Citalone - instructions for use, doses, side effects, contraindications

Name of substance	Content
Name of substance	20 mg	30 mg	40 mg
Active substance:
Citalopram hydrobromide	24.99 mg	37.48 mg	49.98 mg
(in terms of citalopram)	20 mg	30 mg	40 mg
Excipients:
Core:
Corn starch	46.01 mg	69.02 mg	92.02 mg
Lactose Monohydrate	23.00 mg	34.50 mg	46.00 mg
Copovidone	6.00 mg	9.00 mg	12.00 mg
Water	34 μl	51 μl	68 μl
Glycerol 85%	2.00 mg	3.00 mg	4.00 mg
Cellulose microcrystalline	21.00 mg	31.50 mg	42.00 mg
Magnesium stearate	1.00 mg	1.50 mg	2.00 mg
Sodium carboxymethyl starch	6.00 mg	9.00 mg	12.00 mg
Sheath:
Water	39.5 μl	47.4 μl	55.3 μl
Hypromellose	3.45 mg	4.14 mg	4.83 mg
Macrogol-6000	0.85 mg	1.02 mg	1.19 mg
Titanium dioxide, E 171	0.45 mg	0.54 mg	0.63 mg
Talc	0.25 mg	0.30 mg	0.35 mg

Description:

Tablets 20 mg: white oblong biconvex tablets, covered with a film membrane, with engraving C20 on one side and risk on the other, the surface of the tablet is chamfered to the risk.

Tablets 30 mg: white oblong biconvex tablets, covered with a film membrane, with C30 engraving on one side and risk on the other, the surface of the tablet is chamfered to the risk.

Tablets 40 mg: white oblong biconvex tablets, covered with a film membrane, with engraving C40 on one side and risk on the other, the surface of the tablet is chamfered to the risk.

Pharmacotherapeutic group:antidepressant

ATX: & nbsp

N.06.A.B.04 Citalopram

Pharmacodynamics:

The antidepressant, a selective serotonin reuptake inhibitor (SSRI), has a pronounced ability to inhibit the reuptake of serotonin, has virtually no effect on neuronal uptake of norepinephrine, dopamine, and gamma-aminobutyric acid. Citalopram has no or very little affinity for cholinergic, histaminergic and most adrenergic, serotonergic and dopaminergic receptors.

With long-term use, tolerance to the inhibitory effect of citalopram on 5-HT does not develop.

Citalopram is a bicyclic derivative of isobenzofuran, which does not chemically bind to tri- and tetracyclic antidepressants.

The main metabolites of citalopram are also SSRIs, despite this there are no reports of the contribution of citalopram metabolites to the overall antidepressant effect.

Suppression of the "fast sleep" stage is considered a predictor of antidepressant action. Like tricyclic antidepressants, other SSRIs and monoamine oxidase inhibitors (MAO), citalopram suppresses the phase of "fast sleep" and increases the phase of deep slow wave sleep. Citalopram does not affect the content of growth hormone in the serum. Citalopram, like other SSRIs, can increase the level of prolactin in the blood plasma.

Although citalopram does not bind to opioid receptors, it enhances the antinociceptive effect of opioid analgesics. Citalopram does not impair cognitive and psychomotor functions and does not possess or possesses minimal sedative properties.

In a double-blind, placebo-controlled study of ECG in healthy people, the change in the interval QT compared with the original value (correction for Fridericia) was 7.5 ms (90% confidence interval 5.9-9.1 ms) with a dose of 20 mg / day and 16.7 ms (90% confidence interval 15.0-18.4 μs) when applying a dose of 60 mg per day.

Pharmacokinetics:

Citalopram is rapidly absorbed when taken orally, the time to reach the maximum concentration of the drug in the blood plasma (T_max) is achieved on average in 4 (1-7) h. Absorption does not depend on the intake of food. Bioavailability for oral administration is approximately 80%. The main volume of distribution is from 12 to 17 l / kg. The binding of citalopram and its metabolites to plasma proteins is below 80%.

