Amitriptyline Nycomed

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), P-blockers and the latest generation antiarrhythmic drugs (procainamide, phenytoin, propafenone, esmololamiodarone).

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 effects 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 effects of such drugs (for example, phenothiazine derivatives, antiparkinsonian drugs, H1-histamine blockers, atropine, biperiden) on the visual organs, 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 include
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, discordant thinking (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 g 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 CYP3 A4 isoenzyme.

This combination can be used with amitriptyline dose adjustment depending on the results of measuring its concentration in the blood plasma.

Amitriptyline Nycomed, 25 mg, film-coated tablets, 50 pcs.

Reactions to overdose vary significantly among different patients. Moderate/severe intoxication in adults occurs when taking amitriptyline in a dose of more than 500 mg; taking about 1000 mg can be fatal. The main symptoms of an overdose of Amitriptyline Nycomed may occur suddenly or develop gradually. In the first 2 hours, psychomotor agitation or drowsiness, hallucinations and symptoms are observed that are associated with the anticholinergic effect of the drug, in particular, convulsions, tachycardia, mydriasis, dry mucous membranes, urinary retention, weakened intestinal motility, increased body temperature. Then, impaired consciousness, respiratory failure, and severe depression of the functions of the central nervous system, progressing to coma, may occur. Cardiac symptoms manifest as arrhythmia (ventricular tachyarrhythmia, fibrillation and ventricular flutter). Characteristic changes on the ECG are prolongation of the PR interval, widening of the QRS complex, depression of the ST segment, prolongation of the QT interval, inversion or flattening of the T wave and block of intracardiac conduction to varying degrees, which can lead to cardiac arrest. Heart failure, arterial hypotension, cardiogenic shock, metabolic acidosis and hypokalemia, confusion, anxiety, hallucinations and ataxia may occur. Other symptoms: central nervous system: depression of its functions, convulsions, strong craving for sleep, coma; vascular system: hypotension; respiratory system: respiratory failure; psyche: hallucinations, psychomotor agitation; m-anticholinergic effects: muscle cramps, impaired accommodation, dry mouth, urinary retention. In case of overdose, symptomatic and supportive therapy is indicated, including stopping taking Amitriptyline Nycomed, gastric lavage (even if some time has passed since taking the drug), and taking activated charcoal. Even in seemingly uncomplicated cases, the patient's condition must be carefully monitored. It is necessary to monitor heart rate and breathing, level of consciousness, and blood pressure. The level of gases and electrolytes in the blood needs frequent monitoring. In order to prevent respiratory arrest, it is necessary to ensure airway patency and perform artificial ventilation. ECG monitoring is carried out for 3–5 days. When the QRS complex widens, ventricular arrhythmias and heart failure, shifting the blood pH to the alkaline side (using sodium bicarbonate solution or hyperventilation) with rapid administration of a hypertonic sodium chloride solution (100–200 mmol Na+) can be effective. For ventricular arrhythmias, traditional antiarrhythmic drugs can be used, for example, intravenous lidocaine at a dose of 50–100 mg (1–1.5 mg/kg) followed by infusion at a rate of 1 to 3 mg/min. If necessary, defibrillation and cardioversion are prescribed. Circulatory insufficiency can be corrected with the help of plasma replacement solutions, and in severe cases, dobutamine infusion is performed (initial dose - 2-3 mcg/kg/min; subsequently, depending on the effect, the dose can be increased). Convulsions and agitation can be controlled with diazepam. Standard therapy is indicated for patients with metabolic acidosis. Dialysis is ineffective because the concentration of amitriptyline in the blood is low.

special instructions

During the course of treatment, the patient is advised to regularly monitor blood pressure levels (even if there were no problems with the cardiovascular system before). The medicine is intended only for inpatient treatment under medical supervision. In the first days, bed rest is observed. During therapy, you must completely abstain from alcoholic beverages.

