Product Overview
Composition
One film-coated tablet contains:
Dosage 10 mg
active substance:
memantine hydrochloride - 10.0 mg;
Excipients:
microcrystalline cellulose - 152.5 mg;
calcium hydrogen phosphate dihydrag - 50.0 mg;
croscarmellose sodium - 12.5 mg;
lactose monohydrate -10.0 mg;
hyprolose (hydroxypropyl cellulose) - 5.0 mg;
talcum powder - 5.0 mg;
colloidal silicon dioxide - 2.5 mg;
magnesium stearate - 2.5 mg;
film sheath:
[hypromellose - 4,000 mg, hyprolose (hydroxypropyl cellulose) - 1,552 mg, talc - 1,568 mg, titanium dioxide - 0,880 mg] or [dry film coating mixture containing hypromellose (50%), hyprolose (hydroxypropyl cellulose) (19.4%) , talc (19.6%), titanium dioxide (11%)] - 8.0 mg.
pharmachologic effect
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.
Suction
Eating does not affect absorption. After oral administration, memantine is rapidly and completely absorbed from the gastrointestinal tract. The maximum concentration of memantine in blood plasma is reached after 3-8 hours after administration.
Distribution
Daily intake of a daily dose of 20 mg leads to an equilibrium plasma concentration of memantine of 70-150 ng / ml. When applying a daily dose of 5-30 mg, the ratio of the average concentration in cerebrospinal fluid to the concentration in 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. With normal renal function, no cumulation of memantine was noted.
Metabolism
80% of the memantine circulating in the blood is represented by an unchanged substance. The main metabolites are N-3,5-dimethylgludantan, a mixture of isomers of 4- and 6-hydroxyemantine, 1-nitroso-3,5-dimethyladamantane. Metabolites do not have their own pharmacological activity. During in vitro experiments, no metabolism was detected by cytochrome P450 isoenzymes.
Breeding
Memantine is excreted mainly by the kidneys. Excretion occurs single-phase, the half-life is 60-100 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 under conditions of 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 transition 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, which for memantine is 0.5 μmol in the frontal cortex.
Indications
Pregnancy and lactation
The period of breastfeeding There is no information on the allocation of memantine with breast milk, therefore, women taking memantine should stop breastfeeding.
Recommendations for use
Memantine therapy should be started and carried out under the supervision of a physician with experience in the diagnosis and treatment of Alzheimer's type dementia. The diagnosis should be established in accordance with current recommendations.
Treatment should only be started if the person who is constantly caring for the patient will regularly monitor the patient's intake of the drug.
Tolerance and dosage of memantine should be regularly reviewed, preferably within the first three months after the start of treatment. Following this, the clinical efficacy of memantine and patient tolerance to treatment should be reviewed in accordance with current clinical guidelines.
Supportive treatment can be continued indefinitely with a positive therapeutic effect and good tolerance to the drug.
Reception of memantine should be stopped in the absence of a positive therapeutic effect or patient intolerance to the drug.
The drug should be taken orally once a day and always at the same time, regardless of the meal.
Memantine treatment is recommended with minimally effective doses.
Apply during the 1st week of therapy (days 1-7) at a dose of 5 mg / day, during the 2nd week (days 8-14) at a dose of 10 mg / day, during the 3rd week (days 15- 21) at a dose of 15 mg / day, starting from the 4th week - at a dose of 20 mg / day.
The recommended maintenance dose is 20 mg / day.
The maximum daily dose is 20 mg.
Special patient groups
Elderly patients (over 65 years old)
Dose adjustment is not required.
Patients with impaired renal function
In patients with creatinine clearance of 50-80 ml / min, dose adjustment is not required.
In patients with moderate renal failure (creatinine clearance of 30-49 ml / min), the recommended daily dose is 10 mg. With good tolerance of this dose for 7 days, the dose can be increased to 20 mg / day in accordance with the standard scheme.
In patients with severe renal failure (creatinine clearance 5-29 ml / min), the daily dose should not exceed 10 mg.
Patients with impaired liver function
In patients with impaired liver function of mild and moderate degree (class A and B according to the classification of Child-Pyo) dose adjustment is not required.
Patients with severe hepatic insufficiency (class C according to the Child-Pugh classification) use of the drug is contraindicated.
Contraindications
- severe liver failure (class C according to the Child-Pugh classification);
- lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome;
- pregnancy;
- period of breastfeeding;
- age up to 18 years (effectiveness and safety have not been established).
- Thyrotoxicosis;
- epilepsy, predisposition to epilepsy;
- convulsions (including a history);
- simultaneous use of NMDA receptor antagonists (amantadine, ketamine, dextromethorphan);
- the presence of factors that increase the pH of urine (a sharp change in diet, for example, switching to a vegetarian diet, heavy intake of alkaline gastric buffers);
- renal tubular acidosis;
- severe urinary tract infections caused by bacteria of the genus Proteus;
- myocardial infarction (history);
- heart failure (III-IV functional class according to NYHA classification);
- uncontrolled arterial hypertension;
- renal failure;
- liver failure (class A and B according to the Child-Pugh classification).
Side effects
Classification of the incidence of side effects according to the recommendations 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, including single messages; the frequency is unknown - according to available data, it is not possible to establish the frequency of occurrence.
