Memantine Canon - instructions for use, dose, side effects, contraindications

Excipients: calcium hydrophosphate dihydrate 24.3 mg, silicon dioxide colloid 2 mg, croscarmellose sodium 2.8 mg, lactose monohydrate 61.6 mg, magnesium stearate 0.7 mg, povidone K-30 3.6 mg;

film sheath: Fill 3 mg, including: hypromellose (hydroxypropylmethylcellulose) 1.0125 mg, giprolose (hydroxypropyl cellulose) 1.0125 mg, talc 0.6 mg, titanium dioxide 0.375 mg.

Dosage of 10 mg

1 tablet, film-coated, 10 mg contains:

active substance: memantine hydrochloride 10 mg;

Excipients: calcium hydrophosphate dihydrate 50.4 mg, silicon dioxide colloid 3 mg, croscarmellose sodium 3 mg, lactose monohydrate 136 mg, magnesium stearate 1.6 mg, povidone K-30 6 mg;

film sheath: Fill 6 mg, including: hypromellose (hydroxypropylmethylcellulose) 2,025 mg, giprolose (hydroxypropylcellulose) 2,025 mg, talc 1.2 mg, titanium dioxide 0.6984 mg, colorless diamond blue 0.048 mg, iron oxide black dye 0.0036 mg.

Dosage of 15 mg

1 tablet, film-coated, 15 mg contains:

active substance: memantine hydrochloride 15 mg;

Excipients: calcium hydrophosphate dihydrate 45.5 mg, silicon dioxide colloid 4.2 mg, croscarmellose sodium 6 mg, lactose monohydrate 130.3 mg, magnesium stearate 1.5 mg, povidone K-30 7.5 mg;

film sheath: Fill 6 mg, including: hypromellose (hydroxypropylmethylcellulose) 2,025 mg, giprolose (hydroxypropyl cellulose) 2,025 mg, talc 1.2 mg, titanium dioxide 0.75 mg.

Dosage of 20 mg

1 tablet, film-coated, 20 mg contains:

active substance: memantine hydrochloride 20 mg;

Excipients: calcium hydrophosphate dihydrate 55 mg, silicon dioxide colloid 5.2 mg, croscarmellose sodium 7.5 mg, lactose monohydrate 161.1 mg, magnesium stearate 1.8 mg, povidone K-30 9.4 mg;

film sheath: Defect 8 mg, including: hypromellose (hydroxypropylmethylcellulose) 2,7 mg, giprolase (hydroxypropylcellulose) 2.7 mg, talc 1.6 mg, titanium dioxide 1 mg.

Description:

Tablets are round, biconvex, covered with a film coat of white or almost white color (dosages of 5 mg, 15 mg and 20 mg); blue color (dosage of 10 mg). The cross section is almost white.

Pharmacotherapeutic group:Dementia remedy

ATX: & nbsp

N.06.D.X.01 Memantine

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

Pharmacodynamics:

Memantine is a potential-dependent non-competitive blocker NMDA-receptors with moderate affinity to them. Memantine blocks the effects of glutamate, which in pathologically elevated concentrations can lead to neuronal dysfunction.

Pharmacokinetics:

Suction: memantine quickly and completely absorbed from the gastrointestinal tract (GIT), has an absolute bioavailability of about 100%. Eating does not affect absorption. The mean time to reach the maximum concentration in the blood plasma (T_mOh) is from 3 to 8 hours. With normal renal function, no cumulation of memantine was observed.

Distribution: a daily dose of 20 mg creates a constant concentration of memantine in the blood plasma within 70-150 ng / ml (0.5-1 mmol) with large individual variations. The volume of distribution of memantine is 10 l / kg. About 45% of memantine binds to blood plasma proteins.

Metabolism: About 80% of memantine is excreted unchanged. The main metabolites in humans are N-3,5-dimethylgludantan, a mixture of isomers 4- and 6-hydroxymemanthine and 1-nitroso-3,5-dimethyl-adamantane. None of these metabolites has pharmacological activity. In studies in vitro metabolism, catalyzed by cytochrome P-450, was not detected.

