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

core: lactose monohydrate - 170.0 mg, corn starch - 40.55 mg, gelatin - 4.4 mg, calcium stearate - 3.5 mg, talc - 2.5 mg, silicon dioxide colloid - 0.75 mg. shell: simethicone SE-2 - 0,05 mg, macrogol - 0,125 mg, Sepiphilm 3048 Yellow (Sepifilm 3048 Yellow) (hypromellose 40-45%, microcrystalline cellulose 30-40%, polyoxyl 40 stearate 4-12%, titanium dioxide 10-15%, dye Quinoline yellow (Quinolin Yellow) not more than 0.05%) - 10.0 mg.

Description:

Round biconvex tablets, covered with a film coating of yellow color.

Pharmacotherapeutic group:Antidepressant

ATX: & nbsp

N.06.A.A.09 Amitriptyline

Pharmacodynamics:

Amitriptyline is a tricyclic antidepressant (TCA) from a group of non-selective inhibitors of neuronal capture of monoamines.

Pharmacodynamics

Has a strong peripheral and central anticholinergic action due to high affinity for m-holinoretseptoram; strong sedative effect associated with affinity for H₁-histamine receptors, and αadrenoblocking action.

The mechanism of antidepressant action is associated with an increase in the concentration of noradrenaline in synapses and / or serotonin in the central nervous system (CNS). Accumulation of these neurotransmitters occurs as a result of inhibition of their inverse capture by the membranes of presynaptic neurons. With prolonged use reduces the functional activity β-adrenergic and serotonin receptors of the brain, normalizes adrenergic and serotonergic transmission, restores the equilibrium of these systems, disturbed in depressive states. With anxiety-depressive conditions reduces anxiety, agitation and depressive manifestations.

Does not inhibit the enzyme monoamine oxidase (MAO). Antidepressant effect develops within 2-3 weeks after the beginning of application.

Pharmacokinetics:

Suction

After oral administration amitriptyline quickly and completely absorbed from the gastrointestinal tract.

Distribution

The concentration of amitriptyline in the blood plasma of different patients varies significantly. The bioavailability of amitriptyline is approximately 50%. Amitriptyline to a large extent (95%) binds to blood plasma proteins.The time to reach the maximum concentration (T_max) after oral administration - 4-8 hours, and the equilibrium concentration - about a week after the start of treatment. The volume of distribution is approximately 1085 l / kg. AND amitriptyline, and nortriptyline penetrate the placenta and are excreted in breast milk.

Metabolism

Amitriptyline is metabolized in the liver and to a large extent (about 50%) undergoes metabolism during primary passage through the liver. Wherein amitriptyline undergoes N-detylation of cytochrome P450 isoenzymes with the formation of an active metabolite - nortriptyline. AND amitriptyline, and nortriptyline also undergo in the liver hydroxylation. N-hydroxy and 10-hydroxymetabolite amitriptyline and 10-hydroxynortriptyline are also active. AND amitriptyline, and nortriptyline are conjugated to glucuronic acid, and these conjugates become inactive. The main factor determining renal clearance, and, correspondingly, the concentration in the blood plasma, is the rate of hydroxylation. A small proportion of people have a genetically determined delayed hydroxylation. In patients with impaired liver function, the half-life of amitriptyline and nortriptyline in blood plasma is increased.

Excretion

Half-life (T_1/2) from the blood plasma - 9-46 hours for amitriptyline and 18-95 hours for nortriptyline.

Displayed amitriptyline mainly by the kidneys and through the intestines in the form of metabolites. Only a small part of the accepted dose of amitriptyline is excreted through the kidneys unchanged. In patients with impaired renal function, excretion of metabolites of amitriptyline and nortriptyline is slowed, although metabolism as such does not change. Because of the association with blood proteins amitriptyline It is not removed from the blood plasma by hemodialysis.

Elderly patients

In elderly patients there is an increase T_1/2 decrease in clearance of amitriptyline due to decreased metabolic rate.

