Product Information: Memantine - Ebixa

Product Information
The very latest approach for Alzheimer's disease

Memantine is a novel new drug that is showing a lot of promise in the battle against Alzheimer's disease. Although it has been in use in Germany for nearly 10-years (5), it is only recent clinical trials that has highlighted many of its unique properties, particularly for its use in senile dementia.

The majority of current drugs that treat Alzheimer's disease, such as Galantamine, do so by inhibiting an enzyme called acetylcholinesterase. This enzyme breaks down the brain neurotransmitter- acetylcholine. It is acetylcholine that is badly affected in Alzheimer's patients. (It is interesting to note that Memantine appears to be capable of being used alongside such drugs- see reference 1).

Memantine works very differently, it inhibits receptors known as N-Methyl-D-Aspartate or NMDA, because these receptors may underlie the degeneration of cholinergic cells (1). Cholinergic cells are essential for healthy brain function and are also badly affected in Alzheimer's disease.

Over stimulation of NMDA receptors is referred to under the term of excitotoxicity, and excitotoxicity was referred to in a 1994 review (3) as; "The final common pathway for all neurologic disorders." Now even more evidence is accumulating that over activity of NMDA receptors is detrimental to mental health (4). However, experiments have shown that Memantine can significantly protect against traumatic brain injury by inhibiting the activity of NMDA receptors (2), i.e. it acts as an antagonist.

Memantine and Excitotoxins
Biochemist James South MA, pointed out that there are daily factors in everyday lives, (many of them present in certain diets), that cause over excitation of NMDA receptors. Most notably these are some artificial sweeteners, flavor enhancers, (especially MSG) and even hydrolyzed vegetable proteins.

As Alzheimer's disease, vascular and mixed dementia are the commonest forms of dementia in older people, the question is being asked in some circles; Are they nothing more than the result of a long term exposure to a bad diet? A diet, that leads to over stimulation of NMDA receptors? We don't know the answer yet, but we do know enough to take some simple steps to try and avoid some of the issues.

James South went further to say that you will discover why and how certain substances can cause this damage. He also goes on to recommend particular regimes that can help protect against excitotoxins, including Memantine. He also pointed out that learning about, and doing what is necessary to cope with, the brain's tendency to excitotoxically melt down, is the best brain anti-aging insurance available.

Memantine: Alzheimer Clinical Studies
There have been numerous clinical studies with Memantine and Alzheimer's disease. One clinical study, (4) conducted under the proper double-blind placebo-controlled method, concluded that Memantine is a safe drug and may be useful for treating Alzheimer's disease, vascular and mixed dementia of all severities.

Even in elderly patients with general cognitive disturbances, (but not yet diagnosed as a specific senile dementia), Memantine has been shown to enhance vigilance and improve short-term memory and concentration. Furthermore, the tolerance of the drug was good in virtually all cases (8).

After 28-weeks of treatment, a French study with 321 Geriatric patients in 2002 concluded that; "Patients with mild to moderate dementia had improved cognition consistently at 20mg/day Memantine, with no deterioration in functioning and behavior." Furthermore, the study stated that; "Memantine was devoid of concerning side effects." (9)

The beneficial effects of Memantine can be seen quickly. For example, a study with 66 patients aged 65 to 80 and all suffering from mild to moderate dementia (10), indicated that after just 14-days there was significant improvement when compared to placebo. At 42-days the effects were even more pronounced and the study announced that; It was particularly striking in the daily-living tests, of the patients considerable improvement achieved in the quality of performing tasks under Memantine treatment.

Perhaps most interesting of all has been the reports of Memantine's efficacy in late-stage Alzheimer's disease. This distressing phase of the disease is one where other treatments are not currently available. For example, a Swedish study in 1999 confirmed that; The results of the trial support that Memantine treatment leads to functional improvement and reduces care dependence in severely demented patients. (12)

A more recent study with 252 patients studied over a period of 28-weeks, (11) receiving either placebo or 20mg/day of Memantine; it was clearly noted that Memantine reduced the clinical deterioration in moderate to severe Alzheimer's disease. Dr. Hans Joerg Moebius stated that; These promising results represent a breakthrough in terms of significant patient and caregiver benefit by Memantine, in the untapped therapeutic area of advanced dementia. In addition, compared to other anti-dementia drugs, Memantine showed an excellent safety and tolerability profile.

Memantine: Many Other Uses?
However, as is quite usual with most other drugs, there may be numerous other beneficial uses for Memantine. For example, studies indicate that it could be effective for Parkinson's disease. One such clinical study, (6) concluded with the statement; The results suggest that Memantine may improve Parkinsonian symptoms independently of dopaminergic drugs.

