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

Pharmacodynamics:Acetylcholinesterase - an enzyme that cleaves acetylcholine in presynapses of neurons. Galantamine reversibly inhibits acetylcholinesterase, enhances and lengthens the action of endogenous acetylcholine. It facilitates impulses in cholinergic, including neuromuscular, synapses, enhances excitation processes in the reflex zones of the spinal cord and brain. Increases the tone of smooth and skeletal muscles, stimulates the secretion of digestive and sweat glands.Causes miosis and spasm of accommodation, lowers the intraocular pressure in closed-angle glaucoma. When injected into the conjunctival sac, it can cause temporary swelling of the conjunctiva. It penetrates the blood-brain barrier, enhances excitation processes in the central nervous system. In children with infantile cerebral palsy it improves neuromuscular conduction, increases the contractile ability of muscles, positively influences thinking and memory. By increasing the activity of the cholinergic system, cognitive function can improve in patients with dementia such as Alzheimer's.

Pharmacokinetics:After a single oral intake of 8 mg quickly absorbed from the digestive tract, bioavailability - about 90%. Eating slows absorption by 25%. The maximum accumulation of the drug in the plasma occurs in 1.2 hours. The pharmacokinetics of galantamine is linear in the dose range of 4-16 mg twice a day. Binding to plasma proteins - 18%. Plasma clearance - about 300 ml / min, the volume of distribution - 175 liters. The main isoenzymes of the cytochrome P450 system, which metabolize galantamine, are CYP2D6 and CYP3A4. The main metabolite of galantamine, determined in plasma - is its glucuronide.Excretion of a two-phase, final half-life - 7-8 hours. Kidney clearance - 65 ml / min (20-25% of the plasma clearance). It is excreted in the urine almost completely (90-97%, 18-22% of it in unchanged form within 24 hours) and insignificantly with feces (2.2-6.3%).

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

With moderate hepatic insufficiency (7-9 points on the Child-Pugh scale), the area under the time-concentration curve and the half-life of galantamine are increased by 30%.

At moderate chronic renal failure (creatinine clearance 52-104 ml / min), the plasma concentration of galantamine is increased by 38% in severe (creatinine clearance - 9-51 ml / min) - 67%.

Indications:Dementia of the Alzheimer's type of mild or moderate severity, including those with chronic circulatory disorders;

Poliomyelitis (immediately after the termination of the febrile period, as well as in the recovery period and the period of residual events);

Myastenia gravis, progressive muscular dystrophy, myopathy;

Cerebral palsy; neuritis; radiculitis;

Traumatic injuries of the nervous system;

Diseases of the spinal cord (myelitis, poliomyelitis, poliomyelitis form of tick-borne encephalitis), mononeuritis, polyneuritis, polyneuropathy, polyradiculoneuritis, Guillain-Barre syndrome, idiopathic paresis of the facial nerve, myopathy, bedwetting.

In anesthesiology and surgery: as an antagonist of nondepolarizing muscle relaxants and for the treatment of postoperative atony of the intestine and bladder.

In physiotherapy: in the form of iontophoresis in diseases of the peripheral nervous system.

In Toxicology: intoxication with anticholinergic drugs, morphine and its analogues.

In roentgenology: to improve the quality of diagnosis of the digestive system, including the gallbladder.

ICD-10

I.A80-A89.A80 Acute poliomyelitis

I.A80-A89.A84 Tick-borne viral encephalitis

I.B90-B94.B91 Consequences of poliomyelitis

V.F00-F09.F00 * Dementia in Alzheimer's disease (G30 .- +)

VI.G00-G09.G04 Encephalitis, myelitis and encephalomyelitis

VI.G50-G59.G51 Lesions of the facial nerve

VI.G50-G59.G58.9 Mononeuropathy, unspecified

VI.G60-G64.G61.0 Guillain-Barre Syndrome

VI.G60-G64.G62 Other polyneuropathies

VI.G70-G73.G70 Myasthenia gravis and other disorders of the neuromuscular synapse

