Galantamine Canon, 8 mg 56 pcs

A selective, competitive and reversible acetylcholinesterase inhibitor. Stimulates nicotinic receptors and increases sensitivity of postsynaptic membrane to acetylcholine. Facilitates excitation conduction in neuromuscular synapse and restores neuromuscular conduction in cases of its blockade by myorelaxants of non-depolarizing type of action.

It increases tone of smooth muscles, increases secretion of digestive and sweat glands, causes miosis. By increasing the activity of cholinergic system, galantamine improves cognitive functions in patients with Alzheimer type dementia, but does not influence the development of the disease itself.

Pharmacokinetics

The pharmacokinetics of galantamine are linear in the dose range
4 -16 mg 2 times daily.

Intestation

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

Distribution

The absolute bioavailability when taken orally is 88.5%. Taking galantamine with food slows its absorption (Cmax decreases by 25%), but does not affect the area under the curve “concentration-time” (AUC). After multiple doses of galantamine at a dose of 12 mg 2 times per day, the mean end-of-course concentrations and Cmax in plasma vary from 30 ng/ml to 90 ng/ml.

The volume of distribution is 175 ml. The binding of galantamine to plasma proteins is about 18%. In whole blood, galantamine is predominantly found in the form cells (52.7%) and in plasma (39%), whereas its fraction bound to plasma proteins is only 8.4%.

Metabolism

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

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

After a single dose of galantamine, none of the active metabolites (norgalantamine, O-demethylgalantamine and O-demethylnorgalantamine) are present in the plasma of “fast” and “slow” metabolizers in an unconjugated form. Norgalantamine is detected in the plasma of patients after multiple doses of galantamine, but its concentration is no more than 10% of the galantamine concentration.

The elimination of galantamine is bioexponential. The final elimination 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 the urine within 24 hours.

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

Particular group pharmacokinetics

In patients with Alzheimer’s disease, plasma concentrations of galantamine are 30%-40% higher than in healthy individuals.

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

Patients with Alzheimer’s disease with impaired renal function with a creatinine clearance (CK) of at least 9 ml/min do not require dose adjustment of galantamine.

Indications

Active ingredient

Composition

1 tablet contains:

Active ingredients:

Excipients:

calcium hydrophosphate dihydrate,

colloidal silicon dioxide (aerosil),

copovidone (plasdon ES-630 or collidon VA-64),

How to take, the dosage

Overly, with meals, with water.

Adults

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

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

In Alzheimer’s disease, treatment is recommended to start with 4 mg tablets twice daily. Within 4 weeks, the daily dose can be gradually increased to 16 mg – 1 tablet of 8 mg twice a day – in the morning and in the evening. During treatment with the drug it is necessary to ensure intake of sufficient fluids. If during treatment it is necessary to stop taking the drug, restoration of treatment should be started with the lowest dose and gradually increased.

Patients with moderate hepatic and renal impairment

The initial dose is 4 mg once daily taken in the morning for at least 1 week, after which the dose is increased to 4 mg twice daily and taken for 4 weeks.

The total daily dose should not exceed 12 mg.

Interaction

It is not recommended to combine with other cholinomimetics.

It is an opioid antagonist by its effect on the respiratory center. It shows pharmacodynamic antagonism to m-cholinolytics (atropine, homatropine methyl bromide, etc.), ganglioblocators, nondepolarizing myorelaxants, quinidine , procainamide.

Aminoglycoside antibiotics may decrease the therapeutic effect of galantamine. Galantamine increases neuromuscular blockade during general anesthesia (including when using suxamethonium as a peripheral myorelaxant). Drugs that reduce heart rate (digoxin, beta-adrenoblocks) increase the risk of worsening bradycardia.

Cimetidine may increase the bioavailability of galantamine.

All drugs that inhibit both cytochrome P450 system isoenzymes (CYP2D6 and CYP3A4) may increase plasma concentrations of galantamine when used simultaneously, which may result in an increased incidence of cholinergic side effects (mainly nausea and vomiting). In this case, depending on the tolerability of therapy by the individual patient, a reduction in the maintenance dose of galantamine may be necessary.

