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

Excipients: calcium hydrogen phosphate 8.173 mg, silicon dioxide colloid 1.5 mg, croscarmellose sodium 6 mg, lactose anhydrous 60 mg, magnesium stearate 0.7 mg, povidone K-30 2.5 mg, microcrystalline cellulose 16 mg;

composition of pla black sheath: Opadrai II blue 3 mg, including: hypromellose (hydroxypropylmethylcellulose) 0.84 mg, lactose monohydrate 1.08 mg, macrogol (polyethylene glycol) 0.3 mg, titanium dioxide 0.729 mg, dye brilliant blue 0.0471 mg, iron oxide black 0.0039 mg.

Dosage of 8 mg

1 tablet, film-coated, contains:

active substance: galantamine hydrobromide 10,254 mg in terms of galantamine 8 mg;

Excipients: calcium hydrophosphate 12.046 mg, silicon dioxide colloid 2.25 mg, croscarmellose sodium 9 mg, lactose anhydrous 76 mg, magnesium stearate 1 mg, povidone K-30 3.5 mg, microcrystalline cellulose 35.95 mg;

composition of film shell: Opadrai II blue 4 mg, including: hypromellose (hydroxypropylmethylcellulose) 1.12 mg, lactose monohydrate 1.44 mg, macrogol (polyethyl glycol) 0.4 mg, titanium dioxide 0.972 mg, brilliant blue dye 0.0628 mg, iron oxide black 0052 mg.

Dosage of 12 mg

A film coated tablet contains:

active substance: galantamine hydrobromide 15.38 mg in terms of galantamine 12 mg;

Excipients: calcium hydrophosphate 17 mg, silicon dioxide colloid 3.15 mg, croscarmellose sodium 12.6 mg, lactose anhydrous 106.6 mg, magnesium stearate 1.4 mg, povidone K-30 4.9 mg, cellulose microcrystalline 48.97 mg;

composition of film shell: Opadrai II blue 6 mg, including: hypromellose (hydroxypropylmethylcellulose) 1.68 mg,lactose monohydrate 2,16 mg, macrogol (polyethylene glycol) 0.6 mg, titanium dioxide 1.458 mg, dye brilliant blue 0.0942 mg, iron oxide black 0.0078 mg.

Description:The tablets are round biconvex, covered with a film coating of blue color. The cross section is almost white.

Pharmacotherapeutic group:Means of treatment of dementia. Cholinesterase inhibitor

ATX: & nbsp

N.06.D.A.04 Galantamine

Pharmacodynamics:Selective, competitive and reversible inhibitor of acetylcholinesterase. Stimulates nicotinic receptors and increases the sensitivity of the postsynaptic membrane to acetylcholine. It facilitates the conduction of excitation in the neuromuscular synapse and restores neuromuscular conduction in cases of its blockade with muscle relaxants of a nondepolarizing action type. Increases the tone of smooth muscles, increases the secretion of digestive and sweat glands, causes miosis. Increasing the activity of the cholinergic system, galantamine improves cognitive function in patients with dementia of the Alzheimer's type, but does not affect the development of the disease itself.

Pharmacokinetics:

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

Suction

After a single dose of the drug inside at a dose of 8 mg galantamine quickly absorbed from the gastrointestinal tract (GIT). Maximum concentration (FROMmOh) in blood plasma is achieved after 1,2 hours and is a colo 43 ng / ml, the area under the concentration-time curve (AUC) - 427 ng x h / ml.

Distribution

Absolute bioavailability with oral administration is 88.5%. Taking galantami 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 galantamia in a dose of 12 mg twice a day, the average concentration at the end of the course and Cmax in the blood plasma vary from 30 ng / ml to 90 ng / ml. The volume of distribution is 175 ml. The binding of galanthamia to plasma proteins is about 18%. In whole blood galayThe thymine is found predominantly in shaped elements (52.7%) and in plasma (39%), whereas its fraction bound to plasma proteins is only 8.4%.

