APO-DONEPEZIL

What it is

APO-DONEPEZIL is a film-coated tablet containing donepezil hydrochloride, supplied in strengths of 5 mg or 10 mg. Donepezil exerts its therapeutic effect by enhancing cholinergic function in the central nervous system through reversible inhibition of acetylcholinesterase, which increases the concentration of acetylcholine.

Approved indications —

Treatment of mild Alzheimer's disease — Treatment of moderate Alzheimer's disease — Treatment of severe Alzheimer's disease

Dosing overview

Treatment is initiated at 5 mg per day taken once daily. The 5 mg daily dose should be maintained for at least one month to allow the earliest clinical responses to be assessed and to allow steady-state concentrations to be achieved. Following a one-month clinical assessment at 5 mg per day, the dose can be increased to 10 mg per day once daily. The maximum recommended daily dose is 10 mg. APO-DONEPEZIL tablets should be taken orally in the evening, just prior to retiring. The medicine can be taken with or without food.

Key safety warnings

Donepezil may exaggerate succinylcholine-type muscle relaxation during anaesthesia. As a cholinesterase inhibitor, it may have vagotonic effects on heart rate including bradycardia, which may be particularly important in patients with sick sinus syndrome or other supraventricular cardiac conduction conditions such as sinoatrial or atrioventricular block. Post-marketing reports of cardiac conduction conditions including atrioventricular block, QTc interval prolongation and Torsade de Pointes have been received. 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 or bradyarrhythmias, or electrolyte disturbances including hypokalaemia or hypomagnesaemia. Clinical monitoring with ECG may be required. Through their primary action, cholinesterase inhibitors may be expected to increase gastric acid secretion. Patients at increased risk of developing ulcers, such as those with a history of ulcer disease or those receiving concurrent nonsteroidal anti-inflammatory drugs, should be monitored closely for symptoms of active or occult gastrointestinal bleeding. Donepezil has been shown to produce diarrhoea, nausea and vomiting as a predictable consequence of its pharmacological properties. Patients should be observed closely at the initiation of treatment and after dose increases. Because of their cholinomimetic actions, cholinesterase inhibitors should be prescribed with care to patients with a history of asthma or obstructive pulmonary disease.

Contraindications

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

Regulatory history

APO-DONEPEZIL was first registered on the ARTG on 13 May 2011, with registrations for both 5 mg and 10 mg tablet bottle pack formulations. Additional ARTG registrations for blister pack formulations containing donepezil hydrochloride monohydrate in both 5 mg and 10 mg strengths were added on 23 September 2013.