Memantine-Vertex, 10 mg 90 pcs

One film-coated tablet contains:

The dosage is 10 mg.

Active substance:

memantine hydrochloride – 10.0 mg;

Auxiliary substances:

Cellulose microcrystalline – 152.5 mg;

calcium hydrophosphate dihydrate – 50.0 mg;

croscarmellose sodium – 12.5 mg;

lactose monohydrate -10.0 mg;

Hyprolose (hydroxypropyl cellulose) – 5.0 mg;

Taalc, 5.0 mg;

Colloidal silicon dioxide – 2.5 mg;

Magnesium stearate – 2.5 mg;

Film coating:

.[hypromellose – 4,000 mg, hyprolose (hydroxypropyl cellulose) – 1,552 mg, talc – 1,568 mg, titanium dioxide – 0,880 mg] or [dry film coating mixture containing hypromellose (50%), hyprolose (hydroxypropyl cellulose) (19.4%), talc (19.6%), titanium dioxide (11%)] – 8.0 mg.

Indications

Active ingredient

Composition

One film-coated tablet contains:

The dosage is 10 mg.

Active substance:

Memantine hydrochloride – 10.0 mg;

Auxiliary substances:

Cellulose microcrystalline – 152.5 mg;

calcium hydrophosphate dihydrate – 50.0 mg;

croscarmellose sodium – 12.5 mg;

lactose monohydrate -10.0 mg;

Interaction

In concomitant use of memantine with levodopa drugs, dopamine receptor agonists, anticholinergic agents may increase their effect.

In concomitant use of memantine with barbiturates, neuroleptics their effect may be reduced.

In concomitant use of memantine with dantrolene or baclofen, as well as with antispasmodics, their effect may change (increase or decrease), so the doses of drugs should be adjusted individually.

The concomitant use of memantine with amantadine should be avoided because of the risk of psychosis. Both compounds are NMDA receptor antagonists.

The risk of psychosis is also increased when memantine is used concomitantly with phenytoin, ketamine and dextromethorphan.

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

Concomitant use of memantine with hydrochlorthiazide may decrease the plasma concentration of hydrochlorthiazide due to increased excretion.

International normalized ratio (INR) may increase in patients concomitantly taking oral indirect anticoagulants (warfarin). It is recommended to monitor prothrombin time or INR regularly in patients concomitantly taking indirect anticoagulants.

The concomitant use of memantine with antidepressants, selective serotonin reuptake inhibitors and monoamine oxidase inhibitors requires careful patient monitoring.

According to pharmacokinetic studies, no drug interaction effects have been observed in young healthy volunteers when taking memantine with glibenclamide/metformin or donepezil at a single time.

The clinical studies also showed no effect of memantine on galantamine pharmacokinetics in young healthy volunteers.

In in vitro studies, memantine did not inhibit CYP 1A2, 2A6, 2C9, 2D6, 2E1, 3A monooxygenase containing flavin, epoxide hydrolase, and sulfation.When memantine is used simultaneously with levodopa drugs, dopamine receptor agonists, anticholinergic agents may increase their effects.

In concomitant use of memantine with barbiturates, neuroleptics their effect may be reduced.

In concomitant use of memantine with dantrolene or baclofen, as well as with antispasmodics, their effect may change (increase or decrease), so the doses of drugs should be adjusted individually.

The concomitant use of memantine with amantadine should be avoided because of the risk of psychosis. Both compounds are NMDA receptor antagonists.

The risk of psychosis is also increased when memantine is used concomitantly with phenytoin, ketamine and dextromethorphan.

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

Concomitant use of memantine with hydrochlorthiazide may decrease the plasma concentration of hydrochlorthiazide due to increased excretion.

International normalized ratio (INR) may increase in patients concomitantly taking oral indirect anticoagulants (warfarin). It is recommended to monitor prothrombin time or INR regularly in patients concomitantly taking indirect anticoagulants.

The concomitant use of memantine with antidepressants, selective serotonin reuptake inhibitors and monoamine oxidase inhibitors requires careful patient monitoring.

According to pharmacokinetic studies, no drug interaction effects have been observed in young healthy volunteers when taking memantine with glibenclamide/metformin or donepezil at a single time.

The clinical studies also showed no effect of memantine on galantamine pharmacokinetics in young healthy volunteers.

In in vitro studies, memantine did not inhibit the CYP isoenzymes 1A2, 2A6, 2C9, 2D6, 2E1, 3A, monooxygenase containing flavin, epoxide hydrolase, or sulfation.

Directions for use

Memantine therapy should be initiated and administered under the supervision of a physician experienced in the diagnosis and treatment of Alzheimer-type dementia. The diagnosis should be made according to current guidelines.

The treatment should only be started if the patient’s full-time caregiver will monitor the patient’s medication intake regularly.

The tolerability and dosage of memantine should be reviewed regularly, preferably within the first three months of starting treatment. Thereafter, the clinical efficacy of memantine and patient tolerability should be reviewed according to current clinical guidelines.

The maintenance treatment can be continued indefinitely if there is a positive therapeutic effect and good tolerability of the drug. Memantine should be discontinued if there is no positive therapeutic effect or if the patient is intolerant to the drug.

The drug should be taken orally once a day and always at the same time, regardless of meals. It is recommended that treatment with memantine start with the lowest effective dose.

It is used during the 1st week of therapy (days 1-7) in a dose of 5 mg/day, during the 2nd week (days 8-14) in a dose of 10 mg/day, during the 3rd week (days 15-21) in a dose of 15 mg/day, starting from the 4th week in a dose of 20 mg/day.

The recommended maintenance dose is 20 mg/day.

The maximum daily dose is 20 mg.

Patient Special Groups

Patients of advanced age (>65 years)

Dose adjustment is not required.

