SIFROL

What it is

SIFROL contains pramipexole dihydrochloride monohydrate as the active ingredient. 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

SIFROL may be used as monotherapy or in combination with levodopa. **Parkinson's disease:** Dosages should be increased gradually from a starting dose of pramipexole hydrochloride 0.375 mg/day and then increased every five to seven days. The individual dose should be in the range of 0.375 mg to a maximum of pramipexole hydrochloride 4.5 mg/day. Efficacy was observed starting at a daily dose of pramipexole hydrochloride 1.5 mg. **Restless Legs Syndrome:** The recommended starting dose is 0.125 mg taken once daily 2 to 3 hours before bedtime, with doses increased every 4 to 7 days to a maximum of 0.75 mg per day.

Key safety warnings

**Somnolence and sudden sleep onset.** Pramipexole has been associated with somnolence and episodes of sudden sleep onset, particularly in patients with Parkinson's disease, and sudden onset of sleep during daily activities has been reported in some cases without awareness or warning signs such as excessive drowsiness. 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.** Hallucinations and confusion are known side effects of treatment with dopamine agonists and levodopa in Parkinson's disease patients, and 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. **Dyskinesias.** In advanced Parkinson's disease in combination treatment with levodopa, dyskinesias can occur during the initial titration of pramipexole, and if dyskinesias occur the dose of levodopa should be decreased. **Compulsive behaviour.** Compulsive behaviour such as pathological gambling, hypersexuality, compulsive shopping, binge eating, medication use and punding has been reported in patients taking dopamine agonists for the treatment of Parkinson's disease, especially at high doses. **Drug withdrawal syndrome.** A drug withdrawal syndrome has been reported during or after discontinuation of dopamine agonists including pramipexole, and withdrawal symptoms may include apathy, anxiety, depression, fatigue, sweating and pain which may be severe.

Contraindications

Hypersensitivity to pramipexole or any excipients of SIFROL.

Regulatory history

SIFROL immediate-release tablets containing 0.125 mg, 0.25 mg and 1.0 mg pramipexole dihydrochloride monohydrate were first registered on the ARTG on 20 April 1999. Extended-release formulations in strengths of 0.375 mg, 0.75 mg, 1.5 mg, 2.25 mg, 3.0 mg, 3.75 mg and 4.5 mg were registered on 26 March 2010 and 15 March 2011.