Patients with hepatic impairment

Dysfunction of the liver can lead to a slowing of the metabolism of amitriptyline and increase its plasma concentrations.

Patients with impaired renal function

Renal failure does not affect the kinetics of the drug.

Indications:

Endogenous depression and other depressive disorders.

Contraindications:

- Hypersensitivity to the components of the drug.

- Use in conjunction with MAO inhibitors (should be discontinued 14 days before treatment with amitriptyline).

- Myocardial infarction (acute and recovery periods), atrioventricular and intraventricular conduction disorders (blockages of any degree), arrhythmias, heart failure, bradycardia, congenital syndrome of elongated QT, as well as simultaneous use with drugs that lead to lengthening of the interval QT.

- Acute delirium.

- Paralytic ileus, intestinal obstruction.

- Pylorostenosis.

- Breastfeeding period.

- Age to 18 years.

- Acute alcohol intoxication, acute intoxication with sleeping pills, analgesic and psychotropic drugs.

- Closed-angle glaucoma.

- Hyperplasia of the prostate with a delay of urine.

- Hypokalemia.

- Intolerance to galactose, deficiency of lactase or glucose-galactose malabsorption.

Carefully:

With convulsive disorders, in patients with epilepsy in history, with urination disorders, bladder hypotension, prostatic hyperplasia, liver function disorders, coronary heart disease, tachycardia, thyroid gland hyperthyroidism, schizophrenia (although it usually does not exacerbate productive symptoms) , paranoid symptoms,bipolar affective disorder (after withdrawal from the depressive phase), in persons prone to increased intraocular pressure (with a narrow angle of the anterior chamber), chronic alcoholism, simultaneous reception with antipsychotic and hypnotics, oppression of bone marrow hematopoiesis, blood diseases, impaired renal function, bronchial asthma, decreased motor function of the gastrointestinal tract (risk of paralytic intestinal obstruction), in old age, pregnancy (especially I and III trimester), simultaneous administration with selective serotonin reuptake inhibitors (SSRIs) and selective serotonin and norepinephrine reuptake inhibitors (SIOPSiN).

Pregnancy and lactation:

The use of Amitriptyline Zentiva during pregnancy is not recommended. During pregnancy, the drug should only be used if the intended benefit to the mother exceeds the potential risk to the fetus. The use of TCA in high doses in the first trimester of pregnancy can lead to neurological disorders in the newborn.

In the appointment of amitriptyline to pregnant women, newborns were noted for drowsiness, agitation and respiratory depression, and with nortriptyline (amitriptyline metabolite), urine retention. In the case of Amitriptyline Zentiva during pregnancy, especially in the third trimester, it is necessary to warn the patient about the high risk of adverse effects of the drug on the fetus.

The use of Amitriptyline Zentiva during breast-feeding is not recommended, since the active substance penetrates into breast milk. It has been established that the ratio of amitriptyline concentrations "breast milk / blood plasma" is 0.4-1.5. A child who is breastfeeding by a mother receiving amitriptyline, undesirable reactions described in the "Side effect" section may occur. If you need to take the drug Amitriptyline Zentiva should refrain from breastfeeding.

Dosing and Administration:

The dose is determined by the doctor individually for each patient, and should be strictly adhered to. Assign inside during or after a meal.

The initial daily intake for oral administration is 25-50 mg, the dose is taken either once a night, or in parts during the day.Then the dose is gradually increased by 25-50 mg until the desired antidepressant effect is obtained. The optimal daily therapeutic dose is 150-200 mg (the maximum part of the dose is taken at night). In severe depression, resistant to therapy, the dose was increased to 300 mg or more, up to maximum tolerated dose (maximum dose for outpatients - 150 mg / day). In these cases, treatment is advisable to begin with intramuscular or intravenous administration of the drug, while using higher initial doses, accelerating the build-up of dosages under the control of the somatic state.

After obtaining a persistent antidepressant effect, after 2-4 weeks the doses gradually and slowly decrease. In case of signs of depression with decreasing doses, it is necessary to return to the previous dose. If the patient's condition does not improve within 3-4 weeks of treatment, then further therapy is impractical.

