Maruxa, pills 10mg, 30pcs

Composition

for 1 tablet

Core:

Active ingredient:

Memantine Hydrochloride 10.00 mg

Excipients: lactose monohydrate, microcrystalline cellulose, colloidal silicon dioxide, talc, magnesium stearate

Film shell: methacrylic acid and ethyl acrylate copolymer (1 : 1),30% aqueous dispersion 1, talc, triacetin, simethicone

1 30% aqueous dispersion contains, in addition to methacrylic acid and ethyl acrylate copolymer, also sodium lauryl sulfate and polysorbate-80 as emulsifiers.

Pharmacological action

means of treating dementia

Clinical Pharmacology

Pharmacodynamics

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

Pharmacokinetics

Suction

It is rapidly and completely absorbed after oral use. The maximum concentration (cmax) in blood plasma is reached within 3-8 hours after oral use. No accumulation of memantine was observed in patients with normal renal function.

Distribution

When taken daily at a dose of 20 mg per day, the steady-state plasma concentrations of memantine are 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. The volume of distribution is about 10 l/kg. About 45% of memantine binds to plasma proteins.

Metabolism

About 80% of memantine taken orally is excreted unchanged. The main metabolites of N-3,5-dimethyl-gludantane, an isomeric mixture of 4 – and 6-hydroxy-memantine and 1-nitroso-3-5-dimethyl-adamantane does not have its own pharmacological activity. No cytochrome P450 isoenzymes were detected in vitro. In the study, when 14C-memantine was taken orally, an average of 84% of the oral dose was eliminated within 20 days, while more than 99% was excreted by the kidneys.

Deduction

It is removed from the body monoexponentially. The half-life (_half-life) of 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 by tubular secretion. Renal elimination also includes tubular reabsorption, possibly mediated by cationic transport proteins. The rate of renal elimination of memantine under conditions of an alkaline urine reaction can decrease by 7-9 times. Alkalinization of urine can be caused by a sudden change in nutrition, for example, switching from a diet that includes animal products to a vegetarian diet, or due to the intensive use of alkaline gastric buffers.

Linearity

Studies conducted in volunteers showed linearity of 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 value of the inhibition constant (ki), which for memantine is 0.5 mmol in the frontal cortex of the brain.

Indications

Treatment of patients with moderate to severe Alzheimer’s disease.

Use during pregnancy and lactation

Due to the possible delay in intrauterine development, Maruxa® is not used during pregnancy.

There is no information about the excretion of memantine in breast milk. However, given the lipophilicity of memantine, isolation is possible. Therefore, breast-feeding should be discontinued during treatment with Maruxa®.

Contraindications

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

Side effects

World Health Organization (WHO)classification of the incidence of side effects:

very common ≥ 1/10

common ≥ 1/100 to < 1/10

uncommon ≥ 1/1000 to < 1/100

rare ≥ 1/10000 to < 1/1000

very rare < 1/10000

frequency unknown cannot be estimated based on available data.

In clinical trials involving 1,784 patients treated with memantine and 1,595 patients treated with placebo, the overall incidence of adverse reactions did not differ between memantine and placebo. As a rule, they were from mild to moderate severity. The most common adverse reactions in the memantine group compared to placebo were: dizziness (6.3% vs. 5.6%, respectively), headache (5.2% vs. 3.9%), constipation (4.6% vs. 2.6%), drowsiness (3.4% vs. 2.2%, respectively), and hypertension (4.1% vs. 2.8%, respectively).

Side effects are presented in the form of a table according to the MedDRA classification:

1 Hallucinations were observed mainly in patients with Alzheimer’s disease at the stage of severe dementia.

The following adverse reactions have been reported with post-marketing use: dizziness, drowsiness, increased excitability, increased fatigue, anxiety, increased intracranial pressure, nausea, hallucinations, headache, impaired consciousness, muscle hypertonicity, gait disorders, depression, convulsions, psychotic reactions, suicidal thoughts, constipation, nausea, pancreatitis, candidiasis, increased blood pressure, vomiting, cystitis, increased libido, venous thrombosis, thromboembolism, and allergic reactions.

Interaction

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

Effectiveness of barbiturates, antipsychotics (neuroleptics) Concomitant use of memantine reduces the risk of drug withdrawal.

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

Concomitant use of memantine and 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 memantine is co-administered with phenytoin, ketamine, and dextromethorphan.

Concomitant use with cimetidine, ranitidine, procainamide, quinidine, quinine and nicotine increases the risk of increased plasma concentrations of memantine.

When taken concomitantly with hydrochlorothiazide, it is possible to reduce the concentration of hydrochlorothiazide in blood plasma by increasing its excretion from the body.

