Galantamine - instructions for use, dose, side effects, contraindications

Reversible cholinesterase inhibitor. It facilitates the carrying out of nerve impulses in the field of neuromuscular synapses; intensifies excitation processes in the reflex zones of the spinal cord and brain, penetrates well through the blood-brain barrier.Increases the tone and stimulates the reduction of smooth and skeletal muscles, the secretion of digestive and sweat glands, restores neuromuscular conduction blocked by nondepolarizing muscle relaxants. Causes miosis, spasm of accommodation, reduces intraocular pressure in closed-angle glaucoma.

Pharmacokinetics:

Galantamine is rapidly absorbed after subcutaneous injection. The therapeutic concentration in the blood plasma is reached after 30 minutes. There was no statistically significant difference in the area under the concentration-time curve (AUC) after a single dose of 10 mg administered orally or parenterally. The maximum concentration in the blood plasma after a single dose of 10 mg administered orally and parenterally is 1.20 mg / ml and is achieved within 2 hours.

The half-distribution period of galantamine (10 minutes) with parenteral administration is longer than in the half-distribution of neostigmine methyl sulfate and pyridostigmine bromide (0.54-3.5 minutes and 5.0-6.6 minutes, respectively), so it begins to act later than other inhibitors cholinesterase.

The volume of distribution of galantamine is 175 liters, and binding to plasma proteins does not exceed 18%; about 53% of galantamine is in the blood cells.

The half-life period of galantamine is two-phase and takes 7-8 hours.

Metabolism is not characterized by intensity and occurs with the participation of cytochrome P450 isoenzymes (isozymes CYP2D6 and CYP3A4) mainly through N- and O-demethylation (about 5-6% of the preparation), as well as glucuronation, N-oxidation and epimerization. Metabolites of galantamine - epigalanthamine and galantamine are found in plasma and urine.

Galantamine 90-97% is excreted by the kidneys (18-22% unchanged) by glomerular filtration, 2.2-6.3% by the intestine, and about 0.2% by the bile. Kidney clearance is 65-100 ml / min (20-25% of the plasma clearance), which is close to the clearance of inulin. It is established that in patients with Alzheimer's disease the concentration of galantamine in blood plasma is 30-40% higher than in healthy volunteers. With moderate hepatic insufficiency, the elimination of galantamine is slowed by 25%. In chronic renal failure of moderate degree (creatinine clearance 52-104 ml / min), its plasma concentration increases by 38%, with severe (creatinine clearance 9-51 ml / min) - by 67%.

Indications:

In Neurology:

- diseases of the peripheral nervous system (neuritis, polyneuritis, polyneuropathy);

- conditions associated with damage to the anterior horn of the spinal cord (after poliomyelitis, myelitis, spinal muscular atrophy);

- Cerebral palsy (residual phenomena of a stroke, cerebral palsy (spastic forms));

- disorders of neuromuscular conduction (myasthenia gravis gravis).

In anesthesiology and surgery:

- as an antagonist of nondepolarizing muscle relaxants;

- for the treatment of postoperative paresis of the small intestine and bladder.

In physiotherapy:

- for iontophoresis in neurological diseases of the peripheral nervous system.

In Toxicology:

- at a poisoning with cholinesterase inhibitors.

Contraindications:

Increased individual sensitivity, bronchial asthma, severe heart failure (III-IV group by NYHA), bradycardia, stenocardia, atrioventricular blockade, arterial hypertension, chronic obstructive pulmonary disease, epilepsy, hyperkinesia, severe liver dysfunction (more than 9 on the Child-Pugh scale), mechanical intestinal obstruction, renal failure (creatinine clearance less than 9 ml / min ),mechanical impairment of the patency of the urinary tract, recent surgery on the urinary tract or prostate gland, age up to 1 year, pregnancy and the period of breastfeeding.

Carefully:

Hepatic and renal failure, urination disorder, surgical interventions with general anesthesia (anesthesia).

Pregnancy and lactation:

Pregnancy

There is insufficient clinical data on the safety of galantamine during pregnancy, so the use of the drug is contraindicated.

Breastfeeding period

There is no data on the secretion of galantamine with breast milk, therefore, the use of the drug is contraindicated during breastfeeding.

Impact on fertility

Experimental data in animals showed no direct or indirect adverse effect of galantamine on the course of pregnancy, embryonic, fetal and postnatal development of the offspring.

Dosing and Administration:

Intravenously, subcutaneously.

The dose and duration of treatment with galantamine are determined by the doctor, depending on the severity of the symptoms of the disease and the patient's individual response to the treatment.

In neurology according to the declared indications (see section "Indications for use", subsection "In neurology") galantamine in the form of a solution for intravenous and subcutaneous administration is used for short-term treatment in case of inability to take the drug inside. At the first opportunity, they switch to taking the drug inside.

Adults galantamine administered subcutaneously, usually at a dose of 0.03-0.28 mg / kg.

Treatment begins with minimal doses, which gradually increase. The initial dose is 2.5 mg per day. If necessary, it is possible to increase the daily dose every 3-4 days by 2.5 mg to a maximum daily dose of 20 mg in 2-3 doses at equal doses. The maximum single dose for adults is 10 mg, the maximum daily dose is 20 mg.

