APPESE

What it is

APPESE contains ropinirole hydrochloride and is available in four strengths: 0.25 mg, 0.5 mg, 1 mg and 2 mg tablets. Ropinirole hydrochloride is a potent, non-ergoline D2/D3-dopamine agonist. The tablets are pentagon-shaped and each strength is colour-coded for identification.

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 weekly schedule until optimal therapeutic response is achieved, progressing from 1 mg in week 2 to 4 mg in week 7. The mean daily dose in clinical trials was 2 mg per day. Doses above 4 mg per 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). In patients with end stage renal disease receiving regular dialysis, exposure to ropinirole is increased by approximately 27%, and the recommended maximum dose is limited to 3 mg per day in patients with restless legs syndrome. 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 involve drug discontinuation, dose increment, change in dose regimen or changing to alternative treatment modality. 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, ropinirole should ordinarily be discontinued. 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. Symptoms suggestive of neuroleptic malignant syndrome have been reported with abrupt withdrawal of dopaminergic therapy. Therefore, it is recommended to taper treatment. Dopamine agonist withdrawal syndrome has been reported with dopamine agonists, including ropinirole. To discontinue treatment in patients with restless legs syndrome, ropinirole should be tapered off.

Contraindications

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

Regulatory history

APPESE was first approved on 4th August 2008. The product is registered on the ARTG in four strengths (0.25 mg, 0.5 mg, 1 mg and 2 mg tablets), all with first listed dates of 2008-08-04.