Amitriptyline
Amitriptyline: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. Use in childhood
- 11. Use in the elderly
- 12. Drug interactions
- 13. Analogs
- 14. Terms and conditions of storage
- 15. Terms of dispensing from pharmacies
- 16. Reviews
- 17. Price in pharmacies
Latin name: Amitriptyline
ATX code: N06AA09
Active ingredient: amitriptyline (amitriptyline)
Producer: ZAO ALSI Pharma (Russia), OOO Ozone (Russia), OOO Sintez (Russia), Nikomed (Denmark), Grindeks (Latvia)
Description and photo update: 2019-16-08
Prices in pharmacies: from 28 rubles.
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Amitriptyline is an antidepressant with pronounced sedative, antibulimic and antiulcer effects.
Release form and composition
The drug is released in the form of a solution and tablets.
The tablets are biconvex, round, yellow, film-coated.
The active ingredient in the composition of the drug is amitriptyline hydrochloride. Auxiliary components in tablets are:
- Lactose monohydrate;
- Calcium stearate;
- Corn starch;
- Colloidal silicon dioxide;
- Gelatin;
- Talc.
Pharmacological properties
Pharmacodynamics
Amitriptyline is a tricyclic antidepressant belonging to the group of non-selective inhibitors of neuronal monoamine uptake. It is characterized by pronounced sedative and thymoanaleptic effects.
The mechanism of the antidepressant action of the drug is due to the suppression of the reverse neuronal uptake of catecholamines (dopamine, norepinephrine) and serotonin in the central nervous system. Amitriptyline exhibits the properties of an antagonist of muscarinic cholinergic receptors in the peripheral and central nervous system, it is also characterized by peripheral antihistamine associated with H 1 receptors, and antiadrenergic effects. The substance has anti-neuralgic (central analgesic), anti-bulimic and anti-ulcer effects, and also helps to eliminate bedwetting. The antidepressant effect develops within 2-4 weeks after the start of use.
Pharmacokinetics
Amitriptyline is highly absorbed in the body. After oral administration, its maximum concentration is reached in about 4–8 hours and is equal to 0.04–0.16 μg / ml. The equilibrium concentration is determined approximately 1-2 weeks after the start of the course of therapy. The content of amitriptyline in blood plasma is less than in tissues. The bioavailability of the substance, regardless of its route of administration, varies from 33 to 62%, and its pharmacologically active metabolite nortriptyline - from 46 to 70%. The volume of distribution is 5-10 l / kg. Therapeutic blood concentrations of amitriptyline with proven efficacy are 50–250 ng / ml, and the same values for the active metabolite of nortriptyline are 50–150 ng / ml.
Amitriptyline binds to plasma proteins by 92-96%, overcomes histohematological barriers, including the blood-brain barrier (the same applies to nortriptyline) and the placental barrier, and is also determined in breast milk at concentrations similar to plasma ones.
Amitriptyline is metabolized mainly through hydroxylation (the isoenzyme CYP2D6 is responsible for it) and demethylation (the process is controlled by isoenzymes CYP3A and CYP2D6), followed by the formation of conjugates with glucuronic acid. Metabolism is characterized by significant genetic polymorphism. The main pharmacologically active metabolite is a secondary amine, nortriptyline. The metabolites of cis- and trans-10-hydroxynortriptyline and cis- and trans-10-hydroxyamitriptyline have an activity profile that is almost similar to that of nortriptyline, but their effect is less pronounced. Amitriptyline-N-oxide and demethylnortriptyline are determined in blood plasma only in trace concentrations, and the first metabolite has almost no pharmacological activity. Compared with amitriptyline, all metabolites are characterized by a significantly less pronounced m-cholinergic blocking effect. The rate of hydroxylation is the main factor determining renal clearance and, accordingly, the content in blood plasma. A small percentage of patients have a genetically determined decrease in the rate of hydroxylation.
