Amitriptyline is a strong antidepressant. Amitriptyline - dosage, side effects and interactions. Side effects of the substance Amitriptyline

Gross formula

Pharmacological group of the substance Amitriptyline

Nosological classification (ICD-10)

CAS Code

Characteristics of the substance Amitriptyline

Tricyclic antidepressant. Amitriptyline hydrochloride is a white, odorless, crystalline powder, easily soluble in water, ethanol, and chloroform. Molecular weight 313.87.

Pharmacology

Inhibits the reuptake of neurotransmitters (norepinephrine, serotonin) by the presynaptic nerve endings of neurons, causes the accumulation of monoamines in the synaptic cleft and enhances postsynaptic impulses. With long-term use, it reduces the functional activity (desensitization) of beta-adrenergic and serotonin receptors in the brain, normalizes adrenergic and serotonergic transmission, and restores the balance of these systems, disturbed during depressive states. Blocks m-cholinergic and histamine receptors of the central nervous system.

When taken orally, it is quickly and well absorbed from the gastrointestinal tract. The bioavailability of amitriptyline by different routes of administration is 30-60%, its metabolite - nortriptyline - 46-70%. Cmax in the blood after oral administration is achieved within 2.0-7.7 hours. Therapeutic concentrations in the blood for amitriptyline are 50-250 ng/ml, for nortriptyline - 50-150 ng/ml. Blood protein binding is 95%. Easily passes, like nortriptyline, through histohematic barriers, including the BBB, placental, and penetrates into breast milk. T1/2 is 10-26 hours, for nortriptyline - 18-44 hours. In the liver it undergoes biotransformation (demethylation, hydroxylation, N-oxidation) and forms active - nortriptyline, 10-hydroxy-amitriptyline, and inactive metabolites. It is excreted by the kidneys (mainly in the form of metabolites) within several days.

In anxiety-depressive conditions, it reduces anxiety, agitation and depressive symptoms. The antidepressant effect develops within 2-3 weeks after the start of treatment. If you suddenly stop taking it after long-term treatment, withdrawal syndrome may develop.

Use of the substance Amitriptyline

Depression of various etiologies (especially with severe anxiety and agitation), incl. endogenous, involutional, reactive, neurotic, with organic brain damage, medicinal; schizophrenic psychoses, mixed emotional disorders, behavioral disorders, bulimia nervosa, childhood enuresis (except for children with bladder hypotension), chronic pain syndrome (neurogenic), migraine prevention.

Contraindications

Hypersensitivity, use of MAO inhibitors in the previous 2 weeks, myocardial infarction (acute and recovery periods), heart failure in the stage of decompensation, impaired intracardiac conduction, severe arterial hypertension, benign prostatic hyperplasia, bladder atony, paralytic ileus, pyloric stenosis, peptic ulcer stomach and duodenum in the acute stage, acute diseases of the liver and/or kidneys with severe impairment of their function, blood diseases, children under 6 years of age (for injection forms - up to 12 years).

Restrictions on use

Epilepsy, coronary artery disease, arrhythmia, heart failure, angle-closure glaucoma, intraocular hypertension, hyperthyroidism.

Use during pregnancy and breastfeeding

Contraindicated during pregnancy.

Breastfeeding should be stopped during treatment.

Side effects of the substance Amitriptyline

Caused by blockade of peripheral m-cholinergic receptors: dry mouth, urinary retention, constipation, intestinal obstruction, blurred vision, accommodation paresis, increased intraocular pressure, increased sweating.

From the nervous system and sensory organs: headache, dizziness, ataxia, increased fatigue, weakness, irritability, drowsiness, insomnia, nightmares, motor agitation, tremor, paresthesia, peripheral neuropathy, EEG changes, impaired concentration, dysarthria, confusion, hallucinations, tinnitus.

From the cardiovascular system: tachycardia, orthostatic hypotension, arrhythmia, blood pressure lability, widening of the QRS complex on the ECG (impaired intraventricular conduction), symptoms of heart failure, fainting, changes in the blood picture, incl. agranulocytosis, leukopenia, eosinophilia, thrombocytopenia, purpura.

From the gastrointestinal tract: nausea, vomiting, heartburn, anorexia, discomfort in the epigastrium, gastralgia, increased activity of liver transaminases, stomatitis, taste disturbance, darkening of the tongue.

From the side of metabolism: galactorrhea, changes in ADH secretion; rarely - hypo- or hyperglycemia, impaired glucose tolerance.

From the genitourinary system: changes in libido, potency, testicular swelling, glucosuria, pollakiuria.

Allergic reactions: skin rash, itching, angioedema, urticaria.

Others: increase in the size of the mammary glands in women and men, hair loss, enlarged lymph nodes, photosensitivity, weight gain (with long-term use), withdrawal syndrome: headache, nausea, vomiting, diarrhea, irritability, sleep disturbance with vivid, unusual dreams, increased excitability (after long-term treatment, especially in high doses, with abrupt cessation of taking the drug).

Interaction

Incompatible with MAO inhibitors. Strengthens the inhibitory effect on the central nervous system of neuroleptics, sedatives and hypnotics, anticonvulsants, analgesics, anesthetics, alcohol; exhibits synergism when interacting with other antidepressants. When used together with neuroleptics and/or anticholinergic drugs, the development of a febrile temperature reaction and paralytic intestinal obstruction is possible. Potentiates the hypertensive effects of catecholamines and other adrenergic stimulants, which increases the risk of developing heart rhythm disturbances, tachycardia, and severe arterial hypertension. May reduce the antihypertensive effect of guanethidine and drugs with a similar mechanism of action, as well as weaken the effect of anticonvulsants. When used simultaneously with anticoagulants - derivatives of coumarin or indanedione - it is possible to increase the anticoagulant activity of the latter. Cimetidine increases the plasma concentration of amitriptyline with the possible development of toxic effects, inducers of microsomal liver enzymes (barbiturates, carbamazepine) reduce it. Quinidine slows the metabolism of amitriptyline; estrogen-containing oral contraceptives may increase bioavailability. Concomitant use with disulfiram and other acetaldehyde dehydrogenase inhibitors may provoke delirium. Probucol may increase cardiac arrhythmias. Amitriptyline may enhance glucocorticoid-induced depression. When used together with drugs for the treatment of thyrotoxicosis, the risk of developing agranulocytosis increases. Use caution when combining amitriptyline with digitalis and baclofen.

Overdose

Symptoms: hallucinations, convulsions, delirium, coma, cardiac conduction disturbances, extrasystole, ventricular arrhythmia, hypothermia.

Treatment: gastric lavage, taking an activated carbon suspension, laxatives, fluid infusion, symptomatic therapy, maintaining body temperature, monitoring the function of the cardiovascular system for at least 5 days, because relapse of disorders may occur after 48 hours or later. Hemodialysis and forced diuresis are ineffective.

Routes of administration

Inside, intramuscularly.

