SIMIPEX

What it is

SIMIPEX contains pramipexole dihydrochloride monohydrate. SIMIPEX tablets are round and white. Pramipexole is a dopamine agonist that binds with high selectivity and specificity to the dopamine D2 subfamily receptors and has a preferential affinity to D3 receptors.

Approved indications

— Treatment of signs and symptoms of idiopathic Parkinson's disease. — Symptomatic treatment of primary Restless Legs Syndrome.

Dosing overview

For Parkinson's disease, SIMIPEX tablets should be taken orally, swallowed with water, with or without food, in equally divided doses three times per day. Dosages should be increased gradually from a starting dose of pramipexole dihydrochloride monohydrate 0.375 mg per day and then increased every five to seven days, with dosage titrated to achieve maximal therapeutic effect provided patients do not experience intolerable side effects. The individual dose should be in the range of 0.375 mg to a maximum of pramipexole dihydrochloride monohydrate 4.5 mg per day. For Restless Legs Syndrome, tablets are usually taken 2 to 3 hours before bedtime each day. The recommended starting dose is 0.125 mg taken once daily 2 to 3 hours before bedtime, and for patients requiring additional symptomatic relief, the dose may be increased every 4 to 7 days to a maximum of 0.75 mg per day.

Key safety warnings

Pramipexole has been associated with somnolence and episodes of sudden sleep onset, particularly in patients with Parkinson's disease. Sudden onset of sleep during daily activities, in some cases without awareness or warning signs such as excessive drowsiness, has been reported. Some of these events have been reported as late as one year after the initiation of treatment. Patients should neither drive a car nor operate other complex machinery until they have gained sufficient experience with pramipexole to gauge whether or not it affects their mental and/or motor performance adversely. Hallucinations and confusion are known side effects of treatment with dopamine agonists and levodopa in Parkinson's disease patients. Hallucinations were more frequent when pramipexole was given in combination with levodopa in Parkinson's disease patients with advanced disease than monotherapy in patients with early disease. Reports in the literature indicate that treatment of Restless Legs Syndrome with dopaminergic medications can result in augmentation, which refers to the earlier onset of symptoms in the evening (or even the afternoon), increase in symptoms, and spread of symptoms to involve other extremities. The risk of augmentation may increase with higher dose. A drug withdrawal syndrome has been reported during or after discontinuation of dopamine agonists including pramipexole. Withdrawal symptoms including apathy, anxiety, depression, fatigue, sweating and pain may occur when tapering or discontinuing dopamine agonists, including pramipexole and may be severe. Abnormal behaviours (reflecting symptoms of impulse control disorders and compulsive behaviours) such as pathological gambling, hypersexuality, compulsive shopping, binge eating, medication use and punding (repetitive purposeless activity) has been reported in patients taking dopamine agonists for the treatment of Parkinson's disease, especially at high doses. Prescribers, patients and caregivers should be alert to the possibility of such behaviour, which may have serious financial and social consequences.

Contraindications

SIMIPEX is contraindicated in patients with hypersensitivity to pramipexole or any excipients of SIMIPEX.

Regulatory history

SIMIPEX pramipexole dihydrochloride monohydrate tablets in strengths of 0.125 mg, 0.25 mg, 0.5 mg and 1 mg were first listed on the ARTG on 25 October 2011. SIMIPEX XR modified release tablets in strengths of 0.375 mg, 0.75 mg, 1.5 mg, 2.25 mg, 3 mg, 3.75 mg and 4.5 mg were first listed on the ARTG on 17 June 2015.