Amitriptyline pills 25mg №50

Pharmacology

Pharmacodynamics

Amitriptyline is an antidepressant (tricyclic antidepressant). It also provides some analgesic (central genesis), antiserotonin effect, helps to eliminate bed-wetting and reduces appetite.

It has a strong peripheral and central anticholinergic action due to its high affinity for m-cholinergic receptors; strong sedative effect associated with affinity for H1-histamine receptors, and alpha-adreno-blocking action. Possesses the properties of an antiarrhythmic drug (drug) class IA, like quinidine in therapeutic doses slows ventricular conductivity (overdose can cause severe intraventricular blockade).

The mechanism of antidepressant action is associated with an increase in the concentration of norepinephrine and / or serotonin in the central nervous system (CNS) (a decrease in their reabsorption). The accumulation of these neurotransmitters occurs as a result of inhibition of their reuptake by the membranes of presynaptic neurons. With prolonged use reduces the functional activity of beta-adrenergic and serotonin receptors of the brain, normalizes adrenergic and serotonergic transmission, restores the balance of these systems,disturbed in depressive states. In anxiety and depressive states, it reduces anxiety, agitation and depressive manifestations.

The mechanism of anti-ulcer action is due to the ability to have a sedative and m-anticholinergic action.

Efficacy in nocturnal urinary incontinence is apparently due to anticholinergic activity leading to an increase in bladder's ability to stretch, direct beta-adrenergic stimulation, alpha adrenergic agonist activity, accompanied by an increase in sphincter tone, and a 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 the effect on endogenous opioid systems.

The mechanism of action in bulimia nervosa is unclear (may be similar to that in depression). A distinct effect of the drug in case of bulimia in patients with and without depression is shown, and a decrease in bulimia may occur without a concomitant weakening of the depression itself.

When performing general anesthesia, it lowers blood pressure (BP) and body temperature. Does not inhibit monoamine oxidase (MAO).

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

Pharmacokinetics

Absorption is high. Bioavailability of Amitriptyline is 30-60%, its active metabolite nortriptyline is 46-70%.The time to reach the maximum concentration (Tmax) after ingestion of 2.0-7.7 hours. The volume of distribution is 5-10 l / kg. Effective therapeutic blood concentrations for amitriptyline - 50-250 ng / ml, for nortriptyline 50-150 ng / ml. The maximum plasma concentration (Cmax) is 0.04-0.16 mcg / ml. Passes (including nortriptyline) through histohematogenous barriers, including the blood-brain barrier, placental barrier, penetrates into breast milk. Communication with plasma proteins - 96%.

Metabolized in the liver with the participation of CYP2C19, CYP2D6 isoenzymes, has the effect of "first pass" (by demethylation, hydroxylation) with the formation of active metabolites - nortriptyline, 10-hydroxy-amitriptyline, and inactive metabolites. The plasma half-life (T1 / 2) is 10-26 hours for amitriptyline and 18-44 hours for nortriptyline. Excreted by the kidneys (mainly in the form of metabolites) - 80% in 2 weeks, partly with bile.

Indications

Depression (especially with anxiety, agitation and sleep disorders, including in children, endogenous, involutional, reactive, neurotic, drug, with organic brain lesions).

As part of complex therapy, it is used for mixed emotional disorders, psychosis in schizophrenia, alcohol withdrawal, behavioral disorders (activity and attention), nocturnal enuresis in children (except for patients with bladder hypotension), bulimia nervosa, chronic pain syndrome (chronic pain in cancer patients). patients, migraine, rheumatic diseases, atypical pains in the face, postherpetic neuralgia, post-traumatic neuropathy,diabetic or other peripheral neuropathy), headache, migraine (prophylaxis), gastric ulcer and duodenal ulcer.

Contraindications

• Hypersensitivity
• use together with MAO inhibitors and 2 weeks before the start of treatment,
• myocardial infarction (acute and subacute periods),
• acute alcohol intoxication,
• acute intoxication with hypnotics, analgesic and psychoactive drugs,
• angle-closure glaucoma,
• severe AV and intraventricular conduction disorders (blockade of the bundle of the His branch, AV blockade of the second stage),
• lactation period
• children's age up to 6 years.

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

Carefully

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

Pregnanacy and breastfeeding

Contraindicated use during lactation.

Special notes

Before treatment, control of blood pressure is necessary (in patients with low or labile blood pressure, it may decrease even more); during treatment - control of peripheral blood (in some cases, agranulocytosis may develop, and therefore it is recommended to monitor the blood picture, especially when the body temperature rises, the development of flu-like symptoms and angina), with long-term therapy - monitoring the functions of the cardiovascular system and the liver. In the elderly and patients with cardiovascular disease, monitoring of heart rate (HR), blood pressure, ECG is shown. On the ECG, the appearance of clinically insignificant changes is possible (smoothing of the T wave, depression of the ST segment, expansion of the QRS complex).