Excretion: In studies in which ¹⁴C-memantine was taken internally, on average 84% of the dose taken inside was withdrawn within 20 days, with more than 99% excreted by the kidneys. Memantine is excreted from the body by the kidneys monoexpensively. The half-life (T_1/2) is 60-100 hours. It is excreted by the kidneys.

In patients 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 (ki), 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 the active substance or any of the components of the drug;

- severe hepatic insufficiency (class C on the Child-Pugh scale);

- congenital galactose intolerance, lactose deficiency or glucose / galactose absorption disorder;

- pregnancy;

- the period of breastfeeding;

- children under 18 years of age (efficacy and safety not established).

Carefully:

- Epilepsy, a history of convulsive syndrome;

- a history of myocardial infarction;

- heart failure (III-IV Classes by classification NYHA);

- uncontrolled arterial hypertension;

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

- factors that increase the pH of urine (a dramatic change in diet (the transition from meat to vegetarian), copious intake of alkaline gastric buffers, renal tubular acidosis, or severe urinary tract infections caused by Proteus spp.);

- kidney failure;

- liver failure.

Pregnancy and lactation:

In connection with the lack of clinical data on the effect of memantine on the course of pregnancy, the drug Memantine Canon is contraindicated in pregnancy.

Studies conducted on animals indicate the possibility of memantine to cause a delay in intrauterine development 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.

There is no data on the isolation of memantine in breast milk. Taking into account the lipophilic structure of memantine, it can be assumed that it can penetrate into breast milk, so during the intake of Memantine canon breastfeeding should be discontinued.

Clinical data on the effect on fertility are not available.

Dosing and Administration:

Therapy should be carried out under the supervision of a physician experienced in the diagnosis and treatment of dementia in Alzheimer's disease. Therapy should be started if the patient (or a person who is constantly caring for the patient) is ready to regularly monitor the intake of the drug. The diagnosis should be made in accordance with the current recommendations.

The tolerability and dose of Memantine canon should be evaluated on a regular basis, preferably within three months after initiation of therapy. Then, the clinical efficacy of the drug and the tolerability of therapy should be regularly assessed in accordance with current clinical guidelines.

Supportive therapy can be continued indefinitely for the presence of a positive effect and a good tolerability of the drug Memantine Canon. The drug should be discontinued if a positive therapeutic effect is no longer observed or if the patient does not tolerate therapy.

The drug should be administered orally, once a day, at the same time, without chewing, squeezed with enough liquid, regardless of food intake. The maximum daily dose is 20 mg.

The dosage regimen is set individually. It is recommended to begin treatment with the appointment of minimally effective doses. To reduce the risk of unwanted side effects, the constant dose adjustment is performed by increasing titration at 5 mg per week for the first three weeks as follows:

1-I week (days 1-7): one tablet of 5 mg every day for seven days.

2-I week (days 8-14): one tablet of 10 mg every day for seven days.

3-I week (days 15-21): one tablet of 15 mg every day for seven days.

Starting from the 4th week: one tablet of 20 mg every day.

Use in selected patient groups

Elderly patients

For patients older than 65 years, the recommended dose is 20 mg per day.

Patients with impaired renal function

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

In patients with moderate renal impairment (creatinine clearance 30-49 ml / min) the dose of the drug should be 10 mg per day. If this dose is well tolerated for at least 7 days of treatment, then it can be increased to 20 mg per day in accordance with the standard dosage regimen.

In patients with severe renal dysfunction (creatinine clearance 5-29 ml / min), the dose of the drug should not exceed 10 mg per day.

Patients with impaired hepatic function

Patients with mild or moderate hepatic impairment (classes A and B according to the Child-Pugh classification) dose adjustment is not required.

In patients with severe hepatic insufficiency (class C on the Child-Pugh scale), the use of the drug Memantine Canon is contraindicated.

Side effects:

In double-blind, placebo-controlled trials involving patients with dementia who received "Namenda" (memantine) and placebo (940 and 922 patients, respectively), the most common adverse reactions (with a frequency of ≥ 5% and higher than in the placebo group) in patients receiving "Namenda"There was dizziness, headache, confusion and constipation.

