Trade name of the drug: Amitriptyline
International nonproprietary name:
amitriptylineDosage form:
solution for intramuscular administrationCompound
Each ampoule (2 ml) contains:
Active substance:
Amitriptyline 20 mg (as amitriptyline hydrochloride 22.63 mg).
Excipients: glucose (dextrose) - 80.00 mg, water for injection - up to 2 ml.
Description
Transparent, colorless solution.
Pharmacotherapeutic group
Antidepressant
ATX code:
Pharmacological properties
Amitriptyline is a tricyclic antidepressant from the group of non-selective inhibitors of neuronal monoamine uptake.
Pharmacodynamics
It also has some analgesic (central origin), H2-histamine-blocking and antiserotonin effects, helps eliminate bedwetting and reduces appetite.
It has a strong peripheral and central anticholinergic effect due to its high affinity for m-cholinergic receptors; strong sedative effect associated with affinity for H1-histamine receptors and alpha-adrenergic blocking effect. It has the properties of an antiarrhythmic drug of subgroup Ia; like quinidine in therapeutic doses, it slows down ventricular conduction (in overdose it can cause severe intraventricular blockade).
The mechanism of antidepressant action is associated with an increase in the concentration of norepinephrine in synapses and/or serotonin in the central nervous system (CNS) (decreasing their reabsorption). The accumulation of these neurotransmitters occurs as a result of inhibition of their reuptake by the membranes of presynaptic neurons. With long-term use, it reduces the functional activity 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. In anxiety-depressive conditions, it reduces anxiety, agitation and depressive symptoms.
The mechanism of antiulcer action is due to the ability to block H2-histamine receptors in the parietal cells of the stomach, as well as to have a sedative and anticholinergic effect (for gastric and duodenal ulcers, it relieves pain and helps accelerate ulcer healing).
Effectiveness for bedwetting appears to be due to anticholinergic activity leading to increased bladder distensibility, direct beta-adrenergic stimulation, alpha-adrenergic agonist activity leading to increased sphincter tone, and central blockade of serotonin uptake.
It 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 an effect on endogenous opioid systems.
The mechanism of action in bulimia nervosa is unclear (may be similar to that in depression). A clear effect of the drug on bulimia has been shown in patients both without depression and in its presence, while a decrease in bulimia can be observed without a concomitant weakening of depression itself.
During general anesthesia, it reduces blood pressure and body temperature. Does not inhibit MAO. The antidepressant effect develops within 2-3 weeks after the start of use.
Pharmacokinetics
The bioavailability of amitriptyline through various routes of administration is 30 - 60%, its active metabolite nortriptyline is 46 - 70%. Volume of distribution 5-10 l/kg. Effective therapeutic concentrations in the blood of amitriptyline are 50 - 250 ng/ml, for nortriptyline (its active metabolite) 50 - 150 ng/ml. The maximum concentration in blood plasma (Cmax) is 0.04 - 0.16 μg/ml. Passes through histohematic barriers, including the blood-brain barrier (including nortriptyline). The concentration of amitriptyline in tissues is higher than in plasma. Communication with plasma proteins 92 - 96%. Metabolized in the liver (by demethylation, hydroxylation) with the formation of active metabolites - nortriptyline, 10-hydroxy-amitriptyline, and inactive metabolites.
The plasma half-life ranges from 10 to 28 hours for amitriptyline and from 16 to 80 hours for nortriptyline. Excreted by the kidneys - 80%, partly with bile. Complete elimination within 7-14 days.
Amitriptyline crosses the placental barrier and is excreted into breast milk in concentrations similar to plasma concentrations.
Indications for use
Depression (especially with anxiety, agitation and sleep disorders, including in childhood, endogenous, involutional, reactive, neurotic, drug-induced, with organic brain damage, alcohol withdrawal), schizophrenic psychoses, mixed emotional disorders, 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, post-herpetic neuralgia, post-traumatic neuropathy, diabetic or other peripheral neuropathy) , headache, migraine (prevention), peptic ulcer of the stomach and duodenum.
Contraindications
Prescribed intramuscularly.