The plasma half-life of amitriptyline is 10–28 hours for amitriptyline and 16–80 hours for nortriptyline. On average, the total clearance of the active substance is 39.24 ± 10.18 l / h. Excretion of amitriptyline is carried out mainly in the urine and feces in the form of metabolites. Approximately 50% of the administered dose of the drug is excreted through the kidneys in the form of 10-hydroxy-amitriptyline and its conjugate with glucuronic acid, approximately 27% is excreted in the form of 10-hydroxy-nortriptyline and less than 5% of amitriptyline is excreted in the form of nortriptyline and unchanged. The drug is completely excreted from the body within 7 days.
In elderly patients, the metabolic rate of amitriptyline decreases, which leads to a decrease in drug clearance and an increase in the half-life. Liver dysfunctions can provoke a slowdown in the rate of metabolic processes and an increase in the content of amitriptyline in the blood plasma. In patients with renal dysfunction, the excretion of nortriptyline and amitriptyline metabolites is slowed down, but the metabolic processes are similar. Since amitriptyline binds well to blood plasma proteins, it is almost impossible to remove it from the body by dialysis.
Indications for use
According to the instructions, Amitriptyline is prescribed for the treatment of depressive states of an involutional, reactive, endogenous, medicinal nature, as well as depressions against the background of alcohol abuse, organic brain lesions, accompanied by sleep disturbances, agitation, anxiety.
Indications for the use of Amitriptyline are:
- Schizophrenic psychoses;
- Emotional mixed disorders;
- Behavior disorders;
- Nocturnal enuresis (other than that caused by low bladder tone);
- Bulimia nervosa;
- Chronic pain (migraine, atypical facial pain, pain in cancer patients, post-traumatic and diabetic neuropathy, rheumatic pain, post-herpetic neuralgia).
The drug is also used for gastrointestinal ulcers, to relieve headaches and prevent migraines.
Contraindications
- Violations of myocardial conduction;
- Severe hypertension;
- Acute kidney and liver diseases;
- Atony of the bladder;
- Hypertrophy of the prostate;
- Paralytic intestinal obstruction;
- Hypersensitivity;
- Pregnancy and lactation;
- Age up to 6 years.
Instructions for the use of Amitriptyline: method and dosage
Amitriptyline tablets should be swallowed without chewing.
The starting dosage for adults is 25-50 mg, the drug is taken at night. For 5-6 days, the dosage is increased, brought to 150-200 mg / day, they are consumed in 3 doses.
The instructions for Amitriptyline indicate that the dosage is increased to 300 mg / day, if after 2 weeks there is no improvement in the condition. When the symptoms of depression have disappeared, the dosage should be reduced to 50-100 mg / day.
If the patient's condition does not improve within 3-4 weeks of treatment, further therapy is considered inappropriate.
For elderly patients with minor violations, Amitriptyline tablets are prescribed at a dosage of 30-100 mg / day, they are taken at night. After improving the condition, patients are allowed to switch to a minimum dosage of 25-50 mg / day.
Intravenously or intramuscularly, the drug is administered slowly at a dosage of 20-40 mg 4 times a day. The treatment lasts 6-8 months.
The drug for neurological pain (including chronic headaches) and for the prevention of migraine is taken at a dosage of 12.5-100 mg / day.
Children 6-10 years old with nocturnal enuresis are given 10-20 mg of the drug per day, at night, children 11-16 years old - 25-50 mg / day.
For the treatment of depression in children 6-12 years old, the drug is prescribed at a dose of 10-30 mg or 1-5 mg / kg / day, in divided doses.
Side effects
The use of Amitriptyline can cause visual impairment, impaired urination, dry mouth, increased intraocular pressure, increased body temperature, constipation, functional intestinal obstruction.
Usually, all these side effects disappear after a decrease in the prescribed doses or after the patient gets used to the drug.
