Producer: Lundbeck (Lundbek) Denmark
Code of automatic telephone exchange: N06DX01
Release form: Firm dosage forms. Tablets.
General characteristics. Structure:
Active ingredient: 10 mg of a memantin of a hydrochloride.
Excipients: cellulose microcrystallic, sodium of a kroskarmelloz, silicon dioxide colloid anhydrous, magnesium stearate, gipromelloz, macrogoal 400, titanium dioxide (Е 171), ferrous oxide yellow (Е 172).
Pharmacodynamics. In manifestations of symptoms and progressing of neurodegenerative dementia an important role is played by disturbance of glutamatergichesky neurotransmission, especially with NMDA participation (N - methyl - D - aspartate) receptors. Miemangting represents potentsialzavisimy, average affinity the non-competitive antagonist of NMDA receptors. Miemangting modulates effects patholologically of the increased level of a glutamate which can lead to dysfunction of neurons.
Pharmacokinetics. Absorption Absolute bioavailability of a memantin makes about 100%, time of achievement of peak of concentration in a blood plasma (Tmax) - from 3 to 8 hours. There are no signs of influence of meal on absorption.
Distribution. The daily dose of 20 mg causes stable concentration of a memantin in a blood plasma ranging from 70 to 150 ng/ml (0,5-1 µmol) with considerable individual variations. At use of daily doses from 5 to 30 mg the relation of content of drug in cerebrospinal liquid and blood serum it is equal to 0,52. About 45% of a memantin contact proteins of a blood plasma.
Metabolism. In a human body about 80% of a memantin circulate in the form of initial substance, the main metabolites have no NMDA antagonistic properties. Participation of P450 cytochrome in metabolism of in vitro it is not revealed.
Removal. Miemangting is brought in a monoyeksponentsialny way with an interval of T1/2 from 60 to 100 hours. At volunteers with normal function of kidneys the general clearance (Cl tot) is equal to 170 ml/min. / 1,7Z of sq.m. The renal stage of pharmacokinetics of a memantin includes also canalicular reabsorption. Speed of renal elimination of a memantin in the conditions of alkali reaction of urine can decrease by 7-9 times. Alkalization of urine can result from profound changes of a diet, for example change of a diet rich with meat dishes vegetarian or owing to intensive reception of antiacid gastric means.
Linearity. The pharmacokinetics has linear character in the range of doses of 10-40 mg.
Фармакодинамическая / pharmacokinetic communication. At a dose of a memantin of 20 mg the level of content in cerebrospinal liquid corresponds to the size Ki (a braking constant) of a memantin that makes 0,5 µmol in a frontal cerebral cortex of the person.
Indications to use:
Dementia, Alzheimer's disease from moderately severe to severe forms.
Route of administration and doses:
Treatment should be begun and carried out under observation of the doctor having experience of diagnosis and treatment of dementia, Alzheimer's disease. Therapy should be begun only on condition of presence of the trustee who will regularly control administration of drug by the patient. The diagnosis is established according to the existing recommendations.
Adults. Treatment it is necessary to begin with purpose of a dose 5 mg a day (a half of a tablet in the morning) within 1 week. Further purpose of a dose of 10 mg a day (on a half of a tablet 2 times a day) within the 2nd week and 15 mg/days (1 tablet in the morning and a half of a tablet in afternoon) for the 3rd week is recommended. Since 4th week of treatment it is possible to carry out with use of the recommended maintenance dose 20 mg a day (on 1 tablet 2 times a day), the maximum daily dose makes 20 mg. For the purpose of decrease in risk of emergence of negative reactions the maintenance dose is defined by gradual increase in a dosage by 5 mg a week within the first three weeks.
Pill can be taken together with food or irrespective of meal.
Patients of advanced age. On the basis of results of clinical trials the recommended dose for patients is more senior than 65 years makes 20 mg a day (10 mg twice a day) as it is stated above.
Renal failure. With normal function of kidneys or with its disturbance of easy severity (creatinine level in a blood plasma do130 mmol/l) the dose decline of drug is not required from patients. At patients with a renal failure of moderate severity (clearance of creatinine of 40-60 ml/min. / 1,73m2) it is necessary to reduce a daily dose to 10 mg. Concerning patients with heavy renal failures data are absent.
Safety and efficiency of use of a memantin for treatment of children and teenagers is not established.
There are no data on use of a memantin for treatment of patients with an abnormal liver function.
Due to the lack of data on patients with heavy renal failures (clearance of creatinine less than 9 ml/min. / 1,73m2) therapy in such cases is not recommended.
It is necessary to be careful at purpose of drug to patients with epilepsy, patients with episodes of spasms in the anamnesis, and also to patients with risk factors of development of epilepsy.