Citalopram is metabolized to demethylcitalopram, di-demethyl-citalopram, citalopram-Noxide and deaminated derivatives of propionic acid. The derivatives of propionic acid are pharmacologically inactive. The biotransformation of citalopram in demethylcitalopram is mediated by isoenzymes of the cytochrome P450 - CYP2C19 (about 38%), CYP3A4 (about 31%) and CYP2D6 (about 31%). Research in vivo showed that plasma concentrations of citalopram and its metabolites depend on the phenotype of sparteine / debrisoquine and the phenotype of mephenytoin. However, individual dose selection depending on these phenotypes is not mandatory.

Half-life of blood plasma (T_1/2) is approximately 1.5 days. Clearance of the drug in plasma (Cl_oral) after oral administration of about 0.4 l / min.

Citalopram is mainly excreted through the intestine (85%), and also through the kidneys (15%). Unchanged in the urine is derived 12-23% from the accepted dose of citalopram. The clearance of the drug in the liver is approximately 0.3 l / min, in the kidneys - 0.05-0.08 l / min.

In elderly patients, y patients with impaired liver function period half-life (T_1/2) and plasma concentrations increase approximately 2-fold.

The excretion of citalopram slightly slows in patients with mild to moderate renal impairment, without a significant effect on the pharmacokinetics of the drug. There is no information on the use of citalopram the patients with severe renal insufficiency (creatinine clearance less than 20 ml / min).

Equilibrium concentrations of citalopram (Css) in blood plasma are achieved after 1-2 weeks.Between the equilibrium concentrations of the drug in the blood plasma and the dose taken, there is a linear relationship. When taking citalopram in a dose of 40 mg per day, the average concentration of the drug in the blood plasma is about 300 nmol / l. There is no clear relationship between the concentration of citalopram in blood plasma and the therapeutic response or side effects.

Indications:

- Depression of moderate to severe severity and prevention of their recurrence;

- panic disorder with / without agoraphobia.

Contraindications:

- Hypersensitivity to citalopram or any of the excipients that make up the drug.

- rare hereditary forms of lactose intolerance, lactase deficiency or impaired absorption of glucose / galactose (because the composition contains lactose);

- simultaneous administration with monoamine oxidase (MAO) inhibitors (including selegilin at a dose above 10 mg / day). The interval between the end of the intake of irreversible MAO inhibitors and the initiation of citalopram should be at least 14 days. In the case of reversible MAO-A inhibitors, the duration of the break is determined in accordance with the instructions for use of this drug.Treatment with MAO inhibitors can be started no earlier than 7 days after stopping citalopram.

- children and adolescents under 18 years of age (efficacy and safety not established).

- patients with lengthening interval QT (congenital syndrome of an elongated interval QT; simultaneous reception of drugs that can lengthen the interval QT (for example, antiarrhythmic drugs IA and III classes, tricyclic antidepressants, macrolides);

- simultaneous application of linezolid, pimozide.

- simultaneous application of citalopram with drugs that have a serotonergic effect (sumatriptan, tramadol, tryptophan, oxytryptane).

Carefully:Epilepsy (including pharmacologically uncontrolled epilepsy); diabetes mellitus (the control of concentration of a glucose in a blood is necessary); in the anamnesis mania, hypomania; elderly age; convulsive seizures; hepatic and renal failure (mild to moderate); depression with suicidal attempts, a bradycardia, recently transferred acute myocardial infarction, uncompensated heart failure, simultaneous reception with medications that reduce the threshold of convulsive readiness, causing hyponatremia.

Pregnancy and lactation:

The use of the drug is possible only if the intended use for the mother exceeds the potential risk to the fetus or baby. If nevertheless it is necessary to use citalopram during pregnancy, careful monitoring of fetal development, especially in the 3rd trimester of pregnancy, is necessary.

It is also necessary to monitor newborns whose mothers have taken citalopram during pregnancy, because the infant may experience the following symptoms: respiratory distress syndrome, cyanosis, dyspnea, convulsions, impaired body thermoregulation, decreased sucking reflex, vomiting, hypoglycemia, hypertension, hypotension, hyperreflexia, tremor, nervousness, irritability, lethargy, incessant crying , drowsiness and insomnia. These symptoms can be a consequence of immediate serotonergic effects or the cessation of their action. In most cases, complications begin immediately or in the near future (<24 h) after the birth of the baby. Epidemiological data have shown that the use of SSRIs during pregnancy, especially in the last trimester of pregnancy, may increase the risk of persistent pulmonary hypertension in newborns.The observed risk was approximately 5 per 1,000 pregnancies.

