Active substanceMemantineMemantine
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  • Dosage form: & nbspfilm-coated tablets
    Composition:

    One tablet, film-coated, contains:

    Dosage of 10 mg

    active substance: memantine hydrochloride - 10.0 mg;

    Excipients: cellulose microcrystalline - 152.5 mg; calcium hydrophosphate dihydrag - 50.0 mg; croscarmellose sodium - 12.5 mg; lactose monohydrate -10.0 mg; giprolose (hydroxypropyl cellulose) 5.0 mg; talc - 5.0 mg; silicon dioxide colloidal - 2.5 mg; magnesium stearate - 2.5 mg;

    film sheath: [hypromellose - 4,000 mg, giprolose (hydroxypropylcellulose) 1.552 mg, talc 1.568 mg, titanium dioxide 0.880 mg] or [dry film-coating mixture containing hypromellose (50%), giprolose (hydroxynropylcellulose) (19.4%) , talc (19.6%), titanium dioxide (11%)] - 8.0 mg.

    Dosage of 20 mg

    active substance: memantine hydrochloride - 20.0 mg;

    Excipients: cellulose microcrystalline - 142.5 mg; calcium hydrophosphate dihydrate - 50.0 mg; croscarmellose sodium - 12.5 mg; lactose monohydrate - 10,0 mg; giprolose (hydroxypropyl cellulose) 5.0 mg; talc - 5.0 mg; silicon dioxide colloidal - 2.5 mg; magnesium stearate - 2.5 mg;

    film sheath: [Hypromellose - 4,0000 mg giproloza (hydroxypropyl) - 1,5520 mg talc - 1.5408 mg of titanium dioxide - 0.8696 mg yellow ferric oxide (iron oxide) - 0.0376 mg] or [dry mixture film coating containing hypromellose (50%), giproloza (hydroxypropylcellulose) (19.4%), talc (19.26%), titanium dioxide (10.87%), yellow iron oxide (ferric oxide) (0.47 %)] - 8.0 mg.

    Description:

    Oblong, biconvex tablets having a risk on each side, film-coated, white (dosage 10 mg) and yellow (dosage 20 mg). On the cross section, the nucleus is white or almost white in color.

    Pharmacotherapeutic group:Dementia remedy
    ATX: & nbsp

    N.06.D.X.01   Memantine

    N.06.D.X   Other drugs for the treatment of dementia

    Pharmacodynamics:

    The adamantane derivative. Is a non-competitive antagonist N-methyl-D-aspartate (NMDA) Receptor, has a modulating effect on the glutamatergic system.It regulates ion transport, blocks calcium channels, normalizes the membrane potential, improves the process of nerve impulse transmission. Improves cognitive processes, increases daily activity.

    Pharmacokinetics:

    Suction

    Eating does not affect absorption. After oral administration memantine quickly and completely absorbed from the gastrointestinal tract. The maximum concentration of memantine in blood plasma is reached in 3-8 hours after administration.

    Distribution

    Daily intake of a daily dose of 20 mg leads to an equilibrium plasma concentration of memantine 70-150 ng / ml. When a daily dose of 5-30 mg was used, the ratio of the mean concentration in the cerebrospinal fluid to the concentration in the blood plasma was calculated to be 0.52. The volume of distribution is about 10 l / kg. About 45% of memantine binds to blood plasma proteins. With normal renal function, no cumulation of memantine was observed.

    Metabolism

    80% of memantine circulating in the blood is unchanged substance. The main metabolites are N-3,5-dimethylgludantan, a mixture of isomers of 4- and 6-hydroxymemanthine, 1-nitroso-3,5-dimethyladamantane.Metabolites do not have their own pharmacological activity. In the experiments in vitro the metabolism, realized by cytochrome P450 isoenzymes, is not revealed.

