AMITRIPTYLINE

Active material: Amitriptyline
When ATH: N06AA09
CCF: Antidepressant
ICD-10 codes (testimony): F32
When CSF: 02.02.01
Manufacturer: ALSI Pharma Company Inc. (Russia)

Pharmaceutical form, composition and packaging

Pills from white to white with a slightly yellowish brown color, ploskotsilindricheskoy form, chamfered.

Excipients: potato starch, lactose, gelatin, colloidal silicon dioxide (aэrosyl), talc, magnesium stearate.

10 PC. – packings Valium planimetric (1) – packs cardboard.
10 PC. – packings Valium planimetric (2) – packs cardboard.
10 PC. – packings Valium planimetric (3) – packs cardboard.
10 PC. – packings Valium planimetric (4) – packs cardboard.
10 PC. – packings Valium planimetric (5) – packs cardboard.
100 PC. – plastic jars (1) – packs cardboard.

Pharmacological action

Antidepressant from a group of tricyclic compounds, dibenzociklogeptadina derivative.

Antidepressive action associated with higher concentrations of norepinephrine in synapses and/or serotonin in the central nervous system through oppression reverse takeover neironalnogo these mediators. With long-term use reduces the functional activity of β-adrenergic and serotonin receptors in the brain, normalizes and adrenergic serotoninergicescuu transfer, Restores the balance of these systems, breached the depressed conditions. When anxiety-depression reduces anxiety, ajitatia and depressive manifestations.

Also has some analgesic effect, which, believed, may be associated with changes in the concentrations of Monoamines in the CNS, especially serotonin, and the effect on the endogenous opioid system.

Has a pronounced peripheral and Central antiholinergicakim action, owing to high affinity to m-holinoreceptoram; a strong sedative effect, associated with an affinity for gistaminovm H₁-Receptor, and Alpha-adrenoblokirutm action.

Provides protivoyazvennoe action, mechanism which is due to the ability to block gistaminove (H)₂-receptor parietalnah in stomach cells, as well as providing sedative and m-holinoblokirtee effect (When ulcers stomach and duodenal ulcers reduces pain syndrome, accelerates healing of ulcers).

Effective in bedwetting due, apparently, antiholinergičeskoj activity, for improving the capacity of the bladder to stretch, direct β-adrenergic stimulation, α-adrenoceptor agonist activity, accompanied by increased tone of the sphincter and Central blockade of serotonin.

Mechanism of therapeutic action when nervous bulimia is not installed (perhaps similar to that in depression). Shows clear effectiveness of amitriptyline in bulimia patients without depression, and when available, the reduced amount of bulimia can be observed without a concomitant loosening the depression.

During general anaesthesia reduces ad and body temperature. Not ingibiruet Mao.

Antidepressive effects develops over 2-3 weeks after the beginning of.

Pharmacokinetics

Bioavailability amitriptilina is 30-60%. Plasma protein binding 82-96%. V_d – 5-10 l / kg. Metabolised education active metabolita nortriptilina.

T_1/2 – 31-46 no. Report mostly kidneys.

Testimony

Depression (especially with anxiety, ajitaciei and sleep disorders, incl. childhood, endogenous, involutional, reaktivnaя, neurotic, drug, with organic brain lesions, alcohol withdrawal), schizophrenic psychoses, mixed emotional disorders, behavioral disturbances (activity and attention), nocturnal enuresis (with the exception of patients with hypotension bladder), nervnaya bulimia, chronic pain syndrome (chronic pain in cancer patients, migraine, rheumatic pain, atypical facial pain, postgerpeticheskaya neuralgia, Posttraumatic neuropathy, diabetic neuropathy, perifericheskaya neuropathy), prevention of migraine, gastric ulcer and duodenal ulcer.

Dosage regimen

For the reception inside, the initial dose is 25-50 mg at night. Then for 5-6 days dose increase to individually 150-200 mg / day (most of the doses are taken at night). If during the second week of no improvement, the daily dose to 300 mg. The disappearance of signs of depression reduces the dose to 50-100 mg/day and continue therapy at least 3 Months. In elderly patients with light violations dose is 30-100 mg / day, usually 1 time / day at night, After therapeutic effect moving towards the minimum effective dose – 25-50 mg / day.

When night enuresis in children 6-10 years – 10-20 mg/day to night, aged 11-16 years – 25-50 mg / day.

/ M – starting dose is 50-100 mg / day 2-4 introduction. If necessary, the dose can be gradually increased to 300 mg / day, in exceptional cases – to 400 mg / day.

Side effect

From the central and peripheral nervous system: drowsiness, asthenia, fainting, anxiety, disorientation, excitation, hallucinations (particularly in elderly patients and in patients with Parkinson's disease), anxiety, restlessness, maniacal State, elated state, aggressiveness, memory impairment, depersonalization, increased depression, decreased ability to concentrate, insomnia, nightmares, zevota, activating the symptoms of psychosis, headache, myoclonus, dysarthria, tremor (especially hands, heads, language), perifericheskaya neuropathy (paresthesia), myasthenia, myoclonus, ataxia, extrapyramidal syndrome, and increased frequency of epileptic seizures, EEG changes.

Cardio-vascular system: orthostatic hypotension, tachycardia, conduction disorders, dizziness, nonspecific ECG changes (the interval ST or T wave inversion), arrhythmia, labile blood pressure, violation of intraventricular conduction (extension of the QRS complex, change the interval PQ, bundle-branch block).

