Amitriptyline injections. Amitriptyline and funds based on it: indications, instructions, reviews

Date: 23.06.2020

Instructions for medical use

medicinal product

AMITRIPTILINE-AKOS

Tradename

Amitriptyline-AKOS

International non-proprietary name

Amitriptyline

Dosage form

Solution for injection, 20 mg / 2 ml

1 ml of solution contains active substance - amitriptyline hydrochloride (in terms of amitriptyline) 10 mg,

excipients: glucose monohydrate, sodium chloride, benzethonium chloride, water for injection

Description

Transparent colorless or slightly yellowish solution

Pharmacotherapeutic group

Psychoanaleptics. Antidepressants. Monoamine reuptake inhibitors are non-selective. Amitriptyline

ATX code N06AA09

Pharmacological properties

Pharmacokinetics

Absorption is high. The bioavailability of amitriptyline for various routes of administration is 30-60%, its active metabolite, nortriptyline, is 46-70%. Communication with plasma proteins - 96%. The maximum concentration in blood plasma (Cmax) is 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. Easily passes (including nortriptyline) through the histohematological barriers, including the blood-brain barrier (BBB), the placental barrier, and penetrates into breast milk.

It is metabolized in the liver with the participation of the enzyme system CYP 2 C 19, CYP 2 D 6, has a "first pass" effect (by demethylation, hydroxylation, N-oxidation) with the formation of active metabolites - nortriptyline, 10-hydroxyamitriptyline - and inactive metabolites. It is excreted by the kidneys (mainly in the form of metabolites) - 80% in 2 weeks and partly with feces. Plasma half-life (T 1/2) of amitriptyline is 10-26 hours, nortriptyline is 18-44 hours.

Pharmacodynamics

Amitriptyline-AKOS is an antidepressant (tricyclic antidepressant). It also has some analgesic (central genesis), H2-histamine-blocking and antiserotonin effects, helps to eliminate bedwetting and reduces appetite.

It has a strong peripheral and central anticholinergic effect due to a high affinity for m-cholinergic receptors; strong sedative effect associated with an affinity for H1-histamine receptors, and alpha-adrenergic blocking action. It has the properties of an antiarrhythmic drug (MP) of subgroup Ia, like quinidine in therapeutic doses, it slows down ventricular conduction (in case of an overdose, it 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) (a decrease in their reabsorption). The accumulation of these neurotransmitters occurs as a result of inhibition of their reuptake by the membranes of presynaptic neurons. With prolonged use, it reduces the functional activity of beta-adrenergic and serotonin receptors of the naked brain, normalizes adrenergic and serotonergic transmission, restores the balance of these systems, disturbed in depressive conditions. In case of anxiety-depressive states, it reduces anxiety, agitation and depressive manifestations.

The antidepressant effect develops within 2-3 weeks after the start of use.

Indications for use

Severe depression

Depressive states (especially with anxiety, agitation and sleep disorders, endogenous, involutional, reactive, neurotic, medicinal, with organic brain lesions, alcohol withdrawal)

Mode of application and doses

Intramuscularly (i / m).

In / m at a dose of 20-40 mg 4 times a day, gradually replacing with oral administration. The duration of treatment is no more than 6-8 months.

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

Elderly patients are given lower doses and increase them more slowly.

Side effects

Often

Blurred vision, accommodation paralysis, increased intraocular pressure (only in individuals with a local anatomical predisposition - a narrow angle of the anterior chamber), dizziness,

Tachycardia, blood pressure lability (decrease or increase in blood pressure)

Dry mouth

Constipation, paralytic intestinal obstruction

Sometimes

Confusion of consciousness (delirium or hallucinations)

Difficulty urinating

Drowsiness, disorientation, hallucinations (especially in elderly patients and in patients with Parkinson's disease), agitation, restlessness, hypomania, memory impairment, decreased ability to concentrate, insomnia, "nightmares", headache, dysarthria, tremors of small muscles, especially arms, hands, head and tongue, peripheral neuropathy (paresthesias), ataxia, changes in the electroencephalogram (EEG), tinnitus,

Nausea, heartburn, vomiting, gastralgia, stomatitis, taste changes, darkening of the tongue

An increase in the size of the mammary glands, galactorrhea, a decrease or increase in libido, a decrease in potency, a syndrome of inadequate secretion of antidiuretic hormone (ADH), gynecomastia

Retention of urine

Rarely

Asthenia, fainting, anxiety, anxiety, manic state, yawning, aggressiveness, depersonalization, increased depression, activation of psychosis symptoms, myoclonus

Palpitations, nonspecific ECG changes, (interval S- T or prong T) in patients without heart disease, arrhythmia, orthostatic hypotension, impaired intraventricular conduction (expansion of the complex QRS, interval changes P- Q, bundle branch block)

Hepatitis (including increased activity of "liver" transaminases, abnormal liver function and cholestatic jaundice), increased appetite and body weight or decreased appetite and body weight, diarrhea

Increase in size (edema) of the testicles, hypo- or hyperglycemia, glucosuria, impaired glucose tolerance, hyponatremia (decreased production of vasopressin)

Agranulocytosis, leukopenia, thrombocytopenia, purpura, eosinophilia

Skin rash, itchy skin, hives, photosensitivity, swelling of the face and tongue

Hair loss, edema, hyperpyrexia, swollen lymph nodes,

Pollakiuria, hypoproteinemia

Very rarely

Mydriasis

Extrapyramidal syndrome, increased frequency and intensification of epileptic seizures

Withdrawal symptoms: with sudden withdrawal after long-term treatment - nausea, vomiting, diarrhea, headache, malaise, sleep disturbances, unusual dreams, unusual agitation; with gradual withdrawal after long-term treatment - irritability, motor restlessness, sleep disturbances, unusual dreams.

The connection with taking the drug has not been established: lupus-like syndrome (migratory arthritis, the appearance of antinuclear antibodies and positive rheumatoid factor), liver dysfunction, ageusia.

There have been reports of cases of suicidal thoughts or behavior during or after stopping treatment with amitriptyline. Patients over 50 years of age have an increased risk of bone fractures receiving selective serotonin reuptake inhibitors and tricyclic antidepressants.

Contraindications

Hypersensitivity to amitriptyline and auxiliary components of the drug

Application together with MAO inhibitors (monoamine oxidase) and 2 weeks before starting treatment

Myocardial infarction (acute and subacute periods), coronary heart disease

Acute alcohol intoxication

Acute intoxication with hypnotics, analgesic and psychoactive drugs

Closed-angle glaucoma

Epilepsy

Pyloric stenosis

Hyperplasia of the prostate

Paralytic intestinal obstruction

Atony of the bladder

Severe atrioventricular (AV) and intraventricular conduction disorders (bundle branch block, II-III degree AV block)

Pregnancy and lactation

Children and adolescents under 18 years of age

Drug interactions

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

Increases sensitivity to beverages containing ethanol.

Increases the anticholinergic effect of drugs with anticholinergic activity (for example, phenothiazines, antiparkinsonian drugs, amantadine, atropine, biperiden, antihistamines), which increases the risk of side effects (from the central nervous system, vision, intestines and bladder).

When used together with antihistamines, clonidine - an increase in the inhibitory 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 or indadione derivatives), an increase in the anticoagulant activity of the latter is possible.

Amitriptyline may increase depression induced by glucocorticosteroids (GCS).

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

Medicines for the treatment of thyrotoxicosis increase the risk of developing agranulocytosis.

Reduces the effectiveness of phenytoin and alpha-blockers.

Inhibitors of microsomal oxidation (cimetidine) lengthen T 1/2, increase the risk of developing toxic effects of amitriptyline (dose reduction by 20-30% may be required), inducers of microsomal liver enzymes (barbiturates, carbamazepine, phenytoin, nicotine and oral contraceptives) reduce plasma concentration and reduce the effectiveness of amitriptyline.

Fluoxetine and fluvoxamine increase the plasma concentration of amitriptyline (it may be necessary to reduce the dose of amitriptyline by 50%).

When used together with anticholinergics, phenothiazines and benzodiazepines - mutual enhancement of sedative and central anticholinergic effects and an increased risk of epileptic seizures (lowering the threshold of seizure 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 - a decrease in the hypotensive effect of the latter; with cocaine - the risk of developing cardiac arrhythmias.

Combined use with disulfiram and other acetaldehydrogenase inhibitors provokes delirium.

Incompatible with MAO inhibitors (an increase in the frequency of periods of hyperpyrexia, severe convulsions, hypertensive crises and patient death are possible).

