ARAZIL

What it is

ARAZIL is donepezil hydrochloride supplied as film-coated tablets for oral administration containing 5 mg or 10 mg donepezil hydrochloride equivalent to 4.56 mg or 9.12 mg donepezil free base, respectively. ARAZIL 5 mg tablets are white, round, film-coated, debossed tablets marked 'ARICEPT' on one side and '5' on the other side. ARAZIL 10 mg tablets are yellow, round, film-coated, debossed tablets marked 'ARICEPT' on one side and '10' on the other side. ARAZIL exerts its therapeutic effect by enhancing cholinergic function in the central nervous system through increasing the concentration of acetylcholine by reversible inhibition of acetylcholinesterase. ARAZIL is a specific and reversible inhibitor of acetylcholinesterase, the predominant cholinesterase in the brain, and is over 1000 times more potent an inhibitor of this enzyme than of butyrylcholinesterase, an enzyme which is present mainly outside the central nervous system.

Approved indications —

ARAZIL is indicated for the treatment of mild, moderate and severe Alzheimer's disease.

Dosing overview

Treatment is initiated at 5 mg/day (once-a-day dosing). ARAZIL tablets should be taken orally, in the evening, just prior to retiring. ARAZIL can be taken with or without food. 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 ARAZIL 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

As a cholinesterase inhibitor, donepezil is likely to exaggerate succinylcholine-type muscle relaxation during anaesthesia and may have vagotonic effects on heart rate such as bradycardia. Caution is advised in patients with sick sinus syndrome or other supraventricular cardiac conduction conditions, 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, and clinical monitoring including ECG may be required. Through their primary action, cholinesterase inhibitors may be expected to increase gastric acid secretion due to increased cholinergic activity, so 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 hydrochloride has been shown to produce diarrhoea, nausea and vomiting, and patients should be observed closely at the initiation of treatment and after dose increases. Cholinomimetics are believed to have some potential to cause generalised convulsions, although seizure activity may also be a manifestation of Alzheimer's disease. Neuroleptic malignant syndrome has been reported to occur very rarely in patients treated with donepezil, with or without concomitant antipsychotic medication, and 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. ARAZIL should be prescribed with care to patients with a history of asthma or obstructive pulmonary disease, and concomitant use with other inhibitors of acetylcholinesterase, agonists or antagonists of the cholinergic system should be avoided.

Contraindications

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

Regulatory history

ARAZIL donepezil hydrochloride 5 mg tablet was first listed on the ARTG on 2012-10-03 (ARTG 167692, licence category RE) and 10 mg tablet on 2012-10-03 (ARTG 167693, licence category RE).