Precautions for the substance Amitriptyline

Amitriptyline can be taken no earlier than 14 days after stopping MAO inhibitors. Reduced doses are recommended for elderly patients and children. Should not be prescribed to patients with mania. Due to the possibility of suicide attempts in patients with depression, regular monitoring of patients is necessary, especially in the first weeks of treatment, as well as administration in the minimum required doses to reduce the risk of overdose. If there is no improvement in the patient's condition within 3-4 weeks, it is necessary to reconsider the treatment tactics. During treatment, you should avoid drinking alcohol, as well as avoid activities that require increased attention and speed of reactions.

Amitriptyline is a drug belonging to the group of non-selective monoamine uptake inhibitors, used in the presence of depression of various origins, as well as other diseases of the central nervous system and gastrointestinal tract.

Composition and release form

The active substance in this medicine is amitriptyline hydrochloride. The content of this component is: 11.32 mg, or 28.3 mg in each tablet or 1 ml of solution.

Among the excipients, it should be noted the presence of such compounds as: microcrystalline cellulose, lactose monohydrate, pregelatinized corn starch, colloidal silicon dioxide, purified medical talc, magnesium stearate.

The excipients in solutions are water for injection and dextrose. The release is carried out strictly according to the prescription of the attending physician.

Pharmacological action of Amitriptyline

This medicinal substance has a whole range of effects on the human body: antidepressant, analgesic, antihistamine, antiserotonin, and some others.

The antidepressant effect is due to the suppression of the reuptake of neurotransmitters: norepinephrine and serotonin, which leads to an increase in the concentration of these substances in the synaptic cleft. As a result of this, the process of transmission of nerve impulses from one neuron to another is normalized, which improves the functioning of the nervous system.

This effect is expressed in reducing the severity of depressive states, suppressing anxiety, improving mood and other positive effects.

The antihistamine effect is due to partial blocking of histamine receptors located in the parietal cells of the gastric mucosa. This circumstance affects the intensity of hydrochloric acid production and the acceleration of regenerative processes, which can have a positive effect in the presence of ulcers or hyperacid gastritis.

An increase in the concentration of serotonin in the synapses of the central nervous system is the reason for the onset of the analgesic effect. Perhaps there is also stimulation of the activity of internal opioid systems.

The drug can also be used in the presence of bulimia nervosa, and this disease does not necessarily have to be accompanied by depressive symptoms.

The antidepressant effect develops already after 2 or 3 weeks from the start of using Amitriptyline and lasts throughout the entire period of taking this medication.

Indications for use

Amitriptyline is prescribed if the following indications exist:

Depression of various origins, including severe anxiety, sleep pathology, and so on;
Organic lesions of the central nervous system, complicated by the presence of a depressive state;
As part of complex therapy for schizophrenia and psychosis;
Nocturnal enuresis;
Bulimia nervosa;
Chronic pain syndrome in patients with severe cancer;
Migraine conditions;
Peptic ulcer of the stomach and duodenum.

A specialist with appropriate experience should prescribe this remedy, as well as evaluate the effectiveness of its use. Uncontrolled use is fraught with negative consequences.

Contraindications for use

Amitriptyline cannot be prescribed in the presence of the following conditions:

Hypersensitivity to any component of the drug;
Simultaneous use of drugs - monoamine oxidase inhibitors;
Severe cardiac conduction disturbances;
Angle-closure glaucoma;
The patient's age is less than 6 years.

Relative contraindications are the following conditions: alcoholism, severe bronchial asthma, some forms of schizophrenia, epilepsy, severe angina, high blood pressure, intestinal obstruction, acute urinary retention in prostate adenoma and other conditions.

Treatment with Amitriptyline

Application, dosage and administration of Amitriptyline

The tablets should be taken after meals without chewing. You can drink the required amount of plain water. Adult patients with depression should be prescribed 25–50 mg once at night.

If there are positive dynamics, the dosage can be increased to 300 mg per day. It should be remembered that most of the medicine must be taken at night. The duration of therapy is determined by the attending physician and depends on the patient's response to the drug used.

In the form of solutions, Amitriptyline is used according to the following scheme: 10 – 30 mg of the drug is administered intramuscularly, up to 4 times a day. If necessary, the dose can be increased to 150 mg per day. After a couple of weeks, you should switch to using tablet forms.

Overdose

Signs of Amitriptyline poisoning: confusion up to coma, hyperthermia, drowsiness, drop in blood pressure, hallucinations, convulsions, vomiting, abnormal heart rhythm.

In this case, you need to stop using the medication, perform infusion therapy, and take all measures aimed at maintaining the functioning of vital organs.

Side effects

From the central nervous system: increased fatigue, weakness, dizziness, drowsiness, tinnitus, sleep pathology, convulsions, and so on.

From the digestive system: nausea, vomiting, heartburn, damage to the oral mucosa, discoloration of the tongue, stomach pain, liver damage.

Other side effects: allergic reactions, changes in the hemogram, abnormalities in the electrocardiogram, decreased libido and other undesirable manifestations.

Analogs

Analogs of the drug Amitriptyline are the following drugs: Amizol, Amirol, Amitriptyline hydrochloride, Apo-Amitriptyline, Saroten retard, Triptisol, Elivel.

Conclusion

When treating diseases of the central nervous system, it is extremely important to punctually follow all the doctor’s instructions, both in terms of the use of medications, and in relation to the work and rest regime, nutrition, and so on.

Catad_pgroup Antidepressants

Amitriptyline Nycomed - instructions for use

INSTRUCTIONS
on the use of a medicinal product for medical use

Registration number:

P N012536/01-130512

Tradename:

Amitriptyline Nycomed

International nonproprietary name:

amitriptyline

Dosage form:

film-coated tablets

Compound

One film-coated tablet, 10 mg, contains:
active substance: amitriptyline hydrochloride 11.3 mg equivalent to amitriptyline 10 mg;
Excipients: magnesium stearate 0.25 mg, povidone 0.83 mg, talc 2.25 mg, microcrystalline cellulose 9.5 mg, potato starch 28.2 mg, lactose monohydrate 27.0 mg;
shell: propylene glycol 0.2 mg, titanium dioxide 0.8 mg, hypromellose 1.2 mg, talc 0.8 mg.
One film-coated tablet, 25 mg, contains:
active substance: amitriptyline hydrochloride 28.3 mg equivalent to amitriptyline 25 mg;
Excipients: magnesium stearate 0.5 mg, povidone 0.6 mg, talc 4.5 mg, microcrystalline cellulose 18.0 mg, potato starch 38.0 mg, lactose monohydrate 40.2 mg;
shell: propylene glycol 0.3 mg, titanium dioxide 0.9 mg, hypromellose 1.4 mg, talc 0.9 mg.

Description

White film-coated tablets, round, biconvex.

Pharmacotherapeutic group:

antidepressant.