Duration of therapy

Treatment with antidepressants is symptomatic and should be long enough. The average duration of therapy is usually 6 months or more in order to prevent relapse.

Elderly patients (over 65 years of age)

In elderly patients, the initial dose is 25 mg per day and further increases to 75-100 mg once a day at night.

Patients with impaired renal function

If the renal function is not corrected, dose adjustment is not required.

Patients with impaired hepatic function

If the liver function is impaired and metabolism is slowed down, the drug should be used with caution. Depending on the concentration of amitriptyline in the blood plasma, dose adjustment is possible.

Discontinuation of therapy

When discontinuing therapy, it is recommended to cancel the drug gradually over several weeks in order to avoid the development of the "withdrawal" syndrome.

Repeated course of therapy

When appointing a second course of treatment with amitriptyline, the patient needs to undergo an additional general clinical examination.

Side effects:

When amitriptyline is used, the following side effects may occur, which are separated according to the system-organ classes in accordance with the classification of the Medical Dictionary of Regulatory Activities (MedDRA). The WHO classification was used to indicate the incidence of adverse events: very often (≥10 %); often (≥1% and <10%); infrequently (≥0.1% and <1%); rarely (≥0.01% and <0.1%); very rarely (<0.01%); the frequency is unknown (it is not possible to determine the incidence of side effects from the available data).

Violations from the blood and lymphatic system: infrequent - oppression of bone marrow hematopoiesis, agranulocytosis, leukopenia, thrombocytopenia, eosinophilia.

Disorders of the psyche: often - disorientation, anxiety, agitation, irritability, psychosis, hallucinations, nightmares, impaired concentration.

Impaired nervous system: often - headache, fatigue, weakness, drowsiness or insomnia, tremor, paresthesia, ataxia, peripheral neuropathy; infrequently - extrapyramidal disorders (tardive dyskinesia, lubricated speech, increased convulsive readiness, convulsions).

Disorders from the side of the organ of vision: often - blurred vision, disruption of accommodation.

Disturbances from the organ of hearing and balance: very often - dizziness, noise in the ears.

Heart Disease: very often - arrhythmia, violation of the heart Conductivity, recorded only on the ECG, but not manifested clinically (increase QT interval, increase QRS complex), extrasystole, palpitation, tachycardia; infrequent heart failure (worsening of the existing cardiac dysfunction), nonspecific changes on the ECG in patients not suffering from heart disease; very rarely - atrial fibrillation, ventricular fibrillation, asystole, myocardial infarction.

Vascular disorders: very often - orthostatic hypotension.

Disorders from the gastrointestinal tract: often - dryness of the oral mucosa, taste disorders (bitter or salty taste in the mouth), discomfort in the epigastrium, gastralgia, constipation, nausea, diarrhea, vomiting, heartburn, anorexia, stomatitis, darkening of the tongue, enlargement of the salivary glands; rarely - paralytic intestinal obstruction.

Disorders from the liver and bile ducts: infrequently, cholestatic jaundice.

Disturbances from the skin and subcutaneous tissue: very often - increased sweating; rarely - alopecia.

Disorders from the kidneys and urinary tract: often - urinary retention, delay in the onset of urination, pollakiuria.

Violations of the genitals and breast: often - violations of libido, potency, swelling of the testicles; infrequently - gynecomastia, galactorrhea.

Disorders from the endocrine system: infrequently - a change in the secretion of antidiuretic hormone (ADH); rarely - hypo- or hyperglycemia, glucosuria, impaired glucose tolerance.

Immune system disorders: infrequently - skin rash, itching, hives, rarely - photosensitivity, angioedema, edema of the face and lips.

General disorders and disorders at the site of administration: very often fatigue. Disorders from the metabolism and nutrition: infrequently - weight gain with prolonged use; rarely hyperpyrexia, weight loss; frequency is unknown - hyperkalemia.

