DRUG TREATMENT OF ALZHEIMER’S TYPE DEMENTIA

NICE Technology Appraisal TA217 describes the drug treatment of Alzheimer’s disease with cholinesterase inhibitors and memantine.

Summary of the Technology Appraisal

The guidance says that for mild to moderate Alzheimer’s disease, one of the cholinesterase inhibitors should be used, and that the drug with the lowest acquisition cost should be used unless clinically inappropriate.

 Donepezil is by far the most cost effective drug, and should be used first line, unless there are clinical reasons for choosing another drug. The reasons should be documented in the clinical record.  One of the other cholinesterase inhibitors may be prescribed if clinically appropriate, taking into account the side effect profile, potential for interaction, contraindications etc  Side effects and interactions are summarized in the table below. Note: For a comprehensive list see Summary of Product Characteristics  Liquids, orodispersible drugs and patches are very expensive, and should only be used where unavoidable.  Memantine may be used as an alternative to cholinesterase inhibitors in mild to moderate disease for people who are intolerant of cholinesterase inhibitors or in those people for whom they are contra-indicated, and for moderate to severe disease.  NICE TA217 does not recommend combining a cholinesterase inhibitor with memantine, and this combination is not suitable for shared care

Drug Adverse Interaction Interaction Pharmacodynamic effects Plasma level Plasma level interaction increased by decreased by Donepezil Diarrhoea, Ketoconazole, Rifampicin, Anticholinergic drugs, nausea, itraconazole, phenytoin, neuromuscular blocking headache, erythromycin, carbamazepine, agents, ß-blockers, anorexia, quinidine, alcohol cholinergic agonists. hallucinations, fluoxetine. agitation, insomnia, Caution should Caution should be Caution should be vomiting, rash, be exercised exercised when exercised when using fatigue, syncope when using with using with with donepezil donepezil donepezil Rivastigmine Anorexia, Metabolic Anticholinergic and dizziness, interactions cholinomimetic drugs nausea, unlikely such as neuromuscular

vomiting, blocking agents, diarrhoea, cholinergic agonists agitation, such as bethanecol. confusion, headache, somnolence, Caution should be tremor, exercised when using abdominal pain, with rivastigmine weight loss Galantamine Nausea, Ketoconazole, None known Anticholinergics and vomiting, erythromycin, cholinomimetic drugs, decreased ritonavir, possible interaction appetite, quinidine, with drugs that reduce anorexia, paroxetine, heart rate – digoxin, ß- hallucination, fluoxetine, blockers, certain depression, fluvoxamine, calcium channel syncope, amitriptyline. blockers, amiodarone. bradycardia, diarrhoea, Consider dose Caution should be fatigue, weight reduction of exercised when using loss galantamine with galantamine Memantine Somnolence, Cimetidine, None known Effects of L-dopa, dizziness, ranitidine, dopaminergic agonists hypertension, quinidine, and Anticholinergics dyspnoea, quinine, may be enhanced. constipation, nicotine, Effects of barbiturates headache isolated cases and neuroleptics may reported with be reduced. Avoid warfarin – concomitant use with monitor INR. amantadine, dextromethorphan. Caution should be exercised Caution should be when using with exercised when using memantine with memantine