ATX code:

Pharmacological properties

Amitriptyline is a tricyclic antidepressant from the group of non-selective monoamine reuptake inhibitors. It has a strong thymoanaleptic and sedative effect.
Pharmacodynamics
The mechanism of the antidepressant action of amitriptyline is associated with an increase in the content of norepinephrine and serotonin in the synaptic cleft in the central nervous system (CNS).
The accumulation of these neurotransmitters occurs as a result of inhibition of their reuptake by the membranes of presynaptic neurons.
Amitriptyline is a blocker of Ml- and M2-muscarinic cholinergic receptors, H1-histamine receptors and α1-adrenergic receptors. According to the so-called monoamine hypothesis, there is a correlation between emotional tone and the function of neurotransmitters in brain synapses.
A clear correlation between amitriptyline plasma concentrations and clinical effect has not been shown, but optimal clinical effect appears to be achieved at concentrations in the range of 100-260 mcg/L.
Clinical relief of depression is achieved later than equilibrium plasma concentrations are achieved, after 2-6 weeks of treatment.
In addition, amitriptyline has a quinidine-like effect on the innervation of the heart.
Pharmacokinetics
Suction
After oral administration, amitriptyline is quickly and completely absorbed from the gastrointestinal tract. The maximum concentration in blood plasma (Cmax) is achieved within 2-6 hours after administration.
Distribution
The concentration of amitriptyline in the blood plasma of different patients varies significantly.
The bioavailability of amitriptyline is approximately 50%. Amitriptyline is highly (95%) bound to plasma proteins. The time to reach maximum concentration (TCmax) after oral administration is 4 hours, and the equilibrium concentration is approximately a week after the start of treatment. The volume of distribution is approximately 1085 l/kg. Both amitriptyline and nortriptyline cross the placenta and are excreted in breast milk.
Metabolism
Amitriptyline is metabolized in the liver and undergoes significant (about 50%) first-pass metabolism. In this case, amitriptyline undergoes N-demethylation by cytochrome P450 with the formation of an active metabolite - nortriptyline. Both amitriptyline and nortriptyline also undergo hydroxylation in the liver. The N-hydroxy and 10-hydroxy metabolite of amitriptyline and 10-hydroxynortriptyline are also active. Both amitriptyline and nortriptyline are conjugated to glucuronic acid, and these conjugates are inactive.
The main factor determining renal clearance, and, accordingly, plasma concentrations, is the rate of hydroxylation. A small proportion of people exhibit genetically determined delayed hydroxylation. In patients with impaired liver function, the half-life of amitriptyline and nortriptyline in the blood plasma is increased.
Removal
The half-life (T1/2) from blood plasma is 9-46 hours for amitriptyline and 18-95 hours for nortriptyline.
Amitriptyline is excreted primarily by the kidneys and through the intestines in the form of metabolites. Only a small portion of the administered dose of amitriptyline is excreted unchanged through the kidneys. In patients with impaired renal function, the excretion of amitriptyline and nortriptyline metabolites is slowed down, although metabolism as such does not change. Due to its binding to blood proteins, amitriptyline is not removed from the blood plasma by dialysis.

Indications for use

Endogenous depression and other depressive disorders.

Contraindications

Hypersensitivity to the components of the drug;
- use together with MAO inhibitors and 2 weeks before starting treatment;
- myocardial infarction (including recent ones);
- acute alcohol intoxication;
- acute delirium;
- acute intoxication with sleeping pills, analgesics and psychotropic drugs;
- angle-closure glaucoma;
- arrhythmias;
- disturbances of atrioventricular and intraventricular conduction;
- lactation period;
- lactose intolerance, lactase deficiency and glucose-galactose malabsorption;
- prostatic hyperplasia with urinary retention,
- hypokalemia, bradycardia, congenital long QT syndrome, as well as simultaneous use with drugs that lead to prolongation of the QT interval;
- pyloric stenosis, paralytic intestinal obstruction;
- children under 18 years of age.

Carefully

Diseases of the cardiovascular system (angina pectoris, arterial hypertension), blood diseases, increased intraocular pressure, closed-angle glaucoma, flat anterior chamber of the eye and acute angle of the chamber of the eye, urinary retention, prostatic hyperplasia, patients with convulsive conditions, bladder hypotension, hyperthyroidism, bipolar disorder, schizophrenia, epilepsy (amitriptyline reduces the seizure threshold), liver or kidney dysfunction, chronic alcoholism, concomitant use with antipsycholytic and hypnotic drugs, old age.
If you have one of the listed diseases, be sure to consult your doctor before taking the drug.

Use during pregnancy and breastfeeding

Pregnancy
Animal studies have demonstrated side effects at doses several times higher than the standard human dose.
Clinical experience with the use of amitriptyline during pregnancy is limited.
The safety of amitriptyline during pregnancy has not been established.
Amitriptyline is not recommended for use during pregnancy, especially in the first and third trimesters, unless the expected benefit to the mother outweighs the potential risk to the fetus.
If the drug is used by pregnant women, it is necessary to warn about the high risk of such use for 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 used nortriptyline (a metabolite of amitriptyline) during pregnancy, and cases of urinary retention have been reported.
Breast-feeding
Breastfeeding should be discontinued when using amitriptyline. Amitriptyline passes into breast milk. The breast milk/plasma concentration ratio is 0.4-1.5 in a breastfed child. Undesirable reactions may occur.

Directions for use and doses

Administered orally without chewing (immediately after meals).
Adults.
The initial daily dose is 25-50 mg, divided into two doses, or as a single dose at bedtime. If necessary, the daily dose can be gradually increased to 200 mg.
The general course of treatment is usually 6 months or more to prevent relapse.
Elderly
Elderly people are more sensitive to the m-anticholinergic side effects of amitriptyline. Therefore, for them the recommended initial dose is 25-30 mg/day, usually once a day (at night). Further increases in the dose should be carried out gradually, every other day, reaching, if necessary, a dose of 50-100 mg/day, until a response (effect) is achieved. Additional examination is necessary before prescribing a second course of treatment.
Renal dysfunction
In the presence of impaired renal function, the drug can be used at the usual dose.
Liver dysfunction
In patients with liver failure, the dose of amitriptyline should be reduced.
Duration of treatment
The antidepressant effect usually appears within 2-4 weeks.
Treatment with antidepressants is symptomatic and therefore must be long-term, usually for 6 months or more, to prevent relapse of depression.
Cancel
The drug should be discontinued gradually to avoid the development of withdrawal symptoms, such as headache, sleep disturbances, irritability and general poor health. These symptoms are not a sign of drug dependence.