In addition, during treatment with the drug, there may be observed:
- Weakness, drowsiness, and fatigue;
- Ataxia;
- Insomnia;
- Dizziness;
- Nightmares;
- Confusion and irritability
- Tremor;
- Motor agitation, hallucinations, impaired attention;
- Paresthesia;
- Convulsions;
- Arrhythmia and tachycardia;
- Nausea, heartburn, stomatitis, vomiting, discoloration of the tongue, epigastric discomfort;
- Anorexia;
- Increased activity of liver enzymes, diarrhea, jaundice;
- Galactorrhea;
- Change in potency, libido, testicular edema;
- Hives, pruritus, purpura;
- Hair loss;
- Swollen lymph nodes.
Overdose
In different patients, reactions to an overdose of Amitriptyline vary significantly. In adult patients, administration of more than 500 mg of the drug leads to moderate or severe intoxication. Reception of Amitriptyline at a dose of 1200 mg or more provokes death.
Overdose symptoms can develop quickly and suddenly or slowly and imperceptibly. During the first hours, hallucinations, a state of agitation, agitation or drowsiness are noted. When taking high doses of Amitriptyline, the following are often observed:
- neuropsychic symptoms: disruption of the respiratory center, a sharp depression of the central nervous system, seizures, a decrease in the level of consciousness up to a coma;
- anticholinergic signs: slowing down of intestinal motility, mydriasis, fever, tachycardia, dry mucous membranes, urinary retention.
As the symptoms of overdose intensify, changes in the cardiovascular system also increase, expressed in arrhythmias (ventricular fibrillation, heart rhythm disturbances, flowing like Torsade de Pointes, ventricular tachyarrhythmia). ECG shows ST segment depression, lengthening of the PR interval, inversion or flattening of the T wave, lengthening of the QT interval, widening of the QRS complex and intracardiac conduction blockade of varying degrees, which can progress up to increased heart rate, lowering blood pressure, intraventricular blockade, heart failure and cardiac arrest … There is also a correlation between the expansion of the QRS complex and the severity of toxic reactions in the case of acute overdose. Patients often have symptoms such as hypokalemia, metabolic acidosis, cardiogenic shock,lowering blood pressure, heart failure. After the patient wakes up, negative symptoms are again possible, expressed in ataxia, agitation, hallucinations, and confusion.
As a therapeutic measure, it is necessary to stop taking amitriptyline. It is recommended that physostigmine is administered at a dose of 1-3 mg every 1-2 hours intramuscularly or intravenously, maintenance of water-electrolyte balance and normalization of blood pressure, symptomatic therapy, fluid infusion. It is also necessary to monitor cardiovascular activity, carried out by means of an ECG for 5 days, since a relapse of an acute condition can occur 48 hours later or later. The effectiveness of gastric lavage, forced diuresis and hemodialysis is considered low.
special instructions
The antidepressant effect of the drug develops 14-28 days after the start of use.
According to the instructions, the product should be taken with caution when:
- Bronchial asthma;
- Manic-depressive psychosis;
- Alcoholism;
- Epilepsy;
- Oppression of the hematopoietic function of the bone marrow;
- Hyperthyroidism;
- Angina pectoris;
- Heart failure;
- Intraocular hypertension;
- Closed-angle glaucoma;
- Schizophrenia.
During the period of treatment with Amitriptyline, it is prohibited to drive a car and work with potentially dangerous mechanisms that require a high concentration of attention, as well as the use of alcohol.
Application during pregnancy and lactation
The use of Amitriptyline in pregnant women is not recommended. If the drug is prescribed during pregnancy, the patient should be warned of the potentially high risks to the fetus, especially during the third trimester of pregnancy. Taking tricyclic antidepressants in the third trimester of pregnancy can cause the development of neurological disorders in the newborn. There are cases of drowsiness in newborns whose mothers took nortriptyline (a metabolite of amitriptyline) during pregnancy, and some children have cases of urinary retention.
