PRAMIPEXOLE DIHYDROCHLORIDE tablet

United States - English - NLM (National Library of Medicine)

Buy It Now

Active ingredient:
PRAMIPEXOLE DIHYDROCHLORIDE (UNII: 3D867NP06J) (PRAMIPEXOLE - UNII:83619PEU5T)
Available from:
Alembic Pharmaceuticals Limited
Administration route:
ORAL
Prescription type:
PRESCRIPTION DRUG
Therapeutic indications:
Pramipexole dihydrochloride tablets are indicated for the treatment of  Parkinson’s disease. None.    Pregnancy Category C   Risk Summary There are no adequate data on the developmental risk associated with the use of pramipexole dihydrochloride 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
Product summary:
Pramipexole dihydrochloride tablets are available as follows:   0.125 mg: White to off white, circular tablet debossed with “E” on one side and “33” on the other side. Bottles of 90                                       NDC 46708-611-90   0.25 mg: White to off white, oval shaped tablet with break line on both side and debossed with “E E” on one side and “34 34” on other side. Bottles of 90                                       NDC 46708-612-90   0.5 mg: White to off white, oval shaped tablet with break line on both side and debossed with “E E” on one side and “35 35” on other side. Bottles of 90                                       NDC 46708-613-90   1 mg: White to off white, circular tablet with break line on both side and debossed with “E E” on one side and “36 36” on other side. Bottles of 90                                       NDC 46708-614-90 1.5 mg: White to off white, circular tablet with break line on both side and debossed with “E E” on one side and “37 37” on other side. Bottles of 90                                       NDC 46708-615-90 Store at 25°C (77°F); excursions permitted to 15°-30°C (59°-86°F) [see USP Controlled Room Temperature]. Protect from light. Store in a safe place out of the reach of children.
Authorization status:
Abbreviated New Drug Application
Authorization number:
46708-611-90, 46708-612-90, 46708-613-90, 46708-614-90, 46708-615-90

PRAMIPEXOLE DIHYDROCHLORIDE - pramipexole dihydrochloride tablet

Alembic Pharmaceuticals Limited

----------

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use PRAMIPEXOLE DIHYDROCHLORIDE

TABLETS safely and effectively. See full prescribing information for PRAMIPEXOLE DIHYDROCHLORIDE

TABLETS.

PRAMIPEXOLE DIHYDROCHLORIDE tablets, for oral use

Initial U.S. Approval: 1997

INDICATIONS AND USAGE

Pramipexole dihydrochloride tablets are non-ergot dopamine agonist indicated for the treatment of: (1)

· Parkinson’s disease (PD) (1.1) (1)

DOSAGE AND ADMINISTRATION

Parkinson’s Disease-Normal Renal Function* (2.2)

Week

Dosage (mg)

Total Daily Dose (mg)

0.125 TID

0.375

0.25 TID

0.75

0.5 TID

0.75 TID

2.25

1 TID

1.25 TID

3.75

1.5 TID

* Doses should not be increased more frequently than every 5 to 7 days. Titrate to effective dose. If used with levodopa,

may need to reduce levodopa dose.

Parkinson’s Disease-Impaired Renal Function (2.2)

Creatinine Clearance Starting Dose (mg)

Maximum Dose (mg)

> 50 ml/min

0.125 TID

1.5 TID

30 to 50 ml/min

0.125 BID

0.75 TID

15 to 30 ml/min

0.125 QD

1.5 QD

<15 ml/min and hemodialysis patients

Data not available

DOSAGE FORMS AND STRENGTHS

Tablets: 0.125 mg, 0.25 mg, 0.5 mg, 1 mg, and 1.5 mg (3). (3)

CONTRAINDICATIONS

None (4) (4)

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) (5)

· Symptomatic orthostatic hypotension: Monitor during dose escalation (5.2) (5)

· Impulse control/Compulsive behaviors: Patients may experience compulsive behaviors and other intense urges

(5.3) (5)

· Hallucinations and Pschyotic-like Behaviour: May occur; risk increases with age. (5.4) (5)

· Dyskinesia: May be caused or exacerbated by pramipexole dihydrochloride tablets (5.5) (5)

· Events reported with dopaminergic therapy: Include hyperpyrexia and confusion, fibrotic complications, and

melanoma (5.9) (5)

ADVERSE REACTIONS

Most common adverse reactions (incidence >5% and greater than placebo): (6)

Early PD without levodopa: nausea, dizziness,somnolence, insomnia, constipation, asthenia, and hallucinations (6.1).

Advanced PD with levodopa: postural (orthostatic) hypotension, dyskinesia, extrapyramidal syndrome, insomnia,

dizziness, hallucinations, accidental injury, dream abnormalities, confusion, constipation, asthenia,

somnolence, dystonia, gait abnormality, hypertonia, dry mouth, amnesia, and urinary frequency (6.1).

To report SUSPECTED ADVERSE REACTIONS, contact FDA at 1-800-FDA-1088 or www.fda.gov/medwatch (6)

DRUG INTERACTIONS

Dopamine antagonists: May diminish the effectiveness of pramipexole (7.1). (7)

USE IN SPECIFIC POPULATIONS

Pregnancy: Based on animal data, may cause fetal harm (8.1). (8)

See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.

Revised: 9/2019

FULL PRESCRIBING INFORMATION: CONTENTS*

1 INDICATIONS AND USAGE

1.1 Parkinson's Disease

2 DOSAGE AND ADMINISTRATION

2.1 General Dosing Considerations

2.2 Dosing for Parkinson's Disease

3 DOSAGE FORMS AND STRENGTHS

4 CONTRAINDICATIONS

5 WARNINGS AND PRECAUTIONS

5.1 Falling Asleep During Activities of Daily Living and Somnolence

5.2 Symptomatic Orthostatic Hypotension

5.3 Impulse Control/Compulsive Behaviors

5.4 Hallucinations and Psychotic-like Behavior

5.5 Dyskinesia

5.6 Renal Impairment

5.7 Rhabdomyolysis

5.8 Retinal Pathology

5.9 Events Reported with Dopaminergic Therapy

6 ADVERSE REACTIONS

6.1 Clinical Trials Experience

6.2 Post Marketing Experience

7 DRUG INTERACTIONS

7.1 Dopamine Antagonists

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

8.2 Lactation

8.4 Pediatric Use

8.5 Geriatric Use

8.6 Renal Impairment

10 OVERDOSAGE

11 DESCRIPTION

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

12.2 Pharmacodynamics

12.3 Pharmacokinetics

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

13.2 Animal Toxicology and/or Pharmacology

14 CLINICAL STUDIES

14.1 Parkinson's Disease

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied

16.2 Storage and Handling

17 PATIENT COUNSELING INFORMATION

FULL PRESCRIBING INFORMATION

1 INDICATIONS AND USAGE

1.1 Parkinson's Disease

Pramipexole dihydrochloride tablets are indicated for the treatment of Parkinson’s disease.

2 DOSAGE AND ADMINISTRATION

2.1 General Dosing Considerations

Pramipexole dihydrochloride tablets are taken orally, with or without food.

If a significant interruption in therapy with pramipexole dihydrochloride tablets has occurred, re-

titration of therapy may be warranted.

2.2 Dosing for Parkinson's Disease

In all clinical studies, dosage was initiated at a subtherapeutic level to avoid intolerable adverse effects

and orthostatic hypotension. Pramipexole dihydrochloride tablets should be titrated gradually in all

patients. The dose should be increased to achieve a maximum therapeutic effect, balanced against the

principal side effects of dyskinesia, hallucinations, somnolence, and dry mouth.

Dosing in Patients with Normal Renal Function

Initial Treatment

Doses should be increased gradually from a starting dose of 0.375 mg/day given in three divided doses

and should not be increased more frequently than every 5 to 7 days. A suggested ascending dosage

schedule that was used in clinical studies is shown in Table 1:

Table 1 Ascending Dosage Schedule of Pramipexole Dihydrochloride Tablets for Parkinson's

Dis eas e

Week

Dosage (mg)

Total Daily Dose (mg)

0.125 three times a day

0.375

0.25 three times a day

0.75

0.5 three times a day

0.75 three times a day

2.25

1 three times a day

1.25 three times a day

3.75

1.5 three times a day

Sections or subsections omitted from the full prescribing information are not listed.