Side effect

More than 50% of patients receiving Amitriptyline Nycomed may have one or more of the following adverse reactions. Amitriptyline may cause side effects similar to those of other tricyclic antidepressants.
Some of the following adverse reactions, such as headache, tremors, decreased concentration, constipation, and decreased sex drive, may also be symptoms of depression and they usually go away when the depression subsides.
The incidence of side effects is indicated as: very often (>1/10); often (>1/100,<1/10); нечасто (>1/1000, <1/100); редко (>1/10 000, <1/1000); очень редко (<1/10000).
From the cardiovascular system:
Often: palpitations and tachycardia, orthostatic hypotension.
Often: arrhythmia (including conduction disturbances, QT interval prolongation), hypotension, AV block, bundle branch block.
Infrequently: increase in blood pressure.
Rarely: myocardial infarction.
From the nervous system:
Often: sedative effect (lethargy, tendency to sleep), tremor, dizziness, headache.
Often: decreased concentration, taste disturbance, paresthesia, extrapyramidal symptoms: ataxia, akathisia, parkinsonism, dystonic reactions, tardive dyskinesia, slow speech.
Infrequently: convulsions.
From the urinary system:
Often: urinary retention.
From the skin:
Often: hyperhidrosis.
Infrequently: rash, skin vasculitis, urticaria.
Rarely: photosensitivity, alopecia.
From the senses:
Often: decreased visual acuity, impaired accommodation (reading glasses may be required during treatment).
Often: mydriasis
Infrequently: tinnitus, increased intraocular pressure.
Rarely: loss of accommodation ability, worsening narrow-angle glaucoma.
Mental disorder:
Often: confusion (confusion in elderly patients is characterized by anxiety, sleep disturbance, difficulty remembering, psychomotor agitation, confusion of thoughts, delirium), disorientation.
Often: decreased concentration.
Infrequently: cognitive impairment, manic syndrome, hypomania, mania, fear, anxiety, insomnia, nightmares.
Rarely: aggressiveness, delirium (in adults), hallucinations (in patients with schizophrenia).
Very rarely: suicidal thoughts, suicidal behavior.
From the hematopoietic organs:
Rarely: suppression of bone marrow functions, agranulocytosis, leukopenia, eosinophilia, thrombocytopenia.
From the digestive system
Often: dry mouth, constipation, nausea.
Often: gum recession, oral inflammation, dental caries, burning sensation in the mouth.
Infrequently: diarrhea, vomiting, swelling of the tongue.
Rarely: paralytic intestinal obstruction, swelling of the parotid gland, cholestatic jaundice, liver dysfunction, hepatitis.
Common disorders:
Often: weakness.
Infrequently: swelling of the face.
Rarely: increase in body temperature.
From the side of metabolism:
Often: weight gain, increased appetite.
Rarely: decreased appetite.
Very rarely: syndrome of inappropriate secretion of antidiuretic hormone.
From the reproductive system:
Often: weakening or increasing sexual desire.
Often: in men – impotence, erectile dysfunction.
Rarely: in men – delayed ejaculation, gynecomastia; in women – galactorrhea, delayed orgasm, loss of the ability to achieve orgasm.
Laboratory indicators:
Often: ECG changes, prolongation of the QT interval, expansion of the QRS complex.
Rarely: abnormal liver tests, increased activity of alkaline phosphatase, transaminases.
Cancellation effects
Sudden cessation of treatment after long-term use may cause nausea, headache and malaise.
Tapering the drug was associated with transient symptoms such as irritability, agitation, and disturbances in dreams and sleep during the first two weeks of dose reduction.
Rarely, isolated cases of mania or hypomania have occurred within 2 to 7 days after discontinuation of long-term treatment with tricyclic antidepressants.

Overdose

Symptoms
Symptoms of an amitrichilin overdose may develop slowly or occur suddenly. In the first two hours, drowsiness or psychomotor agitation, hallucinations and symptoms associated with the anticholinergic effect of the drug are observed: mydriasis, tachycardia, urinary retention, dry mucous membranes, weakened intestinal motility, convulsions, increased body temperature. In the future, there may be a sharp depression of the functions of the central nervous system, impaired consciousness, progressing to coma, and respiratory failure.
Cardiac symptoms: arrhythmia (ventricular tachyarrhythmia, flutter and ventricular fibrillation). Characteristic changes on the ECG include prolongation of the PR interval, widening of the QRS complex, prolongation of the QT interval, flattening or inversion of the T wave, ST segment depression, and varying degrees of intracardiac conduction block, which can cause cardiac arrest. Heart failure, hypotension, cardiogenic shock, metabolic acidosis and hypokalemia, confusion, agitation, hallucinations and ataxia may develop.
Effect on the central nervous system (CNS): depression of central nervous system functions, strong craving for sleep, convulsions, coma.
Effect on the respiratory system: respiratory failure.
Impact on the mental sphere: psychomotor agitation, hallucinations.
Effect on the vascular system: hypotension.
M-anticholinergic effects: dry mouth, impaired accommodation, urinary retention, muscle cramps.
Treatment:
Treatment is symptomatic and supportive.
Discontinuation of amitriptyline therapy, gastric lavage, even if some time has passed after taking the drug, taking activated charcoal. Even in seemingly uncomplicated cases, the patient should be carefully monitored. The level of consciousness, heart rate, blood pressure and respiratory rate should be monitored. Electrolyte and blood gas levels should be checked frequently. To prevent respiratory arrest, it is necessary to ensure airway patency and perform artificial ventilation. ECG monitoring must be continued for 3-5 days. When the QRS complex widens, heart failure and ventricular arrhythmias, shifting the blood pH to the alkaline side (prescribing sodium bicarbonate solution or hyperventilation) with rapid administration of a hypertonic sodium chloride solution (100-200 mmol Na +) can be effective. For ventricular arrhythmias, it is possible to use traditional antiarrhythmic drugs, for example, 50-100 mg of lidocaine (1-1.5 mg/kg) intravenously with further infusion at a rate of 1-3 mg/min.
Cardioversion and defibrillation are used if necessary.
Circulatory insufficiency is corrected with the help of plasma-substituting solutions, and in severe cases, dobutamine infusion is performed (initially, 2-3 mcg/kg/min with a further increase in dose depending on the effect).
Excitement and convulsions can be controlled with diazepam.
For metabolic acidosis, standard therapy should be started.
Dialysis is ineffective because the concentration of amitriptyline in the blood is low.
Reactions to overdose vary significantly among different patients.
In adults, moderate or severe intoxication develops when taking amitriptyline in a dose of more than 500 mg; when taking a dose of about 1000 mg, death is possible.

