Амитриптилин-Ферейн®

General characteristics. Structure:

Active ingredient: 10 mg or 25 mg of Amitriptylini hydrochloridum in 1 tablet.

Excipients: as a part of a kernel - microcrystallic cellulose, croscarmellose sodium, aerosil, magnesium stearate; as a part of a cover: a gidroksipropilmetiltsellyuloza, polyethyleneglycol - 6000, titanium dioxide, indigo carmine for a dosage of 0,01 g (10 mg) or a gidroksipropilmetiltsellyuloza, polyethyleneglycol - 6000, titanium dioxide, tropeolin O - for a dosage of 0,025 g (25 mg).

Pharmacological properties:

Pharmacodynamics. Amitriptyline - tricyclic antidepressant from group of not selective inhibitors of neyronalny capture of monoamines. Possesses the expressed timoanaleptichesky and sedative action.

Pharmacodynamics. The mechanism of antidepressive effect of amitriptyline is connected with oppression of the return neyronalny capture of catecholamines (noradrenaline, dopamine) in TsNS.

Amitriptyline is an antagonist of muskarinovy cholinergic receptors in TsNS and on the periphery. Also possesses peripheral anti-histamine (H1) and anti-adrenergic properties.

Pharmacokinetics. Absorption is high. At oral administration of amitriptyline the maximum concentration in plasma are reached during 4-8chas. Its bioavailability from 33 to 62%. Time of achievement of the maximum concentration (Cmax) after intake of 2,0-7,7 h. The volume of distribution is 5-10 l/kg. Effective therapeutic concentration in amitriptyline blood - 50-250 ng/ml, for a nortriptilin (its active metabolite) of 50-150 ng/ml. Passes through a blood-brain barrier (including нортриптилин).

Concentration of amitriptyline in fabrics are higher, than in plasma. Communication with proteins of plasma of 92 - 96%.

It is metabolized in a liver (by demethylation, a hydroxylation) with formation of active metabolites - a nortriptilina, 10-hydroxy-amitriptyline, and inactive metabolites.

Plasma elimination half-life from 10 to 28 hours for amitriptyline and from 16 to 80 hours for a nortriptilin. It is allocated, generally with urine. Full removal within 7 days. Amitriptyline gets through a placental barrier, is emitted in breast milk in the concentration similar plasma.

Indications to use:

Depressions of any etiology. Owing to expressiveness of sedation it is especially effective at it is disturbing - depressions.

The mixed emotional frustration and disturbances in behavior, phobic frustration.

Children's enuresis (except for children with a hypotonic bladder).

Psychogenic anorexia, bulimic neurosis.

Neurogenic pains of chronic character, for prevention of migraine.

Route of administration and doses:

Appoint inside (in time or after food). The initial daily dose at intake makes 50-75 mg (25 mg in 2-3 receptions), then the dose is gradually increased by 25-50 mg, before obtaining desirable antidepressive effect. The optimum daily therapeutic dose makes 150-200 mg (the maximum part of a dose is accepted for the night). At heavy depressions, resistant to therapy, the dose is increased to 300 mg and more, to the most tolerable dose (the maximum dose for ambulatories - 150 mg/days). In these cases it is reasonable to begin treatment with intramuscular or intravenous administration of drug, applying at the same time higher initial doses, accelerating building of dosages under control of a somatic state.

After obtaining lasting antidepressive effect in 2-4 weeks of a dose gradually and slowly reduce. In case of symptoms of a depression at decrease in doses it is necessary to return to a former dose.

If the condition of the patient does not improve within 3-4 weeks of treatment, then further therapy is inexpedient.

At patients of advanced age at easy disturbances, in out-patient practice, doses make 25-50-100 mg - as much as possible, in the divided doses or 1 time a day for the night.

At enuresis to children 6 years of 12,5-25 mg before going to bed are more senior (the dose should not exceed 2,5 mg/kg of weight of the child).

For prevention of migraine, chronic pains of neurogenic character (including long headaches) from 12,5-25 mg to 100 mg/days.

Features of use:

Amitriptyline in doses higher than 150 mg/days reduces a threshold of convulsive activity therefore it is necessary to consider possibility of convulsive attacks at patients with those in the anamnesis, and at that category of patients who are predisposed to it because of age or injuries.

Treatment by Amitriptyline has to take place in advanced age under careful somatic control and using the minimum doses of drug, raising them gradually, in order to avoid development of delirious frustration, a hypomania and other complications.

Patients with depressive phase MDP, can pass into a maniacal stage.

Influence on ability to manage vehicles and mechanisms. During reception of Amitriptyline driving of vehicles, service of mechanisms and other types of the works demanding the increased concentration of attention and also alcohol intake is forbidden.

Side effects:

Generally connected with holinoblokiruyushchy effect of drug: a sight illegibility, accommodation paresis, increase in intraocular pressure, dryness in a mouth, a chair delay, impassability of intestines, an urination delay, fervescence. All these phenomena usually pass after adaptation to drug or decrease in doses.

