Memantine pills 10mg, 30pcs – Izvarino

Composition

1 film-coated tablet,10 mg contains:

Composition of the tablet core:

Active ingredient:  memantine hydrochloride – 10.0 mg.

Auxiliary substances:  microcrystalline siliconized cellulose, croscarmellose sodium, sodium stearyl fumarate.

Composition of the tablet shell:  opadray II white (33G28435) (hypromellose, titanium dioxide, lactose monohydrate, triacetin, macrogol).

Pharmacological action

Impaired glutamatergic neurotransmission, especially NMDA receptor function, contributes to both the symptoms and progression of neurodegenerative dementia.

Memantine is a potential-dependent, moderately affine, non-competitive inhibitor of NMDA receptors. The drug modulates a pathological increase in glutamate content, which can lead to neural dysfunction. Improves cognitive processes, increases daily activity.

Pharmacokinetics

Suction

After oral use, memantine is rapidly and completely absorbed from the gastrointestinal tract. Absolute bioavailability is about 100%. The maximum concentration (Cmax) in blood plasma is reached within 3-8 hours. Food intake does not affect the absorption of memantine.

Distribution

When taking a daily dose of 20 mg, a constant concentration of memantine in blood plasma is created in the range of 70-150 ng / ml (0.5-1 mmol) with pronounced individual variations. When using daily doses from 5 to 30 mg, the average ratio of the drug content in the cerebrospinal fluid to the content in the blood serum was 0.52. The volume of distribution is 10 l/kg. About 45% of memantine binds to plasma proteins.

Metabolism

About 80% of memantine taken orally circulates unchanged. The main metabolites in humans are N-3,5-dimethylgludantane, a mixture of 4 – and 6-hydroxymemanthine isomers, and l-nitroso-3,5-dimethyladamantane. None of these metabolites has NMDA antagonistic activity.

In vitro studies did not reveal the involvement of cytochrome P450 isoenzymes in memantine metabolism.

In the study, when labeled 14C-memantine was taken orally, more than 84% of the dose was eliminated within 20 days, and more than 99% was excreted by the kidneys.

Deduction

The elimination of memantine is monoexponential with a half-life (half-life) of 60 to 100 hours. Total clearance is 170 ml / min/1.73 m2, with some of the total renal clearance being achieved by tubular secretion.

There is also a process of tubular reabsorption in the kidneys, probably mediated by proteins involved in cation transport. The rate of renal clearance of memantine may decrease when the urine is alkalized to pH 7-9. Alkalinization of urine can result from sudden changes in diet, such as switching to vegetarianism, or heavy intake of alkaline gastric buffers.

Linearity

Studies involving volunteers demonstrated linear pharmacokinetics in the dose range from 10 to 40 mg.

Relationship between pharmacokinetics and Pharmacodynamics

When using memantine at a dose of 20 mg per day, the drug content in the cerebrospinal fluid corresponds to the value of ki (inhibition constant) of memantine, which is 0.5 mmol of the drug in the frontal lobe of the cerebral cortex.

Indications

Moderate to severe Alzheimer’s dementia.

Contraindications

Hypersensitivity to memantine or other components of the drug; lactose intolerance, lactase deficiency, glucose-galactose malabsorption; severe hepatic insufficiency (Child-Pugh class C); children and adolescents under 18 years of age (efficacy and safety have not been established); pregnancy and lactation.

With caution

Prescribe to patients with thyrotoxicosis, epilepsy, convulsions (including in the anamnesis), with myocardial infarction, heart failure, simultaneous use of NMDA receptor antagonists (amantadine, ketamine, dextromethorphan); the presence of factors that increase the pH of urine (a sharp change in diet (transition from meat to vegetarian), heavy intake of alkaline gastric buffers, severe urinary tract infections (caused by Proteus bacteria)), renal tubular acidosis, uncontrolled arterial hypertension, renal failure, mild or moderate hepatic insufficiency (Child-Pugh class A and B).

Side effects

The frequency of side effects is classified according to the clinical manifestations (according to the lesion of certain organ systems) and frequency of occurrence: very common (≥ 1/10), common (≥ 1/100, < 1/10), infrequent (≥ 1/1000, < 1/100), rare (≥ 1/10000, < 1/1000), very rare (

Infectious and parasitic diseases:  infrequently-fungal infections.

Immune system disorders:  often – hypersensitivity to the drug.

