Instructions for use Memtek tablets 10 mg No. 30
Composition
active ingredient: memantine;
1 orodispersible tablet contains 10 mg of memantine hydrochloride, equivalent to 8.31 mg of memantine;
Excipients: polacrilin, sodium hydroxide, purified water1, lactose monohydrate, microcrystalline cellulose, mannitol (E 421), croscarmellose sodium, aspartame (E 951), colloidal anhydrous silica, red iron oxide (E 172), mint flavor2, magnesium stearate.
1most of it is removed during the process.
2mint flavoring contains: maltodextrin, modified starch (E 1450), peppermint oil.
Dosage form
Orodispersible tablets.
Main physicochemical properties: light pink tablets with specks, round in shape with a flat surface, beveled edges and engraved with "10" on one side.
Pharmacotherapeutic group
Drugs used in dementia. Memantine. ATX code N06D X01.
Pharmacological properties
Pharmacodynamics.
Disturbances in glutamatergic neurotransmission, especially involving NMDA (N-methyl-D-aspartate) receptors, play an important role in the manifestation of symptoms and progression of neurodegenerative dementia.
Memantine is a potential-dependent, medium-affinity, non-competitive NMDA receptor antagonist. Memantine modulates the effects of pathologically elevated levels of glutamate, which can lead to neuronal dysfunction.
Pharmacokinetics.
Absorption: The absolute bioavailability of memantine is approximately 100%, with a time to peak plasma concentration (Tmax) of 3 to 8 hours. There is no evidence of an effect of food on absorption.
Distribution. A daily dose of 20 mg results in steady-state plasma concentrations of memantine ranging from 70 to 150 ng/ml (0.5-1 μmol) with significant interindividual variation. At daily doses of 5 to 30 mg, the ratio of the drug in cerebrospinal fluid to serum is 0.52. Approximately 45% of memantine is bound to plasma proteins.
Biotransformation. In humans, about 80% of memantine circulates as the parent compound, the main metabolites do not have NMDA antagonistic properties. Cytochrome P450 involvement in metabolism in vitro has not been demonstrated.
Elimination: Memantine is eliminated monoexponentially with a T1/2 of 60 to 100 hours. In volunteers with normal renal function, the total clearance (Cltot) was 170 ml/min/1.73 m2. The renal phase of memantine pharmacokinetics also includes tubular reabsorption.
The renal elimination rate of memantine may be reduced by 7-9 times in alkaline urine. Alkalinization of urine may occur as a result of significant dietary changes, such as changing from a meat-rich diet to a vegetarian diet, or as a result of intensive use of antacids.
Linearity: Pharmacokinetics are linear in the dose range of 10-40 mg.
Pharmacodynamic/pharmacokinetic relationship: At a dose of 20 mg memantine per day, the level of content in the cerebrospinal fluid corresponds to the ki value (inhibition constant) of memantine, which is 0.5 μmol in the human frontal cortex.
Indication
Alzheimer's disease from mild to severe forms.
Contraindication
Hypersensitivity to the active substance or to any component of the medicinal product.
Interaction with other medicinal products and other types of interactions
The mechanism of action suggests that the effects of L-dopa, dopaminergic agonists and anticholinergics may be potentiated by concomitant use of NMDA antagonists such as memantine. The effects of barbiturates and neuroleptics may be attenuated.
Concomitant use of memantine and amantadine should be avoided due to the risk of pharmacotoxic psychosis. Both compounds are chemically related NMDA antagonists. The same can be said for ketamine and dextromethorphan. One published report also noted the possible risk of the combination of memantine and phenytoin.
Other drugs such as cimetidine, ranitidine, procainamide, quinidine, quinine and nicotine, which use the same renal cation transport system as amantadine, may also be able to interact with memantine, leading to a potential risk of increased plasma levels of memantine.
Concomitant use of memantine with hydrochlorothiazide (HCTZ) or any combination with HCTZ may result in a decrease in serum HCTZ levels.
