donepezil hydrochloride: clinical use

Prescribing considerations

• Initiation and supervision should involve a clinician experienced in diagnosing and treating Alzheimer’s dementia, with reliable support for administration.
• Regularly reassess cognitive, functional and global benefit, tolerability, and patient and carer views.
• Use caution with bradyarrhythmias, conduction disorders, QT-prolongation risk, electrolyte disturbance, ulcer history, concurrent NSAIDs, asthma or obstructive pulmonary disease, seizures, urinary outflow obstruction and hepatic impairment.
• Alert the anaesthetic team before surgery because neuromuscular blockade may be affected.

Contraindications and cautions

• Hypersensitivity to donepezil hydrochloride, piperidine derivatives or a formulation excipient.
• The oral solution is contraindicated in hereditary fructose intolerance and metabisulphite hypersensitivity; tablet excipients may make particular products unsuitable for specified hereditary carbohydrate disorders.
• Aspartame-containing orodispersible products require consideration in phenylketonuria.

Monitoring

• Check pulse, electrolytes, body weight and liver function before treatment; consider an ECG where QT prolongation or conduction risk is present.
• Monitor pulse after initiation or treatment changes and periodically thereafter; monitor weight when clinically appropriate.
• Investigate syncope or seizures for possible bradycardia, heart block or prolonged sinus pauses.
• Monitor for gastrointestinal bleeding in people with ulcer risk or concurrent NSAID use and reassess ongoing clinical benefit.

Clinical pharmacology

Donepezil is a specific, reversible acetylcholinesterase inhibitor. It is metabolised mainly through CYP3A4 and to a lesser extent CYP2D6; mild-to-moderate hepatic impairment may increase exposure, while renal impairment has little effect on clearance.

Formulation and product differences

• Film-coated tablets are swallowed with water and selected products contain lactose.
• Orodispersible tablets disperse on the tongue and can be swallowed with or without water; excipients differ by product and may include aspartame, lactose, glucose, sucrose or sorbitol.
• The strawberry-scented oral solution contains sorbitol, metabisulphite, benzoate and propylene glycol and should be measured with the supplied device.

Dispersible tablet

Route: Oral

Strengths: 5 mg, 10 mg

Oral solution

Route: Oral

Strengths: 1 mg/1 mL

Tablet

Route: Oral

Strengths: 5 mg, 10 mg