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

Excipients: lactose monohydrate 51.45 mg, microcrystalline cellulose 175.00 mg, silicon dioxide colloid 2.50 mg, talc 9.80 mg, magnesium stearate 1.25 mg

Film sheath: methacrylic acid and ethyl acrylate copolymer (1: 1), 30% aqueous dispersion¹ 0,60² mg, talc 0.27 mg, triacetin 0.12 mg, simethicone 0.01 mg

¹The 30% aqueous dispersion contains, in addition to methacrylic acid and ethyl acrylate copolymer, also sodium lauryl sulfate (0.7% calculated on dry matter in suspension) and polysorbate-80 (2.3% calculated on dry matter in suspension) as emulsifiers.

²It is expressed as the mass of a dry substance entering into a 30% aqueous dispersion.

Description:Oval, biconvex tablets, covered with a film shell of white color, with a risk on one side. View at the break: uneven white surface.

Pharmacotherapeutic group:Treatment for dementia

ATX: & nbsp

N.06.D.X.01 Memantine

N.06.D.X Other drugs for the treatment of dementia

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

Pharmacokinetics:

Suction

Quickly and completely absorbed after ingestion. The maximum concentration in the blood plasma (C_max) is achieved within 3-8 hours after ingestion. In patients with normal renal function, cumulation of memantine was not observed.

Distribution

With daily intake of a dose of 20 mg per day, the equilibrium concentrations of memantine in blood plasma are 70-150 ng / ml. When a daily dose of 5-30 mg was used, the ratio of the mean concentration in the cerebrospinal fluid to the concentration in the blood plasma was calculated to be 0.52. The volume of distribution is about 10 l / kg.About 45% of memantine binds to blood plasma proteins.

Metabolism

About 80% of the memantine taken internally is excreted unchanged. The main metabolites of N-3,5-dimethyl-gludanant, the isomer mixture of 4- and 6-hydroxy-memantine and 1-nitroso-3-5-dimethyl-adamantane do not have intrinsic pharmacological activity. Under conditions of in vitro metabolism, carried out by cytochrome P450 isoenzymes, it was not revealed. In the study with oral administration¹⁴C-memantine averaged 84% of the ingested dose was withdrawn within 20 days, with more than 99% excreted by the kidneys.

Excretion

It is excreted from the body monoexponentially. Half-life (T_1/2) 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 through tubular secretion. Renal excretion also includes tubular reabsorption, possibly mediated by cationic transport proteins. The rate of renal elimination of memantine in conditions of alkaline urine reaction can decrease by 7-9 times. The alkalinization of urine can be caused by a sudden change in diet,for example, a transition from a diet that includes products of animal origin to a vegetarian diet, or due to the intensive use of alkaline gastric buffers.

Linearity

Studies conducted in volunteers showed the linearity of pharmacokinetics in the dose range of 10-40 mg.

Pharmacokinetic / pharmacodynamic dependence

When memantine is used at a dose of 20 mg / day, the concentration level in the cerebrospinal fluid corresponds to the value of the inhibition constant (k_i), that for memantine is 0.5 μmol in the region of the frontal cortex of the brain.

Indications:Treatment of patients with Alzheimer's disease of moderate and severe degree.

Contraindications:

- Hypersensitivity to memantine and other components of the drug.

- Severe hepatic insufficiency (class C on the Child-Pugh scale).

- Pregnancy and the period of breastfeeding.

- Age under 18 years (efficiency and safety not established).

- Deficiency of lactase, lactose intolerance, glucose-galactose malabsorption syndrome; the composition of the drug Maruksu® includes lactose.

Carefully:Epilepsy, thyrotoxicosis, a predisposition to the development of seizures; simultaneous use of NMDA receptor antagonists (amantadine, ketamineDextromethorphan), factors that increase the pH of urine (abrupt change of diet, for example, switching to a vegetarian, abundant reception alkali gastric buffer), renal tubular acidosis, severe urinary tract infection caused by Proteus spp., Myocardial infarction (history), heart failure III-IV functional class according to NYHA classification, uncontrolled arterial hypertension, renal failure, hepatic insufficiency.

Pregnancy and lactation:

In connection with a possible delay in intrauterine development, Maruksa ® is not used in pregnancy.

There is no information on the allocation of memantine to breast milk. However, given the lipophility of memantine, isolation is possible. Therefore, during the treatment with Maruksu®, breastfeeding should be stopped.

Dosing and Administration:Therapy should be carried out under the supervision of a physician experienced in the diagnosis and treatment of dementia in Alzheimer's disease. Therapy should be started only if the person, who regularly cares for the patient, will monitor the taking of the medication. The diagnosis should be made in accordance with the current recommendations.

The tolerability and dose of Marooks® should be evaluated regularly, preferably within three months after initiation of therapy. Then, the clinical efficacy of the drug and the tolerability of therapy should be regularly assessed in accordance with current clinical guidelines.

Supportive therapy can be continued indefinitely, with the therapeutic effect and good tolerability of the Marooks ® preparation. It should stop using Marooks ® 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.

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

The following dosing regimen is recommended:

1-st week (1-7 days): daily dose - 5 mg (1/2 tablet of Maruksa® 10 mg every day for 7 days);

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

Week 3 (15-21 days): daily dose - 15 mg (1 1/2 tablets of Maruksa ® 10 mg every day for 7 days);

Starting with the 4th week: a daily dose of 20 mg (2 tablets Maruksa 10 mg every day).

Patients of advanced age (over 65 years)

Correction of the dose is not required.