Mental disorders:  often-drowsiness; infrequently-confusion, hallucinations (mainly observed in patients with Alzheimer’s disease at the stage of severe dementia); frequency unknown – psychotic reactions (isolated cases reported in the post-marketing period).

Nervous system disorders:  often – dizziness, balance disorders; infrequently-gait disorders; very rarely-convulsions.

Disorders of the cardiovascular system:  often – arterial hypertension; infrequently-heart failure, venous thrombosis/thromboembolism.

Respiratory, thoracic and mediastinal disorders:  often-shortness of breath.

Disorders of the gastrointestinal tract:  often-constipation; infrequently-nausea, vomiting; frequency unknown-pancreatitis (isolated cases reported in the post-marketing period).

Liver and biliary tract disorders:  often-increased biochemical parameters of liver function; frequency unknown-hepatitis.

General disorders and disorders at the injection site:  often – headache, infrequently-fatigue.

Patients with Alzheimer’s disease may experience depression, suicidal thoughts, and suicide attempts. These effects have been reported in clinical practice in patients treated with memantine.

Experience of post-marketing drug use

The following adverse events are described in spontaneous reports during the post-marketing use of memantine, for which a causal relationship with the drug cannot be excluded: agranulocytosis, leukopenia (including neutropenia), pancytopenia, thrombocytopenia, thrombocytopenic purpura, acute renal failure, Stevens-Johnson syndrome.

Interaction

When used concomitantly with levodopa preparations, dopamine receptor antagonists, and m-holinoblockers, the effect of the latter may be enhanced.

When used concomitantly with barbiturates, neuroleptics, the effect of the latter may decrease.

When used together, it can change (increase or decrease) the effect of dantrolene and baclofen, so the dosage of drugs should be selected individually.

Concomitant use with amantadine should be avoided because of the increased risk of psychosis. This risk is also typical for ketamine and dectromethorphan. A risk case for such an interaction between memantine and phenytoin is described. These drugs are chemically related NMDA receptor antagonists.

Plasma concentrations of cimetidine, ranitidine, procainamide, quinidine, quinine, and nicotine may increase when taken concomitantly with memantine.

It is possible to reduce the concentration of hydrochlorothiazide when taken simultaneously with memantine.

An increase in INR (international normalized ratio) may occur in patients taking oral anticoagulants (warfarin). Although no causal relationship has been established, careful monitoring of prothrombin time and INR is recommended in patients taking concomitant oral anticoagulants.

It is possible to reduce the concentration of hydrochlorothiazide in the blood serum when it is used simultaneously with memantine or any combination containing hydrochlorothiazide. Memantine may increase the excretion of hydrochlorothiazide.

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

There are no pharmacokinetic interactions of memantine with glibenclamide, metformin, or donepezil.

There was no significant effect of memantine on the pharmacokinetics of galantamine.

Memantine does not inhibit the activity of CYP isoenzymes 1A2,2A6,2C9,2D6,2E1,3A, flavin monooxydase, epoxidhydrolase, and sulfation in vitro.

How to take it, course of use and dosage

Treatment should be initiated and carried out under the supervision of a physician experienced in the diagnosis and treatment of dementia in Alzheimer’s disease. Therapy should be initiated only if there is a caregiver who will regularly monitor the patient’s medication intake. Diagnosis of the disease should be carried out in accordance with the current recommendations. The tolerability and dosage of memantine should be reviewed on a regular basis, preferably within three months of starting treatment. Thereafter, the clinical benefit of memantine and patient tolerability should be reviewed on a regular basis in accordance with current clinical guidelines.Maintenance treatment can be continued indefinitely as long as the therapeutic effect is favorable and as long as the patient tolerates memantine treatment well. Discontinuation of memantine should be considered if there are no signs of therapeutic efficacy or if the patient is intolerant to the treatment.

The drug should be taken orally once a day and always at the same time, regardless of food intake.

To reduce the risk of adverse reactions, the initial dose is increased to maintenance by titrating 5 mg per week for the first 3 weeks according to the following scheme:

Week 1 (day 1-7): 5 mg per day (½ tablet of 10 mg) for 7 days.

Week 2 (day 8-14): 10 mg per day (1 tablet of 10 mg) for 7 days.

Week 3 (day 15-21): 15 mg daily (1½ tablets of 10 mg) for 7 days.

Starting from the 4th week-20 mg (1 tablet of 20 mg or 2 tablets of 10 mg) per day.

The maximum daily dose is 20 mg per day.

The recommended maintenance dose is 20 mg per day.

