Galantaminum

General characteristics. Structure:

Active agent — Galantaminum hydrobromide of 5,127 mg, 10,254 mg and 15,380 mg in terms of Galantaminum of 4,00 mg, 8,00 mg and 12,00 mg;

excipients — hydrophosphate calcium a dihydrate, silicon dioxide colloid (aerosil), коповидон (пласдон Es-630 or коллидон VA–64), magnesium stearate, sodium of a kroskarmelloz (primelloz), cellulose microcrystallic;

structure of a film cover — Advantiatm Pryma 319974RC09 [a gipromelloz (gidroksipropilmetiltsellyuloz), a macrogoal (polyethyleneglycol), каприн / caprylic triglyceride (glyceryl каприлокапрат), titanium dioxide, an aluminum varnish on the basis of dye quinolinic yellow, an aluminum varnish on the basis of dye diamond blue, an aluminum varnish on the basis of indigo carmine dye.

Description

Tablets, film coated blue color, round, biconvex, on cross section — white color.

Pharmacological properties:

Pharmacodynamics. The selection, competitive and reversible inhibitor of acetylcholinesterase. Stimulates nicotinic receptors and increases sensitivity of a postsynaptic membrane to acetylcholine. Facilitates carrying out excitement in a neuromuscular synapse and recovers neuromuscular conductivity in cases of its blockade by muscle relaxants of not depolarizing action type. Raises a tone of smooth muscles, strengthens secretion digestive and sweat glands, causes a miosis. Increasing activity of cholinergic system, Galantaminum improves cognitive functions at patients with dementia of altsgeymerovsky type, but does not exert impact on development of the disease.

Pharmacokinetics. After intake it is quickly and completely soaked up in digestive tract. Absolute bioavailability is high — to 90%. Therapeutic concentration is reached in 30 min. after reception. The maximum plasma concentration after reception in a dose of 8 mg is observed on the 2nd hour and makes 1,2 mg/ml.

Elimination half-life — 5 h. After multiple dose equilibrium concentration is established.

In insignificant degree contacts blood proteins. Easily passes through a blood-brain barrier. In insignificant degree (about 10%) it is metabolized in a liver by demethylation.

It is removed (in not changed type and a type of metabolites), generally with urine (to 74%). The renal clearance makes about 100 ml/min. At patients with Alzheimer's disease plasma concentration of Galantaminum can increase. At a moderate and heavy abnormal liver function and kidneys plasma concentration of Galantaminum increase.

Indications to use:

- dementia of altsgeymerovsky type of easy or moderate degree;

- poliomyelitis (directly after the termination of the febrile period, and also in the recovery period and the period of the residual phenomena);

- gravis myasthenia, the progressing muscular dystrophy, cerebral palsy, neuritis, radiculitis, a myopathy.

Route of administration and doses:

Inside, during food, washing down with water.

Adults:

The daily dose makes 8–32 mg, divided in 2–4 receptions.

At gravis myasthenia the daily dose is divided into 3 receptions.

At Alzheimer's disease treatment is recommended to begin with reception of tablets on 4 mg
2 times a day. During 4 weeks the daily dose can gradually be raised to 16 mg — on
1 tab. on 8 mg 2 times a day — in the morning and in the evening. During treatment it is necessary to provide with drug reception of enough liquid. If during treatment the termination of administration of drug is required, then recovery of treatment needs to be begun with the lowest dose and gradually to raise it.

To patients with moderately expressed abnormal liver function and kidneys:

Initial dose — 4 mg of 1 times a day which is accepted in the morning, during not less
1 weeks then the dose is increased to 4 mg by 2 times a day and accept during
4 weeks.

The general daily dose should not exceed 12 mg.

Children (since 9 years)

Treatment of poliomyelitis, cerebral palsy:

from 9 to 11 years a daily dose — 4–12 mg, divided into 2–3 receptions;

from 12 to 15 years the daily dose makes — 4–16 mg, divided into 2–4 receptions.

Features of use:

During treatment it is necessary to refrain from performance of work, the demanding increased concentration of attention and speed of psychomotor reactions, including driving.
Treatment by inhibitors of acetylcholinesterase is followed by a body degrowth. Especially it needs to be meant at treatment of patients with Alzheimer's disease at whom weight loss is usually observed. In this regard it is necessary to watch body weight at such patients.

During treatment it is necessary to provide sufficient consumption of liquid.
As well as other cholinomimetics, drug can cause vagotonic effects from cardiovascular system (including bradycardia) that needs to be considered at patients with a sick sinus syndrome and other disturbances of conductivity, and also at simultaneous use with the medicines reducing heart rate (digoxin or beta адреноблокоторы).

At treatment the risk of emergence to a syncope in this connection the thicket needs to control arterial pressure, especially at administration of drug in higher doses (40 mg a daily dose) exists Galantaminum. For the purpose of prevention of similar side effects it is necessary to select attentively a drug dose in an initiation of treatment.
Efficiency of drug at patients with other types of dementia and disturbance of memory is not established.

Drug is not intended for treatment of patients with weak cognitive disturbance, i.e. with the isolated memory disturbance exceeding the expected level for their age and education, but to not meeting criteria of Alzheimer's disease.

Side effects:

From cardiovascular system: decrease or increase in arterial pressure, orthostatic collapse, heart failure, hypostases, atrioventricular block, trembling or atrial fibrillation, lengthening
QT interval, ventrikulyarny and supraventricular tachycardia, supraventricular premature ventricular contraction, "inflows", bradycardia, ischemia or myocardial infarction.

