Some of the views expressed in the following notes on newly approved products should be regarded as preliminary, as there may have been limited published data at the time of publication, and little experience in Australia of their safety or efficacy. However, the Editorial Executive Committee believes that comments made in good faith at an early stage may still be of value. Before new drugs are prescribed, the Committee believes it is important that more detailed information is obtained from the manufacturer's approved product information, a drug information centre or some other appropriate source.
Ebixa (Lundbeck)
10 mg tablets
50 mL bottles containing 10 mg/mL oral solution
Approved indication: Alzheimer's disease
Australian Medicines Handbook section 16.4
The currently available drug treatments for Alzheimer's disease are donepezil, galantamine, rivastigmine and tacrine. These drugs inhibit acetylcholinesterase so cholinergic adverse effects can be a problem. Memantine aims to improve the patient's function by a different mechanism - antagonism at the N-methyl-D-aspartate (NMDA) receptors.
The NMDA receptor is one of the receptors for glutamate, a cerebral neurotransmitter. If neuronal dysfunction in dementia is related to increased concentrations of glutamate, then blocking the receptors could slow progression of the disease.
In a clinical trial 252 patients, with moderate or severe Alzheimer's disease, were randomised to take memantine or a placebo for 28 weeks. Although 71 patients did not complete the trial, those given memantine showed less decline on some of the rating scales used to assess efficacy. These patients' scores were significantly different from placebo on the Alzheimer's Disease Co-operative Study Activities of Daily Living Inventory (ADCS-ADL), the Severe Impairment Battery (SIB) and the Functional Assessment Staging scale (FAST). There was also a significant difference in the clinicians' and carers' assessments of the patients.1
Many patients in the trial had adverse events including agitation, urinary incontinence, diarrhoea and insomnia.1Adverse effects with a higher frequency than placebo include fatigue, headache, dizziness and hallucinations. Approximately 11% of patients will stop treatment because of adverse effects.
To reduce the risk of adverse effects memantine should be started at a low dose and slowly increased over a month. The drug is completely absorbed even if taken with food. Most of the dose is excreted unchanged in the urine, so a lower dose is needed if renal function is reduced. There are potential interactions with drugs such as cimetidine which use the same renal transport system. Memantine may also interact with antipsychotics, levodopa and other dopaminergic drugs.
Although memantine may have an advantage over placebo, it is important to remember that, on average, all the patients in the clinical trial got worse. There was also no significant difference between memantine and placebo in some of the assessments such as the Mini-Mental State Examination, the Global Deterioration Scale and the Neuropsychiatric Inventory. In addition the results can be influenced by how the data from the 28% of patients who dropped out are analysed. A different analysis negates the significant differences in the clinicians' impressions of change.1
Although the options for the treatment of moderate to severe dementia are limited, memantine does not seem to be a major advance. (It has been available in Germany for approximately 20 years.) Further research is exploring whether treating patients with a combination of memantine and an acetylcholinesterase inhibitor will be of greater clinical benefit.