For severe depression resistant to therapy: intramuscularly (administer slowly!) at a dose of 10 - 20 - 30 mg up to 4 times a day, the dose should be increased gradually, the maximum daily dose is 150 mg; after 1-2 weeks they switch to taking the drug orally. Children over 12 years of age and the elderly are given lower doses and increased more slowly. If the patient's condition does not improve within 3-4 weeks of treatment, then further therapy is not advisable. Side effects
Mainly associated with the anticholinergic effect of the drug: accommodation paresis, blurred vision, increased intraocular pressure, dry mouth, constipation, intestinal obstruction, urinary retention, increased body temperature. All these phenomena usually disappear after adaptation to the drug or dose reduction.
From the side of the central nervous system: headache, ataxia, increased fatigue, weakness, irritability, dizziness, tinnitus, drowsiness or insomnia, impaired concentration, nightmares, dysarthria, confusion, hallucinations, motor agitation, disorientation, tremor, paresthesia, peripheral neuropathy, changes in EEG. Rarely - extrapyramidal disorders, seizures, anxiety.
From the cardiovascular system: tachycardia, arrhythmia, conduction disturbance, blood pressure lability, expansion of the QRS complex on the ECG (intraventricular conduction disturbance), symptoms of heart failure, fainting.
From the gastrointestinal tract: nausea, vomiting, heartburn, anorexia, stomatitis, taste disturbances, darkening of the tongue, discomfort in the epigastrium, gastralgia, increased activity of liver transaminases, rarely cholestatic jaundice, diarrhea.
From the endocrine system: an increase in the size of the mammary glands in men and women, galactorrhea, changes in the secretion of antidiuretic hormone (ADH), changes in libido, potency. Rarely - hypo- or hyperglycemia, glucosuria, impaired glucose tolerance, testicular swelling.
Allergic reactions: skin rash, itching, photosensitivity, angioedema, urticaria.
Others: agranulocytosis, leukopenia, eosinophilia, thrombocytopenia, purpura and other blood changes, hair loss, swollen lymph nodes, weight gain with long-term use, sweating, pollakiuria.
With long-term treatment, especially in high doses, with abrupt cessation of treatment, the development of a “withdrawal” syndrome is possible: headache, nausea, vomiting, diarrhea, as well as irritability, sleep disturbance with vivid, unusual dreams, increased excitability. Overdose
Drowsiness, disorientation, confusion, depression of consciousness up to coma, dilated pupils, increased body temperature, shortness of breath, dysarthria, agitation, hallucinations, seizures, muscle rigidity, vomiting, arrhythmia, hypotension, heart failure, respiratory depression.
Help measures: cessation of amitriptyline therapy, fluid infusion, symptomatic therapy, maintenance of blood pressure and water-electrolyte balance. Monitoring of cardiovascular activity (ECG) is indicated for 5 days, because relapse may occur within 48 hours or later. Hemodialysis and forced diuresis are not very effective. Interaction with other drugs
Amitriptyline enhances the inhibitory effect on the central nervous system of the following drugs: antipsychotics, sedatives and hypnotics, anticonvulsants, analgesics, anesthetics, alcohol; exhibits synergism when interacting with other antidepressants.
When amitriptyline is used together with antipsychotics and/or anticholinergic drugs, a febrile temperature reaction and paralytic intestinal obstruction may occur.
Amitriptyline potentiates the hypertensive effects of catecholamines and other adrenergic stimulants, which increases the risk of developing heart rhythm disturbances, tachycardia, and severe arterial hypertension, but inhibits the effects of drugs that affect the release of norepinephrine.
Amitriptyline may reduce the antihypertensive effect of guanethidine, drugs with a similar mechanism of action, and also weaken the effect of anticonvulsants.
With the simultaneous use of amitriptyline and anticoagulants - coumarin derivatives, it is possible to increase the anticoagulant activity of the latter.
When taking amitriptyline and cemitidine simultaneously, it is possible to increase the plasma concentration of amitriptyline with the possible development of toxic effects. Inducers of microsomal liver enzymes (barbiturates, carbamazepine) reduce plasma concentrations of amitriptyline.
Amitriptyline enhances the effect of antiparkinsonian drugs and other drugs that cause extrapyramidal reactions.
Quinidine slows down the metabolism of amitriptyline. Amitriptyline with disulfiram and other acetaldehyde dehydrogenase inhibitors may cause delirium.
Estrogen-containing oral contraceptives may increase the bioavailability of amitriptyline; Pimozide and probucol may increase cardiac arrhythmias.
