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

Has a strong peripheral and central anticholinergic action due to high affinity for m-holinoretseptoram; a strong sedative effect associated with affinity in H1-histamine receptors, and alpha-adrenoblocking action.

Has the properties of antiarrhythmic drug subgroup Ibut, like quinidine in therapeutic doses, it slows the ventricular conduction (overdose can cause severe intraventricular blockage).

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

Antidepressant effect develops within 2-3 weeks after the beginning of application. Has antiulcer action (able to block H2-histamine receptors in parietal cells of the stomach).

Has an anti-bulimic, central analgesic effect; It is effective at night urinary incontinence.

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

Pharmacokinetics:

Absorption is high. With oral administration of amitriptyline, the maximum plasma concentrations are reached within 4-8 hours. The bioavailability of amitriptyline is 33 to 62%, its active metabolite nortriptyline is 46-70%. Time to reach the maximum concentration after ingestion - 2.0-7.7 hours.The volume of distribution is 5-10 l / kg. The maximum concentration in blood plasma is 0.04-0.16 μg / ml. Effective therapeutic concentrations in blood plasma amitriptyline - 50-250 ng / ml, for nortriptyline - 50-150 ng / ml. The connection with plasma proteins is 92-96%. The concentration of amitriptyline in tissues is higher than in plasma. Penetrates through the blood-brain barrier, placental barrier, is excreted in breast milk in concentrations similar to plasma. Metabolised in the liver (by demethylation, hydroxylation) with the formation of active metabolites - nortriptyline, 10-hydroxy-amitriptyline and inactive metabolites. Half-life (T_1/2) from the blood plasma - 10-26 h for amitriptyline and 18-44 h for nortriptyline. It is excreted by the kidneys (mainly in the form of metabolites) - 80% in 2 weeks, in part with feces. Complete excretion within 7-14 days.

Indications:

Apply strictly according to the doctor's prescription.

- mild and severe depression of any etiology. Especially effective in anxious - Depressive states, due to the severity of sedation. Does not cause an exacerbation of productive symptoms (delusions, hallucinations), in contrast to antidepressants with a stimulating effect;

- mixed emotional disorders and neurotic states;

- night enuresis (except for patients with bladder hypotension);

- neurogenic chronic pain, for the prevention of migraine.

Contraindications:

- Hypersensitivity to amitriptyline and other components of the drug;

- use 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 hypnotics, analgesics and psychoactive drugs;

- angle-closure glaucoma;

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

- pregnancy and the period of breastfeeding;

- children's age till 12 years;

- with diseases of the liver and kidneys with a pronounced impairment of function.

Carefully:

- Chronic alcoholism;

- bronchial asthma;

- affective insanity;

- diseases of the cardiovascular system (angina pectoris, arrhythmia, AV blockade of the heart of the I degree, chronic heart failure, postinfarction cardiosclerosis, arterial hypertension);

- decreased motor function of the gastrointestinal tract (riskthe occurrence of paralytic intestinal obstruction);

- urinary retention, bladder hypotension;

- intraocular hypertension;

- thyrotoxicosis;

- hyperplasia of the prostate;

- elderly age.

Dosing and Administration:

Assign inside, not liquid, to reduce irritation of the gastric mucosa, taken after meals, starting at 50-75 mg per day. Then the dose is daily increased by 25-50 mg / day (with the predominant increase in the evening dose) until the "working" dose of 150-200-250 (up to 300) mg / day.

With poor tolerance of amitriptyline, as well as in elderly or somatically weakened patients, in adolescents and young people, in primary (previously untreated) patients or in comparatively mild depression, when there is time to wait for the effect, a slower rate of dose build-up (for example, 25 mg every 2-3 days).

Conversely, in severe, suicidally depressed situations, in situations requiring the fastest antidepressant effect, as well as in patients previously treated with tricyclic antidepressants and well tolerated with this group of drugs, it is permissible to administer the full therapeutic dose from the first days of therapy, or start at a higher dose (for example, 100 mg / day) and a more rapid and aggressive build-up to a "working" dose.The value of the "working" dose, which should be considered when increasing doses, is determined by the degree of severity of depression and the experience of treating previous depressive phases in this particular patient, as well as the tolerability of the drug by this patient.

The average daily dose in the treatment of endogenous depressions is 150 - 250 mg, divided into 2-3-4 admission (during the day and at bedtime). Sometimes you can give the entire daily dose at night, before bed.

In severe depression it is permissible to increase the daily dose of amitriptyline up to 400- 450 mg / day, if tolerability permits, which is greater than the prescribed instruction maximum dose of 300 mg / day.

The therapeutic effect of amitriptyline usually comes in 2-3-4 weeks (sometimes as early as a week), counting from the moment of achieving a "working" antidepressant dose (not less than 150 mg / day). If within 2 weeks there was no improvement, the daily dose is increased to 300 mg. With the disappearance of signs of depression, the dose is reduced to 50-100 mg / day and the therapy is continued for at least 3 months.

With neurotic states appoint inwards in relatively small doses - not more than 25 mg per day.