Metabolism

Research in vitro showed that the main isoenzymes of the system of chlochrome P450 participating in the metabolism of galantamine are isoenzyme CYP2D6, with which the formation of O-dimethylgalanthamine is associated, and isoenzyme CYP3A4, with which the formation Noxygalanthamine.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, most of the radioactive substances are unchanged galantamine and its glucuronide. After a single administration of galantamine in the plasma of "fast" and "slow" metabolizers, none of the active metabolites (norgalanthamn, O-dimethylgalanthamine and O-dimethylnoghalanthamine) is present in the unconjugated form. Norgalantamine is found in the blood plasma of patients after repeated administration of galantamine, but its concentration is no more than 10% of the concentration of galagt;

Excretion

Elimination of galantamine is bioexponential. The final half-life (T1 / 2) is 7-8 hours. The plasma clearance of galantamine is about 200 ml / min. 18-22% of galantamine is excreted unchanged in urine within 24 hours. Kidney clearance is about 65 ml / min, which is 20-25% of the total plasma clearance. Within 7 days after a single oral intake ³N-galantamine in a dose of 4 mg of 90-97% 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 blood plasma is 30% -40% higher than in healthy individuals.

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

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

Indications:

- symptomatic treatment of Alzheimer's dementia of mild to moderate severity;

Contraindications:

Hypersensitivity to any of the components of the drug, bronchial asthma, bradycardia, atrioventricular blockade,

disorders, mechanical intestinal obstruction, chronic obstructive pulmonary disease, chronic obstructive pulmonary disease, chronic obstructive pulmonary disease, chronic obstructive pulmonary disease, chronic obstructive pulmonary disease, hypertension,obstructive diseases or recent surgery on the organs of the gastrointestinal tract, obstructive diseases or the recently transferred surgical treatment of the urinary tract or prostate, children under 18, pregnancy and lactation.

Carefully:Mild and moderate impairment of kidney or liver function; syndrome of sinus node weakness and other supraventricular conduction disorders; simultaneous reception 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).

Pregnancy and lactation:Contraindicated in pregnancy. For the duration of treatment, breastfeeding should be discontinued.

Dosing and Administration:

Inside, with food, washing with water.

Adults

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

With myasthenia gravis gravis The daily dose is divided into 3 doses.

In Alzheimer's disease, treatment should be started with admission tablets of 4 mg twice a day. Within 4 weeks, the daily dose gradually can be increased to 16 mg - 1 tablet of 8 mg 2 times a day - in the morning and in the evening. During drug treatment it is necessary to provide reception of a sufficient amount of liquid. If during treatment you need to stop taking the drug, then restore the treatment it is necessary to start with the lowest dose and gradually increase it.

Patients with moderate impairment of liver and kidney function

The initial dose is 4 mg once a day, which is taken in the morning, during less than 1 week, after which the dose is increased to 4 mg twice a day and take for 4 pedels.

The total daily dose should not exceed 12 mg.

Side effects:

The incidence of adverse events 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).

Impaired immune system

Infrequent: hypersensitivity.

Disorders from the metabolism and nutrition

Often: decreased appetite, anorexia.

Infrequently: dehydration (in rare cases leading to the development of renal

insufficiency).

Mental disturbance

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

Infrequently: visual hallucinations, aggression, agitation.

Disturbances from the nervous system

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

Infrequently: paresthesia, taste distortion, hypersomnia, convulsions (potentially cholinomimetic drugs can cause seizures), cerebrovascular diseases, transient ischemic heart disease.

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

Disturbances on the part of the organ of sight

Infrequent: blurred vision.

Hearing disorder and labyrinthine disorders

Infrequent: noise in the ears.

Violation of the heart

Often: aetiology.

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

Violation of the vessels

Often: arterial hypertension.

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

Disorders from the gastrointestinal tract

Very often: vomiting, nausea.

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

Infrequent: the urge to vomit.

Very rarely: dysphagia, gastrointestinal bleeding.

Disturbances from the liver and bile ducts

Rarely: hepatitis.

Disturbances from the skin and subcutaneous tissues

Often: hyperhidrosis.

Rarely: skin rash.

Disturbances from musculoskeletal and connective tissue

Often: muscle spasms.

Infrequently: muscle weakness.

General disorders and disorders at the site of administration

Often: increased fatigue, asthenia, malaise, weakness.

Laboratory and instrumental data:

Often: weight loss.

Infrequently: increased activity of "liver" enzymes.

Trauma, intoxication and complications of manipulation

Often: falling, injuries.