The dosage of the medication is increased and decreased gradually. An abrupt stop leads to withdrawal syndrome. This is expressed in manic states during the development of depression and other behavioral disorders. If the course lasts several months, caries may develop - a dental examination is required.

Side effects of Amitriptyline

While taking the drug, side effects associated with disorders of various organ systems may occur:

pulse disturbance;
problems with urination;
dry mouth;
headaches;
increased drowsiness;
anxiety;
hypomanic states;
increased depression;
increased epilepsy attacks;
blood pressure surges;
diarrhea;
taste disturbances;
heartburn;
problems with potency;
swelling of the testicles;
ringing in the ears and others.

If the drug is discontinued, there may also be negative consequences associated with sleep disturbances, overexcitation, anxiety, and increased levels of irritability.

Contraindications

The drug is not approved for use in the presence of the following diseases and characteristics:

myocardial infarction;
individual characteristics (intolerance to the active substance);
angle-closure glaucoma;
poisoning with certain drugs (sleeping pills, analgesics);
taking psychoactive substances;
severe alcohol poisoning;
breastfeeding (any period);
disorder of bone marrow hematopoiesis.

In some cases, Amitriptyline can be taken, but only with caution:

bronchial asthma;
digestive system disorders;
stroke;
dysfunction of the liver, kidneys;
increased pressure inside the eye;
pregnancy (any stages);
epilepsy;
urinary retention.

Instructions for use AMITRIPTYLINE

When ethanol is used together with drugs that depress the central nervous system (including antidepressants, barbiturates, benzadiazepines and general anesthetics), a significant increase in the depressant effect on the central nervous system, respiratory depression and hypotensive effect is possible. Increases sensitivity to drinks containing ethanol. Increases the m-anticholinergic effect of drugs with such activity (for example, phenothiazines, antiparkinsonian drugs, amantadine, atropine, biperiden, H1-histamine receptor blockers), which increases the risk of side effects (from the central nervous system, the organ of vision, intestines and urinary bubble).

When used together with H1-histamine receptor blockers, clonidine - increased 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. With the simultaneous use of amitriptyline and indirect anticoagulants (coumarin or indadione derivatives), the anticoagulant activity of the latter may increase.

Amitriptyline may enhance depression caused by glucocorticosteroids.

When used together with anticonvulsants, it is possible to enhance the inhibitory effect on the central nervous system, reduce the threshold of convulsive activity (when used in high doses) and reduce the effectiveness of the latter.

Medicines used to treat thyrotoxicosis increase the risk of developing agranulocytosis.

Reduces the effectiveness of phenytoin and alpha-blockers.

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

Fluxetine and fluvoxamine increase plasma concentrations of amitriptyline (a 50% reduction in amitriptyline dose may be required).

When used together with anticholinergic blockers, phenothiazines and benzodiazepines, there is a mutual enhancement of the sedative and central anticholinergic effects and an increased risk of epileptic seizures (lowering the threshold of convulsive activity); Phenothiazines may also increase the risk of neuroleptic malignant syndrome.

With the simultaneous use of amitriptyline with clonidine, guanethidine, betanidine, reserpine and methyldopa - a decrease in the hypotensive effect of the latter; with cocaine - the risk of developing cardiac arrhythmias.

Estrogen-containing oral contraceptives and estrogens may increase the bioavailability of amitriptyline; antiarrhythmic drugs (such as quinidine) increase the risk of developing rhythm disturbances (possibly slowing down the metabolism of amitriptyline).

Concomitant use with disulfiram and other acetaldehydrogenase inhibitors provokes delirium.

Incompatible with MAO inhibitors (increased frequency of periods of hyperpyrexia, severe convulsions, hypertensive crises and patient death are possible).

Pimozide and probucol may increase cardiac arrhythmias, which is manifested by prolongation of the QT interval on the ECG.

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

When co-administered with alpha-adrenergic agonists for intranasal administration or for use in ophthalmology (with significant absorption), it may enhance the vasoconstrictor effect of the latter.

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

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

When co-administered with other hematotoxic drugs, increased hematotoxicity is possible.