Children galantamine is administered subcutaneously according to the calculation per kg of body weight in the following daily doses:

from 1 year to 2 years - 0.25-1.0 mg (0.02-0.08 mg / kg);

over 3 years of age galantamine prescribe in a dose of 0.03-0.28 mg / kg or:

from 3 to 5 years - 0,5-5,0 mg;

from 6 to 8 years - 0.75-7.5 mg;

from 9 to 11 years - 1.0-10.0 mg;

from 12 to 15 years - 1,25-12,5 mg;

over 15 years of age - 1,25-15,0 mg.

In anesthesiology, surgery and toxicology galantamine appoint:

- with an overdose of peripheral nondepolarizing muscle relaxants intravenously in a dose of 10-20 mg per day;

- with postoperative paresis of the gastrointestinal tract and bladder subcutaneously or intravenously in doses, according to age, distributed on 2-3 injections per day.

Adults treatment starts with minimal doses, which gradually increase. The initial dose is 2.5 mg per day. If necessary, it is possible to increase the daily dose every 3-4 days by 2.5 mg to a maximum daily dose of 20 mg in 2-3 doses at equal doses. The maximum single dose for adults is 10 mg, the maximum daily dose is 20 mg.

Children galantamine is administered subcutaneously according to the calculation per kg of body weight in the following daily doses: from 1 year to 2 years, 0.25-1.0 mg (0.03-0.08 mg / kg);

over 3 years of age galantamine prescribe in a dose of 0.03-0.28 mg / kg or: from 3 to 5 years - 0.5-5.0 mg; from 6 to 8 years - 0.75-7.5 mg;

from 9 to 11 years - 1.0-10.0 mg;

from 12 to 15 years - 1,25-12,5 mg;

older than 15 years and adults - 1,25-15,0 mg.

In physiotherapy galantamine is introduced by iontophoresis in a dose of 2.5 to 5 mg with an electric current value of 1 to 2 mA for 10 minutes for 10-15 days.

Patients with impaired hepatic function

In patients with moderate impaired liver function (7-9 points on the Child-Pugh scale), an increase in the concentration of galantamine in the blood plasma is possible, therefore it is recommended to reduce the daily dose to 15 mg.In patients with severe impairment of liver function (more than 9 on the Child-Pugh scale), the use of the drug is contraindicated.

Patients with impaired renal function

In patients with moderate renal dysfunction, the daily dose of the drug should not exceed 15 mg. In patients with severe renal dysfunction (creatinine clearance less than 10 ml / min), the use of the drug is contraindicated.

Side effects:

Undesirable reactions are classified according to frequency and system-organ classes MedDRA: very often (≥1 / 10), often (≥1 / 100 to <1/10), infrequently (≥1 / 1000 to <1/100), rarely (≥1 / 10000 to <1/1000), very rarely (<1/10000), the frequency is unknown (can not be estimated with the help of available data).

The most common adverse reactions are associated with the pharmacodynamic effects of galanthamine and are mediated by the nicotinic and muscarinic effects characteristic of cholinesterase inhibitors.

Metabolic and nutritional disorders:

Often: loss of appetite, anorexia;

Infrequently: dehydration.

Mental disorders:

Often: hallucinations, depression;

Infrequently: visual and auditory hallucinations.

Disorders from the central nervous system:

Often: dizziness, drowsiness, fainting, tremor, headache, lethargy;

Infrequently: paresthesia, dysgeusia, hypersomnia.

Disturbances on the part of the organ of sight:

Infrequently: impaired vision.

Ear and labyrinth disorders:

Infrequently: noise in ears.

Heart Disease:

Often: bradycardia;

Infrequently: supraventricular extrasystole, atrioventricular blockade, sinus bradycardia, palpitation.

Vascular disorders:

Often: increased blood pressure;

Infrequently: lowering of blood pressure, hot flashes.

Disorders from the gastrointestinal tract:

Often: nausea, vomiting;

Often: abdominal pain, diarrhea, dyspepsia, discomfort in the stomach and intestines;

Infrequently: vomiting;

Unknown frequency: increased peristalsis.

Disturbances from the liver and bile ducts:

Rarely: hepatitis.

Disturbances from the skin and subcutaneous tissues:

Often: increased sweating.

Disturbances from musculoskeletal and connective tissue:

Often: muscle spasms;

Infrequently: muscle weakness.

General disorders and disorders at the site of administration:

Often: asthenia, fatigue, weakness;

Frequency unknown: pain at the injection site, local reactions are possible with parenteral administration.

Laboratory and instrumental data:

Often: weight loss;

Infrequently: increased activity of "liver" transaminases.

Trauma, intoxication and complications of manipulation:

Often: falling.

Overdose:

Symptoms of galantamine overdose: nausea, vomiting, colicky pains (spasms) in the abdomen, diarrhea, increased salivation, lacrimation, urinary and fecal incontinence, severe sweating, lowering of blood pressure, lengthening of the QT interval, bradycardia, bronchospasm, muscle weakness, in more severe cases - seizures and coma . Severe muscle weakness in combination with hypersecretion of the mucous membrane of the trachea and bronchospasm can lead to complete blockade of the airways.