Amitriptyline may enhance corticosteroid-induced depression; combined use with drugs for the treatment of thyrotoxicosis increases the risk of developing agranulocytosis.
Concomitant use of amitriptyline with MAO inhibitors can be fatal. The break in treatment between taking MAO inhibitors and tricyclic antidepressants should be at least 14 days! Special instructions
Amitriptyline in doses above 150 mg/day reduces the threshold for seizure activity, so the possibility of seizures should be taken into account in patients with a history of seizures and in those patients who are predisposed to this due to age or injury.
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 MDP may progress to the manic phase.
While taking amitriptyline, driving vehicles, servicing machinery and other types of work that require increased concentration, as well as drinking alcohol, is prohibited. Release form
Solution for intramuscular administration 10 mg/ml. 2 ml in colorless glass ampoules. 5 ampoules per PVC container. 2 containers (10 ampoules) along with instructions for use are placed in a cardboard box. Storage conditions
In a dry place, protected from light, at a temperature of 10 to 25 ° C. Best before date
3 years.
Do not use after the expiration date stated on the packaging. Conditions for dispensing from pharmacies
According to the recipe. Manufacturer
ZENTIVA a.s., Czech Republic
U Kabelovny 130, 10237, Prague 10, Dolní Mecholupy, Czech Republic Send claims regarding the quality of the drug to the address ZENTIVA PHARMA LLC:
Russia, 119017, Moscow, st. Bolshaya Ordynka, 40, building 4.
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
Trade name:
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. 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.
With caution
Diseases of the cardiovascular system (angina pectoris, arterial hypertension), blood diseases, increased intraocular pressure, angle-closure 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 adverse 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:
Very often: palpitations and tachycardia, orthostatic hypotension.
Often: arrhythmia (including conduction disturbances, QT interval prolongation), hypotension, AV block, bundle branch block.
Uncommon: increase in blood pressure.
Rarely: myocardial infarction.
From the nervous system:
Very 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.
Uncommon: convulsions.
From the urinary system:
Often: urinary retention.
From the skin:
Very often: hyperhidrosis.
Uncommon: rash, skin vasculitis, urticaria.
Rarely: photosensitivity, alopecia.
From the senses:
Very often: decreased visual acuity, impaired accommodation (reading glasses may be required during treatment).
Often: mydriasis
Uncommon: tinnitus, increased intraocular pressure.
Rarely: loss of accommodation ability, worsening narrow-angle glaucoma.
Mental disorder:
Very often: confusion (confusion in elderly patients is characterized by anxiety, sleep disturbance, difficulty remembering, psychomotor agitation, confusion of thoughts, delirium), disorientation.
Often: decreased concentration.
Uncommon: 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
Very often: dry mouth, constipation, nausea.
Often: gum recession, oral inflammation, dental caries, burning sensation in the mouth.
Uncommon: diarrhea, vomiting, swelling of the tongue.
Rarely: paralytic intestinal obstruction, swelling of the parotid gland, cholestatic jaundice, liver dysfunction, hepatitis.
Common disorders:
Often: weakness.
Uncommon: swelling of the face.
Rarely: increase in body temperature.
From the side of metabolism:
Very often: weight gain, increased appetite.
Rarely: decreased appetite.
Very rarely: syndrome of inappropriate secretion of antidiuretic hormone.
From the reproductive system:
Very 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 2-7 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 the treatment period, 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
According to the recipe.
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.
Dosage form: Film-coated tablets are blue, with a biconvex surface, scored on one side.
Before taking this medicine, read the entire leaflet carefully:
Do not throw away this leaflet. You may need to re-read it.
If you have any questions, ask your doctor or pharmacist.
This medicine must be prescribed to you by your doctor. Do not pass it on to others. It can harm them, even if their symptoms are the same as yours.
If any of the side effects become serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.
What is Amitriptyline and what is it used for: Each Amitriptyline tablet contains the active substance - amitriptyline hydrochloride, 25 mg, and excipients: lactose, corn starch, dibasic calcium phosphate, gelatin, talc, magnesium stearate, colloidal anhydrous silicon dioxide, polyethylene glycol 6000, Opadry Blue (hydroxypropyl methylcellulose, titanium dioxide (E) 171), talc, polyethylene glycol, brilliant blue (E 133)).
Belongs to the group of antidepressants, has a sedative effect, improves mood, and helps eliminate bedwetting.
