Galantamine 8 mg, 56 pcs.

1 tablet contains:

Active substances: 

• galantamine hydrobromide, in terms of galantamine - 8 mg.

Excipients: 

• calcium hydrogen phosphate dihydrate, 

• colloidal silicon dioxide (aerosil), 

• copovidone (Esd-630 plasdon or VA-64 collidone)

• magnesium stearate, 

• croscarmellose sodium (primellose), 

• microcrystalline cellulose.

Shell composition: Advantia Prima 319974RC09 (hydroxypropyl methyl cellulose), macrogol (polyethylene glycol), caprine / capryl triglyceride (glyceryl caprylocaprate), titanium dioxide, aluminum varnish based on quinoline yellow dye, aluminum varnish based on brilliant blue dye, aluminum blue dye based on brilliant blue dye indigo carmine.

Selective, competitive and reversible acetylcholinesterase inhibitor. Stimulates nicotinic receptors and increases the sensitivity of the postsynaptic membrane to acetylcholine. It facilitates the excitation in the neuromuscular synapse and restores neuromuscular conduction in cases of its blockade by muscle relaxants of a non-depolarizing type of action. 

Increases the tone of smooth muscles, enhances the secretion of digestive and sweat glands, and causes myosis. By increasing the activity of the cholinergic system, galantamine improves cognitive function in patients with Alzheimer's type dementia, but does not affect the development of the disease itself.

Pharmacokinetics

The pharmacokinetics of galantamine is linear in the dose range 
of 4-16 mg 2 times a day.

Suction

After a single oral dose of 8 mg, galantamine is rapidly absorbed from the gastrointestinal tract (GIT). The maximum concentration (Cmax) in blood plasma is reached after 1.2 hours and is about 43 ng / ml, the area under the concentration-time curve (AUC) is 
427 ng x h / ml.

Distribution

Absolute oral bioavailability is 88.5%. Taking galantamine with food slows down its absorption (Cmax decreases by 25%), but does not affect the area under the concentration-time curve (AUC). After repeated administration of galantamine at a dose of 12 mg 2 times a day, average concentrations at the end of the course and Cmax in blood plasma vary from 30 ng / ml to 90 ng / ml. 

Distribution volume - 175 ml. The binding of galantamine to plasma proteins is about 18%. In whole blood, galantamine is found mainly in the form elements (52.7%) and in plasma (39%), while its fraction associated with plasma proteins is only 8.4%.

Metabolism

In vitro studies have shown that the main isoenzymes of the P450 cytochrome system involved in galantamine metabolism are the CYP2D6 isoenzyme, which is associated with the formation of O-demethylgalantamine, and the CYP3A4 isoenzyme, which is associated with the formation of N-galgantamine. 

The amounts of radioactive substances excreted in urine and feces in people with fast and slow metabolism did not differ. In plasma in people with fast and slow metabolism, the bulk of the radioactive substances are unaltered galantamine and its glucuronide. 

After a single administration of galantamine in the plasma of “fast” and “slow” metabolizers, none of the active metabolites (norgalantamine, O-demethylgalantamine and O-demethylnorgalantamine) is present in unconjugated form. Norgalantamine is found in the blood plasma of patients after repeated administration of galantamine, but its concentration is not more than 10% of the concentration of galantamine. 

Breeding

The elimination of galantamine is bio-exponential. The final half-life (T1 / 2) is 7-8 hours. Plasma clearance of galantamine is about 200 ml / min. 18-22% of galantamine is excreted unchanged in urine within 24 hours. 

Renal clearance is about 65 ml / min, which is 20-25% of the total plasma clearance. Within 7 days after a single oral administration of 3H-galantamine in a dose of 4 mg, 90-97% of the radioactivity was excreted in the urine and 2.2-6.3% with feces.

Pharmacokinetics of individual groups

In patients with Alzheimer's disease, the concentration of galantamine in the blood plasma is 30% -40% higher than in healthy individuals.

In patients with mild hepatic impairment (5-6 points on the Child-Pugh scale), the pharmacokinetic parameters are similar to those in healthy patients. In patients with moderate hepatic impairment 
(7-9 points on the Child-Pugh scale), AUC and T1 / 2 of galantamine increase by about 30%.

Patients with Alzheimer's disease with impaired renal function with creatinine clearance (CC) of at least 9 ml / min dose adjustment of galantamine is not required.

Contraindicated in pregnancy. At the time of treatment should stop breastfeeding.

concomitant use of drugs that slow the heart rate (digoxin, beta-blockers); general anesthesia; peptic ulcer of the stomach and duodenum, increased risk of erosive and ulcerative lesions of the gastrointestinal tract; chronic obstructive pulmonary disease (COPD).

The frequency of side effects is classified according to WHO recommendations: very often (≥1 / 10), often (from ≥1 / 100 to <1/10), infrequently (from ≥1 / 1000 to <1/100), rarely (from ≥1 / 10000 to <1/1000), very rarely (<1/10000).

Immune System Impairment

Infrequently: hypersensitivity.

Metabolic and nutritional disorders

Often: loss of appetite, anorexia.

Infrequently: dehydration (in rare cases, leading to the development of renal failure).

Mental disorder

Often: hallucinations, depression (very rarely with suicide).

Infrequently: visual hallucinations, aggression, agitation.

Disorders of the nervous system

Often: fainting, dizziness, tremor, headache, drowsiness, lethargy, insomnia, fever.

Infrequently: paresthesia, taste perversion, hypersomnia, convulsions (potentially cholinomimetic drugs can cause convulsions), cerebrovascular disease, transient circulatory disturbance of the ischemic type.