Maintenance Treatment

Pramipexole dihydrochloride tablets were effective and well tolerated over a dosage range of 1.5 to

4.5 mg/day administered in equally divided doses three times per day with or without concomitant

levodopa (approximately 800 mg/day).

In a fixed-dose study in early Parkinson’s disease patients, doses of 3 mg, 4.5 mg, and 6 mg per day of

pramipexole dihydrochloride tablets were not shown to provide any significant benefit beyond that

achieved at a daily dose of 1.5 mg/day. However, in the same fixed-dose study, the following adverse

events were dose related: postural hypotension, nausea, constipation, somnolence, and amnesia. The

frequency of these events was generally 2-fold greater than placebo for pramipexole doses greater than

3 mg/day. The incidence of somnolence reported with pramipexole at a dose of 1.5 mg/day was

comparable to placebo.

When pramipexole dihydrochloride tablets are used in combination with levodopa, a reduction of the

levodopa dosage should be considered. In a controlled study in advanced Parkinson’s disease, the

dosage of levodopa was reduced by an average of 27% from baseline.

Dosing in Patients with Renal Impairment

The recommended dosing of pramipexole dihydrochloride tablets in Parkinson’s disease patients with

renal impairment is provided in Table 2.

Table 2 Dosing of Pramipexole Dihydrochloride Tabletsin Parkinson’s Disease Patients with

Renal Impairment

Renal Status

Starting Dose (mg)

Maximum Dose (mg)

Normal to mild impairment

(creatinine Cl >50 mL/min)

0.125 three times a

1.5 three times a day

Moderate impairment

(creatinine Cl =30 to 50 mL/min)

0.125 twice a day

0.75 three times a day

Severe impairment

(creatinine Cl =15 to <30 mL/min)

0.125 once a day

1.5 once a day

Very severe impairment

(creatinine Cl <15 mL/min and

hemodialysis patients)

The use of pramipexole dihydrochloride tablets

has not been adequately studied in this group of

patients.

Discontinuation of Treatment

Pramipexole dihydrochloride 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 (5.9)].

3 DOSAGE FORMS AND STRENGTHS

0.125 mg: White to off white, circular tablet debossed with “E” on one side and “33”on the

other side.

0.25 mg: White to off white, oval shaped tablet with break line on both side and debossed with

“E E” on one side and “34 34” on other side.

0.5 mg: White to off white, oval shaped tablet with break line on both side and debossed with

“E E” on one side and “35 35” on other side.

1 mg: White to off white, circular tablet with break line on both side and debossed with “E

E” on one side and “36 36” on other side.

1.5 mg: White to off white, circular tablet with break line on both side and debossed with “E

E” on one side and “37 37” on other side.

4 CONTRAINDICATIONS

None.

5 WARNINGS AND PRECAUTIONS

5.1 Falling Asleep During Activities of Daily Living and Somnolence

Patients treated with pramipexole have reported falling asleep while engaged in activities of daily

living, including the operation of motor vehicles which sometimes resulted in accidents. Although many

of these patients reported somnolence while on pramipexole tablets, some perceived that they had no

warning signs (sleep attack) such as excessive drowsiness, and believed that they were alert

immediately prior to the event. Some of these events had been reported as late as one year after the

initiation of treatment.

Somnolence is a common occurrence in patients receiving pramipexole at doses above 1.5 mg/day (0.5

mg three times a day) for Parkinson’s disease. It has been reported that falling asleep while engaged in

activities of daily living usually occurs in a setting of pre-existing somnolence, although patients may

not give such a history. For this reason, prescribers should reassess patients for drowsiness or

sleepiness, especially since some of the events occur well after the start of treatment. Prescribers

should also be aware that patients may not acknowledge drowsiness or sleepiness until directly

questioned about drowsiness or sleepiness during specific activities.

Before initiating treatment with pramipexole dihydrochloride tablets, advise patients of the potential to

develop drowsiness and specifically asked about factors that may increase the risk for somnolence

with pramipexole dihydrochloride tablets such as the use of concomitant sedating medications or

alcohol, the presence of sleep disorders, and concomitant medications that increase pramipexole

plasma levels (e.g., cimetidine) [see Clinical Pharmacology (12.3)]. If a patient develops significant

daytime sleepiness or episodes of falling asleep during activities that require active participation (e.g.,

conversations, eating, etc.), pramipexole dihydrochloride tablets should ordinarily be discontinued. If a

decision is made to continue pramipexole dihydrochloride tablets, advise patients not to drive and to

avoid other potentially dangerous activities that might result in harm if the patients become somnolent.

While dose reduction reduces the degree of somnolence, there is insufficient information to establish

that dose reduction will eliminate episodes of falling asleep while engaged in activities of daily living.

5.2 Symptomatic Orthostatic Hypotension

Dopamine agonists, in clinical studies and clinical experience, appear to impair the systemic regulation

of blood pressure, with resulting orthostatic hypotension, especially during dose escalation.

Parkinson’s disease patients, in addition, appear to have an impaired capacity to respond to an orthostatic

challenge. For these reasons, Parkinson’s disease patients being treated with dopaminergic agonists

ordinarily require careful monitoring for signs and symptoms of orthostatic hypotension, especially

during dose escalation, and should be informed of this risk.

In clinical trials of pramipexole, however, and despite clear orthostatic effects in normal volunteers, the

reported incidence of clinically significant orthostatic hypotension was not greater among those

assigned to pramipexole tablets than among those assigned to placebo. This result, especially with the

higher doses used in Parkinson’s disease, is clearly unexpected in light of the previous experience with

the risks of dopamine agonist therapy.

While this finding could reflect a unique property of pramipexole, it might also be explained by the

conditions of the study and the nature of the population enrolled in the clinical trials. Patients were very

carefully titrated, and patients with active cardiovascular disease or significant orthostatic hypotension

at baseline were excluded.

5.3 Impulse Control/Compulsive Behaviors

Case reports and the results of a cross-sectional study suggest that patients can experience intense

urges to gamble, increased sexual urges, intense urges to spend money uncontrollably, binge eating,

and/or other intense urges and the inability to control these urges while taking one or more of the

medications, including pramipexole dihydrochloride tablets, that increase central dopaminergic tone and

that are generally used for the treatment of Parkinson’s disease. In some cases, although not all, these

urges were reported to have stopped when the dose was reduced or the medication was discontinued.

Because patients may not recognize these behaviors as abnormal it is important for prescribers to

specifically ask patients or their caregivers about the development of new or increased gambling urges,

sexual urges, uncontrolled spending or other urges while being treated with pramipexole

dihydrochloride tablets. Physicians should consider dose reduction or stopping the medication if a

patient develops such urges while taking pramipexole dihydrochloride tablets.

5.4 Hallucinations and Psychotic-like Behavior

In the three double-blind, placebo-controlled trials in early Parkinson’s disease, hallucinations were

observed in 9% (35 of 388) of patients receiving pramipexole dihydrochloride tablets, compared with

2.6% (6 of 235) of patients receiving placebo. In the four double-blind, placebo-controlled trials in

advanced Parkinson’s disease, where patients received pramipexole dihydrochloride tablets and

concomitant levodopa, hallucinations were observed in 16.5% (43 of 260) of patients receiving

pramipexole dihydrochloride tablets compared with 3.8% (10 of 264) of patients receiving placebo.

Hallucinations were of sufficient severity to cause discontinuation of treatment in 3.1% of the early

Parkinson’s disease patients and 2.7% of the advanced Parkinson’s disease patients compared with about

0.4% of placebo patients in both populations.

Age appears to increase the risk of hallucinations attributable to pramipexole. In the early Parkinson’s

disease patients, the risk of hallucinations was 1.9 times greater than placebo in patients younger than 65

years and 6.8 times greater than placebo in patients older than 65 years. In the advanced Parkinson’s

disease patients, the risk of hallucinations was 3.5 times greater than placebo in patients younger than 65

years and 5.2 times greater than placebo in patients older than 65 years.