From the digestive system: nausea, heartburn, vomiting, gastralgia, increased or decreased appetite (increase or reduction of body weight), stomatitis, change in taste, diarrhea, darkening of the language; rarely – abnormal liver function, cholestatic jaundice, hepatitis

On the part of the endocrine system: swelling testicle, gynecomastia, breast enlargement, galactorrhea, changes in libido, reduced potency, Hypo- or hyperglycemia, giponatriemiya (reduced production of vasopressin), syndrome of inappropriate secretion of ADH.

From the hematopoietic system: agranulocytosis, leukopenia, thrombocytopenia, purpura, eozinofilija.

Allergic reactions: skin rash, itching, hives, photosensitivity, swelling of the face and tongue.

Effects, due to anticholinergic activity: dry mouth, tachycardia, accommodation disturbances, blurred vision, midriaz, increased intraocular pressure (only in patients with narrow-angle of the anterior Chamber of the eye), constipation, paralysis occlusion, urinary retention, decreased sweating, confusion, delirium or hallucinations.

Other: hair loss, noise in ears, swelling, hyperpyrexia, hyperadenosis, thamuria, hypoproteinemia.

Contraindications

Acute period and early recovery period after myocardial infarction, acute alcohol intoxication, acute intoxication pills, analgesic and psychoactive drugs, zakrыtougolynaya glaucoma, severe violations of AV- and vnutrijeludockova conductivity (bundle-branch block, AV-blokada II degree), lactation, Children up to age 6 years (orally), Children up to age 12 years (for the/m and/in the), simultaneous treatment MAO inhibitors and period for 2 weeks before the start of their application, hypersensitivity to amitriptilino.

Pregnancy and lactation

Amitriptyline should not be used in pregnancy, especially in the I and III trimestrah, except in cases of emergency. Adequate and well-controlled clinical studies safety of amitriptyline during pregnancy has not been.

Is the breast milk and may cause drowsiness in infants.

Admission amitriptilina should gradually abolish, at least, for 7 weeks before the expected birth in order to avoid the development of withdrawal symptoms in a newborn.

IN experimental studies amitriptyline provided teratogenic effects.

Cautions

Be wary of CHD, Arrhythmia, blockades of the heart, Heart Failure, myocardial infarction, hypertension, stroke, alcoholism, thyrotoxicosis, While therapy thyroid drugs.

While therapy amitriptilinom there is a need for caution in a sharp move in the vertical position of the provisions “lying” or “sitting”.

In a dramatic admission may develop withdrawal symptoms.

Amitriptyline in doses more 150 mg/day reduces threshold sudorojna preparedness; account should be taken of the risk of epileptic seizures have predisposed patients, and the presence of other factors, increase the risk of development of convulsive syndrome (incl. When brain damage of any etiology, simultaneous use of antipsychotics, during the period of refraining from ethanol or cancellation of medicines, possessing the protivosudorojna activity).

It should be taken into account, that patients with depression possible suicidal attempt.

In combination with electroconvulsive therapy should only be used with careful medical supervision.

Prone patients and elderly patients can provoke development of medical illness, mostly at night (After the drug disappear within a few days).

Paralitičeskuû can cause intestinal obstruction, mainly in patients with chronic constipation, the elderly or in patients, compelled to observe bed rest.

Before the General or local anesthesia should warn the anesthesiologist about how, that the patient is taking amitriptyline.

With long-term use, there has been an increase in the frequency of caries. May increase the need for riboflavine.

Amitriptyline can apply not earlier than, than 14 days after discontinuation of MAO inhibitors.

It should not be used in conjunction with the adreno- and sympathomimetic, incl. with epinephrine, ephedrine, isoprenalin, norepinephrine, phenylephrine, fenilpropanolaminom.

Be wary used in conjunction with other drugs, okazыvayushtimi antiholinergicheskoe action.

At the time of admission amitriptilina avoid alcohol.

Effects on ability to drive vehicles and management mechanisms

During the period of treatment should refrain from potentially hazardous activities, requiring attention and quick emotional reactions.

Drug Interactions

In an application with drugs, have a depressing effect on the central nervous system, possibly significant strengthening of oppressive action on the central nervous system, gipotenzivnogo actions, respiratory depression.

In an application with drugs, having anticholinergic activity, Perhaps increased anticholinergic effects.

While use may increase in the simpatomimeticakih funds on the cardiovascular system and increase the risk of heart rhythm disorders, tachycardia, severe hypertension.

While the use of antipsychotics (neuroleptics) mutually oppressed metabolism, This is lowering the threshold sudorojna preparedness.

If you are applying with antigipertenzivei means (with the exception of clonidine, guanetidina and their derivatives) antigipertenzivnogo actions and possibly increasing the risk of orthostatic hypotension.

Together with the use of MAO inhibitors may develop gipertoniceski kriza; with clonidine, guanethidine – hypotensive action of clonidine may reduce or guanetidina; barbiturates, karʙamazepinom – may reduce action amitriptilina by raising its metabolism.

Case development of serotonin syndrome when it overlaps with sertralinom.

Together with the use of sukralfatom decreases absorption amitriptilina; with fluvoxamine – concentrations amitriptilina plasma and the risk of toxic effects; fluoxetine – concentrations amitriptilina plasma and develop toxic reaction as a result of oppression izofermenta CYP2D6 under influence of fluoxetine; with quinidine – may slow the metabolism of amitriptyline; with cimetidine – may slow the metabolism of amitriptyline, increase its concentration in the blood plasma and the development of toxic effects.

Together with the use of ethanol is enhanced by the action of ethanol, especially during the first few days of therapy.