It is possible to increase the international normalized ratio (INR) in patients taking concomitant oral indirect anticoagulants (warfarin). Regular monitoring of prothrombin time or INR is recommended. Concomitant use with antidepressants, selective serotonin reuptake inhibitors, and monoamine oxidase inhibitors requires careful monitoring of patients.

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

When co-administered with memantine, no changes in the pharmacokinetics of galantamine were observed in healthy volunteers.

Under in vitro conditionsmemantine does not inhibit CYP isoenzymes 1A2,2A6,2C9,2D6,2 E1,3 A, flavin-containing monooxygenase, epoxidohydrolase, or sulfation.

How to take, course of use and dosage

Therapy should be conducted under the supervision of a doctor who has experience in the diagnosis and treatment of dementia in Alzheimer’s disease. Therapy should only be initiated if the person who regularly cares for the patient monitors their medication intake. The diagnosis should be made in accordance with the current guidelines.

The tolerability and dose of Maruxa should be evaluated regularly, preferably within three months of starting therapy. Then, the clinical efficacy of the drug and the tolerability of therapy should be regularly evaluated in accordance with current clinical guidelines. Maintenance therapy can be continued indefinitely if there is a therapeutic effect and Maruxa®is well tolerated. Discontinue the use of 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 food intake.

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

The following dosage regimen is recommended:

1st week (1-7 days): daily dose-5 mg (½tablet of Maruxa® 10 mg every day for 7 days);

2nd week (8-14 days): daily dose-10 mg (1 tablet of Marux® 10 mg every day for 7 days);

3rd week (15-21 days): daily dose-15 mg (1½ tablets of Maruxa® 10 mg every day for 7 days);

starting from the 4th week: daily dose-20 mg (2 tablets of Maruxa® 10 mg every day).

Elderly patients (over 65 years of age)

No dose adjustment is required.

Impaired renal function

No dose adjustment is required in patients with creatinine clearance (CC) of 50-80 ml / min. In patients with moderate renal insufficiency (creatinine clearance 30-49 ml/min),10 mg/day is recommended. If the drug is well tolerated for 7 days, the dose can be increased to 20 mg / day according to the standard scheme. In patients with severe renal insufficiency (creatinine clearance 5-29 ml / min), the daily dose should be 10 mg/day.

Impaired liver function

In patients with mild to moderate hepatic impairment (Child-Pugh class A and B), no dose adjustment is required.

Overdose

Symptoms: increased severity of side effects, such as fatigue, weakness, diarrhea, confusion, drowsiness, dizziness, agitation, hallucinations, gait disorders, 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). 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 from 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 carry out standard therapeutic measures aimed at removing the Active ingredient from the stomach, for example, gastric lavage, taking activated charcoal, acidification of urine, and possibly forced diuresis.

Description

Oval, biconvex tablets, white film-coated tablets with a risk on one side. Kink view: uneven white surface.

Special instructions

Epilepsy, thyrotoxicosis, a predisposition to the development of seizures, the simultaneous use of antagonists of NMDA receptors (amantadine, ketamine, dextromethorphan), the 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 tubular acidosis, severe urinary tract infection caused by Proteus spp., myocardial infarction (history), heart failure III-IV functional class NYHA classification, uncontrolled hypertension, renal failure, hepatic failure.

Contraindicated in persons under 18 years of age.

Elderly patients (over 65 years of age)

No dose adjustment is required.

Impaired renal function

No dose adjustment is required in patients with creatinine clearance (CC) of 50-80 ml / min. In patients with moderate renal insufficiency (creatinine clearance 30-49 ml/min),10 mg/day is recommended. If the drug is well tolerated for 7 days, the dose can be increased to 20 mg / day according to the standard scheme. In patients with severe renal insufficiency (creatinine clearance 5-29 ml / min), the daily dose should be 10 mg/day.

Impaired liver function

In patients with mild to moderate hepatic impairment (Child-Pugh class A and B), no dose adjustment is required.

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

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

The patient factors influencing the increase in the pH of urine (sudden changes in diet, such as switching from a diet that includes animal products to a vegan diet or an intense consumption of alkaline gastric buffers), and renal tubular acidosis or severe infections of the urinary tract caused by Proteus spp. , require careful monitoring of the patient’s condition.

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

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.

Form of production

Film-coated tablets,10 mg.

10 tablets in a contour cell package made of combined PVC material/PVDH and aluminum foil.

3 or 6 contour cell packages together with the instructions for use are placed in a pack of cardboard.

Storage conditions

At a temperature not exceeding 25 °C, in the original packaging.

Keep out of reach of children.

Shelf

life is 2 years.

Do not use the drug after the expiration date.

Active ingredient

Memantine

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Alcoholism, Concussion and other traumatic brain injuries, Alzheimer’s disease, Stroke effects, Acquired dementia