Amitriptyline


    Mode of action:
Amitriptyline - tricyclic antidepressant group of non-selective inhibitors of neuronal uptake of monoamines. It possesses strong timoanalepticheskim and sedative effect.

Pharmacodynamics
The mechanism of antidepressant action of amitriptyline is associated with inhibition of reverse neuronal uptake of catecholamines (norepinephrine, dopamine) and serotonin in the central nervous system. Amitriptyline is an antagonist of muscarinic cholinergic receptors in the CNS and in the periphery, has a peripheral antihistamine (H1) and antiadrenergic properties. Also of antinevralgicheskoe (central analgesic), anti-ulcer and antibulemicheskoe action effective for bedwetting. The antidepressant effect develops within 2-4 weeks. After the start of the application.

Pharmacokinetics
Bioavailability of amitriptyline for various routes of administration - 30-60%, its active metabolite nortriptyline - 46-70%. The time to maximum concentration (Tmax) after ingestion 2,0, 7.7 hr. The volume of distribution of 5.10 l / kg. Effective therapeutic blood concentration of amitriptyline - 50-250 ng / ml, nortriptyline (its active metabolite) of 50-150 ng / ml. The maximum plasma concentration (Cmax) -0,04-0,16 ug / ml. It passes through the blood-tissue barriers, including the blood-brain barrier (including nortriptyline). Concentration of amitriptyline in tissues than in plasma. Connection with the plasma protein-92-96%. It is metabolized in the liver (by demethylation, hydroxylation) to form active metabolites - nortriptyline, 10-hydroxy-amitriptyline, and active metabolites. The half-life from the blood plasma by 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, excreted in breast milk in concentrations similar to plasma.


Indications for use: & nbsp;
Apply strictly on prescription.
Depression of any etiology. Especially effective for anxiety - depressive states, due to the severity of sedation. There is no acute positive symptoms (delusions, hallucinations), in contrast to antidepressants with a stimulating effect.
Mixed emotional disorders and behavioral disorders, phobic disorders.
Children's enuresis (excluding children with hypotonic bladder).
Psychogenic anorexia, bulimic neurosis.
Neurogenic pain of a chronic nature, for the prevention of migraine.


How to use:
Assign inside (during or after eating).

The initial daily dose ingestion of 50-75mg (25mg in 2-3 hours), then gradually increase the dose 25-50mg, until the desired antidepressant effect. The optimum daily therapeutic dose is 150-200mg (maximum of the dose taken at night). In severe depression resistant to treatment, increase the dose to 300 mg or more, up to the maximum tolerated dose. In these cases it is advisable to start treatment with intramuscular or intravenous injection, applying the higher initial dose, dose escalating accelerating under the control of the medical condition.

Upon receipt of proof of antidepressant effect in 2-4 weeks the dose gradually and slowly reduced. In the case of depression symptoms at lower doses need to go back to the previous dose.

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

In elderly patients with pulmonary disorders in outpatient practice, doses are 25-50-100mg (max) in divided doses, or 1 time a day at night. For the prevention of migraine, chronic pain of neurogenic nature (including long-term headaches) from 12,5-25mg to 100mg / day. Interaction with other drugs Amitriptyline potentiates CNS depression following medicines: antipsychotics, sedatives and hypnotics, anticonvulsants, central and narcotic analgesics, anesthetics, alcohol .

Assign intramuscularly or intravenously. In severe depression resistant to treatment: intramuscularly or intravenously (! Enter slowly) is administered at a dose of 10-20-30 mg up to 4 times a day, an increase in dose should be gradual, the maximum daily dose of 150 mg; 1-2 weeks later, go to the reception of the drug inside. Children older than 12 years of age and the elderly are administered lower doses and increase them slowly.

In a joint application with amitriptyline neuroleptics, and / or anticholinergic drugs can cause febrile temperature reaction, paralytic ileus. Amitriptyline potentiates the hypertensive effects of catecholamines, but inhibits the effects of drugs acting on the release of noradrenaline.

Amitriptyline may reduce the antihypertensive effect simpatolitikov (oktadin, guanethidine and drugs with a similar mechanism of action).

