Memantinol pills 10mg, 90pcs

Composition

Tablets

Active ingredient:

memantine hydrochloride 10 mg;

Auxiliary substances:

lactose monohydrate-169 mg;

MCC-40 mg;

colloidal silicon dioxide-1.2 mg;

sodium starch glycolate (type A) – 10 mg;

hydroxypropylcellulose-7.4 mg;

magnesium stearate-2.4 mg

Pharmacological action

Memantine is a potential-dependent non-competitive inhibitor of NMDA receptors with moderate affinity for them. Modulates the effect of pathologically elevated

pharmacokinetics

Suction and distribution

After oral use, it is rapidly and completely absorbed. Cmax in blood plasma is reached in 3-8 hours after use.

The pharmacokinetics are linear in the dose range from 10 to 40 mg. Daily intake of a daily dose of 20 mg leads to Css from 70 to 150 ng / ml (0.5-1 mmol) with pronounced individual variations.

The Vd is about 10 l / kg. About 45% of memantine binds to plasma proteins. No accumulation of the drug was observed in normal renal function.

Metabolism and elimination

About 80% of memantine is present in the circulating blood as an unchanged compound.

The main metabolites are N-3,5-dimethyl-gludantane, a mixture of isomers of 4 – and 6-hydroxymemanthine and 1-nitroso-3,5-dimethyl-adamantane. None of these metabolites has antagonistic activity against NMDA receptors. Cytochrome P 450 metabolism has not been shown to be involved in in vitro studies.

In studies taking 14C-memantine orally, an average of 84% of the dose was eliminated within 20 days, while more than 99% of the drug was excreted by the kidneys.

Memantine is mainly excreted by the kidneys. Excretion occurs monoexponentially, T1 / 2 is from 60 to 100 hours. In studies in volunteers with normal renal function, the total clearance was 170 ml / min/1.73 m2, part of the total renal clearance was achieved due to secretion by the renal tubules.

Renal elimination also includes tubular reabsorption, which may be carried out by cationic transport proteins. The rate of renal elimination under conditions of an alkaline reaction of urine can decrease by 7-9 times. Alkalinization of urine can result from a sudden change in diet, for example, the transition from eating mainly meat products to vegetarianism, or due to the intensive use of alkaline gastric buffers.

Pharmacokinetic-pharmacodynamic relationship

When taking a maintenance dose of 20 mg/day, the level of memantine concentration in the cerebrospinal fluid corresponds to kj (kj is the inhibition constant), which for memantine is 0.5 mmol in the human frontal cortex.

Indications

Moderate to severe dementia in Alzheimer’s disease.

Contraindications

-pregnancy;

– breast-feeding period;

– age up to 18 years (efficacy and safety have not been established)—

– lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome (since the drug contains lactose)—

– hypersensitivity to memantine or any of the components that make up the drug.

With caution should be taken in patients with thyrotoxicosis, epilepsy, predisposing to the development of seizures (including in the anamnesis), the simultaneous use of antagonists of NMDA receptors (amantadine, ketamine, dextromethorphan), in the presence of factors that increase the pH of urine (abrupt change in diet, for example, the transition to vegetarianism, a generous intake of alkaline gastric buffers), renal kanaltsevam acidosis, severe infections of the urinary tract caused by bacteria of the genus Proteus, myocardial infarction (history), heart failure III-IV functional class (NYHA classification), uncontrolled hypertension, renal failure, liver failure.

Interaction

When used concomitantly with levodopa preparations, dopamine receptor agonists, anticholinergic drugs Drugs the effect of the latter may increase.

When used concomitantly with barbiturates, neuroleptics, the effect of the latter may decrease.

When used concomitantly with dantrolen or baclofen, as well as with antispasmodics, their effect may change (increase or decrease), so the dose of drugs should be adjusted.

Concomitant use of memantine with amantadine should be avoided due to the risk of psychosis. Memantine and amantadine belong to the group of NMDA receptor antagonists. The risk of psychosis is also increased when co-administered with ketamine, dextromethorphan, and phenytoin.

When taken concomitantly with cimetidine, ranitidine, procainamide, quinidine, quinine and nicotine, it is possible to increase the plasma concentration of memantine.

It is possible to reduce the level of hydrochlorothiazide when taken simultaneously with memantine by increasing its excretion from the body.

Possible promotion INR in patients taking concomitant oral indirect anticoagulants (warfarin). It is recommended to constantly monitor PV or INR.

Concomitant use with antidepressants, SSRIs, and MAO inhibitors requires careful monitoring of patients.

According to the pharmacokinetic studies conducted, no drug interaction effects were detected in young healthy volunteers with a single simultaneous use of memantine with glyburide/metformin or donepezil.

Clinical studies also did not reveal the effect of memantine on the pharmacokinetics of galantamine in young healthy volunteers.

