Maruxa pills 20mg №30

Composition

1 pill contains:

Therapeutic indications

• Treatment of patients with Alzheimer's disease of moderate and severe.

Dosage and administration

Therapy should be carried out under the supervision of a physician with expertise in the diagnosis and treatment of dementia in Alzheimer's disease. Therapy should be initiated only if the person who regularly cares for the patient will monitor their drug intake. The diagnosis should be made in accordance with the current recommendations.

It is necessary to regularly assess the tolerability and dose of the drug Maruxa^®preferably within three months after initiation of therapy. Then you should regularly evaluate the clinical efficacy of the drug and the tolerability of therapy in accordance with the current clinical guidelines. Maintenance therapy can be continued indefinitely with a therapeutic effect and good tolerability of Maruxa^®. You should stop using the drug Maruxa^®if the therapeutic effect is no longer observed, or if the patient does not tolerate therapy.

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

Selection of therapy with Maruxa^®, tablets, film coated, in a dose of 20 mg is impossible. Memantine pills in a lower dose of 10 mg can be used for the selection of therapy.

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

The following dosing regimen is recommended:

1st week (1-7 day): daily dose - 5 mg.

2nd week (8-14 day): daily dose - 10 mg.

3rd week (15-21 days): daily dose - 15 mg.

Starting from the 4th week: daily dose - 20 mg.

Elderly patients (over 65)

Dose adjustment is not required.

Renal dysfunction

In patients with creatinine clearance (CK) 50-80 ml / min dose adjustment is not required. Patients with moderate renal insufficiency (CK 30-49 ml / min) recommended 10 mg / day. 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 insufficiency (CC 5-29 ml / min), the daily dose should be 10 mg / day.

Liver dysfunction

In patients with mild and moderate liver dysfunction (class A and B on the Child-Pugh scale) dose adjustment is not required. Patients with severe hepatic impairment (class C on the Child-Pugh scale) drug Maruxa^® contraindicated.

Contraindications

• Hypersensitivity to memantine and other components of the drug.
• Severe hepatic impairment (Child-Pugh class C).
• Pregnancy and breastfeeding period.
• Age up to 18 years (efficacy and safety have not been established).
• Lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome, because part of the drug Maruxa^® lactose is included.

Carefully

Epilepsy, thyrotoxicosis, predisposition to the development of seizures; simultaneous use of NMDA receptor antagonists (amantadine, ketamine, dextromethorphan), factors that increase urine pH (abrupt diet change, for example, switching to vegetarianism, abundant 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 the NYHA classification, uncontrolled arterial hypertension, renal failure, liver failure.

Precautions and special instructions for use

It is recommended to be used with caution in patients with epilepsy, a history of convulsions, or in patients with a predisposition to epilepsy.

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

The patient has factors that influence the increase in urine pH (abrupt changes in nutrition, for example, switching from diets that include animal products to a vegetarian diet or intensive consumption of alkaline gastric buffers), as well as renal tubular acidosis or severe urinary tract infections Proteus spp., require careful monitoring of the patient's condition.

From the majority of clinical studies, patients with a history of myocardial infarction, decompensated chronic heart failure (NYHA class III-IV functional class) or uncontrolled arterial hypertension were excluded. Therefore, data on the use of memantine in these patients is limited, the drug should be taken under the careful supervision of a physician.

Interactions with other drugs and other forms of interactions

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

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

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

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

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

When taken simultaneously with hydrochlorothiazide, it is possible to decrease the concentration of hydrochlorothiazide in the blood plasma by increasing its elimination from the body.

An increase in the International Normalized Relationship (INR) is possible in patients who are simultaneously taking oral indirect anticoagulants (warfarin). It is recommended to regularly monitor prothrombin time or INR.

Simultaneous use with antidepressants, selective serotonin reuptake inhibitors and monoamine oxidase inhibitors requires careful monitoring of patients.

No drug interactions were observed with a single simultaneous use of memantine with glibenclamide / Metformin or donepezil in healthy volunteers.

When applied simultaneously with memantine, no change in the pharmacokinetics of galantamine in healthy volunteers was observed.

In conditions in vitro memantine does not inhibit CYP 1A2, 2A6, 2C9, 2D6, 2E1, 3A isoenzymes, monooxygenase containing flavin, epoxyhydrolase, or sulfation.

Use during pregnancy and lactation

Due to the possible delay in intrauterine development, the drug Maruxa^® not applicable during pregnancy.

