloride extended-release tablets contain pramipexole dihydrochloride (as a monohydrate). Pramipexole is a non-ergot 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. The structural formula is: Pramipexole dihydrochloride USP is a white to off-white powder substance. Melting occurs in the range of 296°C to 301°C, with decomposition.
Pramipexole dihydrochloride USP is more than 20% soluble in water, about 8% in methanol, about 0.5% in ethanol, and practically insoluble in dichloromethane. Pramipexole dihydrochloride extended-release tablets, 0.375 mg: Each extended-release tablet contains 0.375 mg pramipexole dihydrochloride monohydrate equivalent to 0.352 mg pramipexole dihydrochloride, USP. Pramipexole dihydrochloride extended-release tablets, 0.75 mg: Each extended-release tablet contains 0.75 mg pramipexole dihydrochloride monohydrate equivalent to 0.705 mg pramipexole dihydrochloride,USP.
Pramipexole dihydrochloride extended-release tablets, 1.5 mg: Each extended-release tablet contains 1.5 mg pramipexole dihydrochloride monohydrate equivalent to 1.41 mg pramipexole dihydrochloride,USP. Pramipexole dihydrochloride extended-release tablets, 2.25 mg: Each extended-release tablet contains 2.25 mg pramipexole dihydrochloride monohydrate equivalent to 2.12 mg pramipexole dihydrochloride,USP. Pramipexole dihydrochloride extended-release tablets, 3 mg: Each extended-release tablet contains 3 mg pramipexole dihydrochloride monohydrate equivalent to 2.82 mg pramipexole dihydrochloride,USP.
Pramipexole dihydrochloride extended-release tablets, 4.5 mg: Each extended-release tablet contains 4.5 mg pramipexole dihydrochloride monohydrate equivalent to 4.23 mg pramipexole dihydrochloride,USP. Inactive ingredients for all strengths of pramipexole dihydrochloride extended-release tablets consist of hypromellose, mannitol, pregelatinized starch, carbomer homopolymer, colloidal silicon dioxide, and magnesium stearate. prami
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information). Dosing Instructions Instruct patients to take pramipexole dihydrochloride extended-release tablets only as prescribed. If a dose is missed, pramipexole dihydrochloride extended-release tablets should be taken as soon as possible, but no later than 12 hours after the regularly scheduled time.
After 12 hours, the missed dose should be skipped and the next dose should be taken on the following day at the regularly scheduled time. Pramipexole dihydrochloride extended-release tablets can be taken with or without food. If patients develop nausea, advise that taking pramipexole dihydrochloride extended-release tablets with food may reduce the occurrence of nausea.
Pramipexole dihydrochloride extended-release tablets should be swallowed whole. They should not be chewed, crushed, or divided [see Dosage and Administration ( 2.1 )] . Inform patients that residue in stool which may resemble a swollen original pramipexole dihydrochloride extended-release tablet or swollen pieces of the original tablet have been reported [ see Adverse Reactions ( 6.2 ) ].
Instruct patients to contact their physician if this occurs. Pramipexole is the active ingredient that is in both pramipexole dihydrochloride extended-release tablets and immediate-release pramipexole tablets. Ensure that patients do not take both immediate-release pramipexole and pramipexole dihydrochloride extended-release tablets.
Sedating Effects Alert patients to the potential sedating effects of pramipexole dihydrochloride extended-release 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 extended-release 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 extended-release 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 extended-release 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, 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 extended-release 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 Confus…