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

Shell composition: DIAMOND II 85F19250 TRANSPARENT (OPADRY® II 85F19250 CLEAR) [Macrogol 4000 (polyethylene glycol) 0.7 mg, polyvinyl alcohol 2.3 mg, polysorbate 80 0.2 mg, talc 1.3 mg] 4.5 mg.

Description:

Round, biconvex tablets, covered with a film shell of almost white color, with engraving in the form of a circle on one side.

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, by chemical structure and pharmacological properties, is close to amantadine.Is a non-competitive antagonist 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 the background of insufficient isolation of dopamine. 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-dimethylgludantan, isomer mixture of 4- and 6-hydroxymemanthine and 1-nitroso-3,5-dimethyladamantane. None of the metabolites has antagonistic activity in relation to NMDAreceptors. Participation of cytochrome P450 in metabolism in vitro not found.

In studies in which ¹⁴C-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 concentration level in the cerebrospinal fluid corresponds to the value Ki (inhibition constants), which 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 any of the components of the drug, severe hepatic insufficiency (class C according to the Child-Pugh classification), the period of breastfeeding, children under 18 years of age (efficacy and safety not established).

If you have one of the listed diseases (conditions), before taking the drug always consult a doctor.

Carefully:

Be wary appoint patients with thyrotoxicosis, epilepsy, seizures (including in history); simultaneous use of antagonists NMDA-receptors (amantadine, ketamine, dextromethorphan); the presence of factors that increase the pH of urine (a sharp change in diet (the transition from meat to vegetarian), the use of antacid agents, renal tubular acidosis or severe urinary tract infections caused by Proteus spp.); myocardial infarction (in the anamnesis), heart failure III-IV functional class (according to the classification NYHA), uncontrolled arterial hypertension; renal insufficiency, hepatic insufficiency.

Pregnancy and lactation:

Data on the use of pregnancy are limited.

Experimental studies conducted on animals indicate the possibility of slowing intrauterine growth at a level of exposure to identical or slightly higher concentrations of memantine compared to such in humans. A potential risk to a person is not known. The use of the drug in pregnancy is not recommended and is only possible if the expected benefit to the mother exceeds the possible risk to the fetus.

It is not known whether excretion of memantine occurs in breast milk, therefore, women taking memantine, you should refrain from breastfeeding.

There is no data on the effect on fertility.

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 this, 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 20 mg / day.

Treatment Scheme: 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 from the fourth week at a dose of 20 mg / day (given the impossibility of dividing the pill, it is recommended to use the drug memantine in tablets of 5 mg or 10 mg with a risk during the dose-escalating step).

The maximum daily dose of 20 mg.

Dose adjustment in elderly patients (over 65 years) not required.

With moderate renal failure (clearance of creatinine 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 to moderate hepatic impairment (class A and B according to the Child-Pugh classification) correction of the dosing regimen is not required.

Side effects:

In clinical studies in patients with dementia, adverse reactions were observed from mild to moderate severity and occurred with a higher incidence in the memantine group compared with placebo: dizziness (6.3% versus 5.6%), headache (5 , 2% vs. 3.9%), constipation (4.6% vs. 2.6%), drowsiness (3.4% vs. 2.2%) and hypertension (4.1% vs. 2.8%).

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, imbalance;

Infrequent: gait disturbance;

Rarely: increased fatigue;

Very rarely: epileptic seizures, convulsions.

Disorders from the psyche:

Infrequently: depression, increased excitability, sleep disturbance, confusion, agitation, hallucinations;

The frequency is unknown: psychotic reactions, suicidal thoughts.

From the side of the cardiovascular system:

Often: increased blood pressure;

Infrequent: venous thrombosis / thromboembolism, heart disease, heart failure.

From the gastrointestinal tract:

Often: constipation;

Infrequent: nausea, vomiting;

Frequency unknown: pancreatitis.

From the liver and biliary tract:

Often: violation of functional liver tests;

Frequency unknown: hepatitis.

From the respiratory system:

Often: shortness of breath.

Infections:

Infrequently: fungal infections.

From the immune system:

Often: hypersensitivity to the drug.

General reactions:

Infrequent: general weakness, allergic reactions.

If any of the side effects listed in the manual are aggravated, or if you notice any other side effects not listed in the instructions, inform the doctor about it.

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

There are separate reports of the occurrence of adverse reactions when the drug is used in clinical practice: dizziness, drowsiness, increased intracranial pressure, nausea, hallucinations, headache, impaired consciousness, hypertonic muscle,gait disorders, depression, convulsions, psychotic reactions, suicidal thoughts, constipation, nausea, pancreatitis, candidamycosis, increased arterial pressure, vomiting, cystitis, increased libido, venous thrombosis, thromboembolism, allergic reactions.

Overdose:

Clinical experience with memantine has shown a limited amount of information about overdoses.

Symptoms: fatigue, weakness, diarrhea, confusion, drowsiness, dizziness, aggression, agitation, hallucinations, gait disturbance, nausea.

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 symptoms of over-irritation of the central nervous system, symptomatic therapy should be carefully chosen and justified.

In overdoses of 200 mg once or more than 100 mg per day for 3 days, the following symptoms were identified: 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.

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.

Memantine does not inhibit isoenzymes CYP1A2, CYP1A6, CYP2C9, CYP2D6, CYP2E1, CYP3A, flavin-containing monooxygenase, epoxyhydrolase or sulfation in vitro.

In the event that you take other medicines, before taking the drug always consult a doctor.

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 (III-IV functional class by classification NYHA) or uncontrolled arterial hypertension are limited, therefore careful medical supervision of the patient is necessary.

With caution appoint a patient with thyrotoxicosis, epilepsy, convulsions (including in the anamnesis), as well as patients with a predisposition to epilepsy.

It should avoid the appointment of memantine along with other antagonists NMDA-receptors (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, 20 mg.

Packaging:

For 7 or 10 tablets in a contour mesh box made of polyvinyl chloride film and aluminum foil.

By 2, 4, 8, or 14 contour cell packs of 7 tablets or 3, 6 or 9 contour cell packs of 10 tablets together with instructions for use in a pack of cardboard.

Storage conditions:

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

Keep out of the reach of children.

Shelf life:

3 years.

The drug should not be used after the expiry date indicated on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-003513

Date of registration:22.03.2016 / 19.07.2017

Expiration Date:22.03.2021

The owner of the registration certificate:FARMZASCHITA NPC, GP FARMZASCHITA NPC, GP Russia

Manufacturer: & nbsp

FARMZASCHITA NPC, FSUE Russia

Information update date: & nbsp23.04.2018

Illustrated instructions

Instructions

Memantine (Memantin)