    Excretion

    Memantine is excreted mainly by the kidneys. Excretion occurs single-phase, the half-life is 60-100 hours. In volunteers with normal renal function, the total clearance is 170 ml / min / 1.73 m2, part of the total renal clearance is achieved through tubular secretion. Renal excretion also includes tubular reabsorption, possibly mediated by cationic transport proteins. The rate of renal elimination of memantine in conditions of alkaline urine reaction can decrease by 7-9 times. The alkalinization of urine can be caused by a sudden change in diet, for example, a transition from a diet that includes animal products to a vegetarian diet, or from the intensive use of alkaline gastric buffers.

    Linearity

    Studies conducted in volunteers showed the linearity of pharmacokinetics in the dose range of 10-40 mg.

    Pharmacokinetic / pharmacodynamic dependence

    When memantine is used at a dose of 20 mg / day, the concentration level in the cerebrospinal fluid corresponds to the value of the inhibition constant,that for memantine is 0.5 μmol in the region of the frontal cortex of the brain.

    Indications:Dementia of the Alzheimer's type of moderate and severe degree.
    Contraindications:

    - Hypersensitivity to memantine or any of the components included in the formulation;

    - hepatic insufficiency of severe degree (class C according to the Child-Pugh classification);

    - lactose intolerance, lactase deficiency, glucose-galactose syndrome malabsorption;

    - pregnancy;

    - the period of breastfeeding;

    - age to 18 years (efficacy and safety not established).

    Carefully:

    - Thyrotoxicosis;

    - epilepsy, predisposition to epilepsy;

    - convulsions (including in the anamnesis);

    - simultaneous use of antagonists NMDA-receptors (amantadine, ketamine, dextromethorphan);

    - the presence of factors that increase the pH of urine (a sharp change in diet, for example, the transition to a vegetarian diet, a copious intake of alkaline gastric buffers);

    - renal tubular acidosis;

    - severe urinary tract infections caused by bacteria of the genus Proteus;

    - myocardial infarction (in history);

    - heart failure (III-IV functional class by classification NYHA);

    - uncontrolled arterial hypertension;

    - kidney failure;

    - hepatic insufficiency (class A and B according to the Child-Pugh classification).

    Pregnancy and lactation:

    Pregnancy

    The use in pregnancy is contraindicated, since there is no evidence of the effect of memantine on the course of pregnancy. Experimental studies conducted on animals indicate the possibility of slowing intrauterine growth at the level of exposure to identical or slightly higher concentrations of memantine compared to such in humans. The potential risk to humans is unknown.

    Breastfeeding period

    There is no information on the allocation of memantine to breast milk, therefore, women receiving memantine, you should stop breastfeeding.

    Dosing and Administration:

    Therapy with memantine should be initiated and conducted under the supervision of a physician with experience in the diagnosis and treatment of Alzheimer's dementia. The diagnosis should be made in accordance with the current recommendations.

    Treatment should be started only if the person who is in constant care of the patient will regularly monitor the patient taking the drug.

    The tolerability and dosage of memantine should be reviewed regularly, preferably within the first three months after initiation of treatment. After this, the clinical effectiveness of memantine and the patient's tolerability of treatment should be reviewed according to current clinical guidelines.

    Supportive treatment can be continued indefinitely for a positive therapeutic effect and good tolerability of the drug.

    Remission of memantine should be discontinued in the absence of a positive therapeutic effect or patient intolerance to the drug.

    The drug should be taken orally once a day and always at the same time, regardless of food intake.

    Begin treatment memantine recommended with the use of minimally effective doses.

    Applied during the first week of therapy (days 1-7) at a dose of 5 mg / day, during the 2nd week (days 8-14) at a dose of 10 mg / day, during the 3rd week (days 15- 21) at a dose of 15 mg / day, starting from the 4th week - at a dose of 20 mg / day.

    The recommended maintenance dose is 20 mg / day.

    The maximum daily dose is 20 mg.

    Special patient groups

    Patients of advanced age (over 65 years)

    Correction of the dose is not required.

    Patients with impaired renal function

    In patients with a creatinine clearance of 50-80 ml / min, no dose adjustment is required.

