Мемокс

General characteristics. Structure:

Active ingredient: memantina of a hydrochloride of 10 mg or 20 mg;

Excipients: lactoses monohydrate, cellulose microcrystallic, talc, silicon dioxide colloid anhydrous, magnesium stearate; mix for a film covering: lactoses monohydrate, a gipromeloz, titanium dioxide (E 171), polyethyleneglycol 4000 (macrogoal), for tablets of 20 mg: ferrous oxide yellow (E 172), ferrous oxide red (E 172).

Pharmacological properties:

Pharmacodynamics. In manifestations of symptoms and progressing of neurodegenerative dementia an important role is played by disturbance of glutamatergichesky neurotransmission, especially with participation of NMDA-(N - methyl - D - aspartat) - receptors.
Miemangting represents potentsialzavisimy, average affinity the non-competitive antagonist of NMDA-receptors. Miemangting regulates effects patholologically of the increased levels 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 is equal in cerebrospinal liquid and blood serum to 0,52. About 45% of a memantin contact proteins of a blood plasma.
Biotransformation. 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 is not revealed.
Elimination. Miemangting eliminirutsya on curve monoexponential dependence with an interval of t1/2 from 60 to 100 hours. At people with normal function of kidneys the general clearance (Cltot) is equal to 170 ml/min. / 1,73 to 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 essential changes of a diet, for example replacement of a diet rich with myasny 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 a day 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:

Alzheimer's disease from easy degree to severe forms.

Route of administration and doses:

Treatment should be begun and carried out under observation of the doctor. Therapy should be begun only on condition of presence of the trustee who will regularly control administration of drug by the patient.
It is necessary to take a pill 1 time a day every day at the same time. A pill can be taken together with food or irrespective of meal.

Adults.
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 dose by 5 mg a week within the first 3 weeks as follows:
1st week (1-7th day):
to take 1/2 pill of drug of Memoks 10 (5 mg a day) within a week;
2nd week (8-14th day):
to accept 10 mg a day within a week;
3rd week (15-21st day):
to accept 15 mg a day within a week;
since 4th week:
to accept 20 mg a day every day.

The recommended maintenance dose makes 20 mg a day.
Treatment duration is individually determined by the doctor having experience of diagnosis and treatment of Alzheimer's disease. It is regularly necessary to estimate portability and dosing of a memantin, it is the best of all - within three months from an initiation of treatment. Further the clinical effect of a memantin and reaction of the patient to treatment should be estimated regularly according to the existing clinical recommendations. It is possible to continue the supporting treatment until the therapeutic effect remains favorable, and portability of a memantin - good. It is necessary to consider the possibility of the termination of treatment memantiny if signs of therapeutic effect disappear or portability of treatment worsens.

Patients of advanced age.
The recommended dose for patients is more senior than 65 years makes 20 mg a day (2 tablets on 10 mg of 1 times a day) as it is stated above.

Renal failure.
For patients with a renal failure of easy degree (clearance of creatinine of 50-80 ml/min.) the dose decline of drug is not required. Patients with a renal failure of average degree (clearance of creatinine of 30-49 ml/min.) should umenshit a daily dose to 10 mg. It is possible to increase a dose to 20 mg a day according to the standard scheme if there are no negative reactions at least after 7 days of treatment. Patients with a renal failure of heavy degree (clearance of creatinine of 5-29 ml/min.) should umenshit a daily dose to 10 mg.

Abnormal liver function.
For patients with an abnormal liver function of easy or average degree (Child Pugh A, B) dose adjustment is not required. Use of a memantin is not recommended to patients with a heavy abnormal liver function.

Features of use:

Use during pregnancy or feeding by a breast. 
There are no data on influence of a memantin at use during pregnancy. The potential risk for the person is unknown. Miemangting it is not necessary to apply during pregnancy, except for the cases caused by accurate and explicit need.
It is unknown whether there is excretion of a memantin in breast milk that, however, can take place in view of lipophilicity of substance. Women who apply мемантин should refrain from feeding by a breast.

Children.
Drug is not used to children in connection with insufficiency of data on safety and efficiency.

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 essential 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 a condition of tubular renal acidosis (TNA) or owing to the heavy infections of an uric path caused by Proteus bacteria.

There are only limited data on the patients who recently had a myocardial infarction, patients with dekompensirovanny congestive heart failure (the III-IV degrees according to classification of the New York cardiological association), and also with uncontrollable arterial hypertension and those who accepted мемантин. Therefore for patients with such diseases careful observation is necessary.