Amitriptyline is used in the following cases:
severe depression, especially with characteristic signs of anxiety, agitation and sleep disorders;
nocturnal enuresis in children in the absence of organic pathology.
Do not take Amitriptyline if:
hypersensitivity to amitriptyline or to any of the components of this drug;
angle-closure glaucoma;
disturbance of urodynamics due to prostatic hypertrophy or bladder atony;
recent myocardial infarction, cardiac conduction or rhythm disturbances, coronary artery insufficiency;
simultaneous use with MAO inhibitors, sultopride.
Before prescribing Amitriptyline, be sure to inform your doctor about the following changes in your health:
tendency to develop orthostatic hypotension and sedation during treatment with amitriptyline;
chronic constipation;
prostatic hyperplasia;
diseases of the cardiovascular system;
hypothyroidism, taking thyroid hormone medications;
liver or kidney failure.
When prescribing Amitriptyline, be sure to inform your doctor if you are taking any of the following medications:
Antihypertensives – for the treatment of hypertension;
Atropine and other atropine-like substances (sedative H1-histamine, antiparkinsonian, anticholinergic, antispasmodic atropine drugs, disopyramide, phenothiazine neuroleptics) - for the treatment of allergies, Parkinson's disease, eye diseases, mental disorders.
Central nervous system depressants (morphine derivatives - analgesics, antitussives; barbiturates, benzdiazepines; anxiolytics; sedative antidepressants (doxypine, miaserine, mirtazapine, trimipramine), neuroleptics; sedative H1-antihistamines; centrally acting antihypertensives; thalidomide) - for pain relief, treatment of cough, depression, allergies, hypertension.
Baclofen is a muscle relaxant.
Beta blockers (bisoprolol, carvedilol, metoprolol) - for the treatment of heart diseases.
Combinations of Amitriptyline with certain drugs are undesirable and require medical supervision and dose adjustment of drugs:
Medicines containing alcohol.
Clonidine, guanfacine - for the treatment of hypertension.
Selective MAO inhibitors (moclobemide, toloxatone) – for the treatment of depression.
Linezolid – for the treatment of infections.
Alpha and beta sympathomimetics (epinephrine, norepinephrine, adrenaline, norepinephrine, systemic dopamine for parenteral administration).
Antiepileptic drugs, incl. carbamazepine, valproic acid, valpromide - for the treatment of epilepsy.
Antidepressants - selective serotonin reuptake inhibitors (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline).
Alpha and beta sympathomimetics (adrenaline, epinephrine as a local hemostatic and for subcutaneous/subbucal injections).
Phenothiazides (thioridazine) – for the treatment of mental disorders.
The combined use of Amitriptyline and the following medications is contraindicated:
Non-selective monoamine oxidase inhibitors (MAO) - for the treatment of depression, anxiety disorders and other diseases.
Sultopride – for the treatment of mental disorders.
Use of Amitriptyline during pregnancy and lactation:
Taking amitriptyline during pregnancy is possible under medical supervision only in cases where the expected benefit to the mother outweighs the possible risk to the fetus. If amitriptyline therapy is necessary to maintain maternal mental health, treatment with the drug at an effective dose can be continued throughout pregnancy. Newborns may experience some side effects that appear in the first days of life and, as a rule, are short-lived and mild. Be sure to warn your doctor about taking amitriptyline: observation and care of newborns is carried out taking into account the above effects.
Amitriptyline passes into breast milk. If treatment with the drug is necessary during lactation, breastfeeding must be interrupted.
The ability of Amitriptyline to influence the control of vehicles and other mechanisms: the drug may reduce the ability to drive a car and use other machinery, which must be taken into account.
The dose of the drug is determined by the doctor. Take during or after meals with water. To improve sleep, the drug can be taken in the evening. The dose is usually increased by taking the drug in the evening or before bedtime. For maintenance therapy, it can be taken once a day. The withdrawal of the drug is carried out gradually under the supervision of a doctor.
The mark on the tablet is intended solely to facilitate patient administration.
Depression. Treatment begins with low doses and is gradually increased under the close supervision of a physician to assess the effectiveness and tolerability of therapy.
Typically the dose is 75-150 mg per day, higher doses are used in hospital settings. The average daily dose in adults is usually 75 mg (25 mg 3 times a day). After 3 weeks of effective treatment, the daily dose can be revised individually.