Interaction with other drugs

Amitriptyline potentiates the inhibition of the central nervous system by the following drugs: antipsychotics, sedatives and hypnotics, anticonvulsants, central and narcotic analgesics, general anesthesia, alcohol.
Tricyclic antidepressants, including amitriptyline, are metabolized by the hepatic cytochrome P450 isoenzyme CYP2D6. This isoenzyme has several isoforms in humans.
The CYP2D6 isoenzyme can be inhibited by various psychotropic drugs, for example, antipsychotics, serotonin reuptake inhibitors (except citalopram, a very weak inhibitor), β-blockers and the latest generation antiarrhythmic drugs (procainamide, phenytoin, propafenone, esmolol amiodarone).
These drugs can inhibit the metabolism of tricyclic antidepressants and significantly increase their plasma concentrations. In addition, the isoenzymes CYP2C19 and CYP3A are involved in the metabolism of amitriptyline.
Contraindicated combinations:
The use of amitriptyline in combination with MAO inhibitors is contraindicated due to the risk of developing serotonin syndrome, including myoclonus, agitated spasms, delirium and coma.
The use of amitriptyline can be started 2 weeks after discontinuation of the irreversible, non-selective MAO inhibitor and one day after discontinuation of the reversible inhibitor moclobemide.
The use of MAO inhibitors can be started 2 weeks after discontinuation of amitriptyline. In any case, both the MAO inhibitor and amitriptyline should be started at low doses and gradually increased depending on the effect.
Not recommended combinations
Sympathomimetics: amitriptyline enhances the cardiovascular effect of adrenaline, ephedrine, isoprenaline, norepinephrine, dopamine and phenylephedrine, used, for example, for local or general anesthesia or as nasal drops.
Adrenergic blockers: with simultaneous use of amitriptyline with clonidine and methyldopa, the hypotensive effect of the latter may be weakened.
M-anticholinergics: amitriptyline may enhance the effect of such drugs (for example, phenothiazine derivatives, antiparkinsonian drugs, blockers
H1-histamine receptors, atropine, biperiden) on the organs of vision, central nervous system, intestines and bladder.
The simultaneous use of these drugs should be avoided due to the risk of developing, including intestinal obstruction and a strong increase in body temperature.
Drugs that can prolong the QT interval including antiarrhythmics (eg, quinidine), H1 blockers (eg, terfenadine), some antipsychotics (especially pimozide and sertindole), anesthetics (isoflurane, droperidol), chloral hydrate, and sotalol. These drugs, when used together with amitriptyline, may increase the risk of developing ventricular arrhythmias.
Antifungal drugs, for example, fluconazole and terbinafine, increase serum concentrations of amitriptyline and increase associated toxicity. Cases of fainting and ventricular fibrillation and flutter are possible.
Lithium salts (lithium carbonate)
Lithium salts interact with amitriptyline by an unknown mechanism; this interaction may increase lithium toxicity: tremors, tonic-clonic seizures, difficulty remembering, disturbed thinking, hallucinations, neuroleptic malignant syndrome.
Combinations requiring caution
CNS depressants: amitriptyline may enhance the inhibition of central nervous system functions caused by other psychodepressants, such as alcohol, hypnotics, sedatives and strong analgesics.
Barbiturates and other inducers of liver microsomal enzymes - enzyme inducers, for example, rifampicin and carbamazepine, can increase the metabolism of amitriptyline and reduce its concentration in the blood plasma with a corresponding weakening of the antidepressant effect.
Cimetidine, methylphenidate and slow calcium channel blockers increase the concentration of amitriptyline in the blood plasma, which may be accompanied by increased toxicity.
Amitriptyline and antipsychotics can mutually inhibit each other's metabolism. This can lead to a decrease in the seizure threshold and the development of seizures. When used together, a dose adjustment of these drugs may be required.
The simultaneous use of amitriptyline, antipsychotics and hypnotics (droperidol) should be avoided. Extreme caution should be exercised during coadministration.
Sucralfate reduces the absorption of amitriptyline and may reduce the antidepressant effect.
With 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 using amitriptyline and valproic acid together, the concentrations of amitriptyline and nortriptyline in the blood serum should be monitored. Amitriptyline dose reduction may be required.
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. When starting the use of amitriptyline in patients receiving phenytoin, the concentration of the latter in the blood plasma should be monitored due to an increased risk of inhibition of its metabolism. At the same time, the therapeutic effect of amitriptyline should be monitored, as its dose may need to be increased.
Preparations of St. John's wort reduce the AUC0-12 hours and the maximum concentration of amitriptyline in the blood plasma by approximately 20% due to the activation of the hepatic metabolism of amitriptyline by the CYP3A4 isoenzyme.
This combination can be used with amitriptyline dose adjustment depending on the results of measuring its concentration in the blood plasma.

special instructions

Before starting treatment, blood pressure (BP) control is necessary (in patients with low or labile blood pressure, it may decrease even more).
Caution is required when suddenly moving to a vertical position from a lying or sitting position.
Epidemiological studies, which were mainly conducted in patients aged 50 years and older, indicate an increased risk of bone fractures with the use of selective serotonin uptake inhibitors and tricyclic antidepressants. The mechanism of action that increases this risk is unknown.
During treatment, in some cases, agranulocytosis or hypokalemia may develop; therefore, monitoring of peripheral blood is recommended, especially with an increase in body temperature, the development of flu-like symptoms and tonsillitis; with long-term therapy - control of the functions of the cardiovascular system (CVS) and liver. In elderly patients and patients with cardiovascular diseases, heart rate, blood pressure, and electrocardiogram (ECG) should be monitored. Clinically insignificant changes may appear on the ECG (smoothing of the T wave, depression of the S-T segment, widening of the QRS complex).
Caution should be exercised when using amitriptyline in patients receiving inhibitors or inducers of cytochrome P450 3A4.
During the treatment period, in some cases, mydriasis, tachycardia, urinary retention, dry mucous membranes, and decreased intestinal motor function may develop.
Convulsions and increased body temperature are possible. In the future, there may be a sharp depression of the functions of the central nervous system, impaired consciousness, progressing to coma, and respiratory failure.
During the treatment period, the consumption of alcoholic beverages should be avoided.
Amitriptyline should be discontinued gradually, since sudden cessation of use after long-term treatment, especially in high doses, may result in withdrawal syndrome.
Due to the m-anticholinergic effect of amitriptyline, an attack of increased intraocular pressure is possible, as well as a possible decrease in tear production 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.
A case of fatal arrhythmia that occurred 56 hours after an overdose of amitriptyline is described.
In suicidal patients, the risk of suicide continues during treatment until depressive symptoms improve significantly.
Since the effect of amitriptyline occurs after 2-4 weeks, suicidal patients require careful monitoring until their symptoms improve.
Patients who have previously experienced suicidal symptoms or had severe suicidal thoughts, or who have attempted suicide before or during treatment, require constant medical supervision. Storage and distribution of medicines to them must be carried out by authorized persons.
Amitriptyline (like other antidepressants) may itself increase the incidence of suicide in people under 24 years of age, so when prescribing amitriptyline in young people (under 24 years of age), the risk of suicide should be weighed against the benefits of their use.
In patients with manic-depressive syndrome, treatment with amitriptyline may provoke a manic phase. If manic symptoms occur, amitriptyline should be discontinued.
Patients receiving tri/tetracyclic antidepressants, local and general anesthetics may have an increased risk of developing arrhythmia and a drop in blood pressure.
If possible, amitriptyline should be discontinued before surgery. In case of emergency operations, the anesthesiologist should be informed about the use of amitriptyline.
Amitriptyline Nycomed may affect the effect of insulin and changes in glucose concentration after meals. This may require adjustment of hypoglycemic therapy in patients with diabetes.
Depression can also affect glucose metabolism.
The simultaneous use of other m-anticholinergic blockers may enhance the m-anticholinergic effect of amitriptyline.
Patients should inform their dentist about taking amitriptyline. Dry mouth can lead to changes in the oral mucosa, inflammation, burning sensation and dental caries.
It is recommended to undergo regular dental examinations.