Amitriptyline is determined in breast milk. The ratio of its concentrations in breast milk and blood plasma is 0.4-1.5 in breastfed children. During treatment with the drug, it is necessary to stop breastfeeding. If this is impossible for some reason, careful monitoring of the child's condition should be carried out, especially in the first 4 weeks of life. Children whose mothers refuse to stop lactation may experience unwanted side effects.
Pediatric use
In children, adolescents and young patients (under 24 years of age) suffering from depression and other mental disorders, antidepressants, compared with placebo, increase the risk of suicidal thoughts and can provoke suicidal behavior. Therefore, when prescribing amitriptyline, it is recommended to carefully weigh the potential benefits of treatment and the risk of suicide.
Use in the elderly
In elderly patients, amitriptyline can lead to the development of drug psychosis, mainly at night. After discontinuation of the drug, these phenomena disappear within a few days.
Drug interactions
The simultaneous use of amitriptyline and MAO inhibitors can provoke serotonin syndrome, accompanied by hyperthermia, agitation, myoclonus, tremor, confusion.
Amitriptyline can enhance the effects of phenylpropanolamine, epinephrine, norepinephrine, phenylephrine, ephedrine, and isoprenaline on the functioning of the cardiovascular system. In this regard, it is not recommended to prescribe decongestants, anesthetics and other drugs containing these substances, together with Amitriptyline.
The drug can weaken the antihypertensive effect of methyldopa, guanethidine, clonidine, reserpine and betanidine, which may require adjustment of their dosage.
When Amitriptyline is combined with antihistamines, an increase in the suppressive effect on the central nervous system is sometimes observed, and with drugs that provoke extrapyramidal reactions, an increase in the frequency and severity of extrapyramidal effects is observed.
The simultaneous intake of amitriptyline and some antipsychotics (especially sertindole and pimozide, as well as sotalol, halofantrine and cisapride), antihistamines (terfenadine and astemizole) and drugs that prolong the QT interval (antiarrhythmics, for example, quinidine) increases the risk of diagnosing ventricular arrhythmias. Antifungal agents (terbinafine, fluconazole) increase the serum concentration of amitriptyline, thus enhancing its toxic properties. Also, such manifestations as fainting and the development of paroxysms characteristic of ventricular tachycardia (Torsade de Pointes) have been reported.
Barbiturates and other enzyme inducers, in particular carbamazepine and rifampicin, are able to intensify the metabolism of amitriptyline, which leads to a decrease in its concentration in the blood and a decrease in the effectiveness of the latter.
When combined with calcium channel blockers, methylphenidate and cimetidine, inhibition of metabolic processes characteristic of amitriptyline, an increase in its level in blood plasma and the occurrence of toxic reactions are possible.
With the simultaneous use of amitriptyline and antipsychotics, it is necessary to take into account that these drugs mutually suppress each other's metabolism, helping to reduce the threshold of convulsive readiness.
When amitriptyline is prescribed in conjunction with indirect anticoagulants (derivatives of indandione or coumarin), the anticoagulant effect of the latter may increase.
Amitriptyline can worsen the course of depression triggered by glucocorticosteroid drugs. Joint reception with anticonvulsants can enhance the depressive effect on the central nervous system, reduce the threshold of seizure activity (when taken in high doses) and lead to a weakening of the effect of the latter treatment.
The combination of amitriptyline with drugs for the treatment of thyrotoxicosis increases the risk of agranulocytosis. In patients with hyperfunction of the thyroid gland or patients taking thyroid drugs, the risk of developing arrhythmias increases, therefore it is recommended to be careful when using amitriptyline in this category of patients.
Fluvoxamine and fluoxetine can increase the plasma amitriptyline content, which may require a reduction in the dose of the latter. When this tricyclic antidepressant is prescribed in conjunction with benzodiazepines, phenothiazines and anticholinergics, there is sometimes a mutual enhancement of the central anticholinergic and sedative effects and an increase in the risk of developing epileptic seizures due to a decrease in the seizure threshold.
