Pharmacological properties

Pharmacodynamics. in symptomatology and progressing of neurodegenerative dementia, according to modern scientific data, an important role is played by disturbance of glutamatergichesky neuromediation, especially with the participation of nmda (n-methyl-d-aspartate) - receptors.

Miemangting is potentsialzavisimy, average affinity the noncompetitive antagonist of NMDA receptors. Miemangting blocks effects of a glutamate which in patholologically the increased concentration can lead to dysfunction of neurons.

Pharmacokinetics. Miemangting is characterized by absolute bioavailability about 100%; time of achievement of T _max in blood plasma — 3–8 h. Influence of meal on medicament absorption is not revealed.

Daily dose of 20 mg causes stable concentration of a memantin in blood plasma within 70–150 ng/ml (0.5-1 µmol) with considerable individual variations. When assigning a memantin the ratio of content of medicament in cerebrospinal liquid and blood plasma is equal in a daily dose of 5-30 mg to 0.52. About 45% of a memantin contact blood plasma proteins.

In a human body about 80% of a memantin circulate in not changed look, the main metabolites have no NMDA antagonistic activity. Participation of P450 cytochrome in metabolism of in vitro is not revealed.

Miemangting eliminirutsya mainly by kidneys according to curve monoexponential dependence, T _½ — 60–100 h. The general clearance — 170 ml/min. / 1.73 m ² . 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 change of a diet, for example when replacing a diet rich with meat dishes vegetarian, or owing to frequent intake of antiacid drugs.

Pharmacokinetics has linear character in the range of doses of 10-40 mg.

Pharmakodinamichesky and pharmacokinetic communication: at use of a memantin in a dose of 20 mg/days the concentration level in cerebrospinal liquid corresponds to the size Ki (pressure constant) for a memantin that makes 0.5 µmol in a frontal cerebral cortex of the person.

Indication

Alzheimer's disease from lungs to severe forms.

Use

under observation of the doctor. therapy should be begun only on condition of presence of the trustee who will regularly control administration of medicament by the patient.

needs to take the Pill 1 time a day daily at the same time, together with food or irrespective of food.

Adult.

Maximum daily dose makes 20 mg. For the purpose of reduction of risk of emergence of negative reactions the maintenance dose is defined by gradual increase in a dose on 5 mg a week for the first 3 weeks as follows:

• 1st week (1-7th day): 5 mg/days (on ½ tablets a day).
• 2nd week (8-14th day): 10 mg/days (on 1 tablet a day).
• 3rd week (15-21st day): 15 mg/days (1½ tablets in day).
• since 4th week: 20 mg/days (on 2 tablets a day).

Recommended maintenance dose makes 20 mg/days

treatment Duration individually the doctor who has experience of diagnosing and treatment of Alzheimer's disease defines.

Patients of advanced age. On the basis of results of clinical trials the recommended dose for patients aged is more senior than 65 years makes 20 mg/days (2 tablets on 10 mg of 1 times a day) as it is stated above.

Renal failure. With a renal failure of easy degree (clearance of creatinine of 50-80 ml/min.) the dose decline of medicament is not required from patients. At patients with a renal failure of average degree (clearance of creatinine of 30-49 ml/min.) the daily dose should be lowered to 10 mg. The dose can be raised to 20 mg/days 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 lower 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) the dose adjustment is not required. Use of a memantin is not recommended to patients with a heavy abnormal liver function.

Contraindication

Hypersensitivity to active ingredient or any component of drug.

during clinical trials the general frequency of side effects did not differ in

from that against the background of intake of placebo, and side effects were usually characterized easy and moderate severity.

side reactions Given below in the table which noted during clinical trials and medical use are determined by

by frequency as: very often (≥1/10), it is frequent (≥1/100 to 1/10), infrequently (≥1/1000 to 1/100), is rare (≥1/10,000 to 1/1000), is very rare (1/10,000), it is not defined (it is impossible to establish on the available data).

Infection	Infrequently	Fungus diseases
Disturbance of the immune system	It is frequent	Hypersensitivity
Mental disturbances	is frequent	Drowsiness
	Infrequently	Confusion of consciousness
	Infrequently	Hallucination 1
	is not defined	Psychotic reactions 2
Disturbance of central nervous system	Is frequent	Dizziness
	Infrequently	Disturbance of gait
	is Very rare	Attacks of spasms
Warm disturbances	Infrequently	Heart failure
Vascular disorders	Is frequent	AG
	Infrequently	Venous thrombosis / tromboembolizm
Disturbance of a respiratory system	Is frequent	Asthma
Disturbance of a GIT	is frequent	Constipation
	Infrequently	Vomiting
	is not defined	Pancreatitis 2
General disturbances	is frequent	Headache
	Infrequently	Increased fatigue

¹ Hallucinations mainly noted at patients with a severe form of Alzheimer's disease.

² Separate messages at medical use.

Alzheimer's disease is connected by

with a depression, the suicide ideas and a suicide. Such cases are known at medical use of a memantin.

Special instructions

Should be careful when prescribing medicament to patients with epilepsy, patients with episodes of spasms in the anamnesis and also to patients with risk of developing epilepsy.

Some factors causing increase in pH of urine can cause need of careful observation of the patient. They include a significant change in a diet, for example, replacement of a diet rich with meat dishes by vegetarian or frequent intake of antiacid drugs. Besides, pH of urine can raise in tubular renal acidosis or a heavy infection of the urinary tract caused by Proteus bacteria.

Within the majority of clinical trials of patients which transferred a myocardial infarction recently and also patients with dekompensirovanny stagnant heart failure (the III-IV degree according to classification of NYHA), uncontrollable AG, eliminated participants. Thereof there are only limited relevant data, and patients with such diseases need to be observed carefully.

Period of pregnancy and feeding by a breast. 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 identical or a little higher concentrations in comparison with those at the person. The potential risk for the person is unknown. Miemangting it is not necessary to apply during pregnancy except for emergency cases.

whether gets memantin into breast milk that however can take place, considering lipophilicity of substance. At use of a memantin it is necessary to stop feeding by a breast.

Children. B