Membral 10mg 60 tablets — Made in Ukraine — Free Delivery

Pharmacological properties

Pharmacodynamics. In the manifestation of symptoms and the progression of neurodegenerative dementia, impairment of glutamatergic neurotransmission plays an important role, especially with the participation of nmda (n-methyl-d-aspartate) receptors.

Memantine is a voltage-gated, medium affinity, non-competitive NMDA receptor antagonist. Memantine modulates the effects of abnormally elevated glutamate levels that can lead to neuronal dysfunction.

Pharmacokinetics. The absolute bioavailability of memantine is approximately 100%, the time to reach Cmax in blood plasma is from 3 to 8 hours. There are no signs of the effect of food intake on absorption.

Distribution. A daily dose of 20 mg provides a stable plasma concentration of memantine in the range of 70–150 ng / ml (0.5–1 µmol) with significant individual variations. When used in doses of 5-30 mg / day, the ratio of the preparation content in the cerebrospinal fluid and blood serum is 0.52. The volume of distribution is about 10 l / kg of body weight. Approximately 45% of memantine binds to blood plasma proteins.

Biotransformation. In the human body, about 80% of memantine circulates as a starting substance, the main metabolites do not have NMDA antagonistic properties. The participation of cytochrome P450 in in vitro metabolism has not been identified. The main metabolites are N-3,5-dimethylgluantane, an isomeric mixture of 4- and 6-hydroxymemantine and 1-nitroso-3,5-dimethyl-adamantane.

Elimination. Memantine is eliminated monoexponentially with T½ from 60 to 100 hours. In volunteers with normal renal function, the total clearance is 170 ml / min / 1.73 m2. The renal stage of memantine pharmacokinetics also includes tubular reabsorption. The rate of renal elimination of memantine under conditions of an alkaline urine reaction can be reduced by 7-9 times. Alkalinization of urine is possible as a result of significant changes in the diet, for example, replacing a diet rich in meat dishes with a vegetarian one or due to intensive use of antacid stomach preparations.

Linearity. Pharmacokinetics is linear in the dose range of 10–40 mg / day.

Pharmacodynamic / pharmacokinetic relationship. At a dose of memantine of 20 mg / day, the level of content in the cerebrospinal fluid corresponds to the value of ki (inhibition constant) of memantine, which is 0.5 μmol in the area of ​​the human frontal cortex.

Indications

Alzheimer's type dementia, mild to severe.

Application

Inside. the dosage regimen is set by the doctor individually.

Treatment should be started and carried out under the supervision of a physician. Therapy can only be started if there is a guardian who will regularly monitor the patient's intake of the preparation. The tablets should be taken 1 time per day every day at the same time. The tablets can be taken with or without food.

Adults. The maximum daily dose is 20 mg. In order to reduce the risk of adverse reactions, the maintenance dose is determined by gradually increasing the dose by 5 mg / week during the first 3 weeks as follows:

1st week (1-7th day): take ½ tablet (5 mg / day) for a week;

2nd week (8-14th day): take 1 tablet (10 mg / day) for a week;

3rd week (15-21 days): take 1½ tablets (15 mg / day) for a week;

starting from the 4th week: take 2 tablets (20 mg / day) per day.

The recommended maintenance dose is 20 mg / day.

The duration of treatment is individually determined by a physician who has experience in the diagnosis and treatment of dementia in Alzheimer's disease. The tolerance and dosage of memantine should be regularly assessed, preferably within 3 months from the start of treatment. Further, the clinical effect of memantine and the patient's response to therapy should be assessed regularly in accordance with current clinical guidelines.

Maintenance treatment can be continued as long as the therapeutic effect remains favorable and the patient's tolerance of memantine is good. The possibility of discontinuing memantine therapy should be considered if signs of a therapeutic effect disappear or the patient's tolerance to treatment worsens.

Elderly patients. Based on the results of clinical studies, the recommended dose for patients aged ≥65 years is 20 mg / day (2 tablets, 10 mg once a day), as indicated above.

Impaired renal function. For patients with mild renal impairment (creatinine clearance - 50–80 ml / min), it is not required to reduce the dose of the preparation. In patients with moderate renal impairment (creatinine clearance - 30–49 ml / min), the daily dose should be reduced to 10 mg. The dose can be increased to 20 mg / day according to the standard scheme, if there are no negative reactions after at least 7 days of treatment. In patients with severe renal impairment (creatinine clearance - 5-29 ml / min), the daily dose should be reduced to 10 mg.

Liver dysfunction. For patients with mild or moderate hepatic impairment (Child-Pugh A, B), dose adjustment is not required. The use of memantine in patients with severe hepatic dysfunction is not recommended.

Contraindications

Hypersensitivity to the active substance or to any component of the preparation. severe renal dysfunction. During pregnancy and breastfeeding. children's age (up to 18 years old).

Side effects

In studies involving patients with mild to severe dementia who were treated with memantine, and the placebo effect, it was found that the overall incidence of side effects with memantine did not differ from that of patients who received placebo; mild to moderate adverse reactions have been reported. the most common adverse reactions were dizziness, headache, constipation, drowsiness and ag.

Infections and invasions: fungal infections.

From the immune system: hypersensitivity.

From the side of the psyche: drowsiness, confusion, hallucinations (mainly observed in patients with severe Alzheimer's disease), psychotic reactions (isolated reports).