In children, the effective daily dose is no more than 1 mg/kg body weight.
Treatment with antidepressants is symptomatic. The duration of treatment is about 6 months to prevent relapse.
Nocturnal enuresis in children. The doses of amitriptyline used for enuresis are lower than those used to treat depression. The daily dose for children aged 6 to 10 years with a body weight of 25 kg or more is 25 mg per day (1 tablet), from 11 to 16 years - 25 - 50 mg per day (1-2 tablets).
The drug is taken before bedtime. The duration of therapy is no more than 3 months.
Special categories of patients. In patients over the age of 65 years, the initial dose should be reduced (to 50% of the minimum). The daily dose can be divided into several doses or taken once before bedtime. If necessary, the dose is increased gradually, under close medical supervision due to the possibility of serious side effects in this category of patients (fainting, confusion). In case of impaired liver and kidney function, careful selection of an individual dose is recommended, which may be reduced compared to patients with normal function of these organs.
If you take a larger dose of Amitriptyline than your doctor recommends: If the number of tablets per day you take exceeds the number recommended by your doctor, or your child swallows the tablets, consult a doctor or call an ambulance immediately! Stop taking the medicine immediately! Symptoms of overdose will most likely include dry mouth, accommodation disorders, tachycardia, heart rhythm disturbances, decreased blood pressure, increased sweating, and urinary retention. Confusion and coma are possible. As first aid, carry out the following measures: gastric lavage, taking an activated carbon suspension, laxatives, maintaining body temperature, monitoring blood pressure, ECG.
If you forget to take your next dose of Amitriptyline on time: Take the tablet as soon as you remember, making sure there is time before taking the next dose. If there is little time before your next dose, take as directed by your doctor. Do not take a double dose if you miss the next dose!
Possible adverse reactions::
Amitriptyline may cause adverse reactions similar to those that occur with other tricyclic antidepressants. Some of the side effects listed below (headache, tremor, difficulty concentrating, constipation, and decreased libido) may also be symptoms of depression and will subside as the depression resolves.
disturbance of conduction and heart rhythm (in high doses);
breast enlargement, milk secretion from the mammary glands;
an increase in the number of eosinophils, a decrease in the number of leukocytes and platelets in the blood.
dry mouth, constipation, accommodation disorders, tachycardia, increased sweating, urinary retention;
orthostatic hypotension, decreased sexual function;
drowsiness or sedation, tremor, seizures in susceptible individuals, confusion, loss of consciousness, dysarthria;
risk of developing suicidal behavior/thoughts, mood changes with the onset of a manic episode, manifestations of anxiety;
weight gain;
allergic skin reactions;
Adverse reactions in elderly patients. In patients aged 50 years and older, an increased risk of bone fractures was found when taking selective serotonin reuptake inhibitors or tricyclic antidepressants. The mechanism of occurrence of this side effect is not clear.
Special precautions when taking Amitriptyline:
Depression is associated with an increased risk of developing suicidal behavior, self-aggression and suicide. Such a risk may exist until stable remission is achieved and may occur spontaneously throughout the course of therapy, especially in the early stages of remission or when the dosage is changed. When treating with antidepressants, it is necessary to carefully monitor your condition, especially at the beginning of therapy: changes in mood, behavior, clinical deterioration and/or the appearance of suicidal thoughts, the development of side effects. Ask your loved ones to help you assess your condition during treatment. If there is any change in condition or doubt in its assessment, please consult a doctor or tell your loved ones!
If insomnia or nervousness occurs at the beginning of treatment, it is recommended to consult a doctor to reduce the dose of the drug and carry out the necessary symptomatic treatment.
In patients suffering from manic-depressive disorders, the course of the disease may worsen. You should stop taking amitriptyline and consult your doctor for appropriate treatment.
In patients with epilepsy while taking amitriptyline, the seizure threshold may be reduced. If seizures develop, amitriptyline should be discontinued. Consult a doctor for appropriate treatment.
When you stop taking the drug, rare signs of withdrawal syndrome are observed (headache, malaise, nausea, anxiety, sleep disturbances), to prevent which a gradual (over several weeks) dose reduction with careful monitoring of the condition is necessary.
The drug is used with caution in elderly patients.