It should be avoided abrupt cessation of citalopram during pregnancy.

Citalopram is excreted in small amounts into breast milk. Despite the fact that nursing infants, whose mothers used citalopram, there were no or minor side effects, if it is necessary to use the drug during lactation, the question of stopping breastfeeding should be solved.

Animal studies have shown that some SSRIs can affect sperm quality. Reports on the use of some SSRIs in humans suggest that the effect on sperm quality is reversible. Influence on human fertility has not yet been noted.

Dosing and Administration:

Inside, once a day (morning or evening), regardless of food intake.

Depression: the usual dose of 20 mg once a day, the maximum daily dose - 40 mg. The beginning of the therapeutic effect in 2-4 weeks after the start of treatment. As with any antidepressant treatment, the effectiveness of therapy should be evaluated and, if necessary, the dose of citalopram should be adjusted 3-4 weeks after the start of treatment and further depending on the clinical indications.The dose adjustment should be performed depending on the individual response to therapy, to maintain the patient at the lowest effective dose. Taking the drug is recommended to continue for 4-6 months after the disappearance of symptoms.

Panic disorders: the first week is recommended taking a dose of 10 mg once a day, after that the dose can be increased to 20 mg per day. It is necessary to start therapy with low doses in connection with the risk of deterioration of the patient at the beginning of treatment.

Gradually, depending on the tolerability and individual response of the patient, the dose can be increased to 40 mg per day. The first therapeutic effect usually occurs after 2-4 weeks. For development A full therapeutic effect may be required up to 3 months. You may need to continue treatment within a few months.

Patients with defective polymorphism CYP2C19 (slow metabolizers)

The initial dose of 10 mg per day during the first two weeks of treatment, if necessary, the dose may be increased to a maximum of 20 mg per day, depending on the patient's individual response.

Elderly (over 65 years of age): the recommended daily dose is 10 mg, the dose can be increased to a maximum daily dose of 20 mg.

When a violation of liver function: the recommended daily dose is 10 mg, the dose can be increased to a maximum daily dose of 20 mg.

With mild to moderate renal impairment correction of the dose is not required. There is insufficient information on the use of citalopram in patients with severe renal insufficiency (creatinine clearance less than 20 ml / min) to develop recommendations for dose adjustment.

Avoid sudden cessation of treatment. When discontinuing citalopram treatment, the dose should be gradually reduced for a minimum of 1 to 2 weeks in order to reduce the risk of withdrawal symptoms. If there are intolerable symptoms after a dose reduction or after discontinuation of treatment, it is recommended to consider the possibility of resuming treatment at a previously prescribed dose. They usually occur within the first few days after cessation of treatment, but there are reports of very rare cases of developing such symptoms in patients who accidentally missed the dose. Usually, intolerable symptoms are resolved spontaneously within 2 weeks, although in some patients they can be prolonged (2-3 months or more).Therefore, when discontinuing treatment, it is usually recommended that the dose of citalopram is gradually reduced within a few weeks or months, depending on the patient's individual tolerability.

Side effects:

According to the World Health Organization (WHO), undesirable effects are classified according to their frequency of development as follows: very often (≥ 1/10), often (≥1/100, <1/10), infrequently (≥1/1000, <1/100), rarely (≥1/10000, <1/1000) and very rarely (<1/10000); frequency is unknown (the frequency of occurrence of phenomena can not be determined on the basis of available data).

Disorders from the blood and lymphatic system:

frequency is unknown (can not be calculated from available data): thrombocytopenia.

Immune system disorders:

frequency is unknown (can not be calculated from available data): allergic reactions, anaphylactoid reaction.

Disorders of nutrition and metabolism:

often: decreased appetite, weight loss; infrequently: increased appetite, weight gain;

rarely: hyponatremia;

frequency is unknown (can not be calculated from available data): hypokalemia, impaired production of antidiuretic hormone.