Special patient groups

Elderly patients

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

Patients with impaired renal function

In patients with mild renal impairment (creatinine clearance 50-80 ml/min), no dose adjustment is required. For patients with moderate renal insufficiency (creatinine clearance 30-49 ml / min), the daily dose is 10 mg. In the future, if the drug is well tolerated for at least 7 days of treatment, the dose can be increased to 20 mg per day according to the standard scheme. In patients with severe renal insufficiency (creatinine clearance 5-29 ml / min), the daily dose is 10 mg.

Patients with impaired liver function

In patients with mild to moderate hepatic impairment (Child-Pugh class A and B), no dose adjustment is required. The drug is contraindicated in patients with severe hepatic insufficiency (Child-Pugh class C).

Overdose

There are limited overdose data available from clinical trials and post-marketing experience with memantine.

Symptoms: a relatively large overdose (200 mg once and 105 mg daily for 3 days) resulted in fatigue, weakness, and/or diarrhea, or no symptoms. In patients with an overdose of less than 140 mg or with an unknown dose, symptoms such as confusion, hypersomnia, drowsiness, dizziness, agitation, aggression, hallucinations, gait disorders, vomiting, diarrhea were observed.

Taking 2000 mg of memantine did not lead to a fatal outcome, but it was accompanied by nervous system disorders (coma for 10 days, then diplopia and agitation). After symptomatic treatment and plasmapheresis, the patient recovered without further complications.

In another reported case, the patient also recovered. After taking 400 mg of memantine orally, he had the following disorders of the central nervous system: anxiety, psychosis, visual hallucinations, a decrease in the threshold of convulsive readiness, drowsiness, stupor, unconsciousness.

Treatment: gastric lavage, use of activated charcoal, acidification of urine, forced diuresis, symptomatic therapy. There is no specific antidote. If signs and symptoms of general hyperstimulation of the central nervous system appear, symptomatic therapy should be carried out with caution.

Special instructions

The optimal dose is achieved gradually, with an increase in the dose every week.

In patients with epilepsy, a history of seizures, or a predisposition to epilepsy, memantine should be used with caution.

Co-use of memantine with an NMDA receptor antagonist such as amantadine, ketamine, or dextromethorphan should be avoided. These compounds act on the same receptor system as memantine, so undesirable reactions (mainly related to the central nervous system) may occur more often and be pronounced.

The presence of a number of factors that can increase the pH of urine in patients requires careful medical supervision. These include: drastic changes in diet, such as switching from a meat-based diet to a vegetarian one, or heavy consumption of alkaline gastric buffer solutions. Renal tubular acidosis or severe urinary tract infections caused by Proteus spp can also lead to an increase in the pH of urine. Conditions that increase the pH of the urine can reduce the excretion of memantine by the urinary system, which will lead to an increase in the concentration of memantine in plasma.

Patients with a history of myocardial infarction, decompensated chronic heart failure(NYHA functional class III-IV), or uncontrolled hypertension were excluded from most clinical trials. Therefore, data on the use of memantine in such patients are limited, and the use of Memantine should be carried out under the close supervision of a doctor.

The age of most people with Alzheimer’s disease is 65 years or older. In the memantine clinical trials, the average age of patients was about 76 years: more than 90% of patients were aged 65 years and older,60% were aged 75 years and older, and 12% were over the age of 85 years. There were no clinically significant differences in the majority of adverse events in the groups of patients ≥ 65 years and older.

No dose adjustment is required in patients with mild to moderate renal insufficiency. Dose reduction is recommended in patients with severe renal insufficiency.

No dose adjustment is required in patients with mild or moderate hepatic insufficiency (Child-Pugh Class A or B).

Influence of a medicinal product for medical use on the ability to drive vehicles and mechanisms

Patients with moderate to severe Alzheimer’s disease usually have impaired ability to drive vehicles and manage complex mechanisms. In addition, memantine can cause changes in the speed of psychomotor response, so patients should refrain from driving vehicles or working with complex mechanisms.

Storage conditions

Store in a dark place at a temperature not exceeding 25 °C.

Keep out of the reach of children.

Shelf

life is 4 years.

Do not use after the expiration date.

Active ingredient

Memantine

Conditions of release from pharmacies

By prescription

Dosage form

Tablets

Purpose

For adults as directed by your doctor

Indications

Alzheimer’s disease, Concussion and other traumatic brain injuries, Alcoholism, Acquired dementia, Stroke effects