Postmarketing reports with medication used to treat Parkinson’s disease, including pramipexole

dihydrochloride tablets, indicate that patients may experience new or worsening mental status and

behavioral changes, which may be severe, including psychotic-like behavior during treatment with

pramipexole dihydrochloride tablets or after starting or increasing the dose of pramipexole

dihydrochloride tablets. Other drugs prescribed to improve the symptoms of Parkinson’s disease can

have similar effects on thinking and behavior. This abnormal thinking and behavior can consist of one or

more of a variety of manifestations including paranoid ideation, delusions, hallucinations, confusion,

psychotic-like behavior, disorientation, aggressive behavior, agitation, and delirium.

Patients with a major psychotic disorder should ordinarily not be treated with dopamine agonists,

including pramipexole dihydrochloride tablets, because of the risk of exacerbating the psychosis. In

addition, certain medications used to treat psychosis may exacerbate the symptoms of Parkinson’s

disease and may decrease the effectiveness of pramipexole dihydrochloride tablets [see Drug

Interactions (7.1)].

5.5 Dyskinesia

Pramipexole dihydrochloride tablets may potentiate the dopaminergic side effects of levodopa and may

cause or exacerbate preexisting dyskinesia.

5.6 Renal Impairment

Since pramipexole is eliminated through the kidneys, caution should be exercised when prescribing

pramipexole dihydrochloride tablets to patients with renal impairment [see Use in Specific Populations

(8.6), and Clinical Pharmacology (12.3)].

5.7 Rhabdomyolysis

A single case of rhabdomyolysis occurred in a 49-year-old male with advanced Parkinson’s disease

treated with pramipexole dihydrochloride tablets. The patient was hospitalized with an elevated CPK

(10,631 IU/L). The symptoms resolved with discontinuation of the medication.

5.8 Retinal Pathology

Human Data

A two-year open-label, randomized, parallel-group safety study of retinal deterioration and vision

compared pramipexole dihydrochloride tablets and immediate-release ropinirole. Two hundred thirty

four Parkinson’s disease patients (115 on pramipexole, mean dose 3 mg/day and 119 on ropinirole, mean

dose 9.5 mg/day) were evaluated using a panel of clinical ophthalmological assessments. Of 234

patients who were evaluable, 196 had been treated for two years and 29 were judged to have developed

clinical abnormalities that were considered meaningful (19 patients in each treatment arm had received

treatment for less than two years). There was no statistical difference in retinal deterioration between

the treatment arms; however, the study was only capable of detecting a very large difference between

treatments. In addition, because the study did not include an untreated comparison group (placebo

treated), it is unknown whether the findings reported in patients treated with either drug are greater than

the background rate in an aging population.

Animal Data

Pathologic changes (degeneration and loss of photoreceptor cells) were observed in the retina of

albino rats in the 2-year carcinogenicity study. While retinal degeneration was not diagnosed in

pigmented rats treated for 2 years, a thinning in the outer nuclear layer of the retina was slightly greater

in rats given drug compared with controls. Evaluation of the retinas of albino mice, monkeys, and

minipigs did not reveal similar 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 [see Nonclinical Toxicology (13.2)].

5.9 Events Reported with Dopaminergic Therapy

Although the events enumerated below may not have been reported in association with the use of

pramipexole in its development program, they are associated with the use of other dopaminergic drugs.

The expected incidence of these events, however, is so low that even if pramipexole caused these

events at rates similar to those attributable to other dopaminergic therapies, it would be unlikely that

even a single case would have occurred in a cohort of the size exposed to pramipexole in studies to

date.

Hyperpyrexia and Confusion

Although not reported with pramipexole in the clinical development program, a symptom complex

resembling the neuroleptic malignant syndrome (characterized by elevated temperature, muscular

rigidity, altered consciousness, and autonomic instability), with no other obvious etiology, has been

reported in association with rapid dose reduction, withdrawal of, or changes in dopaminergic therapy. If

possible, avoid sudden discontinuation or rapid dose reduction in patients taking pramipexole

dihydrochloride tablets. If the decision is made to discontinue pramipexole dihydrochloride tablets, the

dose should be tapered to reduce the risk of hyperpyrexia and confusion [see Dosage and Administration

(2.2)].

Fibrotic Complications

Cases of retroperitoneal fibrosis, pulmonary infiltrates, pleural effusion, pleural thickening,

pericarditis, and cardiac valvulopathy have been reported in patients treated with ergot-derived

dopaminergic agents. While these complications may resolve when the drug is discontinued, complete

resolution does not always occur.

Although these adverse events are believed to be related to the ergoline structure of these compounds,

whether other, nonergot-derived dopamine agonists can cause them is unknown.

Cases of possible fibrotic complications, including peritoneal fibrosis, pleural fibrosis, and pulmonary

fibrosis have been reported in the post marketing experience with pramipexole dihydrochloride tablets.

While the evidence is not sufficient to establish a causal relationship between pramipexole

dihydrochloride tablets and these fibrotic complications, a contribution of pramipexole dihydrochloride

tablets cannot be completely ruled out.

Melanoma

Epidemiological studies have shown that patients with Parkinson’s disease have a higher risk (2- to

approximately 6-fold higher) of developing melanoma than the general population. Whether the

observed increased risk was due to Parkinson’s disease or other factors, such as drugs used to treat

Parkinson’s disease, is unclear.

For the reasons stated above, patients and providers are advised to monitor for melanomas frequently

and on a regular basis when using pramipexole dihydrochloride tablets for any indication. Ideally,

periodic skin examinations should be performed by appropriately qualified individuals (e.g.,

dermatologists).

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)].

Rhabdomyolysis [see Warnings and Precautions (5.7)].

Retinal Pathology [see Warnings and Precautions (5.8)].

Events Reported with Dopaminergic Therapy [see Warnings and Precautions (5.9)].

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed

in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug

and may not reflect the rates observed in clinical practice.

Parkinson’s Disease

During the premarketing development of pramipexole, patients with either early or advanced

Parkinson’s disease were enrolled in clinical trials. Apart from the severity and duration of their

disease, the two populations differed in their use of concomitant levodopa therapy. Patients with early

disease did not receive concomitant levodopa therapy during treatment with pramipexole; those with

advanced Parkinson’s disease all received concomitant levodopa treatment. Because these two

populations may have differential risks for various adverse reactions, this section will, in general,

present adverse-reaction data for these two populations separately.

Because the controlled trials performed during premarketing development all used a titration design,

with a resultant confounding of time and dose, it was impossible to adequately evaluate the effects of

dose on the incidence of adverse reactions.

Early Parkinson’s Disease

In the three double-blind, placebo-controlled trials of patients with early Parkinson’s disease, the most

common adverse reactions (>5%) that were numerically more frequent in the group treated with

pramipexole dihydrochloride tablets were nausea, dizziness, somnolence, insomnia, constipation,

asthenia, and hallucinations.

Approximately 12% of 388 patients with early Parkinson’s disease and treated with pramipexole

dihydrochloride tablets who participated in the double-blind, placebo-controlled trials discontinued

treatment due to adverse reactions compared with 11% of 235 patients who received placebo. The

adverse reactions most commonly causing discontinuation of treatment were related to the nervous

system (hallucinations [3.1% on pramipexole dihydrochloride tablets vs 0.4% on placebo]; dizziness

[2.1% on pramipexole dihydrochloride tablets vs 1% on placebo]; somnolence [1.6% on pramipexole

dihydrochloride tablets vs 0% on placebo]; headache and confusion [1.3% and 1%, respectively, on

pramipexole dihydrochloride tablets vs 0% on placebo]); and gastrointestinal system (nausea [2.1% on

pramipexole dihydrochloride tablets vs 0.4% on placebo]).

Adverse- reaction Incidence in Controlled Clinical Studies in Early Parkinson's Disease: Table 4 lists

adverse reactions that occurred in the double-blind, placebo-controlled studies in early Parkinson’s

disease that were reported by ≥1% of patients treated with pramipexole dihydrochloride tablets and

were numerically more frequent than in the placebo group. In these studies, patients did not receive

concomitant levodopa.

