Composition, form of production and packaging
Tablets, film-coated 1 tab.
galantamine 4 mg
14 pcs. - blisters (1) - packs of cardboard.
Tablets, film-coated 1 tab.
galantamine 8 mg
14 pcs. - blisters (1) - packs of cardboard.
14 pcs. - blisters (4) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2014.
Galantamine - a tertiary alkaloid - an inhibitor of cholinesterase. The selective competitive and reversible cholinesterase inhibitor enhances and prolongs the action of endogenous acetylcholine on nicotinic receptors, probably due to binding to the allosteric portion of the receptor. By increasing the activity of the cholinergic system, by stimulating central cholinoreactivic systems, it can improve cognitive function in patients with Alzheimer's dementia.
The pharmacokinetics of galantamine is linear in the dose range of 4-16 mg twice a day.
Suction . After a single oral dose of 8 mg galantamine is rapidly absorbed from the digestive tract. With max in blood plasma is achieved after 1.2 hours and is about 43 ng / ml, the area under the curve of AUC is 427 W * h / ml.
Distribution . Absolute bioavailability with oral administration is 88.5%. The intake of galantamine with food slows its absorption (C max decreases by 25%), but does not affect the AUC. After repeated administration of galantamine at a dose of 12 mg twice a day, the average concentrations at the end of the course and C max in the blood plasma varied from 30 ng / ml to 90 ng / ml. The volume of distribution is 175 liters. The binding of galantamine to plasma proteins is about 18%. In the whole blood, galantamine is predominantly in the form elements (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 isoenzymes of the cytochrome P450 system involved in galantamine metabolism are the CYP2D6 isozyme, which is associated with the formation of O-demethylgalanthamine, and the isoenzyme CYP3A4, which is associated with the formation of N-oxide-galanthamine.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 main part of radioactive substances is the 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-demethylgalanthamine and O-demethylnoghalanthamine) was present in the unconjugated form. Norgalantamine was detected in the blood plasma of patients after repeated administration of galantamine, but its concentration was no more than 10% of the concentration of galantamine. Elimination of galantamine is bioexponential. The final T 1/2 is 7-8 hours. The plasma clearance of galantamine is about 200 ml / min. Within 7 days after single ingestion of ZN-galantamine in a dose of 4 mg, 90-97% of radioactivity was excreted in the urine and 2.2-6.3% with feces. After intravenous administration and ingestion, 18-22% of galantamine is excreted unchanged in the urine for 24 hours, the renal clearance is about 65 ml / min, which is 20-25% of the total clearance from the plasma.
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 liver function (5-6 points on the Child-Pugh scale), the pharmacokinetic parameters were similar to those of healthy individuals. In patients with moderate impairment of liver function (7-9 on the Child-Pugh scale), AUC and T 1/2 of galantamine were increased by approximately 30%.
Population pharmacokinetic study and analysis using a number of models showed that in patients with Alzheimer's disease and renal dysfunction in creatinine clearance (CK) of at least 9 ml / min, the dose of galantamine should not be adjusted.
- symptomatic treatment of dementia of the Alzheimer's type of mild and moderate severity.
Inside, 2 times a day, preferably during morning and evening meals. Tablets are swallowed whole, without chewing, squeezed with enough water. The initial dose is 8 mg / day (4 mg twice a day) for 4 weeks. The maintenance dose is 16 mg / day (8 mg twice a day) for at least 4 weeks. The decision on the use of higher doses of the drug Galantamine-Teva should be taken after assessing the clinical condition of the patient, incl. achieved effect and individual tolerance. The maximum recommended dose is 24 mg / day (12 mg twice a day).
If you have a break in taking Galantamine-Teva for a few days, you should resume taking the initial dose, and then increase it to the previous maintenance dose according to the above scheme.
In patients with moderate hepatic impairment, the initial dose is 4 mg 1 time per day, daily, in the morning, for at least 1 week. After that, patients can take 8 mg / day (4 mg twice a day) for at least 4 weeks. The daily dose should not exceed 8 mg / day.
Have patients with impaired renal function (QC more than 9 ml / min) dose adjustment is not required.
The frequency of side effects is classified according to the recommendations of the World Health Organization: very often - not less than 10%; often - not less than 1%, but less than 10%; infrequently - not less than 0,1%, but less than 1%; rarely - not less than 0.01%, but less than 0.1%; very rarely - less than 0.01%, including single messages.
