Amitriptyline Nikomed

General characteristics. Structure:

Active agent: Amitriptylini hydrochloridum of 11,3 mg and 28,3 mg
Excipients: propylene glycol, magnesium stearate, povidone, titanium dioxide, gipromelloza, talc, cellulose microcrystallic, potato starch, lactoses monohydrate.

Description
Round, biconvex tablets, coated white color.

Pharmacological properties:

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 and serotonin) in TsNS.
Amitriptyline is an antagonist of muskarinovy cholinergic receptors in TsNS and on the periphery and therefore, one of the most strong tricyclic antidepressants in this respect. Also has antihistaminic and anti-adrenergic properties.

Pharmacokinetics. At oral administration of amitriptyline peak concentration in plasma are reached within 4-8 hours. Its bioavailability from 33 to 62%. As amitriptyline slows down transit time in a GIT, absorption can be slowed down, especially at overdose. At intramuscular introduction peak concentration in plasma are higher and are reached earlier.
Effective concentration in blood of amitriptyline and a nortriptilin (its active metabolite), on average from 120 to 240 ng/ml.
Concentration of amitriptyline in fabrics is higher, than in plasma where for 92% it is connected with proteins.
Plasma elimination half-life from 10 to 28 hours for amitriptyline and for a nortriptilin is metabolized from 16 to 80 hours in a liver. 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:

To apply strictly on doctor's orders.
• Depressions of any etiology. It is especially effective at it is disturbing - depressions, owing to expressiveness of sedation. Does not cause an aggravation of productive symptomatology (nonsense, hallucinations) unlike antidepressants with a promoting effect.
• 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), intramusculary or intravenously. 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 150-200mg (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 (on average on 10-30 mg to 4 times a day, but no more than 150 mg/days). 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 (max) in the divided doses or 1 time a day for the night.
Children as antidepressant: 6-12 years, in 10-30 mg (1-5 mg/kg) a day in 2 - x the divided doses; 12 years (12-18 years), inside on 10 mg 3 times a day and 20 mg before going to bed are more senior, if necessary, and taking into account portability increase a dose to 100 mg a day in the divided doses or once before going to bed.
For prevention of migraine, chronic pains of neurogenic character (including long headaches) from 12,5-25 mg to 100 mg/days.

Features of use:

Before an initiation of treatment control of the ABP (at patients with the lowered or labile ABP it can decrease still more) is necessary; during treatment - control of peripheral blood (the agranulocytosis in this connection it is recommended to watch a blood picture in some cases can develop, especially at fervescence, development of grippopodobny symptoms and quinsies), at long therapy - control of functions CCC and a liver. At elderly and patients with diseases of CCC control of ChSS, the ABP, an ECG is shown. On an ECG emergence of clinically insignificant changes is possible (smoothing of a tooth T, S-T segment depression, expansion of the QRS complex). Care is necessary upon sharp transition to vertical position from situation "lying" or "sitting".
During treatment it is necessary to exclude the ethanol use.
At the sudden termination of reception after prolonged treatment development of a syndrome of "cancellation" is possible.
To the expressed depressions свойствен risk of suicide actions which can remain up to achievement of essential remission. In this regard in an initiation of treatment the combination with HP from group of benzodiazepines or antipsychotic HP and constant medical control can be shown (to charge to authorized representatives storage and delivery of HP). In combination with electroconvulsive therapy it is appointed only on condition of careful medical observation. (Before carrying out the general or local anesthesia it is necessary to warn the anesthesiologist that the patient accepts amitriptyline.)
Owing to anticholinergic action decrease in a slezootdeleniye and relative increase in amount of slime as a part of the lacrimal liquid is possible that can lead to damage of an epithelium of a cornea at the patients using contact lenses. At prolonged use increase in frequency of developing of caries of teeth is observed. The need for Riboflavinum can be increased.