From TsNS: increased fatigue, irritability, dizziness, drowsiness, confusion of consciousness, hallucination, motive excitement, disorientation, tremor, ataxy, sleeplessness, dreadful dreams, headache, peripheral neuropathy, changes of EEG. Seldom - extrapyramidal frustration, strengthening of alarm.

From cardiovascular system: tachycardia, conductivity disturbance, orthostatic arterial hypotension, expansion of the QRS complex on an ECG, symptoms of heart failure.

From a GIT: nausea, vomiting, anorexia, stomatitis, taste disturbances, darkening of language, a sensation of discomfort in epigastriums, increase in activity of "hepatic" transaminases, seldom cholestatic jaundice.

From endocrine system: gynecomastia, galactorrhoea, change of secretion of antidiuretic hormone (ADG), decrease in a libido, potentiality. Seldom - a hyperglycemia, a glucosuria, disturbance of tolerance to glucose.

Allergic reactions: skin rash, itch, photosensitization, Quincke's disease. Other: an agranulocytosis and other changes of blood, a hair loss, a hyperadenosis, increase in body weight at prolonged use, perspiration, a pollakiuria.

At prolonged treatment, especially in high doses, at the sharp termination of treatment, development of a withdrawal is possible: headache, nausea, vomiting, etc.

Interaction with other medicines:

Amitriptyline strengthens oppression of TsNS the following drugs: neuroleptics, sedative and hypnagogues, anticonvulsant drugs, central and narcotic analgetics, anesthetics, alcohol.

At combined use of Amitriptyline with neuroleptics, and/or anticholinergic drugs there can be a febrile temperature reaction, paralytic intestinal impassability.

Amitriptyline exponentiates hypertensive effects of catecholamines, but inhibits effects of the drugs influencing release of noradrenaline.

Amitriptyline can reduce anti-hypertensive action of a guanetidin and drugs with the similar mechanism of action.

At simultaneous use of Amitriptyline and anticoagulants - derivatives of coumarin increase in anticoagulating activity of the last is possible.

At a concomitant use of Amitriptyline and Cimetidinum increase in concentration in Amitriptyline plasma with possible development of toxic effects is possible. Inductors of microsomal enzymes of a liver (barbiturates, carbamazepine) reduce plasma concentration of Amitriptyline.

Amitriptyline strengthens action of protivoparkinsonichesky means.

Quinidine slows down Amitriptyline metabolism.

Combined use of Amitriptyline with Disulfiramum and other inhibitors of an atsetaldegiddegidrogenaza can provoke a delirium.

The concomitant use of Amitriptyline with MAO inhibitors can lead to a lethal outcome. Having rummaged in treatment between reception of MAO inhibitors and tricyclic antidepressants has to make not less than 14 days!

Contraindications:

• Heart failure in a decompensation stage.
• Acute and recovery period of a myocardial infarction.
• Disturbances of conductivity of a cardiac muscle.
• The expressed arterial hypertension.
• Acute diseases of a liver and kidneys, with the expressed disturbance of functions.
• Blood diseases.
• Peptic ulcer of a stomach and 12 perstny guts in an aggravation stage.
• Prostatauxe.
• Bladder atony.
• Pylorostenosis, paralytic impassability of intestines.
• Simultaneous treatment by MAO inhibitors (see Interaction).
• Pregnancy, breastfeeding period.
• Children up to 6 years.
• Hypersensitivity to Amitriptilin.

With care. Amitriptyline should be applied with care at the persons having alcoholism at bronchial asthma, the maniac-depressive psychosis (MDP) and epilepsy (see. Special instructions), oppression of a marrowy hemopoiesis, a hyperthyroidism, stenocardia and heart failure, and also at closed-angle glaucoma and intraocular hypertensia.

Overdose:

Drowsiness, disorientation, confusion of consciousness, expansion of pupils, fervescence, asthma, dysarthtia, excitement, hallucinations, convulsive attacks, muscle tension, supor, coma, vomiting, arrhythmia, arterial hypotension, heart failure, respiratory depression.

Help measures: therapy termination by Amitriptyline, gastric lavage, liquid infusion, symptomatic therapy, maintenance of the ABP and water and electrolytic balance. Monitoring of cardiovascular activity (ECG) within 5 days since the recurrence can come in 48 hours and later is shown. The hemodialysis and an artificial diuresis are a little effective.

Storage conditions:

List B. In dry, protected from light, the place, unavailable to children, at a temperature from 15 °C to 30 °C. A period of validity - 5 years. Not to use after the term specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Tablets coated 10 mg, 25 mg. Packaging: 10, 20 tablets in a blister strip packaging; 1, 2, 3, 4, 5 blister strip packagings in a pack; 40, 50 tablets in banks of orange glass or banks and bottles from glass melt for medicines; 40, 50, 60, 100 tablets in plastic containers, 1 bank, a bottle, a plastic container in a pack.