    In patients with moderate renal insufficiency (creatinine clearance 30-49 ml / min), the recommended daily dose is 10 mg. With good tolerability of this dose for 7 days, the dose can be increased to 20 mg / day in accordance with the standard scheme.

    In patients with severe renal insufficiency (creatinine clearance 5-29 ml / min), the daily dose should not exceed 10 mg.

    Patients with impaired hepatic function

    Dose correction is not required in patients with a mild or moderate liver function disorder (class A and B according to the Child-Pyo classification).

    Patients with hepatic insufficiency of severe degree (class C according to the Child-Pugh classification) use of the drug is contraindicated.

    Side effects:

    Classification of the incidence of side effects according to the recommendations of the World Health Organization (WHO): very often> 1/10; often from> 1/100 to <1/10; infrequently from> 1/1000 to <1/100; rarely from> 1/10000 to <1/1000; very rarely <1/10000, including individual messages; the frequency is unknown - it is not possible to establish the frequency of occurrence from the available data.

    From the central nervous system:

    often - headache, dizziness, drowsiness, imbalance;

    infrequent - gait disturbance, confusion, hallucinations (hallucinations were observed, mainly, in patients with dementia of the Alzheimer's type of severe degree);

    very rarely - convulsions;

    frequency unknown - psychotic reactions, impaired consciousness, increased excitability, depression, anxiety, suicidal thoughts, increased intracranial pressure, muscle hypertonia.

    From the side of the cardiovascular system:

    often - increased blood pressure;

    infrequently - venous thrombosis / thromboembolism, heart failure.

    From the digestive system:

    often constipation;

    infrequently - nausea, vomiting;

    frequency unknown - pancreatitis, hepatitis.

    From the respiratory system:

    often - shortness of breath.

    From the genitourinary system:

    frequency unknown - acute renal failure, cystitis, increased libido.

    Allergic reactions:

    often - hypersensitivity to the components of the drug;

    frequency is unknown - allergic reactions, Stevens-Johnson syndrome.

    From the skin:

    frequency unknown - thrombocytopenic purpura.

    Laboratory indicators:

    often - increased activity of "liver" enzymes;

    frequency unknown - agranulocytosis, leukopenia (including neutropenia), pancytopenia, thrombocytopenia.

    Other:

    infrequently - increased fatigue;

    rarely fungal infections; frequency unknown - candidiasis.

    Overdose:

    There are limited data on overdose, obtained during clinical trials and post-registration surveillance.

    Symptoms

    Overdosing with relatively large doses of memantine (200 mg once, or 105 mg per day for 3 days) is expressed by symptoms of fatigue, weakness and / or diarrhea or the absence of symptoms. An overdose of a single or unknown amount of memantine when administered to a single dose of 140 mg of memantine is expressed by symptoms associated with the central nervous system (confusion, drowsiness, dizziness, vertigo, anxiety, agitation, hallucinations, gait disturbance) and / or gastrointestinal disturbances (vomiting, diarrhea ).

    In the most serious cases of overdose, the patient survived after taking more than 2000 mg of memantine with adverse effects from the nervous system (coma for 10 days, later diplopia, agitation).The patient received symptomatic therapy and plasmapheresis, and recovered without consequences.

    Another described case of a serious overdose is 400 mg of memantine once. The patient recovered without consequences. There were undesirable phenomena from the nervous system: anxiety, psychosis, visual hallucinations, stupor, seizures, drowsiness, unconsciousness.

    Treatment

    Symptomatic therapy, gastric lavage, intake of adsorbents (activated charcoal), urine acidification, forced diuresis (if necessary). There is no specific antidote.

    Interaction:

    With the simultaneous use of memantine with preparations of levodopa, dopamine receptor agonists, anticholinergic agents, their effect may be enhanced.

    With the simultaneous use of memantine with barbiturates, neuroleptics, their effect may decrease.

    With the simultaneous use of memantine with dantrolene or baclofen, as well as with antispasmodics, their action may vary (increase or decrease), so the doses of the drugs should be selected individually.