Table 4 Adverse-Reactions in Double-Blind, Placebo-Controlled Trials With Pramipexole

Dihydrochloride Tablets in Early Parkinson's Disease

Body System/ Adverse Reaction

Pramipexole Dihydrochloride

(N=388)

%

Placebo

(N=235)

%

Nervous System

Dizziness

Somnolence

Insomnia

Hallucinations

Confusion

Amnesia

Hypesthesia

Dystonia

Akathisia

Thinking abnormalities

Decreased libido

Myoclonus

Digestive System

Nausea

Constipation

Anorexia

Dysphagia

Body as a Whole

Asthenia

General edema

Malaise

Reaction unevaluable

Fever

Metabolic & Nutritional System

Peripheral edema

Decreased weight

Special Senses

Vision abnormalities

Urogenital System

Impotence

In a fixed-dose study in early Parkinson’s disease, occurrence of the following reactions increased in

frequency as the dose increased over the range from 1.5 mg/day to 6 mg/day: postural hypotension,

nausea, constipation, somnolence, and amnesia. The frequency of these reactions was generally 2-fold

greater than placebo for pramipexole doses greater than 3 mg/day. The incidence of somnolence with

pramipexole at a dose of 1.5 mg/day was comparable to that reported for placebo.

Advanced Parkinson’s Disease

In the four double-blind, placebo-controlled trials of patients with advanced Parkinson’s disease, the

most common adverse reactions (>5%) that were numerically more frequent in the group treated with

pramipexole dihydrochloride tablets and concomitant levodopa were postural (orthostatic) hypotension,

dyskinesia, extrapyramidal syndrome, insomnia, dizziness, hallucinations, accidental injury, dream

abnormalities, confusion, constipation, asthenia, somnolence, dystonia, gait abnormality, hypertonia, dry

mouth, amnesia, and urinary frequency.

Approximately 12% of 260 patients with advanced Parkinson’s disease who received pramipexole

dihydrochloride tablets and concomitant levodopa in the double-blind, placebo-controlled trials

discontinued treatment due to adverse reactions compared with 16% of 264 patients who received

placebo and concomitant levodopa. The reactions most commonly causing discontinuation of treatment

were related to the nervous system (hallucinations [2.7% on pramipexole dihydrochloride tablets vs

0.4% on placebo]; dyskinesia [1.9% on pramipexole dihydrochloride tablets vs 0.8% on placebo]) and

cardiovascular system (postural [orthostatic] hypotension [2.3% on pramipexole dihydrochloride tablets

vs 1.1% on placebo]).

Adverse-reaction Incidence in Controlled Clinical Studies in Advanced Parkinson's Disease: Table 5 lists

adverse reactions that occurred in the double-blind, placebo-controlled studies in advanced Parkinson’s

disease that were reported by ≥1% of patients treated with pramipexole dihydrochloride tablets and

were numerically more frequent than in the placebo group. In these studies, pramipexole

dihydrochloride tablets or placebo was administered to patients who were also receiving concomitant

levodopa.

Table 5 Adverse-Reactions in Double-Blind, Placebo-Controlled Trials With Pramipexole

Dihydrochloride Tablets in Advanced Parkinson's Disease

Body

System/

Advers e

Reaction

Pramipexole

Dihydrochloride

(N=260)

%

Placebo

(N = 264)

%

Nervous System

Dyskinesia

Extrapyramidal syndrome

Insomnia

Dizziness

Hallucinations

Dream abnormalities

Confusion

Somnolence

Dystonia

Gait abnormalities

Hypertonia

Amnesia

Akathisia

Thinking abnormalities

Paranoid reaction

Delusions

Sleep disorders

Cardiovascular System

Postural hypotension

Body as a Whole

Accidental injury

17

15

Asthenia

10

8

General edema

4

3

Chest pain

Malaise

Digestive System

Constipation

Dry mouth

Urogenital System

Urinary frequency

Urinary tract infection

Urinary incontinence

Respiratory System

Dyspnea

Rhinitis

Pneumonia

Special Senses

Accommodation Abnormalities

Vision abnormalities

Diplopia

Musculoskeletal System

Arthritis

Twitching

Bursitis

Myasthenia

Metabolic & Nutritional System

Peripheral edema

Increased creatine PK

Skin & Appendages

Skin disorders

Adverse Reactions: Relationship to Age, Gender, and Race

Among the adverse reactions in patients treated with pramipexole dihydrochloride tablets, hallucination

appeared to exhibit a positive relationship to age in patients with Parkinson’s disease. Although no

gender-related differences were observed in Parkinson’s disease patients. Less than 4% of patients

enrolled were non-Caucasian: therefore, an evaluation of adverse reactions related to race is not

possible.

Laboratory Tests

During the development of pramipexole dihydrochloride tablets, no systematic abnormalities on routine

laboratory testing were noted.

6.2 Post Marketing Experience

In addition to the adverse events reported during clinical trials, the following adverse reactions have

been identified during post-approval use of pramipexole dihydrochloride tablets, primarily in

Parkinson’s disease patients. Because these reactions are reported voluntarily from a population of

uncertain size, it is not always possible to reliably estimate their frequency or establish a causal

relationship to drug exposure. Decisions to include these reactions in labeling are typically based on

one or more of the following factors: (1) seriousness of the reaction, (2) frequency of reporting, or (3)

strength of causal connection to pramipexole tablets. Similar types of reactions were grouped into a

smaller number of standardized categories using the MedDRA terminology: cardiac failure,

inappropriate antidiuretic hormone secretion (SIADH), skin reactions (including erythema, rash,

pruritus, urticaria), syncope, vomiting, and weight increase.

7 DRUG INTERACTIONS

7.1 Dopamine Antagonists

Since pramipexole is a dopamine agonist, it is possible that dopamine antagonists, such as the

neuroleptics (phenothiazines, butyrophenones, thioxanthenes) or metoclopramide, may diminish the

effectiveness of pramipexole dihydrochloride tablets.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category C

Risk Summary

There are no adequate data on the developmental risk associated with the use of pramipexole

dihydrochloride 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 rabbits or

humans. Because of pregnancy disruption and early embryonic loss in this study, the teratogenic

potential of pramipexole could not be adequately assessed in rats. The highest no-effect dose for

embryolethality in rats was associated with maternal plasma drug exposures (AUC) approximately equal

to those in humans receiving the maximum recommended human dose (MRHD) of 4.5 mg/day. There

were no adverse effects on embryo-fetal development following oral administration of pramipexole

(0.1, 1, and 10 mg/kg/day) to pregnant rabbits during organogenesis (plasma AUC up to approximately

70 times that in humans at the MRHD). Postnatal growth was inhibited in the offspring of rats treated

with pramipexole (0.1, 0.5, or 1.5 mg/kg/day) during the latter part of pregnancy and throughout

lactation. The no-effect dose for adverse effects on offspring growth (0.1 mg/kg/day) was associated

with maternal plasma drug exposures lower than that in humans at the MRHD.

8.2 Lactation

Risk Summary

There are no data on the presence of pramipexole in human milk, the effects of pramipexole on the

breastfed infant, or the effects of pramipexole on milk production. However, inhibition of lactation is

expected because pramipexole inhibits secretion of prolactin in humans. Pramipexole or metabolites, or

both, are present in rat milk [see Data].

The developmental and health benefits of breastfeeding should be considered along with the mother’s

clinical need for pramipexole dihydrochloride tablets and any potential adverse effects on the breastfed

infant from pramipexole dihydrochloride 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.

8.4 Pediatric Use

Safety and effectiveness of pramipexole dihydrochloride tablets in pediatric patients has not been

established.

8.5 Geriatric Use

Pramipexole total oral clearance is approximately 30% lower in subjects older than 65 years compared

with younger subjects, because of a decline in pramipexole renal clearance due to an age-related

reduction in renal function. This resulted in an increase in elimination half-life from approximately 8.5

hours to 12 hours.

In clinical studies with Parkinson’s disease patients, 38.7% of patients were older than 65 years. There

were no apparent differences in efficacy or safety between older and younger patients, except that the

relative risk of hallucination associated with the use of pramipexole dihydrochloride tablets was

increased in the elderly.

8.6 Renal Impairment

The elimination of pramipexole is dependent on renal function. Pramipexole clearance is extremely low

in dialysis patients, as a negligible amount of pramipexole is removed by dialysis. Caution should be

exercised when administering pramipexole dihydrochloride tablets to patients with renal disease [see

Dosage and Administration (2.2), Warnings and Precautions (5.6), and Clinical Pharmacology (12.3)].

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.