Mental disorders:

Often: sleep disorders;

often: stimulation, decreased libido, anxiety, nervousness, anxiety, confusion, orgasm disorders (in women), "nightmarish" dreams, apathy;

infrequently: aggressive behavior, depersonalization, hallucinations, mania; rarely: increased libido;

frequency is unknown (can not be calculated from available data): panic attacks, bruxism (grinding teeth), anxiety, suicidal thoughts, suicidal attempts, paranoid reaction, confusion of thoughts, mood changes, emotional lability, hypomania, psychosis, excessive fatigue, euphoria, increased libido.

From the nervous system:

Often: drowsiness, insomnia, headache;

often: tremor, paresthesia, dizziness, impaired concentration, migraine, amnesia; infrequently: syncopal condition;

rarely: dyskinesia, tonic-clonic convulsions (grand mal);

frequency is unknown (can not be calculated from available data): serotonin syndrome (agitation, confusion, diarrhea, hyperthermia, hyperreflexia, ataxia, tremor, increased sweating, agitation, uncontrolled behavior), extrapyramidal disorders,panic, sleep disturbance, amnesia, convulsions, akathisia (restlessness, anxiety, in which a person feels an acute, painful need to move and therefore can not take a static posture for a more or less long time).

From the sense organs:

often: noise in ears;

infrequently: mydriasis (increases the risk of development of an angle-closure glaucoma); rarely: perversion of taste;

frequency is unknown (can not be calculated from available data): impaired vision, disruption of accommodation.

From the cardiovascular system:

rarely: bleeding;

infrequently: bradycardia (a decrease in the rhythm of the heart), tachycardia (rapid heartbeat);

frequency is unknown (can not be calculated from available data): orthostatic hypotension, hypo / hypertension; interval lengthening QT, supraventricular and ventricular arrhythmias (including arrhythmias of the type "torsade de pointes"), flutter / atrial fibrillation.

(Interval lengthening cases QT and ventricular arrhythmias, including tachycardia of the "torsade de pointes", were registered in the postmarketing period, mainly in female patients, as well as in patients with hypokalemia or with an already existing interval lengthening QT or other heart diseases).

Co of the respiratory system:

often: yawn;

frequency is unknown (can not be calculated from available data): nosebleeds, cough, rhinitis, sinusitis, dyspnea.

From the gastrointestinal tract:

Often: nausea, dryness of the oral mucosa;

often: vomiting, constipation, diarrhea, indigestion, abdominal pain, flatulence, increased salivation;

rarely: hepatitis;

frequency is unknown (can not be calculated from available data): gastrointestinal bleeding, anorexia, increased activity of "hepatic" enzymes.

Co skin and subcutaneous tissues:

Often: increased sweating; often: itching of the skin;

infrequently: alopecia, rash, photosensitivity, purpura;

frequency is unknown (can not be calculated from available data): epidermal necrolysis, ecchymosis (small hemorrhages in the skin or mucous membrane), angioedema.

Co the side of the musculoskeletal system:

often: myalgia, arthralgia.

From the genitourinary system:

often: impotence, ejaculation disorders, female anorgasmia; infrequently: retention of urine, menorrhagia;

frequency is unknown (can not be calculated from available data): metrorrhagia, priapism, galactorrhea, frequent urination, polyuria, dysmenorrhea, menstrual irregularities.

Systemic disorders:

Often: asthenia; often: fatigue; infrequently: edema;

rarely: hyperthermia (fever), malaise;

frequency is unknown (can not be calculated from available data): mastodynia (painful sensations in the mammary glands).

Epidemiological studies conducted the patients over the age of 50, showed an increased risk of developing bone fractures in patients receiving SSRIs and tricyclic antidepressants. The mechanism leading to this increased risk is unknown.

Symptoms of withdrawal, Observed after discontinuation of SSRI treatment

Discontinuation of citalopram treatment (especially severe) often leads to withdrawal symptoms. Dizziness, sensation disturbance (including paresthesia), sleep disturbance (including insomnia and "bright" dreams), agitation or anxiety, nausea and / or vomiting, tremor, confusion, sweating, headache, diarrhea, palpitations, emotional instability, irritability, impaired vision are the most frequent reactions.As a rule, these phenomena of mild or moderate severity are resolved spontaneously, but in some patients they can be severe and prolonged. In this regard, a gradual cessation of treatment with a dose reduction is recommended.