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

Enhances the effect on CVS of epinephrine, norepinephrine, isoprenaline, ephedrine and phenylephrine (including when these drugs are part of local anesthetics) and increases the risk of developing cardiac arrhythmias, tachycardia, and severe arterial hypertension.

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

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

M-anticholinergics and antipsychotic drugs (antipsychotics) increase the risk of developing hyperpyrexia (especially in hot weather).

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

special instructions

Carefully: chronic alcoholism, bronchial asthma, manic-depressive psychosis, inhibition of bone marrow hematopoiesis, diseases of the cardiovascular system (CVS) (angina pectoris, arrhythmia, AV blockade of the 1st stage of the heart, chronic heart failure (CHF), myocardial infarction, postinfarction arterial cardiosclerosis, hypertension), stroke, decreased motor function of the gastrointestinal tract (risk of paralytic intestinal obstruction), intraocular hypertension, hepatic and / or renal failure, thyrotoxicosis, urinary retention, bladder hypotension, schizophrenia (possible activation of psychosis), old age.

Before starting treatment, blood pressure control is necessary (in patients with low or labile blood pressure, it may decrease even more); during the treatment period - control of peripheral blood (in some cases, agranulocytosis may develop, in connection with which it is recommended to monitor the blood picture, especially with an increase in body temperature, the development of flu-like symptoms and tonsillitis), with prolonged therapy - control of the functions of the CVS and liver. In the elderly and patients with CVD diseases, control over the number of heart contractions (HR), blood pressure, ECG is shown. On the ECG, clinically insignificant changes may appear (smoothing of the tooth T, segment depression S- T, expansion of the complex QRS).

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

Care must be taken when moving abruptly to an upright position from a "lying" or "sitting" position.

During the treatment period, the use of ethanol should be excluded.

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

With a sudden cessation of admission after long-term treatment, the development of a "withdrawal" syndrome is possible.

Amitriptyline in doses above 150 mg / day reduces the threshold of seizure activity (the risk of epileptic seizures in predisposed patients should be taken into account, as well as in the presence of other factors predisposing to the onset of convulsive syndrome, for example, brain damage of any etiology, the simultaneous use of antipsychotic drugs (neuroleptics), during the period of refusal from ethanol or withdrawal of drugs with anticonvulsant properties, such as benzodiazepines).

Severe depression is characterized by the risk of suicidal actions, which can persist until significant remission is achieved. In this regard, at the beginning of treatment, a combination with drugs from the group of benzodiazepines or neuroleptic drugs and constant medical supervision (entrusting authorized persons with the storage and issuance of drugs) may be indicated.

In patients with cyclic affective disorders during the depressive phase during therapy, manic or hypomanic states may develop (it is necessary to reduce the dose or cancel the drug and prescribe an antipsychotic drug). After the relief of these conditions, if there are indications, treatment in low doses can be resumed.

Due to the possible cardiotoxic effects, caution is required when treating patients with thyrotoxicosis or patients receiving thyroid hormone preparations.

In combination with electroconvulsive therapy, it is prescribed only with careful medical supervision.

In predisposed patients and elderly patients, it can provoke the development of drug psychoses, mainly at night (after discontinuation of the drug, they disappear within a few days).

May cause paralytic ileus, an advantage in patients with chronic constipation, the elderly, or in patients who are forced to stay in bed.

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

Due to the anticholinergic effect, it is possible to reduce tearing and a relative increase in the amount of mucus in the tear fluid, which can lead to damage to the corneal epithelium in patients using contact lenses.

With prolonged use, there is an increase in the incidence of dental caries. The need for riboflavin may be increased.

Features of the influence of the drug on the ability to drive a vehicle or potentially dangerous mechanisms

During the period of treatment, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration of attention and speed of psychomotor reactions.

Overdose

Symptoms:

Drowsiness, stupor, coma, ataxia, hallucinations, anxiety, psychomotor agitation, decreased ability to concentrate, disorientation, confusion, dysarthria, hyperreflexia, muscle stiffness, choreoathetosis, epileptic syndrome;

Reduction of blood pressure (BP), tachycardia, arrhythmia, disturbance of intracardiac conduction, changes in the electrocardiogram (ECG) characteristic of intoxication with tricyclic antidepressants (especially QRS), shock; in very rare cases - cardiac arrest;

Respiratory depression, shortness of breath, cyanosis, vomiting, hyperthermia, mydriasis, increased sweating, oliguria or anuria;

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

Treatment: symptomatic and supportive therapy; with severe anticholinergic effects (lowering blood pressure, arrhythmias, coma, myoclonic epileptic seizures) - the introduction of cholinesterase inhibitors (the use of physostigmine is not recommended due to the increased risk of seizures); maintaining blood pressure and water-electrolyte balance. Control of the cardiovascular system functions (including ECG) for 5 days (relapse may occur 48 hours and later), anticonvulsant therapy, artificial lung ventilation (ALV) and other resuscitation measures are shown.

Hemodialysis and forced diuresis are ineffective.

Release form and packaging

Solution for injection 20 mg / 2 ml.

2 ml in colorless neutral glass ampoules.

Self-adhesive labels are glued to the ampoules.

5 ampoules are placed in blisters made of polyvinyl chloride film.

2 blisters are placed in a cardboard box.

Each pack contains instructions for medical use in the state and Russian languages.

The ampoule scarifier is not inserted when using ampoules with a break ring or with a notch and a dot.

Storage conditions

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

Keep out of the reach of children!

Shelf life

Do not use after the expiration date.

Conditions of dispensing from pharmacies

On prescription

Manufacturer

Antidepressant

Active substance

Amitriptyline (amitriptyline)

Release form, composition and packaging

Pills from white to white with a slightly yellowish tinge, flat-cylindrical shape, with a bevel; light marbling is allowed.

Excipients: microcrystalline cellulose - 40 mg, lactose monohydrate (milk sugar) - 40 mg, pregelatinized starch - 25.88 mg, colloidal silicon dioxide (aerosil) - 400 μg, talc - 1.2 mg, magnesium stearate - 1.2 mg.

Pills from white to white with a slightly yellowish tinge of color, flat-cylindrical in shape, with a chamfer and a line; light marbling is allowed.

Excipients: microcrystalline cellulose - 100 mg, lactose monohydrate (milk sugar) - 100 mg, pregelatinized starch - 64.7 mg, colloidal silicon dioxide (aerosil) - 1 mg, talc - 3 mg, magnesium stearate - 3 mg.

10 pieces. - contour cell packaging (1) - cardboard packs.
10 pieces. - contour cell packaging (2) - cardboard packs.
10 pieces. - contour cell packaging (3) - cardboard packs.
10 pieces. - contour cell packaging (4) - cardboard packs.
10 pieces. - contour cell packaging (5) - cardboard packs.
100 pieces. - polymer cans (1) - cardboard packs.

pharmachologic effect

Antidepressant (tricyclic antidepressant). It also has some analgesic (central genesis), antiserotonin effect, helps to eliminate bedwetting and reduces appetite.

It has the properties of a class IA antiarrhythmic drug, like quinidine in therapeutic doses, it slows down ventricular conduction (in case of an overdose, it can cause severe intraventricular blockade).

The mechanism of antidepressant action is associated with an increase in the concentration and / or serotonin in the central nervous system (CNS) (a decrease in their reabsorption).

The accumulation of these neurotransmitters occurs as a result of inhibition of their reuptake by the membranes of presynaptic neurons. With prolonged use, it 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 conditions. In case of anxiety-depressive states, it reduces anxiety, agitation and depressive manifestations.

The mechanism of antiulcer action is due to the ability to provide sedative and m-anticholinergic action. Efficacy for bedwetting is apparently due to anticholinergic activity, leading to an increase in the ability of the bladder to stretch, direct beta-adrenergic stimulation, the activity of alpha-adrenergic agonists, accompanied by an increase in sphincter tone, and central blockade of seizure. 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 the effect on the endogenous opioid systems.

The mechanism of action for bulimia nervosa is unclear (may be similar to that for depression). A clear effect of the drug has been shown in bulimia in patients both without depression and in its presence, while a decrease in bulimia can be noted without a concomitant weakening of depression itself.

During general anesthesia, it lowers blood pressure and body temperature. Does not inhibit monoamine oxidase (MAO).

The antidepressant effect develops within 2-3 weeks after the start of use.

Pharmacokinetics

Absorption is high.

The bioavailability of amitriptyline is 30-60%, its active metabolite nortriptyline is 46-70%. The time to reach C max after ingestion is 2.0-7.7 hours. Vd is 5-10 l / kg. Effective therapeutic blood concentrations for amitriptyline are 50-250 ng / ml, for nortriptyline 50-150 ng / ml.