VI.G70-G73.G71.0 Muscular dystrophy

VI.G70-G73.G72 Other myopathies

VI.G80-G83.G80 Cerebral palsy

VI.G90-G99.G90.9 Disorder of autonomic nervous system, unspecified

XI.K94.K94 * Diagnosis of diseases of the digestive tract

XIII.M50-M54.M54.1 Radiculopathy

XIII.M70-M79.M79.2 Neuralgia and neuritis, unspecified

XIV.N30-N39.N31.2 Neurogenic weakness of the bladder, not elsewhere classified

XIV.N30-N39.N39.4 Other specified incontinence

XIX.T08-T14.T14.4 Injury of nerve (nerves) of unspecified body region

XIX.T36-T50.T40 Poisoning and Drug psychodysleptics [hallucinogens]

XIX.T36-T50.T44 Poisoning by drugs, acting primarily on the autonomic nervous system

Contraindications:Hypersensitivity, epilepsy, hyperkinesis, asthma, angina pectoris, bradycardia, congestive heart failure, atrioventricular blockage, hypertension, chronic obstructive pulmonary disease, mechanical ileus, obstructive pulmonary disease or recent surgery on the digestive tract obstructive disease or recent surgery to the urinary tract and prostate, renal impairment (creatinine clearance less than 9 ml / min) , severe liver function abnormalities (more than 9 points on a scale Child-Pugh)children's age up to 1 year (for solution), up to 9 years (for tablets).

Carefully:General anesthesia, syndrome of weakness of the sinus node, simultaneous reception of drugs that slow down the heart rate (digoxin, beta-adrenoblockers), mild and moderate impairment of liver and / or kidney function.

Pregnancy and lactation:When pregnancy is possible in the event that the potential benefit to the mother exceeds the possible risk to the fetus. The action category for fetus by FDA is B. Women receiving galantamine, should refrain from breastfeeding (it is not known whether galantamine with breast milk).

Dosing and Administration:Galantamine is administered intravenously, intramuscularly, subcutaneously, percutaneously (by iontophoresis), orally in tablets. The dose is selected individually, taking into account the age of the patient, the nature of the disease, the effectiveness and tolerability of the drug. At the beginning of treatment, the minimum effective dose is prescribed, gradually increasing it.

Inside, the maximum daily dose for adults is 10-40 mg in 2-4 admission. When myasthenia gravis The daily dose is divided into 3 doses. In the treatment of dementia of the Alzheimer's type, the recommended initial dose is 8 mg per day - 4 mg twice a day,After 4 weeks, they switch to a maintenance dose of 16 mg (8 mg twice a day), which is taken at least 4 weeks. The question of increasing the maintenance dose to the maximum (24 mg per day) must be addressed after assessing the clinical situation (the effect achieved and tolerability). When switching from the drug in the form of tablets taken 2 times a day to the dosage form in the form of prolonged-action capsules, taken once a day, the total daily dose should remain unchanged.

Subcutaneously, adults: 2.5-10 mg 1-2 times a day, maximum single and daily doses of 10 mg and 20 mg, respectively. Subcutaneously, children: 1-2 times a day, at the age of 1-2 years - 0.25-1.0 mg per day, 3-5 years - 0.5-5.0 mg per day, 6-8 years - 0,75-7,5 mg per day, 9-11 years - 1,0-10,0 mg per day, 12-15 years - 1,25-12,5 mg per day, 15-16 years - 12 , 5-20.0 mg per day. A large dose is divided into 2 injections per day.

The duration of treatment depends on the specificity and severity of the disease, most often 40-60 days, the course of treatment can be carried out 2-3 times with intermediate periods of 1-2 months.

Intravenously, as an antagonist antidepolarizing muscle relaxants: adults - 10-20 mg per day, children from 1 year - 1-2 mg, 3-5 years - 1.5-3 mg, 6-8 years - 2-5 mg, 9-11 years - 3-8 mg, 12-15 years - 5-10 mg.