At simultaneous reception of amitriptyline and cimetidine may increase the concentration of amitriptyline in plasma.

Simultaneous treatment with MAO inhibitors amitriptyline can be fatal. Break in treatment between the intake of MAO inhibitors and tricyclic antidepressants should not be less than 14 days!


Side effects: & nbsp;
In mainly related to the anticholinergic effect of the drug: paresis of accommodation. Blurred vision, increased intraocular pressure, dry mouth, constipation, ileus, urinary retention, increase in body temperature. These effects usually disappear after adaptation to the drug or dose reduction.
CNS: headache, ataxia, fatigue, weakness, irritability, dizziness, tinnitus, drowsiness or insomnia, impaired concentration, nightmares, dysarthria, confusion, hallucinations, motor agitation, confusion, tremor, paresthesia, peripheral neuropathy, changes in the EEG. Rarely, extrapyramidal disorders, convulsions, anxiety. Cardio-vascular system: tachycardia, arrhythmias, conduction disturbances, labile blood pressure, expansion of the QRS complex on the ECG (violation of intraventricular conduction), symptoms of heart failure, syncope. On the part of the digestive tract: nausea, vomiting, heartburn, anorexia, stomatitis, taste disturbances, dark tongue, epigastric discomfort, gastralgia, increased activity of "liver" transaminases, rarely cholestatic jaundice, diarrhea. From 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. Rare hypo- or hyperglycemia, glycosuria, glucose intolerance, swelling of the testicles. Allergic reactions: skin rash, pruritus, photosensitivity, angioedema, urticaria. Other: agranulocytosis, leukopenia, eosinophilia, thrombocytopenia, purpura and other changes in the blood, hair loss, swollen lymph nodes, weight gain during prolonged use, sweating, pollakiuria. With prolonged treatment, especially in high doses, the sudden cessation of treatment may develop withdrawal symptoms: headache, nausea, vomiting, diarrhea, and irritability, sleep disturbance with bright, unusual dreams, irritability


Contraindications:
• Heart failure in decompensation stage
• Acute and recovery phase of myocardial infarction
• conduction disorders of the heart muscle
• Severe hypertension
• Acute liver and kidney disease with significant dysfunction
• Stomach ulcer and 12 duodenal ulcer in the acute stage
• Hypertrophy of prostate
• atony bladder
• Pyloric stenosis, paralytic ileus
• Simultaneous treatment of MAO inhibitors (See Interactions.)
• Pregnancy, lactation
• Children under 6 years
• Hypersensitivity to amitriptyline
Amitriptyline should be used with caution in patients suffering alcoholics-ism, bronchial asthma, manic-depressive psychosis (MDP) and epilepsy (see. Special instructions), with inhibition of bone marrow hematopoiesis, hyperthyroidism, angina and heart failure, angle-closure glaucoma, ocular hypertension , schizophrenia (although his admission usually occurs acute positive symptoms).

Overdose
Drowsiness, disorientation, confusion, dilated pupils, fever, dizziness, dysarthria, agitation, hallucinations, seizures, muscle stiffness, supor, coma, vomiting, arrhythmia, hypotension, heart failure, respiratory depression.
aid measures: stopping amitriptyline therapy, gastric lavage, infusion fluid, symptomatic therapy, blood pressure and maintaining water and electrolyte balance. Results monitoring cardiovascular activity (ECG) for 5 days, as relapse may occur after 48 hours and later. Hemodialysis and forced diuresis are not effective.

