Memantinol tablets p / o 10mg, No. 30

Dementia of moderate to severe severity in Alzheimer's disease.

Dose titration :

In order to reduce the risk of adverse reactions, the dose of the drug is titrated by gradually increasing it by 5 mg every week for the first three weeks:

1st week of therapy (days 1-7) - dose 5 mg / day;

2nd week of therapy (days 8-14) - dose 10 mg / day;

3rd week of therapy (days 15-21) - dose 15 mg / day;

Starting from the 4th week - a dose of 20 mg / day.

The maximum daily dose is 20 mg / day.

The recommended maintenance dose is 20 mg / day.

Elderly patients (over 65 years old)

No dose adjustment is required.

Patients with impaired renal function

In patients with mild renal impairment (creatinine clearance 50-80 ml / min), dose adjustment is not required.

For patients with moderate renal impairment (creatinine clearance 30-49 ml / min), the recommended dose is 10 mg / day. If this dose is well tolerated for at least 7 days, the dose can be increased to 20 mg / day in accordance with the standard titration schedule.

In patients with severe renal insufficiency (creatinine clearance 5-29 ml / min), the daily dose is 10 mg.

Patients with impaired liver function

In patients with mild to moderate hepatic impairment (class A and class B on the Child-Pugh scale), dose adjustment is not required.

The drug is contraindicated in patients with severe hepatic impairment (class C on the Child-Pugh scale).

1 film-coated tablet contains:

Active ingredient: memantine hydrochloride - 10 mg.

Excipients: microcrystalline cellulose, croscarmellose sodium, colloidal silicon dioxide, magnesium stearate.

Shell composition : OpadrayЃ 03B25482 Pink (hypromellose, titanium dioxide E171, macrogol 400, iron dye red oxide E172, iron dye yellow oxide E172).

Individual hypersensitivity to the components of the drug; pregnancy and the period of breastfeeding; age up to 18 years (efficacy and safety have not been established) severe hepatic impairment (class C on the Child-Pugh scale).

Carefully:

It is prescribed with caution to patients with thyrotoxicosis, epilepsy, a predisposition to the development of seizures (including a history); with the simultaneous use of NMDA receptor antagonists (amantadine ketamine dextromethorphan) the presence of factors that increase the pH of urine (a sharp change in diet for example, switching to vegetarianism, an abundant intake of alkaline gastric buffers) renal tubular acidosis severe urinary tract infections caused by bacteria of the genus Proteus myocardial infarction (in history) uncontrolled arterial hypertension, renal failure, mild or moderate hepatic failure (class A and B according to the Child-Pugh classification).

Trade name of the drug

MemantinolЃ

International non-proprietary name

Memantine

Dosage form

film-coated tablets

Composition

1 film-coated tablet contains:

Active ingredient: memantine hydrochloride - 10 mg.

Excipients: microcrystalline cellulose, croscarmellose sodium, colloidal silicon dioxide, magnesium stearate.

Shell composition : OpadrayЃ 03B25482 Pink (hypromellose, titanium dioxide E171, macrogol 400, iron dye red oxide E172, iron dye yellow oxide E172).

Description

Tablets from pink to brownish-pink, oval, film-coated, engraved with '20' on one side and 'MEM' on the other. In cross section, the core of the tablets is white or almost white.

Pharmacotherapeutic group

Dementia cure

ATX code

N06DX01

Pharmacodynamics:

Disruption of glutamatergic neurotransmission, especially the function of NMDA receptors, contributes to both the manifestation of symptoms and the progression of neurodegenerative dementia.

Memantine is a voltage-gated moderately affinity non-competitive inhibitor of NMDA receptors and has a modulating effect on the glutamatergic system.

Improves cognitive processes and increases daily activity.

Pharmacokinetics:

Absorption : after oral administration, it is rapidly and completely absorbed from the gastrointestinal tract. The absolute bioavailability is about 100%. The maximum concentration (Cmax) in blood plasma is reached within 3-8 hours. Food intake does not affect the absorption of memantine.

Distribution : when taking a daily dose of 20 mg, a constant concentration of memantine in blood plasma is created in the range of 70-150 ng / ml (05-1 ?mol) with pronounced individual variations. When using daily doses from 5 to 30 mg, the average ratio of the drug content in the cerebrospinal fluid to the content in the serum was 052. The volume of distribution is 10 l / kg. About 45% of memantine binds to blood plasma proteins.

