Ebixa is a new medicinal product for the treatment of patients with moderately severe to severe Alzheimer’s disease. There are no other medicinal products currently available on the market for the treatment of this group of patients. Its efficacy – in halting the progress of the disease – has been demonstrated compared to placebo in studies with durations of up to 28 weeks. One open, uncontrolled study suggests that this effect may persevere for an additional six months.
Ebixa is relatively expensive: treatment of one patient with 10 mg twice daily costs DKK 41.65 per day.
Ebixa (memantine) is a new medicinal product; it was first marketed on 19 August 2002. The drug is indicated for the treatment of patients with moderately severe to severe Alzheimer’s disease. There are currently three other products on the market that can be used to treat Alzheimer’s disease: the three acetylcholinesterase inhibitors donepezil (Aricept), rivastigmine (Exelon) and galantamine (Reminyl). However, these three products have only been approved for patients with a mild to moderate form of the disease.
The active ingredient in Ebixa is memantine, a derivative of amantadine. Like amantadine, memantine is an NMDA (N-methyl-D-aspartate) glutamate receptor antagonist with a selective effect on receptors in the brain and retina.
Memantine has been marketed in Germany for the past 20 years, where it has especially been used for the treatment of Parkinson’s disease and cerebral spasticity. As a result, there is a great deal of recorded experience with and older clinical documentation for efficacy and dose escalation. Two major clinical studies were conducted to document the efficacy of the drug in the treatment of Alzheimer’s disease.
The largest of these studies had a duration of six months, and its population comprised 252 patients with moderately severe to severe Alzheimer’s disease randomised to memantine 20 mg/day or placebo. The primary efficacy parameters comprised an assessment of both global and functional domain status. In the 181 patients that completed the study, a significantly better global and functional score was seen in the memantine group than in the placebo group (the global assessment favoured memantine by 0.25 on the CIBIC-Plus scale. Also in an assessment of cognition, a secondary parameter in the study, memantine displayed a significantly superior efficacy compared to placebo. In a responder analysis in which a responder was defined as a patient exhibiting stabilisation or improvement in two of the three domains, memantine also displayed significantly better efficacy than placebo.
In the other study, whose population included 79 patients with Alzheimer’s disease, memantine was significantly superior to placebo in both primary efficacy parameters (functional and global assessment), in spite of the fact that patients received only half (10 mg) the approved dose and the study duration was only three months.
Adverse drug reactions
In the 20 years that the product has been in use in Germany, memantine has not given rise to concern about adverse drug effects. In recent clinical trials, the overall incidence of adverse events was about the same for memantine as for placebo, and they were usually mild to moderate in severity. The adverse effects with a higher rate of incidence in the memantine group than in the placebo group were particularly dizziness, fatigue and headache.
Between 75% and 90% of memantine is excreted unchanged in the urine, partly by active secretion. There is a theoretical risk of interaction with other medicinal products excreted through the same tubular transport mechanism (e.g. cimetidine, ranitidine and procainamide). Co-administration of memantine and hydrochlorothiazide has been shown to result in a reduced diuretic effect of the latter. Alkalisation of the urine may lead to an accumulation of the drug. Memantine is converted in the liver to a minor degree only, and in-vitro interaction studies have not found interactions between memantine and most of the hepatic CYP systems.
Administration concomitantly with other medicinal products that affect the NMDA glutamate receptor (e.g. ketamine, fenytoin and dextromethorphan) should be avoided. In-vitro studies have shown that there is no interaction with acetylcholinesterase inhibitors at clinically relevant doses.
Ebixa is a relatively expensive product, at a cost of DKK 41.65 a day for 10 mg twice daily.
The Institute recommends that treatment with Ebixa only be initiated by physicians experienced in the diagnosis and treatment of Alzheimer’s disease. General reimbursement is not granted for this product, although patients may apply for individual reimbursement.
Additional information is available in the summary of product characteristics.
Last modified: August 19th 2002