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

Excipients: dextrose monohydrate - 40.0 mg, (in terms of dextrose), sodium chloride - 2.6 mg, benzethonium chloride-0.1 mg, hydrochloric acid or sodium hydroxide - to pH 4.0-6.0, water for injection - up to 1 ml.

Description:Transparent colorless or slightly colored liquid.

Pharmacotherapeutic group:Antidepressant

ATX: & nbsp

N.06.A.A.09 Amitriptyline

Pharmacodynamics:

Amitriptyline is a tricyclic antidepressant with sedative effect.

Pharmacodynamics

The mechanism of antidepressant action of amitriptyline is associated with the inhibition of reverse neuronal seizure of catecholamines (noradrenaline, dopamine) and serotonin in the central nervous system (CNS).

Amitriptyline is an antagonist of muscarinic cholinergic receptors in the central nervous system and on the periphery, has peripheral antihistamine (H1) and antiadrenergic properties. Also causes antinevralgic action (central analgesic and anti-bulimic action).

Antidepressant effect develops within 2-4 weeks after the beginning of application.

Pharmacokinetics:

Bioavailability of amitriptyline for various routes of administration is 30-60%, its of the active metabolite of nortriptyline - 46-70%. The time to reach the maximum concentration (T_m_Oh) after intake of 2.0-7.7 hours. The volume of distribution is 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 the blood plasma (Cmax) 0.04-0.16 μg / ml. Passes through the histohematological barriers, including the blood-brain barrier (including nortriptyline).

The concentrations of amitriptyline in tissues are higher than in plasma. Relationship with plasma proteins 92 - 96%.

Metabolised in the liver (by demethylation, hydroxylation) with the formation of active metabolites - nortriptyline, 10-hydroxy-amitriptyline, and inactive metabolites.

The half-life of plasma from 10 to 28 hours for amitriptyline and 16 to 80 hours for nortriptyline. It is allocated by the kidneys - 80%, partially with bile. Complete excretion within 7-14 days.

Amitriptyline penetrates the placental barrier, is excreted in breast milk in concentrations similar to plasma.

Indications:

Depression is severe. Due to the severity of the sedative effect is especially effective in anxiety-depressive states.

Contraindications:

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 disease, with marked impairment of functions;

blood diseases;

peptic ulcer of the stomach and 12 duodenal ulcer in the stage of exacerbation;

hypertrophy of the prostate;

atony of the bladder;

pyloric stenosis, paralytic intestinal obstruction;

simultaneous treatment with monoamine oxidase inhibitors (MAO), and within 2 weeks after their withdrawal (see Interaction with other drugs);

pregnancy, the period of breastfeeding;

children under 12 years;

hypersensitivity to amitriptyline.

Carefully:

In persons suffering from alcoholism, with bronchial asthma, manic-depressive psychosis (MDP) and epilepsy (see Special instructions), with oppression of bone marrow hematopoiesis, hyperthyroidism, angina and heart failure, angle-closure glaucoma, intraocular hypertension, schizophrenia (although with its administration usually there is no exacerbation of productive symptoms).

Dosing and Administration:

Assign intramuscularly and intravenously.

In severe depression, resistant to therapy: intramuscularly and intravenously (inject slowly!) Is administered at a dose of 10-20-30 mg up to 4 times a day, increasing the dose should be carried out gradually, the maximum daily dose of 150 mg; after 1-2 weeks go to the drug inside.

Children over 12 years of age and elderly people are given lower doses and increase them more slowly.

If the patient's condition does not improve within 3-4 weeks of treatment, then further therapy is impractical.

Side effects:

Mainly associated with the anticholinergic action of the drug: paresis of accommodation, blurred vision, increased intraocular pressure, dry mouth, constipation, intestinal obstruction, delayed urination, fever. All these phenomena usually pass after adaptation to the drug or reduce doses.