11 DESCRIPTION

Pramipexole dihydrochloride tablets contain pramipexole, a nonergot dopamine agonist. The chemical

name of pramipexole dihydrochloride is (S)-2-amino-4,5,6,7-tetrahydro-6-(propylamino)benzothiazole

dihydrochloride monohydrate. Its empirical formula is C

H N S · 2HCl · H O, and its molecular

weight is 302.26. The structural formula is:

Pramipexole dihydrochloride is a white to off-white powder substance. Melting occurs in the range of

296°C to 301°C, with decomposition. Pramipexole dihydrochloride is more than 20% soluble in water,

about 8% in methanol, about 0.5% in ethanol, and practically insoluble in dichloromethane.

Pramipexole dihydrochloride tablets, for oral administration, contain 0.125 mg, 0.25 mg, 0.5 mg, 1 mg,

or 1.5 mg of pramipexole dihydrochloride monohydrate USP. Inactive ingredients consist of

betacyclodextrin (betadex), corn starch, colloidal silicon dioxide, povidone, magnesium stearate and

microcrystalline cellulose.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Pramipexole is a non-ergot dopamine agonist with high relative in vitro specificity and full intrinsic

activity at the D subfamily of dopamine receptors, binding with higher affinity to D than to D or D

receptor subtypes.

Parkinson’s Disease

The precise mechanism of action of pramipexole as a treatment for Parkinson’s disease is unknown,

although it is believed to be related to its ability to stimulate dopamine receptors in the striatum. This

conclusion is supported by electrophysiologic studies in animals that have demonstrated that

pramipexole influences striatal neuronal firing rates via activation of dopamine receptors in the striatum

and the substantia nigra, the site of neurons that send projections to the striatum. The relevance of D

receptor binding in Parkinson’s disease is unknown.

12.2 Pharmacodynamics

The effect of pramipexole on the QT interval of the ECG was investigated in a clinical study in 60

healthy male and female volunteers. All subjects initiated treatment with 0.375 mg extended release

pramipexole tablets administered once daily, and were up-titrated every 3 days to 2.25 mg and 4.5 mg

daily, a faster rate of titration than recommended in the label. No dose- or exposure-related effect on

mean QT intervals was observed; however, the study did not have a valid assessment of assay

sensitivity. The effect of pramipexole on QTc intervals at higher exposures achieved either due to

drug interactions (e.g., with cimetidine), renal impairment, or at higher doses has not been systematically

evaluated.

Although mean values remained within normal reference ranges throughout the study, supine systolic

blood pressure (SBP), diastolic blood pressure (DBP), and pulse rate for subjects treated with

pramipexole generally increased during the rapid up-titration phase, by 10 mmHg, 7 mmHg, and 10 bpm

higher than placebo, respectively. Higher SBP, DBP, and pulse rates compared to placebo were

maintained until the pramipexole doses were tapered; values on the last day of tapering were generally

similar to baseline values. Such effects have not been observed in clinical studies with Parkinson’s

disease patients, who were titrated according to labeled recommendations.

12.3 Pharmacokinetics

Pramipexole displays linear pharmacokinetics over the clinical dosage range. Its terminal half-life is

about 8 hours in young healthy volunteers and about 12 hours in elderly volunteers. Steady-state

concentrations are achieved within 2 days of dosing.

Absorption

Pramipexole is rapidly absorbed, reaching peak concentrations in approximately 2 hours. The absolute

bioavailability of pramipexole is greater than 90%, indicating that it is well absorbed and undergoes

little presystemic metabolism. Food does not affect the extent of pramipexole absorption, although the

time of maximum plasma concentration (T

) is increased by about 1 hour when the drug is taken with a

meal.

Distribution

Pramipexole is extensively distributed, having a volume of distribution of about 500 L (coefficient of

variation [CV]=20%). It is about 15% bound to plasma proteins. Pramipexole distributes into red blood

cells as indicated by an erythrocyte-to-plasma ratio of approximately 2.

Metabolism

Pramipexole is metabolized only to a negligible extent (<10%). No specific active metabolite has been

identified in human plasma or urine.

Elimination

Urinary excretion is the major route of pramipexole elimination, with 90% of a pramipexole dose

recovered in urine, almost all as unchanged drug. The renal 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 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,

which can cause a large decrease in the ability to eliminate pramipexole, may necessitate dosage

adjustment [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 half-life between males and females.

Age

Pramipexole clearance decreases with age as the half-life and clearance are about 40% longer and 30%

lower, respectively, in 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.

Parkinson’s Disease Patients

A cross-study comparison of data suggests that the clearance of pramipexole may be reduced by about

30% in Parkinson’s disease patients compared with healthy elderly volunteers. The reason for this

difference appears to be reduced renal function in Parkinson’s disease patients, which may be related to

their poorer general health. The pharmacokinetics of pramipexole were comparable between early and

advanced Parkinson’s disease patients.

Hepatic Impairment

The influence of hepatic insufficiency on pramipexole pharmacokinetics has not been evaluated.

Because approximately 90% of the recovered dose is excreted in the urine as unchanged drug, hepatic

impairment would not be expected to have a significant effect on pramipexole elimination.

Renal Impairment

Clearance of pramipexole was about 75% lower in patients with severe renal impairment (creatinine

clearance approximately 20 mL/min) and about 60% lower in patients with moderate impairment

(creatinine clearance approximately 40 mL/min) compared with healthy volunteers [see Warnings and

Precautions (5.6) and Dosage and Administration (2.2)]. In patients with varying degrees of renal

impairment, pramipexole clearance correlates well with creatinine clearance. Therefore, creatinine

clearance can be used as a predictor of the extent of decrease in pramipexole clearance.

Drug Interactions

Carbidopa/levodopa: Carbidopa/levodopa did not influence the pharmacokinetics of pramipexole in

healthy volunteers (N=10). Pramipexole did not alter the extent of absorption (AUC) or the elimination

of carbidopa/levodopa, although it caused an increase in levodopa C

by about 40% and a decrease

in T

from 2.5 to 0.5 hours.

Selegiline: In healthy volunteers (N=11), selegiline did not influence the pharmacokinetics of

pramipexole.

Amantadine: Population pharmacokinetic analyses suggest that amantadine may slightly decrease the oral

clearance of pramipexole.

Cimetidine: Cimetidine, a known inhibitor of renal tubular secretion of organic bases via the cationic

transport system, caused a 50% increase in pramipexole AUC and a 40% increase in half-life (N=12).

Probenecid: Probenecid, a known inhibitor of renal tubular secretion of organic acids via the anionic

transporter, did not noticeably influence pramipexole pharmacokinetics (N=12).

Other drugs eliminated via renal secretion: Population pharmacokinetic analysis suggests that

coadministration of drugs that are secreted by the cationic transport system (e.g., cimetidine, ranitidine,

diltiazem, triamterene, verapamil, quinidine, and quinine) decreases the oral clearance of pramipexole by

about 20%, while those secreted by the anionic transport system (e.g., cephalosporins, penicillins,

indomethacin, hydrochlorothiazide, and chlorpropamide) are likely to have little effect on the oral

clearance of pramipexole. Other known organic cation transport substrates and/or inhibitors (e.g.,

cisplatin and procainamide) may also decrease the clearance of pramipexole.

CYP interactions: Inhibitors of cytochrome P450 enzymes would not be expected to affect pramipexole

elimination because pramipexole is not appreciably metabolized by these enzymes in vivo or in vitro.

Pramipexole does not inhibit CYP enzymes CYP1A2, CYP2C9, CYP2C19, CYP2E1, and CYP3A4.

Inhibition of CYP2D6 was observed with an apparent Ki of 30 μM, indicating that pramipexole will not

inhibit CYP enzymes at plasma concentrations observed following the clinical dose of 4.5 mg/day (1.5

mg TID).

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, 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) for Parkinson’s disease of 4.5 mg/day on a mg/m basis).

Pramipexole wasadministered 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 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.

13.2 Animal Toxicology and/or Pharmacology

Retinal Pathology in 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). 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 (by morphometric

analysis) 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

MRHD on a mg/m 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 MRHD on a mg/m 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 MRHD on a mg/m 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 MRHD on a mg/m basis).

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.