Very rarely: exacerbation of the course of Parkinson's disease, convulsions.

Violations of the organ of vision

Infrequently: blurred visual perception.

Hearing impairment and labyrinthine disorders

Infrequently: tinnitus.

Heart disorder

Often: bradycardia.

Infrequently: supraventricular extrasystole, atrioventricular block I degree, sinus bradycardia, palpitations, arrhythmia, acute myocardial infarction, coronary heart disease, tachycardia.

Violation of the vessels

Often: arterial hypertension.

Infrequently: arterial hypotension, a sensation of "hot flashes."

Gastrointestinal Disorders

Very often: vomiting, nausea.

Often: abdominal pain, pain in the upper abdomen, diarrhea, dyspepsia, a feeling of discomfort in the stomach, a feeling of discomfort in the abdomen.

Infrequently: retching.

Very rare: Dysphagia, gastrointestinal bleeding.

Violations of the liver and biliary tract

Rarely: hepatitis.

Disorders of the skin and subcutaneous tissue

Often: hyperhidrosis.

Rarely: skin rash.

Musculoskeletal and connective tissue disorders

Often: muscle cramps.

Infrequently: muscle weakness.

General disorders and disorders at the injection site

Often: increased fatigue, asthenia, malaise, weakness.

Laboratory and instrumental data:

Often: weight loss.

Infrequently: increased activity of "liver" enzymes.

Injuries, intoxications and complications of manipulations

Often: fall, injuries.

It is not recommended to combine with other cholinomimetics.

It is an opioid antagonist in action on the respiratory center. It exhibits pharmacodynamic antagonism to m-anticholinergics (atropine, homatropin methyl bromide, etc.), ganglion blockers, non-depolarizing muscle relaxants, quinidine, procainamide.

Aminoglycoside antibiotics may reduce the therapeutic effect of galantamine. Galantamine enhances neuromuscular blockade during general anesthesia (including the use of suxamethonium as a peripheral muscle relaxant). Medicines that reduce heart rate (digoxin, beta-blockers) increase the risk of aggravation of bradycardia.

Cimetidine may increase the bioavailability of galantamine.

All drugs that inhibit isoenzymes of the cytochrome P450 system (CYP2D6 and CYP3A4) can increase plasma concentrations of galantamine while they are used, resulting in an increase in the frequency of cholinergic side effects (mainly nausea and vomiting). In this case, depending on the tolerance of therapy to a specific patient, a reduction in the maintenance dose of galantamine may be necessary.

CYP2D6 isoenzyme inhibitors (amitriptyline, fluoxetine, fluvoxamine, paroxetine, quinidine) reduce galantamine clearance by 25-30%. For this reason, it is not recommended to prescribe simultaneously with ketoconazole, zidovudine, erythromycin.

Enhances the inhibitory effect on the central nervous system of ethanol and sedatives.

Inside, with food, washed down with water.

Adults

The daily dose is 8-32 mg, divided into 2-4 doses.

With myasthenia gravis, the daily dose is divided into 3 doses.

In Alzheimer's disease, treatment is recommended to start with taking 4 mg tablets 2 times a day. Within 4 weeks, the daily dose can be gradually increased to 16 mg - 1 tablet of 8 mg 2 times a day - in the morning and in the evening. During treatment with the drug, it is necessary to ensure the intake of a sufficient amount of fluid. If discontinuation of the drug is required during treatment, then restoration of treatment must begin with the lowest dose and gradually increase it.

Patients with moderate hepatic and renal impairment

The initial dose is 4 mg 1 time per day, which is taken in the morning for at least 1 week, after which the dose is increased to 4 mg 2 times a day and taken for 4 weeks.

The total daily dose should not exceed 12 mg.

Symptoms: depression of consciousness (up to coma), convulsions, increased severity of side effects, severe muscle weakness in combination with hypersecretion of the glands of the mucous membrane of the trachea and bronchospasm can lead to fatal airway blockage.

Treatment: gastric lavage, symptomatic therapy. As an antidote, iv administration of atropine in doses of 0.5-1 mg. Subsequent doses of atropine are determined depending on the therapeutic response and the patient's condition.

Treatment with acetylcholinesterase inhibitors is accompanied by a decrease in body weight. This is especially necessary to keep in mind when treating patients with Alzheimer's disease, in which weight loss is usually observed. In this regard, it is necessary to monitor body weight in such patients.

During treatment, it is necessary to ensure sufficient fluid intake. Like other cholinomimetics, the drug can cause vagotonic effects from the cardiovascular system (including bradycardia), which must be taken into account in patients with sinus node syndrome and other conduction disturbances, as well as with the use of drugs that reduce heart rate (digoxin or beta-blockers).

When treating with Galantamine, there is a risk of occurrence, in connection with which it is necessary to control blood pressure more often, especially when taking the drug in higher doses (40 mg daily dose). In order to prevent such side effects, it is necessary to carefully select the dose of the drug at the beginning of treatment. The effectiveness of the drug in patients with other types of dementia and memory impairment has not been established.

The drug is not intended for the treatment of patients with mild cognitive impairment, i.e. with an isolated memory impairment exceeding the expected level for their age and education, but not meeting the criteria for Alzheimer's disease.

Use for impaired liver function

Contraindicated in severe violations of liver function. Precautions for mild to moderate impaired liver function.

Use for impaired renal function

Contraindicated in severe renal impairment. Precautions for mild to moderate impaired renal function.

Pediatric Use

Contraindicated in children under 9 years of age.

Influence on the ability to drive vehicles and control mechanisms

During the treatment period, one should refrain from performing work requiring increased concentration of attention and speed of psychomotor reactions, including driving a car.

pills