What's more, further studies suggest that Memantine and NMDA receptors may have a role in alcoholism and that Memantine could act as an anti-craving drug for alcohol (7). There are also reports that Memantine could be efficacious in the alleviation of some intense pain conditions, particularly for painful neuropathy, with one trial at 40mg/day Memantine, statistically and significantly alleviating night time pain for patients, when compared to placebo (13).

There are even on-going trials utilizing Memantine for glaucoma and ocular hypertension, as well as AIDS related dementia (14).

Whilst further research is needed in these areas, it is becoming apparent that NMDA receptors have a number of negative effects when they are over-stimulated, and that antagonists such as Memantine, are going to become important factors in the management and control of numerous debilitating conditions.

References

1. Wenk GL, Quack G, Moebius HJ, Danysz W. "No interaction of memantine with acetylcholinesterase inhibitors approved for clinical use." Life Sci. 2000 Feb. 11;66(12):1079-83.
2. Roa VL, Dogan A, Todd KG, Bowen KK, Dempsey RJ. "Neuroprotection by memantine, a non-competitive NMDA receptor antagonist after traumatic brain injury in rats." Brain res. 2001 Aug. 17;911(1):96-100.
3. Lipton S. Rosenberg, P. "Excitatory amino acids as a final common pathway for neurologic disorders" NEJM 1994, 330: 613-22.
4. Areosa SA, Sherriff F. "Memantine for dementia." Syst. Rev. 2003; (1):CD003154.
5. Jain KK. "Evaluation of Memantine for neuroprotection in dementia." Expert. Opin. Investig. Drugs 2000 Jun:9(6):1397-406.
6. Merello M, Nouzeilles MI, Cammarota A, Leiguarda R. "Effect of Memantine on Parkinson's disease: A double-blind crossover randomized study." Clin. Neuropharmacol. 1999 Sep-Oct;22(5):273-6.
7. Holter SM, Danysz W, Spanagel R. "Evidence for alcohol anti-craving properties of Memantine." Eur. J. Pharmacol. 1996 Oct. 31;314(3):R1-2.
8. Ambrozi L, Danielczyk W. "Treatment of impaired cerebral function in Psychogeriatric patients with Memantine: Results of a phase II double-blind study." Pharmacopsychiatry 1988 May;21(3):144-6.
9. Orgogozo JM, Rigaud AS, Stoffler A, Mobius HJ, Forette F. "Efficacy and safety of Memantine in patients with mild to moderate vascular dementia." Stroke 2002 Jul;33(7):1834-9.
10. Ditzler K. "Efficacy and tolerability of Memantine in patients with dementia syndrome. A double blind placebo controlled trial." Arneimittelforschung 1991 Aug;41(8):773-80.
11. Reiseberg B, Doody R, Stoffler A, Schmitt F, Ferris S, Mobius HJ. "Memantine in moderate to severe Alzheimer's disease." N. Engl. J. Med. 2003 Apr. 3;348(14):1333-41.
12. Winblad B, Poritis N. "Memantine in severe dementia: The benefit and efficacy in severely demented patients during treatment with Memantine." Int. J. Geriatr. Psychiatry 1999 Feb;14(2):135-46.
13. Results from the 52nd Annual Meeting of the American Academy of Neurology in San Diego, April 29 to May 6, 2000.
14. Kilpatrick GJ, Tilbrook GS. "Abstract." Curr. Opin. Investig. Drugs 2002 May;3(5):798-806.

AXURA® / Memantin Hydrochloride

The active ingredient is memantin hydrochloride.

Other ingredients contained in the tablet are: lactose monohydrate, microcristalline cellulose, colloidal silicium dioxide, talc and magnesium stearate; and in the coating are: methacryl acid - ethyl acrylate copolymer (1:1), sodium dodecyl sulphate, polysorbate 80, talc, triacetin and simethicone emulsion.

What is AXURA and what are the indications for its Use? What is AXURA?
AXURA tablets are white to shaded white long coated tablets with notches on both top and bottom.

Each tablet contains 10 mgs of memantin hydrochloride.

AXURA tablets are available in blister packages of 50 or 100 tablets.

What are indications for the use of AXURA?
AXURA is to be used for treating patients with moderately severe to severe Alzheimer's disease.
Memory loss associated with Alzheimer's is caused by a disruption in the transmission of brain signals. So-called NMDA receptors in the brain assist in transmission of nerve signals essential to learning and memory functions. AXURA belongs to a group of medications called NMDA receptor antagonists. AXURA stimulates these NMDA receptors and improves transmission of nerve signals and thereby the memory.

What should you consider before taking AXURA?
Prior to taking AXURA, it is important that you carefully read the following paragraphs and discuss any questions you may have with your doctor. You may wish to go through all the details you would like to discuss first with your carer.

AXURA must not be taken:
If you have had allergic reactions to memantin hydrochloride or any of the other ingredients of AXURA tablets listed above.

