Memantine-Vertex, 10 mg 30 pcs

Name: Memantine-Vertex, 10 mg 30 pcs
SKU: 294447
Availability: InStock

€14.94

EAN: 4607003248550 SKU: 294447 Categories: Alzheimer's disease, Medicine, Neurology and Psychiatry

Description

Dementia treatment.

Pharmacodynamics:

Adamantan derivative. It is a noncompetitive N-methyl-D-aspartate (NMDA)-receptor antagonist and has a modulatory effect on the glutamatergic system. It regulates ion transport, blocks calcium channels, normalizes membrane potential, improves nerve impulse transmission. Improves cognitive processes, increases daily activity.

Pharmacokinetics:

Intake

Eating does not affect absorption. After ingestion, memantine is rapidly and completely absorbed from the gastrointestinal tract. Maximum concentration of memantine in blood plasma is reached 3-8 hours after intake.

Distribution

Daily administration of a daily dose of 20 mg results in an equilibrium plasma concentration of memantine of 70-150 ng/ml. When a daily dose of 5-30 mg was administered, the ratio of average cerebrospinal fluid concentration to plasma concentration was calculated to be 0.52. The volume of distribution is about 10 l/kg. About 45% of memantine is bound to plasma proteins. No memantine cumulation was noted in normal renal function.

Metabolism

80% of circulating memantine in blood is represented by unchanged substance. The major metabolites are N-3,5-dimethylgludantane, a mixture of isomers of 4- and 6-hydroxymemantine, and 1-nitroso-3,5-dimethyladamantane. The metabolites have no pharmacological activity of their own. No metabolism by cytochrome P450 isoenzymes was detected in in vitro experiments.

Memantine is primarily excreted by the kidneys. Excretion is single-phase with a half-life of 60-100 hours. In volunteers with normal renal function, total clearance is 170 ml/min/1.73 m2, a portion of total renal clearance is achieved through tubular secretion. Renal excretion also includes tubular reabsorption, possibly mediated by cationic transport proteins. The rate of renal elimination of memantine under conditions of alkaline urine reaction can decrease by a factor of 7-9. Urinary alkalinization can be caused by a dramatic change in diet, such as switching from a diet that includes animal products to a vegetarian diet, or by intensive use of alkaline gastric buffers.

Linearity

Studies conducted in volunteers have shown linearity in pharmacokinetics over the 10-40 mg dose range.

Pharmacokinetic/pharmacodynamic relationship

When memantine is administered at a dose of 20 mg/day, the level of concentration in cerebrospinal fluid corresponds to the value of the inhibition constant, which for memantine is 0.5 μmol in the frontal cortex region of the brain.

Indications

Moderate to severe dementia of the Alzheimer type.

Active ingredient

Memantine

Composition

One film-coated tablet contains:

Dosage 10 mg

active ingredient:

memantine hydrochloride – 10.0 mg;

excipients:

Microcrystalline cellulose – 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;

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.

Interaction

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

Simultaneous use of memantine with barbiturates, neuroleptics may decrease their effect.
Simultaneous use of memantine with dantrolene or baclofen and antispasmodics may change their effect (increase or decrease), so the drug doses should be adjusted individually.

Simultaneous use of memantine with amantadine should be avoided because of the risk of psychosis. Both compounds are antagonists of NMDA-receptors.

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 hydrochlorothiazide may decrease the plasma concentration of hydrochlorothiazide due to increased excretion.

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

Simultaneous use of memantine with antidepressants, selective serotonin reuptake inhibitors and monoamine oxidase inhibitors requires close monitoring of patients.

According to pharmacokinetic studies, no drug interaction effects were found in young healthy volunteers when taking memantine simultaneously with glibenclamide/metformin or donepezil.