Metabolism : about 80% of ingested memantine is excreted unchanged. The main metabolites in humans are N-35-dimethylgludantane, a mixture of isomers of 4- and 6-hydroxymemantine and 1-nitroso-35-dimethyladamantane. None of these metabolites have NMDA antagonistic activity.

In in vitro studies, the participation of isoenzymes of the cytochrome P450 system in the metabolism of memantine was not revealed.

In the study, when ingestion of labeled 14C-memantine, about 84% of the dose was excreted within 20 days, more than 99% was excreted by the kidneys.

Excretion : the elimination of memantine is monoexponential in nature with a half-life (T1 / 2) of 60 to 100 hours. The total clearance is 170 ml / min / 173 m2, while part of the total renal clearance is achieved by tubular secretion.

Also in the kidneys there is a process of tubular reabsorption, probably mediated by proteins involved in the transport of cations. The rate of renal clearance of memantine can be reduced when urine alkalizes to pH 7-9. Alkalization of urine can be the result of drastic changes in diet, such as a switch to a vegetarian diet or heavy intake of alkaline gastric buffers.

Linearity : Studies in volunteers have demonstrated linear pharmacokinetics over a dose range of 10 to 40 mg.

The relationship between pharmacokinetics and pharmacodynamics: when using memantine at a dose of 20 mg per day, the content of the drug in the cerebrospinal fluid corresponds to the ki value (inhibition constant) of memantine, which is 05 ?mol of the drug in the frontal lobe of the cerebral cortex.

Indications:

Dementia of moderate to severe severity in Alzheimer's disease.

Contraindications:

Individual hypersensitivity to the components of the drug; pregnancy and the period of breastfeeding; age up to 18 years (efficacy and safety have not been established) severe hepatic impairment (class C on the Child-Pugh scale).

Carefully:

It is prescribed with caution to patients with thyrotoxicosis, epilepsy, a predisposition to the development of seizures (including a history); with the simultaneous use of NMDA receptor antagonists (amantadine ketamine dextromethorphan) the presence of factors that increase the pH of urine (a sharp change in diet for example, switching to vegetarianism, an abundant intake of alkaline gastric buffers) renal tubular acidosis severe urinary tract infections caused by bacteria of the genus Proteus myocardial infarction (in history) uncontrolled arterial hypertension, renal failure, mild or moderate hepatic failure (class A and B according to the Child-Pugh classification).

Pregnancy and lactation:

Pregnancy : the drug is contraindicated in pregnancy as there are no clinical data on the effect of memantine on the course of pregnancy. Studies conducted on animals indicate the possibility of the drug to cause intrauterine growth retardation when used in doses similar to those used in humans. Memantine should not be taken during pregnancy unless absolutely necessary.

Breastfeeding : there is no data on whether memantine is excreted in breast milk, however, given the lipophilic properties of the substance, this is likely therefore women taking memantine should refrain from breastfeeding.

Fertility : preclinical studies of male and female fertility have not revealed any adverse effects of memantine.

Method of administration and dosage:

Memantine treatment should be initiated and supervised by a physician experienced in diagnosing and treating dementia in Alzheimer's disease. The diagnosis should be made in accordance with current guidelines.

Treatment should only be initiated if the patient's caregiver regularly monitors the patient's intake of the drug.

The tolerance and dosage of memantine should be regularly reviewed, preferably within the first three months from the start of therapy. After this period, the clinical efficacy of memantine and the patient's tolerance to treatment should be regularly reviewed in accordance with current clinical guidelines.

Supportive treatment can be continued indefinitely if there is a positive effect of the therapy and the treatment is well tolerated.

In the absence of a positive therapeutic effect or patient intolerance to treatment, the possibility of discontinuing memantine should be considered.

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

Adults

Dose titration :

In order to reduce the risk of adverse reactions, the dose of the drug is titrated by gradually increasing it by 5 mg every week for the first three weeks:

1st week of therapy (days 1-7) - dose 5 mg / day;

2nd week of therapy (days 8-14) - dose 10 mg / day;

3rd week of therapy (days 15-21) - dose 15 mg / day;

Starting from the 4th week - a dose of 20 mg / day.

The maximum daily dose is 20 mg / day.