Particular caution is required when taking AXURA:
If you have a history of epileptic seizures
If you have recently suffered a myocardial infarction (heart attack) or if you suffer from under-compensated cardiac insufficiency or untreated high blood pressure.
Under these circumstances treatment must be carefully monitored and the clinical use of AXURA regularly re-evaluated by your doctor.
If you suffer from moderately severe kidney dysfunction, your doctor should carefully monitor your kidney function and adapt the memantin dosage appropriately. The use of memantin is not recommended for patients with severe kidney dysfunction.
Simultaneous use of medications with active ingredients such as amantadine, ketamine, dextromethorphane as well as other NMDA antagonists should be avoided.
The use of AXURA is not recommended for children or anyone under the age of 18.

Taking AXURA with food and drink
Please inform your doctor if you have recently undergone major dietary changes (for example from a normal diet to a strictly vegetarian diet) or if you intend to do so, if you suffer from renal tubular acidosis (RTA - an excess of acid forming substances in the blood due to kidney dysfunction) or a severe infection of the urinary tract. Your doctor may need to adjust the dosage of your medication in such circumstances.

Pregnancy
Tell your doctor if you are pregnant or wish to become pregnant. The use of memantin is not recommended during pregnancy.

Breast-feeding
Women must not breast-feed while taking AXURA.

Operating vehicles or machinery:
Your doctor will advise you whether your condition allows you to drive or operate machinery without danger to yourself or others.

Moreover, taking AXURA may alter your reaction time significantly, so that safe driving and safe operation of machinery may no longer be possible.

Interaction with other medications
Please inform your doctor or pharmacist if you are taking other medications or have done so until recently, even if these are not prescription medicines.
The following medications specifically may be affected by taking AXURA and necessitate an adjustment to your dosage by your doctor:
Amantadine, ketamine, dextromethorphane
Dantrolen, baclofen
Cimetidine, ranitidine, procainamide, quinidine, quinine, nicotine
Hydrochlorothiazide (or combined preparations containing hydrochlorothiazide)
Anticholinergics (substances normally prescribed to treat motor dysfunction or enterospasm)
Anticonvulsives (substances used to prevent or treat cramping)
Barbiturates (substances normally used to induce sleep)
Dopaminergic antagonists (substances such as L-dopa and bromocriptine)
Neuroleptics (substances that treat mental dysfunction)
If you are admitted to hospital, inform the hospital doctor that you are taking AXURA.

How should AXURA be taken?
Always follow your doctor's instructions when taking AXURA. You should take the medication regularly on a daily basis for optimum effect. Please ask your doctor or pharmacist if you have any doubts.

Dosage
The recommended AXURA dose for adults and older patients is 20 mgs (2 x 1 tablet) every day. In order to lower the risk of side effects, this dose should be introduced gradually according to the following daily treatment plan:

The usual starting dose consists of half a tablet (1 x 5mgs) once a day during the first week. This dose is increased to a half a tablet twice a day (2 x 5 mgs) in the second week and to one tablet (1 x 10mgs) and a half tablet (1 x 5mgs) daily at different times during the third week. Starting in the fourth week the normal dose will be one tablet twice a day (2 x 10mgs).
Dosage for patients with decreased kidney function
If you suffer from kidney dysfunction, your doctor must decide what dosage is appropriate for your disease. In this case, kidney function should be monitored by your doctor at regular intervals.
Instructions for use
AXURA should be taken orally twice a day (except for the first week of treatment). Tablets should be swallowed with water. The tablets may be taken with or without food.
Duration of treatment
Continue taking AXURA as long as the medication helps and you are not experiencing any unacceptable side effects. Treatment should be regularly assessed by a doctor.

If you have taken a larger dose of AXURA than required:
In general, taking more AXURA than prescribed should not have any adverse effects. It is possible that you may experience a more severe form of the symptoms detailed in paragraph 4 - "What are the potential side effects?"
If you have taken a large overdose of AXURA, consult your doctor or seek other medical advice, as you may require medical treatment.

If you have forgotten to take AXURA:
If you realize that you have forgotten to take your dose of AXURA, wait and take your next dose at the usual time.
Do not double your dose to compensate for the missed dose.

What are the potential side effects?
As with all medications, AXURA can produce side effects.
In general, side effects have been observed to be weak or only moderately severe. Most frequent side effects (frequency of 2% or less) include hallucinations, confusion, dizziness, headache and fatigue. Occasional side effects include anxiety, hyper tonus (heightened muscle tension), vomiting, bladder infections and increased sexual drive.
If you have a history of epileptic seizures, there is a slight chance that AXURA may increase the probability of an attack.
Please inform your doctor or pharmacist should you experience side effects not included in this pamphlet.

How should AXURA be stored?
Keep medications out of the reach of children.
There are no specific storage instructions applicable to this medication.
Do not use this medication after the expiration date shown on the box and the blister package.