Impact on the ability to drive vehicles and moving machinery

Release form

Film-coated tablets 10 mg and 25 mg.
50 tablets in a dark glass bottle, sealed with a screw cap made of polypropylene, under which there is a gasket with a tear ring, ensuring control of the first opening.
One bottle along with instructions for use is placed in a cardboard box.

Storage conditions

At temperatures from 15 to 25 °C.
Keep out of the reach of children.

Best before date

5 years.
Do not use after expiration date.

Conditions for dispensing from pharmacies

On prescription.

Legal entity in whose name the registration certificate was issued

Takeda Pharma A/S, Denmark
Dubendal Alle 10, 2630 Taastrup, Denmark
Takeda Pharma A/S, Denmark
Dybendal Alle 10, 2630 Taastrup, Denmark

Manufacturer
Takeda Pharma A/S, Denmark
Apothekerstein 9, 9500 Hobro, Denmark
Takeda Pharma A/S, Denmark
Apotekerstien 9, 9500 Hobro, Denmark

Packer/Packer
Takeda Pharma AS, Estonia
Takeda Pharma AS, Estonia
55B Jaama St., Polva 63308, Estonia

Issue quality control
Takeda Pharma A/S, Denmark Langebjerg 1, 4000 Roskilde, Denmark
Takeda Pharma A/S, Denmark Langebjerg 1, 4000 Roskilde, Denmark
Takeda Pharma AS, Estonia
55B st. Jaama, Põlva 63308, Estonia
Takeda Pharma AS, Estonia
55B Jaama St., Polva 63308, Estonia

Consumer complaints should be sent to:
LLC "Takeda Pharmaceuticals"
119048 Moscow, st. Usacheva, 2, building 1.

A classic and very effective tricyclic antidepressant is the drug Amitriptyline Nycomed. Reviews about it are usually positive. This medicine has a wide range of uses.

pharmachologic effect

The drug "Amitriptyline" is an antidepressant from a number of tricyclic compounds. It is a derivative of dibenzocycloheptadine. The action of amitriptyline is associated with stimulation of serotonergic and adrenergic mechanisms of the brain by suppressing the reuptake of mediators. It gives a sedative effect and exhibits antihistamine and anticholinergic activity. The antidiuretic benefit for nighttime urinary incontinence is achieved through anticholinergic activity. The drug has an analgesic effect, which is believed to be associated with changes in the concentration of monoamines in the central nervous system and the effect of tricyclic compounds on endogenous opioid systems.

Pharmacokinetics

It is believed that the drug Amitriptyline has good bioavailability. Reviews, as a rule, confirm this. Bioavailability of the drug is 31-61%. It binds to blood proteins by 82-96%. Metabolization occurs with the formation of the metabolite nortriptyline (active). The half-life is 31-46 hours. The drug is excreted primarily through the kidneys.

Indications

The drug is used during the depressive phase of manic-depressive psychoses, various depressions (including childhood depression), mixed emotional disorders, and pathological behavioral disorders. For childhood enuresis (except for patients with hypotonic bladder pathology), the drug Amitriptyline has proven itself quite well. Reviews about its action are good. The drug is also prescribed for bulimia nervosa and chronic pain syndromes. This drug is also prescribed for the treatment of bulimic neuroses, psychogenic anorexia, for chronic neurogenic pain, and for the prevention of migraines.

Dosing

Amitriptyline tablets are taken orally (without chewing) after meals. For adults, the initial dose is 25 mg 2 to 4 times a day. The maximum dosage for outpatient treatment is 150 mg per day, for inpatient treatment - 300 mg per day, and for elderly people 100 mg. The drug can be administered intravenously or intramuscularly at a dose of 20-40 mg four times a day. Over time, injections can be replaced by oral administration. The course is no more than 6 months. For children, the medicine is prescribed as an antidepressant in dosages of 10-30 mg, for adolescents - 10 mg three times a day, for the treatment of enuresis in children over six years of age - 12-25 mg at night. The dosage should not exceed the proportion of 2.5 mg per 1 kg of weight.

Side effects

As a rule, Amitriptyline is well tolerated. Feedback on use is positive. However, various side effects are possible. CNS: disorientation, hallucinations, drowsiness, extrapyramidal disorders, fatigue, anxiety, trembling. Cardiovascular system: tachycardia, orthostatic hypotension, conduction disturbances. Gastrointestinal tract: cholestatic jaundice, vomiting, stomatitis. Reproductive system: delayed ejaculation, various disorders, changes in libido, decreased potency. Endocrine system: diabetes mellitus, glycosuria, hyperglycemia, decreased glucose tolerance, inadequate secretion of ADH. Metabolism: weight gain. Allergic reactions: skin rashes, itching. Effects caused by anticholinergic activity: disturbances of accommodation, dry mouth, urinary retention, increased intraocular pressure, blurred vision, constipation. Side effects do not occur often when taking the drug Amitriptyline. Reviews about it are generally positive.

Contraindications

The drug should not be prescribed against the background of the following diseases: angle-closure glaucoma, bladder atony, prostate hypertrophy, paralytic ileus, pyloric stenosis, epilepsy, early recovery period after a heart attack. The medicine should also not be used simultaneously with MAO inhibitors. The use of the drug is also contraindicated for decompensated heart defects, blood diseases, glaucoma, severe liver and kidney diseases, stomach ulcers and hypersensitivity to the active substance and other components of the drug.

Pregnancy and lactation

The drug "Amitriptyline" should not be used during pregnancy, and especially in the 1st-3rd trimesters. The drug should be used only when absolutely necessary. The fact is that adequate clinical studies of the effect of the drug on the fetus and the mother’s body have not been conducted. Therefore, it is not known how safe it is. In experimental studies, the drug gave a teratogenic effect in dosages much higher than normal.

special instructions

This drug is used with great caution for heart failure, arrhythmias, and coronary artery disease. Abruptly stopping the medication may lead to withdrawal symptoms. This drug can be used no earlier than two weeks after taking MAO inhibitors. The medicine should not be used simultaneously with sympathomimetic medications: epinephrine, isoprenaline, ephedrine, phenylephrine, norepinephrine, phenylpropanolamine. With great caution, this medicine is prescribed together with drugs that have an anticholinergic effect. You should not drink alcohol while taking the medication. The drug "Amitriptyline" affects the ability to control mechanisms. During therapy, you should refrain from activities associated with potential danger that require good reaction speed and increased attention. This drug was included in the list of vital and essential drugs. In case of an overdose of Amitriptyline, the following symptoms are observed: disorientation, drowsiness and confusion, fever, dysarthria, shortness of breath, dilated pupils, hallucinations, stupor, convulsions, arrhythmia, muscle rigidity, hypotension, respiratory depression, heart failure.

