Amitriptilin-Grindeks
Producer: AS Grindex (JSC Grindeks) Latvia
Code of automatic telephone exchange: N06AA09
Release form: Firm dosage forms. Tablets.
General characteristics. Structure:
Active ingredient: 10 mg or 25 mg of amitriptyline.
Excipients: lactoses monohydrate, povidone, silicon dioxide, magnesium stearate, starch corn.
Cover of 10 mg: Opadry II Blue 85 F 20753 dye, karnaubsky wax.
Cover of 25 mg: Opadry II Yellow 85 F 22450 dye, karnaubsky wax.
Antidepressive, sedative, anti-dysuric means.
Pharmacological properties:
Pharmacodynamics. Antidepressant from group of tricyclic connections, derivative a dibenzotsiklogeptadina.
The mechanism of antidepressive action is connected with increase in concentration of noradrenaline in synapses and/or serotonin in TsNS due to oppression of the return neyronalny capture of these mediators. At prolonged use reduces functional activity of β-adrenoceptors and serotoninovy receptors of a brain, normalizes adrenergic and serotonergic transfer, recovers the balance of these systems broken at depressions. At alarming depressions reduces alarm, agitation and depressive manifestations.
Has also some analgeziruyushchy effect which as believe, can be connected with changes of concentration of monoamines in TsNS, especially serotonin, and influence on endogenous opioid systems.
Possesses the expressed peripheral and central anticholinergic action caused by high affinity to m-holinoretseptoram; the strong sedation connected with affinity to histamine H1 receptors and alpha and adrenoceptor blocking action.
Action has antiulcerous effect which mechanism is caused by ability to block histamine H2 receptors in covering cells of a stomach, and also to render sedative and m-holinoblokiruyushchee (at a peptic ulcer of a stomach and duodenum reduces a pain syndrome, promotes acceleration of healing of an ulcer).
Efficiency at bed wetting is caused, apparently, by the anticholinergic activity leading to increase in ability of a bladder to stretching, direct β-adrenergic stimulation, activity of α-adrenoceptors of agonists, followed increase in a tone of a sphincter and the central blockade of serotonin reuptake.
The mechanism of therapeutic action at nervous bulimia is not installed (it is perhaps similar to that at a depression). Clear efficiency of amitriptyline at bulimia at patients is shown both without depression, and at its existence, at the same time decrease in bulimia can be noted without the accompanying easing of the depression.
When carrying out the general anesthesia reduces the ABP and body temperature. Does not inhibit MAO.
Antidepressive action develops within 2-3 weeks after the beginning of use.
Pharmacokinetics. Bioavailability of amitriptyline at various ways of introduction - 30-60%, its active metabolite of a nortriptilin - 46-70%. Time of achievement of the maximum concentration (Tmax) 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. The maximum concentration in a blood plasma (Cmax) of-0,04-0,16 mkg/ml.
Passes through gistogematichesky barriers, including 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 of blood from 10 to 28 hours for amitriptyline and from 16 to 80 hours for a nortriptilin. It is allocated with kidneys - 80%, partially with bile. Full removal within 7-14 days. Amitriptyline gets through a placental barrier, is emitted in breast milk in the concentration similar plasma.
Indications to use:
Depressions (especially with alarm, agitation and sleep disorders, including at children's age, endogenous, involutional, reactive, neurotic, medicinal, at organic lesions of a brain, alcoholic abstinence), schizophrenic psychoses, the mixed emotional frustration, behavior disorders (activity and attention), night enuresis (except for patients with bladder hypotonia), nervous bulimia, a chronic pain syndrome (chronic pains at oncological patients, migraine, rheumatic diseases, atypical pains in a face, post-herpetic neuralgia, a posttraumatic neuropathy, diabetic or other peripheral neuropathy), a headache, migraine (prevention), a peptic ulcer of a stomach and a 12-perstny gut.
Route of administration and doses:
Features of use:
The concomitant use with MAO inhibitors can lead to a lethal outcome.
Having rummaged in treatment between reception of MAO inhibitors and amitriptyline (and other tricyclic antidepressants) has to make not less than 14 days.
Amitriptyline in a dose higher than 150 mg/days reduces a threshold of convulsive activity therefore the risk of developing of convulsive attacks at patients with those in the anamnesis increases.
For the period of treatment the driving of vehicles, service of mechanisms and other types of works requiring special attention is forbidden.
Treatment of elderly patients needs to be controlled carefully, applying the minimum doses of drug, raising them gradually.
Transition from a depressive phase of maniac-depressive psychosis to a maniacal stage is possible.
