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

Excipients: lactose monohydrate 25,874 mg / 51,747 mg, microcrystalline cellulose 25,280 mg / 50,560 mg, crospovidone 3,000 mg / 6,000 mg, silicon dioxide colloid 0,300 mg / 0,600 mg, magnesium stearate 0.420 mg / 0.840 mg:

sheath Opadrai II 85F32121 yellow / 85F23470 pink: polyvinyl alcohol 0,800 mg / 1,600 mg, titanium dioxide (E 171) 0,498 mg / 0,984 mg, macrogol 4000 0,404 mg / 0,808 mg, talc 0,296 mg / 0,592 mg, ferric oxide yellow oxide (E172) 0.002 mg / 0.005 mg, dye iron oxide red (E 172) - / 0.010 mg, ferric oxide black oxide (E 172) - / 0.001 mg.

Description:

Tablets 4 mg. Capsule tablets covered with a film shell from almost white to light yellow with an engraving "602" on one side and "93" on the other.

Tablets 8 mg. Capsule pills covered with a pink film shell with a "689" engraving on one side and "93" on the other.

Pharmacotherapeutic group:Dementia remedy

ATX: & nbsp

N.06.D.A.04 Galantamine

Pharmacodynamics:

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 cholinergic systems, it can improve cognitive function in patients with Alzheimer's dementia.

Pharmacokinetics:

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 quickly absorbed from the gastrointestinal tract (GIT). The maximum concentration (C_mOh) in blood plasma is achieved after 1.2 hours and is about 43 ng / ml. area under the concentration-time curve (AUFROM) - 427 ng h / ml.

Distribution

Absolute bioavailability with oral administration is 88.5%. Taking galantamine with food slows down its absorption (C_mOh decreases by 25%), but does not affect 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_mOh in the blood plasma was 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 whole blood galantamine (52.7%) and plasma (39%), whereas its fraction bound to plasma proteins is only 8.4%.

Metabolism

Research in vitro showed that the main isoenzymes of the cytochrome P450 system involved in the metabolism of galantamine are isoenzyme CYP2D6, which is associated with the formation Odimethylgalanthamine, and isoenzyme CYP3A4, which is associated with 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, the bulk of radioactive substances are unchanged galantamine and its glucuronide. After a single dose of galanthamine in the plasma of "fast" and "slow" metabolizers of any one of the active metabolites (norgalantamin, O-O-demethylgalanthamine and demetilnorgalantamin) is present in an 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 half-life (T_1/2) - 7-8 hours. The plasma clearance of galantamine is about 200 ml / min. Within 7 days after a single ingestion of 3H-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 oral administration of galanthamine 18-22% is excreted unchanged in the urine within 24 hours, renal clearance - about 65 ml / min, accounting for 20-25% of the total plasma clearance.

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

In patients with lungs impaired hepatic function (5-6 points on the Child-Pugh scale) pharmacokinetic parameters were similar to those in healthy individuals.

In patients with moderate impairment of liver function (7-9 points on the Child-Pugh scale) AUC and T_1/2 galantamine were increased by about 30%.

Population pharmacokinetic study and analysis using a number of models have shown that in patients with Alzheimer's disease and impaired renal function when creatinine clearance (CC) is not less than 9 ml / min, the dose of galantamine should not be adjusted.

Indications:

Symptomatic treatment of dementia of Alzheimer's type of mild and moderate severity.

Contraindications:

- Hypersensitivity to galantamine and other components of the drug;

- severe violation of liver function (more than 9 points on the Child-Pugh scale);

- severe renal dysfunction (CK less than 9 ml / min);

lactose intolerance;

- deficiency of lactase;

- a syndrome of glucose-galactose malabsorption;

- children's age till 18 years;

- pregnancy, the period of breastfeeding.

Carefully:

- Obstructive diseases of the gastrointestinal tract (GIT) or a recent surgery on the organs of the gastrointestinal tract;

- Obstructive diseases of the urinary tract or a recent surgical operation on the organs of the urinary tract, including the bladder;

- peptic ulcer of stomach and duodenum;

- syndrome of sinus node weakness, bradycardia, violations of supraventricular conduction;

- Hyperkalemia;

- hypokalemia;

- the period after acute myocardial infarction;

- first detected atrial fibrillation;

- atrioventricular block II-III degree;

- unstable angina;

- Chronic heart failure (CHF) of III and IV functional class by classification NYHA;

- simultaneous use with drugs that reduce the heart rate (heart rate) (digoxin, beta-adrenoblockers), sedatives, ethanol;

- epilepsy;

- bronchial asthma; chronic obstructive pulmonary disease (COPD);

- infectious lung diseases;

- Anesthesia.

Pregnancy and lactation:

There are no clinical data on the use of the drug in pregnant women. Studies in animals have shown reproductive toxicity. The use of the drug Galantamine-Teva during pregnancy is contraindicated.

During treatment with the drug Galantamine-Teva breastfeeding should be discontinued.

Dosing and Administration:

Inside.