Clinical studies also showed no effect of memantine on galantamine pharmacokinetics in young healthy volunteers.
In in vitro studies, memantine did not inhibit CYP isoenzymes 1A2, 2A6, 2C9, 2D6, 2E1, 3A, monooxygenase containing flavin, epoxide hydrolase, and 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.

Special patient groups

Patients in the elderly (over 65 years)

Dose adjustment is not required.

Patients with impaired renal function

Dose adjustment is not required in patients with a creatinine clearance of 50-80 ml/min.

In patients with moderate renal insufficiency (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-Pugh class A and B) no dose adjustment is required.

Patients with severe hepatic impairment (Child-Pugh class C) are contraindicated.

Special Instructions

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

Data on memantine administration in patients with myocardial infarction in anamnesis, chronic heart failure (functional class III-IV according to NYHA classification) or uncontrolled arterial hypertension are limited, therefore careful medical observation of such patients is necessary.

Use with caution in patients with thyrotoxicosis, epilepsy, seizures (including anamnesis) and predisposition to epilepsy.
Concomitant use of memantine and NMDA-receptor antagonists such as amantadine, ketamine and dextromethorphan should be avoided. These compounds affect the same receptor system as memantine, so adverse reactions (mainly from the central nervous system) may occur more frequently and be more pronounced.

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

Influence on ability to drive motor vehicles and operate machinery:

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

Contraindications

– Hypersensitivity to memantine or any of the ingredients of the drug;
– severe hepatic insufficiency (class C according to the Child-Pugh classification);
– Lactose intolerance, lactase deficiency, glucose-galactose malabsorption syndrome;
– pregnancy;
– period of breastfeeding;
– age under 18 years (effectiveness and safety are not established).

With caution:
– Thyrotoxicosis;
– epilepsy, predisposition to epilepsy;
– seizures (including anamnesis);
– simultaneous use of NMDA-receptor antagonists (amantadine, ketamine, dextromethorphan);
– presence of factors that increase urine pH (sudden change in diet, e.g., switching to a vegetarian diet, heavy intake of alkaline gastric buffers);
– Renal tubular acidosis;
– Severe urinary tract infections caused by Proteus bacteria;
– Myocardial infarction (history);
– Heart failure (functional class III-IV according to NYHA classification);
– uncontrolled arterial hypertension;
– renal insufficiency;
– hepatic insufficiency (class A and B according to the Child-Pugh classification).

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.

Central nervous system disorders:

often – headache, dizziness, somnolence, impaired balance;

infrequent – gait disturbance, confusion, hallucinations (hallucinations have been observed mainly in patients with severe Alzheimer-type dementia);

very rarely – seizures;

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

The cardiovascular system:

often – increased blood pressure;

infrequent – venous thrombosis/thromboembolism, heart failure.

Digestive system disorders:

often – constipation;

infrequent – nausea, vomiting;

frequency unknown – pancreatitis, hepatitis.

Respiratory system disorders:

often – shortness of breath.

Anxiety of the genitourinary system:

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

Allergic reactions:

often – hypersensitivity to the components of the drug;

frequency unknown – allergic reactions, Stevens-Johnson syndrome.

Skin disorders:

incidence unknown – thrombocytopenic purpura.

Laboratory findings:

often – increased activity of “liver” enzymes;

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

Other:

infrequent – increased fatigue;

rarely – fungal infections; frequency unknown – candidiasis.

Overdose

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

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, adsorbents (activated charcoal), urine acidification, forced diuresis (if necessary). There is no specific antidote.

Pregnancy use

Pregnancy

Use in pregnancy is contraindicated because there is no data on the effect of memantine on pregnancy.

Similarities

Acathinol Memantine, Noogeron, Maruksa, Memantal, Memaneirin

Additional information

Weight	0.100 kg
Shelf life	3 years. Do not use after the expiration date.
Conditions of storage	Store in the dark place at a temperature not exceeding 25 °С. Store out of the reach of children.
Manufacturer	Vertex, Russia
Medication form	pills
Brand	Vertex