Amitriptyline-Grindeks 10 mg 50 pcs film-coated tablets

Action of amitriptyline

The main effect of amitriptyline is antidepressant.
It also has a sedative (calming), hypnotic and anti-anxiety effect. It has no effect on a healthy person with a normal psychological state. These effects appear only in the presence of depression, restlessness, anxiety and insomnia, respectively. In addition to the effects of amitriptyline, there are other effects:

• Anesthetic.
• Vegetative stabilizing.
• Antidiarrheal (fixing).
• Removes psychosomatic symptoms: skin rash, high blood pressure, restores appetite, etc.
• Effective for some forms of enuresis (bedwetting).

Compound

Indications for use

As doctors and scientists accumulate experience in the use of amitriptyline and clarify the mechanisms of development of many diseases, the indications for its use are constantly expanding. Main indications:

• Endogenous depression.
• Depressive psychosis.
• Anxiety disorders: generalized anxiety disorder, panic disorder, phobias, obsessive-compulsive disorder.
• Organic anxiety and depression.
• Schizotypal disorder, schizophrenia with depressive symptoms.
• Addictions (alcohol, drug, polydrug addiction).
• Neuroses.
• Personality disorders (psychopathy).
• Somatoform and psychosomatic diseases.
• Eating disorders.
• Pain syndrome.
• Enuresis.

Directions for use and doses

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, to a maximum of 300 mg/day in 3 doses (the largest part 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 tolerability of the therapy and can range from several months to 1 year, and if necessary, 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, psychoses in schizophrenia and alcohol withdrawal, prescribed in a dose of 25–100 mg/day (at night), after achieving a therapeutic effect, switch for 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 and duodenal ulcers - from 10–12.5–25 to 100 mg/day (maximum dose taken at night).

Children

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

For 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

From the nervous system and sensory organs: disturbance of accommodation, increased intraocular pressure, drowsiness.

From the cardiovascular system and blood (hematopoiesis, hemostasis): tachycardia, arrhythmia, orthostatic arterial hypertension, changes in the blood picture, incl. agranulocytosis.

From the gastrointestinal tract: stomatitis, taste disturbance, anorexia, nausea, vomiting, epigastric discomfort, dry mouth, stool retention, intestinal obstruction, liver dysfunction (rare).

Other: skin rash, hair loss, swollen lymph nodes, fever, gynecomastia, galactorrhea, changes in ADH secretion, decreased libido, potency, increased body weight with long-term use, urinary retention.

Precautionary measures

Concomitant use with MAO inhibitors can be fatal. The treatment break between taking MAO inhibitors and amitriptyline (and other tricyclic antidepressants) should be at least 14 days.

Amitriptyline at a dose above 150 mg/day lowers the threshold for seizure activity, therefore the risk of seizures increases in patients with a history of seizures.

During treatment, driving vehicles, servicing machinery and other types of work that require increased attention are prohibited.

Treatment of elderly patients must be carefully monitored, using minimal doses of the drug, increasing them gradually.

A transition from the depressive phase of manic-depressive psychosis to the manic stage is possible.

If the patient's condition does not improve within 3–4 weeks, further therapy is not advisable.

Contraindications

Hypersensitivity, toxic depression of the central nervous system, decompensated heart disease, acute and recovery period of myocardial infarction, cardiac muscle conduction disturbances, stage III hypertension, acute liver and kidney diseases, blood diseases, gastric and duodenal ulcers in the acute stage, glaucoma, prostate hypertrophy glands, atony of the bladder, pyloric stenosis, paralytic ileus, combined use with MAO inhibitors, pregnancy, breastfeeding, children under 6 years of age.

Pharmacokinetics

When taken orally, its bioavailability is 33–62%, Cmax in blood plasma is achieved after 4–8 hours. Metabolized in the liver to form the active metabolite nortriptyline. Therapeutic blood concentrations for amitriptyline and nortriptyline are 120–240 ng/ml. Excretion is mainly renal. Complete elimination occurs within 7 days. T1/2 of amitriptyline is 10–28 hours, nortriptyline is 16–80 hours. Amitriptyline passes through the placental barrier and penetrates into breast milk, creating concentrations similar to plasma concentrations.

Amitriptyline (Amixid, Sarotene)

Clinical and pharmacological group

Antidepressant

Indications

Depression (especially with anxiety, agitation and sleep disorders, including in childhood, endogenous, involutional, reactive, neurotic, drug-induced, with organic brain damage).

