Indications
Moderate to severe dementia in Alzheimer’s disease.
$2.00
Active ingredient: | |
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Dosage form: | |
Indications for use: | Alcoholism, Alzheimer's disease, Concussion and other brain injuries, Consequences of a stroke, Dementia |
Out of stock
Moderate to severe dementia in Alzheimer’s disease.
Individual hypersensitivity to memantin or any of the components that make up the drug; pregnancy and lactation; age up to 18 years (efficacy and safety have not been established); lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome, since the composition of the drug Memantinol ® includes lactose.
With caution:
Thyrotoxicosis, epilepsy, predisposition to seizures (including in the anamnesis), simultaneous use of NMDA receptor antagonists (amantadine, ketamine, dextromethorphan), the presence of factors that increase the pH of urine (sudden change of diet, for example, switching to vegetarianism, heavy intake of alkaline gastric buffers), renal tubular acidosis, severe urinary tract infections caused by bacteria of the genus Proteus, a history of myocardial infarction, NYHA functional class III-IV heart failure, uncontrolled arterial hypertension, renal failure, and liver failure.
1 film-coated tablet contains:
active substance:
excipients:
Shell composition: Opadray II white OY-L-28900 (lactose monohydrate-36%, hypromellose -28%, titanium dioxide-26%, macrogol 4000-10%) 7 mg.
1 film-coated tablet contains: Active ingredient:
excipients:
Shell composition: Opadray II white OY-L-28900 (lactose monohydrate-36%, hypromellose -28%, titanium dioxide-26%, macrogol 4000-10%) 7 mg
Pharmacodynamics
Memantine is a potential-dependent non-competitive inhibitor of NMDA receptors with moderate affinity for them. It modulates the effect of pathologically elevated tonic glutamate content, which can lead to neuronal dysfunction.
Pharmacokinetics
After oral use, it is rapidly and completely absorbed. The maximum concentration in the blood plasma is reached 3-8 hours after use.
The pharmacokinetics are linear in the dose range from 10 to 40 mg.
Daily intake of a daily dose of 20 mg leads to an equilibrium plasma concentration of 70 to 150 ng / ml (0.5-1 mmol) with pronounced individual variations. The volume of distribution is about 10 l / kg. About 45% of – memantine binds to plasma proteins. No accumulation of the drug was observed in normal renal function.
About 80% of memantine is present in the circulating blood as an unchanged compound. The main metabolites are N-3,5-dimethyl-gludantane, a mixture of isomers of 4 – and 6-hydroxy-memantine and 1-nitroso-3,5-dimethyl-adamantane. None of these metabolites has antagonistic activity against NMDA receptors.
Cytochrome P 450 metabolism has not been shown to be involved in in vitro studies. In studies taking 14C-memantine orally, an average of 84% of the dose was eliminated within 20 days, while more than 99% of the drug was excreted by the kidneys.
Memantine is mainly excreted by the kidneys. Elimination is monoexponential, with a half-life of 60 to 100 hours. In studies in volunteers with normal renal function, the total clearance was 170 ml / min/1.73 m2, part of the total renal clearance was achieved due to secretion by the renal tubules.
Renal elimination also includes tubular reabsorption, which may be carried out by cationic transport proteins. The rate of renal elimination under conditions of an alkaline reaction of urine can decrease by 7-9 times.
Alkalinization of urine can result from a sudden change in diet, for example, the transition from eating mainly meat products to vegetarianism, or due to the intensive use of alkaline gastric buffers.
Pharmacokinetic-pharmacodynamic relationship:
When taking a maintenance dose of 20 mg/day, the level of memantine concentration in the cerebrospinal fluid corresponds to kj (kj is the inhibition constant), which for memantine is 0.5 mmol in the human frontal cortex.
Moderate to severe dementia in Alzheimer’s disease.
It is contraindicated during pregnancy, as there are no clinical data on the effect of memantine on the course of pregnancy. Studies conducted in animals indicate that the drug can cause intrauterine growth retardation at the level of exposure to identical or slightly higher concentrations of memantine compared to those in humans. The potential risk to humans is not known. It is not known whether memantine is excreted in breast milk, so women taking memantine should refrain from breast-feeding.