Drug interactions

As a rule, when using Amitriptyline simultaneously with other drugs that have a depressant effect on the central nervous system, as well as with alcohol, an excessive increase in depression of the central nervous system is possible. The effect of alcohol increases. In addition, hypotensive effects and respiratory depression may be observed. If you take the medicine together with other drugs that have anticholinergic activity, the anticholinergic effect may be enhanced. Taking the drug "Amitriptyline" with symptomatic medications enhances their effect on the heart and cardiovascular system as a whole. Because of this, the risk of developing various rhythm disturbances, arterial hypertension (severe forms), and tachycardia increases. Taking with guanethidine and clonidine reduces the hypotensive effect of these drugs. Use together with barbiturates: with quinidine - slowing down the metabolism of the drug "Amitriptyline", with carbozepine - a significant decrease in the effect of the drug due to the strong acceleration of its metabolism. Simultaneous use with cimetidine also slows down the metabolism of Amitriptyline, and also increases its concentration in plasma and increases the risk of toxic effects.

Dosage form

Film-coated tablets, 25 mg

Compound

One tablet contains

active substance - amitriptyline 25 mg (in the form of amitriptyline hydrochloride 0.0283 g),

excipients: lactose monohydrate, corn starch, gelatin, calcium stearate, talc, silicon dioxide colloidal anhydride

shell composition: sepifilm 3048 yellow (hydroxypropyl methylcellulose, microcrystalline cellulose, polyoxyl 40 stearate, titanium dioxide E171, quinoline yellow E 104), silicone antifoam emulsion SE-2, macrogol 6000

Description

Film-coated tablets, yellow, round, biconvex surface

Pharmacotherapeutic group

Psychoanaleptics. Antidepressants.

Monoamine reuptake inhibitors are non-selective. Amitriptyline.

ATX code N06AA09

Pharmacological properties

Pharmacokinetics

Amitriptyline is almost completely absorbed from the digestive tract, the maximum concentration is reached within 4-8 hours, about 95% is bound to plasma proteins. It is metabolized mainly to desmethylamitriptyline (nortriptyline, the main active metabolite). The biological half-life ranges from 10 to 28 hours, for nortriptyline - from 16 to 80 hours. Elderly patients are predisposed to higher plasma concentrations and longer half-life than younger patients. Amitriptyline is excreted primarily through the kidneys in the form of several metabolites, both free and conjugated, less than 5% is excreted unchanged. A certain amount of the drug is excreted in the feces.

Amitriptyline crosses the placental barrier and also enters breast milk.

Pharmacodynamics

Amitriptyline is a tricyclic antidepressant from the group of non-selective inhibitors of neuronal monoamine uptake. It has a pronounced thymoleptic effect, like imipramine, but its sedative and calming effects are more pronounced. The mechanism of the antidepressant action of amitriptyline is associated with inhibition of the reverse neuronal uptake of catecholamines (norepinephrine, dopamine) and serotonin in the central nervous system. Amitriptyline is an antagonist of muscarinocholinergic receptors in the central nervous system and in the periphery, has antihistamine (H1) and α1-adrenolytic properties. Consequently, it causes antineuralgic (central analgesic), antiulcer and antibulimic effects. Helps reduce the tone of the smooth muscles of the bladder, increase capacity and, on the contrary, increases the tone of the bladder sphincter. This explains its effectiveness in the treatment of enuresis.

Indications for use

Mild, moderate and severe depressive phases with or without psychotic features in all types of mood disorders, such as bipolar disorder, recurrent depressive disorder and organic affective disorder

Schizoaffective disorders of depressive type; depression associated with schizophrenia (against the background of constant treatment with antipsychotic drugs)

Depressions previously defined as reactive and neurotic depression: dysthymia, mixed anxiety-depressive disorder, depressive disorders arising as a reaction to severe stress or as a manifestation of adjustment disorder

Depression developing during treatment with reserpine, non-organic enuresis (i.e. primary) not accompanied by a hypotonic bladder, non-organic encopresis (fecal incontinence), anorexia nervosa and irritable bowel syndrome

Used for long-term treatment of pain in complex therapy

Directions for use and doses

The drug is intended for use in adults. The actual dose is selected individually for each patient, and this dosage should be strictly adhered to.

The starting dose is usually 25-50 mg, taken at bedtime, then gradually increase doses depending on tolerance over 5-6 days up to 150-200 mg daily, with the maximum portion of the daily dose taken at bedtime. If the patient's condition does not improve during the second week of therapy, the dose is increased to 300 mg per day. This dose is then gradually reduced as symptoms of depression subside, with reduced doses of 50-100 mg per day usually taken for 3 months.

Elderly patients

Elderly patients or patients with mild depressive syndrome receiving outpatient treatment use lower doses of 50-100 mg as one daily dose at bedtime. The therapeutic effect usually appears 7-10 days after the start of treatment. Amitriptyline therapy can be considered ineffective only if there is no improvement in the patient's condition after 3 weeks of treatment.

The onset of antidepressant action can be accelerated by co-administration of amitriptyline with nortriptyline. In most cases, treatment with amitriptyline for more than 6-8 months is ineffective. To prevent the expected periodic phase of depression, lithium is more appropriate. For this purpose, amitriptyline can be prescribed only to those patients for whom the use of lithium preparations is contraindicated.

Side effects

The expected frequency of adverse effects is 16 - 20%, and they most often occur in the elderly and children under 5 years of age.

The incidence of adverse reactions is assessed as follows: “very often” (> 1/10), “common” (from ≥ 1/100 to< 1/10), «нечасто» (от >1/1000 to< 1/100), «редко» (от >1/10000 to< 1/1000), «очень редко» (< 1/10000), «частота не известна» (нельзя установить исходя из имеющихся данных).

Often

Vertigo

Tachycardia, arrhythmia (extrasystole, palpitations, cardiac conduction disturbances)

Orthostatic hypotension-hyperhidrosis

Fatigue

Disorientation, agitation, psychosis, hallucinations

Drowsiness, tremor

Accommodation disturbance, blurred vision

Dry mouth, taste disturbances (bitter and sour taste in the mouth), constipation

Urinary retention, delayed urination at the beginning of treatment

Changes in libido, potency

Hematopoiesis disorder

Extrapyramidal disorders (tardive dyskinesia, slurred speech, reduced seizure threshold)

Worsening of existing heart failure

Paralytic ileus

Jaundice

Skin reactions

Gynecomastia, galactorrhea

Very rarely

Atrial fibrillation, ventricular fibrillation, cardiac arrest

Increased transaminase activity

Frequency unknown

Hyperglycemia

In exceptional cases, transient delusional states and paranoid states accompanied by hallucinations are observed, especially in elderly people with organic cerebral syndrome after abrupt cessation of high doses of the drug.

There have been reports of suicidal thoughts or behavior during or after discontinuation of treatment with amitriptyline.

Group effects

Epidemiological studies conducted primarily in patients aged 50 years and older show an increased risk of bone fractures in patients receiving selective serotonin reuptake inhibitors and tricyclic antidepressants. The mechanism leading to this risk is unclear.