As part of complex therapy, it is used for mixed emotional disorders, psychoses 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), headaches, migraines (prevention), gastric and duodenal ulcers.

Contraindications

Hypersensitivity, use in conjunction 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, angle-closure glaucoma, severe AV and intraventricular conduction disorders (branch block His bundle, AV block II stage), lactation period, children under 6 years of age.

Due to the content of lactose monohydrate (milk sugar) in the tablets, the drug should not be taken by patients with rare hereditary diseases such as galactose intolerance, lactase deficiency or glucose-galactose malabsorption.

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

Dosage

Administered 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 gradually the dose can be increased taking into account the effectiveness and tolerability of the drug to a maximum of 300 mg/day. in 3 doses (the largest part 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 tolerability of the therapy and can range from several months to 1 year, and if necessary, 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, a dose of 25-100 mg/day is prescribed. (at night), after achieving a therapeutic effect, switch to the minimum effective dose - 10-50 mg/day.

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

Children

For 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.

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

Side effects

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

From the central nervous system: drowsiness, fainting, fatigue, irritability, anxiety, disorientation, hallucinations (especially in elderly patients and patients with Parkinson's disease), anxiety, psychomotor agitation, mania, hypomania, memory impairment, decreased ability to concentrate, insomnia, nightmares, asthenia; headache; dysarthria, tremor of small muscles, especially the 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 cardiovascular system: tachycardia, palpitations, dizziness, orthostatic hypotension, nonspecific changes in the electrocardiogram (ECG) (S-T interval or T wave) in patients without heart disease; arrhythmia, blood pressure lability (decrease or increase in blood pressure), intraventricular conduction disturbances (widening of the QRS complex, changes in the PQ interval, bundle branch block).

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

From the endocrine system: increase in size (swelling) of the testicles, gynecomastia; increase in the size of the mammary glands, galactorrhea; decreased or increased libido, decreased potency, hypo- or hyperglycemia, hyponatremia (decreased vasopressin production), syndrome of inappropriate secretion of antidiuretic hormone (ADH). Allergic reactions: skin rash, itching, photosensitivity, angioedema, urticaria.

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

With long-term treatment, especially in high doses, if it is abruptly stopped, withdrawal syndrome may develop: 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), impaired liver function, ageusia.

Overdose

Symptoms

.

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

From the cardiovascular system: decreased blood pressure, tachycardia, arrhythmia, intracardiac conduction disturbances, ECG changes (especially QRS) characteristic of intoxication with tricyclic antidepressants, shock, heart failure; in very rare cases - cardiac arrest.

Other: 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; for severe anticholinergic effects (lowering blood pressure, arrhythmia, coma, myoclonic epileptic seizures) - administration of cholinesterase inhibitors (the use of physostigmine is not recommended due to the increased risk of seizures); maintaining blood pressure and water-electrolyte balance. Monitoring of cardiovascular functions (including ECG) for 5 days (relapse may occur after 48 hours or later), anticonvulsant therapy, artificial pulmonary ventilation (ALV) and other resuscitation measures are indicated. Hemodialysis and forced diuresis are ineffective.

Drug interactions

When ethanol is used together with drugs that depress the central nervous system (including other antidepressants, barbiturates, benzadiazepines and general anesthetics), a significant increase in the depressant effect on the central nervous system, respiratory depression and hypotensive effect is possible. Increases sensitivity to drinks containing ethanol.

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 used together with anticholinergic blockers, phenothiazine derivatives and benzodiazepines, there is a mutual enhancement of the sedative and central anticholinergic effects and an increased risk of epileptic seizures (lowering the threshold of convulsive activity); Phenothiazine derivatives may also increase the risk of neuroleptic malignant syndrome.

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

When used together with antihistamines, clonidine - increased 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), the anticoagulant activity of the latter may increase. Amitriptyline may enhance depression caused by glucocorticosteroids (GCS). Medicines used to treat thyrotoxicosis increase the risk of developing agranulocytosis. Reduces the effectiveness of phenytoin and alpha-blockers.

Inhibitors of microsomal oxidation (cimetidine) prolong T1/2, increase the risk of developing 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.

Combined use with disulfiram and other acetaldehydrogenase inhibitors provokes delirium.