Side effects:

Generally connected with cholinolytic effect of drug, accommodation disturbance, increase in intraocular pressure, dryness in a mouth, a chair delay, impassability of intestines, an urination delay, fervescence, drowsiness. All these phenomena usually pass after adaptation to drug or decrease in doses.
From cardiovascular system: tachycardia, arrhythmias, orthostatic arterial hypotonia.
From a GIT: nausea, vomiting, anorexia, stomatitis, taste disturbances, a sensation of discomfort in epigastriums, seldom abnormal liver functions.
From endocrine system: gynecomastia, galactorrhoea, change of secretion of ADG, decrease in a libido, potentiality.
Others: an agranulocytosis and other changes of blood, skin rash, a hair loss, a hyperadenosis, increase in body weight at prolonged use.
Amitriptyline in doses higher than 150 mg/days reduces a threshold of convulsive activity therefore it is necessary to consider risk of developing 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 avoidance of development of delirious frustration, a hypomania and other complications.
Patients with depressive phase MDP, can pass into a maniacal stage. Anticholinergic effects: a sight illegibility, accommodation paralysis, a mydriasis, increase in intraocular pressure (only at persons with local anatomic predisposition - a narrow corner of an anterior chamber), tachycardia, dryness in a mouth, confusion of consciousness, a delirium or hallucinations, locks, paralytic intestinal impassability, difficulty of an urination, decrease in sweating. From a nervous system: drowsiness, an adynamy, unconscious states, concern, a disorientation, hallucinations (especially at patients of advanced age and at patients with Parkinson's disease), uneasiness, excitement, motive concern, a maniacal state, a hypomaniacal state, aggression, memory disturbance, depersonalization, strengthening of a depression, decline in the ability to concentration of attention, sleeplessness, "dreadful" dreams, yawning, an adynamy; activation of symptoms of psychosis; headache, myoclonus; dysarthtia, tremor of small muscles, especially hands, brushes, head and language, peripheral neuropathy (paresthesias), myasthenia, myoclonus; ataxy, extrapyramidal syndrome, increase and strengthening of epileptic seizures; changes on EEG. From CCC: tachycardia, heartbeat, dizziness, orthostatic hypotension, nonspecific changes on an ECG, (an interval of S-T or a tooth of T) at the patients who do not have heart diseases; arrhythmia, lability of the ABP (decrease or increase in the ABP), disturbance of intra ventricular conductivity (expansion of the QRS complex, change of an interval of P-Q, blockade of legs of a ventriculonector). From the alimentary system: nausea, it is rare - hepatitis (including an abnormal liver function and cholestatic jaundice), heartburn, vomiting, taste change, diarrhea, darkening of language.
From endocrine system: increase in sizes (hypostasis) of testicles, a gynecomastia; increase in the sizes of mammary glands, galactorrhoea; decrease or increase in a libido, decrease in a potentiality, hypo - or a hyperglycemia, a hyponatremia (decrease in production of vasopressin), a syndrome of inadequate secretion of ADG.
From bodies of a hemopoiesis: agranulocytosis, leukopenia, thrombocytopenia, purpura. eosinophilia.
Allergic reactions: skin rash, skin itch, small tortoiseshell, photosensitization, puffiness of the person and language.
Others: hair loss, sonitus, hypostases, hyper pyrexia, hyperadenosis, ischuria, pollakiuria, hypoproteinemia.
Cancellation symptoms: at sudden cancellation after prolonged treatment - nausea, vomiting, diarrhea, a headache, an indisposition, sleep disorders, unusual dreams, unusual excitement; at gradual cancellation after prolonged treatment - irritability, motive concern. sleep disorders. unusual dreams.
Connection with administration of drug is not established: volchanochnopodobny syndrome (palindromic rheumatism, emergence of antinuclear antibodies and positive rhematoid factor), abnormal liver function, ageusia, gastralgia, increase in appetite and body weight or loss of appetite and body weights, stomatitis.
During reception of amitriptyline driving of vehicles is forbidden. service of mechanisms and other types of the works demanding the increased concentration of attention.

