Amitriptilin-Borimed

General characteristics. Structure:

Active ingredient: 10 mg of amitriptyline (in the form of a hydrochloride) in 1 ml of solution.

Excipients: sodium chloride, methylparahydroxybenzoate (нипагин), пропилпарагидроксибензоат (нипазол), water for injections.

Pharmacological properties:

Pharmacodynamics. Amitriptyline - tricyclic antidepressant, non-selective inhibitor of the return neyronalny capture of monoamines. Has the expressed timoleptichesky effect which is combined with the expressed sedation. Renders also antiserotoninovy, antihistaminic and anticholinergic actions.

Pharmacokinetics. Bioavailability of amitriptyline makes 31 - 61%. Linkng with proteins of plasma of 82 - 96%. Distribution volume - 5 - 10 l/kg. It is metabolized in a liver with formation of active metabolites - a nortriptilina, 10-gidroksi-amitriptilina-and inactive metabolites. Therapeutic concentration in blood for amitriptyline - 50 - 250 ng/ml, for a nortriptilin - 50 - 150 ng/ml.

Easily passes (including нортриптилин) through gistogematichesky barriers, including a blood-brain barrier, the placental barrier, gets into breast milk. Amitriptyline T1/2 - 31 - 46 h. It is removed preferential by kidneys.

Indications to use:

Endogenous depressions, especially alarming depressions.

Route of administration and doses:

At heavy depressions treatment can be begun with parenteral administration of medicine - intramusculary or intravenously slowly - the adult in a dose of 25-40 mg 3-4 times a day. A course of treatment - 3-12 introductions. After that purpose of Amitriptylini hydrochloridum inside in the form of tablets is reasonable.

To elderly people medicine is appointed in smaller doses.

Depression of function of kidneys of moderate degree: to apply with care.

Depression of function of a liver moderated degrees: careful selection of a dose and if it is possible, determination of content of medicine in blood serum is recommended.

Features of use:

It is not necessary to appoint amitriptyline along with MAO inhibitors (see sections of "Contraindication" and "Interaction with Other Medicines and Other Types of Interactions"). Co-administration of amitriptyline and MAO inhibitors can lead to development of a serotoninovy syndrome (alarming excitement, confusion, a tremor, a myoclonus and a hyperthermia). It is possible to begin treatment using amitriptyline in 14 days after the termination of reception of the MAO non-selective inhibitors, and also not less than in 1 hour after the termination of administration of drugs of reversible action of a moklobemid and a seleginin.

When using high doses the probability of development of disturbances of a heart rhythm and heavy arterial hypotension increases. Development of such states is possible also at use of usual doses for patients with already available heart diseases.

It is necessary to appoint amitriptyline with care the patient with a convulsive syndrome, an ischuria, a hyperthyroidism, in the presence of paranoid symptoms, and also diseases of a liver or cardiovascular system.

The risk of a depression connected with the increased risk of a suicide can exist before achievement of permanent remission and arise spontaneously during a therapy course. Against the background of treatment by antidepressants it is necessary to watch carefully a condition of patients, especially at the beginning of therapy, for the purpose of identification of clinical deterioration and/or emergence of suicide thoughts and behavior.

Patients with tendency to a suicide should not have access to a large amount of medicines.

The special attention is required at purpose of amitriptyline by a sick hyperthyroidism or that who accepts drugs of thyroid hormones as development of disturbances of a heart rhythm is possible.

Patients of advanced age are especially subject to development postural hypotension during treatment by amitriptyline.

At patients with maniac-depressive frustration transition of a disease to a maniacal phase is possible, from the moment of the beginning of a maniacal phase of a disease of the patient it is necessary to stop therapy by amitriptyline.

At use of amitriptyline concerning a depressive component of schizophrenia strengthening of psychotic symptoms is possible. It is necessary to appoint amitriptyline in a combination with neuroleptics.

At patients with a rare condition of small depth and a narrow corner of a chamber of the eye provoking of attacks of acute glaucoma owing to iris dilatation is possible (see the section "Contraindications").

Use of anesthetics against the background of therapy три-/tetracyclic antidepressants can increase risk of arrhythmias and arterial hypotension.

If it is possible, it is necessary to stop use of amitriptyline several days prior to surgical intervention. At inevitability of an urgent operative measure informing the anesthesiologist on treatment by amitriptyline is obligatory.

