Mémicare - instructions for use, dose, side effects, contraindications

Name of substance	No. mg / tablet	Compliance
Active substance
Memantine hydrochloride	10,00	Company ND
Excipients:
Lactose Monohydrate	206,00	USP NF
Corn starch	16,00	USP NF
Povidone (PVP K-30)	8,00	USP
Silica colloidal dioxide	1,20	USP NF
Talc	6,80	USP
Magnesium stearate	2,00	USP NF
Shell
Fault gray 03B17618 **	-6,75	Company Standard

** Composition: hypromellose (6sR) 60.00% USP NF, EP, JP; titanium dioxide 31.80% USP NF, EP, JP; macrogol 400 8.00% USP NP, EP, JP; dye iron black oxide (E 172) / 0.20 % JPE.

Description:From gray to light gray, oblong, biconvex tablets, resembling "8", covered with a film membrane, with a dividing risk on both sides.

Pharmacotherapeutic group:Miorelaxant of central action

ATX: & nbsp

N.06.D.X.01 Memantine

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

Pharmacodynamics:

Mechanism of action

Obviously, disrupting the operation of glutamatergic neurotransmission, in particular N-methyl-D-aspartate (NMDA) -receptors, contributes both to the beginning of the expression of symptoms and to the progression of the disease of neurodegenerative dementia.

Memantine is a potential-dependent, non-competitive NMDA receptor antagonist with moderate affinity for them. It modulates the effect of pathologically tinted glutamate, which can lead to neuronal dysfunction.

Pharmacokinetics:

Suction

Memantine - has an absolute bioavailability of about 100%. The mean time to reach the maximum plasma concentration (T_max) is from 3 to 8 hours. There are no data on the effect of food on the absorption of memantine.

Distribution

A daily dose of 20 mg creates a constant concentration of memantine in the blood plasma in the range of 70-150 ng / ml (0.5-1 mmol) with large individual variations. With the appointment of a daily dose of 5-30 mg, the ratio of the mean concentration in the cerebrospinal fluid to the plasma concentration equal to 0.52 was calculated.The volume of distribution is about 10 l / kg. About 45% of memantine binds to blood plasma proteins.

Metabolism

In the body, about 80% of circulating memantine-related compounds are present in the form of the ancestors of the class. The main metabolites: N-3,5-dimethyl-glutanate, isomer mixture of 4- and 6-hydroxy-memantine and 1-nitroso-3,5-dimethyl-adamantane. None of these metabolites shows activity against NMDA receptors. In laboratory conditions (in vitro), no metabolism was detected, catalyzed by cytochrome P450.

Excretion

Memantine is excreted monoexponentially with a half-life (t_1/2) 60-100 hours.

In healthy volunteers with normal renal function, total clearance (Cl_tot) is 170 ml / min / 1.73 m², and part of the total renal clearance is achieved through tubular secretion. Renal excretion also includes tubular reabsorption, possibly mediated by the cationic transport of proteins. The rate of renal clearance of memantine during alkalinization of urine (pH 7-9) can be reduced by 4-9 factors. The alkalinization of urine can be caused by a dramatic change in diet, for example, from meat to vegetarian, or from the massive intake of alkaline gastric buffers.

Indications:

Alzheimer's disease:

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

Contraindications:

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

- pregnancy and lactation;

- intolerance to galactose;

- deficiency of lactase;

- age to 18 years.

Carefully:

Epilepsy

Use with caution in patients with epilepsy, history of seizures, or in patients with a predisposition to epilepsy.

Combined use of NMDA receptor antagonists

The joint use of memantine and NMDA receptor antagonists should be avoided, such as amantadine, ketamine or dextromethorphan. These compounds act on the same receptor system as memantine, therefore, unwanted reactions (mainly associated with the central nervous system) can occur more often and be more pronounced.

Factors affecting the increase in the pH of urine

The presence of a number of factors that can increase the pH of the urine in patients requires careful monitoring of the patient. These include: sudden changes in diet, for example, the transition from a meat diet to a vegetarian diet, or a large intake of alkaline gastric buffers.Also, urinary pH can be increased by renal tubular acidosis or severe urinary tract infections caused by Proteus spp.

Patients with a history of myocardial infarction decompensated by chronic heart failure or uncontrolled hypertension

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

Lactose

The drug Mémicar contains lactose monohydrate. Patients with hereditary intolerance to galactose, lactase deficiency Lappa, or glucose-galactose malabsorption should not take Medikar.

Pregnancy and lactation:

Fertility

No relevant data.

Pregnancy

In each individual case, it is necessary to evaluate the possible risk to the fetus and the expected benefit to the mother. There are no clinical data obtained in pregnant women.Animal studies show the possibility of reducing intrauterine growth of the fetus at exposure levels that are identical or slightly higher than the effects on humans. The possible risk in humans is unknown.

Memantine should not be administered during pregnancy.