Contraindications

Hypersensitivity to the active and auxiliary components of the drug (see section "Composition")

Acute intoxication with drugs that depress the central nervous system

Alcohol poisoning

Acute delirium

Glaucoma

Paralytic ileus (due to the anticholinergic effect of amitriptyline)

Epilepsy

Pyloric stenosis

Concomitant therapy with MAO inhibitors (MAO inhibitors must be discontinued at least 14 days before starting treatment with amitriptyline)

Children and teenagers up to 18 years of age

Pregnancy and lactation

Cardiac ischemia

Heart failure

Heart rhythm disturbance

Prostatic hypertrophy

Urinary retention

Drug interactions

Amitriptyline enhances the anticholinergic effect of drugs used to treat Parkinson's disease, phenothiazine derivatives, thiazide diuretics and vasodilators.

Amitriptyline enhances the effects that narcotic analgesics and barbiturates have on the central system.

Amitriptyline worsens the response to disulfiram.

Amitriptyline potentiates the effect of alcohol (mainly vegetative disorders and poor health may occur), enhances symptomatic and psychostimulant effects.

Concomitant use with other serotonergic active substances (such as selective serotonin reuptake inhibitors (SSRIs), selective serotonin-norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors, lithium preparations, triptan, tramadol, linezolid, L-tryptophan and St. John's wort preparations - Hypericum perforatum) can lead to the development of serotonin syndrome. Therapy with amitriptyline in combination with any of these substances must be carried out under the close supervision of a physician. In any case, irreversible monoamine oxidase inhibitors should be discontinued at least 14 days before starting amitriptyline therapy.

Amitriptyline may improve the effectiveness of some antiarrhythmic drugs used to treat type 1 and type 3 arrhythmias.

Substances that alkalinize urine and methylphenidate enhance the effect of amitriptyline.

Amitriptyline reduces the antihypertensive effect of reserpine and guanethidine and reduces the activity of anticonvulsants.

Urinary alkalinizers, methylphenidate, increase the effectiveness of amitriptyline.

Induction of enzyme synthesis caused by the intake of barbiturates leads to a decrease in the level of amitriptyline to the level of one twentieth.

special instructions

The use of amitriptyline is not recommended in the following conditions or the risk-benefit ratio must be carefully weighed: coronary heart disease, heart failure, prostatic hypertrophy, urinary retention, any condition associated with tachycardia or cardiac arrhythmia.
Do not drink alcoholic beverages while taking amitriptyline!
During the period of taking amitriptyline, it is recommended to periodically monitor: blood pressure control, electrocardiogram (ECG), blood test monitoring, liver function tests, possible use of electroencephalography (EEG)

Amitriptyline in doses above 150 mg/day lowers the threshold for seizure activity, so the possibility of seizures should be considered in patients who are predisposed to this due to age or injury.

Amitriptyline should be used with caution in persons suffering from alcoholism, bronchial asthma, suppression of bone marrow hematopoiesis, hyperthyroidism, schizophrenia (although there is usually no exacerbation of productive symptoms when taking it).

Treatment with amitriptyline in old age should be carefully monitored, using minimal doses of the drug and gradually increasing them, in order to avoid the development of delirious disorders, hypomania and other complications.

Patients with the depressive phase of manic-depressive syndrome may progress to the manic phase.

Suicidal attempts/suicidal thoughts

Depression is associated with an increased risk of suicidal ideation and suicide attempts. The risk exists until stable remission occurs. Improvement may not be observed during the first weeks or more of treatment, so patients should be monitored by a physician until signs of improvement appear. According to general clinical experience, the risk of suicide increases during the early stages of the recovery period.

Other psychiatric conditions for which amitriptyline is prescribed may also be associated with an increased risk of suicide. Therefore, during the treatment of patients with other mental disorders, the same precautions should be observed as with major depressive disorders, namely, patients should be under strict medical supervision.

Patients with a history of suicide attempt or a high likelihood of suicidal ideation before starting amitriptyline should be closely monitored during treatment as they are at greater risk of suicidal ideation or suicide attempt. In adult patients with mental disorders, the risk of suicidal behavior is increased with antidepressants compared with placebo in patients under 25 years of age.

Patients (and those caring for them) should be alerted to the need for monitoring and possible clinical worsening, and if suicidal behavior or thoughts or unusual changes in behavior occur, seek immediate medical attention.

Hyperglycemia/diabetes

Epidemiological studies have revealed an increased risk of developing diabetes mellitus in patients with depression who received tricyclic antidepressants. Blood glucose levels should be carefully monitored in patients with established diabetes mellitus or with risk factors for diabetes mellitus who initiate amitriptyline therapy.

Serotonin syndrome

Serotonin syndrome may develop if tricyclic antidepressants are used concomitantly with other serotonergic active substances (see section on drug interactions). Serotonin syndrome, which is caused by excess serotonin, can be fatal and includes the following symptoms:

Neuromuscular agitation (muscle twitching, hyperreflexia, myoclonus, muscle rigidity);

Autonomic changes (hyperthermia, tachycardia, changes in blood pressure, sweating, tremor, hyperemia, dilated pupils, diarrhea);

Changes in mental state (anxiety, agitation, confusion, coma).

Therapy in which serotonergic active substances are combined with amitriptyline must be carried out under the close supervision of a physician. If serotonin syndrome develops, amitriptyline therapy should be discontinued.

Due to the presence of lactose, the drug is not recommended for patients with hereditary lactose intolerance, Lapp-lactase enzyme deficiency, or glucose-galactose malabsorption.

Pregnancy

The use of amitriptyline during pregnancy is not recommended, especially in the first trimester. Application is possible only after careful comparison of benefits and risks. To date, no developmental abnormalities have been reported with therapeutic doses of amitriptyline.

Lactation period

It is not recommended to use the drug during breastfeeding, since the active substance passes into breast milk in small quantities. If it is unavoidable to prescribe the drug during breastfeeding, it is recommended to stop feeding.

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

While taking amitriptyline, driving vehicles, servicing machinery, working at high altitudes and other types of work that require increased concentration are prohibited.

Overdose

Symptoms: agitation, psychomotor agitation with pronounced antimuscarinic effects, such as dry mouth, dilated pupils, tachycardia, urinary retention, enteral hypotension.

With more severe intoxication, the following symptoms are observed: loss of consciousness, convulsions, myoclonus, hyperreflexivity, arterial hypotension, depression of respiratory and cardiac activity with life-threatening arrhythmia, which may recur after recovery. Overdose can be fatal.

Treatment: symptomatic and supportive therapy. It is necessary to carry out monitoring: recording an ECG and monitoring blood pressure.

In case of severe intoxication, administer 1-3 mg of physostigmine salicylate intravenously. Since physostigmine salicylate is rapidly metabolized, the drug is administered repeatedly in the event of any of the following life-threatening complications (arrhythmias, convulsions, deep coma). Due to the toxic effect of physostigmine salicylate, after its administration it is necessary to monitor the patient's clinical condition.

Storage conditions

Store in a dry place, protected from light at a temperature of 15 - 25°C.

Keep out of the reach of children!

Shelf life

Conditions for dispensing from pharmacies

On prescription

Manufacturer

Saneka Pharmaceuticals a.s., Slovak Republic