The recommended maintenance dose is 20 mg / day.

Elderly patients (over 65 years old)

No dose adjustment is required.

Patients with impaired renal function

In patients with mild renal impairment (creatinine clearance 50-80 ml / min), dose adjustment is not required.

For patients with moderate renal impairment (creatinine clearance 30-49 ml / min), the recommended dose is 10 mg / day. If this dose is well tolerated for at least 7 days, the dose can be increased to 20 mg / day in accordance with the standard titration schedule.

In patients with severe renal insufficiency (creatinine clearance 5-29 ml / min), the daily dose is 10 mg.

Patients with impaired liver function

In patients with mild to moderate hepatic impairment (class A and class B on the Child-Pugh scale), dose adjustment is not required.

The drug is contraindicated in patients with severe hepatic impairment (class C on the Child-Pugh scale).

Side effect

From the immune system: often - hypersensitivity reactions.

From the side of the psyche: often - drowsiness; infrequently - confusion, hallucinations (mainly observed in patients with Alzheimer's disease at the stage of severe dementia), the frequency is unknown - mental reactions.

From the nervous system: often - dizziness, imbalance; infrequently - gait disturbance; very rarely - convulsions.

From the side of the cardiovascular system: often - increased blood pressure; infrequently - heart failure, venous thrombosis and / or thromboembolism.

From the digestive system: often - constipation; infrequently - vomiting, nausea; frequency unknown - pancreatitis.

On the part of the liver and biliary tract: often - increased indices of 'hepatic' enzymes; frequency unknown - hepatitis.

From the hematopoietic system: the frequency is unknown - agranulocytosis, leukopenia (including neutropenia), pancytopenia, thrombocytopenia, thrombocytopenic purpura.

Others: often - headache, shortness of breath; infrequently - fungal infections, fatigue; frequency unknown - acute renal failure, Stevens-Johnson syndrome.

Overdose:

There are limited data on overdose obtained in the course of clinical studies and post-registration experience with the use of memantine.

Symptoms : With relatively large overdoses (200 mg once and 105 mg / day for 3 days), the following symptoms were observed: fatigue, weakness and / or diarrhea, or there were no symptoms. In cases of an overdose in a dose of less than 140 mg once or in the case of an unknown dose, patients experienced side reactions from the central nervous system: confusion of consciousness, hypersomnia, drowsiness, dizziness, agitation, aggression, hallucinations, gait disturbance and / or from the digestive system: vomiting, diarrhea.

In the most severe case of an overdose (2000 mg memantine), the patient survived, while he had side reactions from the central nervous system (coma for 10 days, then diplopia and agitation).

After symptomatic treatment and plasmapheresis, he recovered without further complications.

In another case of severe overdose, the patient survived and recovered after taking memantine 400 mg once. The patient had side reactions from the central nervous system: anxiety, psychosis, visual hallucinations, decreased threshold of convulsive readiness, drowsiness, stupor, and loss of consciousness.

Treatment : in case of overdose, treatment is symptomatic.

There is no specific antidote. It is necessary to carry out standard therapeutic measures aimed at removing the substance from the body, such as gastric lavage; intake of activated carbon; acidification of urine; it is possible to carry out forced diuresis. When signs and symptoms of general hyperstimulation of the central nervous system appear, symptomatic therapy should be carried out with caution.

Interaction:

Given the pharmacological action and mechanism of action of memantine, the following interactions are possible:

With simultaneous use with drugs levodopa antagonists of dopamine receptors m-anticholinergic blockers, the effect of the latter may increase.

When used simultaneously with barbiturates or antipsychotics, the effect of the latter may decrease.

The simultaneous use of memantine with the antispasmodics dantrolene or baclofen can change their effect and require an individual dose selection.

Simultaneous administration of memantine with amantadine should be avoided due to the risk of developing pharmacotoxic psychosis. Both substances are chemically related NMDA antagonists. The same is true for ketamine and dextromethorphan. The literature also describes a case of a similar risk of combined use of memantine and phenytoin.

It is possible to increase the plasma concentration of cimetidine ranitidine procainamide quinidine quinine and nicotine while taking it with memantine.

There is a possibility of a decrease in the level of hydrochlorothiazide in the blood serum while taking it with memantine or any combination containing hydrochlorothiazide. Memantine can increase the excretion of hydrochlorothiazide.

