Home › NDC Lookup › Ingredients › Pramipexole Dihydrochloride › 46708-0574-30
Pramipexole Dihydrochloride .375 mg Tablet, Extended Release, 30-count — NDC 46708-0574-30 package photo
Label image from the product's FDA listing (DailyMed) — may show a different pack size or an older label revision.

Pramipexole Dihydrochloride .375 mg Tablet, Extended Release, 30-count — NDC 46708-574-30 (Billing 46708-0574-30)

by Alembic Pharmaceuticals Limited · 30 TABLET, EXTENDED RELEASE in 1 BOTTLE

This is a package of 30 tablets of Pramipexole Dihydrochloride .375 mg Tablet, Extended Release from Alembic Pharmaceuticals Limited, marketed since Jan 2019 and currently FDA-listed. It is this product's only package size.

NDC 46708-0574-30
🏷️ FDA NDC (as labeled) 46708-574-30 billing pads the product segment with a zero
Rx only Generic On market Non-controlled ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 1, 2026 · this listing last changed Jul 24, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

This page is curated, coded, and maintained by

Compiled from public FDA, CMS, DailyMed, NADAC, and related drug data sources. Editorial policy

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 46708-574-30
Product NDC 46708-574
11-digit billing NDC 46708057430
RxCUI 901534, 901541, 901546, 901550, 901555, 1114479, 1114485
UNII 3D867NP06J
UPC 0346708574307, 0346708579302, 0346708578305, 0346708575304 +1 more
Application # ANDA204518
SPL Set ID b6935240-ee81-49ef-adad-fb900d7f5127
Established class (EPC) Nonergot Dopamine Agonist
Mechanism of action Dopamine Agonists
DEA schedule Non-controlled
Marketing category ANDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2019-01-03
Route ORAL
Dosage form TABLET, EXTENDED RELEASE
Substance PRAMIPEXOLE DIHYDROCHLORIDE
TE code (Orange Book) AB · RLD · RS
Quick answers
  • RxCUI (RxNorm): 901534
Why two NDCs? The FDA registers this code as 46708-574-30 — a 5-3-2 layout, and that's what's printed on the package and shown on DailyMed. For insurance claims, every NDC is standardized to a uniform 11-digit 5-4-2 format by adding a zero to the product segment → 46708-0574-30. Same drug, same package — only the format differs.
Where does this data come from?
Identifiers from the FDA openFDA NDC Directory and Structured Product Labeling; RxCUI from RxNorm (NLM); GPI from Medi-Span; GCN / HIC / AHFS / legend from First Databank.

RxNorm drug class

This medicine belongs to the Nonergot Dopamine Agonist class.

Pharmacologic class Nonergot Dopamine Agonist
Drug family (ATC) Dopamine agonists
How it works Dopamine Agonists
Where does this data come from?
Therapeutic classes from RxNorm RxClass (U.S. National Library of Medicine) — Established Pharmacologic Class (FDA), ATC drug family (WHO) and mechanism of action, matched by this product’s RxCUI.

Clinical

📗 Our plain-language guide HelloPharmacist
  • It treats Parkinson’s disease. The immediate-release tablet is also approved for moderate-to-severe primary Restless Legs Syndrome. The extended-release tablet is for Parkinson’s d...
  • Take it by mouth, with or without food, exactly as prescribed. Extended-release tablets are once daily and must be swallowed whole. Your dose is raised slowly, so don’t change it o...
  • Be careful. Some people fell asleep suddenly during daily activities, including driving, sometimes with no warning. If you feel sleepy, don’t drive, and tell your doctor right away...
  • Common ones are nausea, dizziness, sleepiness, trouble sleeping, constipation and weakness. Call your doctor if you have hallucinations, fainting, or new strong urges to gamble, sp...
📖 Read our full Pramipexole guide →

Supplement & herbal interactions

🌿 Drug–supplement interaction checker →
Where does this data come from?
Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

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 systemPer eachPer package
Retail pharmacies payNADAC · weekly Not in the retail survey — common for institutional, discontinued, or low-volume packs.
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?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

Packaging — all sizes for this product

Package NDCDescription Marketing startMarketing endStatus
46708-0574-30 You're viewing this Main listing 30 TABLET, EXTENDED RELEASE in 1 BOTTLE 2019-01-03 — Active

