ARIDON

What it is

ARIDON contains donepezil hydrochloride, a specific and reversible inhibitor of the enzyme acetylcholinesterase. ARIDON APN tablets come in two strengths and contain either 5 mg or 10 mg of donepezil hydrochloride.

Approved indications —

Mild Alzheimer's disease — Moderate Alzheimer's disease — Severe Alzheimer's disease

Dosing overview

Treatment is initiated at 5 mg/day (once-a-day dosing). Donepezil hydrochloride should be taken orally, in the evening, just prior to retiring. The 5 mg/day dose should be maintained for at least one month in order to allow the earliest clinical responses to treatment to be assessed and to allow steady-state concentrations of donepezil hydrochloride to be achieved. Following a one-month clinical assessment of treatment at 5 mg/day, the dose of donepezil hydrochloride can be increased to 10 mg/day (once-a-day dosing). The maximum recommended daily dose is 10 mg. A similar dose schedule can be followed for patients with renal or hepatic impairment as clearance of donepezil hydrochloride is not significantly affected by these conditions.

Key safety warnings

Donepezil, as a cholinesterase inhibitor, is likely to exaggerate succinylcholine-type muscle relaxation during anaesthesia. Because of their pharmacological action, cholinesterase inhibitors may have vagotonic effects on heart rate such as bradycardia, which may be particularly important in patients with sick sinus syndrome or other supraventricular cardiac conduction conditions, such as sinoatrial or atrioventricular block. There have been post-marketing reports of cardiac conduction conditions including atrioventricular block, QTc interval prolongation and Torsade de Pointes. Caution is advised in patients with pre-existing or family history of QTc prolongation, in patients being treated with drugs affecting the QTc interval, or in patients with relevant pre-existing cardiac disease such as uncompensated heart failure, recent myocardial infarction, bradyarrhythmias, or electrolyte disturbances. Clinical monitoring (ECG) may be required. Through their primary action, cholinesterase inhibitors may be expected to increase gastric acid secretion due to increased cholinergic activity. Therefore, patients at increased risk of developing ulcers, such as those with a history of ulcer disease or those receiving concurrent nonsteroidal anti-inflammatory drugs (NSAIDs), should be monitored closely for symptoms of active or occult gastrointestinal bleeding. Donepezil hydrochloride, as a predictable consequence of its pharmacological properties, has been shown to produce diarrhoea, nausea and vomiting. Patients should be observed closely at the initiation of treatment and after dose increases. Neuroleptic Malignant Syndrome (NMS) has been reported to occur very rarely in patients treated with donepezil, with or without concomitant antipsychotic medication. NMS is a potentially life-threatening condition characterised by hyperthermia, muscle rigidity, autonomic instability, altered consciousness and elevated serum creatine phosphokinase levels; additional signs may include myoglobinuria (rhabdomyolysis) and acute renal failure. If a patient develops signs and symptoms indicative of NMS or presents with unexplained high fever without additional clinical manifestations of NMS, treatment should be discontinued immediately. Because of their cholinomimetic actions, cholinesterase inhibitors should be prescribed with care to patients with a history of asthma or obstructive pulmonary disease.

Contraindications

Donepezil hydrochloride is contraindicated in patients with a known hypersensitivity to donepezil hydrochloride, piperidine derivatives, or to any excipients used in the formulation.

Regulatory history

ARIDON APN 5 mg and 10 mg tablets were first listed on the ARTG on 2 March 2011. Film-coated tablet formulations (ARIDON 5 and ARIDON 10) and orally disintegrating tablet formulations (ARIDON ODT 5 and ARIDON ODT 10) were subsequently listed on 18 January 2012.