C max 0.04-0.16 μg / ml. Passes (including nortriptyline) through the histohematological barriers, including the blood-brain barrier, placental barrier, and enters breast milk. Protein binding - 96%.

It is metabolized in the liver with the participation of isoenzymes CYP2C19, CYP2D6, has a "first pass" effect (by demethylation, hydroxylation) with the formation of active metabolites - nortriptyline, 10-hydroxy-amitriptyline, and inactive metabolites. T 1/2 from blood plasma - 10-26 hours for amitriptyline and 18-44 hours for nortriptyline. It is excreted by the kidneys (mainly in the form of metabolites) - 80% in 2 weeks, partly with bile.

Indications

Depression (especially with anxiety, agitation and sleep disorders, including in childhood, endogenous, involutional, reactive, neurotic, medicinal, with organic brain lesions).

As part of complex therapy, it is used for mixed emotional disorders, psychosis in schizophrenia, alcohol withdrawal, behavioral disorders (activity and attention), nocturnal enuresis (except for patients with bladder hypotension), bulimia nervosa, chronic pain syndrome (chronic pain in cancer patients, migraine, rheumatic diseases, atypical pain in the face, postherpetic neuralgia, post-traumatic neuropathy, diabetic or other peripheral neuropathy), headache, migraine (prevention), gastric ulcer and duodenal ulcer.

Contraindications

Hypersensitivity, use in conjunction with MAO inhibitors and 2 weeks before starting treatment, myocardial infarction (acute and subacute periods), acute alcohol intoxication, acute intoxication with hypnotics, analgesic and psychoactive drugs, angle-closure glaucoma, severe AV and intraventricular conduction block ( bundle of His, AV block II degree), lactation period, children's age up to 6 years.

Carefully. Amitriptyline should be used with caution in persons with alcoholism, with bronchial asthma, schizophrenia (possible activation of psychosis), bipolar disorder, epilepsy, with suppression of bone marrow hematopoiesis, diseases of the cardiovascular system (CVS) (angina pectoris, arrhythmia, heart block, chronic insufficiency, myocardial infarction, arterial hypertension), intraocular hypertension, stroke, decreased motor function of the gastrointestinal tract (GIT) (risk of paralytic intestinal obstruction), hepatic and / or renal failure, thyrotoxicosis, prostatic hyperplasia, urinary retention, hypotension bladder, during pregnancy (especially the first trimester), in old age.

Dosage

Assign orally, without chewing, immediately after meals (to reduce irritation of the gastric mucosa).

Adults

For adults with depression, the initial dose is 25-50 mg at night, then the dose can be gradually increased, taking into account the effectiveness and tolerability of the drug, up to a maximum of 300 mg / day. in 3 divided doses (most of the dose is taken at night). When a therapeutic effect is achieved, the dose can be gradually reduced to the minimum effective, depending on the patient's condition. The duration of the course of treatment is determined by the patient's condition, the effectiveness and tolerance of the therapy and can range from several months to 1 year, and, if necessary, even more. In old age, with mild disorders, as well as with bulimia nervosa, as part of complex therapy for mixed emotional disorders and behavioral disorders, psychosis with schizophrenia and alcohol withdrawal, it is prescribed at a dose of 25-100 mg / day. (at night), after reaching the therapeutic effect, they switch to the minimum effective dose - 10-50 mg / day.

For the prevention of migraine, with chronic pain syndrome of a neurogenic nature (including prolonged headaches), as well as in the complex therapy of gastric ulcer and duodenal ulcer - from 10-12.5-25 to 100 mg / day. (the maximum part of the dose is taken at night).

Children

Children as an antidepressant: from 6 to 12 years old - 10-30 mg / day. or 1-5 mg / kg / day. fractionally, in adolescence - up to 100 mg / day.

With nocturnal enuresis in children 6-10 years old - 10-20 mg / day. at night, 11-16 years old - up to 50 mg / day.

Side effects

Associated with the anticholinergic action of the drug: blurred vision, accommodation paralysis, mydriasis, increased intraocular pressure (only in persons with a local anatomical predisposition - a narrow angle of the anterior chamber), tachycardia, dry mouth, confusion (delirium or hallucinations), constipation, paralytic intestinal obstruction, difficulty urinating.

From the side of the central nervous system: drowsiness, fainting, fatigue, irritability, anxiety, disorientation, hallucinations (especially in elderly patients and in patients with Parkinson's disease), anxiety, psychomotor agitation, mania, hypomania, memory impairment, decreased ability to concentrate, insomnia, "nightmarish "dreams, asthenia; headache; dysarthria, tremor of small muscles, especially arms, hands, head and tongue, peripheral neuropathy (paresthesia), myasthenia gravis, myoclonus; ataxia, extrapyramidal syndrome, increased frequency and intensification of epileptic seizures; changes in the electroencephalogram (EEG).

From the CCC side: tachycardia, palpitations, dizziness, orthostatic hypotension, nonspecific changes in the electrocardiogram (ECG) (S-T interval or T wave) in patients without heart disease; arrhythmia, lability of blood pressure (decrease or increase in blood pressure), violation of intraventricular conduction (expansion of the QRS complex, changes in the P-Q interval, bundle branch block).

From the gastrointestinal tract: nausea, heartburn, gastralgia, hepatitis (including liver dysfunction and cholestatic jaundice), vomiting, increased appetite and weight or decreased appetite and weight, stomatitis, taste changes, diarrhea, darkening of the tongue.

From the endocrine system: enlargement (swelling) 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 production of vasopressin), syndrome of inappropriate secretion of antidiuretic hormone (ADH). Allergic reactions: skin rash, itching, photosensitivity, angioedema, urticaria.

Others: hair loss, tinnitus, edema, hyperpyrexia, swollen lymph nodes, urinary retention, pollakiuria.

With long-term treatment, especially in high doses, with its abrupt termination, it is possible development of withdrawal syndrome: nausea, vomiting, diarrhea, headache, malaise, sleep disturbances, unusual dreams, unusual agitation; with gradual withdrawal after long-term treatment - irritability, motor restlessness, sleep disturbances, unusual dreams.

The connection with taking the drug has not been established: lupus-like syndrome (migratory arthritis, the appearance of antinuclear antibodies and positive rheumatoid factor), liver dysfunction, ageusia.

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, muscle stiffness, choreoathetosis, epileptic syndrome.

From the CCC side: decrease in blood pressure, tachycardia, arrhythmia, intracardiac conduction disturbance, ECG changes (especially QRS) characteristic of intoxication with tricyclic antidepressants, shock, heart failure; in very rare cases, cardiac arrest.

Others: respiratory depression, shortness of breath, cyanosis, vomiting, hyperthermia, mydriasis, increased sweating, oliguria or anuria.

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

Treatment: for oral administration: gastric lavage, intake of activated charcoal; symptomatic and supportive therapy; with severe anticholinergic effects (lowering blood pressure, arrhythmias, coma, myoclonic epileptic seizures) - the introduction of cholinesterase inhibitors (the use of physostigmine is not recommended due to the increased risk of seizures); maintaining blood pressure and water-electrolyte balance. Shown monitoring the functions of the CVS (including ECG) for 5 days (relapse can occur after 48 hours and later), anticonvulsant therapy, artificial ventilation (ALV) and other resuscitation measures. Hemodialysis and forced diuresis are ineffective.

Drug interactions

Increases the anticholinergic effect of drugs with anticholinergic activity (for example, phenothiazine derivatives, antiparkinsonian drugs, atropine, biperiden, antihistamines), which increases the risk of side effects (from the central nervous system, vision, intestines and bladder). When combined with anticholinergics, phenothiazine derivatives and benzodiazepines - mutual enhancement of sedative and central anticholinergic effects and an increased risk of epileptic seizures (lowering the threshold of seizure activity); derivatives of phenothiazine, in addition, may increase the risk of neuroleptic malignant syndrome.

When used together with antihistamines, clonidine - an increase in the inhibitory effect on the central nervous system; c - 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 or indadione derivatives), an increase in the anticoagulant activity of the latter is possible. Amitriptyline may increase depression induced by glucocorticosteroids (GCS). Medicines for the treatment of thyrotoxicosis increase the risk of developing agranulocytosis. Reduces the effectiveness of phenytoin and alpha-blockers.

Combined use with disulfiram and other acetaldehydrogenase inhibitors provokes delirium.

Fluoxetine and fluvoxamine increase the plasma concentration of amitriptyline (it may be necessary to reduce the dose of amitriptyline by 50%).