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Pramipexole Dihydrochloride .375 mg 16714-0916-01 NorthStar 30 tablets $0.948 AB Availability likely —
Pramipexole Dihydrochloride .375 mg 33342-0208-07 Macleods 30 tablets $0.948 AB Availability likely —
Pramipexole dihydrochloride .375 mg 50742-0331-30 Ingenus 30 tablets $0.948 AB Availability likely —
Pramipexole dihydrochloride .375 mg 55111-0611-30 Dr. 30 tablets $0.948 AB Availability likely —
Pramipexole Dihydrochloride .375 mg 62332-0154-30 Alembic 30 tablets $0.948 AB Availability likely —
Pramipexole Dihydrochloride Extended-Release .375 mg 69680-0145-30 Vitruvias 30 tablets $0.948 AB Availability likely —
Pramipexole Dihydrochloride .375 mgthis 46708-0574-30 Alembic 30 tablets — AB FDA listed —
Pramipexole Dihydrochloride Extended-Release .375 mg 71034-0002-30 Xiamen 30 tablets — AB FDA listed —
About this product: this is a generic version of the medicine. FDA equivalence ratings are shown when available, and other versions are listed above, least expensive first.
Where does this data come from?
Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

Availability & generic status

🏛️
2019
On the market since
Jan 2019
📍
2026
Currently FDA-listed
7 years listed
🔓
·
Generic on the market
this product is a generic
✅This is a generic drug

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?
Patents and exclusivity from the FDA Orange Book (small-molecule drugs), refreshed from public FDA data. Generic launch timing is an estimate, not a guarantee.

What it looks like

Color White
ShapeOval
Imprint405;ER
Size16 mm
ScoringNot scored
One label can cover several strengths, so colors may be combined — always confirm a loose pill against the dispensed prescription label or a pharmacist.
Where does this data come from?
Physical description (imprint, shape, color, scoring, coating) from this product’s FDA Structured Product Labeling (SPL), mirrored from DailyMed / openFDA.

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.

Loading inactive ingredients from the official FDA label in the background. No external source is being called by this page request.
Where does this data come from?
Source: official FDA Structured Product Labeling (SPL) via DailyMed and the openFDA label index. Structured IACT rows and label-wide narrative are kept separate; availability and product-level specificity depend on the submitted label.

Inactive ingredient FAQ

Are inactive ingredients the same for every manufacturer?
No. Inactive ingredients can differ by manufacturer, dosage form, strength, and package / product version.
Why might an inactive ingredient be missing?
Some SPLs do not provide a complete structured inactive-ingredient list, and older or unusual labels may only include the information in narrative text.
Can inactive ingredients matter?
Yes. They can matter for allergies, intolerances, dyes, gluten / lactose concerns, preservatives, and formulation differences — but confirm with a pharmacist or the manufacturer when it’s clinically important.

Manufacturer & labeler

LabelerAlembic Pharmaceuticals Limited
Application holderALEMBIC PHARMACEUTICALS LTD
FDA applicationANDA204518 (ANDA)
Labeler code46708
First marketedJan 2019
Product typeHuman Prescription Drug
Portfolio502 products on file
The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Very long sections are excerpted here and marked; the full text is on DailyMed (linked in the sources below). Jump with a chip, search within the label, or expand everything.
🎯 Indications and Usage ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications ⚠️ Warnings and Cautions 🤒 Adverse Reactions 🔄 Drug Interactions 👥 Use in Specific Populations 🤰 Pregnancy 🧒 Pediatric Use 🧓 Geriatric Use 🆘 Overdosage 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📋 Description 💬 Information for Patients 🧬 Pharmacokinetics 🧬 Pharmacodynamics 🔬 Clinical Studies 🧪 Nonclinical Toxicology 📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 📄 Patient Package Insert 📄 Recent Major Changes 📄 Package Label / Principal Display Panel
🎯 Indications and Usage 31 words ▾

1 INDICATIONS AND USAGE Pramipexole dihydrochloride extended-release tablets are indicated for the treatment of Parkinson’s disease. Pramipexole dihydrochloride is a non-ergot dopamine agonist indicated for the treatment of Parkinson’s disease (PD)(1)

⏱️ Dosage and Administration ~2 min read ▾

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.