Interaction with other drugs
Amitriptyline dampening effect on the central nervous system following medicines: antipsychotics, sedatives and hypnotics, anticonvulsants, analgesics, anesthetics, alcohol; exhibits synergism when interacting with other antidepressants. In a joint application with amitriptyline neuroleptics, and / or anticholinergic drugs can cause febrile temperature reaction, paralytic ileus. Amitriptyline potentiates the hypertensive effects of catecholamines and other agonists that increases the risk of cardiac arrhythmias, tachycardia, severe hypertension, but inhibits the effects of drugs acting on the release of noradrenaline. Amitriptyline may reduce the antihypertensive effect of guanethidine and drugs with a similar mechanism of action, as well as weaken the effect of anticonvulsants. With simultaneous use of amitriptyline and anticoagulants - coumarin derivatives or indandiona may increase the anticoagulant activity of the latter. At the same time taking amitriptyline and cimetidine may increase the plasma concentrations of amitriptyline with the possible development of toxic effects. Inductors of microsomal liver enzymes (barbiturates, carbamazepine) reduces plasma concentrations of amitriptyline. Amitriptyline increases the effects of anti-funds and other drugs that cause extrapyramidal reactions. Quinidine slows the metabolism of amitriptyline. The combined use of amitriptyline with disulfiram and other inhibitors of acetaldehyde dehydrogenase can cause delirium. Estrogensoderjath oral contraceptives may increase the bioavailability of amitriptyline; pimozide probucol and can enhance cardiac arrhythmias. Amitriptyline may enhance the depression caused by corticosteroids; concomitant use with medicinal products for the treatment of hyperthyroidism increases the risk of agranulocytosis. Simultaneous treatment with MAO inhibitors amitriptyline can be fatal. Break in treatment between receiving MAO inhibitors and tricyclic antidepressants should not be less than 14 days!

Cautions
Amitriptyline in doses above 150 mg / day reduces the threshold for seizure activity, therefore it is necessary to take into account the possibility of seizures in patients with such a history, and that category of patients who are predisposed to it due to age or injury. amitriptyline in treatment of the elderly should take place under the close supervision and with the use of minimal doses, increasing them gradually in order to avoid the development of delirium disorders, hypomania, and other complications. Patients with depressive phase TIR can go to the manic phase. While receiving amitriptyline prohibited from driving vehicles sredst, machinery maintenance and other work requiring high concentration, and alcohol intake.


Product form: & nbsp;
There are such forms of release:
Packaging - 50 Tablets, each containing 25 mg of active substance
. Packages 20, 50 and 100 film-coated tablets.
2 ml colorless glass vials. 5 vials are packed in a container molded from PVC. On 2 molded container (10 vials) with instructions for use placed in a cardboard box.
Injectable solution 10 mg / ml in 2 ml ampoules by 5 or 10 ampoules per ream of paperboard; 5 ampoules in blisters, 1 or 2 contour cell packages in the pile of cardboard together with instructions for use.

solution Description:
The clear, colorless, free of mechanical impurities, it may be slightly colored.



At a temperature of 10 ° C to 25 ° C in a dry, protected from light and the reach of children.

Shelf life - 2-3 years (depending on the form of release and the manufacturer). Do not take after the expiry date stated on the package!

Conditions of supply of pharmacies -. Prescription


Synonyms:
Teperin, Triptizol, Adepril, Adepress, Atriptal, Damilya, Daprimen, Elatral, Lantron, Laroksal, Novotriptin, Redomeks, Saroj, Saroteks, triptych, Triptanol, Elavil, Amiprin, Larox, Lentizol, Progeptadien, Triptopol, amitriptyline hydrochloride, amitriptyline, Slovakofarma, Lechiva Amitriptyline, Amitriptyline-Agos
Amitriptylin-Slovakopharma


Ingredients:
Film-coated Tablets contain at 0.0283 g (28,3mg) of amitriptyline hydrochloride, corresponding to 0,025g (25mg) amitriptyline
.
On 1 ml solution for injection Amitriptyline Hydrochloride 10 mg (calculated as amitriptyline)
Excipients: glucose, sodium chloride, benzethonium chloride, water for injections
.



Pharmacological group:
Drugs that act primarily on the central nervous system

Optional:
Manufacturers:
1. A pharmaceutical company "MAGIC" Serta-Belgium.
2. Slovakofarma.
3. "ZENTIVA AS" Czech Republic


Warning!
Product description " Amitriptyline "on this page is a simplified and enlarged version of the official instructions for use. Before purchasing or using the product, you should consult your doctor and see the summary approved by the manufacturer.
Information about the preparation is provided solely for informational purposes and should not be used as a guide to self-healing. Only a doctor can decide on the appointment of the drug, and to determine the doses and methods of application.