There is no information about the allocation of memantine with breast milk. However, given the lipophilicity of memantine, excretion is possible. Therefore, at the time of treatment with the drug Maruxa^® breastfeeding must stop.

Influence on ability to drive a car and other mechanisms

In patients with Alzheimer's disease at the stage of moderate and severe dementia, the ability to drive vehicles and manage complex mechanisms is usually impaired. In addition, memantine may cause a change in the reaction rate, so patients should refrain from driving or working with complex mechanisms.

Side effects

Classification of the incidence of side effects of the World Health Organization (WHO): very often (1/10), often (from ≥ 1/100 to <1/10), infrequently (from ≥ 1/1000 to <1/100), rarely ( from ≥ 1/10000 to <1/1000), very rarely (<1/10000), the frequency is unknown (the frequency of occurrence cannot be estimated based on existing data).

Violations of the blood and lymphatic system: the frequency is unknown - agranulocytosis, leukopenia (including neutropenia), pancytopenia, thrombocytopenia, thrombocytopenic purpura.

Immune system disorders:often - hypersensitivity to the drug.

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

Nervous system disorders: often - dizziness, imbalance; infrequently - gait disturbance; very rarely cramps.

Heart disorders: infrequently - heart failure.

Vascular disorders: often - increase in blood pressure; infrequently - venous thrombosis / thromboembolism

Disorders of the respiratory system, organs of the chest and mediastinum: often - shortness of breath.

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

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

Kidney and urinary tract disorders: frequency unknown - acute renal failure .

Violations of the skin and subcutaneous tissues: frequency is unknown - Stevens-Johnson syndrome.

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

When post-registration use, the following adverse reactions were reported: dizziness, drowsiness, irritability, fatigue, anxiety, increased intracranial pressure, nausea, hallucinations, headache, impaired consciousness, muscle hypertonus, gait disturbance, depression, convulsions, psychotic reactions, suicidal thoughts, constipation, nausea, pancreatitis, candidiasis, increased blood pressure, vomiting, cystitis, increased libido, venous thrombosis, thromboembolism and allergic eaktsii.

Overdose

Symptoms: increased severity of side effects such as fatigue, weakness, diarrhea, confusion, drowsiness, dizziness, agitation, hallucinations, gait disturbance, nausea.

In the most severe case of overdose (2000 mg of memantine), the patient survived, with adverse reactions from the nervous system (coma for 10 days, then diplopia and agitation) were observed. The patient received symptomatic treatment and plasmapheresis. The patient recovered without further complications. In another case of severe overdose (400 mg), the patient also survived and recovered. Adverse reactions of the central nervous system are described: anxiety, psychosis, visual hallucinations, convulsive readiness, drowsiness, stupor and loss of consciousness.

Treatment: in case of overdose, treatment is symptomatic. There is no specific antidote. It is necessary to conduct standard therapeutic measures aimed at removing the active substance from the stomach, for example, washing the stomach, taking activated charcoal, acidifying urine, it is possible to conduct forced diuresis.

Pharmacodynamic properties

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

Pharmacokinetic properties

Suction

Quickly and completely absorbed after ingestion. Maximum plasma concentration (C_max) is achieved within 3-8 hours after ingestion. In patients with normal renal function, there is no accumulation of memantine.

Distribution

When taken daily at a dose of 20 mg per day, the equilibrium concentration of memantine in the blood plasma is 70-150 ng / ml. When using a daily dose of 5-30 mg, the ratio of the average concentration in the cerebrospinal fluid to the plasma concentration was calculated to be 0.52. The volume of distribution is about 10 l / kg. About 45% of memantine is bound to plasma proteins .

Metabolism

About 80% of ingested memantine is excreted unchanged.

The major metabolites of N-3,5-dimethylgludantan, an isomeric mixture of 4- and 6-hydroxy-memantine and 1-nitroso-3-5-dimethyl-adamantane do not possess their own pharmacological activity. In conditions in vitro no metabolism carried out by cytochrome P450 isoenzymes has been identified. In the study by ingestion ¹⁴On average, C-memantine 84% of the ingested dose was eliminated within 20 days, with more than 99% eliminated by the kidneys.

Removal

Excreted mono-exponentially. The half-life (T_½a) the terminal phase is from 60 to 100 hours. It is excreted by the kidneys. 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 canalicular secretion. Renal excretion also includes tubular reabsorption, possibly mediated by cationic transport.