Maruksa (Memantine)

Active substance:

memantine hydrochloride;

Excipients:

 lactose monohydrate - 51.45 mg;

MCC - 175 mg;

colloidal silicon dioxide - 2.5 mg;

talc - 9.8 mg;

magnesium stearate - 1.25 mg

Maruksa - neurometabolic, nootropic.

Pharmacodynamics

Adamantane derivative. It is a non-competitive antagonist of N-methyl-D-aspartate (NMDA) receptors, has a modulating effect on the glutamatergic system. Regulates ion transport, blocks calcium channels, normalizes membrane potential, improves the transmission of nerve impulses. Improves cognitive processes, increases daily activity.

Pharmacokinetics

Suction

Quickly and completely absorbed after oral administration. Tmax in plasma - 3-8 hours after ingestion. In patients with normal renal function, cumulation of memantine was not observed.

Distribution

With a daily dose of 20 mg / day, Css memantine in the blood plasma is 70-150 ng / ml. When applying a daily dose of 5-30 mg, the ratio of the average concentration in the cerebrospinal fluid to the concentration in the blood plasma was calculated, equal to 0.52. Vd is about 10 l / kg. About 45% of memantine binds to plasma proteins.

Metabolism

About 80% of memantine taken internally is excreted unchanged. The main metabolites of N-3,5-dimethyl-gludantan, an isomeric mixture of 4- and 6-hydroxy-memantine and 1-nitroso-3-5-dimethyl-adamantane do not have their own pharmacological activity. Under in vitro conditions, metabolism carried out by cytochrome P450 isoenzymes was not detected.

Breeding

In the study, when 14C-memantine was taken orally, an average of 84% of the oral dose was excreted within 20 days, with more than 99% excreted by the kidneys. It is excreted monoexponentially from the body. T1 / 2 of the terminal phase is from 60 to 100 hours. In volunteers with normal renal function, the total clearance is 170 ml / min / 1.73 m2, part of the total renal clearance is achieved due to tubular secretion. Renal excretion also includes tubular reabsorption, possibly mediated by cationic transport proteins. The rate of renal elimination of memantine in an alkaline urine reaction may decrease by 7–9 times. Alkalization of urine can be caused by a sharp change in diet, for example, a shift from a diet including animal products to a vegetarian diet, or due to the intensive use of alkaline gastric buffers.

Linearity

Studies conducted in volunteers showed linear pharmacokinetics in the dose range of 10–40 mg.

Pharmacokinetic / pharmacodynamic dependence

When using memantine at a dose of 20 mg / day, the concentration level in the cerebrospinal fluid corresponds to the inhibition constant (ki), which for memantine is 0.5 μmol in the frontal cortex.

Dementia of moderate and severe severity in Alzheimer's disease.

• hypersensitivity to memantine and other components of the drug;
• severe liver failure (class C on the Child-Pugh scale);
• lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome, because the composition of the drug Maruks® includes lactose;
• pregnancy, the period of breastfeeding;
• age up to 18 years (efficacy and safety not established).

Precautions: epilepsy; thyrotoxicosis; predisposition to the development of seizures; simultaneous use of other antagonists of NMDA receptors (amantadine, ketamine, dextromethorphan); factors that increase the pH of urine (a sharp change in diet, for example, switching to vegetarianism, heavy intake of alkaline gastric buffers); renal tubular acidosis; severe urinary tract infections caused by Proteus spp .; myocardial infarction (history); heart failure III – IV functional class according to NYHA classification; uncontrolled arterial hypertension; renal failure; liver failure.

Infectious and parasitic diseases: rarely - fungal infections.

On the part of the immune system: often - hypersensitivity to the components of the drug.

Mental disorders: often - drowsiness; infrequently - confusion, hallucinations *; frequency unknown - psychotic reactions.

From the nervous system: often - dizziness, imbalance; infrequently - gait disturbance; very rarely - cramps.

From the side of the heart: infrequently - heart failure.

On the part of the vessels: often - increased blood pressure; infrequently - venous thrombosis / thromboembolism.

From the respiratory system, chest and mediastinal organs: often - shortness of breath.

From the gastrointestinal tract: often - constipation; infrequently - nausea, vomiting; frequency is unknown - pancreatitis.

On the part of the liver and biliary tract: often - increased activity of liver enzymes; frequency unknown - hepatitis.

General disorders and disorders at the injection site: often - headache; infrequently - fatigue.

The effects of levodopa, dopamine receptor agonists and anticholinergic drugs are potentiated.

The effectiveness of barbiturates, antipsychotic (antipsychotics) drugs decreases with the simultaneous use of memantine.

