Amitriptyline-AKOS - instructions for use, dose, side effects, contraindications

Excipients: dextrose monohydrate (glucose monohydrate, glucose (C * PharmDex)), sodium chloride, benzethonium chloride (benzethonium chloride), water for injection.

Description:

Transparent colorless or slightly yellowish solution.

Pharmacotherapeutic group:Antidepressant

ATX: & nbsp

N.06.A.A.09 Amitriptyline

Pharmacodynamics:

Antidepressant (tricyclic antidepressant). It also has some analgesic (central genesis), H2-histamine-blocking and antiserotonin action, contributes to the elimination of urinary incontinence and reduces appetite.

Has a strong peripheral and central anticholinergic action due to high affinity for m-holinoretseptoram; a strong sedative effect associated with affinity for H1-histamine receptors, and alpha-adrenoblocking action. Has the properties of antiarrhythmic drug (LS) subgroup 1a, similar to quinidine in therapeutic doses, slows the ventricular conduction (with an overdose can cause severe intraventricular blockade).

The mechanism of antidepressant action is associated with an increase in the concentration of norepinephrine in synapses and / or serotonin in the central nervous system (CNS) (reducing their reverse absorption).Accumulation of these neurotransmitters occurs as a result of inhibition of their inverse capture by the membranes of presynaptic neurons. With prolonged use reduces the functional activity of beta-adrenergic and serotonin receptors in the brain, normalizes adrenergic and serotonergic transmission, restores the balance of these systems, disturbed in depressive states. With anxiety-depressive states reduces anxiety, agitation and depressive manifestations.

The mechanism of antiulcer action is due to the ability to block H2-histamine receptors in the parietal cells of the stomach, as well as to have sedative and m-holin-blocking effects (in stomach ulcer and duodenal ulcer relieves pain, promotes the healing of ulcers).

Efficacy in bedwetting due, apparently, anticholinergic activity, leading to an increase in bladder capacity stretchability, direct beta-adrenergic stimulation, the activity of alpha-adrenergic agonists, is accompanied by an increase in sphincter tone, and central serotonin reuptake blockade.

Has a central analgesic effect, which is believed to be associated with changes in the concentration of monoamines in the central nervous system, especially serotonin, and influence on endogenous opioid systems.

The mechanism of action for bulimia nervosa is unclear (it may be similar to that in depression). It shows a distinct effect of the drug with bulimia in patients with both depression and its presence, while a decrease in bulimia can be noted without the concomitant weakening of depression itself.

When general anesthesia reduces blood pressure (BP) and body temperature. Does not inhibit monoamine oxidase (MAO).

Antidepressant action develops within 2-3 weeks after the beginning of application.

Pharmacokinetics:

Absorption is high. Bioavailability of amitriptyline for various routes of administration is 30-60 %, its active metabolite - nortriptyline - 46-70%. The connection with plasma proteins is 96%. The maximum concentration in the blood plasma (Cmah) - 0.04-0.16 μg / ml. The volume of distribution is 5-10 l / kg. Therapeutic blood concentrations for amitriptyline are 50-250 ng / ml, for nortriptyline 50-150 ng / ml. It easily passes (including nortriptyline) through the histohematetic barriers, including the blood-brain barrier (GEB), the placental barrier, penetrates into breast milk.

Metabolized in the liver with the participation of the enzyme system CYP_2C19, SRM_2D6, has the effect of "first passage" (by demethylation, hydroxylation, N-oxidation) with the formation of active metabolites - nortriptyline, 10-hydroxy-amitriptyline - and inactive metabolites. It is excreted by the kidneys (mainly in the form of metabolites) - 80 % for 2 weeks and partly with calves. The half-life of blood plasma (T_1/2) amitriptyline - 10-26 h, nortriptyline - 18-44 h.

Indications:

Depression (especially with anxiety, agitation and sleep disorders, including in childhood, endogenous, involutional, reactive, neurotic, drug-induced, with organic brain lesions, alcohol withdrawal), schizophrenic psychoses, mixed emotional disorders, behavioral disorders and attention), nocturnal enuresis (except for patients with bladder hypotension), bulimia nervosa, chronic pain disorders, including neurogenic nature, headache, migraine (prophylaxis), ulcer disease udka and 12 duodenal ulcer (in complex therapy).

Contraindications:

- PTreatment with MAO inhibitors and 2 weeks before treatment;

- myocardial infarction (acute and subacute periods);

- acute alcohol intoxication;

- acute intoxication with hypnotics, analgesics and psychoactive drugs (LS);

- angle-closure glaucoma,

- severe violations of atrioventricular (AV) and intraventricular conduction (blockade of the legs of the bundle of His, AV blockade II - III century);

- lactation period;

- children's age till 12 years;

- hypersensitivity to amitriptyline.

