Alzeim (Tablets) Instructions for Use

Marketing Authorization Holder

Laboratorios Bagó, S.A. (Argentina)

ATC Code

N06DX01 (Memantine)

Active Substance

Memantine (Rec.INN registered by WHO)

Dosage Form

Alzeim

Film-coated tablets, 10 mg: 30 or 60 pcs.

Dosage Form, Packaging, and Composition

10 pcs. – blisters (3) – carton packs.
10 pcs. – blisters (6) – carton packs.

Clinical-Pharmacological Group

Glutamate NMDA-receptor blocker. Drug for the treatment of dementia

Pharmacotherapeutic Group

Dementia treatment agent

Pharmacological Action

An adamantane derivative, it is close to amantadine in chemical structure and pharmacological properties. It is a non-competitive antagonist of N-methyl-D-aspartate (NMDA) receptors (including in the substantia nigra), thereby reducing the excessive stimulatory influence of cortical glutamatergic neurons on the neostriatum, which develops against the background of insufficient dopamine release. By reducing the influx of calcium ions into neurons, it reduces the possibility of their destruction.

It has nootropic, cerebrovasodilating, antihypoxic, and psychostimulating effects. It has a greater effect on stiffness (rigidity and bradykinesia). It improves weakened memory, concentration, reduces fatigue, and symptoms of depression.

Pharmacokinetics

Absorption

Memantine is rapidly and completely absorbed from the gastrointestinal tract and has an absolute bioavailability of about 100%. The time to reach C_max in blood plasma is 3-8 hours.

Distribution

After a 20 mg dose, the memantine concentration in blood plasma is 70-150 ng/ml. V_d is about 10 L/kg. Plasma protein binding is 45%.

Biotransformation

About 80% of memantine is in the form of the parent drug. The main metabolites in humans are N-3.5-dimethylgludantan, a mixture of 4- and 6-hydroxymemantine isomers, and 1-nitroso-3.5-dimethyl-adamantane. None of these metabolites possess pharmacological activity.

Elimination

It is excreted by the kidneys. Elimination occurs in a monophasic manner, T_1/2 is 60-100 hours; clearance is 170 ml/min/173 m², the drug is partially secreted by the renal tubules. Excretion of the drug is slowed when urine is alkaline.

Indications

Moderate to severe dementia in Alzheimer’s disease.

ICD codes

Dosage Regimen

Orally. With meals. The dosage regimen is established individually. It is recommended to start treatment with the minimum effective doses.

First week: daily dose – 5 mg (1/2 tablet in the morning);

Second week: daily dose – 10 mg (1/2 tablet twice a day);

Third week: daily dose – 15 mg (1 tablet in the morning and 1/2 tablet in the evening);

Fourth week: daily dose – 20 mg (1 tablet twice a day);

Maximum daily dose – 20 mg per day.

Elderly patients (over 65 years) dose adjustment is not required.

Renal impairment in case of impaired renal function, the dose of the drug should be reduced. For patients with creatinine clearance (CrCl) of 50-80 ml/min, dose adjustment is not required. For patients with moderate renal impairment (CrCl 30-49 ml/min) – 10 mg/day. If the drug is well tolerated for 7 weeks, the dose can be increased to 20 mg/day according to the standard scheme. The use of the drug in patients with severe renal impairment (CrCl 5-29 ml/min) is not recommended due to insufficient data.

Hepatic impairment: in patients with mild and moderate hepatic impairment (Child-Pugh class A and B), no adjustment of the dosing regimen is required.

Adverse Reactions

Dizziness, drowsiness, increased excitability, increased fatigue, anxiety, increased intracranial pressure, nausea, hallucinations, headache, impaired consciousness, muscle hypertonia, gait disturbance, depression, seizures, psychotic reactions, suicidal thoughts, constipation, nausea, pancreatitis, candidiasis, increased blood pressure, vomiting, cystitis, increased libido, venous thrombosis, thromboembolism, allergic reactions.

Contraindications

Hypersensitivity to any component of the drug, severe renal failure (CrCl 5-29 ml/min), severe hepatic failure, congenital galactose intolerance, lactase deficiency or glucose-galactose malabsorption syndrome, pregnancy, lactation, children under 18 years of age (efficacy and safety not established).

With caution. Epilepsy, thyrotoxicosis, history of convulsive syndrome, concurrent use of NMDA receptor antagonists (amantadine, ketamine, dextromethorphan); factors that increase urine pH (sudden change in diet, e.g., switching to vegetarianism, abundant intake of alkaline gastric buffers); severe urinary tract infections, myocardial infarction (in history), heart failure (NYHA functional class III-IV), uncontrolled arterial hypertension, renal failure, hepatic failure.

Use in Pregnancy and Lactation

Contraindicated during pregnancy and lactation.

Use in Hepatic Impairment

Contraindicated in severe hepatic failure.

In patients with mild and moderate hepatic impairment (Child-Pugh class A and B), no adjustment of the dosing regimen is required.

Use in Renal Impairment

Contraindicated in severe renal failure (CrCl 5-29 ml/min).

In case of impaired renal function, the dose of the drug should be reduced.

Pediatric Use

Contraindicated in children and adolescents under 18 years of age (efficacy and safety not established).

Geriatric Use

In elderly patients (over 65 years), dose adjustment is not required.

Special Precautions

Memantine should not be prescribed together with other NMDA receptor antagonists (such as amantadine, ketamine, dextromethorphan), as adverse reactions, mainly at the CNS level, may occur more frequently and with greater intensity.

Effect on the ability to concentrate

Alzheimer’s disease significantly affects the ability to drive vehicles and operate machinery requiring increased attention; moreover, Memantine alters the speed of psychomotor reactions, therefore, one should refrain from driving vehicles and working with complex machinery.

Overdose

Symptoms dizziness, tremor, agitation, drowsiness, confusion, excitation, stupor, seizures, psychosis, aggressiveness, hallucinations, unsteady gait, vomiting, diarrhea.

Treatment in case of overdose, treatment is symptomatic. There is no specific antidote. Standard therapeutic measures aimed at removing the active substance from the stomach should be performed, for example, gastric lavage, administration of activated charcoal, acidification of urine; forced diuresis may be performed.

Drug Interactions

Memantine effects may be enhanced when used concomitantly with anticholinergic drugs, levodopa preparations, dopaminergic agonists (e.g., bromocriptine). Concomitant use of memantine and 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 possible with the concomitant use of memantine with phenytoin, ketamine, and dextromethorphan.

Concomitant use with memantine reduces the effect of barbiturates and neuroleptics.

Concomitant administration with antidepressants, selective serotonin reuptake inhibitors, and MAO inhibitors requires careful monitoring of patients.

Concomitant use of memantine with dantrolene and baclofen, as well as with antispasmodics, may be accompanied by a change in their effect, which requires adjustment of the dose of these drugs.

Concomitant use with cimetidine, ranitidine, procainamide, quinidine, quinine, and nicotine increases the risk of elevated memantine plasma concentrations.

Cases of increased INR (International Normalized Ratio) are possible in patients simultaneously taking oral anticoagulants (warfarin). It is recommended to regularly monitor prothrombin time or INR. The excretion of hydrochlorothiazide may increase.

Storage Conditions

Store the drug in a dry, light-protected place at a temperature not exceeding 25°C (77°F). Keep out of reach of children.

Shelf Life

Shelf life – 2 years. Do not use the drug after the expiration date.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.