Breastfeeding period

Women receiving memantine, you should stop breastfeeding. No data, does it penetrate memantine in breast milk, but, taking into account the lipophilicity of the substance, excretion of it with breast milk is possible.

Dosing and Administration:

For oral administration.

Treatment should be prescribed and conducted under the supervision of a physician with experience in the diagnosis and treatment of Alzheimer's dementia dementia. Therapy should be started only if the person who provides regular patient care will monitor the patient taking the medication. The diagnosis should be made in accordance with the current recommendations. The tolerability and dose of the drug should be evaluated regularly, mainly within 3 months after the start of treatment.Then, the clinical efficacy of the drug and the tolerability of the treatment should be regularly assessed in accordance with current clinical guidelines. Supportive treatment can be continued indefinitely for a therapeutic effect and a good tolerability of the drug Mémicar. It should be considered the abolition of Medikar if the therapeutic effect is no longer observed or if the patient does not tolerate treatment.

The drug Mémicare is prescribed once a day, the drug should be taken at the same time every day, regardless of food intake.

Adults

The maximum daily dose is 20 mg. To reduce the risk of adverse reactions, selection of a maintenance dose is carried out by increasing titration at 5 mg per week for the first three weeks according to the following scheme.

Week 1 (days 1-7)

The recommended dose of Medikar is 5 mg per day for 7 days.

Week 2 (days 8-14)

The recommended dose of Medikar is 10 mg per day for 7 days.

Week 3 (days 15-21)

The recommended dose of Medikar is 15 mg per day for 7 days.

Starting from the 4th week

The recommended dose of Medikar is 20 mg per day.

Maintenance dose

The recommended maintenance dose of the drug Mémicare: 20 mg per day.

Special patient groups

Children

The drug Mémicar is contraindicated in children under 18 years of age because of insufficient data on safety and efficacy.

Elderly patients

Based on clinical data for the Nazis over 65, the recommended dose of the drug is 20 mg per day, as described above.

Patients with impaired renal function

In patients with mild violations of the function of the nights (clearance of creatinine 50-80 ml / min), dose adjustment is not required.

In patients with an average degree of impaired renal function (creatinine clearance 30-49 ml / min), the daily dose should be 10 mg per day. If this dose of chorone is tolerated for at least 7 days of treatment, then it may be increased to 20 mg per day in accordance with the standard titration scheme.

In patients with severe renal impairment (creatinine clearance 5-29 ml / min), the daily dose should be 10 mg per day.

Patients with impaired hepatic function

Patients with a severe degree of impaired hepatic function Medikar is not recommended.

There are no available data on the use of Mémicare in patients with severe liver function impairment.

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

Side effects:

In clinical studies of the treatment of dementia from mild to severe, comprising 1,784 patients who received memantine, and 1595 patients who received placebo, the overall incidence of adverse reactions with memantine ns was different from that with placebo; Unwanted reactions were mostly mild or moderate but severe. The most frequent adverse reactions that occurred more frequently in the memantine group than in the placebo group were dizziness (6.3% and 5.6%, respectively), headache (5.2% and 3.9%, respectively), constipation (4, 6% and 2.6%, respectively), drowsiness (3.4% and 2.2%, respectively) and hypertension (4.1% and 2.8%, respectively).

The undesirable reactions presented below are listed in accordance with the damage to organs and organ systems and frequency of occurrence. Frequency of occurrence is defined as follows: very often (≥1 / 10), often (≥1 / 100 and <1/10), infrequently (≥1 / 1,000 and <1/100), rarely (≥1 / 10,000 and <1/1000),very rarely (<1/10 000), is unknown (the frequency can not be estimated from the data available). Frequency categories were formed on the basis of clinical studies of the drug and post-registration surveillance.

Frequency of occurrence of undesirable reactions

Immune system disorders

Often: hypersensitivity to the drug.

Infectious or parasitic diseases

Infrequently: fungal infections.

Disorders of the psyche

Infrequently: confusion, hallucinations *.

Unknown: psychotic reactions **.

Disturbances from the nervous system

Often: dizziness, headache, drowsiness, imbalance.

Infrequent: a violation of gait.

Very rarely: convulsions.

Heart Disease

Infrequent: heart failure.

Vascular disorders

Often: arterial hypertension.

Infrequent: venous thrombosis and / or thromboembolism.

Disturbances from the respiratory system, chest and mediastinal organs

Often: shortness of breath.

Disorders from the gastrointestinal tract

Often: constipation.

Infrequently: vomiting.

Unknown: pancreatitis **.

Disturbances from the liver and bile ducts

Often: increased liver function.

Unknown: hepatitis.

General disorders and disorders at the site of administration

Uncommon: fatigue.

* Hallucinations were mainly observed in patients with severe Alzheimer's disease.

** Separate reports received in the period of astrasonic observation.

Concomitant Alzheimer's conditions are depression, suicidal thoughts and suicidal attempts. Post-registration studies reported on these reactions in patients who took memantine.