2.2Dosing for Parkinsons Disease 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)]. Dosing 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 Extended-Release Pramipexole Tablets Patients with Parkinson’s disease may be switched overnight from immediate-release pramipexole tablets to extended-release pramipexole tablets at the same daily dose. When switching between immediate-release pramipexole tablets and extended-release pramipexole tablets, patients should be monitored to determine if dosage adjustment is necessary.

💊 Dosage Forms and Strengths 177 words ▾

3 DOSAGE FORMS AND STRENGTHS 0.375 mg: white to off white, round, biconvex, uncoated extended-release tablets debossed with ‘401’ on one side and ‘ER’ on other side. 0.75 mg: white to off white, round, biconvex, uncoated extended-release tablets debossed with ‘402’ on one side and ‘ER’ on other side. 1.5 mg: white to off white, oval, biconvex, uncoated extended-release tablets debossed with ‘403’ on one side and ‘ER’ on other side.

2.25mg: white to off white, oval, biconvex, uncoated extended-release tablets debossed with ‘413’ on one side and ‘ER’ on other side. 3 mg: white to off white, oval, biconvex, uncoated extended-release tablets debossed with ‘404’ on one side and ‘ER’ on other side. 3.75 mg: white to off white, oval, biconvex, uncoated extended-release tablets debossed with ‘414’ on one side and ‘ER’ on other side.

4.5mg: white to off white, oval, biconvex, uncoated extended-release tablets debossed with ‘405’ on one side and ‘ER’ on other side. Extended-release tablets: 0.375 mg, 0.75 mg, 1.5 mg, 2.25 mg, 3 mg, 3.75 mg, and 4.5 mg (3)

⛔ Contraindications 5 words ▾

4 CONTRAINDICATIONS None. None (4)

⚠️ Warnings and Cautions ~3 min read ▾

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(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 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 respond to an orthostatic challenge. For these reasons,… [Excerpted — this section continues on DailyMed.]

🤒 Adverse Reactions ~2 min read ▾

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)] 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 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 to 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-releasetablets 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 / Adverse Reaction Placebo Extended-Release Pramipexole Immediate- Release Pramipexole (n=103) (n=223) (n=213) % % % Nervous system disord… [Excerpted — this section continues on DailyMed.]

🔄 Drug Interactions 45 words ▾

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 ~3 min read ▾

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 <65… [Excerpted — this section continues on DailyMed.]

🤰 Pregnancy ~1 min read ▾

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 18 words ▾

8.4Pediatric Use Safety and effectiveness of pramipexole dihydrochloride extended-release tablets in pediatric patients have not been evaluated.

🧓 Geriatric Use 110 words ▾

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 115 words ▾

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 ~3 min read ▾

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 Extended-release pramipexole 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 differences are not… [Excerpted — this section continues on DailyMed.]

🧬 Mechanism of Action 129 words ▾

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 ~1 min read ▾

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1How Supplied Pramipexole Dihydrochloride Extended-Release Tablets are available as follows: 0. 375 mg: white to off white, round, biconvex, uncoated extended-release tablets debossed with ‘401’ on one side and ‘ER’ on other side. NDC 46708-574-30 bottle of 30 tablets 0.75 mg: white to off white, round, biconvex, uncoated extended-release tablets debossed with ‘402’ on one side and ‘ER’ on other side.

NDC 46708-575-30 bottle of 30 tablets 1.5 mg: white to off white, oval, biconvex, uncoated extended-release tablets debossed with ‘403’ on one side and ‘ER’ on other side. NDC 46708-576-30 bottle of 30 tablets 2.25 mg: white to off white, oval, biconvex, uncoated extended-release tablets debossed with ‘413’ on one side and ‘ER’ on other side. NDC 46708-577-30 bottle of 30 tablets 3 mg: white to off white, oval, biconvex, uncoated extended-release tablets debossed with ‘404’ on one side and ‘ER’ on other side.