14 CLINICAL STUDIES

14.1 Parkinson's Disease

The effectiveness of pramipexole dihydrochloride tablets in the treatment of Parkinson’s disease was

evaluated in a multinational drug development program consisting of seven randomized, controlled

trials. Three were conducted in patients with early Parkinson’s disease who were not receiving

concomitant levodopa, and four were conducted in patients with advanced Parkinson’s disease who

were receiving concomitant levodopa. Among these seven studies, three studies provide the most

persuasive evidence of pramipexole's effectiveness in the management of patients with Parkinson’s

disease who were and were not receiving concomitant levodopa. Two of these three trials enrolled

patients with early Parkinson’s disease (not receiving levodopa), and one enrolled patients with

advanced Parkinson’s disease who were receiving maximally tolerated doses of levodopa.

In all studies, the Unified Parkinson’s Disease Rating Scale (UPDRS), or one or more of its subparts,

served as the primary outcome assessment measure. The UPDRS is a four-part multi-item rating scale

intended to evaluate mentation (part I), Activities of Daily Living (ADL) (part II), motor performance

(part III), and complications of therapy (part IV).

Part II of the UPDRS contains 13 questions relating to ADL, which are scored from 0 (normal) to 4

(maximal severity) for a maximum (worst) score of 52. Part III of the UPDRS contains 27 questions (for

14 items) and is scored as described for part II. It is 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.

instability, etc.), scored for different body regions, and has a maximum (worst) score of 108.

Studies in Patients with Early Parkinson's Disease

Patients (N=599) in the two studies of early Parkinson’s disease had a mean disease duration of 2 years,

limited or no prior exposure to levodopa (generally none in the preceding 6 months), and were not

experiencing the "on-off" phenomenon and dyskinesia characteristic of later stages of the disease.

One of the two early Parkinson’s disease studies (N=335) was a double-blind, placebo-controlled,

parallel trial consisting of a 7-week dose-escalation period and a 6-month maintenance period. Patients

could be on selegiline, anticholinergics, or both, but could not be on levodopa products or amantadine.

Patients were randomized to pramipexole dihydrochloride tablets or placebo. Patients treated with

pramipexole dihydrochloride tablets had a starting daily dose of 0.375 mg and were titrated to a

maximally tolerated dose, but no higher than 4.5 mg/day in three divided doses. At the end of the 6-

month maintenance period, the mean improvement from baseline on the UPDRS part II (ADL) total score

was 1.9 in the group receiving pramipexole dihydrochloride tablets and -0.4 in the placebo group, a

difference that was statistically significant. The mean improvement from baseline on the UPDRS part III

total score was 5 in the group receiving pramipexole dihydrochloride tablets and -0.8 in the placebo

group, a difference that was also statistically significant. A statistically significant difference between

groups in favor of pramipexole dihydrochloride tablets was seen beginning at week 2 of the UPDRS

part II (maximum dose 0.75 mg/day) and at week 3 of the UPDRS part III (maximum dose 1.5 mg/day).

The second early Parkinson’s disease study (N=264) was a double-blind, placebo-controlled, parallel

trial consisting of a 6-week dose-escalation period and a 4-week maintenance period. Patients could be

on selegiline, anticholinergics, amantadine, or any combination of these, but could not be on levodopa

products. Patients were randomized to 1 of 4 fixed doses of pramipexole dihydrochloride tablets (1.5

mg, 3 mg, 4.5 mg, or 6 mg per day) or placebo. At the end of the 4-week maintenance period, the mean

improvement from baseline on the UPDRS part II total score was 1.8 in the patients treated with

pramipexole dihydrochloride tablets, regardless of assigned dose group, and 0.3 in placebo-treated

patients. The mean improvement from baseline on the UPDRS part III total score was 4.2 in patients

treated with pramipexole dihydrochloride tablets and 0.6 in placebo-treated patients. No dose-response

relationship was demonstrated. The between-treatment differences on both parts of the UPDRS were

statistically significant in favor of pramipexole dihydrochloride tablets for all doses.

No differences in effectiveness based on age or gender were detected. There were too few non-

Caucasian patients to evaluate the effect of race. Patients receiving selegiline or anticholinergics had

responses similar to patients not receiving these drugs.

Studies in Patients with Advanced Parkinson's Disease

In the advanced Parkinson’s disease study, the primary assessments were the UPDRS and daily diaries

that quantified amounts of “on” and “off” time.

Patients in the advanced Parkinson’s disease study (N=360) had a mean disease duration of 9 years, had

been exposed to levodopa for long periods of time (mean 8 years), used concomitant levodopa during

the trial, and had “on-off” periods.

The advanced Parkinson’s disease study was a double-blind, placebo-controlled, parallel trial

consisting of a 7-week dose-escalation period and a 6-month maintenance period. Patients were all

treated with concomitant levodopa products and could additionally be on concomitant selegiline,

anticholinergics, amantadine, or any combination. Patients treated with pramipexole dihydrochloride

tablets had a starting dose of 0.375 mg/day and were titrated to a maximally tolerated dose, but no higher

than 4.5 mg/day in three divided doses. At selected times during the 6-month maintenance period,

patients were asked to record the amount of “off,” “on, “or” on with dyskinesia” time per day for several

sequential days. At the end of the 6-month maintenance period, the mean improvement from baseline on

the UPDRS part II total score was 2.7 in the group treated with pramipexole dihydrochloride tablets and

0.5 in the placebo group, a difference that was statistically significant. The mean improvement from

baseline on the UPDRS part III total score was 5.6 in the group treated with pramipexole

dihydrochloride tablets and 2.8 in the placebo group, a difference that was statistically significant. A

statistically significant difference between groups in favor of pramipexole dihydrochloride tablets was

seen at week 3 of the UPDRS part II (maximum dose 1.5 mg/day) and at week 2 of the UPDRS part III

(maximum dose 0.75 mg/day). Dosage reduction of levodopa was allowed during this study if

dyskinesia (or hallucinations) developed; levodopa dosage reduction occurred in 76% of patients

treated with pramipexole dihydrochloride tablets versus 54% of placebo patients. On average, the

levodopa dose was reduced 27%.

The mean number of "off" hours per day during baseline was 6 hours for both treatment groups.

Throughout the trial, patients treated with pramipexole dihydrochloride tablets had a mean of 4 "off"

hours per day, while placebo-treated patients continued to experience 6 "off" hours per day.

No differences in effectiveness based on age or gender were detected. There were too few non-

Caucasian patients to evaluate the effect of race.

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied

Pramipexole dihydrochloride tablets are available as follows:

0.125 mg: White to off white, circular tablet debossed with “E” on one side and “33” on the other side.

Bottles of 90 NDC 46708-611-90

0.25 mg: White to off white, oval shaped tablet with break line on both side and debossed with “E E” on

one side and “34 34” on other side.

Bottles of 90 NDC 46708-612-90

0.5 mg: White to off white, oval shaped tablet with break line on both side and debossed with “E E” on

one side and “35 35” on other side.

Bottles of 90 NDC 46708-613-90

1 mg: White to off white, circular tablet with break line on both side and debossed with “E E” on one

side and “36 36” on other side.

Bottles of 90 NDC 46708-614-90

1.5 mg: White to off white, circular tablet with break line on both side and debossed with “E E” on one

side and “37 37” on other side.

Bottles of 90 NDC 46708-615-90

16.2 Storage and Handling

Store at 25°C (77°F); excursions permitted to 15°-30°C (59°-86°F)[see USP Controlled Room

Temperature]. Protect from light.

Store in a safe place out of the reach of children.

17 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Patient Information).

Dosing Instructions

Instruct patients to take pramipexole dihydrochloride tablets only as prescribed. If a dose is missed,

advise patients not to double their next dose.

Pramipexole dihydrochloride tablets can be taken with or without food. If patients develop nausea,

advise that taking pramipexole dihydrochloride tablets with food may reduce the occurrence of nausea.

Pramipexole is the active ingredient that is in both pramipexole dihydrochloride tablets and extended-

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

pramipexole dihydrochloride tablets.

Sedating Effects

Alert patients to the potential sedating effects associated with pramipexole dihydrochloride tablets,

including somnolence and the possibility of falling asleep while engaged in activities of daily living.