Due to the presence of lactose in the drug, the drug is contraindicated in persons with congenital galactosemia, impaired absorption of glucose and galactose, or lactose deficiency.
Storage conditions:
Store in a place protected from moisture and light at a temperature not exceeding 25C.
Keep out of the reach of children.
Package: 50 tablets in polymer jars or 10 tablets in a blister pack. One can or 5 blister packs together with an insert sheet are placed in a cardboard pack.
Best before date: 3 years.
Vacation conditions: By doctor's prescription
Manufacturer information:
Belarusian-Dutch joint venture limited liability company "Farmland", Republic of Belarus, Minsk region, Nesvizh, st. Leninskaya, 124, building 3
Amitriptyline is an antidepressant from the group of tricyclic compounds, a dibenzocycloheptadine derivative.
The drug has a pronounced sedative (calming), thymoanaleptic (the ability to suppress depression) and anxiolytic (the ability to suppress anxiety and fear) effects.
Does not cause exacerbation of productive symptoms: hallucinations or delusions. In special cases, it is prescribed for menopause with severe central nervous system disorders. The therapeutic effect develops 2 weeks after the start of treatment.
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 due to inhibition of the reverse neuronal uptake of these mediators.
With long-term use, Amitriptyline reduces the functional activity of adrenergic and serotonin receptors in the brain, normalizes adrenergic and serotonergic transmission, and restores the balance of these systems, disturbed during depressive states. In anxiety-depressive conditions, it reduces anxiety, agitation and depressive symptoms.
The mechanism of therapeutic action of Amitriptyline in bulimia nervosa has not been established (possibly similar to that in depression). Amitriptyline has been shown to be clearly effective against bulimia in patients both without and with depression, while a decrease in bulimia can be observed without a concomitant decrease in depression itself.
The drug is well absorbed from the gastrointestinal tract. The binding of amitriptyline to blood proteins reaches 90-95%. The plasma half-life ranges from 10 to 28 hours for amitriptyline and from 16 to 80 hours for nortriptyline. Excreted by the kidneys - 80%, partly with bile. Complete elimination within 7-14 days. Amitriptyline crosses the placental barrier and is excreted into breast milk in concentrations similar to plasma concentrations.
Available in the form of dragees or tablets, solution for injection. Injections Amitriptyline is administered intramuscularly. At home, dragees are most often used.
Indications for use
What does Amitriptyline help with? The drug is prescribed in the following cases/pathologies:
- persistent depression;
- neurosis;
- significant behavioral disturbance;
- phobias;
- emotional disorders;
- anorexia;
- migraine prevention;
- chronic pain syndrome due to nerves.
A direct indication for treatment with Amitriptyline is a confirmed diagnosis:
- Autism;
- Alcoholism;
- Depression;
- Hypochondria.
To treat mild sleep disorders and mood swings, “milder” drugs are used.
Instructions for use of Amitriptyline and dosage
Take orally, without chewing, immediately after meals (to reduce irritation of the gastric mucosa).
The initial dose for adults is 25-50 mg at night, then the dose is increased over 5-6 days to 150-200 mg/day in 3 divided doses (the maximum dose is taken at night). If there is no improvement within 2 weeks, the daily dose is increased to 300 mg.
When signs of depression disappear, the dose is reduced to 50-100 mg/day and therapy is continued for at least 3 months.
In old age, with mild disorders, a dose of 30-100 mg/day (at night) is prescribed; after achieving a therapeutic effect, they switch to the minimum effective dose - 25-50 mg/day. IM or IV (administer slowly) at a dose of 20-40 mg 4 times a day, gradually replacing oral administration. The duration of treatment is no more than 6-8 months.
For nocturnal enuresis in children 6-10 years old - 10-20 mg/day at night, 11-16 years old - 25-50 mg/day.
For children as an antidepressant: from 6 to 12 years - 10-30 mg or 1-5 mg/kg/day in fractions, in adolescence - 10 mg 3 times a day (if necessary, up to 100 mg/day).
For the prevention of migraine, for chronic pain of a neurogenic nature (including prolonged headaches) - from 12.5-25 to 100 mg/day (the maximum dose is taken at night).
Amitriptyline injections:
IM – the initial dose is 50-100 mg/day in 2-4 injections. If necessary, the dose can be gradually increased to 300 mg/day, in exceptional cases – up to 400 mg/day.