From the side. CNS: headache, ataxia, fatigue, weakness, irritability, dizziness, tinnitus, drowsiness or insomnia, impaired concentration, nightmarish dreams, dysarthria, confusion, hallucinations, motor excitement, disorientation, tremor, paresthesia, peripheral neuropathy, changes in the EEG. Rarely, extrapyramidal disorders, convulsions, anxiety.

From the cardiovascular system: tachycardia, arrhythmia, conduction disorders, lability of arterial pressure, expansion of the complex QRS on ECG (violation of intraventricular conduction), symptoms of heart failure, fainting. From the gastrointestinal tract (GIT): nausea, vomiting, heartburn, anorexia, stomatitis, taste disorders, darkening of the tongue, a feeling of discomfort in the epigastrium, gastralgia, increased activity of "liver" transaminases, rarely cholestatic jaundice, diarrhea.

On the part of the endocrine system: an increase in the size of the mammary glands in men and women, galactorrhea, a change in the secretion of antidiuretic hormone (ADH), a change in libido, potency. Rarely - hypo- or hyperglycemia, glucosuria, impaired glucose tolerance, edema of the testicles.

Allergic reactions: skin rash, itching, photosensitivity, angioedema, hives.

Other: agranulocytosis, leukopenia, eosinophilia, thrombocytopenia, purpura and other blood changes, hair loss, enlarged lymph nodes, weight gain with prolonged use, sweating, pollakiuria.

With long-term treatment, especially in high doses, with a sudden cessation of treatment, it is possible to develop withdrawal syndrome: headache, nausea, vomiting, diarrhea, as well as irritability, sleep disturbance with bright, unusual dreams, increased excitability.

Overdose:

Drowsiness, disorientation, confusion, pupil dilated, fever, dyspnea, dysarthria, agitation, hallucinations, convulsive attacks, muscle stiffness, stupor, coma, vomiting, arrhythmia, arterial hypotension, heart failure, respiratory depression.

Measures of assistance: discontinuation of amitriptyline therapy, gastric lavage, fluid infusion, symptomatic therapy, maintenance of blood pressure and water electrolyte balance. Monitoring of cardiovascular activity (ECG) for 5 days is shown, since relapse can occur after 48 hours and later. Hemodialysis and forced diuresis are of little effect.

Interaction:

Amitriptyline increases the anticholinergic effect of drugs with anticholinergic activity (phenothiazines, antiparkinsonian drugs, amantadine, atropine, biperidene,antihistamines), which increases the risk of side effects (from the central nervous system, vision, intestine and bladder).

With the joint use of amitriptyline with antihistamine drugs, clonidine - an increase in the inhibitory effect on the central nervous system; with atropine - increases the risk of paralytic intestinal obstruction; with drugs that cause extrapyramidal reactions - an increase in the severity and frequency of extrapyramidal effects.

Reduces the effectiveness of phenytoin and alpha-blockers. Fluoxetine and fluvoxamine increase the concentration of amitriptyline in blood plasma (may require a reduction in the dose of amitriptyline by 50%).

When used together with holinoblokatorami, phenothiazines and benzodiazepines - mutual enhancement of sedative and central cholinoblocking effects and increased risk of epileptic seizures (lowering the threshold of convulsive activity); phenothiazines, in addition, may increase the risk of neuroleptic malignant syndrome.

With the simultaneous use of amitriptyline with clonidine, guanethidine, betanidine, reserpine and methyldopa - reducing the hypotensive effect of the latter. Antiarrhythmic drugs (such as quinidine) increase the risk of heart rhythm disturbances (possibly slowing metabolism of amitriptyline).

Strengthens the effect on the cardiovascular system of epinephrine, norepinephrine, isoprenaline, ephedrine and phenylephrine (including when these drugs are part of local anesthetics) and increases the risk of heart rhythm disturbances, tachycardia, severe arterial hypertension, but inhibits the effects of drugs affecting the release of norepinephrine.

When co-administered with alpha-adrenostimulants for intranasal administration or for use in ophthalmology (with significant systemic absorption), the vasoconstrictor effect of the latter may be enhanced.

Amitriptyline may reduce the effect of anticonvulsants.