Overdose:

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

Symptoms

A relatively large overdose (200 mg (single dose) or 105 mg / day for 3 days) was manifested only by symptoms such as fatigue, weakness and / or diarrhea, or no symptoms. In patients with an overdose of <140 mg (single dose) or with an unknown dose, symptoms such as confusion, hypersomnia, drowsiness, vestibular dizziness, psychomotor agitation, aggression, hallucinations, gait disturbance, vomiting and diarrhea have been observed.

In the most serious case of an overdose, the patient survived after oral intake of a total of 2000 mg memantine. The effect of the drug on the central nervous system (coma for 10 days, and later diplopia and psychomotor agitation) was noted.

Symptomatic treatment and plasmapheresis were performed. The patient recovered without permanent consequences. In another case of an overdose, the patient also survived and recovered. The patient received 400 mg of memantine orally. The patient had symptoms of the central nervous system, such as anxiety, psychosis, drowsiness, stupor, unconsciousness, a tendency to develop seizures.

Treatment

In case of an overdose, symptomatic treatment is performed. There is no specific antidote used for intoxication or overdose. Use standard clinical procedures to remove the active substance, for example, taking activated charcoal (disrupts possible intestinal hepatic recirculation), urine acidification, forced diuresis. In the presence of signs and symptoms of general hyperstimulation of the central nervous system, a thorough symptomaticclinical treatment.

Interaction:

Levodopa, dopamine receptor agonists and m-cholinoblocking agents

Based on the mechanism of action, it is possible to assume a possible enhancement of the effect of levodopa, dopamine receptor agonists and m-cholinoblocking agents when used simultaneously with NMDA receptor antagonists, such as memantine.

Barbiturates and antipsychotics

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

Anticonvulsants, dantrolene, baclofen

The simultaneous use of memantine and anticonvulsants dantrolene or baclofen may alter their effect, so dose adjustment may be required.

Amantadine, ketamine, dextromethorphan

Simultaneous administration with amantadine, ketamine and dextromethorphan should be avoided because of the risk of pharmacotoxic psychosis. These drugs are chemically coupled NMDA receptor antagonists. Phenytoin

There is one published case of a possible risk with simultaneous use of memantine with phenytoin.

Cimetidine, ranitidine, procainamide, quinidine, quinine and nicotine Other active substances, such as cimetidine, ranitidine, procainamide, quinidine, quinine and nicotine, which use the same renal cationic transport system as amantadine, probably can interact with memantine, leading to a potential risk of an increase in the content of the substances calmed down in the blood plasma.

Hydrochlorothiazide

It is possible to reduce the concentration of hydrochlorothiazide (HCT) in the blood serum with simultaneous use of memantine and HCT or any combination with HCT.

Indirect anticoagulants

In post-marketing studies, individual cases of an increase in the international normalized ratio (INR, ratio of prothrombin time of patient plasma and prothrombin time of standard plasma adjusted for the activity of thromboplastin used) in patients simultaneously taking warfarin and memantine.

Despite the absence of a cause-effect relationship, careful monitoring of prothrombin time or INR in patients simultaneously taking memantine and indirect anticoagulants.

Lack of interactions

In pharmacokinetic studies of a single administration of memantine by young healthy volunteers, no interactions of the active substance memantine with glibenclamide or metformin or donepezil have been identified.

Clinical studies in young healthy volunteers did not reveal any effects of memantine on the pharmacokinetics of galatactin.

Memantine does not inhibit the isoenzymes CYPIA2, CYP2A6, CYP2C9, CYP2D6, CYP2E1, CYP3A, flavin-containing monooxygenase, epoxide hydrolase or in vitro sulphation.

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

Alzheimer's disease in the middle or severe degree usually causes frustration in the ability to drive vehicles and mechanisms.

Moreover, the use of memantine can have an effect, from minimal to moderate, on the ability to drive vehicles and mechanisms. Therefore, outpatient patients should be warned and especially attentive to this type of activity.

It is not recommended to carry out potentially dangerous activities requiring an increased concentration of attention and speed of psychomotor reactions (driving, etc.)vehicles, work with moving mechanisms, the work of a dispatcher and operator, etc.).

Form release / dosage:Tablets, film-coated, 10 mg.

Packaging:For 10 tablets in a blister of PVC / aluminum foil, laminated paper. By 3, 6,12 blisters together with instructions for use in a cardboard bundle.

Storage conditions:

In a dry, dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

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

Terms of leave from pharmacies:On prescription

Registration number:LP-001463

Date of registration:26.01.2012

Expiration Date:26.01.2017

The owner of the registration certificate:GlaxoSmithKline Trading, ZAO GlaxoSmithKline Trading, ZAO Russia

Manufacturer: & nbsp

DR. REDDY`S LABORATORIES, LTD. India

Representation: & nbspGlaxoSmithKline Trading, ZAOGlaxoSmithKline Trading, ZAO

Information update date: & nbsp28.04.2018

Illustrated instructions

Instructions

Mémique (Memicar)