Donepezil

Donepezil is a reversible inhibitor of acetylcholinesterase, the enzyme that breaks down acetylcholine, a chemical messenger the brain relies on for memory and attention. Slowing that breakdown leaves more acetylcholine available between nerve cells. According to the UK SmPC, it is indicated for the symptomatic treatment of mild to moderately severe dementia of the Alzheimer's type. It does not halt the illness itself; in people who respond, it can help memory, thinking and everyday functioning for a period. Treatment should be started and supervised by a doctor experienced in diagnosing and managing dementia, and someone close to the patient should be available to keep an eye on daily doses.

The product supplied here is an imported generic containing donepezil hydrochloride. The 5 mg tablets come in packs of 30, 60, 90, 120, 180 and 360, while the 10 mg tablets are offered in packs of 30, 60, 90, 120 and 180. These are the same two strengths licensed for this medicine in the UK.

A course of donepezil begins with 5 mg once a day, taken in the evening shortly before going to bed. The SmPC advises staying on this dose for at least one month, which lets the earliest effects be judged and blood levels settle; after that, the doctor may increase it to 10 mg once daily. Ten milligrams a day is the maximum licensed dose, and the higher-strength packs are intended for that maintenance stage. The tablet can be swallowed with water, with or without food. If an evening dose is forgotten, simply take the next one at the normal time the following day rather than doubling up. Benefit should be reassessed regularly, and treatment continued only while it still seems to help. No dose change is needed for kidney problems; with mild to moderate liver impairment, the dose is raised according to how well it is tolerated. It is not recommended for children.

In the UK, donepezil is a prescription-only medicine (POM). The original brand is Aricept, and the MHRA has licensed numerous generic film-coated tablets in 5 mg and 10 mg. Orodispersible tablets and an oral solution exist as alternatives for people who struggle to swallow. NICE recommends it, alongside galantamine and rivastigmine, as an option for mild to moderate Alzheimer's disease. Whether this medicine suits a particular patient, and at which strength, is decided by the prescriber.

The tablets must not be taken by anyone allergic to donepezil hydrochloride, to other piperidine derivatives or to any of the excipients. Because the drug can slow the heart, special care is needed with sick sinus syndrome, sinoatrial or atrioventricular heart block and other conduction problems; fainting, a very slow pulse and QT prolongation have been reported. Medicines of this kind may also provoke seizures and can cause bladder outflow obstruction, and they call for care in people with asthma or obstructive airways disease. People with a past stomach or duodenal ulcer, or who take NSAIDs regularly, should be watched for signs of gastrointestinal bleeding. The anaesthetist must be told before surgery, since the effect of suxamethonium-type muscle relaxants can be exaggerated. Ketoconazole, itraconazole, erythromycin, quinidine and fluoxetine can raise blood levels, whereas rifampicin, phenytoin, carbamazepine and alcohol may lower them. Anticholinergic drugs can work against it, beta-blockers may add to the slowing of the heart, and caution is advised with other medicines that lengthen the QT interval. Use in pregnancy is reserved for clear need, and women taking it should not breast-feed.

Most unwanted effects of donepezil reflect increased cholinergic activity and tend to appear when treatment starts or the dose goes up. Diarrhoea, nausea and headache are very common. Common effects include vomiting, loss of appetite, stomach discomfort, muscle cramps, tiredness, dizziness, difficulty sleeping, vivid dreams or nightmares, agitation, hallucinations, fainting, falls, rash, itching, urinary incontinence and cold-like symptoms. Less often there may be a slow heartbeat, fits, stomach or duodenal ulcers or bleeding from the gut; liver problems, heart block and movement disorders are rare. Black or bloodstained stools, blackouts, a high temperature with muscle stiffness or dark urine with muscle weakness need urgent medical attention or a trip to A&E. Dementia itself, as well as the tiredness, dizziness or cramps this medicine may cause, can affect driving, so the treating doctor should review fitness to drive regularly.