From the side of the cardiovascular system: hypertension, venous thrombosis / thromboembolism, heart failure.

From the respiratory system: shortness of breath.

From the digestive tract: constipation, nausea, vomiting, pancreatitis (isolated messages).

From the side of the central nervous system: dizziness, gait disturbance, imbalance, convulsions.

From the hepatobiliary system: increased liver function indicators, hepatitis.

General disorders: headache, fatigue.

Liver dysfunction and / or jaundice may occur with an increase in the level of AST (glutamate oxaloacetate transaminase), ALAT (glutamate pyruvate transaminase), alkaline phosphatase, bilirubin. Patient health should be closely monitored. If there are any atypical indicators, the preparationshould be discontinued and appropriate measures taken.

Alzheimer's disease is associated with depression, suicidal ideation and suicide. Such cases are known with the use of memantine.

Reports of suspected adverse reactions. During the use of the preparation, it is important to report the suspicion of any adverse reactions. This makes it possible to continuously monitor the benefit / risk ratio of the preparation.

Special instructions

Caution should be exercised when prescribing the preparation to patients with epilepsy, to persons with a history of seizure episodes, as well as to patients with risk factors for the development of epilepsy.

Simultaneous use with N-methyl-D-aspartate (NMDA) antagonists such as amantadine, ketamine or dextromethorphan should be avoided. These compounds affect the same receptor system as memantine, so side effects (mainly related to the central nervous system) may be more frequent or more pronounced.

Several factors that cause an increase in urine pH may necessitate close monitoring of the patient's health. These factors include profound dietary changes, such as replacing a meat-rich diet with a vegetarian one, or heavy use of antacid stomach preparations. In addition, urine pH may rise due to conditions of renal tubular acidosis (TPA) or severe urinary tract infections caused by Proteus bacteria.

In most clinical trials, patients who have recently suffered myocardial infarction and persons with decompensated chronic heart failure (III – IV degrees), as well as with uncontrolled hypertension, were excluded from the number of participants. As a result, only limited relevant data are available, and patients with these conditions require careful monitoring.

Use during pregnancy and lactation. The use of the preparation is contraindicated. Women using memantine should refrain from breastfeeding.

Children. The preparation is not prescribed to children (under 18 years of age) due to insufficient data on safety and efficacy.

The ability to influence the reaction rate when driving or working with other mechanisms. Patients with Alzheimer's disease at the stage of moderate to severe dementia usually have impaired ability to drive or operate other machinery. In addition, memantine can cause a change in the reaction rate, therefore, patients receiving treatment on an outpatient basis should be especially careful when driving or operating other mechanisms.

Interactions

The simultaneous use of memantine and amantadine should be avoided due to the risk of pharmacotoxic psychosis. both compounds are chemically bound nmda antagonists. the same may be true for ketamine and dextromethorphan. reported the possible risk of the combined use of memantine and phenytoin.

The mechanism of action provides for the possible enhancement of the effects of levodopa, dopaminergic agonists and anticholinergics with the simultaneous use of NMDA antagonists such as memantine. It is possible to weaken the effects of barbiturates and antipsychotics. The combined use of memantine and antispasmodics, dantrolene or baclofen can modify their effects, which may necessitate dose adjustments.

Other preparations such as cimetidine, ranitidine, procainamide, quinidine, quinine, and nicotine, which use the same renal cationic transport system as amantadine, may also interact with memantine, posing a potential risk of increased plasma levels.

With the combined use of memantine with hydrochlorothiazide or any combination with hydrochlorothiazide, a decrease in the level of the latter in the blood serum is possible.

There have been reports of isolated cases of an increase in the international normalized ratio with the use of memantine in patients using warfarin. Although a causal relationship has not been established, careful monitoring of prothrombin time or international normalized ratio is required in patients concomitantly using oral anticoagulants.

In the course of pharmacokinetic studies among healthy volunteers, significant effects of the interaction of memantine with glyburide / metformin, donepezil or galantamine were not revealed.

Memantine in vitro is not an inhibitor of CYP 1A2, 2A6, 2C9, 2D6, 2E1, 3A, flavin-containing monooxygenase, epoxide hydrolase or sulfathione.

Overdose

Experience is limited.

Symptoms Overdose in relatively large volumes (200 and 105 mg / day for 3 days) is associated either only with symptoms such as fatigue, weakness and / or diarrhea, or the complete absence of any symptoms. When taking doses of 140 mg / day or unknown doses, patients noted disorders from the central nervous system (confusion, drowsiness, vertigo, agitation, aggressiveness, hallucinations and gait disturbances) and / or from the digestive tract (vomiting and diarrhea).

In the most famous severe case of an overdose, the patient survived after oral administration of a total dose of 2000 mg of memantine, and he had CNS disorders (coma for 10 days, later diplopia and agitation). The patient underwent symptomatic treatment and plasmapheresis. The patient recovered completely without any permanent residual effects.

Treatment. In case of an overdose, symptomatic treatment is performed. There is no specific antidote. If necessary, standard clinical procedures are carried out to remove the active substance from the body, namely, gastric lavage, the use of activated carbon (to disrupt possible intestinal-hepatic recirculation), acidification of urine, forced diuresis.

Storage conditions

At a temperature not higher than 25 ° C.