Antiarrhythmic drugs (such as quinidine) increase the risk of rhythm disturbances (possibly slowing down the metabolism of amitriptyline).

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

When administered together with alpha-adrenergic agonists for intranasal administration or for use in ophthalmology (with significant systemic absorption), the vasoconstrictor effect of the latter may increase.

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

M-anticholinergics and antipsychotic drugs (antipsychotics) increase the risk of developing hyperpyrexia (especially in hot weather).

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

Incompatible with MAO inhibitors (there may be an increase in the frequency of periods of hyperpyrexia, severe convulsions, hypertensive crises and patient death).

special instructions

Before starting treatment, blood pressure control is necessary (in patients with low or labile blood pressure, it may decrease even more); during the treatment period - control of peripheral blood (in some cases, agranulocytosis may develop, and therefore it is recommended to monitor the blood picture, especially with an increase in body temperature, the development of flu-like symptoms and tonsillitis), with prolonged therapy - control of the functions of the CVS and liver. In the elderly and patients with CVS diseases, monitoring of heart rate, blood pressure, ECG is shown. On the ECG, clinically insignificant changes may appear (smoothing of the T wave, depression of the S-T segment, expansion of the QRS complex).

Care must be taken when moving abruptly to an upright position from a "lying" or "sitting" position.

During the treatment period, the use of ethanol should be excluded.

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

With a sudden cessation of admission after long-term treatment, the development of a "withdrawal" syndrome is possible.

Amitriptyline in doses above 150 mg / day. reduces the threshold of seizure activity (the risk of epileptic seizures in predisposed patients should be taken into account, as well as in the presence of other factors predisposing to the onset of seizure syndrome, for example, brain damage of any etiology, the simultaneous use of antipsychotic drugs (neuroleptics), during the period of refusal from ethanol or withdrawal of drugs with anticonvulsant properties, such as benzodiazepines). Severe depression is characterized by the risk of suicidal actions, which can persist until significant remission is achieved. In this regard, at the beginning of treatment, a combination with drugs from the benzodiazepine group or antipsychotic drugs and constant medical supervision (entrusting authorized persons with the storage and dispensing of drugs) may be indicated. In children, adolescents and young people (under 24 years of age) with depression and other mental disorders, antidepressants, compared with placebo, increase the risk of suicidal thoughts and suicidal behavior. Therefore, when prescribing amitriptyline or any other antidepressants in this category of patients, the risk of suicide and the benefits of their use should be correlated. In short-term studies, the risk of suicide did not increase in people over 24 years old, and in people over 65 years old it was slightly reduced. During treatment with antidepressants, all patients should be monitored for early detection of suicidal tendencies.

In patients with cyclic affective disorders during the depressive phase during therapy, manic or hypomanic states may develop (a dose reduction or withdrawal of the drug and the appointment of an antipsychotic drug are necessary). After the relief of these conditions, if there are indications, treatment in low doses can be resumed.

Due to the possible cardiotoxic effects, caution is required when treating patients with thyrotoxicosis or patients receiving thyroid hormone preparations.

In combination with electroconvulsive therapy, it is prescribed only with careful medical supervision.

In predisposed patients and elderly patients, it can provoke the development of drug psychoses, mainly at night (after discontinuation of the drug, they disappear within a few days).

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

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

With prolonged use, there is an increase in the incidence of dental caries. The need for riboflavin may be increased.

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

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

Pregnancy and lactation

In pregnant women, the drug should be used only if the intended benefit to the mother outweighs the potential risk to the fetus.

It passes into breast milk and may cause drowsiness in infants. To avoid the development of withdrawal syndrome in newborns (manifested by shortness of breath, drowsiness, intestinal colic, increased nervous irritability, increased or decreased blood pressure, tremors or spastic phenomena), amitriptyline is gradually canceled at least 7 weeks before the expected birth.

Childhood use

Contraindicated in children under 6 years of age.

In children, adolescents and young people (under 24 years of age) with depression and other mental disorders, antidepressants, compared with placebo, increase the risk of suicidal thoughts and suicidal behavior. Therefore, when prescribing amitriptyline or any other antidepressants in this category of patients, the risk of suicide and the benefits of their use should be correlated

Conditions of dispensing from pharmacies

The drug is available with a prescription.

Storage conditions and periods

Store the drug in a dry, dark place at a temperature not exceeding 25 ° C. Keep out of the reach of children.

Shelf life is 3 years. Do not use after the expiration date.

Read this leaflet carefully before you start taking / using this medication.
Save the instructions as you may need them again.
If you have any questions, see your doctor.
This medicine has been prescribed for you personally and should not be passed on to others as it may harm them even if they have the same symptoms as you.

INSTRUCTIONS FOR MEDICAL APPLICATION OF THE MEDICINAL PREPARATION AMITRIPTILINE

Registration number: Р N002756 / 02-071114
Trade name: Amitriptyline
International non-proprietary name: Amitriptyline
Chemical name: 3- (10,11-Dihydro-5H-dibenzo [a, d] -cyclohepten-5-ylidene) -N, N-dimethylpropan-1-amine hydrochloride
Dosage form: solution for intravenous and intramuscular administration

Composition
1 ml of solution contains:
Active substance:
amitriptyline hydrochloride - 11.31 mg,
equivalent to 10.0 mg amitriptyline
Excipients:
dextrose monohydrate
in terms of dextrose - 40.0 mg,
sodium chloride - 2.6 mg,
benzethonium chloride - 0.1 mg,
hydrochloric acid or sodium hydroxide - up to pH 4.0-6.0,
water for injection - up to 1 ml.

Description: clear, colorless or slightly colored liquid.

Pharmacotherapeutic group: antidepressant

ATX code: N06AA09

Pharmacological properties

Amitriptyline is a sedative tricyclic antidepressant.
Pharmacodynamics
Amitriptyline equally inhibits the reuptake of norepinephrine and serotonin in the presynaptic nerve ending. The main metabolite of amitriptyline, nortriptyline, inhibits the reuptake of norepinephrine rather than serotonin. It has anticholinergic and H1-histamine activity. It has a powerful antidepressant, sedative and anxiolytic effect.
Pharmacokinetics
Suction
Amitriptyline is highly absorbed. The time to reach the maximum concentration (Tcmax) after oral administration is 4-8 hours, Cmax is 0.04-0.16 μg / ml. Equilibrium concentration is achieved approximately 1-2 weeks after the start of the course of treatment. Tissue concentrations of amitriptyline are higher than those in plasma. The bioavailability of amitriptyline for various routes of administration is 33-62%, its active metabolite nortriptyline is 46-70%. The volume of distribution (Vd) is 5-10 l / kg. Effective therapeutic concentrations of amitriptyline in the blood are 50-250 ng / ml, for nortriptyline (its active metabolite) - 50-150 ng / ml. The connection with plasma proteins is 92-96%. Amitriptyline passes through the histohematological barriers, including the blood-brain barrier (including nortriptyline), crosses the placental barrier, and is excreted into breast milk in concentrations similar to plasma ones.
Metabolism
Metabolism of amitriptyline is carried out mainly through demethylation (isoenzymes CYP2D6, CYP3A) and hydroxylation (isoenzyme CYP2D6), followed by conjugation with glucuronic acid. Metabolism is characterized by significant genetic polymorphism. The main active metabolite is a secondary amine, nortriptyline. The metabolites cis- and trans-10-hydrosiamitriptyline and cis- and trans-10-hydroxynortriptyline are characterized by a profile of activity similar to nortriptyline, although their effect is much weaker. Demethylnortriptyline and amitriptyline-N-oxide are present in blood plasma in negligible concentrations; the latter metabolite is practically devoid of pharmacological activity. In comparison with amitriptyline, all metabolites have a significantly less pronounced m-anticholinergic blocking effect.
The main factor determining renal clearance, and, accordingly, concentration in blood plasma, is the rate of hydroxylation. In a small proportion of people, genetically determined delayed hydroxylation is observed.
Withdrawal
The half-life (T1 / 2) from blood plasma is 10-28 hours for amitriptyline, for nortriptyline - 16-80 hours. The average total clearance of amitriptyline is 39.24 ± 10.18 l / h. Amitriptyline is excreted mainly by the kidneys and through the intestines in the form of metabolites. About 50% of the administered amitriptyline is excreted in the urine in the form of 10-hydroxyamitriptyline and its conjugate with glucuronic acid, about 27% is excreted in the form of 10-hydroxy-nortriptyline and less than 5% of amitriptyline is excreted in the form of the parent substance and nortriptyline. Complete elimination of amitriptyline from the body occurs within 7 days.
Elderly patients
In elderly patients, there is an increase in the half-life and a decrease in the clearance of amitriptyline due to a decrease in the metabolic rate.
Patients with impaired liver function
Liver dysfunction can lead to a slowdown in the metabolism of amitriptyline and an increase in its plasma concentrations.
Patients with impaired renal function
In patients with impaired renal function, excretion of the metabolites of amitriptyline and nortriptyline is slowed down, although the metabolism itself does not change. Due to its connection with blood proteins, amitriptyline is not removed from blood plasma by dialysis.

