Application

Is it necessary to take Axura® at a certain daytime?

It is recommended to give one dose in the morning and one in the afternoon. If for given reasons the dosage is 10 mg per day, this dose should be given in the morning.

Does it matter if Axura® is taken with a meal or not?

Axura® can be taken with or without food.

Is it possible to mash up the tablet and apply it e.g. via a tube?

Yes, this is possible. In addition, in some countries, Axura® is also available in liquid form.

What should I do when the patient has forgotten to take Axura®?

Due to the long elimination half-life, the next dose should simply be applied at the usual time. The dose should not be doubled to compensate for the forgotten tablet.

How should I proceed if Axura® was discontinued e.g. during hospitalization. Can I prescribe the medication again?

There is no reason for not resuming Axura® treatment after it has been discontinued accidentally. However, one should investigate if there were any medical reasons for discontinuing the drug. If the patient is off drug for 7 days or longer, Axura® needs to be uptitrated again (5 mg/day first week, 10 mg/day second week, 15 mg/day third week, 20 mg/d from fourth week on).

If a patient has progressed to an advanced stage of disease while being treated with cholinesterase inhibitors, how do I best switch them to Axura®?

While upcoming treatment guidelines may include this aspect, so far no fixed protocol exists. Discontinuation of AChEI treatment should be done according to the respective product information. Start Axura® by titrating up: 5mg/day for the first week, 10mg/day for the second week, 15mg/d for the third week and 20mg/day thereafter.

Is it possible to combine Axura® and cholinesterase inhibitors, and are there any studies on this?

Currently, there are first results from a clinical trial in moderate to severe Alzheimer patients on the combination of memantine and donepezil(6). 403 patients on an individual stable donepezil dose for at least 3 months received either 20 mg memantine per day or placebo as an additional medication. The study design was 6 months double-blind and placebo-controlled. In this study patients treated with memantine showed a significant improvement in cognition compared to patients treated with placebo over the entire treatment period. The Alzheimer's Disease Cooperative Study Activities of Daily Living (ADCS-ADL) and the Clinician's Interview-Based Impression of Change plus Caregiver Input (CIBIC-Plus) showed significantly better results in the memantine group than in the placebo group. Tolerability was very good in both groups, and there was no difference as regards the number of adverse events in the trial. In addition a postmarketing surveillance of 158 patients treated with an individual constant dose of cholinesterase inhibitors who were also treated with memantine showed good safety results(7).

Which patients would benefit from a combined treatment?

There have been no trials as yet to address this point. With the current indication for Axura®, a combination would only be feasible for patients with moderate Alzheimer's disease. Based on the available combination trial(4), and taking into account the different mechanisms of action, one may however assume that a combination therapy is beneficial.

Can I prescribe Axura® in agitated Alzheimer's patients?

Memantine seems to have a positive effect on agitated patients. In the memantine trials, agitation as an adverse event was seen more frequently in the placebo group (17.4%) than in the memantine group (9%).

Can I prescribe Axura® for patients who suffer from tachycardia?

Tachycardia is not a contraindication for Axura®. However, special care should be taken in case of some other heart diseases: In most clinical trials, patients with recent myocardial infarction, congestive heart failure (NYHA III IV), and uncontrolled hypertension were excluded. As a consequence, only limited data are available and patients with these conditions should be closely supervised.

How is Axura® eliminated from the body?

Memantine and its metabolites are mainly excreted via the kidneys (75-90%) and around 10-25% of the dose are recovered in the bile and feces. Renal excretion is higher at acidic urine pH (4.96-5.27) compared with alkaline (7.62-8.18) conditions (7-9 fold higher) indicating that the urine pH is a major factor influencing renal clearance of memantine. Changes in urinary flow have a statistically significant influence on renal excretion of memantine, but the clinical relevance seems to have minor importance. When steady-state conditions have been established, alterations of the urine pH towards alkaline conditions may lead to an accumulation of the drug with a possible increase of side effects. For instance, a drastic change to vegetarian diet should be avoided during treatment with memantine because the urine pH changes to alkaline and could lead to an accumulation of the drug.