Memantal^® (Tablets) Instructions for Use

Marketing Authorization Holder

Pharmfirma Sotex, CJSC (Russia)

Manufactured By

Synthon Hispania, S.L. (Spain)

Packaging and Quality Control Release

Pharmfirma Sotex, CJSC (Russia)

Contact Information

Pharmfirma Sotex CJSC (Russia)

ATC Code

N06DX01 (Memantine)

Active Substance

Memantine (Rec.INN registered by WHO)

Dosage Form

Memantal®

Film-coated tablets, 10 mg: 30, 60, or 90 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets white, round, biconvex, with a wide score on one side and the marking “M9MN” and “10” on the other.

Excipients : lactose monohydrate – 149.75 mg, microcrystalline cellulose – 27.1 mg, talc – 11.15 mg, colloidal silicon dioxide – 1.25 mg, magnesium stearate – 0.75 mg.

Shell composition Opadry^® white (lactose monohydrate – 2.16 mg, hypromellose – 1.68 mg, titanium dioxide – 1.56 mg, macrogol 4000 – 0.6 mg) – 6 mg.

10 pcs. – blisters (3) – cardboard packs.
10 pcs. – blisters (6) – cardboard packs.
10 pcs. – blisters (9) – cardboard packs.
10 pcs. – blisters (10) – cardboard packs.
14 pcs. – blisters (2) – cardboard packs.
14 pcs. – blisters (8) – cardboard 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 a non-competitive antagonist of N-methyl-D-aspartate (NMDA) receptors, exerts a modulating effect on the glutamatergic system.

It regulates ion transport, blocks calcium channels, normalizes the membrane potential, and improves the process of nerve impulse transmission. It improves cognitive processes and increases daily activity.

Pharmacokinetics

Absorption and distribution

After oral administration, Memantine is rapidly and completely absorbed from the gastrointestinal tract. C_max in blood plasma is reached within 2-6 hours. No accumulation of memantine has been noted with normal renal function.

Metabolism and excretion

Excretion occurs in two phases. T_1/2 averages 4-9 hours in the first phase and 40-65 hours in the second phase. About 80% of memantine is excreted unchanged. Metabolites do not possess their own pharmacological activity. It is excreted in the urine. Excretion is slowed in alkaline urine.

Indications

• Moderate to severe Alzheimer’s-type dementia.

ICD codes

Dosage Regimen

Therapy should be conducted under the supervision of a physician experienced in the diagnosis and treatment of dementia in Alzheimer’s disease. Therapy should only be initiated if a person providing regular care for the patient will monitor the patient’s medication intake. The diagnosis should be made in accordance with current guidelines.

Tolerance and the dose of the drug should be regularly assessed, primarily within 3 months after the start of therapy. The clinical efficacy of the drug and the tolerability of therapy should then be regularly assessed in accordance with current clinical guidelines. Maintenance therapy can be continued indefinitely if there is a therapeutic effect and good drug tolerance. The drug should be discontinued if a therapeutic effect is no longer observed or if the patient does not tolerate the treatment.

The drug is taken orally, once a day, always at the same time, regardless of meals. The dosage regimen is set individually. It is recommended to start treatment with the minimum effective dose.

The drug is prescribed during the 1st week of therapy (days 1-7) at a dose of 5 mg/day, during the 2nd week (days 8-14) – at a dose of 10 mg/day, during the 3rd week (days 15-21) – at a dose of 15 mg/day, during the 4th week (days 22-28) – at a dose of 20 mg/day. The maximum daily dose is 20 mg.

For patients over 65 years of age, as well as for patients with CrCl 50-80 ml/min, no dose adjustment is required. For patients with moderate renal impairment (CrCl 30-49 ml/min) the daily dose is 10 mg. Subsequently, with good drug tolerance for 7 weeks, the dose can be increased to 20 mg according to the standard scheme.

Tablet splitting instructions

Place the tablet with the rounded side on a hard surface with the score facing up. Press with the index finger and thumb of one hand on opposite sides of the tablet, continue to apply pressure with your fingers until the tablet breaks into two parts.

Adverse Reactions

The frequency of adverse reactions was classified as follows: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1000, <1/100), rare (≥1/10000, <1/1000), very rare (<1/10000), frequency not known (currently no data on the prevalence of side effects).

Infections and infestations: uncommon – fungal infections.

Immune system disorders: common – hypersensitivity to memantine or other components included in the drug.