Interaction with other medicines:

Amitriptyline exponentiates oppression of TsNS the following drugs: neuroleptics, sedative and hypnagogues, anticonvulsant drugs, the central and narcotic analgetics, means for the general anesthesia, 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 sympatholytics (Octadinum, a guanetidin and drugs with the similar mechanism of action). At a concomitant use of amitriptyline and Cimetidinum increase in concentration in amitriptyline plasma is possible.
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!
Pimozidum and probucol can strengthen heart arrhythmias that is shown in lengthening of an interval of R-t on an ECG.
Strengthens action on CCC Epinephrinum, Norepinephrinum, the izoprenatina, ephedrine and Phenylephrinum (including and when these HP are a part of local anesthetics) and increases risk of development of disturbances of a cordial rhythm, tachycardia, heavy arterial hypertension. Parenteral use is possible only in the conditions of a hospital, under observation of the doctor, with observance of a bed rest in the first days of therapy.
Care is necessary upon sharp transition to vertical position from situation "lying" or "sitting".
During treatment it is necessary to exclude the ethanol use.
Appoint not earlier than in 14 days after cancellation of MAO inhibitors. since small doses. At the sudden termination of reception after prolonged treatment development of a syndrome of "cancellation" is possible.
Amitriptyline in doses higher than 150 mg/days reduces a threshold of convulsive activity (it is necessary to consider risk of emergence of epileptic attacks at predisposed patients, and also in the presence of the factors contributing to emergence of other convulsive syndrome, for example injuries of a brain of any etiology, simultaneous use of antipsychotic HP (neuroleptics), during refusal of ethanol or cancellation of the HP having anticonvulsant properties, for example benzodiazepines).
The risk of suicide actions which can remain up to achievement of essential remission is inherent to the expressed depressions. In this regard in an initiation of treatment the combination with HP from group of benzodiazepines or antipsychotic HP and constant medical control can be shown (to charge to authorized representatives storage and delivery of HP). At patients with cyclic affective frustration in the period of a depressive phase against the background of therapy maniacal or hypomaniacal symptoms can develop.

Contraindications:

• Dekompensirovanny heart diseases.
• Acute and recovery period of a myocardial infarction.
• Disturbances of conductivity of a cardiac muscle.
• Idiopathic hypertensia of 3 St.
• Acute diseases of a liver and kidneys, with the expressed disturbance of functions.
• Blood diseases.
• A peptic ulcer of a stomach and 12 perstny guts in an aggravation stage.
• Glaucoma.
• Prostate hypertrophy.
• Bladder atony.
• Pylorostenosis, paralytic impassability of intestines.
• Simultaneous treatment by MAO inhibitors.
• Pregnancy, breastfeeding period.
• Children up to 6 years (injection forms up to 12 years).
• Hypersensitivity to amitriptyline.
With care: an alcoholism, bronchial asthma, maniac-depressive psychosis, diseases of CCC (stenocardia, arrhythmia, heart blocks, HSN, a myocardial infarction, arterial hypertension), a stroke, a liver and/or renal failure, a thyrotoxicosis, an ischuria, bladder hypotonia, schizophrenia (activation of psychosis is possible), epilepsy, advanced age.

Overdose:

Drowsiness, disorientation, confusion of consciousness, expansion of pupils, fervescence, asthma, dysarthtia, excitement, hallucinations, convulsive attacks, muscle tension, supor, coma, vomiting, arrhythmia, hypotonia, heart failure, respiratory depression.
Help measures: the therapy termination by amitriptyline, a gastric lavage, liquid infusion, administration of physostigmine of 1-3 mg each 1/2-2 hours in oil or in/in (to children administration of physostigmine is begun with 0,5 mg, then the dose is repeated with a 5-minute interval for definition of a minimal effective dose, but it is no more than 2 mg), physostigmine it is necessary to apply only at patients in a coma, with respiratory depression, epileptic seizures, heavy hypotension and the expressed cardiac arrhythmia; 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.

Storage conditions:

List B. To store at a temperature of 15 ° -25 °C, in the place, unavailable to children. Period of validity: 5 years. Not to use after a period of validity, mazanny on packaging!

Issue conditions:

According to the recipe

Packaging:

On 50 tablets in the bottle from dark glass corked by the screw-on cover from polypropylene under which the laying with a ring for a separation providing control of the first opening is built in. A part of the label is attached to a bottle by a special adhesive tape which allows to raise the label. The application instruction is made in the form of the developing leaf placed under a mobile part of the label.