    Simultaneous use of memantine with amantadine should be avoided because of the risk of developing psychosis.Both compounds are antagonists NMDAreceptors.

    The risk of developing psychosis is also increased with simultaneous use of memantine with phenytoin, ketamine and dextromethorphan.

    With the simultaneous use of memantine with cimetidine, ranitidine, procainamide, quinidine, quinine and nicotine, the risk of increasing memantine concentration in the blood plasma increases.

    With the simultaneous use of memantine with hydrochlorothiazide, a decrease in the concentration of hydrochlorothiazide in the blood plasma is possible due to an increase in its excretion from the body.

    It is possible to increase the international standardized ratio (INR) in patients taking concomitantly oral indirect anticoagulants (warfarin). It is recommended to regularly monitor prothrombin time or INR in patients taking concomitantly indirect anticoagulants.

    Simultaneous use of memantine with antidepressants, selective serotonin reuptake inhibitors and monoamine oxidase inhibitors requires close monitoring of patients.

    According to the results of pharmacokinetic studies,in young healthy volunteers with single simultaneous administration of memantine with glibenclamide / metformin or donepezil the effects of drug interaction were not revealed.

    Clinical studies also did not reveal the effect of memantine on the pharmacokinetics of galantamine in young healthy volunteers.

    In studies in vitro memantine did not inhibit isoenzymes CYP 1A2, 2A6, 2C9, 2D6, 2E1, 3A, monooxygenase containing flavin, epoxide hydrolase, and also sulfation.

    Special instructions:

    With an alkaline urine reaction, patients need more careful monitoring of such patients because of the slower release of memantine. Factors that cause an increase in the pH of urine include: sudden changes in diet, for example, replacing a diet rich in meat dishes for vegetarian or intensive use of alkaline gastric buffers. In addition, urine pH may increase due to renal tubular acidosis or a severe urinary tract infection caused by bacteria of the genus Proteus.

    Data on the use of memantine in patients with a history of myocardial infarction, chronic heart failure (III-IV functional class by classification NYHA) or uncontrolled arterial hypertension are limited, therefore careful medical supervision of such patients is necessary.

    Use with caution in patients with thyrotoxicosis, epilepsy, seizures (including history) and predisposition to epilepsy.

    The simultaneous use of memantine and antagonists should be avoided NMDA-receptors, such as amantadine, ketamine and dextromethorphan. These compounds act on the same receptor system as memantine, and therefore, adverse reactions (mainly from the central nervous system) can occur more often and be more pronounced.

    A drug Memantine contains lactose monohydrate. Patients with hereditary intolerance to galactose, lactase deficiency, or glucose-galactose malabsorption should not take the drug Memantine.

    Effect on the ability to drive transp. cf. and fur:

    In patients with Alzheimer's dementia of moderate to severe severity, the ability to drive vehicles and manage complex mechanisms is usually impaired. Besides, memantine can cause a change in reaction rate,so patients need to refrain from driving or working with complex machinery.

    Form release / dosage:

    Tablets, film-coated, 10 mg and 20 mg.

    Packaging:

    10, 15 or 30 tablets in a contoured cell pack of a polyvinyl chloride film and aluminum foil.

    30 tablets in a can of high-density polyethylene.

    3, 6 or 9 contiguous cell packs of 10 tablets, 2, 4 or 6 contiguous cell packs of 15 tablets, 1, 2 or 3 contourcell packs of 30 tablets or one pot together with instructions for use in a pack of cardboard.

    Storage conditions:

    Store in a dark place at a temperature of no higher than 25 ° C.

    Keep out of the reach of children.

    Shelf life:

    3 years.

    Do not use after expiry date.

    Terms of leave from pharmacies:On prescription
    Registration number:LP-003419
    Date of registration:20.01.2016
    Expiration Date:20.01.2021
    The owner of the registration certificate:VERTEKS, AO VERTEKS, AO Russia
    Manufacturer: & nbsp
    Representation: & nbspVERTEKS CJSC VERTEKS CJSC Russia
    Information update date: & nbsp23.04.2018
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