Intramuscularly, with X-ray studies used in adults at a dose of 1-5 mg.In diseases of the peripheral nervous system and for the treatment of urinary incontinence, it is used in children in the form of iontophoresis in a dose of 1-2 ml of 0.25% solution.

Application in elderly patients

Use in the elderly has not been systematically studied. Due to the large number of contraindications most applicable to elderly people (for example, chronic heart failure or long-term use of beta-blockers), a thorough examination and subsequent active monitoring of the condition of such patients is necessary.

Use in children

The application is possible according to the dosing regimen. Contraindicated in children under 1 year (for solution), up to 9 years (for tablets).

Side effects:From the side of the cardiovascular system and blood (hematopoiesis, hemostasis): decrease or increase of arterial pressure, orthostatic collapse, heart failure, edema, AV block, flutter or atrial fibrillation, QT interval prolongation, ventricular and supraventricular tachycardia, supraventricular extrasystole, flushing of the face, bradycardia, ischemia or myocardial infarction, thrombocytopenia, purpura , anemia.

On the part of the digestive system: Nausea, vomiting, abdominal pain, diarrhea, bloating, dyspepsia, gastrointestinal discomfort, anorexia, gastritis, dysphagia, dry mouth, increased salivation, diverticulitis, gastroenteritis, duodenitis, hepatitis, perforation of the esophagus mucosa, bleeding from the upper and lower departments of the gastrointestinal tract, increased activity of hepatic transaminases.

From the musculoskeletal system: muscle spasms, muscle weakness.

From the genitourinary system: urinary incontinence, hematuria, frequent urination, urinary tract infections, urinary retention, calculosis, renal colic.

From the nervous system and sensory organs: tremor, syncope, inhibition, taste perversion, visual and auditory hallucinations, behavioral reactions, including agitation / aggression; transient impairment of cerebral circulation or stroke; fatigue, headache, dizziness, drowsiness, insomnia, cramps, muscle spasms, paresthesia, ataxia, hypo- or hyperkinesia, depression (very rarely with suicide), apathy, paranoid reactions, delirium, apraxia, aphasia, vision impairment (spasm accommodation), tinnitus (infrequently).

Other: pain in the chest, excessive sweating, fever, weight loss, nosebleeds, rhinitis, dehydration (in rare cases - with the development of kidney failure), bronchospasm, increased libido, hypokalemia, increased sugar or alkaline phosphatase in the blood.

Overdose:Symptoms: muscle weakness or fasciculation, severe nausea, vomiting, abdominal cramping, increased salivation, lacrimation, urinary and fecal incontinence, severe sweating, lowering of blood pressure, bradycardia, collapse and convulsions. Pronounced muscular weakness in combination with hypersecretion of the mucous membrane of the trachea and bronchospasm can lead to a lethal blockade of the airways.

Treatment: gastric lavage (with oral administration), symptomatic therapy, administration of anticholinergics - atropine (0.5-1.0 mg intravenously); the frequency and magnitude of subsequent doses depend on the dynamics of the clinical state of the patient.

Interaction:It is an antagonist of morphine and its structural analogues in relation to the inhibitory effect on the respiratory center.

It restores neuromuscular conduction,blocked by curare like antidepolarizing action (tubocurarine and others).

Strengthens the effect of depolarizing muscle relaxants (dithiline).

Cholinolytic agents (atropine and others) eliminate the peripheral muscarine-like effects of galantamine.

Curare-like substances and ganglion blockers eliminate the nicotine-like effects of galantamine.

Aminoglycosides can reduce the therapeutic effect of galantamine.

When appointed in conjunction with drugs that reduce heart rate (digoxin, beta-adrenoblockers), there is a risk of aggravation of bradycardia.

Galantamine increases the inhibitory effect on the CNS of ethanol and sedatives.

Special instructions:In severe violations of kidney function, the dose of the drug should be reduced. In case of impaired motor activity, treatment should be combined with physiotherapeutic procedures (massage, medical gymnastics), which should be started 1-2 hours after the administration of galantamine.

Instructions

Galantamine (Galantaminum)