Carefully:

Chronic alcoholism, bronchial asthma, manic-depressive psychosis, oppression of bone marrow hematopoiesis, diseases of the cardiovascular system (CVS) (angina pectoris, arrhythmia, AV blockade of the I st. heart failure, chronic heart failure (CHF), myocardial infarction, postinfarction cardiosclerosis, arterial hypertension), stroke, decreased motor function of the gastrointestinal tract (risk of paralytic intestinal obstruction), intraocular hypertension, hepatic and / or renal insufficiency, thyrotoxicosis, prostatic hyperplasia, delay urine, bladder hypotension, schizophrenia (possible activation of psychosis), epilepsy, pregnancy (especially I trimester), advanced age.

Pregnancy and lactation:

Dosing and Administration:

Intramuscularly (i / m).

In / m in a dose of 20-40 mg 4 times a day, gradually replacing the intake. Duration of treatment - no more than 6-8 months.

Children over 12 years of age and elderly people are given lower doses and increase them more slowly.

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

Side effects:

Anticholinergic effects: blurred vision, paralysis of accommodation, mydriasis, increased intraocular pressure (only in individuals with local anatomical predisposition - narrow angle of anterior chamber), tachycardia, dry mouth, confusion (delirium or hallucinations), constipation, paralytic intestinal obstruction, difficulty urinating, decreased sweating.

From the nervous system: drowsiness, asthenia, fainting, anxiety, disorientation, hallucinations (especially in elderly patients and patients with Parkinson's disease), anxiety, agitation, motor anxiety, manic state, hypomanic state, aggressiveness, memory impairment, depersonalization, increased depression,loss of ability to concentrate attention, insomnia, nightmarish dreams, yawning, activation of symptoms of psychosis, headache, myoclonus, dysarthria, tremor of small muscles, especially hands, hands, head and tongue, peripheral neuropathy (paresthesia), myasthenia gravis, ataxia, extrapyramidal syndrome, increased and increased epileptic seizures, changes in the electroencephalogram (EEG).

On the part of the CAS: tachycardia, palpitation, dizziness, orthostatic hypotension, nonspecific changes on the ECG, (interval S-T or T wave) in patients not suffering from heart disease; arrhythmia, lability of blood pressure (decrease or increase in blood pressure), violation of intraventricular conduction (expansion of the complex QRS, interval changes P-Q, blockade of the legs of the bundle of His).

From the digestive system: nausea, rarely - hepatitis (including liver dysfunction and cholestatic jaundice), heartburn, vomiting, gastralgia, increased appetite and body weight or decreased appetite and body weight, stomatitis, taste change, diarrhea, darkening of the tongue.

From the endocrine system: an increase in the size (edema) of the testicles,gynecomastia; an increase in the size of the mammary glands, galactorrhea; decreased or increased libido, decreased potency, hypo- or hyperglycemia, hyponatremia (decreased vasopressin production), and syndrome of inadequate secretion of antidiuretic hormone (ADH).

On the part of the organs of hematopoiesis: agranulocytosis, leukopenia, thrombocytopenia, purpura, eosinophilia.

Allergic reactions: skin rash, itchy skin, hives, photosensitization, swelling of the face and tongue.

Other: hair loss, tinnitus, edema, hyperpyrexia, enlarged lymph nodes, urinary retention, pollakiuria, hypoproteinemia.

Symptoms of withdrawal: with sudden cancellation after prolonged treatment - nausea, vomiting, diarrhea, headache, malaise, sleep disturbances, unusual dreams, unusual arousal; with a gradual cancellation after a long treatment - irritability, motor anxiety, sleep disturbances, unusual dreams.

Connection with the drug is not established: lupus-like syndrome (migratory arthritis, the appearance of antinuclear antibodies and a positive rheumatoid factor), a violation of liver function, agevia.

Overdose:

Symptoms:

From the side of the central nervous system: drowsiness, stupor, coma, ataxia, hallucinations, anxiety, psychomotor agitation, decreased ability to concentrate, disorientation, confusion, dysarthria, hyperreflexia, rigidity of muscles, choreoathetosis, epileptic syndrome.

On the part of the CAS: decrease in arterial pressure (BP), tachycardia, arrhythmia, intracardiac conduction disturbance, changes in the electrocardiogram (ECG), characteristic for intoxication with tricyclic antidepressants (especially QRS), shock; in very rare cases - cardiac arrest.

Other: respiratory depression, dyspnea, cyanosis, vomiting, hyperthermia, mydriasis, increased sweating, oliguria or anuria.