Lactose is a part of drug. Patients with rare hereditary intolerance of a galactose, a lactose intolerance or disturbances of absorption of glucose galactose should not accept it.

Ability to influence speed of response at control of motor transport or work with other mechanisms.
Alzheimer's disease from average degree to severe forms usually causes deterioration in ability to drive the car and to work with other mechanisms. Moreover, мемантин exerts insignificant or moderate impact on the speed of response 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.

Side effects:

The side reactions given in the table which were observed are determined by frequency as:
very frequent (> 1/10), frequent (> 1/100 to <1/10), infrequent (> 1/1000 to <1/100), rare (> 1/10000 to <1/1000), very rare (<1/10000), frequency is unknown (it is impossible to establish according to the available data).

Infections	Infrequent	Fungus diseases
From immune system	Frequent	Hypersensitivity
From mentality	Frequent  Infrequent   Frequency is unknown	Drowsiness Confusion of consciousness Gallyutsinatsii1 Psychotic reaktsii2
From a nervous system	Frequent  Infrequent Very rare	Dizziness Gait disturbance Convulsive attacks
From cardiovascular system	Frequent   Infrequent	Arterial hypertension Heart failure Venous thrombosis / thromboembolism
From respiratory system	Frequent	Asthma
From the alimentary system	Frequent Infrequent Frequency is unknown	Lock Vomiting Pankreatit2
General disturbances	Frequent Infrequent	Headache Increased fatigue

1 Hallucinations were generally observed at patients with a severe form of Alzheimer's disease.
2 Separate messages at a medical use.

Alzheimer's disease is connected with a depression, the suicide ideas and a suicide. Such cases are known at a medical use of a memantin.

Interaction with other medicines:

It is necessary to avoid one temporary use of N - methyl - D - aspartat (NMDA) - antagonists (амантадин, ketamine or dextromethorphan). The specified connections influence the same system of receptors, as мемантин therefore the side effects (which are generally connected with the central nervous system) can be more frequent or more expressed. In one published report it was told also about possible risk of a combination of a memantin and Phenytoinum.

The mechanism of action assumes possible strengthening of effects of L-dopa, dopaminergic agonists and anticholinergics at simultaneous use of such NMDA-antagonists as мемантин. Easing of effects of barbiturates and neuroleptics is possible. Joint purpose of a memantin and antispasmodics, a dantrolen or Baclofenum can change their effects that 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 these drugs of contents in a blood plasma.

At joint purpose of a memantin with a hydrochlorothiazide or any combined drug which contains a hydrochlorothiazide decrease in level of content of the last in blood serum is possible.

There were messages on separate cases of increase in the international normalized ratio (INR) at use of a memantin to the patients accepting warfarin. Though the causal relationship is not established, careful monitoring of a prothrombin time or the Ministry of Taxes and Tax Collection at the patients who are at the same time accepting peroral anticoagulants is necessary.

Essential effects of interaction of a memantin with Glyburidum/Metforminum, donepezil or Galantaminum are not revealed.

Miemangting of in vitro is not RMS 1A2, 2A6, 2C9, 2D6, 2E1, 3A inhibitor, flavinsoderzhashchey monooxygenases, epoxide of hydrolase or a sulfation.

Contraindications:

Hypersensitivity to active ingredient or to any component of drug.

Overdose:

Experience is limited.
Symptoms
Considerable overdoses (200 mg and 105 mg a day for 3 days) were connected with symptoms of fatigue, weakness and/or diarrhea or had an asymptomatic current. At overdose to 140 mg or an unspecified dose symptoms of disturbance of the central nervous system, for example confusion of consciousness, drowsiness, dizziness, excitement, aggression, hallucinations, disturbances of gait and/or gastrointestinal disturbances (vomiting and diarrhea) were noted. After reception of 2000 mg of a memantin at the patient the coma (10 days), a lateral diplopia and excitement developed. After a symptomatic treatment and a plasma exchange the patient recovered without effects.

Treatment
Symptomatic, the specific antidote does not exist. It is necessary to apply standard clinical procedures to removal of active ingredient from an organism, for example a gastric lavage, reception of absorbent carbon, urine reaction acidulation, an artificial diuresis. In case of excessive general stimulation of the central nervous system symptomatic medical events should be held with care.

Storage conditions:

To store in the place, unavailable to children, in original packaging at a temperature not above 25 °C.

Issue conditions:

According to the recipe

Packaging:

Мемокс 10: on 10 tablets in the blister; on 3 or 6 blisters in a cardboard pack;
Мемокс 20: on 10 tablets in the blister; on 3 blisters in a cardboard pack.