Indications for use

Endogenous depression and other depressive disorders.

Contraindications

Hypersensitivity, myocardial infarction (acute and subacute periods), arrhythmias, severe violations of atrioventricular and intraventricular conduction (bundle branch block, II degree atrioventricular block), heart failure, acute alcohol intoxication, acute intoxication with hypnotics, glautocoactive drugs and urinary retention, including with prostatic hyperplasia, paralytic intestinal obstruction, pyloric stenosis, hypokalemia, concomitant use of drugs that prolong the QT interval, or cause hypokalemia, lactation period, children under 18 years of age.
Simultaneous use with monoamine oxidase inhibitors (MAO) and their use within 14 days before and after the end of treatment is contraindicated.

Carefully

Convulsive disorders, chronic alcoholism, prostatic hyperplasia, severe diseases of the liver and cardiovascular system, bronchial asthma, manic-depressive psychosis (MDP) and epilepsy (see the section "Special instructions"), inhibition of bone marrow hematopoiesis, hyperthyroidism, thyrotoxicosis, delay urination, bladder hypotension, angina pectoris, increased intraocular pressure, decreased motor function of the gastrointestinal tract (the risk of paralytic intestinal obstruction), schizophrenia (although when taken, there is usually no exacerbation of productive symptoms), old age, pregnancy, breastfeeding.
If you have one of the listed diseases, be sure to consult your doctor before taking the drug.

Application during pregnancy and during breastfeeding

Use during pregnancy is not recommended.
If the drug is used by pregnant women, it is necessary to warn about the high risk of such an admission to the fetus, especially in the third trimester of pregnancy. The use of high doses of tricyclic antidepressants in the third trimester of pregnancy can lead to neurological disorders in the newborn. Cases of drowsiness have been reported in newborns whose mothers have used nortriptyline (a metabolite of amitriptyline) during pregnancy, and cases of urinary retention have been reported.
Amitriptyline passes into breast milk. The concentration ratio of breast milk / plasma is 0.4-1.5 in a breastfed baby.
When using amitriptyline, breastfeeding should be discontinued.
If this is not done, the baby's condition should be monitored, especially during the first four weeks after birth.
Undesirable reactions may occur in a breastfed baby (see the "Side Effects" section).

Method of administration and dosage

Assign intramuscularly and intravenously.
Doses of the drug are selected individually, depending on the age and condition of the patient.
In case of depression resistant to therapy: intramuscularly and intravenously (inject slowly!) In a dose of 10-20-30 mg up to 4 times a day, the dose should be increased gradually, the maximum daily dose is 150 mg; after 1-2 weeks, they switch to taking the drug inside.
Older 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 inappropriate.
Cancellation
The drug should be withdrawn gradually to avoid the development of withdrawal symptoms.
Withdrawal symptoms: after long-term use with a sudden discontinuation of the drug, undesirable reactions such as nausea, vomiting, diarrhea, headache, malaise, insomnia, unusual dreams, unusual agitation, irritability may occur; after prolonged use with gradual withdrawal - irritability, sleep disturbances, unusual dreams. These symptoms do not indicate the development of addiction to the drug.

Side effect

WHO classification of unwanted adverse reactions by frequency of development
Very frequent - 1/10 appointments (≥ 10%)
Frequent - 1/100 appointments (≥ 1%, but< 10 %)
Uncommon - 1/1000 appointments (≥ 0.1%, but< 1 %)
Rare - 1/10000 appointments (≥ 0.01%, but< 0,1 %)
Very rare - less than 1/10000 appointments (< 0,01 %)
Disturbances from the blood and lymphatic system: rarely - inhibition of bone marrow hematopoiesis, agranulocytosis, leukopenia, thrombocytopenia, eosinophilia.
Metabolic and nutritional disorders: very often - weight gain; rarely - weight loss, decreased appetite.
Mental disorders: often - confusion, decreased libido; infrequently - hypomania, mania, anxiety, insomnia, "nightmares"; rarely - delirium (in elderly patients), hallucinations (in patients with schizophrenia).
Nervous system disorders: very often - drowsiness, tremors, dizziness, headaches; often - impaired concentration, dysgeusia, paresthesia, ataxia; infrequently - convulsions.
Violations of the organ of vision: very often - violation of accommodation; often - mydriasis; infrequently - increased intraocular pressure.
Hearing disorders and labyrinthine disorders: infrequently - tinnitus.
Heart disorders: very often - increased heart rate, tachycardia, orthostatic hypotension; often - atrioventricular block (AV block), bundle branch block, intracardiac conduction disturbances recorded only on the ECG, but not clinically manifested (increase in the QT interval, increase in the QRS complex); infrequently - arterial hypertension; rarely - arrhythmia.
Disturbances from the gastrointestinal tract: very often - dry mouth, constipation, nausea; infrequently - diarrhea, vomiting, swelling of the tongue; rarely - an increase in the salivary glands, paralytic intestinal obstruction.
Liver and biliary tract disorders: rarely - jaundice, impaired liver function indicators, increased blood alkaline phosphatase (ALP) activity and transaminases.
Skin and subcutaneous tissue disorders: very often - hyperhidrosis; infrequently - skin rash, hives, swelling of the face; rarely - alopecia, photosensitivity reactions.
Renal and urinary tract disorders: infrequently - urinary retention.
Genital and breast disorders: often - erectile dysfunction; rarely - gynecomastia.
General disorders and disorders at the injection site: often - fatigue; rarely - pyrexia.
Withdrawal symptoms: after long-term use, with a sharp discontinuation of use, undesirable reactions such as nausea, vomiting, diarrhea, headache, malaise, insomnia, unusual dreams, unusual agitation, irritability may occur; after prolonged use with gradual withdrawal - irritability, sleep disturbances, unusual dreams. These symptoms do not indicate the development of addiction to the drug.
Some of the adverse reactions, such as headache, tremors, impaired concentration, constipation and decreased libido, can be manifestations of depression and disappear as the depression resolves.
If any of the side effects indicated in the instructions are aggravated, or you notice any other side effects that are not listed in the instructions, inform your doctor.

Overdose

Overdose reactions vary significantly in different patients.
In adult patients, taking more than 500 mg causes moderate or severe intoxication.
The lethal dose of amitriptyline is 1200 mg.
Symptoms
Symptoms can develop slowly and imperceptibly, or abruptly and suddenly. During the first hours, drowsiness or agitation, agitation and hallucinations are observed.
Anticholinergic symptoms: mydriasis, tachycardia, urinary retention, dry mucous membranes, fever, slowing of intestinal motility.
Neuropsychic signs: convulsions, sudden depression of the central nervous system (CNS), a decrease in the level of consciousness up to coma, respiratory depression.
Symptoms from the heart: As signs of overdose increase, changes in the cardiovascular system increase. Arrhythmias (ventricular tachyarrhythmia, heart rhythm disturbances like Torsade de Pointes, ventricular fibrillation). The ECG is characterized by prolongation of the PR interval, expansion of the QRS complex, prolongation of the QT interval, simplification or inversion of the T wave, depression of the ST segment and intracardiac conduction blockade of varying degrees, which can progress to cardiac arrest, lowering blood pressure, heart failure, intraventricular blockade, frequent pulse.
Expansion of the QRS complex usually correlates with the severity of toxic effects due to acute overdose.
Heart failure, lowering blood pressure, cardiogenic shock. Metabolic acidosis, hypokalemia.
After awakening, confusion, agitation, hallucinations, ataxia are possible again.
Treatment: cessation of therapy with amitriptyline, administration of physostigmine 1-3 mg every 1-2 hours intramuscularly or intravenously, fluid infusion, symptomatic therapy, maintenance of blood pressure and water-electrolyte balance. Shown monitoring of cardiovascular activity (ECG) for 5 days, because relapse may occur 48 hours later or later. Hemodialysis and forced diuresis, gastric lavage are ineffective.