Symptoms develop 4 hours after an overdose, peak at 24 hours and last 4-6 days. If a suspected overdose, especially in children, the patient should be hospitalized.

Treatment: symptomatic and supportive therapy; with severe anticholinergic effects (lowering blood pressure, arrhythmia, coma, myoclonic seizures) - the administration of cholinesterase inhibitors (the use of physostigmine is not recommended because of the increased risk of seizures); maintenance of blood pressure and water-electrolyte balance.Control of CAS functions (including ECG) is shown for 5 days (relapse may occur after 48 hours and later), anticonvulsant therapy, artificial lung ventilation (ALV) and other resuscitation measures.

Hemodialysis and forced diuresis are ineffective.

Interaction:

With the combined use of ethanol and drugs, depressing the central nervous system (including other antidepressants, barbiturates, benzodiazepines and general anesthetics), a significant increase in the inhibitory effect on the central nervous system, respiratory depression and hypotensive effect.

Increases sensitivity to drinks containing ethanol.

Increases the anticholinergic effect of drugs with anticholinergic activity (eg phenothiazines, antiparkinson drugs, amantadine, atropine, biperiden, antihistamine drugs), which increases the risk of side effects (from the central nervous system, vision, intestine and bladder).

When combined with antihistamine drugs, clonidine - increased oppressive effect on the central nervous system; with atropine - increases the risk of paralytic intestinal obstruction; with drugs that cause extrapyramidal reactions - an increase in the severity and frequency of extrapyramidal effects.

With the simultaneous use of amitriptyline and indirect anticoagulants (coumarin derivatives or indadion), an increase in anticoagulant activity of the latter is possible.

Amitriptyline may increase depression caused by glucocorticosteroids (GCS).

When combined with anticonvulsant drugs, it is possible to increase the oppressive effect on the central nervous system, reduce the threshold of convulsive activity (when used in high doses), and reduce the effectiveness of the latter.

Drugs for the treatment of thyrotoxicosis increase the risk of agranulocytosis.

Reduces the effectiveness of phenytoin and alpha-blockers.

Inhibitors of microsomal oxidation (cimetidine) extend T_1/2, increase the risk of developing toxic effects of amitriptyline (a 20-30% dose reduction may be required), inducers of microsomal liver enzymes (barbiturates, carbamazepine, phenytoin, nicotine and oral contraceptives) reduce plasma concentrations and reduce the effectiveness of amitriptyline.

Fluoxetine and fluvoxamine increase the concentration of amitriptyline in plasma (may require a decrease in the dose of amitriptyline by 50%).

When combined with holinoblokatorami, phenothiazines and benzodiazepines - mutual enhancement of sedative and central cholinoblocking effects and increased risk of epileptic seizures (lowering the threshold of convulsive activity); phenothiazines, in addition, may increase the risk of neuroleptic malignant syndrome.

With the simultaneous use of amitriptyline with clonidine, guanethidine, betanidine, reserpine and methyldopa - reducing the hypotensive effect of the latter; with cocaine - the risk of arrhythmia of the heart.

Estrogen-containing oral contraceptive drugs and estrogens can increase the bioavailability of amitriptyline; antiarrhythmic drugs (such as quinidine) increase the risk of developing rhythm disturbances (possibly slowing the metabolism of amitriptyline).

Joint use with disulfiram and other inhibitors of adetaldehydrogenase provokes delirium.

Incompatible with MAO inhibitors / there may be an increase in the frequency of periods of hyperopyrexia, severe seizures, hypertensive crises and death of the patient.

Pimozide and probucol may increase cardiac arrhythmias, which is manifested in the lengthening of the interval Q-T on the ECG.

It enhances the effect of the SCA epinephrine, norepinephrine, isoprenaline, ephedrine and phenylephrine (including when these drugs are part of the local anesthetic) and increases the risk of cardiac arrhythmias, tachycardia, severe hypertension.

When co-administered with alpha-adrenostimulants for intranasal administration or for use in ophthalmology (with significant systemic absorption), the vasoconstrictor effect of the latter may be enhanced.

With a joint admission with thyroid hormones - a mutual enhancement of the therapeutic effect and toxic effects (include cardiac arrhythmias and a stimulating effect on the central nervous system).

M-holinoblokatory and antipsychotic drugs (neuroleptics) increase the risk of hyperpyrexia (especially in hot weather).

When co-administered with other hematotoxic drugs, an increase in hematotoxicity is possible.