Laboratory and instrumental data: very rarely - increased activity of "liver" transaminases.

The withdrawal syndrome: after prolonged use with a sharp discontinuation of reception can occur such undesirable reactions as nausea, vomiting, diarrhea, headache, malaise, insomnia, unusual dreams, unusual arousal, irritability; after a long application with a gradual cancellation - irritability, sleep disturbances, unusual dreams.These symptoms do not indicate the development of addiction to the drug.

There was reported the development of suicidal thoughts or behavior during treatment with amitriptyline or after its withdrawal.

Class - the effect of antidepressants

Epidemiological studies involving patients over the age of 50 demonstrated an increased risk of fracture in individuals taking SSRIs and TCAs. The mechanism leading to an increased risk of fractures is unknown.

Overdose:

There is no specific antidote for the relief of symptoms of acute TCA poisoning.

In adults, taking more than 500 mg of the drug causes mild or severe intoxication. An overdose of amitriptyline (more than 1000 mg) can lead to death. There is a report of a fatal arrhythmia that occurred 56 hours after an overdose of amitriptyline.

Symptoms

Symptoms can develop slowly and imperceptibly, or abruptly and suddenly. During the first hours there is drowsiness or agitation, agitation and hallucinations. Anticholinergic symptoms: mydriasis, tachycardia, urinary retention, dryness mucous membranes, intestinal motility slowing. Convulsions.Temperature increase. Sudden CNS depression. Reducing the level of consciousness down to coma. Suppression of respiration.

Symptoms from the heart: arrhythmias (ventricular tachyarrhythmia, cardiac rhythm disturbances by type torsade des pointes, ventricular fibrillation). The ECG is characterized by an elongation of the interval PR, expansion of the complex QRS, interval lengthening QT, flattening or inversion of the T wave, segment depression ST and blockade of intracardiac conduction of various degrees, which can progress up to cardiac arrest. Expansion of the complex QRS usually correlates with the severity of toxic effects due to acute overdose. Heart failure, lowering blood pressure, cardiogenic shock.

Metabolic acidosis, hypokalemia.

After awakening, confusion, excitement, hallucinations, and ataxia are again possible.

Treatment

Hospitalization (in the intensive care unit). Treatment is symptomatic and supportive. Probing and gastric lavage, even if after taking the drug inside a long time, with a preliminary appointment activated carbon.In case of severe intoxication, 1-3 mg of physostigmine intravenously should be administered. Since physostigmine salicylate is rapidly metabolized, it must be re-administered several times in the event of any life-threatening complication (arrhythmia, convulsions, deep coma). Because of the toxicity of physostigmine, monitoring of the patient's condition after the administration of this drug is necessary. Careful observation, even if the case seems uncomplicated. Observation of the level of consciousness, pulse, arterial pressure and respiration. Frequent control of electrolytes in blood plasma and blood gases. The control of airway passages, if necessary, should be performed using intubation. To prevent possible stopping of breathing, it is recommended to use a ventilator (IVL). Constant ECG monitoring and control of heart function within 3-5 days after taking a toxic dose. When expanding the intervals QRS, heart failure and heart rhythm disturbances of a positive effect can be achieved by shifting the pH to the alkaline side (through the introduction of bicarbonate or moderate hyperventilation) and by rapid infusion of hypertonic sodium chloride solution (100-200 mmol Na⁺). It is possible to use appropriate antiarrhythmics, for example, lidocaine in ventricular arrhythmias at a dose of 50-100 mg IV (1-1.5 mg / kg), then 1-3 mg / min by IV infusion.

Amitriptyline is not excreted by hemodialysis.

If necessary, cardioversion is performed, defibrillation. For the treatment of circulatory failure should use plasma substitutes, and in severe cases - infusion of dobutamine with an initial rate of 2-3 mcg / kg per minute with an increase in dose, depending on the response. With excitation and convulsions, diazepam can be used.