Interaction with other medicinal products

Simultaneous administration of amitriptyline and MAO inhibitors can cause serotonin syndrome (possible agitation, confusion, tremor, myoclonus, hyperthermia).
Amitriptyline can be prescribed 14 days after stopping treatment with irreversible MAO inhibitors and at least 1 day after stopping therapy with a reversible MAO inhibitor type A - moclobemide. MAO inhibitors can be prescribed 14 days after the end of amitriptyline.
Amitriptyline can enhance the effects of alcohol, barbiturates and other substances that depress the central nervous system.
Since tricyclic antidepressants, including amitriptyline, can enhance the effect of anticholinergic drugs on the organs of vision, central nervous system, intestines and bladder, their simultaneous use should be avoided due to the risk of developing paralytic intestinal obstruction and hyperpyrexia.
When taking tricyclic antidepressants in combination with anticholinergic drugs or antipsychotics, especially in hot weather, hyperpyrexia may develop.
Amitriptyline can enhance the effects of epinephrine, ephedrine, isoprenaline, norepinephrine, phenylephrine, and phenylpropanolamine on the cardiovascular system; as a result, anesthetics, decongestants and other drugs containing these substances should not be used simultaneously with amitriptyline.
May reduce the antihypertensive effect of guanethidine, betanidine, reserpine, clonidine and methyldopa. With the simultaneous administration of tricyclic antidepressants, it is necessary to adjust antihypertensive therapy.
When used together with antihistamines, it is possible to increase the inhibitory effect on the central nervous system; with drugs that cause extrapyramidal reactions - an increase in the severity and frequency of extrapyramidal effects.
Concomitant use of amitriptyline and drugs that lengthen the QT interval (antiarrhythmics (quinidine), antihistamines (astemizole and terfenadine), some antipsychotics (cisapride, halofantrine and sotalol, especially pimozide and sertindole)) increases the risk of ventricular arrhythmia.
Antifungal drugs, such as fluconazole, terbinafine, increase the serum concentration of tricyclic antidepressants and, consequently, their toxicity. Fainting and development of paroxysms of ventricular tachycardia (Torsade de Pointes) are possible.
Barbiturates and other enzyme inducers, for example, rifampicin and carbamazepine, etc. can increase the metabolism of tricyclic antidepressants, and as a result, lower the concentration of tricyclic antidepressants in the blood plasma and reduce their effectiveness.
With simultaneous use with cimetidine, methylphenidate and calcium channel blockers, it is possible to slow down the metabolism of amitriptyline, increase its concentration in blood plasma and develop toxic effects.
When administered together with antipsychotics, it should be borne in mind that tricyclic antidepressants and antipsychotics mutually inhibit each other's metabolism, lowering the threshold for convulsive readiness.
With the simultaneous use of amitriptyline and indirect anticoagulants (coumarin or indandione derivatives), an increase in the anticoagulant activity of the latter is possible.
Amitriptyline may increase depression induced by glucocorticoid drugs (GCS).
When used together with anticonvulsant drugs, it is possible to increase the inhibitory effect on the central nervous system, reduce the threshold of seizure activity (when used in high doses) and reduce the effectiveness of the latter.
Simultaneous administration with drugs for the treatment of thyrotoxicosis increases the risk of developing agranulocytosis.
Due to the risk of arrhythmias, special care must be taken when prescribing amitriptyline to patients with hyperthyroidism or to patients receiving thyroid medications.
Fluoxetine and fluvoxamine can increase the concentration of amitriptyline in the blood plasma (a decrease in the dose of amitriptyline may be required).
When combined with anticholinergics, phenothiazines and benzodiazepines, it is possible to mutually enhance the sedative and central anticholinergic effects and increase the risk of epileptic seizures (lowering the threshold of seizure activity).
Estrogen-containing oral contraceptives and estrogens can increase the bioavailability of amitriptyline. A dose reduction of either estrogen or amitriptyline may be necessary to restore efficacy or reduce toxicity. However, it may be necessary to discontinue the drug.
Concomitant use with disulfiram and other acetaldehydrogenase inhibitors may increase the risk of developing psychotic conditions and confusion.
When amitriptyline is used together with phenytoin, the metabolism of the latter is inhibited, and the risk of its toxic effects (ataxia, hyperreflexia, nystagmus, tremor) increases. At the beginning of the use of amitriptyline in patients receiving phenytoin, the concentration of the latter in the blood plasma should be monitored due to the increased risk of inhibition of its metabolism. At the same time, the therapeutic effect of amitriptyline should be monitored, because an increase in its dose may be required.
St. John's wort preparations reduce the maximum concentration of amitriptyline in blood plasma by about 20% due to the activation of hepatic metabolism of amitriptyline by the CYP3A4 isoenzyme. Which increases the risk of serotonin syndrome. This combination can be used with dose adjustment of amitriptyline, depending on the results of measuring its concentration in blood plasma.
With the simultaneous use of valproic acid, the clearance of amitriptyline from blood plasma decreases, which can lead to an increase in the concentration of amitriptyline and its metabolite, nortriptyline. When amitriptyline and valproic acid are used together, serum concentrations of amitriptyline and nortriptyline should be monitored. Dose reduction of amitriptyline may be required.
With the simultaneous use of amitriptyline in a high dose and lithium preparations for more than six months, the development of seizures, cardiovascular complications is possible. It is also possible the appearance of signs of a neurotoxic effect in the form of tremors, memory impairments, distraction, disorganization of thinking, even with a normal concentration of lithium in the blood and moderate doses of amitriptyline.

special instructions

Tricyclic antidepressants should not be prescribed to children and adolescents under the age of 18 due to insufficient data on the efficacy and safety of drugs in this group of patients.
Amitriptyline in doses above 150 mg / day lowers the threshold of seizure activity, therefore, the possibility of seizure disorders in patients with a history of seizure disorders, and in case of brain damage of any etiology, the simultaneous use of neuroleptics, during the period of refusal of ethanol or withdrawal of drugs with anticonvulsant properties (benzodiazepines).
Any depressive disorder in itself increases the risk of suicide. Therefore, during antidepressant treatment, all patients should be monitored for early detection of behavioral disturbances or changes, as well as suicidal tendencies.
The use of anesthetics during the course of treatment with tri- and tetracyclic antidepressants can increase the risk of arrhythmias and lower blood pressure. If possible, stop using amitriptyline a few days before surgery. If an urgent surgical intervention is necessary, the anesthesiologist should be warned about treating the patient with amitriptyline.
Dry mouth and decreased tear production are possible with a relative increase in the amount of mucus in the lacrimal fluid, which can damage the corneal epithelium in contact lens wearers.

Influence on the ability to drive vehicles and mechanisms

Release form
Solution for intravenous and intramuscular administration of 10 mg / ml in 2 ml ampoules.
5 ampoules in a blister strip made of polyvinyl chloride film and lacquered aluminum foil, or flexible packaging based on aluminum foil, or without foil.
1 or 2 blister packs with instructions for use, knife or ampoule scarifier in a cardboard box.
20, 50 or 100 blisters with foil with 10, 25 or 50 instructions for use, knives or ampoule scarifiers in cardboard boxes or in corrugated cardboard boxes (for hospital).
When packing ampoules with notches, rings or break points, ampoule knives or scarifiers are not inserted.

Composition

Dragee and amitriptyline tablets contain 10 or 25 mg of active ingredient in the form amitriptyline hydrochloride.

Additional substances in tablets are: microcrystalline cellulose, talc, lactose monohydrate, silicon dioxide, magnesium stearate, pregelatinized starch.

Additional substances in the dragee are: magnesium stearate, potato starch, talc, polyvinylpyrrolidone, lactose monohydrate.

1 ml of solution contains 10 mg of active ingredient. Additional substances are: hydrochloric acid (sodium hydroxide), dextrose monohydrate, water for infusion, sodium chloride, benzethonium chloride.

Release form

The drug is available in the form of tablets, pills and solution.

pharmachologic effect

Tricyclic antidepressant ... It has a sedative, thymoleptic effect. It has an additional analgesic effect of central genesis.

Pharmacodynamics and pharmacokinetics

INN: Amitriptyline.

The drug reduces appetite, eliminates urinary incontinence, has antiserotonin action. The drug has a strong central and peripheral anticholinergic effect. Antidepressant effect is achieved by increasing the concentration of serotonin in the nervous system and norepinephrine in synapses. Long-term therapy leads to a decrease in the functional activity of serotonin and beta-adrenergic receptors in the brain. Amitriptyline reduces the severity of depressive manifestations, agitation , anxiety at anxiety-depressive states ... By blocking the H2-histamine receptors in the stomach wall (parietal cells), an antiulcer effect is provided. The medication is able to reduce body temperature, level during general anesthesia. The drug does not inhibit monoamine oxidase. The antidepressant effect appears after 3 weeks of therapy.