Treatment: symptomatic therapy, control of respiratory and cardiovascular systems. As an antidote, you can use atropine in a dose of 0.5-1.0 mg intravenously; the dose can be re-entered depending on the clinical picture.

Interaction:

It is a weak antagonist of morphine and its structural analogues.

Galantamine not only does not weaken, but on the contrary, enhances the effect of muscle relaxants depolarizing type (suxamethonium iodide, etc.).

Simultaneous use of a number of antiarrhythmics (quinidine), antidepressants (paroxetine, fluoxetine, amitriptyline), antifungal (ketoconazole), antiviral (zidovudine), antibacterial (erythromycin) of agents that suppress isoenzymes CYP2D6 and CYP3A4 cytochrome P450, involved in the metabolism of galantamine, can lead to an increase in its concentration in the blood serum, resulting in increased frequency of cholinergic side effects (mainly nausea and vomiting). AUC galantamine is increased by 30-40% with simultaneous application of it with ketoconazole and paroxetine, respectively. With simultaneous application with erythromycin AUC galantamine increases by 10%.

Inhibitor inhibitors CYP2D6 (amitriptyline, fluoxetine, fluvoxamine, quinidine) reduce the clearance of galantamine by 25-33%. In this case, depending on the tolerability of therapy by a specific patient, a reduction in the maintenance dose of galantamine may be necessary.

Between galantamine and m-holinoblokatorami (atropine, gomatropin), ganglion blockers (hexamethonium benzenesulfonate, azamethonium bromide, pakhikarpine hydroiodide), nondepolarizing muscle relaxants (tubocurarine chloride, etc.), quinine and procainamide, antagonism is possible.

Aminoglycoside antibiotics (gentamicin, amikacin) can reduce the therapeutic effect of galantamine.

When a combination of galantamine with drugs that reduce heart rate (β-blockers, digoxin) increases the risk of aggravation of the bradycardia.

Cimetidine can increase the bioavailability of galantamine.

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

With the simultaneous use of galantamine with other cholinomimetics (such as donepisil, neostigmine, pyridostigmine, pilocarpine), an increase in the cholinomimetic effect can be observed, therefore, their simultaneous application is not recommended.

Galantamine does not affect the pharmacokinetics of warfarin.

Special instructions:

The vagotonic effect on the sinoatrial node may contribute to the onset of bradycardia and AV blockade.This effect is of great importance for patients with supraventricular rhythm disorders and patients taking medications that cause a reduction in heart rate. However, according to the results of post-registration observations, a slowing of the heart rate was observed in patients without heart diseases. Therefore, all patients are at risk for impaired intracardiac conduction.

Cholinomimetics can increase gastric secretion, so it is necessary to establish monitoring of patients at risk for ulcerative lesions of the gastrointestinal tract, as well as gastrointestinal bleeding.

Cholinomimetics can cause a violation of the outflow of urine.

Galantamine should be administered with caution to patients with chronic obstructive pulmonary disease.

Cholinomimetics can potentiate the effect of neuromuscular blockade of muscle relaxants of the depolarizing type during anesthesia.

It is necessary to control the weight of the patient, as with galantamine therapy, weight loss can occur.

Parasympatomimetics can cause seizures.

Increased convulsive activity was observed in patients with Alzheimer's disease.

In rare cases, parasympatomimetics can increase cholinergic tone and cause worsening of Parkinson's symptoms.

Galantamine should be administered with caution in patients with renal insufficiency and reduce the dose of the drug in accordance with the value of creatinine clearance.

Treatment should be carried out in conjunction with physiotherapeutic procedures (massage, medical gymnastics), which should be started 1-2 hours after the administration of the drug.

In the period of galantamine treatment, the use of ethanol and sedatives is unacceptable.

Effect on the ability to drive transp. cf. and fur:During treatment with galantamine it is necessary to refrain from driving vehicles and practicing other potentially dangerous activities that require increased concentration and speed of psychomotor reactions, since the use of galantamine can cause drowsiness, dizziness, and visual impairment.

Form release / dosage:

Solution for intravenous and subcutaneous administration, 1 mg / ml and 5 mg / ml.

Packaging:

1 ml in a vial of neutral glass or in an ampoule for ISO.

5 ampoules in a contoured cell package (with foil or paper, or without foil and paper).

2 contour squares in a pack of cardboard.

For 10 ampoules in a pack of cardboard with a loose leaf of paper or with special pockets.

In each pack you put the instruction on application and scarifier. When using ampoules with notches, rings and fracture points, the scarifiers do not insert into the pack.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

4 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-001166

Date of registration:11.11.2011 / 29.12.2016

Expiration Date:Unlimited

The owner of the registration certificate:VIFITEH, CJSC VIFITEH, CJSC Russia

Manufacturer: & nbsp

VIFITEH, CJSC Russia

Representation: & nbspVIFITEH, CJSCVIFITEH, CJSC

Information update date: & nbsp03.04.2017

Illustrated instructions

Instructions

Galantamine (Galantamine)