As well as other psychotropic drugs, amitriptyline it is capable to change sensitivity to insulin and glucose that demands correction of antidiabetic therapy from patients with a diabetes mellitus, besides, the depressive disease, actually, can be shown by changes of balance of glucose in the patient's organism.

It was reported about hyper pyrexia cases against the background of use of tricyclic antidepressants in case of appointment along with anticholinergic or antipsychotic medicines, especially in hot weather.

The sudden termination of therapy after prolonged treatment is capable to cause cancellation symptoms in the form of a headache, an indisposition, sleeplessnesses and irritability. Such symptoms are not signs of medicinal dependence.

During treatment it is not necessary to take alcohol.

Pregnancy and feeding by a breast. Medicine it is contraindicated at pregnancy. During treatment it is necessary to stop feeding by a breast.

Influence on ability to drive the car and to work with mechanisms. During treatment it is necessary to abstain from the dangerous types of activity requiring special attention and bystry psychomotor reactions, including, control of motor transport.

Use at children's age. Amitriptillin is contraindicated for treatment of a depression at children (aged up to 18 years) because of insufficiency of data on safety and efficiency. Treatment by amitriptyline is connected with risk of development of side reactions from cardiovascular system in all age groups.

Side effects:

Frequency of emergence of side reactions: very often (> 1/10), it is frequent (1/100, to <1/10), infrequently (1/1000 to <1/10), is rare (1/1 0000 to <1/100), is very rare (<1/10000).

Blood and lymphatic system: seldom: oppression of marrow, agranulocytosis, leukopenia, eosinophilia, thrombocytopenia.

Metabolism disturbances: seldom: loss of appetite.

Psychiatric frustration: often: state confusion of consciousness, decrease in a libido. Infrequently: hypomania, mania, alarming state, sleeplessness, terrible dreams. Seldom: a delirium (at elderly patients), hallucinations (at patients with schizophrenia).

Disturbances from a nervous system: very often: drowsiness, tremor, dizziness, headache. Often: disorders of attention, dysgeusia, paresthesias, ataxy. Infrequently: spasms.

From organs of sight: very often: accommodation disturbance. Often: mydriasis. Infrequently: increase in intraocular pressure.

From acoustic organs: infrequently: sonitus.

From cardiovascular system: very often: the strengthened heartbeat, tachycardia, orthostatic hypotension, atrioventricular blocks, blockade of legs of the carrying-out system. Often: disturbance of indicators of an electrocardiography (lengthening of an interval of QT and QRS complex). Infrequently: arterial hypertension. Seldom: arrhythmia.

From the alimentary system: very often: dryness in a mouth, a lock, nausea. Not often: diarrhea, vomiting, paraglossa. Seldom: increase in sialadens, paralytic intestinal impassability.

From a liver and biliary tract: seldom: jaundice. Disturbance of indicators of a functional condition of a liver, increase in activity of an alkaline phosphatase of blood and transaminases.

Skin and hypodermic cellulose: very often: hyperhidrosis. Infrequently: rashes, urticarias, face edema. Seldom: alopecia, photosensitization.

From kidneys and urinary tract: infrequently: ischuria.

From reproductive system and mammary glands: often: erectile dysfunction. Seldom: gynecomastia.

General disturbances: often: fatigue. Seldom: pyrexia.

Other manifestations: very often: increase in body weight. Seldom: body degrowth.

Interaction with other medicines:

Contraindicated combinations. MAO inhibitors (non-selective, and also the selection And (моклобемид) and In (селегилин)) - risk of a serotoninovy syndrome (see the section "Contraindications").

Undesirable combinations. Sympathomimetics: amitriptyline is capable to potentsiirovat cardiovascular effects of adrenaline, ephedrine, an izoprenalin, noradrenaline, Phenylephrinum and fenilpropanolamin.

Blockers of adrenergic neurons: tricyclic antidepressants can interfere with anti-hypertensive effect of a guanetidin, betanidin, Reserpinum, clonidine and Methyldopums.

It is recommended to revise all scheme of anti-hypertensive therapy during treatment by tricyclic antidepressants.

Anticholinergics: tricyclic antidepressants are capable to exponentiate effects of the specified medicines from organs of sight, TsNS, intestines and a bladder; it is necessary to avoid use, simultaneous with them, because of the increased risk of paralytic intestinal impassability, a hyper pyrexia.