The maximum concentration of the substance in the blood occurs after a few hours, usually after 2-12 hours. Excreted by metabolites in the urine. It binds well to proteins.

Indications for the use of Amitriptyline

From what tablets and solution are usually prescribed?

The drug is indicated for depression (agitation, anxiety, sleep disorders, alcohol withdrawal, with organic brain lesions, neurotic withdrawal), with behavioral disturbances, mixed emotional disorders, nocturnal enuresis , chronic pain syndrome (with oncopathology, with postherpetic neuralgia ), with bulimia nervosa, with migraine (for prevention), with. Indications for the use of Amitriptyline in tablets and in other forms of release are the same.

Contraindications

According to the annotation, the medicine is not used for, intolerance to the main component, with angle-closure glaucoma , acute intoxication with psychoactive, analgesic, hypnotics, with acute alcohol intoxication. The medication is contraindicated in breastfeeding, severe violations of intraventricular conduction, antioventricular conduction. With pathology of the cardiovascular system, with inhibition of bone marrow hematopoiesis, manic-depressive psychosis , chronic alcoholism, decreased motor function of the digestive system, stroke, liver and kidney pathology, intraocular hypertension , urinary retention, prostatic hyperplasia, with hypotension of the bladder, thyrotoxicosis, pregnancy, epilepsy Amitriptyline is prescribed with caution.

Side effects of Amitriptyline

Nervous system: agitation, hallucinations, fainting, asthenia, drowsiness, anxiety, hypomanic state, increased depression, depersonalization, motor restlessness, increased epileptic seizures, extrapyramidal syndrome , ataxia, myoclonus, paresthesia in the form of peripheral neuropathy, tremor of small muscles, headaches.

Anticholinergic effects: increase, blurred vision, mydriasis, dry mouth, tachycardia , difficulty urinating, paralytic ileus, delirium, confusion, decreased sweating.

The cardiovascular system: instability of blood pressure, intraventricular conduction disorders , arrhythmia, orthostatic hypotension , dizziness, palpitations, tachycardia.

Digestive tract: darkening of the tongue, diarrhea, changes in taste, vomiting, gastralgia, hepatitis, cholestatic jaundice.

Endocrine system: galactorrhea, hyperglycemia, decreased potency or increased libido, an increase in the size of the mammary glands, gynecomastia, testicular edema, syndrome of inappropriate secretion of ADH, hyponatremia. Also noted hypoproteinemia , pollakiuria, urinary retention, swollen lymph nodes, hyperpyrexia, swelling, tinnitus, hair loss.

When the drug is discontinued, unusual agitation, sleep disturbances, malaise, headache, diarrhea, nausea, unusual dreams, motor restlessness, irritability ... When administered intravenously, there is a burning sensation, lymphangitis, thrombophlebitis ,.

Reviews of the side effects of Amitriptyline are quite frequent. When using the drug, addiction may occur.

Amitriptyline, application instruction (Way and dosage)

The medicine is taken orally immediately after a meal, without chewing, which ensures the least irritation of the stomach walls. The initial dosage is 25-50 mg per night for adults. Within 5 days, the amount of the drug is increased to 200 mg per day in 3 divided doses. If there is no effect within 2 weeks, the dose is increased to 300 mg.

The solutions are injected slowly intravenously and intramuscularly, 20-40 mg 4 times a day with a gradual transition to oral administration. The course of therapy is no more than 8 months. With prolonged headaches, with migraines, chronic pain syndrome of neurogenic origin, with migraines, 12.5-100 mg per day are prescribed.

Instructions for use of Amitriptyline Nycomed are similar. Before use, you should definitely familiarize yourself with the contraindications for the drug.

Overdose

Side manifestations nervous system: coma, stupor, increased drowsiness, anxiety, hallucinations, ataxia, epileptic syndrome, choreoathetosis , hyperreflexia, muscle tissue rigidity, confusion, disorientation, impaired concentration, psychomotor agitation.

Manifestations of an overdose with Amitriptyline from the side of cardio-vascular system: impaired intracardiac conduction, arrhythmia, tachycardia, drop in blood pressure, shock, heart failure , rarely - cardiac arrest.

Also noted, oliguria, increased sweating, hyperthermia , vomiting, shortness of breath, depression of the respiratory system, cyanosis. Potentially drug poisoning.

To avoid the negative consequences of an overdose, emergency gastric lavage, the introduction of cholinesterase inhibitors with pronounced anticholinergic manifestations are required. It also requires maintaining water and electrolyte balance, blood pressure levels, monitoring the work of the cardiovascular system, carrying out resuscitation and anticonvulsant measures if necessary. Forced diuresis , as well as hemodialysis have not been proven to be effective in overdose with amitriptyline.

Interaction

Antihypertensive effect, respiratory depression , a depressing effect on the nervous system is observed with the joint appointment of medications that inhibit the work of the central nervous system: general anesthetics, benzodiazepines, barbiturates, antidepressants and others. The drug enhances the severity of anticholinergic effects when taken , antihistamines , biperiden, atropine, antiparkinsonian drugs, phenothiazine. The drug enhances the anticoagulant activity of indadione, coumarin derivatives, indirect anticoagulants. There is a decrease in efficiency alpha blockers , phenytoin. , increase the concentration of the drug in the blood. The risk of developing epileptic seizures increases, and the central anticholinergic and sedative effects are enhanced when combined therapy with benzodiazepines, phenothiazines, anticholinergics. Simultaneous reception methyldopa , betanidine, guanethidine, reduces the severity of their hypotensive effect. When taking cocaine, arrhythmia develops. Delirium develops when taking acetaldehydrogenase inhibitors,. Amitriptyline enhances the effects on the cardiovascular system , norepinephrine, , isoprenaline. The risk of hyperpyrexia increases with the use of antipsychotics, m-anticholinergics.

Terms of sale

Prescription or not? The medicine is not sold without a prescription.

Storage conditions

Store in a dry, dark place inaccessible to children at a temperature of no more than 25 degrees Celsius.

Shelf life

No more than 3 years.

special instructions

Before starting therapy, it is mandatory to monitor the blood pressure level. Parenteral Amitriptyline is administered exclusively under the supervision of a physician in a hospital environment. In the first days of treatment, bed rest must be observed. A complete rejection of ethanol is required. Abrupt withdrawal from therapy can cause withdrawal syndrome ... A drug in a dose of more than 150 mg per day leads to a decrease in the seizure threshold, which is important to consider when developing epileptic seizures in patients with a predisposition. Perhaps the development of hypomanic or manic states in individuals with cyclical, affective disorders during the depressive phase. If necessary, treatment is resumed with low doses after the relief of these conditions. Care must be taken when treating people taking thyroid hormone medications, when treating patients with because of the possible risk of developing cardiotoxic effects. The medication can provoke the development of paralytic intestinal obstruction in the elderly, as well as those prone to chronic constipation. It is imperative to warn anesthesiologists about taking amitriptyline before performing local or general anesthesia. Long-term therapy provokes development. The need for riboflavin may increase. Amitriptyline passes into breast milk, causing increased drowsiness in infants. The medication has an effect on driving.

The medication is described on Wikipedia.

Amitriptyline and alcohol

Analogs of Amitriptyline

Matching ATX level 4 code:

The analogs of the drug are: Saroten and Amitriptyline Hydrochloride .

In this article, you can read the instructions for the use of the medicinal product. Amitriptyline... The reviews of site visitors - consumers of this medication, as well as opinions of doctors of specialists on the use of Amitriptyline in their practice are presented. A big request is to actively add your reviews about the drug: whether the medicine helped or did not help get rid of the disease, what complications and side effects were observed, which may not have been declared by the manufacturer in the annotation. Analogs of Amitriptyline in the presence of available structural analogs. Use for the treatment of depression, psychosis and schizophrenia in adults, children, as well as during pregnancy and lactation. The combination of the drug with alcohol.

Amitriptyline- antidepressant (tricyclic antidepressant). It also has some analgesic (central genesis), antiserotonin effect, helps to eliminate bedwetting and reduces appetite.

The mechanism of antidepressant action is associated with an increase in the concentration of norepinephrine and / or serotonin in the central nervous system (CNS) (a decrease in their reabsorption).

The mechanism of antiulcer action is due to the ability to provide sedative and m-anticholinergic action. Efficacy in bedwetting is apparently due to anticholinergic activity, leading to an increase in the ability of the bladder to stretch, direct beta-adrenergic stimulation, the activity of alpha-adrenergic agonists, accompanied by an increase in sphincter tone, and central blockade of serotonin uptake. 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 the effect on the endogenous opioid systems.

