Amitriptyline (Amitriptyline)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceAmitriptylineAmitriptyline
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    • Dosage form: & nbsppills
    Composition:

    One tablet contains:

    active substance: amitriptyline hydrochloride - 11.32 mg or 28.30 mg, corresponding to 10 mg and 25 mg of amitriptyline;

    Excipients: microcrystalline cellulose - 40/100 mg, lactose monohydrate (milk sugar) - 40/100 mg, pregelatinized starch - 25.88 / 64.70 mg, silicon dioxide colloid (aerosil) - 0.4 / 1 mg, talc - 1 , 2/3 mg, magnesium stearate - 1,2 / 3 mg.

    Description:

    Tablets from white to white with a yellowish tinge of color, light marbles are allowed.

    For a dosage of 10 mg - flat cylindrical with a bevel.

    For dosage of 25 mg - flat-cylindrical with a facet and a risk.

    Pharmacotherapeutic group:Antidepressant
    ATX: & nbsp

    N.06.A.A.09   Amitriptyline

    Pharmacodynamics:

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

    Has a strong peripheral and central anticholinergic action due to high affinity for m-holinoretseptoram; a strong sedative effect associated with affinity for H1-histamine receptors, and alpha-adrenoblocking action. Has the properties of antiarrhythmic drug (LS) IA class, like quinidine in therapeutic doses slows the ventricular conduction (with an overdose can cause severe intraventricular blockade).The mechanism of antidepressant action is associated with an increase in the concentration of noradrenaline and / or serotonin in the central nervous system (CNS) (a decrease in their reverse absorption).

    Accumulation of these neurotransmitters occurs as a result of inhibition of their inverse capture by the membranes of presynaptic neurons. With prolonged use reduces the functional activity of beta-adrenergic and serotonin receptors in the brain, normalizes adrenergic and serotonergic transmission, restores the balance of these systems, disturbed in depressive states. With anxiety-depressive states reduces anxiety, agitation and depressive manifestations.

    The mechanism of antiulcer action is due to the ability to exert sedative and m-anticholinergic action. Efficacy at night urinary incontinence is apparently due to anticholinergic activity leading to increased bladder capacity for stretching, direct beta adrenergic stimulation, alpha-adrenergic agonist activity accompanied by increased 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 influence on endogenous opioid systems. The mechanism of action for bulimia nervosa is unclear (it may be similar to that in depression). It shows a distinct effect of the drug with bulimia in patients with both depression and its presence, while a decrease in bulimia can be noted without the concomitant weakening of depression itself.

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

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

    Pharmacokinetics:

    Absorption is high.

    Bioavailability of amitriptyline 30-60%, its active metabolite nortriptyline - 46-70%. The time to reach the maximum concentration (Tmah) after intake of 2.0-7.7 hours. The volume of distribution is 5-10 l / kg. Effective therapeutic concentrations in the blood for amitriptyline are 50-250 ng / ml, for nortriptyline 50-150 ng / ml. The maximum concentration in the blood plasma (Cmah) 0.04-0.16 μg / ml. Passes (including nortriptyline) through the histohematological barriers, including the blood-brain barrier, the placental barrier, "penetrates into breast milk.The connection with plasma proteins is 96%. Metabolized in the liver with the participation of isoenzymes CYP2C19, CYP2D6, has the effect of "first passage" (by demethylation, hydroxylation) with the formation of active metabolites - nortriptyline, 10-hydroxy-amitriptyline, and inactive metabolites. The half-life of blood plasma (T1 / 2) is 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, in part 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 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), headache, migraine (prophylaxis), gastric ulcer and duodenal ulcer.

    Contraindications:

    Hypersensitivity, application in conjunction with MAO inhibitors and 2 weeks before the start of treatment, myocardial infarction (acute and subacute periods), acute alcohol intoxication, acute intoxication with sleeping pills, analgesic and psychoactive drugs, closed-angle glaucoma, severe disorders AV and intraventricular conduction (blockade of the legs of the bundle of His, AV blockade of the II century), lactation period, children under 6 years old.

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

    Carefully:

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

    Pregnancy and lactation:

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

    Penetrates into breast milk and can cause drowsiness in infants.
    Dosing and Administration:

    Assign inside, not liquid, immediately after meals (to reduce irritation of the gastric mucosa).

    Adults

    Adults with depression, the initial dose - 25-50 mg per 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 divided doses (most of the dose is taken at night).When the 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, effectiveness and tolerability of the therapy and can range from several months to 1 year, and, if necessary, more.

    In elderly patients with mild disorders, as well as with nervous bulimia, as part of complex therapy for mixed emotional disorders and behavioral disorders, psychoses in schizophrenia and alcohol withdrawal are prescribed at a dose of 25-100 mg / day (at night), after reaching a therapeutic effect, they switch over at minimal effective doses -10-50 mg / day.

    For the prevention of migraine, with a chronic pain syndrome neurogenic in nature (including long-term headaches), as well as in the complex therapy of peptic ulcer of the stomach and duodenum - from 10-12,5-25 to 100 mg / day (maximum part of the dose is taken at night).

    Children

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

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

    Side effects:

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

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

    From the CAS side: tachycardia, palpitations, dizziness, orthostatic hypotension, nonspecific changes on the electrocardiogram (ECG) (interval S-T 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 complex QRS, interval changes P-Q, blockade of the legs of the bundle of His).

