Apo-Pramipexole Dosage/Direction for Use

APO-PRAMIPEXOLE (pramipexole dihydrochloride monohydrate) should be taken orally, three times daily. The tablets can be taken with or without food.
Missed Dose: Patients should be advised that if a dose is missed, they should not take a double dose, but continue with the regular treatment schedule.
Dosing Considerations: Adults: In all clinical studies, dosage was initiated at a subtherapeutic level to avoid orthostatic hypotension and severe adverse effects. APO-PRAMIPEXOLE should be titrated gradually in all patients. The dosage should be increased to achieve maximal therapeutic effect, balanced against the principal adverse reactions of dyskinesia, nausea, dizziness and hallucinations.
Initial treatment: Dosages 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: See Table 7.

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Maintenance treatment: Pramipexole dihydrochloride monohydrate was 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, as monotherapy or in combination with levodopa (approximately 800 mg/day). In a fixed-dose study in patients with early Parkinson's disease, pramipexole dihydrochloride monohydrate at doses of 3, 4.5 and 6 mg/day was not shown to provide any significant benefit beyond that achieved at a daily dose of 1.5 mg/day. For individual patients who have not achieved efficacy at 1.5 mg/day, higher doses can result in additional therapeutic benefit.
When pramipexole dihydrochloride monohydrate is used in combination with levodopa, a reduction of the levodopa dosage should be considered. In the controlled study in advanced Parkinson's disease, the dosage of levodopa was reduced by an average of 27% from baseline.
Discontinuation of Treatment: It is recommended that pramipexole dihydrochloride monohydrate be discontinued over a period of one week.
Recommended Dose and Dosage Adjustment: The maximal recommended dose of pramipexole dihydrochloride monohydrate is 4.5 mg per day. Pramipexole dihydrochloride monohydrate is not recommended at the 6 mg per day dose since the incidence of some adverse reactions is higher.
Dosing in patients with concomitant levodopa therapy: In patients with concomitant levodopa therapy, it is recommended that the dosage of levodopa is reduced during both dose escalation and maintenance treatment with pramipexole dihydrochloride monohydrate. This may be necessary in order to avoid excessive dopaminergic stimulation.
Patients with renal impairment: Since the clearance of pramipexole dihydrochloride monohydrate is reduced in patients with renal impairment (see Pharmacology: Pharmacokinetics under Actions), the following dosage recommendation should be considered: See Table 8.

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Patients with a creatinine clearance above 50 ml/min require no reduction in daily dose.
If renal function declines during maintenance therapy, reduce APO-PRAMIPEXOLE daily dose by same percentage as decline in creatinine clearance, i.e. if creatinine clearance declines by 30%, then reduce APO-PRAMIPEXOLE daily dose by 30%. The daily dose can be administered in two divided doses if creatinine clearance is between 20 and 50 ml/min and as a single daily dose if creatinine clearance is less than 20 ml/min.
Patients with hepatic impairment: Dose reduction not considered necessary.
Dosing in children and adolescents: Safety and efficacy of pramipexole dihydrochloride have not been established in children and adolescents up to 18 years of age.