If the condition of the patient does not improve within 3–4 weeks, further therapy is inexpedient.
Side effects:
Caused by blockade of peripheral m-holinoretseptorov: dryness in a mouth, an urination delay, a lock, intestinal impassability, a vision disorder, accommodation paresis, increase in intraocular pressure, the strengthened sweating.
From a nervous system and sense bodys: a headache, dizziness, an ataxy, increased fatigue, weakness, irritability, drowsiness, an insomniya, dreadful dreams, motive excitement, a tremor, paresthesia, peripheral neuropathy, changes on EEG, disturbance of concentration of attention, a dysarthtia, confusion of consciousness, a hallucination, a sonitus.
From cardiovascular system: tachycardia, orthostatic hypotension, arrhythmia, lability of the ABP, expansion of the QRS complex on an ECG (disturbance of intra ventricular conductivity), symptoms of heart failure, a faint, change of a picture of blood, including an agranulocytosis, a leukopenia, an eosinophilia, thrombocytopenia, a purpura.
From bodies of a GIT: nausea, vomiting, heartburn, anorexia, a sensation of discomfort in epigastriums, a gastralgia, increase in activity of hepatic transaminases, stomatitis, taste disturbance, darkening of language.
From a metabolism: galactorrhoea, change of secretion of ADG; seldom — hypo - or a hyperglycemia, disturbance of tolerance to glucose.
From urinogenital system: change of a libido, potentiality, hypostasis of testicles, glucosuria, pollakiuria.
Allergic reactions: skin rash, itch, Quincke's disease, small tortoiseshell.
Others: increase in the sizes of mammary glands at women and men, a hair loss, a hyperadenosis, a photosensitization, increase in body weight (at prolonged use), a withdrawal: a headache, nausea, vomiting, diarrhea, irritability, a sleep disorder with bright, unusual dreams, a hyperexcitability (after prolonged treatment, especially in high doses, at the sharp termination of administration of drug).
Interaction with other medicines:
At simultaneous use with the drugs exerting the oppressing impact on TsNS, perhaps considerable strengthening of the oppressing action on TsNS, hypotensive action, respiratory depression.
At simultaneous use with the drugs having anticholinergic activity strengthening of anticholinergic effects is possible.
At simultaneous use strengthening of action of sympathomimetic funds for cardiovascular system and increase in risk of development of disturbances of a cordial rhythm, tachycardia, heavy arterial hypertension is possible.
At simultaneous use with antipsychotic means (neuroleptics) metabolism is mutually oppressed, at the same time there is a reduction of the threshold of convulsive readiness.
At simultaneous use with anti-hypertensive means (except for a clonidine, a guanetidin and their derivatives) strengthening of anti-hypertensive action and risk of development of orthostatic hypotension is possible.
At simultaneous use with MAO inhibitors development of hypertensive crisis is possible; with a clonidine, guanetidiny - reduction of hypotensive action of a clonidine or guanetidin is possible; with barbiturates, carbamazepine - reduction of effect of amitriptyline owing to increase in his metabolism is possible.
The case of development of a serotoninovy syndrome at simultaneous use with sertraline is described.
At simultaneous use with sukralfaty amitriptyline absorption decreases; with fluvoksaminy - concentration of amitriptyline in a blood plasma and risk of development of toxic action increases; with fluoxetine - concentration of amitriptyline in a blood plasma increases and toxic reactions owing to oppression of an isoenzyme of CYP2D6 under the influence of fluoxetine develop; with quinidine - amitriptyline metabolism delay is possible; with Cimetidinum - amitriptyline metabolism delay, increase in its concentration in a blood plasma and development of toxic effects is possible.
At simultaneous use with ethanol effect of ethanol, especially during the first several days of therapy amplifies.
Contraindications:
Overdose:
Symptoms: drowsiness, disorientation, confusion of consciousness, expansion of pupils, fervescence (fever), asthma, dysarthtia, excitement, hallucinations, convulsive attacks, muscle tension, stupor, coma, vomiting, arrhythmia, arterial hypotension, heart failure, respiratory depression.
Treatment: the therapy termination, a gastric lavage, infusion of liquid, in oil or in/in administration of physostigmine of 1-3 mg each 0,5–2 h (to children administration of physostigmine begin 0,5 mg with a dose, 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 should be applied only at a coma, respiratory depression and other heavy disturbances; 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:
In the dry, protected from light place, at a temperature not above 25 °C, in the place, unavailable to children.
Issue conditions:
According to the recipe
Packaging:
On 10 tablets in the blister from PVC/Al. On 5 blisters in cardboard packaging together with the instruction.