NDC 46708-578-30 bottle of 30 tablets 3.75 mg: white to off white, oval, biconvex, uncoated extended-release tablets debossed with ‘414’ on one side and ‘ER’ on other side. NDC 46708-579-30 bottle of 30 tablets 4.5 mg: white to off white, oval, biconvex, uncoated extended-release tablets debossed with ‘405’ on one side and ‘ER’ on other side. NDC 46708-580-30 bottle of 30 tablets

16.2Storage and Handling Store at 25°C (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 140 words ▾

11 DESCRIPTION Pramipexole dihydrochloride extended-release tablets contain pramipexole, a non-ergot 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 · H 2 O, and its molecular weight is 302.26.

The structural formula is: Pramipexole dihydrochloride monohydrate USP is a white to almost white crystalline powder. Melting occurs in the range of 296°C to 301°C, with decomposition. Pramipexole dihydrochloride monohydrate USP is freely soluble in water, soluble in methanol, slightly soluble in alcohol, practically insoluble in methylene chloride.

Pramipexole dihydrochloride extended-release tablets, for oral administration, contain 0.375 mg, 0.75 mg, 1.5 mg, 2.25 mg, 3 mg, 3.75 mg or 4.5 mg of pramipexole dihydrochloride monohydrate USP. Inactive ingredients are betadex, microcrystalline cellulose, ethylcellulose, hydroxypropyl methyl cellulose, colloidal silicon dioxide, and magnesium stearate. Structure

💬 Information for Patients ~2 min read ▾

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 extended-release pramipexole tablets and immediate-release pramipexole tablets. Ensure that patients do not take both immediate-release pramipexole and extended-release pramipexole.

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)] .

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 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 extended-release tablets [see Warnings and Precautions (5.2)].

Pregnancy Because the teratogenic potential of pramipexole has not been completely established in… [Excerpted — this section continues on DailyMed.]

🧬 Pharmacokinetics ~3 min read ▾

12.3Pharmacokinetics Extended-release pramipexole 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 differences are not considered to be clinically relevant [see Dosage and Administration (2.1)] .

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 clearance of pramipexole is approximately 400 mL/min (CV=25%), approximately three times higher than the glomerular filtration rate. Thus, pramipexole is secreted by the renal tubules, probably by the organic cation transport system. Pharmacokinetics in Specific Populations Because therapy with pramipexole dihydrochloride extended-release tablets is initiated at a low dose and gradually titrated upward according to clinical tolerability to obtain the optimum therapeutic effect, adjustment of the initial dose based on gender, weight, race, or age is not necessary.

However, renal insufficiency causes a large decrease in the ability to eliminate pramipexole. This will necessitate dosage adjustment in patients with moderate to severe renal impairment [see Dosage and Administration (2.2)] . Gender Pramipexole clearance is about 30% lower in women than in men, but this difference can be accounted for by differences in body weight.

There is no difference in plasma half-life between males and females. Age Pramipexole clearance is reduced by approximately 30% in the elderly (aged 65 years or older) compared with young, healthy volunteers (aged less than 40 years). This difference is most likely due to the reduction in renal function with age, since pramipexole clearance is correlated with renal function, as measured by creatinine clearance.

Race No racial differences in metabolism and elimination have been identified. Hepatic Impairment The influence of hepatic insufficiency on pramipexole pharmacokinetics has not been evaluated. Because approximately 90%… [Excerpted — this section continues on DailyMed.]

🧬 Pharmacodynamics 213 words ▾

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.

🔬 Clinical Studies ~2 min read ▾

14 CLINICAL STUDIES The effectiveness of pramipexole dihydrochloride extended-release tablets in the treatment of Parkinson’s disease was supported by clinical pharmacokinetic data [see Clinical Pharmacology (12.3)] and two randomized, double-blind, placebo-controlled, multicenter clinical trials in early and advanced Parkinson’s disease. In both randomized studies, the Unified Parkinson’s Disease Rating Scale (UPDRS) served as a primary outcome assessment measure. The UPDRS is a four-part multi-item rating scale intended to evaluate mentation (Part I), activities of daily living (Part II), motor performance (Part III), and complications of therapy (Part IV).