Patients with impaired renal function

In patients with a creatinine clearance of 50-80 ml/min, no dose adjustment is required.

In patients with moderate renal impairment (creatinine clearance 30-49 ml/min), the recommended daily dose is 10 mg. If this dose is well tolerated for 7 days, the dose can be increased to 20 mg/day according to the standard regimen.

In patients with severe renal insufficiency (creatinine clearance 5-29 ml/min), the daily dose should not exceed 10 mg.

Patients with hepatic impairment

In patients with mild to moderate hepatic impairment (Child-Puo Class A and B) no dose adjustment is required.

Patients with severe hepatic impairment (Child-Pugh class C) use of the drug is contraindicated.

Special Instructions

In alkaline urine patients, closer monitoring of these patients is required because of the delayed excretion of memantine. Factors that cause an increase in urine pH include: abrupt changes in diet, such as changing a meat-rich diet to a vegetarian diet or heavy use of alkaline gastric buffers. In addition, urine pH may be elevated due to renal tubular acidosis or a severe urinary tract infection caused by bacteria of the genus Proteus.

The data on the use of memantine in patients with a history of myocardial infarction, chronic heart failure (NYHA functional class III-IV) or uncontrolled arterial hypertension are limited, so close medical monitoring of these patients is necessary.

Cautiously use in patients with thyrotoxicosis, epilepsy, seizures (including history) and predisposition to epilepsy.

The concomitant use of memantine and NMDA receptor antagonists such as amantadine, ketamine and dextromethorphan should be avoided. These compounds act on the same receptor system as memantine, and adverse reactions (mainly central nervous system) may be more frequent and severe.

The drug Memantine contains lactose monohydrate. Patients with hereditary galactose intolerance, lactase deficiency or glucose-galactose malabsorption should not take Memantine.

Influence on driving and mechanics ability:

Patients with moderate to severe Alzheimer’s dementia usually have impaired ability to drive vehicles and operate complex machinery. In addition, memantine may cause changes in reaction speed, so patients should refrain from driving or operating complex machinery.

Contraindications

– Hypersensitivity to memantine or any of the ingredients of the drug;

– severe hepatic impairment (Child-Pugh Class C);

– lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome;

– pregnancy;

– breastfeeding period;

– age less than 18 years (effectiveness and safety are not established).

With caution:

– Thyrotoxicosis;

– epilepsy, predisposition to epilepsy;

– seizures (including history);

– concomitant use of NMDA-receptor antagonists (amantadine, ketamine, dextromethorphan);

– presence of factors that increase urine pH (sudden change in diet, e.g., switch to a vegetarian diet, heavy intake of alkaline gastric buffers);

– Renal tubular acidosis;

– Severe urinary tract infections caused by Proteus genus bacteria;

– Myocardial infarction (history);

– Heart failure (NYHA functional class III-IV);

– uncontrolled arterial hypertension;

– renal failure;

– hepatic failure (Child-Pugh class A and B).

Side effects

Classification of the frequency of side effects according to the recommendations of the World Health Organization (WHO): Very common >1/10; common >1/100 to <1/10; infrequent >1/1000 to <1/100; rare >1/10000 to <1/1000; very rare <1/10000, including individual reports; frequency unknown – the incidence cannot be determined from available data.

From the central nervous system:

frequently – headache, dizziness, drowsiness, impaired balance;

not infrequently- gait disturbance, confusion, hallucinations (hallucinations were observed mainly in patients with severe Alzheimer’s type dementia);

very rarely – seizures;

frequency unknown – psychotic reactions, impaired consciousness, increased agitation, depression, anxiety, suicidal thoughts, increased intracranial pressure, muscle hypertonicity.

Cardiovascular system side:

frequently – increased blood pressure;

infrequently – venous thrombosis/thromboembolism, heart failure.

Digestive system disorders:

frequent – constipation;

infrequent – nausea, vomiting;

frequency unknown – pancreatitis, hepatitis.

Respiratory system:

often – shortness of breath.

Urogenital system disorders:

frequency unknown – acute renal failure, cystitis, increased libido.

Allergic reactions:

frequent – hypersensitivity to the components of the drug;

frequency unknown – allergic reactions, Stevens-Johnson syndrome.

Skin side effects:

frequency unknown – thrombocytopenic purpura.

Laboratory findings:

frequent – increased activity of “liver” enzymes;

frequency unknown – agranulocytosis, leukopenia (including neutropenia), pancytopenia, thrombocytopenia.

Others:

infrequent – increased fatigue;

rarely – fungal infections; frequency unknown – candidiasis.

Overdose

There are limited data on overdose from clinical studies and post-registration follow-up.

Symptoms

Overdose with relatively large doses of memantine (200 mg once, or 105 mg daily for 3 days) is expressed by symptoms of fatigue, weakness and/or diarrhea or no symptoms. Overdose with up to 140 mg of memantine once or an unknown amount of memantine is expressed by symptoms related to the central nervous system (confusion, drowsiness, dizziness, vertigo, anxiety, agitation, hallucinations, gait disturbances) and/or gastrointestinal disturbances (vomiting, diarrhea).

In the most serious cases of overdose, the patient survived after taking more than 2000 mg of memantine with adverse nervous system events (coma for 10 days, later diplopia, agitation). The patient received symptomatic therapy and plasmapheresis and recovered without sequelae.

The other described case of a serious overdose was 400 mg of memantine once. The patient recovered without sequelae. There were adverse effects on the nervous system: anxiety, psychosis, visual hallucinations, stupor, seizures, somnolence, unconsciousness.

Treatment

Symptomatic therapy, gastric lavage, taking adsorbents (activated charcoal), urine acidification, forced diuresis (if necessary). There is no specific antidote.

Pregnancy use

Similarities