In vitro studies, memantine did not inhibit the isoenzymes CYP1A2,2A6,2C9,2D6,2E1,3A, flavin-containing monooxygenase, epoxidohydrolase, or sulfation.

How to take, course of use and dosage

Inside, once a day and always at the same time, regardless of food intake.

Treatment with memantine should be initiated and conducted under the supervision of a physician experienced in the diagnosis and treatment of dementia in Alzheimer’s disease. The diagnosis should be made in accordance with the current guidelines. Treatment should only be initiated if the patient’s permanent caregiver regularly monitors the patient’s medication intake.

The tolerability and dosage of memantine should be reviewed regularly, preferably within the first 3 months of starting 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. Maintenance treatment can be continued indefinitely if there is a positive effect of the therapy and the treatment is well tolerated. Memantine should be discontinued if there is no positive therapeutic effect or if the patient is intolerant to the treatment.

For adults

Titration of the dose. The maximum daily dose is 20 mg/day. In order to reduce the risk of adverse reactions, the dose of the drug is titrated by increasing it sequentially by 5 mg every week for the first 3 weeks: during the 1st week of therapy (days 1 to 7), the patient should take memantine at a dose of 5 mg/day (0.5 table 10 mg), during the 2nd week (days 8 to 14)-at a dose of 10 mg/day (1 table 10 mg), during the 3rd week (days 15 to 21)-at a dose of 15 mg/day (1.5 tablets of 10 mg). Starting from the 4th week, the patient is prescribed memantine at a dose of 20 mg / day (2 tablets of 10 mg). The recommended maintenance dose is 20 mg / day.

Special patient groups

Older age (over 65 years). No dose adjustment is required.

Impaired renal function. In patients with creatinine clearance 50-80 ml/min, no dose adjustment is required. For patients with moderate renal insufficiency (creatinine clearance 30-49 ml / min), the recommended daily dose is 10 mg/day. If this dose is well tolerated for 7 days, it can be increased to 20 mg / day in accordance with the standard titration scheme. In patients with severe renal insufficiency (creatinine clearance 5-29 ml / min), the daily dose should not exceed 10 mg / day.

Impaired liver function. In patients with mild to moderate hepatic impairment (Class A and Class B B on the Child-Pugh scale) no dose adjustment is required. There are no data on the use of memantine in patients with severe hepatic impairment, so the appointment of memantine in such patients is not recommended.

Overdose

There are limited overdose data available from clinical trials and post-marketing experience with memantine.

Symptoms:  a relatively large overdose (200 mg once or 105 mg / day for 3 days) resulted in fatigue, weakness and/or diarrhea, or no symptoms. In the case of overdose at a dose of less than 140 mg once or taking an unknown dose, patients experienced adverse reactions from the central nervous system — confusion, hypersomnia, drowsiness, dizziness, agitation, aggression, hallucinations, gait disorders and/or from the digestive system — vomiting, diarrhea.

In the most severe case of overdose, the patient survived after taking a dose of 2000 mg of 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, a patient survived and recovered after taking memantine 400 mg once. The patient experienced adverse reactions from the central nervous system — anxiety, psychosis, visual hallucinations, a decrease in the threshold of convulsive readiness, drowsiness, stupor and loss of consciousness.

Treatment: symptomatic. It is necessary to carry out standard medical measures aimed at removing the substance from the stomach, for example, gastric lavage, use of activated charcoal, acidification of urine, and possibly forced diuresis. There is no specific antidote.

Special instructions

It is recommended to use with caution in patients with thyrotoxicosis, epilepsy, seizures (including in the anamnesis), as well as in patients with a predisposition to epilepsy. Concomitant use of NMDA receptor antagonists (amantadine, ketamine, dextromethorphan) and memantine should be avoided. These compounds act on the same receptor system as memantine, and therefore adverse reactions (mainly from the central nervous system) may occur more often and be more pronounced.

Given the slow elimination of memantine in patients with an alkaline urine reaction, patients who have factors that affect the increase in the pH of urine (a sharp change in diet, for example, when switching from eating mainly meat products to vegetarianism, intensive consumption of alkaline gastric buffers), as well as in cases of renal tubular acidosis or severe urinary tract infection caused by bacteria of the genus Proteus.

Data on the use of memantine in patients with a history of myocardial infarction, with chronic heart failure of functional class III–IV (NYHA classification) and uncontrolled arterial hypertension are limited, so careful medical monitoring of such patients is necessary.

Influence of a medicinal product for medical use on the ability to drive vehicles and mechanisms. Patients with moderate to severe Alzheimer’s disease usually have impaired ability to drive vehicles and manage complex mechanisms. In addition, memantine can cause changes in the reaction rate, so patients should refrain from driving vehicles or working with complex mechanisms.

Active ingredient

Memantine

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Acquired Dementia, Alcoholism, Stroke Effects, Concussion and Other Traumatic brain injuries, Alzheimer ‘s Disease