With nocturnal enuresis in children 12-16 years of age - 25-50 mg / day.

For the prevention of migraine, with chronic pain of a neurogenic nature (including long-term headaches) - from 25 to 100 mg / day (the maximum part of the dose is taken at night).

In elderly patients with mild violations in outpatient practice Doses are 25-50-100 mg maximum, in divided doses or once a day at night.

Side effects:

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

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

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

From the digestive system: nausea, hepatitis (including impaired liver function and cholestatic jaundice), heartburn, vomiting, gastralgia, increased appetite and weight body or loss of appetite and body weight, stomatitis, taste change, diarrhea, darkening language.

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

From the hematopoiesis: agranulocytosis, leukopenia, thrombocytopenia, purpura, eosinophilia.

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

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

Symptoms of cancellation: with sudden cancellation after long-term treatment - 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.

Overdose:

Symptoms:

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

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

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

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

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

Treatment: symptomatic, and maintenance therapy; in severe anticholinergic - effects (lowering of blood pressure, arrhythmias, coma, myoclonic seizures) - administering a cholinesterase inhibitor (physostigmine use is not recommended because of the increased risk of seizures); maintenance of blood pressure and water-electrolyte balance.

Control of CAS functions (including ECG) is shown for 5 days (relapse may occur after 48 hours and later), anticonvulsant therapy, artificial lung ventilation (ALV) and other resuscitation measures.

Hemodialysis and forced diuresis are ineffective.

Interaction:

With simultaneous application:

- with drugs that exert a depressing effect on the central nervous system, a significant increase in the inhibitory effect on the central nervous system, hypotensive action, respiratory depression;

- with drugs with anticholinergic activity, anticholinergic effects may be enhanced;

- it is possible to increase the effect of sympathomimetic drugs on CAS and increase the risk of heart rhythm disturbances, tachycardia, severe arterial hypertension;

- with antipsychotic drugs (neuroleptics) is mutually inhibited metabolism, with a decrease in the threshold of convulsive readiness;

- with antihypertensive drugs (with the exception of clonidine, guanethidine and their derivatives) may increase the antihypertensive effect and the risk of developing orthostatic hypotension;

- with MAO inhibitors may develop a hypertensive crisis; with clonidine,guanethidine - a decrease in the hypotensive effect of clonidine or guanethidine is possible; with barbiturates, carbamazepine - possible decrease in the effect of amitriptyline due to increased metabolism;

- with sucralfate decreases the absorption of amitriptyline; with fluvoxamine - increases the concentration of amitriptyline in the blood plasma and the risk of developing toxic effects; with fluoxetine - increases the concentration of amitriptyline in the blood plasma, and toxic reactions develop due to oppression of the isoenzyme CYP2D6 under the influence of fluoxetine; with quinidine - possibly slowing the metabolism of amitriptyline; with cimetidine - possibly slowing the metabolism of amitriptyline, increasing its concentration in the blood plasma and the development of toxic effects;

- with ethanol - the action of ethanol is intensified, especially during the first few days of therapy.

The case of the development of serotonin syndrome with simultaneous application with sertraline is described.

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); During the treatment period, control of peripheral blood (in some cases,develop agranulocytosis, so it is recommended to monitor the blood picture, especially with an increase in body temperature, the development of influenza-like symptoms and sore throats), with prolonged therapy - monitoring the functions of the cardiovascular system (SSS) and liver. In the elderly and patients with SSS diseases, control over the number of heartbeats (HR), BP, electrocardiogram (ECG) is shown. On the ECG the appearance of clinically insignificant changes (smoothing of the tooth T, depression segment S-T, expansion of the complex QRS).

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

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

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

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

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

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

Depression is characterized by the risk of suicidal actions, which can persist until a significant remission is achieved. Therefore, at the beginning of treatment, a combination with drugs from the group of benzodiazepines or neuroleptic drugs with permanent medical supervision (entrusting trusted persons with storage and dispensing of drugs) can be indicated. Therefore, patients with severe endogenous depression and high suicidal danger can be treated only in a psychiatric hospital.

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

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

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

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

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

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

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

The case of the development of serotonin syndrome with simultaneous application with sertraline is described.

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

During the reception of amitriptyline, driving of vehicles, as well as servicing of mechanisms and performance of other works requiring increased concentration of attention, speed of psychomotor reactions and precise movements are prohibited.

Form release / dosage:

Tablets 25 mg.

Packaging:

50 tablets per can of polymer.

For 10 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

5 contour mesh packages or each jar together with the instruction for use is placed in a pack of cardboard.

Storage conditions:

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

Keep out of the reach of children.

Shelf life:

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

Terms of leave from pharmacies:On prescription

Registration number:P N000221 / 02-2001

Date of registration:12.01.2012

Expiration Date:Unlimited

The owner of the registration certificate:DALHIMFARM, OJSC DALHIMFARM, OJSC Russia

Manufacturer: & nbsp

DALHIMFARM, OJSC Russia

Information update date: & nbsp12.08.2017

Illustrated instructions

Instructions

Amitriptyline (Amitriptyline)