2 times a day, preferably during the morning and evening meals. Tablets are swallowed whole, without chewing, squeezed with enough water.

Initial dose - 8 mg / day (4 mg twice a day) for 4 weeks.

Maintenance dose - 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 insufficiency the initial dose is 4 mg once a 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.

In patients with impaired renal function (SC more than 9 ml / min) correction of the dose is not required.

Side effects:

Frequency of collateraleffects are 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 immune system: infrequently - hypersensitivity

From the side of metabolism and nutrition: often - anorexia, weight loss; rarely - dehydration, hypokalemia.

From the side of the psyche: often hallucinations, depression.

From the central nervous system: often - dizziness, headache, drowsiness, hypersomnia (pathological drowsiness), fainting, tremor, lethargy; infrequently - a perversion of taste, paresthesia, convulsions.

From the organ of hearing: infrequently - tinnitus

From the side of the organ of vision: infrequent - impaired vision

From the cardiovascular system: often bradycardia; infrequently - supraventricular extrasystole, palpitation, atrioventricular blockade of the first degree.

From the side of the vessels: often - increased blood pressure; infrequently - lowering of arterial pressure, hyperemia.

From the gastrointestinal tract: very often - vomiting, nausea; often - abdominal pain, diarrhea, dyspepsia, discomfort in the stomach and intestines.

From the side of the liver: infrequently - increased activity of hepatic enzymes; rarely - hepatitis.

From the skin and subcutaneous tissues: often - increased sweating.

From the osteomuscular system and connective tissue: often - falling, cramps in the muscles of the legs, infrequently - muscle weakness.

General disorders: often - asthenia, fatigue, malaise.

Overdose:

Symptoms: there may be muscle weakness, fasciculation. some or all of the symptoms of the cholinergic crisis (severe nausea, vomiting, abdominal cramps, increased salivation, lacrimation, urinary and fecal incontinence, increased sweating, bradycardia, lowering of blood pressure, collapse, convulsions). 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 messages received in the postmarketing period, cases of development of bidirectional-spindle-shaped ventricular tachycardia, lengthening of the interval QT, ventricular tachycardia, accompanied by a short-term loss of consciousness, with the occasional intake of 32 mg galantamine.

Treatment: if necessary, conduct symptomatic therapy. In severe cases, as an antidote, IV is administered atropine (the initial dose is 0.5-1 mg, the frequency of administration and subsequent doses depend on the dynamics of the clinical state of the patient).

Interaction:

Simultaneous food intake slows down the absorption rate of galantamine somewhat, but does not affect its volume. Patients are recommended to take galantamine together with food to minimize possible cholinergic adverse events.

The simultaneous use of galantamine with other cholinomimetic drugs is contraindicated.

Pharmacodynamic interaction galantamine is possible with drugs that significantly reduce heart rate, such as digoxin, beta-adrenoblockers, blockers of "slow" calcium channels and amiodarone. Caution should be exercised when using simultaneously with medications 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 simultaneous application 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 isoenzymes CYP2D6 or CYP3A4 (such as ketoconazole, paroxetine, erythromycin, amitriptyline, fluoxetine, fluvoxamine, quinidine), AUC (the area under the concentration-time curve) increases by 10-40% and the risk of unwanted effects (mainly nausea and vomiting) is increased due to the cholinergic effect of galantamine, which may require a reduction in the dose of galantamine.

When used in doses up to 12 mg twice a day galantamine did not change 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.

Special instructions:

The drug Galantamine-Teva is used in patients with dementia of the Alzheimer's type of mild and moderate severity. The effectiveness of 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 Galantamine-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 II-III degree; unstable angina, CHF III and IV functional class by classification NYHA.

When treating Alzheimer's dementia with Galantamine-Teva, the risk of developing unwanted reactions from the cardiovascular system may increase (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 noted 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.

Effect on the ability to drive transp. cf. and fur:

During therapy with Galantamine-Teva, one should refrain from driving and controlling other mechanisms that require increased attention and speed of psychomotor reactions.

Form release / dosage:

Tablets, film-coated, 4 mg and 8 mg.

Packaging:

Dosages of 4 mg. For 14 tablets in a blister of PVC / PE / PVDC / Al foil. 1 blister together with instructions for use are placed in a cardboard box.

Dosage of 8 mg. For 14 tablets in a blister of PVC / PE / PVDC / Al foil. 1 or 4 blisters together with instructions for use are placed in a cardboard box.

Storage conditions:

At a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2.5 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-001539

Date of registration:27.02.2012 / 28.02.2017

Expiration Date:Unlimited

The owner of the registration certificate:Teva Pharmaceutical Enterprises Co., Ltd.Teva Pharmaceutical Enterprises Co., Ltd. Israel

Manufacturer: & nbsp

TEVA Pharmaceutical Industries, Ltd. Israel

Representation: & nbspTeva Teva Israel

Information update date: & nbsp03.04.2017

Illustrated instructions

Instructions

Galantamine-Teva (Galantamine-Teva)