Part II of the UPDRS contains 13 questions related to activities of daily living, which are scored from 0 (normal) to 4 (maximal severity) for a maximum (worst) score of 52. Part III of the UPDRS contains 14 items designed to assess the severity of the cardinal motor findings in patients with Parkinson’s disease (e.g., tremor, rigidity, bradykinesia, postural instability, etc.), scored for different body regions and has a maximum (worst) score of 108. Early Parkinson’s Disease The effectiveness of pramipexole dihydrochloride extended-release tablets in early Parkinson’s disease patients (Hoehn & Yahr Stages I to III) who were not on levodopa therapy was established in a randomized, double-blind, placebo-controlled, 3-parallel-group clinical study.

Patients were treated with extended-release pramipexole tablets, immediate-release pramipexole tablets, or placebo; those treated with extended-release pramipexole tablets or immediate-release pramipexole tablets had a starting dose of 0.375 mg/day followed by a flexible up-titration, based on efficacy and tolerability, up to 4.5 mg/day. Levodopa was permitted during the study as rescue medication. Stable doses of concomitant MAO-B inhibitors, anticholinergics, or amantadine, individually or in combination, were allowed.

The primary efficacy endpoint was the mean change from baseline in the UPDRS Parts II+III score for pramipexole dihydrochloride extended-release tablets versus placebo following 18 weeks of treatment. At 18 weeks of treatment, the mean change from baseline UPDRS Parts II+III score was –8.1 points in patients receiving pramipexole dihydrochloride extended-release tablets (n=102) and –5.1 points in patients receiving placebo (n=50), a difference that was statistically significant (p<0.03). Seven patients treated with placebo (14%) and 3 patients treated with pramipexole dihydrochloride extended-release tablets (3%) received levodopa rescue medication.

At 18 weeks, the mean dose of pramipexole dihydrochloride extended-release tablets was 3 mg/day. At 33-weeks the adjusted mean improvement from baseline UPDRS Parts II+III score was –8.6 points in patients receiving pramipexole dihydrochloride extended-release tablets (n=213), compared to –3.8 points in patients receiving placebo (n=103). At 18 and 33 weeks, the mean dose of pramipexole dihydrochloride extended-release tablets was approximately 3 mg/day.

Twenty-two patients treated with placebo (21%) and 15 patients treated with pramipexole dihydrochloride extended-release tablets (7%) received levodopa rescue medication before the final assessment. No differences in effectiveness based on age or gender were detected. Patients receiving MAOB-I, anticholinergics, or amantadine had responses similar to patients not receiving these drugs.

Advanced Parkinson’s Disease The effectiveness of pramipexole dihydrochloride extended-release tablets in advanced Parkinson’s disease patients (Hoehn & Yahr Stages II to IV at "on" time) who were on concomitant levodopa therapy (at an optimized dose) and who had motor fluctuations (at least 2 cumulative hours of "off" time per day) was established in a randomized, double-blind, placebo-controlled, 3-parallel-group clinical study. Patients were treated with extended-release pramipexole tablets, immediate-release pramipexole tablets, or… [Excerpted — this section continues on DailyMed.]

🧪 Nonclinical Toxicology ~3 min read ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Two-year carcinogenicity studies with pramipexole have been conducted in mice and rats. Pramipexole was administered in the diet to mice at doses up to 10 mg/kg/day [or approximately 10 times the maximum recommended human dose (MRHD) of 1.5 mg TID on a mg/m 2 basis]. Pramipexole was administered in the diet to rats at doses up to 8 mg/kg/day.

These doses were associated with plasma AUCs up to approximately 12 times that in humans at the MRHD. No significant increases in tumors occurred in either species. Pramipexole was not mutagenic or clastogenic in a battery of in vitro (bacterial reverse mutation, V79/HGPRT gene mutation, chromosomal aberration in CHO cells) and in vivo (mouse micronucleus) assays.

In rat fertility studies, pramipexole at a dose of 2.5 mg/kg/day (5 times the MRHD on a mg/m 2 basis) prolonged estrus cycles and inhibited implantation. These effects were associated with reductions in serum levels of prolactin, a hormone necessary for implantation and maintenance of early pregnancy in rats.

13.2Animal Pharmacology and/or Toxicology Retinal Pathology in Albino Rats Pathologic changes (degeneration and loss of photoreceptor cells) were observed in the retina of albino rats in the 2-year carcinogenicity study with pramipexole. These findings were first observed during week 76 and were dose-dependent in animals receiving 2 or 8 mg/kg/day (plasma AUCs equal to 2.5 and 12.5 times that in humans at the MRHD of 1.5 mg TID). In a similar study of pigmented rats with 2-years exposure to pramipexole at 2 or 8 mg/kg/day, retinal degeneration was not observed.