¬озможно повышение международного нормализованного отношени¤ (ћЌќ) у пациентов одновременно принимающих пероральные антикоагул¤нты (варфарин). Ќесмотр¤ на то что причинно-следственной св¤зи установлено не было у пациентов одновременно принимающих пероральные антикоагул¤нты рекомендуетс¤ проводить тщательный контроль протромбинового времени или ћЌќ.

ќдновременное применение с антидепрессантами селективными ингибиторами обратного захвата серотонина и ингибиторами моноаминооксидазы требует тщательного наблюдени¤ за пациентами.

‘армакокинетическое взаимодействие мемантина с глибенкламидом метформином или донепезилом отсутствует.

Ќе вы¤влено никакого значимого вли¤ни¤ мемантина на фармакокинетику галантамина.

ћемантин не ингибирует активность изоферментов CYP 1ј2 2ј6 2—9 2D6 2?1 3ј флавинмонооксигеназы эпоксидгидролазы и сульфатирование in vitro.

ќсобые указани¤:

ќптимальна¤ доза достигаетс¤ постепенно при увеличении дозы каждую неделю.

” пациентов с эпилепсией судорогами в анамнезе или у пациентов с предрасположенностью к эпилепсии мемантин следует примен¤ть с осторожностью.

—ледует избегать совместного применени¤ мемантина с антагонистами NMDA-рецепторов каких как амантадин кетамин или декстрометорфан. Ёти соединени¤ воздействуют на ту же систему рецепторов что и мемантин поэтому нежелательные реакции (в основном св¤занные с центральной нервной системой) могут возникать чаще и быть выраженными.

ѕрисутствие р¤да факторов которые могут повысить уровень pH мочи у пациентов требует тщательного медицинского наблюдени¤.   ним относ¤тс¤: резкие изменени¤ в диете например переход от м¤сной диеты к вегетарианской или большое потребление щелочных желудочных буферных растворов. “акже к повышению pH мочи могут привести почечный тубул¤рный ацидоз или т¤желые инфекции мочевывод¤щих путей вызванные Proteus spp. ”слови¤ которые повышают pH мочи могут снизить выведение мемантина мочевыделительной системой что приведет к увеличению концентрации мемантина в плазме.

»з большинства клинических исследований исключались пациенты с инфарктом миокарда в анамнезе декомпенсированной хронической сердечной недостаточностью (III-IV функциональный класс NYHA) или неконтролируемой артериальной гипертензией. ѕоэтому данные о применении мемантина у таких пациентов ограничены и прием препарата ћемантинолЃ должен осуществл¤тьс¤ под тщательным контролем врача.

¬озраст большинства людей с болезнью јльцгеймера 65 лет и старше. ¬ клинических исследовани¤х мемантина средний возраст пациентов составил около 76 лет: более 90% пациентов были в возрасте 65 лет и старше 60% были в возрасте 75 лет и старше а 12% были в возрасте старше 85 лет.  линически значимые различи¤ большинства неблагопри¤тных событий отсутствовали по группам пациентов ? 65 лет и < 65 лет.

Ќе требуетс¤ регулировать дозу у пациентов с легкой и умеренной почечной недостаточностью. ”меньшение дозы рекомендуетс¤ у пациентов с т¤желой почечной недостаточностью.

Ќе требуетс¤ регулировать дозу у пациентов с легкой или умеренной печеночной недостаточностью (класс ј или ¬ классификации „айлд-ѕью).

¬ли¤ние на способность управл¤ть трансп. ср. и мех.:

” пациентов с болезнью јльцгеймера на стадии умеренной и т¤желой деменции обычно нарушена способность к вождению автотранспорта и управлению сложными механизмами.  роме того мемантин может вызывать изменение скорости психомоторной реакции поэтому пациентам необходимо воздержатьс¤ от управлени¤ автотранспортом или работы со сложными механизмами.

‘орма выпуска/дозировка:

“аблетки покрытые пленочной оболочкой 20 мг.

”паковка:

On 10 tablets in a blister strip packaging from a film of polyvinyl chloride and printed aluminum foil varnished.

3 or 6 blisters, together with instructions for use, are placed in a cardboard box.

Storage conditions:

Store in a dark place at a temperature not exceeding 25 ? C. Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date indicated on the package.

Vacation conditions

On prescription