The overall profile of adverse reactions and their frequencies for individual adverse reactions in a subpopulation of patients with moderate to severe Alzheimer's disease did not differ from those of the profile and frequency described above for dementia in general.

Below are presented the undesirable reactions, obtained both during the conducted researches, and from spontaneous reports.

WHO classification of the incidence of adverse reactions:

very often - ≥1/10 appointments (> 10%)

often from ≥1 / 100 to <1/10 of appointments (> 1% and <10%)

infrequently - from ≥1 / 1000 to <1/100 of prescriptions (> 0.1% and <1%)

rarely from ≥1 / 10000 to <1/1000 appointments (> 0.01% and <0.1%)

very rarely - <1/10000 prescriptions (<0.01%)

frequency is unknown - but it is not possible to establish the frequency of occurrence of available data.

Infectious and parasitic diseases

Infrequently: fungal infections.

Frequency unknown: Candidiasis.

Violations of the blood and lymphatic system

The frequency is unknown: agranulocytosis, leukopenia (including neutropenia), pancytopenia, thrombocytopenia.

Immune system disorders

Often: hypersensitivity to the components of the drug.

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

Disorders of the psyche

Infrequently: hallucinations (observed mainly in patients with severe Alzheimer's disease).

The frequency is unknown: psychotic reactions, increased excitability, depression, anxiety, suicidal thoughts.

Disturbances from the nervous system

Often: headache, dizziness, drowsiness, imbalance.

Infrequently: confusion, violation of gait.

Very rarely: seizures, epileptic seizures.

The frequency is unknown: impaired consciousness, increased intracranial pressure, muscle hypertonia.

Heart Disease

Infrequent: heart failure, heart defects.

Vascular disorders

Often: increased blood pressure.

Infrequent: venous thrombosis and / or thromboembolism.

Disturbances from the respiratory system, organs of the chest and the mediastinum

Often: shortness of breath.

Disorders from the gastrointestinal tract

Often: constipation.

Infrequent: nausea, vomiting.

Frequency unknown: pancreatitis.

Disturbances from the liver and bile ducts

Often: impaired functional liver tests.

Frequency unknown: hepatitis.

Disturbances from the skin and subcutaneous tissues

Frequency unknown: thrombocytopenic purpura.

Disorders from the kidneys and urinary tract

The frequency is unknown: cystitis, acute renal failure.

Violations of the genitals and mammary gland

Frequency is unknown: increased libido.

General disorders and disorders at the site of administration

Infrequent: fatigue, general weakness.

Laboratory and instrumental data

Often: increased activity of "liver" enzymes.

In Alzheimer's disease, depression, suicidal thoughts and suicide cases were recorded in post-marketing studies.

Overdose:

Symptoms

In cases of an overdose in a dose of less than 140 mg once, or in the case of taking an unknown dose, patients experienced side reactions from the central nervous system: confusion, hypersomnia, drowsiness, dizziness, agitation, hallucinations, gait disturbance; as well as violations of the cardiovascular system: vomiting, diarrhea.

With relatively large overdoses (200 mg once and 105 mg / day for 3 days), the following symptoms were noted: fatigue, weakness and / or diarrhea or symptoms were absent.

In the worst case of overdose, the patient survived after taking a dose of 2000 mg memantine, he had adverse reactions from the central nervous system (coma for 10 days, then diplopia and agitation). The patient received symptomatic treatment and plasmapheresis. The patient recovered without further complications.

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

Treatment

There is no specific antidote for memantine intoxication.It is necessary to carry out standard measures aimed at removing the drug from the body: washing the stomach, taking activated charcoal, carrying out forced diuresis, increasing the acidity of urine.

Interaction:

Levodopa, dopamine receptor agonists and m-holinoblocking agents. With the simultaneous use of memantine with levodopa preparations, dopamine receptor antagonists, m-holinoblockers, the effect of the latter may be enhanced, as well as with simultaneous use with other NMDA receptor antagonists.