Animals given drug had thinning in the outer nuclear layer of the retina that was only slightly greater than that seen in control rats. Investigative studies demonstrated that pramipexole reduced the rate of disk shedding from the photoreceptor rod cells of the retina in albino rats, which was associated with enhanced sensitivity to the damaging effects of light. In a comparative study, degeneration and loss of photoreceptor cells occurred in albino rats after 13 weeks of treatment with 25 mg/kg/day of pramipexole (54 times the highest clinical dose on a mg/m 2 basis) and constant light (100 lux), but not in pigmented rats exposed to the same dose and higher light intensities (500 lux).

Thus, the retina of albino rats is considered to be uniquely sensitive to the damaging effects of pramipexole and light. Similar changes in the retina did not occur in a 2-year carcinogenicity study in albino mice treated with 0.3, 2, or 10 mg/kg/day (0.3, 2.2, and 11 times the highest clinical dose on a mg/m 2 basis). Evaluation of the retinas of monkeys given 0.1, 0.5, or 2 mg/kg/day of pramipexole (0.4, 2.2, and 8.6 times the highest clinical dose on a mg/m 2 basis) for 12 months and minipigs given 0.3, 1, or 5 mg/kg/day of pramipexole for 13 weeks also detected no changes.

The potential significance of this effect in humans has not been established, but cannot be disregarded because disruption of a mechanism that is universally present in vertebrates (i.e., disk shedding) may be involved. Fibro-osseous Proliferative Lesions in Mice An increased incidence of fibro-osseous proliferative lesions occurred in the femurs of female mice treated for 2 years with 0.3, 2, or 10 mg/kg/day (0.3, 2.2, and 11 times the highest clinical dose on a mg/m 2 basis). Lesions occurred at a lower rate in control animals.

Similar lesions were not observed in male mice or rats and monkeys of either sex that were treated chronically with pramipexole. The significance of this lesion to humans is not known.

📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 170 words ▾

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Two-year carcinogenicity studies with pramipexole have been conducted in mice and rats. Pramipexole was administered in the diet to mice at doses up to 10 mg/kg/day [or approximately 10 times the maximum recommended human dose (MRHD) of 1.5 mg TID on a mg/m 2 basis]. Pramipexole was administered in the diet to rats at doses up to 8 mg/kg/day.

These doses were associated with plasma AUCs up to approximately 12 times that in humans at the MRHD. No significant increases in tumors occurred in either species. Pramipexole was not mutagenic or clastogenic in a battery of in vitro (bacterial reverse mutation, V79/HGPRT gene mutation, chromosomal aberration in CHO cells) and in vivo (mouse micronucleus) assays.

In rat fertility studies, pramipexole at a dose of 2.5 mg/kg/day (5 times the MRHD on a mg/m 2 basis) prolonged estrus cycles and inhibited implantation. These effects were associated with reductions in serum levels of prolactin, a hormone necessary for implantation and maintenance of early pregnancy in rats.

📄 Patient Package Insert ~3 min read ▾

Patient Information Pramipexole Dihydrochloride ( PRAM-i-PEX-ole dye-HYE-droe-KLOR-ide) Extended-Release Tablets Read this Patient Information before you start taking pramipexole dihydrochloride extended-release tablets and each time you get a refill. There may be new information. This information does not take the place of talking with your doctor about your medical condition or your treatment.

What is pramipexole dihydrochloride extended-release tablet? Pramipexole dihydrochloride extended-release tablets are a prescription medicine used to treat the signs and symptoms of Parkinson’s disease. It is not known if pramipexole dihydrochloride extended-release tablets are safe and effective in children.

What should I tell my doctor before taking pramipexole dihydrochloride extended-release tablets? Before taking pramipexole dihydrochloride extended-release tablets, tell your doctor if you: · feel sleepy during the day • have low blood pressure, or if you feel dizzy or faint, especially when getting up from sitting or lying down. · have trouble controlling your muscles (dyskinesia). · have kidney problems. · drink alcohol. Alcohol can increase the chance that pramipexole dihydrochloride extended-release tablets will make you feel sleepy or fall asleep when you should be awake. · are pregnant or plan to become pregnant.