Individual hypersensitivity to memantin or any of the components that make up the drug; pregnancy and lactation; age up to 18 years (efficacy and safety have not been established); lactase deficiency, lactose intolerance, glucose-galactose malabsorption syndrome, since the composition of the drug Memantinol ® includes lactose. With caution: Thyrotoxicosis, epilepsy, predisposition to seizures (including in the anamnesis), simultaneous use of NMDA receptor antagonists (amantadine, ketamine, dextromethorphan), the presence of factors that increase the pH of urine (sudden change of diet, for example, switching to vegetarianism, heavy intake of alkaline gastric buffers), renal tubular acidosis, severe urinary tract infections caused by bacteria of the genus Proteus, a history of myocardial infarction, NYHA functional class III-IV heart failure, uncontrolled arterial hypertension, renal failure, and liver failure.
Adverse reactions are classified according to clinical manifestations (according to damage to certain organ systems) and frequency of occurrence according to the classification of the World Health Organization (WHO): very common (>1/10), common (>>1/100 to >><1/10), infrequent (>1/1000 to <1/10), infrequent (><1/100), rare (>1/10000 to <1/100), rare (><1/1000), very rare (In clinical trials for moderate and severe dementia, including 1,784 patients treated with memantine and 1,595 patients treated with placebo, the overall incidence of adverse reactions with memantine did not differ from that with placebo. As a rule, adverse reactions were observed-mild or moderate severity. The most common adverse reactions in the memantine group compared to the placebo group 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%), and hypertension (4.1% vs. 2.8%, respectively). Adverse reactions are presented in a table:
Infectious and parasitic diseases | Infrequently | Fungal infections |
Immune system disorders | are Common | Hypersensitivity to the components of the drug |
Mental disorders | Are Common | Drowsiness |
Infrequently | Confusion | |
Hallucinations 1 | ||
Frequency not established | Psychotic reactions 2 | |
Nervous system disorders | are Common | Dizziness, disbalance |
Infrequently | Gait disorder | |
Very rare | Convulsions | |
Disorders of the cardiovascular system | are common | Increased blood pressure |
Infrequently | Venous thrombosis/thromboembolism | |
Respiratory, thoracic, and mediastinal | disorders are common | Shortness of breath |
Gastrointestinal disorders | Often | Constipation |
Infrequently | Nausea, vomiting | |
Frequency not established | Pancreatitis | |
Liver and biliary tract disorders | are common | Elevated liver test rates |
Frequency not established | Hepatitis | |
Common Reactions | Often | Headache |
Infrequently | Fatigue |
1 Hallucinations were observed mainly in patients with Alzheimer’s disease at the stage of severe dementia. 2 Separate reports received during the post-marketing experience with memantine.
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, allergic reactions.
When used concomitantly with levodopa preparations, dopamine receptor agonists, and anticholinergic drugs, the effect of the latter may be enhanced.When used concomitantly with barbiturates, neuroleptics, the effect of the latter may decrease. When used concomitantly with dantrolen or baclofen, as well as with antispasmodics, their effect may change (increase or decrease), so the dose of drugs should be adjusted. Concomitant use of memantine with 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 co-administered with ketamine, dextromethorphan, and phenytoin. When taken concomitantly with cimetidine, ranitidine, procainamide, quinidine, quinine and nicotine, it is possible to increase the plasma concentration of memantine. It is possible to reduce the level of hydrochlorothiazide when taken simultaneously with memantine by increasing its excretion from the body. An increase in MHO (International normalized ratio) may occur in patients taking concomitant oral indirect anticoagulants (warfarin). It is recommended to constantly monitor prothrombin time or MHO. Concomitant use with antidepressants, selective serotonin reuptake inhibitors, and monoamine oxidase inhibitors requires careful monitoring of patients. According to the data of pharmacokinetic studies conducted in young healthy volunteers, no drug interaction effects were detected with a single simultaneous use of memantine with glyburide/metformin or donepezil. Clinical studies also did not reveal the effect of memantine on the pharmacokinetics of galantamine in young healthy volunteers. In vitro studies, memantine did not inhibit the isoenzymes CYP1A2,2A6,2C9,2D6,2E1A, flavin-containing monooxygenase, epoxidohydrolase, or sulfation.
