REPREVE

What it is

Repreve contains ropinirole hydrochloride and is available in four tablet strengths: 0.25 mg, 0.5 mg, 1 mg and 2 mg. Ropinirole hydrochloride is a potent, non-ergoline D2/D3-dopamine agonist.

Approved indications

— Treatment of primary restless legs syndrome, including the reduction of associated periodic limb movement and episodes of nocturnal arousal.

Dosing overview

Individual dose titration against efficacy and tolerability is recommended. Ropinirole should be taken once-daily before bedtime, however the dose can be taken up to three hours before retiring. The recommended initial dose is 0.25 mg once daily for two days. If this dose is well tolerated the dose may be increased to 0.5 mg once daily for the remainder of week 1. Following treatment initiation, the daily dose can be increased according to a stepped regimen over subsequent weeks until optimal therapeutic response is achieved, with doses of 1 mg, 1.5 mg, 2 mg, 2.5 mg, 3 mg and 4 mg across weeks 2–7. The mean daily dose in clinical trials was 2 mg/day. Doses above 4 mg/day have not been investigated in patients with restless legs syndrome. No dosage adjustment is necessary in patients with mild to moderate renal impairment (creatinine clearance 30 to 50 mL/minute). The recommended maximum dose is limited to 3 mg/day in patients with restless legs syndrome who have end stage renal disease receiving regular dialysis. Dosing adjustment is not necessary in the elderly.

Key safety warnings

Paradoxical worsening of restless legs syndrome symptoms described as augmentation (either earlier onset, increased intensity, or spread of symptoms to previously unaffected limbs), or early morning rebound (reoccurrence of symptoms in the early morning hours), have been observed during treatment with ropinirole. If this occurs, treatment review may be required in some cases, which could be in the form of drug discontinuation, dose increment, change in dose regimen or changing to alternative treatment modality. Patients should be regularly monitored for the development of impulse control disorders. Impulsive control symptoms, including compulsive behaviours (including pathological gambling, increased libido, hypersexuality, compulsive shopping, binge eating and compulsive eating) have been reported in patients treated with dopaminergic agents, including ropinirole. These were generally reversible upon dose reduction or treatment discontinuation. Patients should be regularly monitored for the development of mania. Patients and carers should be made aware that symptoms of mania can occur with or without the symptoms of impulse control disorders in patients treated with ropinirole. Dose reduction/tapered discontinuation should be considered if such symptoms develop. Patients treated with ropinirole 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 ropinirole, 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 have been reported as late as 1 year after initiation of treatment. If a patient develops significant daytime sleepiness or episodes of falling asleep during activities that require active participation (e.g. conversations, eating, etc), ropinirole should ordinarily be discontinued. Dopamine agonist withdrawal syndrome (DAWS) has been reported with dopamine agonists, including ropinirole. To discontinue treatment in patients with Restless Legs Syndrome, ropinirole should be tapered off. Withdrawal symptoms may include apathy, anxiety, depression, fatigue, sweating and pain and do not respond to levodopa. Prior to tapering off and discontinuing ropinirole, patients should be informed about potential withdrawal symptoms.

Contraindications

Hypersensitivity to ropinirole hydrochloride or any of the listed excipients. Pregnancy and lactation. Severe renal impairment (creatinine clearance <30 mL/min) without regular haemodialysis. Severe hepatic impairment.

Regulatory history

Repreve was first approved on 4 August 2008. The four Repreve tablet strengths (0.25 mg, 0.5 mg, 1 mg and 2 mg) were first listed on the ARTG on 7 November 2017.