Overdose:Symptoms: depression of consciousness (up to coma), seizures, 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 a legal blockade of the airways.

The case of galantamine and a dose of 40 mg (vomiting) with complete recovery is described. The patient (who was prescribed 16 mg / day.galantamine, oral solution) an hour after the accidental use of galantamine 160 mg (40 ml solution for oral administration) increased sweating, vomiting, bradycardia and a condition close to fainting, which required hospitalization of the patient. Symptoms of an overdose disappeared within 24 hours.

Treatment: gastric lavage, symptomatic therapy. As an antidote - iv 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.

Interaction:

Pharmacodynamic interactions

Simultaneous application with other cholinomimetic preparations (ambenonium chloride, donepezil, neostigmine methylsulfate, pyridostigmine bromide, rivastigmine or pilocarpine systemic action) is contraindicated.

Galantamia is an antagonist of anticholinergic drugs. With a sudden reversal of the anticholinergic drug, for example, atropine, the effect of galantamine may be enhanced. As with other cholinomimetic drugs, pharmacodynamic interaction with drugs contributing to a decrease in heart rate is possibledigoxin, beta-adrenoblockers), some blockers of "slow" calcium channels (BCCC) and amidarone. Caution should be exercised when using drugs that have the potential to cause polymorphic ventricular tachycardia but do not "pirouette". In such cases it is necessary to undergo ECG-controlled treatment.

Galantamine, which is holinomimetic, can enhance the blockade of neuromuscular transmission of the depolarizing type (myorelaxation) caused by general anesthesia (when used as a peripheral muscle relaxant suksametonium), especially when pseudocholinesterase is deficient.

With simultaneous application galantamine intensifies the effect of depolarizing muscle relaxants, weakens - nondepolarizing muscle relaxants, is a weak antagonist of morphine and its structural analogues in relation to the depressant effect on the respiratory center. Strengthens the action of ethanol and sedative drugs. It restores neuromuscular conduction, blocked by nondepolarizing muscle relaxants (tubocuranine bromide, etc.). M-holinoblokatory (atropine and others) eliminate peripheral muscarin-like effects of galanthamia, nondepolarizing muscle relaxants and ganglion blockers - nicotine-like effects of galantamine.

Pharmacokinetic interactions

All drugs that inhibit the isoenzymes of the cytochrome P450 system (CYP2D6 and CYP3A4), can increase plasma concentrations of galantamine while simultaneously applying them, resulting in a higher incidence of cholinergic side effects (mainly nausea and vomiting). In this case, depending on the tolerability of therapy by a specific patient, a reduction in the maintenance dose of galantamine may be necessary.

Inhibitor inhibitors CYP2D6 (amitriptyline, fluoxetine, fluvoxamine, paroxetia, quinidine) reduce the clearance of galantamine by 25-30%. For this reason galantamine it is not recommended to appoint simultaneously with ketoconazole, zidovudine, erythromycin. Increases the inhibitory effect on the central nervous system of ethanol and sedatives.

The influence of galantamine on the metabolism of other drugs (LC)

Galantamine in therapeutic doses (24 mg / day) did not affect pharmacokinetics of digoxin, while not excluding pharmacodynamic interaction.

Galantamine at therapeutic doses (24 mg / day) had no effect on the pharmacokinetics of warfarin and prolongation of prothrombin time.

Research in vitro showed that galantamine has a very weak ability to inhibit the main forms of the human isoenzyme P450.

Special instructions:

Galantamine Canon drug indicated for the treatment of dementia of the Alzheimer type mild to moderate severity. Efficacy of galantamine in patients with other types of dementia and other memory disorders has not been established. It is also not found a positive effect of galantamine (within 2 years) on slowing of cognitive impairment and deceleration transition symptomatic dementia in patients with the syndrome of "soft" cognitive decline ( "soft" types of memory disorders, not meeting the criteria altsgeymerovekogo type dementia ). Mortality galantamine group was significantly higher than in the placebo group, 14/1026 (1.4%) patients treated with galantamine, and 3/1022 (0.3%) of patients receiving placebo. The causes of deaths were different. About half of the cases of deaths in the galantamine group was a result of various vascular causes (myocardial infarction, stroke, and sudden death).The significance of the data obtained for the treatment of patients with Alzheimer's dementia is unknown. Placebo-controlled studies of patients with Alzheimer's dementia were performed only for 6 months. In these studies, mortality in the galantamine group did not increase.