Amitriptyline should be used with caution in case of arrhythmia, coronary heart disease, heart block, myocardial infarction, heart failure, stroke, arterial hypertension, chronic alcoholism, thyrotoxicosis, and during treatment with thyroid medications.
Withdrawal syndrome may develop if you abruptly stop taking it.
Use cautiously with other drugs that have anticholinergic effects. During therapy with amitriptyline, alcohol should not be consumed. During treatment, you should refrain from potentially dangerous activities that require rapid psychomotor reactions and increased attention.
Contraindications
Amitriptyline is contraindicated in the following cases:
- Heart failure in the stage of decompensation
- Acute and recovery period of myocardial infarction
- Conduction disorders of the heart muscle
- Severe arterial hypertension
- Acute liver and kidney diseases with severe dysfunction
- Peptic ulcer of the stomach and duodenum in the acute stage
- Prostatic hypertrophy
- Bladder atony
- Pyloric stenosis, paralytic ileus
- Concomitant treatment with MAO inhibitors (see Use)
- Pregnancy, breastfeeding period
- Children under 6 years old
- Increased sensitivity to amitriptyline
Caution should be exercised when using the product in the following categories:
- Severe alcoholism
- Asthma in the bronchi
- Manic-depressive psychosis
- Frequent seizures
- Heart rhythm disturbances
- Closed-type glaucoma
- Increased intraocular pressure
Overdose
The main symptoms of overdose are hallucinations, convulsions, coma, impaired cardiac conduction, extrasystole, ventricular arrhythmia, hypothermia.
It is recommended to lavage the stomach, take an activated carbon suspension, laxatives, fluid infusion, symptomatic therapy, maintain body temperature, monitor 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.
Use during pregnancy and lactation
Amitriptyline is contraindicated during pregnancy. During treatment it is necessary to stop breastfeeding.
Analogues and prices of Amitriptyline, list of drugs
If necessary, you can replace Amitriptyline with an analogue according to the ATC code, list of drugs:
- Amizol,
- Amirol,
- Saroten retard,
- Tryptisol,
- Elivel
When choosing analogues, it is important to understand that the instructions for use of Amitriptyline, price and reviews do not apply to drugs with similar effects. It is important to consult a doctor and not change the drug yourself.
The price of Amitriptyline tablets in Russian pharmacies is on average 30-55 rubles per pack.
Store at temperatures between 10 °C and 25 °C in a dry, dark place out of the reach of children. Shelf life – 2-3 years (depending on the form of release and manufacturer). Do not take after the expiration date indicated on the package! Conditions for dispensing from pharmacies - according to a doctor's prescription.
Amitriptyline is a drug from the pharmacological group of antidepressants that has thymoleptic, antidepressant, anxiolytic and sedative effects. Due to the development of tolerance with regular use of amitriptyline and the tendency for side effects such as constipation, use of the drug in elderly patients is not recommended.
Active ingredient: Amitriptyline hydrochloride
Release form: film-coated tablets
Pharmacological effects
Amitriptyline acts primarily as a serotonin and norepinephrine reuptake inhibitor, with sufficient inhibition of serotonin transport and moderate effects on norepinephrine transport. The drug has little effect on dopamine transport and therefore does not affect dopamine reuptake. During exposure, amitriptyline derivatives are metabolized to nortriptyline, a more potent and selective norepinephrine reuptake inhibitor, which complements its effect on norepinephrine reuptake.
Amitriptyline additionally has 5-HT-2A, 5-HT-2C, 5-HT-3, 5-HT-6, 5-HT-7 and α-1-adrenergic effects. In addition, the drug inhibits sodium channels, L-type calcium channels and closes some potassium pathways. Amitriptyline also acts as a functional inhibitor of sphingomyelinase in an acidic environment.
Indications for use
Amitriptyline is a drug often used in the treatment of the following psychopathological conditions and disorders:
- All types of schizophrenia.
- Inorganic psychoses of unspecified etiology and genesis.
- Depressive symptoms of all types.
- Recurrent depressive disorder.
- Emotionally unstable personality disorder.
- Behavioral and social adaptation disorders.
- Inorganic enuresis.
- Migraine.
- Constant pain resistant to therapy.
In addition, the experimental use of amitriptyline is being widely studied for:
- Eating disorders of various types. Several randomized controlled studies have shown the drug's effectiveness in the palliative treatment of eating disorders.
