ARICEPT

What it is

ARICEPT is donepezil hydrochloride supplied as film-coated tablets for oral administration, available in 5 mg and 10 mg strengths.

Approved indications

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

Dosing overview

Treatment with ARICEPT is initiated at 5 mg per day administered once daily. ARICEPT tablets should be taken orally, in the evening, just prior to retiring. The 5 mg per 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 per day, the dose of ARICEPT can be increased to 10 mg per day. The maximum recommended daily dose is 10 mg.

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. The potential for this action may be particularly important to 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 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. 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

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

PBS listing

ARICEPT 5 mg tablets are listed on the PBS with 2 items under streamlined authority required restriction, at an ex-manufacturer price of A$8.38. ARICEPT 10 mg tablets are listed on the PBS with 2 items under streamlined authority required restriction, at an ex-manufacturer price of A$8.35.

Regulatory history

ARICEPT was first registered on the ARTG on 30 March 1998, with registrations for both 5 mg and 10 mg tablet formulations.