Overdose:

Toxic manifestations

Complete clinical data on the overdose of citalopram are limited, and often these cases are associated with concomitant overdoses of other drugs / alcohol. There have been reports of fatal outcomes with an overdose of citalopram in monotherapy, but in most cases, an overdose of concomitant medications has also occurred. The magnitude of the lethal dose is unknown, but there are data on patients who experienced a one-time intake of more than 2 g of citalopram. In the case of an overdose, the toxic effects of citalopram may increase with the use of alcohol.

Symptoms: dizziness, drowsiness, dysarthria, sinus tachycardia, drowsiness, hypotension, arterial hypertension, nodal rhythm on the ECG, bradycardia, bundle bund block, expansion of the complex QRS, lengthening the interval Q-T, arrhythmia of the pirouette type, atrial and ventricular arrhythmias, increased sweating, vomiting, cyanosis, hyperventilation of the lungs, tremor, amnesia, confusion, changes in the electroencephalogram (nodal rhythm), rhabdomyolysis, seizures, coma, cardiac arrest, serotonin syndrome, mydriasis, stupor, hyperpyrexia, increased serum creatinine levels. At the expressed toxic defeat it was informed about rare cases of development of a serotonin syndrome which is shown by change of a mental status, a neuromuscular hyperactivity and frustration of a vegetative nervous system.

Treatment: Activated carbon, osmotic laxatives (such as sodium sulfate) and gastric lavage, provided that the drug was taken no more than 7 hours ago. When oppression of consciousness, the patient should be transferred to artificial ventilation in the monitoring of ECG and vital functions. In case of an overdose, ECG monitoring is recommended in patients with congestive heart failure / bradyarrhythmias, in patients using concomitant medications that extend the interval QT, or in patients with altered metabolism, for example, with liver damage. There is no specific antidote.

Interaction:

Pharmacodynamic interactions

When assessing pharmacodynamics, there were cases of the development of serotonin syndrome with simultaneous application of citalopram, moclobemide and buspirone.

The simultaneous use of citalopram is contraindicated

With MAO inhibitors

The simultaneous use of citalopram and MAO inhibitors can lead to serious undesirable effects, including the development of serotonin syndrome.

There have been reports of serious and sometimes fatal reactions in patients receiving SSRIs in combination with MAO inhibitors, including those with an irreversible MAO inhibitor selegiline, as well as with reversible MAO inhibitors - linezolid and moclobemide, and in patients who have recently stopped treatment with SSRIs and started treatment with MAO inhibitors. Sometimes only the appearance of signs resembling a serotonin syndrome, including excitation, tremor, myoclonia and hyperthermia is possible.

Pimozide

The combined use of a single dose of pimozide 2 mg in patients receiving racemic citalopram 40 mg / day for 11 days, led to an increase in the indices AUC (the area under the concentration-time curve) and the maximum plasma concentration of pimozide, although this was not observed continuously throughout the study. The combined use of pimozide and citalopram led to an increase in the interval QT an average of 10 ms. In connection with this interaction, noted with the use of a low dose of pimozide, the simultaneous use of citalopram and pimozide is contraindicated.

Interval lengthening QT

Pharmacokinetic and pharmacodynamic studies of citalopram and other drugs that extend the interval QT, were not conducted. The additive effect when using citalopram and these drugs can not be ruled out. Therefore, the combined use of citalopram and drugs, which extend the interval QT, such as antiarrhythmic drugs of class IA and III, antipsychotics (eg, phenothiazine derivatives, pimozide, haloperidol), tricyclic antidepressants, some antimicrobial drugs (for example, sparfloxacin, moxifloxacin, erythromycin for intravenous administration, pentamidine, antimalarial drugs, in particular halofantrine), some antihistamines (astemizole, misolastine).

