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

Composition:For one tablet, film-coated:
Kernel composition:
Active substance
Memantine hydrochloride 10.00 mg
Excipients
Lactose monohydrate 140.00 mg
Microcrystalline cellulose 24.00 mg
Silica colloidal dioxide 1.00 mg
Carboxymethyl starch sodium (type A) 8.00 mg
Talc 8.00 mg
Povidone-K25 (Plasdon K-25, Kollidon 25) 8.00 mg
Magnesium stearate 1.00 mg
Shell composition:
Aquarius Prime In AR218010 White [hypromellose - 65%, titanium dioxide-25%, macrogol (polyethylene glycol) -10%] - 6.00 mg

Description:Round, biconvex tablets, covered with a film coat of white color. The core of the tablet is white or almost white.

Pharmacotherapeutic group:Means of treatment of dementia.

ATX: & nbsp

N.06.D.X.01 Memantine

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

Pharmacodynamics:The adamantane derivative, by chemical structure and pharmacological properties, is close to amantadine. It is a noncompetitive antagonist of N-methyl-D-aspartate (NMDA) -receptors (including in black matter), thereby reducing the excessive stimulating effect of cortical glutamate neurons on the neostriatum, which develops against a background of insufficient dopamine excretion. Improves the process of nerve impulse transmission. Improves cognitive processes, increases daily activity.

Pharmacokinetics:Eating does not affect absorption. After oral administration, it is quickly and completely absorbed from the gastrointestinal tract. The maximum concentration is achieved 3-8 hours after administration. Pharmacokinetics is linear in the dose range of 10-40 mg. A daily dose of 20 mg results in an equilibrium plasma concentration of 70 to 150 ng / ml. 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. 80% of memantine circulating in the blood is unchanged substance. The main metabolites are N-3,5-dimethylgoldantane, isomer mixture of 4- and 6-hydroxymemanthine and 1-nitroso-3,5-dimethyladamantane.None of the metabolites has antagonistic activity with respect to NMDA receptors. The involvement of cytochrome P450 in in vitro metabolism has not been revealed.
In studies in which¹⁴C -memantine was taken orally, on average 84% of the dose was excreted for 20 days, while> 99% was excreted in the urine.
Memantine is excreted mainly by the kidneys. Excretion occurs single-phase, the half-life is 60-100 h; clearance is 170 ml / min / 1.73 m², partially secreted by the renal tubules.
With an alkaline urine reaction, the removal of memantine is slowed (on average by 80% with a pH of 8).
Pharmacodynamic and pharmacokinetic connection
When memantine is used at a dose of 20 mg / day, the level of concentration in the cerebrospinal fluid corresponds to the value of Ki (pressure constant), which for memantine is 0.5 μmol in the region of the frontal cortex of the brain.

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

Contraindications:Hypersensitivity to any of the components of the drug, severe hepatic insufficiency, lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome, pregnancy, breastfeeding, children under 18 years of age (due to insufficient data).

Carefully:With caution appoint a patient with thyrotoxicosis, 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 sudden change in diet, for example, the transition to vegetarianism, a copious intake of alkaline gastric buffers); severe urinary tract infections, myocardial infarction (history), heart failure (NYHA class III-IV functional class), uncontrolled arterial hypertension, renal failure, hepatic insufficiency.

Pregnancy and lactation:Contraindicated in pregnancy, as there is no evidence of the effect of memantine on pregnancy. Experimental studies conducted on animals indicate the possibility of slowing intrauterine growth at the level of exposure to identical or somewhat higher concentrations of memantine compared to such in humans. The potential risk to humans is unknown. It is not known whether memantine is excreted into breast milk, so women who take memantine, you should refrain from 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. Before the start of treatment it is necessary to provide care for the patient with a view to regular monitoring of the patient's drug intake. The diagnosis is made in accordance with the current recommendations. The tolerability and dosage of memantine should be reviewed regularly, preferably within the first three months after initiation of treatment. After that, the clinical effectiveness of memantine and the patient's tolerability of treatment should be reviewed according to current clinical guidelines. Supportive treatment can continue until a positive therapeutic effect is achieved, and while the patient normally tolerates memantine treatment. Remission of memantine should be discontinued in the absence of a positive therapeutic effect or if the patient is intolerant of 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 appointment of minimally effective doses.
The estimated value of the maintenance dose is 10-20 mg / day.
During the first week of therapy (days 1-7) at a dose of 5 mg / day, during the second week (days 8-14) at a dose of 10 mg / day, during the third week (days 15-21) at a dose of 15 mg / day, starting with the fourth week at a dose of 20 mg / day.
The maximum daily dose of 20 mg.
Dose adjustments in elderly patients (over 65 years) are not required.
With moderate renal failure (creatinine clearance 50-80 ml / min), dose adjustment is usually not required. With creatinine clearance of 30-49 ml / min, the daily dose initially does not exceed 10 mg, then after 7 weeks, with good tolerability, the dose can be increased up to 20 mg according to the standard schedule. In severe renal failure (creatinine clearance 5-29 ml / min) daily dose should not exceed 10 mg.
In patients with mild and moderate liver disorders (class A and B according to the Child-Pugh classification) correction of the dosing regimen is not required.