Barbiturates and antipsychotics. With simultaneous use with barbiturates, neuroleptics, the effect of the latter may decrease. When combined, the effect of dantrolene or baclofen can be altered (enhanced or decreased), so the doses of the drugs should be selected individually.

Amantadine, ketamine, dextromethorphan. Simultaneous application with amantadine, ketamine, phenytoin and dextromethorphan should be avoided because of the increased risk of developing psychosis. These drugs are chemically bound antagonists NMDAreceptors.

Phenytoin. The joint use of memantine with phenytoin should be avoided.

Cimetidine, ranitidine, procainamide, quinidine, quinine, nicotine. Possible increase in plasma concentrations of cimetidine, ranitidine, procainamide, quinidine, quinine and nicotine while taking with memantine due to the use of the same renal cationic transport system.

Hydrochlorothiazide. It is possible to reduce the concentration of hydrochlorothiazide or any combination with hydrochlorothiazide when taken concomitantly with memantine.

Indirect anticoagulants. It is possible to increase the international standardized ratio (INR) in patients taking indirect anticoagulants (warfarin). Despite the absence of a cause-effect relationship, careful monitoring of prothrombin time and INR in patients simultaneously taking warfarin and memantine.

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

Lack of interactions. In pharmacokinetic studies of a single administration of memantine, no interactions of memantine with glibenclamide or metformin or donepezil or galantamineit was not revealed. Memantine does not inhibit isoenzymes CYP1A2, CYP2A6, CYP2C9, CYP2D6, CYP2E1, CYP3A, flavin-containing monooxidase, epoxyhydrolase or sulfation in vitro.

Special instructions:

It is recommended to be used with caution in patients with epilepsy, history of seizures or in patients with a predisposition to epilepsy.

It should avoid the appointment of memantine along with other antagonists NMDA-receptors (amantadine, ketamine, dextromethorphan), since unwanted reactions can occur more often and more intensively, mainly at the CNS level.

The presence of factors influencing the pH of the urine (abrupt changes in diet, for example, the transition from a diet that includes animal products to a vegetarian diet, or intensive consumption of alkaline gastric buffers), as well as renal tubular acidosis or severe urinary tract infections, caused by Proteus spp., require careful monitoring of the patient's condition.

Of the majority of clinical studies, patients with a history of myocardial infarction decompensated by chronic heart failure (III-IV functional class by classification NYHA) or uncontrolled hypertension were excluded. Therefore, data on the use of memantine in these patients are limited, the drug should be taken under close medical supervision.

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

In patients with Alzheimer's disease, the ability to drive vehicles and manage complex mechanisms is usually impaired in the stage of moderate and severe dementia. In addition, the Memantine Canon product can cause a change in the reaction rate. Therefore, patients need to refrain from managing motor vehicles and working with complex mechanisms.

Form release / dosage:

Tablets, film-coated, a set of tablets: 5 mg, 10 mg, 15 mg and 20 mg.

Packaging:

For 7 tablets with a dosage of 5 mg; 7 tablets each with a dosage of 10 mg; 7 tablets with a dosage of 15 mg; 7 tablets with a dosage of 20 mg in a contour cell packaging made of a polyvinylchloride film and aluminum foil printed lacquered.

4 contour cellular packs (1 circuit pack of tablets of each dosage) together with instructions for use are placed in a pack of cardboard.

Storage conditions:

At a temperature of no higher than 25 ° C, in the manufacturer's packaging.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-004067

Date of registration:10.01.2017

Expiration Date:10.01.2022

The owner of the registration certificate:CANONFARMA PRODUCTION, CJSC CANONFARMA PRODUCTION, CJSC Russia

Manufacturer: & nbsp

CANONFARMA PRODUCTION, CJSC Russia

Representation: & nbspCANONFARMA PRODUCTION CJSC CANONFARMA PRODUCTION CJSC Russia

Information update date: & nbsp29.01.2017

Illustrated instructions

Instructions

Memantine Canon (Memantin Canon)