Memantine is a medium-affinity, non-competitive, NMDA receptor antagonist (N-methyl-D-aspartic acid). It modifies the effects of pathologically increased concentrations of glutamate, which can lead to neuronal dysfunction. Following oral administration, the absolute bioavailability of memantine is approximately 100%. The maximum concentration in blood occurs between 3 and 8 hours after taking the drug. Memantine binds to approximately 45% of plasma proteins. About 80% of memantine occurs in the unchanged form. The major metabolites are N-3,5-dimethyl-gludantane, a mixture of 4- and 6-hydroxy-memantine isomers and 1-nitroso-3,5-dimethyl-adamantane. These metabolites have no NMDA antagonistic activity. Memantine is mainly excreted in the urine. T0,5 is 60-100 h. In the kidneys there is a process of reabsorption from the tubules, probably with the participation of proteins involved in the transport of cations. In the case of alkalinisation of urine, the rate of excretion of memantine by the kidneys may be slowed down by 7-9 times.
Contraindications:
Hypersensitivity to the active substance or to any of the excipients.
Precautions:
Caution is advised in patients with epilepsy, history of seizures or patients with predisposing factors for epilepsy. The simultaneous use of NMDA antagonists (amantadine, ketamine, dextromethorphan) should be avoided. Careful monitoring of patients with factors that may lead to an increase in urine pH (eg drastic changes in diet, eg meat and vegetarian diets, high doses of stomach alkalising preparations, renal tubular acidosis, severe urinary tract infections caused by bacteria with kind ofProteus), because in the case of alkalinisation of urine the rate of excretion of the drug may be 7-9 times released. Patients with recent myocardial infarction, uncompensated congestive heart failure (NYHA III-IV) or uncontrolled hypertension should be carefully monitored (limited data are available for the administration of memantine to these patients). It is not recommended for use in children and adolescents under 18 years due to a lack of data on safety and efficacy. It is not recommended for patients with severe hepatic impairment (no data).
Pregnancy and lactation:
It must not be used during pregnancy unless clearly necessary. Women taking memantine should not breast-feed.
Side effects:
Common: hypersensitivity to the drug, drowsiness, dizziness, balance disorders, hypertension, dyspnoea, constipation, increased liver enzymes, headache. Uncommon: fungal infections, confusion, hallucinations (mainly in patients with severe Alzheimer's disease), abnormal gait, heart failure, venous thrombosis / embolism, vomiting, fatigue. Very rare: epileptic seizures. Frequency unknown: psychotic reactions, pancreatitis, hepatitis. After the introduction of the drug, cases of depression, suicidal thoughts and suicides were also reported.
Dosage:
Treatment should be started and supervised by a doctor who has experience in the diagnosis and therapy of Alzheimer's disease. Treatment can only be started if the carer provides constant supervision over the patient's use of the medicine. The tolerance and dosage of memantine should be regularly evaluated, especially during the first 3 months after starting treatment. Then, the therapeutic effect of memantine and treatment tolerance should be regularly assessed in accordance with current guidelines. Maintenance treatment can be continued as long as the beneficial therapeutic effect is maintained and the patient tolerates well the memantine treatment. Discontinuation of treatment should be considered if there is no evidence of therapeutic effect or if treatment tolerance is poor. Orally.Adults: the maximum daily dose is 20 mg. In order to reduce the risk of adverse reactions within the first 4 weeks, the dose should be increased gradually, by 5 mg every week, until the maintenance dose is reached, according to the following scheme: in the first week (day 1-7) the dose of 5 mg per day , in the second week (day 8-14) 10 mg per day, in the third week (day 15-21) 15 mg per day. From the fourth week of treatment: 20 mg per day. The recommended maintenance dose is 20 mg per day. No dosage adjustment is necessary for patients over 65 years of age. In patients with slightly impaired renal function (creatinine clearance 50-80 ml / min) dose modification is not required. In patients with moderate renal impairment (creatinine clearance 30-49 ml / min), the daily dose should be 10 mg. If the treatment is well tolerated for at least 7 days, the dose may be increased to 20 mg per day according to the standard schedule. In patients with severe renal impairment (creatinine clearance 5-29 ml / min), the daily dose should be 10 mg. In patients with mild or moderate hepatic impairment (Child-Pugh A and B), no dose adjustment is required. The preparation is not recommended in patients with severe hepatic impairment. The drug should be taken once a day, at the same time each day, with or without food.
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