Interaction:

Co-administration with serotonergic active substances (such as SSRIs, SSRIs, MAO inhibitors, lithium preparations, triptans, tramadol, linezolid, L-tryptophan, preparations of St. John's wort) can cause the development of serotonin syndrome.

Inhibitors of monoamine oxidase

Simultaneous reception of amitriptyline and MAO inhibitors can cause serotonin syndrome (agitation, confusion, tremor, myoclonus, hyperthermia are possible). Amitriptyline can be appointed 14 days after cessation of treatment by irreversible MAO inhibitors and at least 1 day after discontinuation of therapy with a reversible MAO inhibitor of type A - moclobemide.

MAO inhibitors can be prescribed 14 days after the end of amitriptyline intake.

Selective serotonin reuptake inhibitors

Caution should be exercised when amitriptyline is used together with selective serotonin reuptake inhibitors (fluoxetine, fluvoxamine). Their simultaneous administration leads to an increase in the concentration of amitriptyline in blood plasma due to inhibition of the isoenzyme CYP2D6, involved in TCA metabolism. Patients receiving such therapy should be under strict medical supervision because of the risk of developing toxic reactions.

Anticholinergic drugs

Since TCAs, including amitriptyline, can enhance the effect of anticholinergic drugs on the organs of vision, central nervous system, intestine and bladder, should avoid their simultaneous use because of the risk of developing paralytic intestinal obstruction.

When taking TCAs in combination with anticholinergic drugs or neuroleptics, especially in hot weather, the development of hyperpyrexia is possible.

Sympathomimetics

Amitriptyline can enhance the effect of epinephrine, norepinephrine, ephedrine, isoprenaline, phenylephrine and phenylpropanolamine on the cardiovascular system.Therefore, anesthetics, decongestants and other preparations containing these substances should not be used simultaneously with amitriptyline.

Drugs that reduce sympathetic activity

Amitriptyline may reduce the hypotensive effect of guanethidine, betanidine, reserpine, clonidine and methyldopa. At simultaneous admission TCA it is necessary to correct hypotensive therapy.

Drugs that depress the central nervous system

When used simultaneously with blockers Hi-gistaminovyh receptors, clonidine, alcohol and barbiturates may increase the inhibitory effect on the central nervous system. Amitriptyline can enhance the effects of other drugs that depress the central nervous system.

Drugs that extend the interval QT

Simultaneous reception of amitriptyline and drugs that extend QT interval, - antiarrhythmics (quinidine), antihistamines (astemizole and terfenadine), some neuroleptics (especially pimozide and sertindole), cisapride, halofantrine and sotalol - increases the risk of ventricular arrhythmia.

Antifungal drugs

Antifungal drugs, for example, fluconazole, terbinafine, increase the concentration of tricyclic antidepressants in serum and, accordingly, their toxicity. Possible syncope and development of paroxysms of ventricular tachycardia (torsade de pointes).

Barbiturates and inducers of microsomal liver enzymes

Barbiturates and other inducers of microsomal liver enzymes, for example, rifampicin and carbamazepine can enhance the metabolism of TCAs, and as a result, reduce the concentration of TCAs in the blood plasma and reduce their effectiveness.

Cimetidine, methylphenidate and blockers of "slow" calcium channels With simultaneous use with cimetidine, methylphenidate and blockers of "slow" calcium channels, it is possible to slow the metabolism of amitriptyline, increase its concentration in the blood plasma and develop toxic effects.

Neuroleptics

When co-administered with neuroleptics, it should be borne in mind that TCAs and neuroleptics mutually inhibit each other's metabolism, reducing the threshold of convulsive readiness.

Indirect anticoagulants

With the simultaneous use of amitriptyline and indirect anticoagulants (coumarin derivatives or indadion), an increase in anticoagulant activity of the latter is possible.

Glucocorticosteroid agents

Amitriptyline may increase depression caused by glucocorticosteroid agents (SCS).

Anticonvulsants

When combined with anticonvulsant drugs, it is possible to increase 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.