Treatment with memantine should be initiated and supervised by a physician experienced in the diagnosis and treatment of dementia in Alzheimer’s disease. The diagnosis should be made in accordance with the current guidelines. Treatment should only be initiated if the patient’s permanent caregiver regularly monitors the patient’s medication intake. The tolerability and dosage of memantine should be reviewed regularly, preferably within the first three months of starting therapy. After this period, the clinical efficacy of memantine and the patient’s tolerance to treatment should be regularly reviewed in accordance with current clinical guidelines. Maintenance treatment can be continued indefinitely if there is a positive effect of the therapy and the treatment is well tolerated. Memantine should be discontinued if there is no positive therapeutic effect or if the patient is intolerant to the treatment. The drug should be taken orally once a day and always at the same time, regardless of food intake. Adults:Dose titration:The maximum daily dose is 20 mg/day. In order to reduce the risk of adverse reactions, the dose of the drug is titrated by increasing it sequentially by 5 mg every week for the first three weeks:during the 1st week of therapy (days 1-7), the patient should take memantine at a dose of 5 mg/day (half a 10 mg tablet), during the 2nd week (days 8-14)-at a dose of 10 mg/day (one 10 mg tablet), during the 3rd week (days 15-21)-at a dose of 15 mg/day (one and a half 10 mg tablets). Starting from the 4th week, the patient is prescribed memantine at a dose of 20 mg / day (two tablets of 10 mg). The recommended maintenance dose is 20 mg per day. Special patient groups
Elderly patients (over 65 years of age)
No dose adjustment is required.
Patients with impaired renal function
In patients with a creatinine clearance of 50-80 ml/min, no dose adjustment is required. For patients with moderate renal insufficiency (creatinine clearance 30-49 ml / min), the recommended daily dose is 10 mg/day. If this dose is well tolerated for 7 days, the dose can be increased to 20 mg / day in accordance with the standard titration scheme.
In patients with severe renal insufficiency (creatinine clearance 5-29 ml / min), the daily dose should not exceed 10 mg/day.
Patients with impaired liver function
In patients with mild to moderate hepatic impairment (Child-Pugh class A and Class B), no dose adjustment is required. There are no data on the use of memantine in patients with severe hepatic impairment, so the appointment of memantine in such patients is not recommended.
There are limited overdose data available from clinical trials and post-marketing experience with memantine. Symptoms:
Relatively large overdoses (200 mg once and 105 mg / day for 3 days) were observed. the following symptoms: fatigue, weakness, and / or diarrhea, or no symptoms.
In cases of overdose at a dose of less than 140 mg once or when taking an unknown dose, patients experienced adverse reactions from the central nervous system: confusion, hypersomnia, drowsiness, dizziness, agitation, aggression, hallucinations, gait disorders) and/or from the digestive system: vomiting, diarrhea.
In the most severe case of overdose, the patient survived after taking a dose of 2000 mg of memantine, he had adverse reactions from the central 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, the patient survived and recovered after taking memantine 400 mg once. The patient experienced adverse reactions from the central nervous system: anxiety, psychosis, visual hallucinations, a decrease in the threshold of 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 medical measures aimed at the complete elimination of the substance from the stomach, for example, gastric lavage, taking activated charcoal, acidification of urine, and possibly forced diuresis.
It is recommended to use with caution in patients with thyrotoxicosis, epilepsy, seizures (including in the anamnesis), as well as in patients with a predisposition to epilepsy. Concomitant use of NMDA receptor antagonists (amantadine, ketamine, dextromethorphan) and memantine should be avoided. These compounds act on the same receptor system as memantine, and therefore adverse reactions (mainly from the central nervous system) may occur more often and be more pronounced. Given the slow elimination of memantine in patients with an alkaline urine reaction, patients with factors that affect the increase in urine pH (a sharp change in diet, for example, when switching from eating mainly meat products to vegetarianism, intensive consumption of alkaline gastric buffers), as well as in cases of renal tubular acidosis or severe urinary tract infection caused by bacteria of the genus Proteus, need more careful monitoring. Data on the use of memantine in patients with a history of myocardial infarction, with chronic heart failure of functional class III-IV (NYHA classification) and uncontrolled arterial hypertension. They are limited, so careful medical monitoring of such patients is necessary.
Effect of the drug on the ability to drive vehicles, mechanisms
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.
Store in a dry place protected from light at a temperature not exceeding 25°C. Keep out of reach of children!
life is 2 years.
Memantine
By prescription
Tablets
For adults as directed by your doctor
Consequences of stroke, Alzheimer’s disease, Concussion and other traumatic brain injuries, Alcoholism, Acquired dementia
Out of stock
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