The simultaneous use of citalopram with caution

Selegiline (selective MAO inhibitor of type B)

Pharmacokinetic / pharmacodynamic studies of interaction with concurrent use of citalopram (20 mg per day) and selegiline (10 mg per day) showed no clinically significant interactions. The simultaneous use of citalopram and selegiline (in doses above 10 mg per day) is contraindicated.

Serotonergic drugs

Lithium and tryptophan

Pharmacokinetic interactions were not detected with the simultaneous use of citalopram with lithium. However, there have been cases of increased efficacy in the use of SSRIs concomitantly with lithium or tryptophan, so simultaneous use of citalopram with these drugs should be done with caution. It is recommended that the serum concentration of lithium be monitored regularly.

Simultaneous use of serotonergic drugs (for example, tramadol, sumatriptan) can lead to an increase in the effects associated with 5-hydroxytryptophan. Until further data are obtained, simultaneous use of citalopram and agonists of 5-hydroxytryptophan (sumatriptan and other triptans) is contraindicated.

Preparations of St. John's wort

Dynamic interactions between SSRIs and herbal preparations based on St. John's Wort can be observed (Hypericum perforatum), with the possibility of an increase in the frequency of undesirable effects. Pharmacokinetic interactions have not been studied.

Caution should be exercised while using citalopram and medicines, affecting the function of platelets, such as non-steroidal anti-inflammatory drugs (NSAIDs), acetylsalicylic acid, dipyridamole, ticlopidine or other drugs (eg, atypical antipsychotics, phenothiazines, tricyclic antidepressants), which can increase the risk of bleeding.

There are no clinical studies on the risks and benefits of combined use electroconvulsive therapy (ECT) and citalopram.

Ethanol

Pharmacodynamic or pharmacokinetic interactions between citalopram and ethanol were not observed, however, their simultaneous application is not recommended.

Drugs that reduce the convulsive threshold SSRIs can reduce the convulsive threshold, so caution should be exercised while using citalopram with other medicinal drugs that can reduce the convulsive threshold (eg, antidepressants, neuroleptics (phenothiazines, thioxanthenes, and butyrophenones)), mefloquine, bupropion and tramadol).

Imipramine and desipramine

In a pharmacokinetic study, no effect was shown on the concentrations of citalopram or imipramine, although the concentration of desipramine, the main metabolite of imipramine, was increased. With the use of desipramine in combination with citalopram, an increase in the concentration of desipramine in the plasma was not observed. It may be necessary to reduce the dose of desipramine.

Neuroleptics

To date, there have been no clinically significant interactions of citalopram with neuroleptics. However, as with the use of other SSRIs, the possibility of pharmacodynamic interactions can not be ruled out.

Pharmacokinetic interactions

The biotransformation of citalopram in demethylcitalopram is mediated by isoenzymes of the cytochrome P450 - CYP2C19 (about 38%), CYP3A4 (about 31%) and CYP2D6 (about 31%). The fact that citalopram metabolized with the participation of more than one CYP means that inhibition of its biotransformation is unlikely, since inhibition of one enzyme can be compensated by another. Therefore, when citalopram is used together with other medicinal products in clinical practice, there is a very low probability of pharmacokinetic drug interactions.

Food

Eating does not affect the absorption and other pharmacokinetic properties of citalopram.

The effect of other drugs on the pharmacokinetics of citalopram

Simultaneous application with ketoconazole (a potent inhibitor CYP3A4) does not affect the pharmacokinetics of citalopram.

Study of pharmacokinetic interactions lithium and citalopram did not reveal any pharmacokinetic interactions (also see above). Cimetidine (a potent inhibitor CYP2D6, 3A4 and 1A2) caused a moderate increase in the average equilibrium concentration of citalopram. Caution is advised when using citalopram in combination with cimetidine. Dose adjustment may be required.

Simultaneous application escitalopram (active enantiomer citalopram) from omeprazole in a dose of 30 mg once a day (inhibitor CYP2C19) resulted in a moderate (about 50%) increase in the plasma concentration of escitalopram. Therefore, care should be taken when applying simultaneously with inhibitors CYP2C19 (eg, omeprazole, esomeprazole, Fluvoxamine, lansoprazole, ticlopidine) or cimetidine. It may be necessary to reduce the dose of citalopram based on the monitoring of adverse effects during concomitant treatment.