The simultaneous use of memantine with dantrolene and baclofen, as well as antispasmodics, may be accompanied by a change in their effect, which requires dose adjustment of these drugs.

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

With simultaneous use with cimetidine, ranitidine, procainamide, quinidine, quinine and nicotine, the risk of increasing the concentration of memantine in the blood plasma increases.

With simultaneous administration with hydrochlorothiazide, a decrease in the concentration of hydrochlorothiazide in blood plasma is possible due to an increase in its excretion from the body.

May increase MHO in patients simultaneously taking oral indirect anticoagulants (warfarin). Regular monitoring of PV or MHO is recommended.

The simultaneous use of antidepressants, SSRIs and MAO inhibitors requires careful monitoring of patients.

No drug interaction was observed with a single simultaneous use of memantine with glibenclamide / metformin or donepezil in healthy volunteers.

With simultaneous use with memantine, no pharmacokinetics of galantamine were observed in healthy volunteers.

In vitro, memantine does not inhibit CYP1A2, 2A6, 2C9, 2D6, 2E1, 3A isoenzymes, monooxygenase containing flavin, epoxyhydrolase or sulfation.

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

Therapy should be under the supervision of a physician with experience in the diagnosis and treatment of dementia in Alzheimer's disease. Therapy should only be started if the person who regularly cares for the patient monitors their medication. The diagnosis should be made in accordance with current recommendations. The tolerance and dose of the Maruks® preparation should be regularly evaluated, preferably within 3 months after the start of therapy. Then, the clinical efficacy of the drug and the tolerability of the therapy should be regularly evaluated in accordance with current clinical guidelines. Supportive therapy can be continued indefinitely with a therapeutic effect and good tolerance of Maruks®. You should stop using the drug Maruks®,

In order to reduce the risk of side effects, a gradual increase in dose is recommended: 5 mg / week during the first 3 weeks of therapy. The recommended maintenance dose is 20 mg / day.

The following dosage regimen is recommended:

• 1st week (1st – 7th day): daily dose - 5 mg (½ tablet of Maruks® 10 mg every day for 7 days);
• 2nd week (8-14th day): daily dose - 10 mg (1 tablet of Maruks® 10 mg every day for 7 days);
• 3rd week (15–21st day): daily dose - 15 mg (1½ tablets of Maruks® 10 mg every day for 7 days);
• starting from the 4th week: daily dose - 20 mg (2 tablets of Maruks® 10 mg every day).

Special patient groups

Elderly patients (over 65 years old). Dose adjustment is not required.

Impaired renal function. In patients with Cl creatinine 50–80 ml / min, dose adjustment is not required. A dose of 10 mg / day is recommended for patients with moderate renal failure (creatinine Cl 30–49 ml / min). With good tolerability of the drug for 7 days, the dose can be increased to 20 mg / day according to the standard scheme. In patients with severe renal failure (Clcreatinin 5–29 ml / min), the dose should be 10 mg / day.

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

Symptoms: increased severity of side effects such as fatigue, weakness, diarrhea, confusion, drowsiness, dizziness, agitation, hallucinations, impaired gait, nausea. In the most severe case of an overdose (2000 mg of memantine), the patient survived, with adverse reactions from the nervous system (coma for 10 days, then diplopia and agitation). The patient received symptomatic treatment and plasmapheresis. The patient recovered without subsequent complications. In another case of severe overdose (400 mg), the patient also survived and recovered. Adverse reactions from the central nervous system are described: anxiety, psychosis, visual hallucinations, convulsive readiness, drowsiness, stupor and loss of consciousness.

Treatment: symptomatic. A specific antidote to the drug does not exist. It is necessary to carry out standard therapeutic measures aimed at removing the active substance from the stomach, for example, washing the stomach, taking activated charcoal, acidifying urine, and it is possible to conduct forced diuresis.

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

The simultaneous use of memantine and other NMDA receptor antagonists such as amantadine, ketamine or dextromethorphan should be avoided. These compounds act on the same receptor system as memantine; therefore, undesirable reactions (mainly related to the central nervous system) can occur more often and be more pronounced.

The presence of factors affecting the increase in urine pH (dramatic changes in diet, for example, a switch from a diet including 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.

Patients with a history of myocardial infarction, decompensated heart failure (NYHA class III – IV functional class), or uncontrolled hypertension were excluded from most clinical trials. Therefore, data on the use of memantine in such patients are limited, the drug should be administered under close medical supervision.

Influence on the ability to drive vehicles and work with mechanisms. In patients with moderate to severe dementia, Alzheimer's disease usually impairs the ability to drive vehicles and control complex mechanisms. In addition, memantine can cause a change in the reaction rate, so patients need to refrain from driving or working with complex mechanisms.

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