Impaired renal function

In patients with a creatinine clearance (CK) of 50-80 ml / min, no dose adjustment is required. Patients with moderate renal failure (CK 30-49 ml / min) are recommended 10 mg / day. If the drug is well tolerated within 7 days, the dose can be increased to 20 mg / day according to the standard scheme. In patients with severe renal failure (SC 5-29 ml / min) daily dose should be 10 mg / day.

Impaired liver function

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

Side effects:

Classification of the frequency of development 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 of the unknown can not be estimated from the available data.

In clinical trials, including 1784 patients who received memantine, And 1595 patients treated with placebo, the overall incidence of adverse events did not differ when receiving memantine and placebo. As a rule, they were from mild to moderate severity. The most frequent adverse reactions were memantine group compared to placebo: dizziness (6.3% versus 5.6%, respectively), headache (5.2% vs. 3.9%), constipation (4.6% vs. 2 , 6%), somnolence (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:

Infectious and parasitic diseases	Rarely	Fungal infections
Violations of the blood and lymphatic system	Frequency unknown	Agranulocytosis, leukopenia (including neutropenia), pancytopenia, thrombocytopenia, thrombocytopenic purpura
Immune system disorders	Often	Hypersensitivity to the drug components
Disorders of the psyche	Often	Drowsiness
	Infrequently	Confusion of consciousness Hallucinations¹
	Frequency unknown	Psychotic reactions
Disturbances from the nervous system	Often	Dizziness, imbalance
	Infrequently	Violation of gait
	Rarely	Convulsions
Heart Disease	Infrequently	Heart failure
Vascular disorders	Often	Increased blood pressure
Vascular disorders	Infrequently	Venous thrombosis / thromboembolism
Disturbances from the respiratory system, chest and mediastinal organs	Often	Dyspnea
Disorders from the gastrointestinal tract	Often	Constipation
	Infrequently	Nausea, vomiting
	Frequency unknown	Pancreatitis
Disturbances from the liver and bile ducts	Often	Increased activity of "liver" enzymes
Disturbances from the liver and bile ducts	Frequency unknown	Hepatitis
Disorders from the kidneys and urinary tract	Frequency unknown	Acute kidney failure
Disturbances from the skin and subcutaneous tissues	Frequency unknown	Stevens-Johnson Syndrome
General disorders and disorders at the site of administration	Often	Headache
	Infrequently	Fatigability

¹Hallucinations were observed, mainly, in patients with Alzheimer's disease at the stage of severe dementia. In the post-marketing application, the following adverse reactions were reported: dizziness, drowsiness, increased excitability, increased fatigue, anxiety,increased intracranial pressure, nausea, hallucinations, headache, impairmente consciousness, muscular giPertonus, gait disturbance, depression, convulsions, psychotic reactions, suicidal thoughts, constipation, nausea, pancreatitis, candidiasis, increased blood pressure, vomiting, cystitis, increased libido, venous thrombosis, thromboembolism and allergic reactions.

Overdose:

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

In the worst case of overdose (2000 mg 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. Described side reactions from the central nervous system: anxiety, psychosis, visual hallucinations, convulsive alertness, drowsiness, stupor and loss of consciousness.

Treatment:

In case of an overdose, treatment is symptomatic. There is no specific antidote. It is necessary to conduct standard medical measures aimed at removing the active substance from the stomach, for example, gastric lavage, taking activated charcoal, urine acidification, it is possible to carry out forced diuresis.

Interaction:

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

The effectiveness of barbiturates, antipsychotic (antipsychotics) drugs is reduced against the background of simultaneous application of memantine.

Simultaneous use of memantine with dantrolene and baclofen, as well as with spasmolytics may be accompanied by a change in their effect, which requires correction of the dose of these drugs.

Simultaneous use of memantine and amantadine should be avoided in connection with 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 simultaneous use of memantine with phenytoin, ketamine and dextromethorphan.

When used simultaneously with cimetidine, ranitidine, procainamide, quinidine, quinine and nicotine, the risk of increasing memantine concentration in the blood plasma increases.

With simultaneous administration with hydrochlorothiazide, a decrease in the concentration of hydrochlorothiazide in the blood plasma is possible by increasing its excretion from the body. It is possible to increase the International Normalized Ratio (INR) in patients who simultaneously take oral indirect anticoagulants (warfarin). It is recommended that prothrombin time or INR is monitored regularly. Simultaneous use with antidepressants, selective serotonin reuptake inhibitors and monoamine oxidase inhibitors requires close monitoring of patients.

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

With simultaneous use with memantine, there have been no changes in the pharmacokinetics of galantamine in healthy volunteers.

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

Special instructions:

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

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

The presence of factors influencing the pH of the urine (sudden changes in diet, for example, the transition from a diet that includes 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.

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

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 managing motor vehicles or working with complex mechanisms.

Form release / dosage:Tablets, film-coated, 10 mg.

Packaging:

For 10 tablets in a contour mesh box made of a combined material of PVC / PVDC and aluminum foil.

For 3 or 6 contour squares, together with the instruction for use, they are placed in a pack of cardboard.

Storage conditions:

At a temperature of no higher than 25 ° C, in the original packaging.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-002372

Date of registration:13.01.2014

Expiration Date:13.01.2019

The owner of the registration certificate:KRKA-RUS, LLC KRKA-RUS, LLC Russia

Manufacturer: & nbsp

KRKA-RUS, LLC Russia

Representation: & nbspKRKA, dd, Novo mesto, AOKRKA, dd, Novo mesto, AO

Information update date: & nbsp26.03.2018

Illustrated instructions

Instructions

Maruksa® (Maruxa®)