Since somnolence is a frequent adverse reaction with potentially serious consequences, patients should

neither drive a car nor engage in other potentially dangerous activities until they have gained sufficient

experience with pramipexole dihydrochloride tablets to gauge whether or not it affects their mental

and/or motor performance adversely. Advise patients that if increased somnolence or new episodes of

falling asleep during activities of daily living (e.g., conversations or eating) are experienced at any time

during treatment, they should not drive or participate in potentially dangerous activities until they have

contacted their physician. Because of possible additive effects, advise caution when patients are taking

other sedating medications or alcohol in combination with pramipexole dihydrochloride tablets and

when taking concomitant medications that increase plasma levels of pramipexole (e.g., cimetidine) [see

Warnings and Precautions (5.1)].

Impulse Control Symptoms Including Compulsive Behaviors

Alert patients and their caregivers to the possibility that they may experience intense urges to spend

money uncontrollably, intense urges to gamble, increased sexual urges, binge eating and/or other

intense urges and the inability to control these urges while taking pramipexole dihydrochloride tablets

[see Warnings and Precautions (5.3)].

Hallucinations and 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 tablets [see Warnings and Precautions (5.2)].

Pregnancy

Because the teratogenic potential of pramipexole has not been completely established in laboratory

animals, and because experience in humans is limited, advise women to notify their physicians if they

become pregnant or intend to become pregnant during therapy [see Use in Specific Populations (8.1)].

Lactation

Because of the possibility that pramipexole may be excreted in breast milk, advise women to notify their

physicians if they intend to breast-feed or are breast-feeding an infant [see Use in Specific Populations

(8.2)].

Manufactured by:

Alembic Pharmaceuticals Limited (Formulation Division),

Village Panelav, P. O. Tajpura, Near Baska,

Taluka-Halol, Panchmahal, Gujarat, India.

Revised: 09/2019

PATIENT INFORMATION

Pramipexole Dihydrochloride (PRAM-i-PEX-ole Dye-HYE-droe-KLOR-ide) Tablets

Read this Patient Information before you start taking pramipexole dihydrochloride 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 tablet?

Pramipexole dihydrochloride tablet is a prescription medicine used to treat:

signs and symptoms of Parkinson’s disease (PD)

It is not known if pramipexole dihydrochloride is safe and effective in children.

What should I tell my doctor before taking pramipexole dihydrochloride?

Before taking pramipexole dihydrochloride, tell your doctor if you:

feel sleepy during the day from a sleep problem

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 will make you feel

sleepy

or fall asleep when you should be awake.

have any other medical conditions

are pregnant or plan to become pregnant. It is not known if pramipexole dihydrochloride will harm your

unborn baby.

are breastfeeding or plan to breastfeed. It is not known if pramipexole dihydrochloride passes into

your breast milk. You and your doctor should decide if you will take pramipexole dihydrochloride or

breastfeed. You should not do both.

Tell your doctor about all the medicines you take, including prescription and nonprescription

medicines, vitamins, and herbal supplements.

The combination of pramipexole dihydrochloride and other medicines may affect each other and may

cause side effects. Pramipexole dihydrochloride may affect the way other medicines work, and other

medicines may affect how pramipexole dihydrochloride works.

Especially tell your doctor if you take:

medicines called neuroleptics (phenothiazines, butyrophenones, thioxanthenes) or metoclopramide.

Pramipexole dihydrochloride may not work as well if you take these medicines.

extended-release pramipexole (pramipexole dihydrochloride tablets ER). Pramipexole is the active

ingredient in both pramipexole dihydrochloride tablets and pramipexole dihydrochloride tablets ER. If

you are taking pramipexole dihydrochloride tablets ER, you should not take pramipexole

dihydrochloride tablets.

any other medicines that make you sleepy or may increase the effects of pramipexole dihydrochloride

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?

Take pramipexole dihydrochloride tablets exactly as your doctor tells you to take it.

Your doctor will tell you how much pramipexole dihydrochloride tablets to take and when to take it.

Do not take more or less pramipexole dihydrochloride tablets than your doctor tells you to.

Your doctor may change your dose if needed.

Pramipexole dihydrochloride tablets can be taken with or without food. Taking pramipexole

dihydrochloride tablets with food may lower your chances of getting nausea.

If you take more pramipexole dihydrochloride tablets than your doctor recommends, call your doctor

or go to the nearest hospital emergency room right away.

If you miss a dose, do not double your next dose. Skip the dose you missed and take your next

regular dose.

If you have Parkinson’s disease and your doctor tells you to stop taking pramipexole dihydrochloride

tablets, you should stop pramipexole dihydrochloride tablets slowly as directed by your doctor. If you

stop pramipexole dihydrochloride tablets too quickly you may have withdrawal symptoms such as:

fever

confusion

severe muscle stiffness

Do not stop taking pramipexole dihydrochloride tablets without talking to your doctor.

What should I avoid while taking pramipexole dihydrochloride tablets?

Do not drink alcohol while taking pramipexole dihydrochloride tablets. It can increase your chance of

having serious side effects. See “What are the possible side effects of pramipexole dihydrochloride

tablets?”

Do not drive a car, operate a machine, or do other dangerous activities until you know how

pramipexole dihydrochloride tablets affects you. Sleepiness caused by pramipexole dihydrochloride

tablets can happen as late as 1 year after you start your treatment.

What are the possible side effects of pramipexole dihydrochloride tablets?

Pramipexole dihydrochloride tablets may cause serious side effects, including:

falling asleep during normal daily activities. Pramipexole dihydrochloride tablets may cause you to

fall asleep while you are doing daily activities such as driving, talking with other people, or eating.

oSome people taking the medicine in pramipexole dihydrochloride tablets have had car accidents

because they fell asleep while driving.

oSome patients did not feel sleepy before they fell asleep while driving. You could fall asleep without

any warning.

Tell your doctor right away if you fall asleep while you are doing activities such as talking, eating,

driving, or if you feel sleepier than normal for you.

low blood pressure when you sit or stand up quickly. You may have:

dizziness

nausea

fainting

sweating

Sit and stand up slowly after you have been sitting or lying down.

unusual urges. Some people who take certain medicines to treat Parkinson’s disease, including

pramipexole dihydrochloride tablets, have reported problems, such as gambling, compulsive eating,

compulsive buying, and increased sex drive.

If you or your family members notice that you are developing unusual urges or behaviors, talk to your

doctor.

hallucinations and other psychotic-like behavior (seeing visions, hearing sounds or feeling

sensations that are not real, confusion, excessive suspicion, aggressive behavior, agitation, delusional

beliefs and disorganized thinking). Your chance of having hallucinations and other psychotic-like

behavior is higher if you are elderly (age 65 or older).

If you have hallucinations or other psychotic-like changes, talk with your doctor right away.

uncontrolled sudden movements (dyskinesia).

If you have new dyskinesia or your existing dyskinesia gets worse tell your doctor.

skin cancer (melanoma). Some people with Parkinson’s disease may have a higher chance of having

melanoma than people who do not have Parkinson’s disease. It is not known if the chance of having

melanoma is higher because of the medicines to treat Parkinson’s disease, like pramipexole

dihydrochloride tablets, or from the Parkinson’s disease. People who take pramipexole

dihydrochloride tablets should have regular skin examinations to check for melanoma.

The most common side effects in people taking pramipexole dihydrochloride tablets for Parkinson’s

disease are:

nausea

dizziness

insomnia

constipation

muscle weakness

abnormal dreams

confusion

memory problems (amnesia)

urinating more often than normal

These are not all the possible side effects of pramipexole dihydrochloride tablets Tell your doctor if

you have any side effect that bothers you.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-

FDA-1088.

How should I store pramipexole dihydrochloride tablets?

Store pramipexole dihydrochloride tablets at 15º-30ºC (59º-86ºF).

Keep pramipexole dihydrochloride tablets out of the light.

Keep pramipexole dihydrochloride tablets and all medicines out of the reach of children.

General Information about the safe and effective use of pramipexole dihydrochloride tablets.

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet.

Do not use pramipexole dihydrochloride tablets for a condition for which it was not prescribed. Do not

give pramipexole dihydrochloride tablets to other people, even if they have the same symptoms that you

have. It may harm them.

This Patient Information leaflet summarizes the most important information about pramipexole

dihydrochloride tablets. If you would like more information, talk with your doctor. You can ask your

pharmacist or doctor for information about pramipexole dihydrochloride tablets that is written for

healthcare professionals.

What are the ingredients in pramipexole dihydrochloride tablets?