Estrogens and estrogen-containing oral contraceptives can increase the bioavailability of amitriptyline. Reducing the dose of either amitriptyline or estrogen is recommended to maintain efficacy or reduce toxicity. Also, in some cases, they resort to discontinuation of the drug.
The combination of amitriptyline with disulfiram and other acetaldehydrogenase inhibitors may increase the risk of developing psychotic disorders and confusion. When the drug is prescribed together with phenytoin, the metabolic processes of the latter are inhibited, which sometimes leads to an increase in its toxic effect, accompanied by tremor, ataxia, nystagmus, and hyperreflexia. At the beginning of treatment with amitriptyline in patients taking phenytoin, it is necessary to control the content of the latter in the blood plasma due to the increased risk of suppressing its metabolism. You should also carry out constant monitoring of the severity of the therapeutic effect of amitriptyline, since its dose may need to be adjusted upward.
Hypericum perforatum preparations reduce the maximum concentration of amitriptyline in blood plasma by approximately 20%, which is due to the activation of the metabolism of this substance, which is carried out in the liver using the isoenzyme CYP3A4. This phenomenon increases the risk of developing serotonin syndrome, and therefore it may be necessary to adjust the dose of amitriptyline in accordance with the results of determining its concentration in the blood plasma.
The combination of amitriptyline and valproic acid reduces the clearance of amitriptyline from blood plasma, which may increase the content of amitriptyline and its metabolite nortriptyline. In this case, it is recommended to constantly monitor the level of nortriptyline and amitriptyline in blood plasma in order to reduce the dose of the latter if necessary.
Taking high doses of amitriptyline and lithium preparations for more than 6 months can provoke the development of cardiovascular complications and seizures. Also in this case, signs of neurotoxic action are sometimes determined, namely: disorganization of thinking, tremors, poor concentration, memory impairment. This is possible even with the appointment of amitriptyline in medium doses and a normal concentration of lithium ions in the blood.
Analogs
The analogs of Amitriptyline are: Amitriptyline Nycomed, Amitriptyline-Grindeks, Apo-Amitriptyline and Vero-Amitriptyline.
Terms and conditions of storage
The drug must be stored in a dry place, out of reach of children, at a temperature of 15-25 ° C.
Shelf life 4 years.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews about Amitriptyline
Doctors usually leave positive reviews about Amitriptyline, considering it a good antidepressant. However, many patients complain of a large number of adverse reactions during treatment (dry mouth, apathy, drowsiness). Addiction to the drug also sometimes develops. Amitriptyline should be used only as directed by a specialist. There are also reports of the narcotic effect of the drug.
The price of Amitriptyline in pharmacies
The approximate price for Amitriptyline in the form of tablets with a dosage of 10 mg is 24-33 rubles, and with a dosage of 25 mg - 20-56 rubles (the package contains 50 pieces). The cost of the drug in the form of a solution varies from 42 to 47 rubles (the package contains 10 ampoules).
Amitriptyline: prices in online pharmacies
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Drug name Price Pharmacy |
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Amitriptyline 25 mg tablets 50 pcs. 28 RUB Buy |
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Amitriptyline 10 mg tablets 50 pcs. RUB 31 Buy |
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Amitriptyline 25 mg tablets 50 pcs. RUB 33 Buy |
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Amitriptyline 10 mg / ml solution for intravenous and intramuscular administration 2 ml 10 pcs. 41 rbl. Buy |
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Amitriptyline 25 mg tablets 50 pcs. 43 rbl. Buy |
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Amitriptyline solution for intravenous and intramuscular injection. 10mg / ml 2ml 10 pcs. RUB 47 Buy |
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Amitriptyline 25 mg tablets 50 pcs. RUB 59 Buy |
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Amitriptyline Nycomed 25 mg film-coated tablets 50 pcs. RUB 65 Buy |
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Anna Kozlova Medical journalist About the author
Education: Rostov State Medical University, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