Care must be taken when abruptly moving to a vertical position from a "lying" or "sitting" position.

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

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

With a sudden cessation of treatment after prolonged treatment may develop a syndrome of "cancellation."

Amitriptyline in doses above 150 mg / day reduces the threshold of seizure activity (the risk of epileptic seizures in susceptible patients should be considered, as well as in the presence of others.factors predisposing to the onset of convulsive syndrome, for example, brain damage of any etiology, simultaneous use of antipsychotic drugs (neuroleptics), in the period of refusal from ethanol or withdrawal of drugs with anticonvulsant properties, such as benzodiazepines).

Severe depression is characterized by the risk of suicidal acts, which can persist until a significant remission is achieved. In this regard, at the beginning of treatment, a combination with drugs from the group of benzodiazepines or neuroleptic drugs and constant medical supervision (to entrust the storage and distribution of drugs to trusted persons) can be shown.

In children, adolescents and young people (under 24 years) with depression and other mental disorders, antidepressants, compared with placebo, increase the risk of suicidal thoughts and suicidal behavior. Therefore, when prescribing amitriptyline or any other antidepressants in this category of patients, the risk of suicide should be correlated with the benefits of their use. In short-term studies, the risk of suicide was not increased in people over 24 years of age, and in people over 65 years of age it was somewhat reduced. During antidepressant treatment, all patients should be monitored for the purpose of early detection of suicidal tendencies.

In patients with cyclic affective disorders during the depressive phase during therapy, manic or hypomania states may develop (dose reduction or drug withdrawal and prescription of an antipsychotic drug are necessary).After stopping these conditions, if there are indications, treatment in low doses can be resumed.

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

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

In predisposed patients and elderly patients, it can provoke the development of medicinal psychoses, mainly at night (after discontinuation of the drug, they disappear within a few days).

It can cause paralytic intestinal obstruction, mainly in patients with chronic constipation, the elderly or in patients forced to adhere to bed rest.

Prior to general or local anesthesia, the anesthetist should be warned that the patient is taking amitriptyline.

Due to the anticholinergic action, there can be a decrease in tearing and a relative increase in the amount of mucus in the composition of the tear fluid, which can lead to corneal epithelium damage in patients using contact lenses.

With prolonged use, an increase in the incidence of dental caries is observed. The need for riboflavin may be increased.

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

Penetrates into breast milk and may cause drowsiness in infants.

In order to avoid the development of the "cancellation" syndrome in newborns (manifested by shortness of breath, drowsiness, intestinal colic, increased nervous irritability, increased or decreased blood pressure, tremor or spastic phenomena), amitriptyline is gradually canceled at least 7 weeks before the expected birth.

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

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

Composition

1 tablet contains:
active substance: amitriptyline hydrochloride - 28.30 mg, which corresponds to 25 mg of amitriptyline

Dosage and administration

Assign inside, without chewing, immediately after eating (to reduce irritation of the gastric mucosa).

Adults

Adults with depression, the initial dose - 25-50 mg at night, then gradually the dose can be increased, taking into account the effectiveness and tolerability of the drug to the maximum
300 mg / day in 3 doses (the largest part of the dose is taken at night). When a therapeutic effect is achieved, the dose can be gradually reduced to the minimum effective, depending on the condition of the patient.The duration of the course of treatment is determined by the patient's condition, the effectiveness and tolerability of the therapy being performed and can range from several months to 1 year, and, if necessary, even more.

In old age, with light disorders, as well as with nervous boulemia, as part of complex therapy for mixed emotional disorders and behavioral disorders, psychosis in schizophrenia and alcohol withdrawal, 25-100 mg / day is prescribed (overnight), after reaching the therapeutic effect at the minimum effective dose - 10-50 mg / day.

For the prevention of migraine, with chronic pain syndrome of a neurogenic nature (including prolonged headaches), as well as in the treatment of gastric ulcer and duodenal ulcer from 10-12.5-25 to 100 mg / day (maximum part of the dose is taken at night).

Children

Children as an antidepressant: from 6 to 12 years old - 10-30 mg / day or 1-5 mg / kg / day fractional, in adolescence - up to 100 mg / day. The main part of the dose is taken at night.

With nocturnal enuresis in children 6-10 years old - 10-20 mg / day for the night, 11-16 years - up to 50 mg / day.

Side effects

Associated with anticholinergic effect of the drug: blurred vision, accommodation paralysis, mydriasis, increased intraocular pressure (only in individuals with local anatomical predisposition - narrow anterior chamber angle), tachycardia, dry mouth, confusion (delirium or hallucination), constipation, paralytic intestinal obstruction, difficulty urinating.