Treatment with Galantamine Canon should be done only under the supervision of a doctor and under the supervision of the person providing care for the patient.

In patients with Alzheimer's disease, body weight decreases. Treatment with cholinomimetic agents, including galantamine, accompanied by a decrease in body weight, so during therapy should monitor this figure.

Like other holinomimeticheskie means, the drug Galantamine Canon should be used cautiously in the following diseases:

Diseases of the cardiovascular system

Due to pharmacological action holinomimeticheskie funds can cause vagotonic effects (for example, bradycardia). It should be used with caution in patients with SSSU and other disorders of supraventricular conduction, with simultaneous therapy with drugs that lower heart rate (digoxin and beta-adrenoblockers) and in patients with electrolyte metabolism disorders (hyperkalemia, hypokalemia), in the period after acute myocardial infarction; with newly diagnosed atrial fibrillation; in patients with atrioventricular blockade of grade II-III, unstable angina or chronic heart failure, especially III-IV functional class according to the NYHA classification.

Against the background of therapy with the drug Galantamine Canon dementia Alzheimer's type increases the risk of developing unwanted reactions from the cardiovascular system.

Diseases of the digestive system

In patients with an increased risk of developing erosive-ulcerative gastrointestinal lesions (eg, peptic ulcer and 12-gut disease in history, therapy with NSAIDs), it is necessary to monitor the condition for the purpose of early detection of the corresponding pathological symptoms. The drug Galantamine Canon is not recommended for patients with gastrointestinal obstruction or after a recent surgery on the gastrointestinal tract.

Diseases of the nervous system

The use of cholinomimetic agents can cause seizures.It should be remembered that convulsive activity may be a manifestation of Alzheimer's disease itself. In rare cases, the strengthening of cholinergic tone may cause a worsening of Parkinson's disease.

In patients with dementia of the Alzheimer's type, galantamine, rarely noted the development of cerebrovascular events. This should be considered in the appointment of galantamine to patients with cerebrovascular disease.

Diseases of the respiratory system

Canon drug galantamine should be given with caution to patients with severe asthma, COPD, pulmonary acute infectious diseases (such as pneumonia).

Diseases of the kidneys and urinary tract

Canon drug galantamine is not recommended in patients with obstruction of the urinary tract, recently underwent surgery on the bladder.

General anesthesia

Galantamine being cholinomimetics, blockade can enhance neuromuscular transmission depolarizing type (muscle relaxation) caused by general anesthesia (when used as a peripheral muscle relaxant suxamethonium), especially when failure pseudocholinesterase.

With the sudden cessation of treatment (for example, before surgery), the "cancellation" syndrome does not develop.

Effect on the ability to drive transp. cf. and fur:Galantomia canon, like other holinomimeticheskie funds, can cause drowsiness and dizziness, which adversely affect the management of transport and other mechanisms, especially in the first weeks after the start of treatment.

Form release / dosage:Tablets, film-coated, 4 mg, 8 mg and 12 mg.

Packaging:By 7, 10, 15 or 30 tablets in a contour mesh box made of a PVC film, PVC / PVC film or PVC / PCTFE film and aluminum foil printed lacquer.

According to 1, 2, 4, 8 contour cell packs of 7 tablets or 1, 3, 6 contour cell packs of 10 tablets or 1, 2, 4 contour cell packs of 15 tablets or 1, 2, 3 cell containers 30 tablets together with instructions for use are placed in a pack of cardboard.

Storage conditions:At a temperature of no higher than 25 ° C in the manufacturer's packaging. Keep out of the reach of children.

Shelf life:2 years. Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-003645/10

Date of registration:30.04.2010 / 20.09.2016

Expiration Date:Unlimited

The owner of the registration certificate:CANONFARMA PRODUCTION, CJSC CANONFARMA PRODUCTION, CJSC Russia

Manufacturer: & nbsp

CANONFARMA PRODUCTION, CJSC Russia

Information update date: & nbsp12.03.2017

Illustrated instructions

Instructions

Galantamine Canon (Galantamine Canon)