The 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.

It increases the depressant effect on the central nervous system of ethanol and sedatives.

Special Instructions

Treatment with acetylcholinesterase inhibitors is accompanied by a decrease in body weight. This is especially important to keep in mind when treating patients with Alzheimer’s disease who usually lose weight. Because of this, it is necessary to monitor body weight in such patients.

A sufficient fluid intake is necessary during treatment. As other cholinomimetics, the drug may cause vagotonic effects on the cardiovascular system (including bradycardia), which should be considered in patients with sinus node weakness syndrome and other conduction disorders, as well as in concurrent use with drugs which reduce heart rate (digoxin or beta-adrenoblocks).

When treating with Galantamine there is a risk of side effects and therefore blood pressure should be monitored more frequently, especially when taking the drug at higher doses (40 mg daily dose). In order to prevent such side effects it is necessary to choose the drug dose carefully 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 indicated to treat patients with mild cognitive impairment, i.e., with isolated memory impairment greater than expected for their age and education, but not meeting the criteria for Alzheimer’s disease.

Use in liver dysfunction

Contraindicated in severe liver dysfunction. With caution in mild to moderate hepatic impairment.

Preventive use in renal dysfunction

Contraindicated in severe renal dysfunction. With caution in mild to moderate renal dysfunction.

Pediatric use

Contraindicated in children under 9 years of age.

Impact on ability to drive and operate machinery

At the time of treatment, one should refrain from performing work requiring increased concentration and quick psychomotor reactions, including driving.

Contraindications

concurrent administration of drugs that slow heart rate (digoxin, beta-adrenoblocks); general anesthesia; gastric and duodenal ulcer, increased risk of gastrointestinal erosive ulcers; chronic obstructive pulmonary disease (COPD).

Side effects

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

Immune system disorders

Infrequent: hypersensitivity.

Metabolism and nutrition disorders

Often: decreased appetite, anorexia.

Infrequent: dehydration (in rare cases leading to renal failure).

Mental disorders

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

Infrequent: visual hallucinations, aggression, agitation.

Nervous system disorders

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

Infrequent: paresthesia, perversion of taste, hypersomnia, seizures (potentially cholinomimetic drugs can cause seizures), cerebrovascular disease, transient ischemic-type circulatory disorders.

Very rare: exacerbation of the course of Parkinson’s disease, seizures.

Visual organ disorders

Infrequent: blurred vision.

Hearing and labyrinth disorders

Infrequent: tinnitus.

Heart disorder

Often: bradycardia.

Infrequent: supraventricular extrasystoles, 1st degree atrioventricular block, sinus bradycardia, palpitations, arrhythmia acute myocardial infarction, coronary heart disease, tachycardia.

Vascular disorders

Often: arterial hypertension.

Infrequent: arterial hypotension, feeling of “hot flashes”.

Gastrointestinal disorders

very often: vomiting, nausea.

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

Infrequent: urge to vomit.

Very rare: Dysphagia, gastrointestinal bleeding.

Liver and biliary tract disorders

Rarely: hepatitis.

Skin and subcutaneous tissue disorders

Often: hyperhidrosis.

Rarely: skin rash.

Muscular and connective tissue disorders

Often: muscle spasms.

Infrequent: muscle weakness.

General disorders and disorders at the site of administration

Often: increased fatigue, asthenia, malaise, weakness.

Laboratory and instrumental findings:

Often: decreased body weight.

Infrequent: increased activity of “liver” enzymes.

Injuries, intoxications and complications of manipulations

Often: falls, injuries.

Overdose

Symptoms: depression of consciousness (up to coma), convulsions, increased severity of side effects, marked muscle weakness, combined with hypersecretion of glands of the tracheal mucosa and bronchospasm may lead to fatal airway blockage.

Treatment: gastric lavage, symptomatic therapy. As an antidote, intravenous injection 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.

Pregnancy use

It is contraindicated in pregnancy. Breastfeeding should be stopped during treatment.

Similarities