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

From the CCC: tachycardia, palpitations, dizziness, orthostatic hypotension, nonspecific changes on the electrocardiogram (ECG) (ST interval or T wave) in patients without heart disease; arrhythmia, lability of blood pressure (decrease or increase in blood pressure), violation of intraventricular conduction (expansion of the QRS complex, changes in the P-Q interval, blockade of the bundle of the His bundle).

From the gastrointestinal tract: nausea, heartburn, gastralgia, hepatitis (including abnormal liver function and cholestatic jaundice), vomiting, increased appetite and body weight or decreased appetite and body weight, stomatitis, change in taste, diarrhea, darkening of the tongue.

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

Allergic reactions: skin rash, pruritus, photosensitivity, angioedema, urticaria.

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

With long-term treatment, especially in high doses, with its abrupt cessation it is possible development withdrawal syndrome: nausea, vomiting, diarrhea, headache, malaise, sleep disturbances, unusual dreams, unusual agitation; with gradual cancellation after long-term treatment - irritability, motor restlessness, sleep disturbances, unusual dreams.

The connection with taking the drug has not been established: lupus-like syndrome (migratory arthritis, the appearance of antinuclear antibodies and a positive rheumatoid factor), abnormal liver function, agevziya.

Drug interaction

When combined use of ethanol and drugs that depress the central nervous system (including other antidepressants, barbiturates, benzadiazepines and general anesthetics), a significant increase in the inhibitory effect on the central nervous system, respiratory depression and hypotensive effect is possible.

Increases sensitivity to ethanol-containing beverages.

Increases the anticholinergic effect of drugs with anticholinergic activity (for example, phenothiazine derivatives, antiparkinsonian drugs, amantadine, atropine, biperiden, antihistamine drugs), which increases the risk of side effects (from the central nervous system, vision, bowel and bladder).When combined with anticholinergics, phenothiazine derivatives and benzodiazepines, mutual enhancement of the sedative and central anticholinergic effects and an increased risk of epileptic seizures (lowering the seizure threshold); phenothiazine derivatives, in addition, may increase the risk of neuroleptic malignant syndrome.

When combined with anticonvulsant drugs may increase the inhibitory effect on the central nervous system, reducing the threshold of seizure activity (when used in high doses) and reduce the effectiveness of the latter.

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

With the simultaneous use of amitriptyline and indirect anticoagulants (coumarin or indadione derivatives), the anticoagulant activity of the latter can be increased.

Amitriptyline can strengthen the depression caused by glucocorticosteroids (GKS).

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

Reduces the effectiveness of phenytoin and alpha-blockers.

Inhibitors of microsomal oxidation (cimetidine) lengthen T1 / 2, increase the risk of developing toxic effects of amitriptyline (a dose reduction of 20-30% may be required),inducers of liver microsomal enzymes (barbiturates, Carbamazepine, phenytoin, nicotine, and oral contraceptives) decrease plasma concentrations and decrease the effectiveness of amitriptyline.

Combined use with disulfiram and other acetaldehyde hydrogenase inhibitors provokes delirium.

Fluoxetine and fluvoxamine increase plasma concentration of amitriptyline (it may be necessary to reduce the dose of amitriptyline by 50%).

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

With the simultaneous use of amitriptilin with clonidine, guanethidine, betanidin, reserpine and methyldopa - reducing the hypotensive effect of the latter; with cocaine - the risk of heart arrhythmias.

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

Pimozide and probucol can enhance cardiac arrhythmias, which is manifested in the prolongation of the Q-T interval on the ECG.

It enhances the effect on the CVS of epinephrine, norepinephrine, isoprenaline, ephedrine and phenylephrine (including when these drugs are part of local anesthetics) and increases the risk of developing heart rhythm disorders, tachycardia, and severe arterial hypertension.

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

When taken together with thyroid hormones, mutual enhancement of the therapeutic effect and toxic action (including cardiac arrhythmias and a stimulating effect on the central nervous system).

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

With a joint appointment with other hematotoxic drugs may increase hematotoxicity.

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

On the part of the cardiovascular system: decrease in blood pressure, tachycardia, arrhythmia, impaired intracardiac conduction, ECG changes (especially QRS) that are characteristic of intoxication with tricyclic antidepressants, shock, heart failure; in very rare cases, cardiac arrest.

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

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

Treatment: when taken orally: gastric lavage, activated charcoal intake; symptomatic and supportive therapy; with severe anticholinergic effects (lowering blood pressure, arrhythmias, coma, myoclonic epileptic seizures) - administration of cholinesterase inhibitors (the use of physostigmine is not recommended due to the increased risk of seizures); maintaining blood pressure and water-electrolyte balance. The monitoring of CVS functions (including ECG) for 5 days (relapse may occur after 48 hours and later), anticonvulsant therapy, artificial lung ventilation (ALV), and other resuscitation measures are shown. Hemodialysis and forced diuresis are ineffective.

In a dry, dark place at a temperature not higher than 25 ° C.