Special instructions:

Before the start of treatment, it is necessary to control blood pressure (in patients with low or labile blood pressure it can decrease even more); in the period of treatment - control of peripheral blood (in some cases, agranulocytosis,in connection with which it is recommended to monitor the blood picture, especially with an increase in body temperature, the development of influenza-like symptoms and sore throats), with prolonged therapy - monitoring the functions of the CCC and liver. The elderly and patients with SSS diseases are shown control over the number of heartbeats (heart rate), blood pressure, and ECG. On the ECG, the appearance of clinically insignificant changes (smoothing of the tooth G, depression of the segment S-T, expansion of the complex QRS).

The use of the drug is possible only in a hospital, under the supervision of a doctor, with the observance of bed rest during the first days of therapy.

Care must be taken when jumping to a vertical position from the "lying" or "sitting" position.

During the treatment should be excluded from the use of ethanol.

Assign no earlier than 14 days after the abolition of MAO inhibitors, starting with small doses.

With a sudden discontinuation after long-term treatment, the syndrome of "withdrawal" may develop.

Amitriptyline in doses above 150 mg / day reduces the threshold of convulsive activity (it should take into account the risk of epileptic attacks in predisposed patients, as well as in the presence of other factors predisposing to the onset of convulsive syndrome, for example, brain damage of any etiology,simultaneous use of antipsychotic drugs (neuroleptics), in the period of rejection of ethanol or withdrawal of drugs that have anticonvulsant properties, for example, benzodiazepines).

Depression is characterized by the risk of suicidal actions, which can persist until a significant remission is achieved. In this regard, at the beginning of treatment, a combination with drugs from the benzodiazepine group or neuroleptic medicines and constant medical supervision (entrusting trusted persons with storage and dispensing of drugs) can be indicated.

In patients with cyclical affective disorders in the period of the depressive phase, manic or hypomanic conditions may develop on the background of therapy (dose reduction or drug withdrawal and antipsychotic drug administration are necessary). After the relief of these conditions, if there are indications, treatment at low doses can be resumed.

Due to possible cardiotoxic effects, care must be taken when treating patients with thyrotoxicosis or patients receiving thyroid hormone preparations.

In combination with electroconvulsive therapy is prescribed only under the condition of careful medical supervision.

At predisposed patients and patients of advanced age can provoke the development of drug psychoses, mainly at night (after the drug is withdrawn for several days).

May cause paralytic intestinal obstruction, mainly in patients with chronic constipation, the elderly or in patients who are obliged to comply with bed rest.

Before conducting general or local anesthesia, an anesthesiologist should be warned that the patient is taking amitriptyline.

Due to the anticholinergic effect, tearing can be reduced and the relative amount of mucus in the tear fluid can be increased, which can damage the epithelium of the cornea in patients using contact lenses.

With prolonged use, there is an increase in the frequency of tooth decay. The need for riboflavin may be increased.

The study of reproduction on animals has revealed an unfavorable effect on the fetus, and adequate and strictly controlled studies in pregnant women have not been conducted. In pregnant women, the drug should be used only if the intended benefit to the mother exceedspotential risk to the fetus.

Penetrates into breast milk and can cause drowsiness in infants.

In order to avoid the syndrome of "cancellation" in neonates (manifested by shortness of breath, drowsiness, intestinal colic, irritability, hypotension or hypertension, tremor or spastic phenomena) receiving amitriptyline gradually canceled at least 7 weeks before the expected birth.

Children are more sensitive to acute overdose, which should be considered dangerous and potentially fatal for them.

Effect on the ability to drive transp. cf. and fur:

During the period of treatment must be careful when driving and other lesson. Potentially hazardous activities that require high concentration and psychomotor speed reactions.

Form release / dosage:Solution for intramuscular injection 10 mg / ml.

Packaging:

2 ml into ampoules of colorless neutral glass HC-3.

10 ampoules are placed in boxes of cardboard.

5 ampoules are placed in contoured cell packs.

1, 2 contour squares are placed in packs of cardboard.

In each pack, the box is attached instructions for use, the ampullar scarifier.

Ampoule scapper does not invest when using ampoules with a kink ring or with an incision and a point.

Storage conditions:

In a dry, dark place at a temperature of 15 to 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years. Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:P N002755 / 01

Date of registration:30.11.2009

Expiration Date:Unlimited

The owner of the registration certificate:SYNTHESIS, JSC Joint-stock Kurgan Society of Medical Preparations and Products SYNTHESIS, JSC Joint-stock Kurgan Society of Medical Preparations and Products Russia

Manufacturer: & nbsp

SYNTHESIS, OJSC Russia

Representation: & nbspSYNTHESIS JSC Joint-Stock Kurgan Society of Medical Preparations and Products SYNTHESIS JSC Joint-Stock Kurgan Society of Medical Preparations and Products Russia

Information update date: & nbsp13.09.2017

Illustrated instructions

Instructions

Amitriptyline-AKOS (Amitriptyline-AKOS)