From the central nervous system:
often - headache, dizziness, drowsiness, imbalance;
infrequently - gait disturbance, confusion, hallucinations (hallucinations were observed mainly in patients with severe Alzheimer's type dementia);
very rarely - cramps;
the frequency is unknown - psychotic reactions, impaired consciousness, increased irritability, depression, anxiety, suicidal thoughts, increased intracranial pressure, muscle hypertonicity.
From the cardiovascular system:
often - increase in blood pressure;
infrequently - venous thrombosis / thromboembolism, heart failure.
From the digestive system:
often constipation;
infrequently - nausea, vomiting;
frequency is unknown - pancreatitis, hepatitis.
From the respiratory system:
often shortness of breath.
From the genitourinary system:
the frequency is unknown - acute renal failure, cystitis, increased libido.
Allergic reactions:
often - hypersensitivity to the components of the drug;
frequency unknown - allergic reactions, Stevens-Johnson syndrome.
On the part of the skin:
frequency unknown - thrombocytopenic purpura.
Laboratory indicators:
often - increased activity of "liver" enzymes;
the frequency is unknown - agranulocytosis, leukopenia (including neutropenia), pancytopenia, thrombocytopenia.
Other:
infrequently - increased fatigue;
rarely, fungal infections; frequency unknown - candidiasis.
Interaction
With the simultaneous use of memantine with barbiturates, antipsychotics, their effect may decrease.
With the simultaneous use of memantine with dantrolene or baclofen, as well as with antispasmodics, their effect may change (increase or decrease), so the doses of drugs should be selected individually.
The simultaneous use of memantine with amantadine should be avoided because of the risk of developing psychosis. Both compounds are antagonists of NMDA receptors.
The risk of developing psychosis is also increased with the simultaneous use of memantine with phenytoin, ketamine and dextromethorphan.
With the simultaneous use of memantine with cimetidine, ranitidine, procainamide, quinidine, quinine and nicotine, the risk of increasing the concentration of memantine in the blood plasma increases.
With the simultaneous use of memantine with hydrochlorothiazide, a decrease in the concentration of hydrochlorothiazide in blood plasma is possible due to an increase in its excretion from the body.
An increase in the international normalized ratio (INR) is possible in patients taking simultaneously oral indirect anticoagulants (warfarin). It is recommended to regularly monitor prothrombin time or INR in patients taking indirect anticoagulants at the same time.
The simultaneous use of memantine with antidepressants, selective serotonin reuptake inhibitors and monoamine oxidase inhibitors requires careful monitoring of patients.
According to pharmacokinetic studies, in young healthy volunteers with a single simultaneous administration of memantine with glibenclamide / metformin or donepezil, no drug interaction effects were detected.
Clinical studies also did not reveal the effect of memantine on the pharmacokinetics of galantamine in young healthy volunteers.
In in vitro studies, memantine did not inhibit CYP 1A2, 2A6, 2C9, 2D6, 2E1, 3A isoenzymes, monooxygenase containing flavin, epoxyhydrolase, and sulfation.
Overdose
Limited overdose data are available from clinical trials and post-registration monitoring.
Symptoms
An overdose when taking relatively large doses of memantine (200 mg once, or 105 mg per day for 3 days) is expressed by symptoms of fatigue, weakness and / or diarrhea, or lack of symptoms. An overdose when taking up to 140 mg of memantine once or an unknown amount of memantine is expressed by symptoms associated with the central nervous system (confusion, drowsiness, dizziness, vertigo, anxiety, agitation, hallucinations, impaired gait) and / or gastrointestinal disturbances (vomiting, diarrhea )
In the most serious cases of overdose, the patient survived after taking more than 2000 mg of memantine with adverse effects from the nervous system (coma for 10 days, later diplopia, agitation). The patient received symptomatic therapy and plasmapheresis, and recovered without consequences.
Another described case of a serious overdose is 400 mg of memantine once. The patient recovered without consequences. Undesirable effects from the nervous system were noted: anxiety, psychosis, visual hallucinations, stupor, bouts of seizures, drowsiness, unconsciousness.
Treatment
Symptomatic therapy, gastric lavage, intake of adsorbents (activated carbon), urine acidification, forced diuresis (if necessary). There is no specific antidote.
Special instructions
The data on the use of memantine in patients with a history of myocardial infarction, chronic heart failure (NYHA class III-IV functional class), or uncontrolled hypertension are limited, therefore careful medical monitoring of such patients is necessary.
Use with caution in patients with thyrotoxicosis, epilepsy, seizures (including a history) and a predisposition to epilepsy.
The simultaneous use of memantine and antagonists of NMDA receptors such as amantadine, ketamine and dextromethorphan should be avoided. These compounds act on the same receptor system as memantine, and therefore adverse reactions (mainly from the central nervous system) can occur more often and be more pronounced.
Memantine contains lactose monohydrate. Patients with hereditary galactose intolerance, lactase deficiency or glucose-galactose malabsorption should not take the drug Memantine.
In patients with moderate to severe Alzheimer's type dementia, the ability to drive vehicles and control complex mechanisms is usually impaired. In addition, memantine can cause a change in the reaction rate, so patients need to refrain from driving or working with complex mechanisms.
Release form
Storage conditions
Store in a dark place at a temperature of no higher than 25 ° C.
Keep out of the reach of children.