From the side of metabolism and nutrition: often - anorexia, weight loss; rarely dehydration (in rare cases leading to the development of renal failure), hypokalemia.
From the side of the central nervous system: often - dizziness, headache, drowsiness, fainting, tremor, confusion, depression (very rarely with suicide), insomnia, asthenia, malaise, fatigue, fever; infrequently - paresthesia, cerebrovascular disease, transient ischemic heart disease, aggression, agitation, hallucinations, tinnitus;very rarely - exacerbation of Parkinson's disease, convulsions, sweating.
From the side of the cardiovascular system: infrequently - arrhythmia, acute myocardial infarction, ischemic heart disease, tachycardia; rarely - bradycardia; very rarely - atrioventricular block.
From the digestive tract: very often - vomiting, nausea; often - abdominal pain, diarrhea, indigestion; very rarely - dysphagia, gastrointestinal bleeding.
From the skin and subcutaneous tissues: rarely - skin rash.
From the osteomuscular system and connective tissue: often - fall, injury; infrequently - a cramp in the muscles of the legs, muscle weakness.
From the side of the kidneys and urinary tract: often - infection of the urinary tract.
Other: often - infectious rhinitis.
- hypersensitivity to galantamine and other components of the drug;
- severe impairment of liver function (Child-Pugh type C);
- severe renal dysfunction (CK less than 9 ml / min);
- deficiency of lactase;
- a syndrome of glucose-galactose malabsorption;
- children's age till 18 years;
- the period of breastfeeding;
- Obstructive diseases of the gastrointestinal tract and urinary tract or a recent surgery on the organs of the gastrointestinal tract and urinary tract, including the bladder.
Syndrome of weakness of the sinus node; violations of supraventricular conductivity; hyperkalemia; hypokalemia; period after acute myocardial infarction; At first detected atrial fibrillation; atrioventricular blockade of II-III degree, unstable angina; chronic heart failure (CHF) of III and IV functional class according to NYHA classification; simultaneous use with medications that help to reduce heart rate (digoxin, beta-blockers), sedatives, ethanol; arterial hypertension; epilepsy; COPD;infectious lung diseases; anesthesia.
PREGNANCY AND LACTATION
The use of the drug Galantamine-Teva during pregnancy is contraindicated.
During treatment with the drug Galantamine-Teva breastfeeding should be discontinued.
APPLICATION FOR FUNCTIONS OF THE LIVER
The drug is contraindicated in patients with severe renal dysfunction (CC less than 9 ml / min).
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
The drug is contraindicated in patients with severe impairment of liver function (Child-Pugh type C).
APPLICATION FOR CHILDREN
The drug is contraindicated for children under 18 years.
The drug Galantamine-Teva is used in patients with dementia of the Alzheimer's type of mild and moderate severity. The effectiveness of the use of the drug Galantamine-Teva in patients with other types of dementia and other types of memory impairment is not established.
There is also no positive effect of the drug on slowing cognitive impairment or slowing the transition to clinically pronounced dementia in patients with mild cognitive decline syndrome ("soft" types of memory impairment that do not meet dementia criteria in Alzheimer's disease). Therapy with Galantamine-Teva should be performed under the supervision of a doctor and under the supervision of a person who cares for the patient.
Taking Galaitamip-Teva is accompanied by a decrease in body weight, so during treatment it is necessary to monitor this figure.
The drug Galantamine-Teva can not be used concomitantly with other cholinesterase inhibitors.
The drug Galantamine-Teva should be used with caution in diseases of the cardiovascular system, tk. due to its pharmacological action holinomimetiki can cause vagotonic effects (for example, bradycardia). Caution is used Galantamine-Teva (like other cholinomimetics) in patients with sinus node weakness syndrome; disorders of supraventricular conduction; with simultaneous therapy with medications that lower heart rate (digoxin, beta-blockers); disturbances of electrolyte metabolism (hyperkalemia, hypokalemia); in the period after acute myocardial infarction; with newly diagnosed atrial fibrillation, atrioventricular blockade of II-III degree;unstable angina pectoris, CHF III and IV functional class according to the NYHA classification.
In the treatment of Alzheimer's dementia, the drug Galantamine-Teva may increase the risk of developing unwanted reactions from the cardiovascular system (see section "Side effect").