From the alimentary system: abdominal distention, dyspepsia, gastrointestinal discomfort, anorexia, diarrhea, abdominal pain, nausea, vomiting, gastritis, a dysphagy, dryness in a mouth, the raised salivation, a diverticulitis, a gastroenteritis, a duodenitis, hepatitis, perforation of a mucous membrane of a gullet, bleeding from upper and lower parts of digestive tract.

From a musculoskeletal system: muscular spasms, muscular weakness, fever.

Laboratory indicators: increase in activity of liver enzymes, anemia, a hypopotassemia, increase in level of sugar or an alkaline phosphatase in blood.

Hematologic: thrombocytopenia, purpura.

From an urinary system: an urine incontience, a hamaturia, the speeded-up urination, infections of urinary tract, an ischuria, калькулез, renal colic.

From a nervous system: often a tremor, a syncope, block, a food faddism, visual and auditory hallucinations, behavioural reactions, including excitement/aggression; passing disturbance of cerebral circulation or stroke; a headache, dizziness, spasms, muscular spasms, paresthesia, an ataxy, hypo - or hyperkinesias, apraxia, aphasia, anorexia, drowsiness, sleeplessness.

From sense bodys: rhinitis, nasal bleeding, vision disorders, an accommodation spasm, infrequently — a sonitus.

From mentality: a depression (it is very rare — with a suicide), apathy, paranoid reactions, increase in a libido, a delirium.

The general: a stethalgia, the increased perspiration, a body degrowth, feeling of fatigue, dehydration (in rare instances — with development of a renal failure), a bronchospasm.

Interaction with other medicines:

It is not recommended to combine with other cholinomimetics.

Is an antagonist of opioids on action on a respiratory center.
Shows pharmakodinamichesky antagonism to m cholinolytics (to atropine, homatropine to methylbromide, etc.), to ganglioblokator, not depolarizing muscle relaxants, quinine, procaineamide.

Aminoglikozidny antibiotics can reduce therapeutic action of Galantaminum.
Galantaminum strengthens neuromuscular blockade during the general anesthesia (including when using as a peripheral muscle relaxant of succinylcholine).

The medicines reducing heart rate (digoxin, beta адреноблокоторы) — risk of aggravation of bradycardia.

Cimetidinum can increase bioavailability of Galantaminum.

All drugs which inhibit also isoenzymes of system of P450 cytochrome (CYP2D6 and CYP3A4) can increase plasma concentration of Galantaminum at their simultaneous use therefore the frequency of cholinergic side effects can increase (mainly nausea and vomitings). In this case, depending on portability of therapy by the specific patient, decrease in a maintenance dose of Galantaminum can be necessary.

CYP2D6 isoenzyme inhibitors (amitriptyline, fluoxetine, флувоксамин, пароксетин, quinidine) reduce clearance of Galantaminum by 25–30%. For this reason it is not recommended to appoint along with ketokonazoly, a zidovudine, erythromycin.
Strengthens the oppressing action on the central nervous system of ethanol and sedatives.

Contraindications:

Hypersensitivity to any of drug components; bronchial asthma; bradycardia; atrioventricular block;

arterial hypertension, stenocardia; chronic heart failure; epilepsy; hyperkinesias;

heavy renal (clearance of creatinine — less than 9 ml/min.) and hepatic (more than 9 points on Child-Pugh scale) disturbances; mechanical intestinal impassability; chronic obstructive pulmonary disease; obstructive diseases or recently postponed operative measure on bodies of digestive tract;

obstructive diseases or recently postponed operational treatment of urinary tract or prostate; children's age up to 9 years; pregnancy and period of a lactation.

With care:

easy and moderate renal failures or liver;

sick sinus syndrome and other supraventricular disturbances of conductivity;

concomitant use of the drugs which are slowing down heart rate (digoxin, beta адреноблокоторы); general anesthesia; a peptic ulcer of a stomach and duodenum, the increased risk of development of an erosive canker of digestive tract.

Use at pregnancy and feeding by a breast

Contraindicated at pregnancy. For the period of treatment it is necessary to stop breastfeeding.

Overdose:

Symptoms: consciousness oppression (up to a coma), spasms, strengthening of degree of manifestation of side effects, the expressed muscular weakness in combination with hypersecretion of glands of a mucous membrane of a trachea and a bronchospasm can lead to lethal blockade of respiratory tracts.

Treatment: gastric lavage, symptomatic therapy. As an antidote — in/in administration of atropine in doses of 0,5-1 mg. The subsequent doses of atropine are defined depending on the therapeutic answer and a condition of the patient.

Storage conditions:

In the dry, protected from light place at a temperature not above 25 °C. To store in the place, unavailable to children. Period of validity 2 years. Not to apply after a period of validity.

Issue conditions:

According to the recipe

Packaging:

Tablets, film coated, 4 mg, 8 mg and 12 mg.

On 7, 10, 15 or 30 tablets in a blister strip packaging from a film of the polyvinyl chloride and printing aluminum foil varnished.

On 1, 2, 4, 8 blister strip packagings on 7 tablets or on 1, 3, 6 blister strip packagings on 10 tablets or on 1, 2, 4 blister strip packagings on 15 tablets or on 1, 2, 3 blister strip packagings on 30 tablets together with the application instruction place in a pack from a cardboard.