Antithyroid drugs

Because of the risk of developing arrhythmias, special care should be taken when prescribing amitriptyline to patients with thyroid hyperthyroidism or to patients receiving antithyroid drugs.

Simultaneous reception with drugs for the treatment of thyrotoxicosis increases the risk of agranulocytosis.

Holin blockers, phenothiazines and benzodiazepines

When combined with holinoblokatorami, phenothiazines and benzodiazepines, mutual strengthening of sedative and central cholinoblocking effects and the risk of epileptic seizures (decrease in the threshold of convulsive activity)

Oral contraceptives

Estrogen-containing oral contraceptive medications and estrogens can increase the bioavailability of amitriptyline.To restore efficacy or reduce toxicity, it may be necessary to reduce the dose or estrogen, or amitriptyline. However, it may be necessary and cancellation of the drug.

Inhibitors of acetaldehyde dehydrogenase

Co-administration with disulfiram and other acetaldehyde dehydrogenase inhibitors may increase the risk of developing psychotic conditions and confusion.

Phenytoin

TCAs can increase the serum concentration of phenytoin and, accordingly, increase the risk of its toxic effects (ataxia, hyperreflexia, nystagmus, tremor).

St. John's wort perforated

Simultaneous use of amitriptyline and preparations containing St. John's wort can lead to increased metabolism of amitriptyline and a decrease in the maximum serum concentration of amitriptyline by 20 %, due to the induction of its metabolism by isoenzyme CYP3A4 liver. Theoretically, an increased risk of developing a serotonin syndrome is possible.

Lithium

With the simultaneous use of lithium and TCA drugs, the risk of psychotic symptoms and toxic complications from the central nervous system may increase, even against the background of therapeutic concentrations of lithium in blood plasma.Described cases of mania, myoclonus, tremor, tonic-clonic seizures, memory disorders, confusion, disorganized thinking, hallucinations, serotonin syndrome and neuroleptic malignant syndrome, begins a few days after the start of the combination therapy; in most cases, it was necessary to cancel therapy with either TCAs or lithium preparations. Elderly patients are particularly prone to the occurrence of such reactions.

Special instructions:

Depression is accompanied by an increased risk of suicidal thoughts, self-harm and suicide (suicidal events). This risk persists until the state of significant improvement. Since the improvement may not occur during the first few weeks of treatment or longer, patients should be carefully monitored until such an improvement occurs. In clinical practice, an increased risk of suicide in the early stages of recovery is widespread. Other psychiatric conditions that are prescribed for amitriptyline, may also be accompanied by an increased risk of suicidal events.In addition, these conditions may accompany a major depressive disorder. Therefore, when treating patients with other psychiatric conditions, the same precautions should be followed as in the treatment of patients with major depressive disorder.

It is known that patients with a history of suicide-related events or who have a significant degree of suicidal thinking prior to starting treatment have a greater risk of suicidal thoughts or suicidal actions and should be carefully observed during treatment. A meta-analysis of placebo-controlled trials of antidepressants with adult patients with psychiatric disorders demonstrated an increased risk of suicidal behavior in patients younger than 25 years of age receiving antidepressants compared to the placebo group.

Careful monitoring of patients, especially those at high risk, should accompany drug therapy, especially in its early stages and after dose changes. It is necessary to warn patients (and caregivers) about the need to monitor any clinical deterioration,suicidal behavior or suicidal thoughts, unusual behavioral changes, and immediately seek medical advice when such symptoms appear.

Care must be taken when using the drug Amitriptyline Zentiva in patients receiving inhibitors or inducers of isoenzyme CYP3A4 systems of cytochrome P450.

Medicinal preparation amitriptyline contains lactose. Patients with rare congenital conditions accompanied by galactose intolerance, lactase deficiency or glucose-galactose malabsorption, this medication should not be taken.

Amitriptyline Zentiva should not be given to children under the age of 18 due to insufficient data on the efficacy and safety of TCAs in this group of patients.

The use of Amitriptyline Zentiva in patients of all age groups is associated with a risk of side effects from the cardiovascular system.