Psychiatric disorders: uncommon – confusion, hallucinations (mainly in patients with severe Alzheimer’s disease); frequency not known – psychotic reactions.

Nervous system disorders: common – headache, drowsiness, dizziness, balance disorder; uncommon – gait disturbance; very rare – convulsions, epileptic seizures.

Cardiac disorders: uncommon – heart failure, heart defects.

Vascular disorders: common – increased blood pressure, venous thrombosis and/or thromboembolism.

Respiratory, thoracic and mediastinal disorders: common – dyspnea.

Gastrointestinal disorders: common – constipation; rare – nausea, vomiting; frequency not known – pancreatitis.

Hepatobiliary disorders: common – abnormal liver function tests.

General disorders and administration site conditions: uncommon – fatigue, general weakness.

In Alzheimer’s disease patients, depression, suicidal thoughts, and cases of suicide have been reported in post-registration studies.

The following adverse reactions have been reported during the post-marketing period: agranulocytosis, leukopenia (including neutropenia), pancytopenia, thrombocytopenia, thrombocytopenic purpura, hepatitis, acute renal failure, Stevens-Johnson syndrome.

Contraindications

• Individual hypersensitivity to the drug;
• Severe renal impairment (CrCl less than 5-29 ml/min);
• Severe hepatic insufficiency;
• Pregnancy;
• Breastfeeding;
• Children under 18 years of age (efficacy and safety have not been established);
• Lactose intolerance, lapp lactase deficiency or glucose-galactose malabsorption (the drug contains lactose monohydrate).

With caution should be prescribed to patients with thyrotoxicosis, epilepsy; predisposition to the development of seizures; with the simultaneous use of NMDA receptor antagonists (amantadine, ketamine, dextromethorphan), the presence of factors that increase urine pH (sudden change in diet, abundant intake of alkaline gastric buffers), renal tubular acidosis, severe urinary tract infections, history of myocardial infarction, heart failure of functional class III-IV (according to NYHA classification), uncontrolled arterial hypertension, renal and hepatic insufficiency.

Use in Pregnancy and Lactation

There are no data on the use of memantine in pregnant women. Memantine should be used only when the expected benefit to the mother outweighs the potential risk to the fetus.

There are no data on the penetration of memantine into breast milk. Considering the lipophilic structure of the active substance of the drug, it can be assumed that Memantine may penetrate into breast milk, therefore it is recommended to stop breastfeeding while taking the drug.

Use in Hepatic Impairment

Contraindicated in severe hepatic insufficiency.

The drug should be prescribed with caution in hepatic insufficiency.

Use in Renal Impairment

Contraindicated in severe renal impairment (CrCl less than 5-29 ml/min).

The drug should be prescribed with caution in renal insufficiency.

Pediatric Use

Contraindicated in children under 18 years of age.

Geriatric Use

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

Special Precautions

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

Effect on the ability to drive vehicles and machinery

Memantine may cause changes in reaction speed, so it is necessary to refrain from potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Overdose

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

Treatment: gastric lavage, administration of activated charcoal, symptomatic therapy. There is no specific antidote.

Drug Interactions

With simultaneous use with drugs of levodopa, dopamine receptor antagonists, m-anticholinergics, the effect of the latter may be enhanced.

With simultaneous use with barbiturates and neuroleptics, the effect of the latter may be reduced.

When used concomitantly, it may change (enhance or reduce) the effect of dantrolene or baclofen, so the doses of the drugs should be selected individually.

Concomitant use with amantadine, ketamine, phenytoin and dextromethorphan should be avoided due to an increased risk of psychosis.

An increase in the plasma concentration of cimetidine, ranitidine, procainamide, quinidine, quinine and nicotine is possible when taken concomitantly with memantine.

A decrease in the level of hydrochlorothiazide is possible with concomitant use with memantine. Memantine is able to increase the excretion of hydrochlorothiazide.

An increase in INR is possible in patients taking oral anticoagulants (warfarin).

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

Under in vitro conditions, Memantine does not inhibit the isoenzymes CYP1A2, 2A6, 2C9, 2D6, 2E1, 3A, flavin-containing monooxygenase, epoxide hydrolase or sulfation.

Storage Conditions

The drug should be stored out of the reach of children at a temperature not exceeding 25°C (77°F).

Shelf Life

Shelf life – 5 years. Do not use 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.