Escitalopram is an enzyme inhibitor CYP2D6. It is necessary to use caution citalopram together with medicines, which are mainly metabolized by this enzyme, and which have a narrow therapeutic index, for example, flecainide, propafenone and metoprolol (when used to treat heart failure), or with some CNS-acting drugs that are mainly metabolized CYP2D6, for example, antidepressants (such as desipramine, clomipramine and nortriptyline) or antipsychotics (such as risperidone, thioridazine and haloperidol). Dose adjustment may be required.

Simultaneous application with metoprolol led to a two-fold increase in the level of metoprolol in plasma, but did not lead to a statistically significant increase in the effect of metoprolol on blood pressure and heart rhythm.

Effect of citalopram on other drugs

Pharmacokinetic / pharmacodynamic studies of interactions with the concomitant use of citalopram and metoprolol see above.

Citalopram and demethyl citalopram are minor inhibitors CYP2C9, CYP2E1 and CYP3A4, and only weak inhibitors CYP1A2, CYP2C19 and CYP2D6 in comparison with other SSRIs that are significant inhibitors. Thus, the absence or only very small changes, not having clinical significance, were observed with concurrent use of citalopram and Substrates CYP1A2 (clozapine and theophylline), CYP2C9 (warfarin), CYP2C19 (imipramine and mephenytoin), CYP2D6 (sparteine, imipRamine, amitriptyline, rispeRidon) and CYP3A4 (warfarin, carbamazepine (and its metabolite carbamazepine-epoxide) and triazolam).

There was no pharmacokinetic interaction between citalopram and levomepromazine or digoxin (indicates that citalopram does not induce or inhibit P-glycoprotein).

Special instructions:

Before the beginning of treatment with Citalon®, it is necessary to check the electrolyte composition of the blood (for the detection of hyponatremia, hypokalemia), ECG to detect an elongated QT interval.

Determined that citalopram can cause a dose-dependent interval lengthening QT. Caution is recommended in patients with severe bradycardia or in patients with recent acute myocardial infarction or decompensated heart failure.

Electrolyte disturbances, such as hypokalemia and hypomagnesemia, increase the risk of developing malignant arrhythmias, so they must be adjusted before treatment with citalopram. When using SSRIs, probably because of inadequate secretion of antidiuretic hormone, there may be hyponatremia, which can cause heart rhythm disturbances. The risk of hyponatremia in elderly female patients is especially high, therefore it is recommended to regularly monitor the electrolyte composition of blood during treatment with Citalon®.

When prescribing treatment with Citalon® to patients with stable heart disease, the need for an ECG study should be considered before starting treatment.

If there are signs of cardiac arrhythmia during treatment with Citalon®, treatment should be discontinued, and an ECG test should be performed.

Suicide / suicidal thoughts or clinical worsening

Depression is associated with an increased risk of suicidal thoughts, self-harm and suicide (phenomena associated with suicide). This risk persists until a stable remission is achieved. Since there may be no improvement during the first two weeks or a longer period of treatment, patients should be closely monitored until such improvements develop. General clinical experience suggests that in the early stages of recovery, the risk of suicide may increase.

Other mental disorders in which Citalon® is administered may also be associated with an increased risk of developing phenomena associated with suicide. In addition, with these conditions there may be a concomitant major depressive disorder.Therefore, when treating patients with other mental disorders, the same precautions should be followed as in the treatment of patients with major depressive disorder.

In patients with a history of suicidal-related phenomena, and if there are pronounced suicidal intentions before starting treatment, there is an increased risk of suicidal thoughts or suicide attempts, so patients should be closely monitored during treatment. A meta-analysis of placebo-controlled clinical trials of the use of antidepressants in adult patients with psychiatric illnesses showed an increased risk of suicidal behavior when using antidepressants (compared to placebo) in patients younger than 25 years of age.

Drug therapy of patients, especially high-risk patients, must be accompanied by careful monitoring. Of particular importance is the period of treatment initiation and dose changes. Patients (and caregivers) should be warned about the need to monitor for any clinical deterioration, suicidal behavior and thoughts, unusual behavioral changes, and the need to seek medical help while maintaining such symptoms.