During general anesthesia, it lowers blood pressure and body temperature. Does not inhibit monoamine oxidase (MAO).

The antidepressant effect develops within 2-3 weeks after the start of use.

Pharmacokinetics

Absorption is high. Passes (including nortriptyline - a metabolite of amitriptyline) through the histohematological barriers, including the blood-brain barrier, placental barrier, and penetrates into breast milk. It is excreted by the kidneys (mainly in the form of metabolites) - 80% in 2 weeks, partly with bile.

Indications

depression (especially with anxiety, agitation and sleep disorders, including in childhood, endogenous, involutional, reactive, neurotic, drug, with organic brain lesions);
as part of complex therapy, it is used for mixed emotional disorders, psychosis in schizophrenia, alcohol withdrawal, behavioral disorders (activity and attention), nocturnal enuresis (except for patients with bladder hypotension), bulimia nervosa, chronic pain syndrome (chronic pain in cancer patients, migraine, rheumatic diseases, atypical pain in the face, postherpetic neuralgia, post-traumatic neuropathy, diabetic or other peripheral neuropathy), headache, migraine (prevention), gastric ulcer and 12 duodenal ulcer.

Forms of issue

Tablets 10 mg and 25 mg.

Dragee 25 mg.

Solution for intravenous and intramuscular administration (injections in ampoules for injection).

Instructions for use and dosage

Assign orally, without chewing, immediately after meals (to reduce irritation of the gastric mucosa).

Adults

For adults with depression, the initial dose is 25-50 mg at night, then the dose can be gradually increased, taking into account the effectiveness and tolerability of the drug, up to a maximum of 300 mg per day in 3 divided doses (most of the dose is taken at night). When a therapeutic effect is achieved, the dose can be gradually reduced to the minimum effective, depending on the patient's condition. The duration of the course of treatment is determined by the patient's condition, the effectiveness and tolerance of the therapy and can range from several months to 1 year, and, if necessary, even more. In old age, with mild disorders, as well as with bulimia nervosa, as part of complex therapy for mixed emotional disorders and behavioral disorders, psychosis with schizophrenia and alcohol withdrawal, it is prescribed in a dose of 25-100 mg per day (at night), after reaching a therapeutic effect, they are transferred for the minimum effective dose - 10-50 mg per day.

For the prevention of migraine, with chronic pain syndrome of a neurogenic nature (including prolonged headaches), as well as in the complex therapy of gastric ulcer and duodenal ulcer - from 10-12.5-25 to 100 mg per day (the maximum part of the dose taken at night).

Children

For children as an antidepressant: from 6 to 12 years old - 10-30 mg per day or 1-5 mg / kg per day in divided doses, in adolescence - up to 100 mg per day.

With nocturnal enuresis in children 6-10 years old - 10-20 mg per day at night, 11-16 years old - up to 50 mg per day.

Side effect

blurred vision;
mydriasis;
increased intraocular pressure (only in individuals with a local anatomical predisposition - a narrow angle of the anterior chamber);
drowsiness;
fainting;
fatigue;
irritability;
anxiety;
disorientation;
hallucinations (especially in elderly patients and in patients with Parkinson's disease);
anxiety;
mania;
memory impairment;
decreased ability to concentrate;
insomnia;
"nightmarish" dreams;
asthenia;
headache;
ataxia;
increased frequency and intensification of epileptic seizures;
changes in the electroencephalogram (EEG);
tachycardia;
palpitations;
dizziness;
orthostatic hypotension;
arrhythmia;
lability of blood pressure (decrease or increase in blood pressure);
dry mouth;
constipation;
nausea, vomiting;
heartburn;
gastralgia;
an increase in appetite and body weight, or a decrease in appetite and body weight;
stomatitis;
change in taste;
diarrhea;
darkening of the tongue;
enlargement (swelling) of the testicles;
gynecomastia;
an increase in the size of the mammary glands;
galactorrhea;
decreased or increased libido;
decreased potency;
skin rash;
photosensitivity;
angioedema;
hives;
hair loss;
noise in ears;
swelling;
hyperpyrexia;
swollen lymph nodes;
retention of urine.

Contraindications

hypersensitivity;
use in conjunction with MAO inhibitors and 2 weeks before starting treatment;
myocardial infarction (acute and subacute periods);
acute alcohol intoxication;
acute intoxication with hypnotics, analgesic and psychoactive drugs;
angle-closure glaucoma;
severe violations of AV and intraventricular conduction (blockade of the bundle of His, AV block 2 tbsp.);
lactation period;
children under 6 years of age;
intolerance to galactose;
lactase deficiency;
glucose-galactose malabsorption.

Application during pregnancy and lactation

In pregnant women, the drug should be used only if the intended benefit to the mother outweighs the potential risk to the fetus.

Application in children

Contraindicated in children under 6 years of age.

special instructions

Before starting treatment, blood pressure control is necessary (in patients with low or labile blood pressure, it may decrease even more); during the treatment period - control of peripheral blood (in some cases, agranulocytosis may develop, and therefore it is recommended to monitor the blood picture, especially with an increase in body temperature, the development of flu-like symptoms and tonsillitis), with prolonged therapy - control of the functions of the CVS and liver. In the elderly and patients with CVS diseases, monitoring of heart rate, blood pressure, ECG is shown. On the ECG, clinically insignificant changes may appear (smoothing of the T wave, depression of the S-T segment, expansion of the QRS complex).

Care must be taken when moving abruptly to an upright position from a "lying" or "sitting" position.

During the treatment period, the use of ethanol should be excluded.

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

With a sudden cessation of admission after long-term treatment, the development of a "withdrawal" syndrome is possible.

Amitriptyline in doses above 150 mg per day reduces the threshold of seizure activity (the risk of epileptic seizures in predisposed patients should be taken into account, as well as in the presence of other factors predisposing to the onset of convulsive syndrome, for example, brain damage of any etiology, the simultaneous use of antipsychotic drugs (neuroleptics ), during the period of refusal from ethanol or withdrawal of drugs with anticonvulsant properties, for example, benzodiazepines). Severe depression is characterized by the risk of suicidal actions, which can persist until significant remission is achieved. In this regard, at the beginning of treatment, a combination with drugs from the benzodiazepine group or antipsychotic drugs and constant medical supervision (entrusting authorized persons with the storage and dispensing of drugs) may be indicated. In children, adolescents and young people (under 24 years of age) with depression and other mental disorders, antidepressants, compared with placebo, increase the risk of suicidal thoughts and suicidal behavior. Therefore, when prescribing amitriptyline or any other antidepressants in this category of patients, the risk of suicide and the benefits of their use should be correlated. In short-term studies, the risk of suicide did not increase in people over 24 years old, and in people over 65 years old it was slightly reduced. During treatment with antidepressants, all patients should be monitored for early detection of suicidal tendencies.

Due to the possible cardiotoxic effects, caution is required when treating patients with thyrotoxicosis or patients receiving thyroid hormone preparations.

In combination with electroconvulsive therapy, it is prescribed only with careful medical supervision.

In predisposed patients and elderly patients, it can provoke the development of drug psychoses, mainly at night (after discontinuation of the drug, they disappear within a few days).

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

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

With prolonged use, there is an increase in the incidence of dental caries. The need for riboflavin may be increased.

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

Drug interactions

With the combined use of ethanol (alcohol) and drugs that depress the central nervous system (including other antidepressants, barbiturates, benzadiazepines and general anesthetics), a significant increase in the inhibitory effect on the central nervous system, respiratory depression and hypotensive effect is possible. Increases sensitivity to beverages containing ethanol (alcohol).

Increases the anticholinergic effect of drugs with anticholinergic activity (for example, phenothiazine derivatives, antiparkinsonian drugs, amantadine, atropine, biperiden, antihistamines), which increases the risk of side effects (from the central nervous system, vision, intestines and bladder). When combined with anticholinergics, phenothiazine derivatives and benzodiazepines - mutual enhancement of sedative and central anticholinergic effects and an increased risk of epileptic seizures (lowering the threshold of seizure activity); derivatives of phenothiazine, in addition, may increase the risk of neuroleptic malignant syndrome.

Inhibitors of microsomal oxidation (cimetidine) lengthen T1 / 2, increase the risk of developing the toxic effects of amitriptyline (a dose reduction of 20-30% may be required), inducers of microsomal liver enzymes (barbiturates, carbamazepine, phenytoin, nicotine and oral contraceptives) reduce plasma concentrations and reduce the effectiveness of amitriptyline.