Pramipexole Dihydrochloride

PRAMIPEXOLE DIHYDROCHLORIDE- pramipexole dihydrochloride tablet
Glenmark Generics Inc., USA

1 INDICATIONS AND USAGE

1.1 Parkinson’s Disease

Pramipexole dihydrochloride tablets are indicated for the treatment of the signs and symptoms of idiopathic 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 Parkinson’s Disease

In all clinical studies, dosage was initiated at a subtherapeutic level to avoid intolerable adverse effects and orthostatic hypotension. Pramipexole dihydrochloride tablets should be titrated gradually in all patients. The dose should be increased to achieve a maximum therapeutic effect, balanced against the principal side effects of dyskinesia, hallucinations, somnolence, and dry mouth.

Dosing in Patients with Normal Renal Function

Initial Treatment

Doses should be increased gradually from a starting dose of 0.375 mg/day given in three divided doses and should not be increased more frequently than every 5 to 7 days. A suggested ascending dosage schedule that was used in clinical studies is shown in the following table:

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

Week

Dosage (mg)

Total Daily Dose (mg)

1

0.125 TID

0.375

2

0.25 TID

0.75

3

0.5 TID

1.5

4

0.75 TID

2.25

5

1 TID

3

6

1.25 TID

3.75

7

1.5 TID

4.5

Maintenance Treatment

Pramipexole dihydrochloride tablets were effective and well tolerated over a dosage range of 1.5 to 4.5 mg/day administered in equally divided doses three times per day with or without concomitant levodopa (approximately 800 mg/day).

In a fixed-dose study in early Parkinson’s disease patients, doses of 3 mg, 4.5 mg, and 6 mg per day of pramipexole dihydrochloride tablets were not shown to provide any significant benefit beyond that achieved at a daily dose of 1.5 mg/day. However, in the same fixed-dose study, the following adverse events were dose related: postural hypotension, nausea, constipation, somnolence, and amnesia. The frequency of these events was generally 2-fold greater than placebo for pramipexole doses greater than 3 mg/day. The incidence of somnolence reported with pramipexole at a dose of 1.5 mg/day was comparable to placebo.

When pramipexole dihydrochloride tablets are used in combination with levodopa, a reduction of the levodopa dosage should be considered. In a controlled study in advanced Parkinson’s disease, the dosage of levodopa was reduced by an average of 27% from baseline.

Dosing in Patients with Renal Impairment

Table 2 Dosing of Pramipexole Dihydrochloride Tablets in Parkinson’s Disease Patients with Renal Impairment

Renal Status

Starting Dose (mg)

Maximum Dose (mg)

Normal to mild impairment (creatinine Cl >50 mL/min)

0.125 TID

1.5 TID

Moderate impairment (creatinine Cl =30 to 50 mL/min)

0.125 BID

0.75 TID

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

0.125 QD

1.5 QD

Very severe impairment (creatinine Cl <15 mL/min and hemodialysis patients)

The use of pramipexole dihydrochloride tablets has not been adequately studied in this group of patients.

Discontinuation of Treatment

Pramipexole dihydrochloride tablets should be tapered off at a rate of 0.75 mg per day until the daily dose has been reduced to 0.75 mg. Thereafter, the dose should be reduced by 0.375 mg per day. In some studies, however, abrupt discontinuation was uneventful.

3 DOSAGE FORMS AND STRENGTHS

0.125 mg: circular, white, flat beveled tablets engraved with ‘PX’ on one side and plain on the other side.
0.25 mg: oval, white, flat beveled tablets engraved with ‘PX’ and ‘1’ on either side of the breakline on one side and breakline on the other side.
0.5 mg: oval, white, flat beveled tablets engraved with ‘PX’ and ‘2’ on either side of the breakline on one side and breakline on the other side.
1 mg: oval, white, flat beveled tablets engraved with ‘PX’ and ‘3’ on either side of the breakline on one side and breakline on the other side.
1.5 mg: oval, white, flat beveled tablets engraved with ‘PX’ and ‘4’ on either side of the breakline on one side and breakline on the other side.

4 CONTRAINDICATIONS

None.

5 WARNINGS AND PRECAUTIONS

Click here to enter text.

5.1 Falling Asleep During Activities of Daily Living

Patients treated with pramipexole have reported falling asleep while engaged in activities of daily living, including the operation of motor vehicles which sometimes resulted in accidents. Although many of these patients reported somnolence while on pramipexole tablets, some perceived that they had no warning signs such as excessive drowsiness, and believed that they were alert immediately prior to the event. Some of these events had been reported as late as one year after the initiation of treatment.

Somnolence is a common occurrence in patients receiving pramipexole at doses above 1.5 mg/day (0.5 mg TID) for Parkinson’s disease.

Many clinical experts believe that falling asleep while engaged in activities of daily living always occurs in a setting of pre-existing somnolence, although patients may not give such a history. For this reason, prescribers should continually reassess patients for drowsiness or sleepiness, especially since some of the events occur well after the start of treatment. Prescribers should also be aware that patients may not acknowledge drowsiness or sleepiness until directly questioned about drowsiness or sleepiness during specific activities.

Before initiating treatment with pramipexole dihydrochloride tablets, advise patients of the potential to develop drowsiness and specifically asked about factors that may increase the risk with pramipexole dihydrochloride tablets such as the use of concomitant sedating medications or alcohol, the presence of sleep disorders, and concomitant medications that increase pramipexole plasma levels (e.g., cimetidine) [see Clinical Pharmacology (12.3) ]. If a patient develops significant daytime sleepiness or episodes of falling asleep during activities that require active participation (e.g., conversations, eating, etc.), pramipexole dihydrochloride tablets should ordinarily be discontinued. If a decision is made to continue pramipexole dihydrochloride tablets, advise patients not to drive and to avoid other potentially dangerous activities. While dose reduction reduces the degree of somnolence, there is insufficient information to establish that dose reduction will eliminate episodes of falling asleep while engaged in activities of daily living.

All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.

This site is provided for educational and informational purposes only, in accordance with our Terms of Use, and is not intended as a substitute for the advice of a medical doctor, nurse, nurse practitioner or other qualified health professional.

Privacy Policy | Copyright © 2020. All Rights Reserved.