When developing a manic condition, the drug Amitriptyline Zentiva should be canceled.

Hyperglycemia / Diabetes mellitus

Epidemiological studies have revealed an increased risk of developing diabetes in depressed patients receiving TCAs.Thus, patients with an established diagnosis of diabetes mellitus or risk factors for developing diabetes who take the drug Amitriptyline Zentiva should undergo an appropriate examination with the determination of blood glucose.

In patients with diabetes, treatment with Amitriptyline Zentiva can alter the action of insulin and the concentration of glucose in the blood, so you may need to adjust the doses of insulin and / or oral hypoglycemic drugs.

The use of anesthetics during a course of treatment with three / tetracyclic antidepressants may increase the risk of arrhythmia and lowering blood pressure. It should be possible to stop taking the drug Amitriptyline Zentiva a few days before surgery. In case of urgent surgical intervention, the anesthetist should be warned about the patient's treatment with the drug.

During the treatment should be excluded from drinking alcohol.

After a long period of use, a sharp cessation of therapy in some patients can lead to a "cancellation" syndrome.To avoid their occurrence, gradual withdrawal of the drug Amitriptyline Zentiva within several weeks is recommended.

Treatment with amitriptyline in old age should be carefully controlled, with minimum doses of the drug and gradually increased, in order to avoid the development of delirious disorders, hypomania and other complications.

In patients using contact lenses, reducing the formation of tears and accumulation of mucous secretions, due to the m-holinoblokiruyuschey action of TCAs, can lead to damage to the epithelium of the cornea. Due to the anticholinergic effect of amitriptyline, an attack of increased intraocular pressure is possible. Dry mucosa the shell of the oral cavity can lead to the appearance of changes on its surface, inflammatory reactions, a burning sensation and caries. Regular visits to the dentist are recommended. When TCAs are used in combination with other serotonergic drugs, serotonin syndrome may occur. The syndrome caused by excess serotonin can lead to a fatal outcome and includes the following symptoms: neuromuscular excitation (muscle twitching, hyperreflexia,myoclonus, rigidity), vegetative changes (hyperthermia, tachycardia, changes in blood pressure, increased sweating, tremor, flushing of the skin, dilated pupils, diarrhea), changes in mental state (anxiety, agitation, confusion, coma).

Due to the drug Amitriptyline Zentiva, it is possible to develop agranulocytosis. The drug Amitriptyline Zentiva should be used with extreme caution in patients with convulsive disorders and epilepsy in the anamnesis, since amitriptyline reduces the threshold of convulsive readiness, which may lead to a decrease in the effectiveness of treatment with antiepileptic drugs. This group of patients has an increased risk of developing convulsive seizures amitriptyline. Epidemiological studies involving patients over the age of 50 demonstrated an increased risk of fracture in individuals taking selective serotonin reuptake inhibitors and TCAs. The mechanism leading to an increased risk of fractures is unknown.

Before starting treatment with Amitriptyline Zentiva, the patient needs to undergo correction of hypokalemia.

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

During the application of the drug Amitriptyline Zentiva, it is prohibited to drive vehicles, service mechanisms and other types of work that require a high concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Film-coated tablets, 25 mg.

Packaging:For 10 tablets in a blister of PVC / Al. For 2, 5 or 10 blisters together with the instructions for use are placed in a cardboard box.

Storage conditions:

At a temperature of up to 25 ° C in a dry, dark place.

Keep out of the reach of children.

Shelf life:

4 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N016138 / 01

Date of registration:05.02.2010 / 21.03.2014

Expiration Date:Unlimited

Date of cancellation:2017-11-14

The owner of the registration certificate:Zentiva as.Zentiva as. Czech Republic

Manufacturer: & nbsp

Saneka Pharmaceuticals as. The Slovak Republic

Representation: & nbspZENTIVA ZENTIVA Czech Republic

Information update date: & nbsp14.11.2017

Illustrated instructions

Instructions

Amitriptyline Zentiva (Amitriptylin Zentiva)