It is not known if pramipexole dihydrochloride extended-release tablets will harm your unborn baby. · are breastfeeding or plan to breastfeed. It is not known if pramipexole dihydrochloride will pass into your breast milk. You and your doctor should decide if you will take pramipexole dihydrochloride extended-release tablets or breast-feed.

You should not do both. Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Pramipexole dihydrochloride extended-release tablets and other medicines may affect each other causing side effects.

Pramipexole dihydrochloride extended-release tablets may affect the way other medicines work, and other medicines may affect how pramipexole dihydrochloride extended-release tablets works. Especially tell your doctor if you take: · medicines called neuroleptics (phenothiazines, butyrophenones, thioxanthenes) or metoclopramide. Pramipexole dihydrochloride extended-release tablets may not work as well if you take these medicines. · pramipexole dihydrochloride tablets.

Pramipexole is the active ingredient in both pramipexole dihydrochloride extended-release tablets and pramipexole dihydrochloride tablets. If you are taking pramipexole dihydrochloride tablets, you should not take pramipexole dihydrochloride extended-release tablets. · any other medicines that make you sleepy or may increase the effects of pramipexole dihydrochloride extended-release tablets, such as cimetidine (Tagamet). Ask your doctor for a list of these medicines if you are not sure.

Know the medicines you take. Keep a list of them and show it to your doctor and pharmacist when you get a new medicine. How should I take pramipexole dihydrochloride extended-release tablets? · Pramipexole dihydrochloride extended-release tablet is taken once daily. .

Your doctor will tell you how much pramipexole dihydrochloride extended-release tablets to take and when to take it. Do not take more or less pramipexole dihydrochloride extended-release tablets than your doctor tells you to. · Swallow pramipexole dihydrochloride extended-release tablets whole. Do not chew, crush, or cut pramipexole dihydrochloride extended-release tablets. · Pramipexole dihydrochloride extended-release tablets can be taken with or without food.

Taking pramipexole dihydrochloride extended-release tablets with food may lower your chances of getting nausea. • You may see something that looks like a swollen original tablet or swollen pieces of the original tablet in your stool. If this happens, tell your doctor. . If you miss a dose of pramipexole dihydrochloride extended-release t… [Excerpted — this section continues on DailyMed.]

📄 Recent Major Changes 19 words ▾

Warnings and Precautions, Postural Deformity (5.6) 5/2018 Warnings and Precautions, Events Reported with Dopaminergic Therapy (5.10); Melanoma Removed 5/2018

📄 Package Label / Principal Display Panel ~1 min read ▾

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL - 0.375 mg NDC 46708-574-30 Pramipexole Dihydrochloride Extended-Release Tablets 0.375 mg Once Daily PHARMACIST: Dispense the accompanying patient information leaflet to each patient. Rx only 30 Tablets 30's bottle pack

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL - 0.75 mg NDC 46708-575-30 Pramipexole Dihydrochloride Extended-Release Tablets 0.75 mg Once Daily PHARMACIST: Dispense the accompanying patient information leaflet to each patient. Rx only 30 Tablets 30's bottle pack

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL - 1.5 mg NDC 46708-576-30 Pramipexole Dihydrochloride Extended-Release Tablets 1.5 mg Once Daily PHARMACIST: Dispense the accompanying patient information leaflet to each patient. Rx only 30 Tablets 30's bottle pack

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL - 3 mg NDC 46708-578-30 Pramipexole Dihydrochloride Extended-Release Tablets 3 mg Once Daily PHARMACIST: Dispense the accompanying patient information leaflet to each patient. Rx only 30 Tablets 30's bottle pack

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL - 2.25 mg NDC 46708-577-30 Pramipexole Dihydrochloride Extended-Release Tablets 2.25 mg Once Daily PHARMACIST: Dispense the accompanying patient information leaflet to each patient. Rx only 30 Tablets 30's bottle pack

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL - 3.75 mg NDC 46708-579-30 Pramipexole Dihydrochloride Extended-Release Tablets 3.75 mg Once Daily PHARMACIST: Dispense the accompanying patient information leaflet to each patient. Rx only 30 Tablets 30's bottle pack