Some factors causing increase рН urine can cause need of careful observation of the patient. The specified factors include profound changes of a diet, for example, replacement of a diet rich with meat dishes by vegetarian or intensive reception of antiacid gastric means. Besides, рН urine can raise because of the condition of tubular renal acidosis (TNA) or heavy infections of an uric path caused by Proteus bacteria.
Within the majority of clinical trials the patients who recently had a myocardial infarction who had dekompensirovanny congestive heart failure (the III-IV degrees according to classification of the New York cardiological association) and also uncontrollable arterial hypertension, were eliminated participants. Thereof there are only limited relevant data, and for patients with such diseases careful supervision is necessary.
Features of use:
Pregnancy and lactation. Pregnancy. There are no data on influence of a memantin during pregnancy. Pilot studies on animals indicate a possibility of delay of pre-natal growth at levels of influence identical or several big concentration in comparison with those at the person. The potential risk at the person is unknown. Miemangting it is not necessary to apply at pregnancy except for the cases stipulated by accurate and explicit need.
Lactation. It is unknown whether there is excretion of a memantin to breast milk that however can take place, considering lipophilicity of substance. To women, apply мемантин, it is necessary to refrain from feeding by a breast.
Influence on ability to manage vehicles and to work with mechanisms. Alzheimer's disease from moderately severe to severe forms usually causes deterioration in an opportunity to drive the car and disturbance of ability to work with mechanisms. Moreover, мемантин it is capable to change reaction of the person therefore ambulatory patients should be warned about need of respect for extra care at control of motor transport or work with the equipment.
During clinical trials at medium-weight - heavy dementia the general frequency of the adverse phenomena did not differ from that against the background of placebo reception, and actually negative phenomena were usually characterized from easy to moderate severity.
The general data on the most frequent (> 4% for a memantin) side effects (irrespective of a causal relationship) which were observed in populations of the studied patients with medium-weight and heavy dementia, are provided in the table.
|The applied term on WHO ART classification – terminology of side reactions of WHO||Miemangting n=299||N=288 placebo|
|Concern||27 (9,0%)||50 (17,4%)|
|Accidental mutilation||20 (6,7%)||20 (6,9%)|
|Urine incontience||17 (5,7%)||21 (7,3%)|
|Diarrhea||16 (5,4%)||14 (4,9%)|
|Sleeplessness||16 (5,4%)||14 (4,9%)|
|Dizziness||15 (5,0%)||8 (2,8%)|
|Headache||15 (5,0%)||9 (3,1%)|
|Hallucinations||15 (5,0%)||6 (2,1%)|
|Falling||14 (4,7%)||14 (4,9%)|
|Lock||12 (4,0%)||13 (4,5%)|
|Cough||12 (4,0%)||17 (5,9%)|
Frequent adverse reactions (1-10% and more frequent in comparison with placebo) for the patients accepting мемантин and placebo, were presented: hallucinations (2 against 0,7%), confusion of consciousness (1,3 against 0,3%), dizziness (1,7 against 1,0%), a headache (1,7 against 1,4%) and feeling of fatigue (1,0 against 0,3%).
Interaction with other medicines:
It is necessary to avoid simultaneous use N-methyl-D-aspartate (NMDA) - antagonists (амантадин, ketamine or dextromethorphan). The specified connections influence the same system of receptors, and мемантин therefore the side effects (which are generally connected with TsNS, for example, risk of pharmakotoksichesky psychosis) can be more frequent or more expressed. There are published data on cases of possible risk at combined use of a memantin and Phenytoinum.
Considering the action mechanism, at simultaneous use of NMDA antagonists strengthening of effects of the drugs L-dopa, dopaminergic agonists and anticholinergics is possible. Decrease in expressiveness of effects of barbiturates and neuroleptics is possible. Joint purpose of a memantin and spasmolytic drugs, a dantrolen and Baclofenum can change effects which can cause need of correction of doses.
Other medicines, such as Cimetidinum, ranitidine, procaineamide, quinidine, quinine and nicotine which use the same cationic transport system of kidneys as амантадин, perhaps, are also capable to interact with memantiny, causing potential risk of increase in levels of content in plasma.
At joint purpose of a memantin with Hydrochlorthiazidum or any combined drug which contains a hydrochlorothiazide decrease in level of content of the last in blood serum is possible.
Hypersensitivity to active ingredient or to any of drug components.
Period of validity - 4 years. There are no special storage conditions. To store in the place, unavailable to children.
According to the recipe
On 14 tablets at blisters, on 2 or 4 blisters at cardboard to packaging.