Akathisia / psychomotor anxiety

The use of SSRIs / SSRIs and norepinephrine was associated with the development of akathisia characterized by subjectively unpleasant or painful anxiety and the need to move frequently, as well as the inability to sit or stand still. Most often this occurs during the first few weeks of treatment. In patients who develop these symptoms, increasing the dose may have undesirable consequences.

Mania

In patients with manic-depressive psychosis, there may be a tendency to transform into a manic phase. If the patient enters the manic phase, treatment with Citalon® should be discontinued.

Convulsions

The development of seizures is a potential risk in the use of antidepressants. With the development of seizures in any patient should stop treatment with Citalon®. The use of citalopram should be avoided in patients with unstable epilepsy, and careful monitoring of patients with controlled epilepsy is necessary. Also, treatment with Citalon® should be discontinued if there is an increase in the frequency of epileptic seizures.

Diabetes

In patients with diabetes mellitus, the treatment of SSRIs can alter the concentration of glucose in the blood, which may require correction of the dose of insulin and / or oral hypoglycemic drugs.

Serotonin syndrome

In rare cases, patients taking SSRIs have a serotonin syndrome. The presence of a combination of symptoms such as agitation, tremor, myoclonia and hyperthermia may indicate the development of this condition. Treatment with Citalon® should be stopped immediately and symptomatic treatment started.

Serotonergic drugs

Citalon® should not be used concomitantly with drugs with serotonergic effects, such as sumatriptan or other triptans, tramadol, oxytryptan and tryptophan.

Bleeding

There have been cases of increased bleeding time and pathological bleeding, such as ecchymosis, gynecological bleeding, gastrointestinal bleeding and other skin bleeding or from mucous membranes with SSRIs. It is advisable to take care when treating patients with SSRIs, in particular, with simultaneous use of drugs,which affect the function of platelets or other drugs that may increase the risk of bleeding, as well as in patients with history of clotting disorders (see "Interaction with other drugs").

ECT (electroconvulsive therapy)

There is limited clinical experience in the simultaneous use of SSRIs and ECT, so caution is recommended.

Reversible selective inhibitors of MAO type A

The combined use of Citalon® with MAO type A inhibitors is generally not recommended due to an increased risk of developing serotonin syndrome (see section "Interaction with Other Drugs").

Preparations of St. John's wort

Unwanted effects can occur more often with the simultaneous use of Citalon® and herbal preparations containing St. John's Wort (Hypericum perforatum) (see the section "Interaction with other medicinal products").

Symptoms of withdrawal observed after discontinuation of SSRI treatment

With a sharp withdrawal of the drug there is a "cancellation" syndrome. In a clinical study of the prevention of recurrences with citalopram, adverse events after cessation of active treatmentwere observed in 40% of patients compared with 20% of patients who continued treatment with citalopram.

The risk of withdrawal may depend on several factors, including the duration of the therapy and the dose, as well as the rate of dose reduction (see "Dosage and administration", "Side effects").

Psychosis

When citalopram treatment of patients with psychoses and episodes of depression, psychotic symptoms can be amplified.

There is no need for special precautions when destroying an unused preparation.

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

Psychoactive drugs can reduce the ability to make quick decisions and respond to emergencies. Patients should be informed of these effects and be warned that their ability to drive a car or work with machinery can be reduced.

Form release / dosage:

The film-coated tablets are 20 mg, 30 mg and 40 mg.

Packaging:

For 7, 10 or 14 tablets are placed in a blister of PVDH-PVC / aluminum foil.

By 1,2, 3, 4, 5 or 10 blisters are placed in a cardboard box together with instructions for medical use.

Storage conditions:

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.

Terms of leave from pharmacies:On prescription

Registration number:LSR-010625/09

Date of registration:25.12.2009

The owner of the registration certificate:Sandoz d.Sandoz d. Slovenia

Manufacturer: & nbsp

SALUTAS PHARMA, GmbH Germany

Representation: & nbspSANDOZ SANDOZ Switzerland

Information update date: & nbsp27.09.2015

Illustrated instructions

Instructions

Citalon® (Citalon®)