In patients with an increased risk of developing erosive-ulcerative gastrointestinal lesions, for example having a history of peptic ulcer, it is necessary to monitor the condition for the purpose of early detection of the corresponding pathological symptoms. The drug Galantamine-Teva is not recommended for use in patients with gastrointestinal obstruction, as well as in patients who have recently undergone surgical intervention on the digestive system.
Cholinomimetics have a certain ability to cause generalized convulsions. It should be remembered that convulsive activity may be a manifestation of Alzheimer's disease itself. Cases of worsening of Parkinson's disease are described. It is impossible to exclude the possibility of developing cerebral circulation disorders in patients with Alzheimer's disease against the background of cerebrovascular disease. With caution use the drug Galantamine-Teva in patients with severe bronchial asthma, COPD and infectious diseases of the lungs because of its cholinomimetic activity.
The drug Galantamine-Teva is not recommended for patients with obstruction of the urinary tract, as well as for people who have recently undergone a bladder surgery.
It should be borne in mind that the preparation of Galantamine-Teva, as holinomimetik, increases miorelaxation in the succinyl-holin type of anesthesia.
After a sharp abolition of the drug Galantamine-Teva (for example, when preparing for surgery), there is no aggravation of symptoms.
Impact on the ability to drive transport and management of machinery
During therapy with Galantamine-Teva, one should refrain from driving and controlling other mechanisms that require an increased concentration of attention and speed of psychomotor reactions.
Symptoms: There may be muscle weakness, fasciculation, some or all of the symptoms of the cholinergic crisis (severe nausea, vomiting, abdominal cramping, increased salivation, lacrimation, urinary and fecal incontinence, increased sweating, bradycardia, decreased blood pressure, collapse, seizure). The expressed muscular weakness in a combination to a hypersecretion of a mucosa of a trachea and a bronchospasm can lead to a lethal outcome. In reports received in the postmarketing period, cases of development of bidirectional-spindle ventricular tachycardia, prolongation of the QT interval, ventricular tachycardia accompanied by a short-term loss of consciousness, with the occasional ingestion of 32 mg galantamine are described.
Treatment: if necessary, conduct symptomatic therapy. In severe cases, atropine is administered as the antidote IV, the initial dose is 0.5-1 mg, the frequency of administration and subsequent doses depend on the dynamics of the patient's clinical condition.
Simultaneous food intake slows down the absorption rate of galantamine somewhat, but does not affect its volume. Patients are advised to take galantamine along with food to minimize possible cholinergic adverse events.
The simultaneous use of galantamine with other cholinomimetic drugs is contraindicated.
Pharmacodynamic interaction of galantamine is possible with drugs that significantly reduce heart rate, such as digoxin, beta-blockers, "slow" calcium channel blockers and amiodarone. Caution should be exercised when using simultaneously with drugs that have the potential to cause pirouette-type arrhythmias. In these cases it is necessary to carry out treatment under the control of electrocardiogram indicators.
Galantamine can enhance the blockade of neuromuscular transmission of the depolarizing type during general anesthesia (when used as a peripheral muscle relaxant suksametonium).
With the simultaneous use of galantamine enhances the effect of depolarizing muscle relaxants, weakens - nondepolarizing muscle relaxants; is a weak antagonist of morphine and its structural analogues in relation to the inhibitory effect on the respiratory center. Strengthens the action of ethanol and sedative drugs. It restores neuromuscular conduction, blocked by nondepolarizing muscle relaxants (tubocurarine, etc.).
M-holinoblokatory (atropine, etc.) eliminate peripheral muscarin-like effects of galantamine, nondepolarizing muscle relaxants and ganglion blockers - nicotine-like effects of galantamine.
When used simultaneously with drugs that are active inhibitors of CYP2D6 or CYP3A4 isoenzymes (such as ketoconazole, paroxetine, erythromycin, amitriptyline, fluoxetine, fluvoxamine, quinidine), AUC increases by 10-40% and the risk of unwanted effects increases (mainly nausea and vomiting) due to the cholinergic effect of galantamine, which may require a reduction in the dose of galantamine.
When used at doses up to 12 mg twice a day, galantamine did not alter the pharmacokinetic parameters of digoxin and warfarin and did not affect the increase in prothrombin time caused by warfarin.
Galantamine is an antagonist of morphine and its structural analogues in relation to the inhibitory effect on the respiratory center.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
At a temperature of no higher than 25 В° C. Keep out of the reach of children. Shelf life - 2,5 years.