    From the digestive tract: nausea, heartburn, gastralgia, hepatitis (including liver and cholestatic icterus), vomiting, increased appetite and weight gain or reduction of appetite and body weight, disease, change in taste, diarrhea, darkening of the tongue.

    On the part of the endocrine system, an increase in the size (swelling) of the testicles, gynecomastia; an increase in the size of the mammary glands, galactorrhea; decrease or increase libido, reduction of potency, hypo- or hyperglycemia, hyponatremia (decreased production of vasopressin), antidiuretic hormone syndrome of inappropriate secretion (ADH).

    Allergic reactions: skin rash, itching, photosensitivity, angioedema, hives.

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

    With long-term treatment, especially in high doses, when it is abruptly terminated, it is possible development of withdrawal syndrome: nausea, vomiting, diarrhea, headache, malaise, sleep disorders, unusual dreams, unusual arousal; with a gradual cancellation after a long treatment - irritability, motor anxiety, sleep disturbances, unusual dreams.

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

    Overdose:

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

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

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

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

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

    Interaction:

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

    Increases sensitivity to drinks containing ethanol.

    Increases the anticholinergic effect of drugs with anticholinergic activity (for example, phenothiazine derivatives, antiparkinsonian drugs, amantadine, atropine, biperiden, antihistamine drugs), which increases the risk of side effects (from the side of the central nervous system, vision, intestine and bladder). When combined with the use holinoblokatorami, derivatives of phenothiazine and benzodiazepine - mutual enhancement of sedation and central anticholinergic effects and increase the risk of seizures (seizure threshold reduction); derivatives of phenothiazine, in addition, may increase the risk of neuroleptic malignant syndrome.

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

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

    With the simultaneous use of amitriptyline and indirect anticoagulants (coumarin derivatives or indadion), an increase in anticoagulant activity of the latter is possible. Amitriptyline can enhance depression caused by glucocorticosteroids (GCS).

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

    Reduces the effectiveness of phenytoin and alpha-blockers.

    Inhibitors of microsomal oxidation (cimetidine) prolong T1 / 2, increase the risk of development of 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 decrease the effectiveness of amitriptyline.

    Joint use with disulfiram and other inhibitors of acetaldehyde genase provokes delirium.

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

    Estrogen-containing oral contraceptive drugs and estrogens can increase the bioavailability of amitriptyline.

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

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

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

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

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

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

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

    With joint appointment with others.hematotoxic drugs may increase hematotoxicity.

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

    Special instructions:

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

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

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

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

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

    Amitriptyline at a dose higher than 150 mg / day decreases the threshold for seizure activity (note the risk of epileptic attacks in predisposed patients, and also in the presence of others. Predisposing to seizures factors such as brain damage of any etiology, the simultaneous use of antipsychotic drugs (neuroleptics) , during the period of rejection of ethanol or the abolition of drugs that have anticonvulsant properties, for example, benzodiazepines). Depression is characterized by the risk of suicidal actions, which can persist until a significant remission is achieved. In this connection, in the beginning of treatment with a combination of drugs from the benzodiazepine or neuroleptic drugs and constant medical supervision (charging proxies storage and distribution of drugs) can be displayed.

    In children, adolescents and young people (under 24 years) with depression and other mental disorders, antidepressants, compared with placebo, increase the risk of suicidal thoughts and suicidal behavior.Therefore, the appointment of amitriptyline or any other. Antidepressant in these patients should be related to the risk of suicide and benefit from their use. In short-term studies in people over 24 years of age, the risk of suicide did not increase, but in people older than 65 years, it declined slightly. 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 of manic or hypomanic state may develop during therapy (required dose reduction or withdrawal of the drug and antipsychotic drugs). After the relief of these conditions, if there are indications, treatment at low doses can be resumed.

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

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

    In predisposed patients and elderly patients, it can provoke the development ofpsychosis, mainly at night (after the drug is withdrawn for several days).

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

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

    Due to the anticholinergic effect, a decrease in tearing and a relative increase in the amount of mucus in the tear fluid can occur, which may cause 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.

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

    Penetrates into breast milk and can cause drowsiness in infants.

    To avoid the development of the "cancellation" syndrome in newborns (manifested by shortness of breath, drowsiness, intestinal colic, increased nervous excitability, increase or decrease in blood pressure, tremor, or spastic phenomena), amitriptyline is gradually withdrawn at least 7 weeks before the expected delivery.

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

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

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

    Form release / dosage:

    Tablets of 10 mg or 25 mg.

    Packaging:

    10 tablets per contour cell pack.

    1, 2, 3, 4 or 5 contour mesh packages with instructions for use in a pack of cardboard.

    100 tablets per can of polymer.

    By 500, 600,1000, 1200 tablets in a can of polymer (for hospitals).

    Each jar with instructions for use in a pack of cardboard.
    Storage conditions:

    In a dry, protected from light place at a temperature of no higher than 25 ° C.

    Keep out of the reach of children.

    Shelf life:

    3 years. Do not use after the expiration date.

    Terms of leave from pharmacies:On prescription
    Registration number:LS-001144
    Date of registration:15.03.2011
    Expiration Date:Unlimited
    The owner of the registration certificate:ALSI Pharma, ZAO ALSI Pharma, ZAO Russia
    Manufacturer: & nbsp
    Information update date: & nbsp12.08.2017
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