The medicines causing lengthening of an interval of QT of the electrocardiogram, including antiarrhytmic drugs (quinidine) antihistaminic (астемизол and терфенадин), some antipsychotic means (in particular Pimozidum and сертиндол), цизаприд, галофантрин and соталол can increase probability of ventricular arrhythmia in case of reception together with tricyclic antidepressants.

Antifungal means, such as флуконазол and тербинафин, can lead to increase in concentration in blood serum of tricyclic antidepressants and expressiveness of the accompanying toxicity. There are cases of a loss of consciousness and developing of polymorphic ventricular tachycardia.

TsNS depressants: amitriptyline is capable to strengthen effects of alcohol, barbiturates and other means, the oppressing TsNS.

Pharmacokinetic interactions. Tricyclic antidepressants, including amitriptyline, are metabolized by a liver P450 cytochrome CYP2D6 isoenzyme. CYP2D6 is characterized by polymorphism in population, and its activity can change many psychotropic, and also other medicines, such as, neuroleptics, inhibitors of the return serotonin reuptake, except for a tsitalopram (which is very weak inhibitor of an isoenzyme), blockers of β-adrenoceptors, and also antiarrhytmic means. Isoenzymes of CYP2C19 and CYP3A also participate in amitriptyline metabolism.

Barbiturates, as well as other stimulators of enzymes, for example rifampicin and carbamazepine, can strengthen metabolism and, thereby, cause decrease in content of tricyclic antidepressants in a blood plasma and reduction of antidepressant effect.

Cimetidinum and methylphenidate, and also drugs of blockers of calcium channels, increase the level of tricyclic connections in plasma and respectively toxicity.

Tricyclic antidepressants and neuroleptics mutually suppress metabolism of each other, it can lead to decrease in a convulsive threshold and emergence of spasms. Correction of doses of the specified medicines can be required.

Contraindications:

Hypersensitivity, simultaneous treatment by inhibitors of a monoaminooxidase and in 2 weeks before an initiation of treatment, the acute period and the early recovery period after a myocardial infarction, coronary heart disease against the background of tachycardia, arterial hypertension, arrhythmias (especially heavy disturbances of atrioventricular and intra ventricular conductivity), maniacal phase MDP, an alarming and paranoid syndrome at depressions (a possibility of a suicide), epilepsy, a peptic ulcer of a stomach and duodenum, a pylorostenosis, closed-angle glaucoma, a prostatauxe, a bladder atony, paralytic impassability of intestines, an acute drunkenness, intoxication somnolent, analgeziruyushchy and psychoactive medicines, a serious illness of a liver, children's age (up to 18 years).

Overdose:

Symptoms:

From the central nervous system: drowsiness, a stupor, a coma, an ataxy, hallucinations, concern, psychomotor excitement, decline in the ability to concentration of attention, a disorientation, confusion of consciousness, a dysarthtia, a hyperreflexia, muscle tension, a choreoathetosis, an epileptic syndrome.

From cardiovascular system: the lowering of arterial pressure, tachycardia, arrhythmia, disturbance of endocardiac conductivity characteristic of intoxication tricyclic antidepressants of change of an ECG (especially QRS), shock, seldom or never - a cardiac standstill.

Others: respiratory depression, short wind, cyanosis, vomiting, a hyperthermia, a mydriasis, the increased sweating, an oliguria or an anury.

Symptoms develop in 4 h after overdose, reach a maximum in 24 h and 4-6 days last. At suspicion on overdose, especially at children, the patient should be hospitalized.

Treatment: at heavy anticholinergic effects (a lowering of arterial pressure, arrhythmia, a coma, myoclonic epileptic seizures) – administration of inhibitors of cholinesterase (use of physostigmine is not recommended because of the increased risk of developing of spasms); maintenance of arterial pressure and water and electrolytic balance. Are shown control of functions of cardiovascular system (including an ECG) within 5 days (the recurrence can come in 48 h and later), anticonvulsant therapy, etc. resuscitation actions. The hemodialysis and an artificial diuresis are inefficient.

Storage conditions:

In the place protected from light, at a temperature from 10 °C to 25 °C. To store in the place, unavailable to children. A period of validity - 2 years. Not to use after expiry date.

Issue conditions:

According to the recipe

Packaging:

In ampoules on 2 ml in packaging No. 10, in packaging No. 10 x 1.