There have been isolated reports of increased international normalized ratio (INR) with memantine in patients taking warfarin. Although a causal relationship has not been established, careful monitoring of prothrombin time or INR is necessary in patients taking concomitant oral anticoagulants.
In pharmacokinetic studies in healthy volunteers, no significant interaction effects of memantine with glyburide/metformin, donepezil, or galantamine were found.
Memantine is not an inhibitor of CYP 1A2, 2A6, 2C9, 2D6, 2E1, 3A, flavin-containing monooxygenase, epoxide hydrolase, or sulfation in vitro.
Application features
Caution should be exercised when prescribing the drug to patients with epilepsy, patients with a history of seizure episodes, as well as patients with risk factors for developing epilepsy.
Concomitant use of the drug with N-methyl-D-aspartate (NMDA) antagonists such as amantadine, ketamine or dextromethorphan should be avoided. These compounds act on the same receptor system as memantine, so side effects (mainly related to the central nervous system) may be more frequent or more pronounced. Some factors that cause an increase in urine pH may require careful monitoring of the patient. These factors include significant changes in diet, such as changing from a meat-rich diet to a vegetarian diet, or intensive use of gastric antacids. In addition, urine pH may increase due to states of renal tubular acidosis (RTA) or severe urinary tract infections caused by Proteus bacteria.
Patients with recent myocardial infarction, decompensated congestive heart failure (stage III-IV), and uncontrolled hypertension were not included in the study and therefore only limited data are available. Patients with these conditions should be closely monitored.
Important information about excipients.
The medicinal product contains lactose, therefore it should not be administered to patients with rare hereditary forms of galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome.
Use during pregnancy or breastfeeding
There are no clinical data on the effects of memantine during pregnancy. Experimental studies in animals indicate the possibility of intrauterine growth retardation at exposure concentrations identical to or slightly higher than those used in humans. The potential risk for humans is unknown. Memantine should not be used during pregnancy unless clearly necessary.
It is not known whether memantine is excreted in breast milk, which, however, may occur, given the lyophilicity of the substance. Women taking memantine should refrain from breastfeeding.
Ability to influence reaction speed when driving vehicles or other mechanisms
Moderate to severe Alzheimer's disease usually impairs the ability to drive and use machines. In addition, memantine has a minor to moderate effect on the reaction time, so outpatients should be warned about the need to exercise special caution when driving or operating machinery.
Method of administration and doses
Treatment should be initiated and continued under the supervision of a physician. Therapy should only be initiated with a caregiver who will regularly monitor the patient's medication intake.
The tablets should be taken once a day at the same time each day. The tablets can be taken regardless of food intake.
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 per week during the first 3 weeks as follows:
Week 1 (days 1-7): take 5 mg per day for a week;
Week 2 (days 8-14): take 10 mg per day for a week;
Week 3 (days 15-21): take 15 mg per day for a week;
starting from week 4: take 2 tablets (20 mg per day) every day.
The recommended maintenance dose is 20 mg per day.
The duration of treatment should be determined individually by a physician who should have experience in the diagnosis and treatment of Alzheimer's disease. The tolerability and dosage of memantine should be assessed regularly, especially during the first 3 months of treatment. Thereafter, the clinical effect of memantine and the patient's response to treatment should be assessed regularly in accordance with current clinical guidelines. Maintenance treatment can be continued as long as the therapeutic effect remains favorable and memantine is well tolerated.
Discontinuation of memantine treatment should be considered if signs of therapeutic effect disappear or treatment tolerability deteriorates.
Elderly patients.
Based on clinical trial results, the recommended dose for patients aged 65 years and over is 20 mg per day (2 tablets of 10 mg once a day), as indicated above. Decreased renal function.