- Insomnia.
- Urinary incontinence. In most cases, amitriptyline helps to increase the urge to urinate.
- Cyclic vomiting syndrome.
- Chronic cough.
- Preventive support for patients with recurrent biliary dyskinesia - sphincter of Oddi dysfunction.
- Attention deficit hyperactivity disorder - in addition to the classic scheme of using stimulant drugs.
Side effects of amitriptyline and contraindications
Common, approximately 1% frequency, side effects from amitriptyline include dizziness, frequent headaches, weight gain, and side effects common to anticholinergic drugs. These include cognitive impairment such as delirium and confusion, affective disorders such as anxiety and agitation, as well as cardiovascular disorders such as orthostatic hypotension and tachycardia. In addition, sexual disorders in the form of impotence and decreased or complete absence of libido are possible. Sleep disorders - drowsiness and insomnia are also possible with regular use of amitriptyline.
Known contraindications for amitriptyline are:
- Hypersensitivity to tricyclic antidepressants or any of their excipients.
- History of myocardial infarction.
- Chronic heart failure of any degree.
- Other complicated cardiac pathologies.
- Insufficiency of the coronary arteries.
- Mania and paranoia.
- Severe liver diseases.
- Age up to 7 years.
- Breast-feeding.
- Patients who are taking monoamine oxidase inhibitors or have taken them within the last 14 days.
Interaction of amitriptyline with other drugs
Amitriptyline, having a specific broad effect on the regulatory functions of the nervous system, interacts with a significant number of drugs, the use of which in therapy with amitriptyline is not recommended:
- Monoamine oxidase inhibitors, which can potentially cause serotonin deficiency syndrome.
- CYP2D6 inhibitors and substrates, such as, due to the risk of increasing plasma concentrations of the drug;
- Guanethidine. The antihypertensive effects of this drug may be suppressed.
- Anticholinergics such as benztropine, hyoscine (scopolamine) and atropine, which can exacerbate the mutual anticholinergic effect, usually expressed in the form of intestinal obstruction and tachycardia.
- Neuroleptics. Their use with amitriptyline can cause increased sedative, anticholinergic, epileptogenic and temperature-stimulating effects. Also, this combination of drugs increases the risk of neuroleptic malignant syndrome.
- Cimetidine - due to impaired hepatic metabolism of amitriptyline and, consequently, an increase in drug concentrations in the blood plasma.
- Disulfiram, due to the tendency to develop delusional syndrome.
- Antithyroid drugs and amitriptyline tablets may increase the risk of agranulocytosis.
- Thyroid hormones and amitriptyline have the potential for increased side effects such as excessive CNS stimulation and arrhythmia.
- Analgesics, such as tramadol, in combination with amitriptyline can increase the risk of developing heart failure.
- Levodopa, due to delayed gastric emptying and decreased intestinal motility.
Amitriptyline overdose
Symptoms and treatment for amitriptyline overdose are largely the same as for other tricyclic antidepressants. Many studies confirm that amitriptyline can be especially dangerous in overdose, so its use as first-line treatment for depression is not recommended.
Possible symptoms of an amitriptyline overdose include:
- drowsiness;
- hypothermia;
- tachycardia;
- other arrhythmias with disorders in the bundle branches;
- ECG indicates conduction disturbances;
- chronic heart failure;
- dilated pupils;
- convulsions, often myoclonic type;
- severe hypotension;
- stupor;
- coma;
- polyradiculoneuropathy;
- hyperactive reflexes;
- increased tone of skeletal muscles;
- vomiting
There are no specific antidotes for the treatment of amitriptyline overdose. Activated charcoal may reduce the absorption of the drug if taken within 1-2 hours after the overdose. If the victim is unconscious or has an impaired gag reflex, it is possible to use a nasogastric tube to deliver activated charcoal to the stomach.
All manipulations to neutralize amitriptyline should be carried out against the background of ECG monitoring and over the next five days after improvement. Cardiac arrhythmias are recommended to be controlled with propranolol, and heart failure with digitalis.
Amitriptyline increases the depressant effect on the central nervous system, but does not reverse the anticonvulsant effect of barbiturates; inhalation is recommended to control seizures. Dialysis does not make sense due to the high degree of protein binding of amitriptyline.