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL - 4.5 mg NDC 46708-580-30 Pramipexole Dihydrochloride Extended-Release Tablets 4.5 mg Once Daily PHARMACIST: Dispense the accompanying patient information leaflet to each patient. Rx only 30 Tablets 30's bottle pack

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗

Medicare Part D spend CMS · PART D · 2026 (Q1)

Medicare Part D (outpatient prescription) spending for Pramipexole Dihydrochloride — the program that covers self-administered drugs. 9 manufacturers.
⚠️ Drug-level data: CMS publishes Part D spending by drug, not by NDC — these figures combine every manufacturer, strength and package size sold under the name Pramipexole Dihydrochloride. That’s a different level of aggregation than the Medicaid card above, which is specific to this exact 11-digit NDC (pack size included), so the two aren’t directly comparable.
Period
Total Part D spend
$7.11M
Claims incl. refills
420K
Beneficiaries
274.6K
Spend / beneficiary
$25.88
Spend / claim
$16.92
Trend by period
💵 About the dollar figures: spending is what Part D plans paid before confidential manufacturer rebates, so the program’s real net cost is lower. A blank patient count means fewer than 11 people — CMS hides counts that small to protect privacy. Source: CMS Medicare Quarterly Part D Spending by Drug (data.cms.gov), updated quarterly.

About this NDC listing & data coverage

Finished prescription product
What data is (and isn’t) available for this NDC — tap to expand
NDC identity (package / product / labeler codes) ✓ Available
Labeler ✓ Available
Product & package description ✓ Available
Marketing category & status ✓ Available
Active ingredient / dosage form / route ✓ Available
FDA label (SPL via DailyMed) ✓ Available
Package photos ✓ Available
Inactive ingredients (structured) — Not published for this NDC The labeler did not submit a structured excipient list, or no SPL is available.
NADAC pharmacy acquisition price (CMS) — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey.
Orange Book / therapeutic-equivalence data ✓ Available
HCPCS J-code billing crosswalk — Not published for this NDC Most self-administered / retail products have no J-code — that is normal.
Medicaid utilization (CMS SDUD) — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold.
“Not published” reflects what the public FDA / CMS / NLM sources provide for this exact package code — it is a property of the data feeds, not a judgment about the product.

Questions about this listing

Why is there no price listed?
The pricing shown on our NDC pages comes from CMS NADAC, a voluntary survey of retail community pharmacy invoices. CMS does not publish a NADAC for every NDC — packages outside the retail survey (institutional and hospital products, bulk packages, discontinued items, and many OTC items) may never receive one. A missing price reflects the survey's scope, not this product's actual cost, and does not mean the product is free or unavailable.
Is the NDC printed on the package the same as the 11-digit billing NDC?
Yes, they identify this exact package in different formats. The form printed on the packaging and shown on DailyMed is the one the FDA registered. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero and the dashes are dropped. The Identity section at the top of this page lists each form of this code.
Is this package still being marketed?
Yes, per the latest FDA NDC Directory data on this page: this package is listed as actively marketed, with no marketing end date reported by Alembic Pharmaceuticals Limited. Listing status can change — the directory data on this page refreshes weekly.
Who lists this product with the FDA?
Alembic Pharmaceuticals Limited is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.
Do I need a prescription for this product?
This NDC is listed with FDA as a prescription product, so it is dispensed under a prescriber's order. Your pharmacist can tell you whether any over-the-counter forms of the same medication exist.
This page identifies an FDA-listed package (the NDC) and reports public regulatory and pricing data about the listing. It is reference information, not a medical recommendation — talk to your pharmacist or prescriber about your own medication.
Where does this data come from?
Listing facts (marketing category, packager status, marketing dates) from the FDA openFDA NDC Directory; label availability from DailyMed; pricing coverage from CMS NADAC; equivalence scope from the FDA Orange Book.
← 46708-0567-30 · Alembic 46708-0575-30 · Alembic →
For educational and professional reference only — not medical advice. Pricing reflects published NADAC and CMS ASP (free public data) and may differ from your acquisition cost; always verify before billing or dispensing.