Pramipexole

Brand names: MIRAPEX, Mirapex, PRAMIPEXOLE DIHYDROCHLORIDE, Pramipexole Dihydrochloride, Pramipexole dihydrochloride, pramipexole dihydrochloride, PRAMIPEXOLE

Warnings

No boxed warning, and no absolute contraindications are listed. Major warnings include "falling asleep during activities of daily living," including "sudden onset of sleep... without warning" while driving, which has resulted in accidents; impaired systemic regulation of blood pressure causing orthostatic hypotension and syncope; risk of "compulsive behaviors and other intense urges" such as gambling, hypersexuality, and compulsive spending or eating; hallucinations and other psychotic-like behavior; and potential to cause or worsen dyskinesia.

Contraindications

4 CONTRAINDICATIONS None. None (4)

Overdose

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 events 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.

Drug interactions

7 DRUG INTERACTIONS See also Dosage and Administration (2.2) and Clinical Pharmacology ( 12.3 ) Dopamine antagonists may diminish the effectiveness of pramipexole ( 7.1 ). 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. 7.2 Drug/Laboratory Test Interactions There are no known interactions between pramipexole and laboratory tests.

Uses

Pramipexole tablets are indicated for "treatment of the signs and symptoms of idiopathic Parkinson's disease" and for "treatment of moderate-to-severe primary Restless Legs Syndrome (RLS)."

Dosage forms & strengths

Tablet Tablet, Extended Release TABLET

PRAMIPEXOLE 0.125 mg PRAMIPEXOLE 0.25 mg PRAMIPEXOLE 0.5 mg PRAMIPEXOLE 1 mg PRAMIPEXOLE DIHYDROCHLORIDE 0.125 mg PRAMIPEXOLE DIHYDROCHLORIDE 0.25 mg PRAMIPEXOLE DIHYDROCHLORIDE 0.375 mg PRAMIPEXOLE DIHYDROCHLORIDE 0.5 mg PRAMIPEXOLE DIHYDROCHLORIDE 0.75 mg PRAMIPEXOLE DIHYDROCHLORIDE 1 mg PRAMIPEXOLE DIHYDROCHLORIDE 1.5 mg PRAMIPEXOLE DIHYDROCHLORIDE 2.25 mg PRAMIPEXOLE DIHYDROCHLORIDE 3 mg PRAMIPEXOLE DIHYDROCHLORIDE 3.75 mg PRAMIPEXOLE DIHYDROCHLORIDE 4.5 mg Pramipexole Dihydrochloride 0.125 mg Pramipexole Dihydrochloride 0.25 mg Pramipexole Dihydrochloride 0.5 mg Pramipexole Dihydrochloride 1 mg Pramipexole Dihydrochloride 1.5 mg pramipexole dihydrochloride .250 mg pramipexole dihydrochloride .500 mg pramipexole dihydrochloride .750 mg pramipexole dihydrochloride 0.125 mg pramipexole dihydrochloride 0.250 mg pramipexole dihydrochloride 0.500 mg pramipexole dihydrochloride 1 mg pramipexole dihydrochloride 1.5 mg PRAMIPEXOLE DIHYDROCHLORIDE .125 mg/1 PRAMIPEXOLE DIHYDROCHLORIDE 1 mg/1 PRAMIPEXOLE DIHYDROCHLORIDE .5 mg/1 PRAMIPEXOLE DIHYDROCHLORIDE .75 mg/1 PRAMIPEXOLE DIHYDROCHLORIDE .25 mg/1 PRAMIPEXOLE DIHYDROCHLORIDE 1.5 mg/1

2 DOSAGE AND ADMINISTRATION Parkinson's Disease-Normal Renal Function* ( 2.2 ) 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 * Doses should not be increased more frequently than every 5-7 days. Titrate to effective dose. If used with levodopa, may need to reduce levodopa dose. Parkinson's Disease-Impaired Renal Function ( 2.2 ) Creatinine Clearance Starting Dose (mg) Maximum Dose (mg) > 50 mL/min 0.125 TID 1.5 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 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 Parkinson's Disease-Normal Renal Function*(2.2) 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 *Doses should not be increased more frequently than every 5-7 days. Titrate to effective dose. If used with levodopa, may need to reduce levodopa dose. 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. [see Warnings and Precautions(5.9)].