Side effects:Adverse reactions are classified according to the clinical manifestations (in accordance with the damage of certain organ systems) and the frequency of occurrence: very often - ≥1 / 10; often - ≥1 / 100 to <1/10; infrequently - ≥1 / 1000 to <1/100; rarely - ≥1 / 10000 to <1/1000; very rarely - <1/10000, including individual messages.
From the central and peripheral nervous system:
Often: headache, dizziness, drowsiness;
Infrequent: gait disturbance;
Rarely: increased fatigue;
Very rarely: epileptic seizures, seizures, increased intracranial pressure.
Mental disorders:
Infrequently: depression, increased excitability, sleep disturbance, confusion, agitation, hallucinations;
Very rarely: psychotic reactions, suicidal thoughts.
From the cardiovascular system:
Often: increased blood pressure;
Infrequent: venous thrombosis / thromboembolism, heart disease, heart failure.
From the gastrointestinal tract:
Often: constipation;
Infrequent: nausea, vomiting;
Very rarely: pancreatitis.
From the respiratory system:
upper respiratory tract infection, bronchitis, flu-like syndrome, dyspnea.
From the urinary system: cystitis.
Infections:
Rarely: fungal diseases.
From the immune system:
Often: hypersensitivity to the drug.
Common reactions:
Infrequent: general weakness, allergic reactions.

Overdose:Clinical experience with memantine has shown a limited amount of information about overdoses.
Symptoms: If enough overdose (200 mg once or more than 100 mg per day for 3 days), the following symptoms were found: weakness, fatigue, diarrhea, or absence of symptoms. An overdose of less than 140 mg or an overdose of an unknown amount of memantine revealed the following adverse effects on the part of the nervous system: confusion, lethargy, drowsiness, dizziness, agitation, aggression, hallucinations, gait abnormalities and gastrointestinal tract: vomiting and diarrhea.
In the most serious cases of overdose, the patient survived after taking more than 2000 mg 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 any consequences.
Another described case of a serious overdose is 400 mg once. The patient recovered without consequences. There were reactions from the nervous system: anxiety, psychosis, visual hallucinations, stupor, seizures, drowsiness, unconsciousness.
Treatment: In case of an overdose, symptomatic treatment should be performed. There is no specific antidote for memantine intoxication. Carry out standard procedures for evacuating the drug by washing the stomach, using activated charcoal (to prevent further absorption of the drug in the intestine), forced diuresis, methods of acidifying the urine reaction.
In the case of the appearance of symptoms of over-irritation of the central nervous system, symptomatic therapy should be carefully chosen and justified.

Interaction:With the simultaneous use with preparations of levodopa, dopamine receptor agonists, m-holinoblokatorami action of the latter can be strengthened.
With simultaneous use with barbiturates, neuroleptics, the effect of the latter may decrease.
When combined, the effect of spasmolytic drugs, dantrolene or baclofen may be altered (enhanced or decreased), so the dosage of the drugs should be selected individually.
Simultaneous administration with amantadine, phenytoin, ketamine and dextromethorphan should be avoided because of the increased risk of developing pharmacotoxic psychosis.Other medicines, such as cimetidine, ranitidine, procainamide, quinidine, quinine and nicotinewhich use the same cationic kidney transport system as memantine, can also interact with memantine, causing a potential risk of elevated levels in the blood plasma.
It is possible to reduce the concentration of hydrochlorothiazide when taken concomitantly with memantine. Memantine can increase the excretion of hydrochlorothiazide.
There are cases of an increase in INR (an international normalized ratio) in patients taking indirect anticoagulants simultaneously (warfarin). It is recommended that prothrombin time or INR is monitored regularly.
In pharmacological studies in healthy young volunteers with a single administration of memantine with glibenclamide / metformin or donepezil, no interaction effects were recorded.
Also in such studies, no interaction with galantamine was found.

Special instructions:An alkaline urine reaction requires a more careful observation of such patients because of the slower release of memantine.Some factors that cause an increase in the pH of the urine may necessitate careful monitoring of the patient. These factors include dramatic changes in diet, such as replacing a meat-rich diet for vegetarian or intensive use of antacid agents. In addition, urine pH may increase due to tubular renal acidosis or a severe urinary tract infection caused by Proteus spp.
Data on the use of memantine in patients with a history of myocardial infarction, with chronic heart failure (NYHA class III-IV functional class) or uncontrolled hypertension are limited, and careful medical supervision of the patient is therefore necessary.
With caution appoint patients with epilepsy, seizures (including in the anamnesis) or suggesting to epilepsy factors.
Memantine should be avoided together with other NMDA receptor antagonists (amantadine, ketamine, dextromethorphan), since adverse reactions can occur more often and more intensively, mainly at the level of the central nervous system.

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. Besides, memantine can cause a change in the reaction rate, so patients need to refrain from driving vehicles and working with complex mechanisms.

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

Packaging:For 10 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.
For 30 or 90 tablets per can of polymer for medicines.
Free space in the bank is filled with cotton hygroscopic cotton.
For 30 or 90 tablets in a jar of orange glass with triangular corolla type BDS, ukuporennuyu cover lid with a sealing element.
Each jar, 3 or 9 contour squares, together with the instruction for use, is placed in a pack of cardboard box.

Storage conditions:In a dry, protected from light 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 expiry date.

Terms of leave from pharmacies:On prescription

Registration number:LP-001952

Date of registration:25.12.2012

Expiration Date:25.12.2017

The owner of the registration certificate:TECHNOLOGY OF DRUGS, LTD. TECHNOLOGY OF DRUGS, LTD. Russia

Manufacturer: & nbsp

TECHNOLOGY OF DRUGS, LTD. Russia

Information update date: & nbsp2016-12-07

Illustrated instructions

Instructions

Memantine-TL (Memantin-TL)