When combined with thyroid hormones - mutual reinforcement of the therapeutic effect and toxic effects (cardiac arrhythmias and stimulating effect on the central nervous system); with medicines fortreatment of thyrotoxicosis increases the risk of agranulocytosis.

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

With the simultaneous use of amitriptyline and anticoagulants - derivatives of coumarin or indanedione, an increase in the anticoagulant activity of the latter is possible.

With the simultaneous administration of amitriptyline and cimetidine, an increase in plasma concentration of amitriptyline is possible with the possible development of toxic effects. Inducers of microsomal liver enzymes (barbiturates, carbamazepine) reduce the plasma concentrations of amitriptyline.

The combined use of amitriptyline with disulfiram and other acetal dehydrogenase inhibitors can provoke delirium.

Estrogen-containing oral contraceptives can increase the bioavailability of amitriptyline; pimozide and probucol may increase cardiac arrhythmias.

Amitriptyline may increase depression caused by glucocorticosteroids.

When co-administered with other hematotoxic drugs, it is possible to increase hematotoxicity.

Simultaneous administration of amitriptyline with MAO inhibitors can lead to death. A 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 of convulsive activity, therefore, one should consider the possibility of occurrence of convulsive seizures in patients with those in the anamnesis, as well as brain damage of any etiology, simultaneous use of antipsychotics, in the period of refusal of ethanol, or drug withdrawal , possessing anticonvulsant properties (benzodiazepines).

In children, adolescents and young people (under 24 years) with depression, other disorders, antidepressants, compared with placebo, increase the risk of suicidal thoughts and suicidal behavior. Therefore, with the appointment of amitriptyline or any other antidepressant in children, adolescents and young people (under 24 years), the risk of suicide and the benefits of their use should be correlated. In short-term studies in people over 24 years of age, the risk of suicide did not increase, but in people older than 65 years, it declined slightly. Any depressive disorder in itself increases the risk of suicide.Therefore, during treatment with antidepressants, all patients should be monitored for early detection of abnormalities or behavioral changes, as well as suicidal tendencies.

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

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

Form release / dosage:Solution for intravenous and intramuscular injection 10.0 g.

Packaging:2 ml per ampoule of glass grades HC-1 or NS-3, according to OST 64-2-485-85 or imported "first hydrolytic class" according to ISO 9187-1.

On the ampoules stick labels self-adhesive according to TU 5457-002-34911995-97, TU 5457-005-55275020-06, TU 9572-001-95194604-2010 or imported.

For 5 ampoules are placed in a contour mesh package made of a polyvinyl chloride film in accordance with GOST 25250-88 or imported, approved for use in the Russian Federation and aluminum foil printed lacquer according to TU 9572-005-34911995-01 or GOST 745-2003, or imported, application in the Russian Federation; or flexible packaging on the basis of aluminum foil according to TU 1811-002-45094918-97, or imported, approved for use in the Russian Federation; or without foil.For 1 or 2 contour squares with instructions for use, a knife or a scarifier ampoule placed in a pack of cardboard for consumer packaging according to GOST 7933-89 or imported.

For 20, 50 or 100 contour, cell packs with foil with 10, 25 or 50 instructions for use, respectively, with knives or scarifier ampoules are placed in boxes of cardboard in accordance with GOST 7933-89, GOST 7376-89 or in boxes of corrugated cardboard according to GOST 9142-90 (for the hospital). When packing ampoules with incisions, rings or break points, the ampoule or scarifier knives are not inserted.

Group packing and transport packaging in accordance with GOST 17768-90.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:3 years. Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:P N002756 / 02

Date of registration:25.06.2008 / 19.03.2014

Expiration Date:Unlimited

The owner of the registration certificate:MOSCOW ENDOCRINE FACTORY, FSUE MOSCOW ENDOCRINE FACTORY, FSUE Russia

Manufacturer: & nbsp

MOSCOW ENDOCRINE FACTORY, FSUE Russia

Information update date: & nbsp13.08.2017

Illustrated instructions

Instructions

Amitriptyline (Amitriptyline)