Active Ingredient: Pramipexole dihydrochloride monohydrate USP

Inactive Ingredients: betacyclodextrin (betadex), corn starch, colloidal silicon dioxide, povidone,

magnesium stearate and microcrystalline cellulose.

This Patient Information has been approved by the U.S. Food and Drug Administration.

Manufactured by:

Alembic Pharmaceuticals Limited (Formulation Division),

Village Panelav, P. O. Tajpura, Near Baska,

Taluka-Halol, Panchmahal, Gujarat, India.

Revised: 09/2019

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL - 0.125 mg

NDC 46708-611-90

Pramipexole

Dihydrochloride

Tablets

0.125 mg

Rx only

90 Tablets

Alembic

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL - 0.25 mg

NDC 46708-612-90

Pramipexole

Dihydrochloride

Tablets

0.25 mg

Rx only

90 Tablets

Alembic

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL - 0.5 mg

NDC 46708-613-90

Pramipexole

Dihydrochloride

Tablets

0.5 mg

0.5 mg

Rx only

90 Tablets

Alembic

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL - 1 mg

NDC 46708-614-90

Pramipexole

Dihydrochloride

Tablets

1 mg

Rx only

90 Tablets

Alembic

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL - 1.5 mg

NDC 46708-615-90

Pramipexole

Dihydrochloride

Tablets

1.5 mg

Rx only

90 Tablets

Alembic

PRAMIPEXOLE DIHYDROCHLORIDE

pramipexole dihydrochloride tablet

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:46 70 8 -6 11

Route of Administration

ORAL

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

PRAMIPEXO LE DIHYDRO CHLO RIDE (UNII: 3D8 6 7NP0 6 J) (PRAMIPEXOLE -

UNII:8 36 19 PEU5T)

PRAMIPEXOLE

DIHYDROCHLORIDE

0 .125 mg

Inactive Ingredients

Ingredient Name

Stre ng th

BETADEX (UNII: JV0 39 JZZ3A)

STARCH, CO RN (UNII: O8 232NY3SJ)

SILICO N DIO XIDE (UNII: ETJ7Z6 XBU4)

PO VIDO NE K3 0 (UNII: U725QWY32X)

MICRO CRYSTALLINE CELLULO SE (UNII: OP1R32D6 1U)

MAGNESIUM STEARATE (UNII: 70 0 9 7M6 I30 )

Product Characteristics

Color

WHITE (White to o ff white)

S core

no sco re

S hap e

ROUND (Circular)

S iz e

6 mm

Flavor

Imprint Code

E;33

Contains

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NDC:46 70 8 -6 11-9 0

9 0 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

0 3/22/20 16

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA0 78 8 9 4

0 3/22/20 16

PRAMIPEXOLE DIHYDROCHLORIDE

pramipexole dihydrochloride tablet

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:46 70 8 -6 12

Route of Administration

ORAL

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

PRAMIPEXO LE DIHYDRO CHLO RIDE (UNII: 3D8 6 7NP0 6 J) (PRAMIPEXOLE -

UNII:8 36 19 PEU5T)

PRAMIPEXOLE

DIHYDROCHLORIDE

0 .25 mg

Inactive Ingredients

Ingredient Name

Stre ng th

BETADEX (UNII: JV0 39 JZZ3A)

STARCH, CO RN (UNII: O8 232NY3SJ)

SILICO N DIO XIDE (UNII: ETJ7Z6 XBU4)

PO VIDO NE K3 0 (UNII: U725QWY32X)

MICRO CRYSTALLINE CELLULO SE (UNII: OP1R32D6 1U)

MAGNESIUM STEARATE (UNII: 70 0 9 7M6 I30 )

Product Characteristics

Color

WHITE (White to o ff white)

S core

2 pieces

S hap e

OVAL

S iz e

8 mm

Flavor

Imprint Code

E;E;34;34

Contains

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NDC:46 70 8 -6 12-9 0

9 0 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

0 3/22/20 16

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA0 78 8 9 4

0 3/22/20 16

PRAMIPEXOLE DIHYDROCHLORIDE

pramipexole dihydrochloride tablet

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:46 70 8 -6 13

Route of Administration

ORAL

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

PRAMIPEXO LE DIHYDRO CHLO RIDE (UNII: 3D8 6 7NP0 6 J) (PRAMIPEXOLE -

UNII:8 36 19 PEU5T)

PRAMIPEXOLE

DIHYDROCHLORIDE

0 .5 mg

Inactive Ingredients

Ingredient Name

Stre ng th

BETADEX (UNII: JV0 39 JZZ3A)

STARCH, CO RN (UNII: O8 232NY3SJ)

SILICO N DIO XIDE (UNII: ETJ7Z6 XBU4)

PO VIDO NE K3 0 (UNII: U725QWY32X)

MICRO CRYSTALLINE CELLULO SE (UNII: OP1R32D6 1U)

MAGNESIUM STEARATE (UNII: 70 0 9 7M6 I30 )

Product Characteristics

Color

WHITE (White to o ff white)

S core

2 pieces

S hap e

OVAL

S iz e

10 mm

Flavor

Imprint Code

E;E;35;35

Contains

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NDC:46 70 8 -6 13-9 0

9 0 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

0 3/22/20 16

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA0 78 8 9 4

0 3/22/20 16

PRAMIPEXOLE DIHYDROCHLORIDE

pramipexole dihydrochloride tablet

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:46 70 8 -6 14

Route of Administration

ORAL

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

PRAMIPEXO LE DIHYDRO CHLO RIDE (UNII: 3D8 6 7NP0 6 J) (PRAMIPEXOLE -

UNII:8 36 19 PEU5T)

PRAMIPEXOLE

DIHYDROCHLORIDE

1 mg

Inactive Ingredients

Ingredient Name

Stre ng th

BETADEX (UNII: JV0 39 JZZ3A)

STARCH, CO RN (UNII: O8 232NY3SJ)

SILICO N DIO XIDE (UNII: ETJ7Z6 XBU4)

PO VIDO NE K3 0 (UNII: U725QWY32X)

MICRO CRYSTALLINE CELLULO SE (UNII: OP1R32D6 1U)

MAGNESIUM STEARATE (UNII: 70 0 9 7M6 I30 )

Product Characteristics

Color

WHITE (White to o ff white)

S core

2 pieces

S hap e

ROUND (Circular)

S iz e

9 mm

Flavor

Imprint Code

E;E;36 ;36

Contains

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NDC:46 70 8 -6 14-9 0

9 0 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

0 3/22/20 16

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA0 78 8 9 4

0 3/22/20 16

PRAMIPEXOLE DIHYDROCHLORIDE

pramipexole dihydrochloride tablet

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:46 70 8 -6 15

Route of Administration

ORAL

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

PRAMIPEXO LE DIHYDRO CHLO RIDE (UNII: 3D8 6 7NP0 6 J) (PRAMIPEXOLE -

UNII:8 36 19 PEU5T)

PRAMIPEXOLE

DIHYDROCHLORIDE

1.5 mg

Inactive Ingredients

Ingredient Name

Stre ng th

BETADEX (UNII: JV0 39 JZZ3A)

STARCH, CO RN (UNII: O8 232NY3SJ)

SILICO N DIO XIDE (UNII: ETJ7Z6 XBU4)

PO VIDO NE K3 0 (UNII: U725QWY32X)

MICRO CRYSTALLINE CELLULO SE (UNII: OP1R32D6 1U)

MAGNESIUM STEARATE (UNII: 70 0 9 7M6 I30 )

Product Characteristics

Color

WHITE (White to o ff white)

S core

2 pieces

S hap e

ROUND (Circular)

S iz e

11mm

Flavor

Imprint Code

E;E;37;37

Contains

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NDC:46 70 8 -6 15-9 0

9 0 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

0 3/22/20 16

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA0 78 8 9 4

0 3/22/20 16

Labeler -

Alembic Pharmaceuticals Limited (650574663)

Establishment

Name

Ad d re s s

ID/FEI

Busine ss Ope rations

Alembic Pharmaceuticals Limited

6 50 5746 71 MANUFACTURE(46 70 8 -6 11, 46 70 8 -6 12, 46 70 8 -6 13, 46 70 8 -6 14, 46 70 8 -6 15)

Alembic Pharmaceuticals Limited

Revised: 9/2019

Similar products

Search alerts related to this product

View documents history

Share this information