Memorel^® (Tablets) Instructions for Use

ATC Code

N06DX01 (Memantine)

Active Substance

Memantine (Rec.INN registered by WHO)

Clinical-Pharmacological Group

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

Pharmacotherapeutic Group

Dementia treatment agent

Pharmacological Action

Glutamate NMDA-receptor blocker. Drug for the treatment of dementia. It has nootropic, cerebrovasodilating, antihypoxic, and psychostimulating effects.

An adamantane derivative, it is close to amantadine in chemical structure and pharmacological properties. It blocks glutamate N-methyl-D-aspartate (NMDA) receptors (including in the substantia nigra), thereby reducing the excessive stimulatory influence of cortical glutamate neurons on the neostriatum that develops against the background of insufficient dopamine release. By reducing the influx of ionized calcium into neurons, it reduces the possibility of their destruction. It has a greater effect on rigidity (stiffness and bradykinesia).

In addition to its action on the CNS, Memantine affects efferent innervation. It improves weakened memory, concentration, reduces fatigue and symptoms of depression, reduces skeletal muscle spasticity caused by brain diseases and injuries, and increases daily activity.

Pharmacokinetics

Absorption

After oral administration, it is rapidly and completely absorbed from the gastrointestinal tract. C_max is reached in 3-8 hours. Food intake does not affect the absorption of the drug.

Distribution

Administration of the drug at a daily dose of 20 mg leads to the achievement of C_ss ranging from 70 to 150 mg/ml. V_d is about 10 L/kg. Plasma protein binding is 45%. No accumulation of memantine has been observed with normal renal function.

Metabolism

80% of memantine circulating in the blood is the unchanged substance. Metabolism occurs without the involvement of cytochrome P450. The main metabolites are N-3,5-dimethylgludantan, an isomeric mixture of 4- and 6-hydroxymemantine, and 1-nitroso-3,5-dimethyladamantane. None of the metabolites have antagonistic activity against NMDA receptors.

Excretion

It is excreted primarily by the kidneys. Excretion occurs in one phase, T_1/2 is 60-100 hours; clearance is 170 ml/min/1.73 m², and it is partially secreted by the renal tubules. When urine is alkaline, the excretion of the drug slows down (on average by 80% at urine pH 8).

Indications

• Moderate to severe dementia in Alzheimer’s disease.

ICD codes

Dosage Regimen

Tablets

The drug is taken orally, regardless of meals.

During the first week, the daily dose is 5 mg (in the morning). During the second week, the daily dose is 10 mg (5 mg twice a day). During the third week, the daily dose is 15 mg/day (10 mg in the morning and 5 mg in the evening). From the fourth week, the daily dose is 20 mg/day. The maximum daily dose is 20 mg/day.

No dose adjustment is required for elderly patients (over 65 years of age).

In moderate renal impairment (creatinine clearance 50-80 ml/min), dose adjustment is usually not required; with creatinine clearance of 30-49 ml/min, the daily dose should initially not exceed 10 mg, then after 7 days, if well tolerated, the dose can be increased up to 20 mg. In severe renal impairment (creatinine clearance 5-29 ml/min), the daily dose should not exceed 10 mg.

In mild and moderate hepatic impairment (Child-Pugh class A and B), no dose adjustment is required.

Adverse Reactions

Nervous system disorders dizziness, headache, drowsiness, gait disturbance, confusion, hallucinations, seizures, psychosis, increased excitability.

Digestive system disorders: constipation, vomiting, pancreatitis, nausea.

Infections and infestations fungal infections.

Cardiovascular system disorders increased blood pressure, venous thrombosis, thromboembolism.

General disorders general weakness, increased fatigue, allergic reactions.

Contraindications

• Severe hepatic impairment;
• Lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome (the drug contains lactose);
• Pregnancy;
• Lactation period (breastfeeding);
• Age under 18 years;
• Hypersensitivity to the components of the drug.

Use with caution in thyrotoxicosis, epilepsy, seizures (including history), with simultaneous use of NMDA receptor antagonists (amantadine, ketamine, dextromethorphan), in the presence of factors that increase urine pH (sudden change in diet, abundant intake of alkaline gastric buffers), in severe urinary tract infections, in myocardial infarction (in history), heart failure of functional class III-IV (according to NYHA classification), uncontrolled arterial hypertension, in renal impairment, hepatic impairment.

Use in Pregnancy and Lactation

The use of the drug Memorel^® is contraindicated during pregnancy and lactation.

Memantine has the ability to slow down fetal development.

Breastfeeding should be discontinued during treatment with memantine.

Use in Hepatic Impairment

In mild and moderate hepatic impairment (Child-Pugh class A and B), no dose adjustment is required.

Contraindicated in severe hepatic impairment.

Use in Renal Impairment

In moderate renal impairment (creatinine clearance 50-80 ml/min), dose adjustment is usually not required; with creatinine clearance of 30-49 ml/min, the daily dose should initially not exceed 10 mg, then after 7 days, if well tolerated, the dose can be increased up to 20 mg. In severe renal impairment (creatinine clearance 5-29 ml/min), the daily dose should not exceed 10 mg.

Pediatric Use

Contraindicated in children under 18 years of age.

Geriatric Use

No dose adjustment is required for elderly patients (over 65 years of age).

Special Precautions

In case of alkaline urine reaction, more careful monitoring of patients is required due to the slowed excretion of memantine.

Effect on ability to drive vehicles and operate machinery

Caution should be exercised when driving and performing work that requires increased concentration.

Overdose

Symptoms dizziness, tremor, agitation, drowsiness, clouding of consciousness, excitation, stupor, seizures, aggressiveness, hallucinations, unsteady gait, vomiting, diarrhea.

Treatment gastric lavage, administration of activated charcoal; symptomatic therapy. There is no specific antidote. The elimination of the drug can be accelerated by acidifying the urine.

Drug Interactions

When used concomitantly, it may weaken the effect of barbiturates and neuroleptics.

The action of baclofen and dantrolene may change under the influence of memantine, so dose adjustment may be required.

When memantine is used concomitantly with levodopa preparations, dopamine agonists, and anticholinergic agents, the effect of the latter may be enhanced.

Since Memantine and amantadine are NMDA receptor antagonists, their simultaneous use should be avoided due to the risk of toxic effects. Combinations of memantine with ketamine, dextromethorphan, and phenytoin are also potentially toxic.

The same renal cation system is used for the transport of amantadine, cimetidine, ranitidine, quinidine, procainamide, quinine, and nicotine in the body, which may cause interaction of these drugs with memantine, leading to an increase in its plasma concentration.

When used concomitantly, Memantine may cause a decrease in the serum concentration of hydrochlorothiazide.

When used concomitantly with warfarin and other indirect anticoagulants, careful monitoring of prothrombin time and international normalized ratio is required.

Storage Conditions

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

Shelf Life

Shelf life – 2 years.

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.