For patients with mild renal impairment (creatinine clearance 50-80 ml/min), no dose reduction is required. For patients with moderate renal impairment (creatinine clearance 30-49 ml/min), the daily dose should be reduced to 10 mg. The dose may be increased to 20 mg per day according to the standard regimen if there are no adverse reactions after at least 7 days of treatment. For patients with severe renal impairment (creatinine clearance 5-29 ml/min), the daily dose should be reduced to 10 mg.
Decreased liver function.
No dose adjustment is required for patients with mild or moderate hepatic impairment (Child Pugh A, B). The use of memantine in patients with severe hepatic impairment is not recommended.
The drug is not used in children due to insufficient data on the safety and effectiveness of its use.
Overdose
Experience is limited.
Symptoms
Relatively large overdoses (200 mg and 105 mg per day for 3 days, respectively) were either associated with symptoms such as fatigue, weakness and/or diarrhea, or were asymptomatic. Overdoses of up to 140 mg or an unknown dose have been associated with symptoms of central nervous system disorders (confusion, lethargy, drowsiness, dizziness, agitation, aggression, hallucinations, gait disturbances) and/or gastrointestinal disorders (vomiting and diarrhea).
After taking 2000 mg of memantine, the patient developed a coma lasting 10 days, later developing diplopia and agitation. After symptomatic treatment and plasmapheresis, the patient recovered without adverse effects.
Treatment
Symptomatic, no specific antidote exists. Standard clinical procedures should be used to remove the active substance from the body, such as gastric lavage, administration of activated charcoal, acidification of the urine reaction, forced diuresis.
In case of excessive general stimulation of the central nervous system, symptomatic treatment measures should be used with caution.
Side effects
According to available data, it is known that during clinical trials of memantine, the overall frequency of adverse events did not differ from that observed with placebo, and adverse events were usually mild or moderate in severity.
The adverse reactions observed during clinical trials and medical use are listed in the table below and are defined by frequency as: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10000 to <1/1000), very rare (<1/10000), unknown (cannot be determined from the available data).
| System, body, class | Frequency | Adverse reactions |
| Infections | Infrequently | Fungal diseases |
| Immune system disorders | Often | Hypersensitivity |
| Mental disorders | Often | Drowsiness |
| Infrequently | Confusion of consciousness |
| Infrequently | Hallucinations1 |
| Unspecified | Psychotic reactions2 |
| Nervous system disorders | Often | Dizziness |
| Often | Disequilibrium |
| Infrequently | Gait disturbance |
| Very rare | Convulsive seizures |
| Cardiac disorders | Infrequently | Heart failure |
| Vascular disorders | Often | Arterial hypertension |
| Infrequently | Venous thrombosis/thromboembolism |
| Respiratory system disorders | Often | Dyspnea |
| Gastrointestinal disorders | Often | Constipation |
| Infrequently | Vomiting |
| Unspecified | Pancreatitis2 |
| Liver and biliary tract disorders | Often | Increased liver function tests |
| Undetermined | Hepatitis |
| General violations | Often | Headache |
| Infrequently | Increased fatigue |
1Hallucinations were mainly observed in patients with severe Alzheimer's disease.
2Special notices for medical use
Alzheimer's disease is associated with depression, suicidal ideation, and suicide. Such cases have been reported with the medical use of memantine.
Reporting of suspected adverse reactions.
Reporting suspected adverse reactions after the marketing authorisation of a medicinal product is an important procedure. It allows for continued monitoring of the benefit-risk balance of the medicinal product in question. Healthcare professionals should report any suspected adverse reactions via the national reporting system.
Expiration date
3 years.
Storage conditions
Store in the original packaging at a temperature not exceeding 25 °C.
Keep out of reach of children.
Packaging
15 tablets in a blister; 2 blisters in a pack.
Vacation category
According to the recipe.
Producer
Genepharm S.A.
Location of the manufacturer and address of its place of business
18 Km Merezonos Avenue, Pallini, 153 51, Greece.
Applicant
PrJSC "Pharmaceutical Company "Darnitsa".
Location of the applicant and address of its place of business
Ukraine, 02093, Kyiv, Boryspilska St., 13.