Fluoxetine and fluvoxamine increase plasma concentrations of amitriptyline (a 50% reduction in amitriptyline dose may be required).

Estrogen-containing oral contraceptives and estrogens may increase the bioavailability of amitriptyline.

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.

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

Pimozide and probucol may increase cardiac arrhythmias, which is manifested by prolongation of the QT interval on the ECG.

It enhances the effect of epinephrine, norepinephrine, isoprenaline, ephedrine and phenylephrine on the cardiovascular system (including when these drugs are part of local anesthetics) and increases the risk of developing heart rhythm disturbances, tachycardia, and severe arterial hypertension.

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

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

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

When co-administered with other hematotoxic drugs, increased hematotoxicity is possible.

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

special instructions

Before starting treatment, blood pressure monitoring 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, development of flu-like symptoms and sore throat), during long-term therapy - control of the functions of the cardiovascular system and liver. In the elderly and patients with cardiovascular diseases, monitoring of heart rate, blood pressure, and ECG is indicated. Clinically insignificant changes may appear on the ECG (smoothing of the T wave, depression of the ST segment, widening of the QRS complex).

Caution is required when suddenly moving to a vertical position from a “lying” or “sitting” position.

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

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

If you suddenly stop taking it after long-term treatment, it is possible that withdrawal syndrome may develop in newborns (manifested by shortness of breath, drowsiness, intestinal colic, increased nervous excitability, increased or decreased blood pressure, tremor or spastic phenomena); amitriptyline is gradually discontinued at least 7 weeks before the expected childbirth

Use in childhood

Contraindicated for children under 6 years of age.

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

For impaired renal function

Use with caution in case of renal failure.

For liver dysfunction

Use with caution in case of liver failure.

Use in old age

Use with caution in elderly people.

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

Conditions
for dispensing from pharmacies
The drug is dispensed with a prescription.

Storage conditions and periods

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

Release form, composition and packaging

Pills

from white to white with a slightly yellowish tint, flat-cylindrical in shape, with a chamfer; 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 mcg, talc - 1.2 mg, magnesium stearate - 1.2 mg.

10 pieces. — cellular contour packages (1) — cardboard packs. 10 pieces. — contour cell packaging (2) — cardboard packs. 10 pieces. — cellular contour packages (3) — cardboard packs. 10 pieces. — contour cell packaging (4) — cardboard packs. 10 pieces. — contour cell packaging (5) — cardboard packs. 100 pieces. — polymer jars (1) — cardboard packs.

Pills

from white to white with a slightly yellowish tint, flat-cylindrical in shape, with a chamfer and a notch; 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. — cellular contour packages (1) — cardboard packs. 10 pieces. — contour cell packaging (2) — cardboard packs. 10 pieces. — cellular contour packages (3) — cardboard packs. 10 pieces. — contour cell packaging (4) — cardboard packs. 10 pieces. — contour cell packaging (5) — cardboard packs. 100 pieces. — polymer jars (1) — cardboard packs.

Interaction

Neuroleptics, sedatives and hypnotics, anticonvulsants, central and narcotic analgesics, anesthetics, and alcohol potentiate the inhibitory effect on the central nervous system. Enhances the hypertensive effect of catecholamines, blocks the antihypertensive effect of guanethidine and drugs with a similar mechanism of action. Cimetidine increases plasma concentrations of amitriptyline.

Combination with neuroleptics and/or anticholinergic drugs can cause a febrile temperature reaction, paralytic intestinal obstruction.

Overdose

Symptoms: drowsiness, disorientation, confusion, dilated pupils, increased body temperature (fever), shortness of breath, dysarthria, agitation, hallucinations, seizures, muscle rigidity, stupor, coma, vomiting, arrhythmia, hypotension, heart failure, respiratory depression.

Treatment: cessation of therapy, gastric lavage, fluid infusion, intramuscular or intravenous administration of physostigmine 1–3 mg every 0.5–2 hours (for children, physostigmine administration begins with a dose of 0.5 mg, then the dose is repeated with a 5-minute interval to determine the minimum effective dose, but not more than 2 mg). Physostigmine should be used only for coma, respiratory depression and other severe disorders; symptomatic therapy, maintaining blood pressure and water-electrolyte balance. Monitoring of cardiovascular activity (ECG) is indicated for 5 days, because relapse may occur within 48 hours or later.