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

Excipients: starch corn 46.1 mg / 92.2 mg, lactose monohydrate 23.1 mg / 46.1 mg, copovidone 6.25 mg / 12.5 mg, glycerol 85% 2.5 mg / 5 mg, microcrystalline cellulose 18, 8 mg / 37.5 mg, croscarmellose sodium 2.5 mg / 5 mg, magnesium stearate 0.87 mg / 1.74 mg;

shell: hypromellose 5 2.04 mg / 3.26 mg, macrogol 400 0.408 mg / 0.652 mg, titanium dioxide (E 171) 0.679 mg / 1.09 mg.

Description:

20 mg - oval, white-colored tablets, film-coated, with a risk labeled "C" and "N"Symmetrically about the risks;

40 mg - oval, white colored tablets, film-coated,with a risk labeled "C" and "R"Symmetrically about the risks.

Pharmacotherapeutic group:antidepressant

ATX: & nbsp

N.06.A.B.04 Citalopram

Pharmacodynamics:

Citalopram is a highly selective serotonin reuptake inhibitor (SSRI) without or with minimal effect on the capture of noradrenaline, dopamine and gamma-aminobutyric acid.

Citalopram does not have at all or has a very weak ability to bind to a number of receptors, including 5-HT_1A-, 5-HT₂-serotonin, D₁- and D₂dopamine, α₁-,α₂- and β-adrenergic receptors, H₁-gistaminovye, muscarinic cholinergic receptors, benzodiazepine and opioid receptors.

Suppression of the stage of fast sleep (REM) is considered a predictor of antidepressant action. Like tricyclic antidepressants, other SSRIs and MAO inhibitors, citalopram suppresses a fast sleep and increases a deep slow wave sleep.

In a single-dose study conducted on healthy volunteers, citalopram did not reduce salivation and in no study on healthy volunteers had a significant effect on cardiovascular performance. Citalopram does not affect the content of growth hormone in the serum. Citalopram, like other SSRIs, can increase prolactin levels in plasma.

In a double-blind, placebo-controlled study of ECG in healthy volunteers, a change QTc (correction according to the Fridericia formula), compared with the baseline data, was 7.5 (90% confidence interval 5.9-9.1) ms for a dose of 20 mg / day and 16.7 (90% confidence interval 15.0-18, 4) ms for a dose of 60 mg / day.

Pharmacokinetics:

Absorption

Absorption of the drug is almost complete and does not depend on food intake (mean time to reach the maximum concentration in the blood plasma (T_max) for about 3 hours). Bioavailability with oral administration is approximately 80%.

Distribution

Apparent volume of distribution (V_d) β is about 12-17 l / kg. The binding of citalopram and its major metabolites to plasma proteins is less than 80%.

Biotransformation

Citalopram is metabolized to active metabolites: demethylcitalopram, didemethylcitalopram, citaloprama-N-oxide and an inactive derivative of deaminated propionic acid. All active metabolites are also SSRIs, although their action is weaker than the original compound. The predominant component in blood plasma is unchanged citalopram. The concentration of demethyl citalopram and didemethylcitalopram is usually 30-50% and 5-10% of citalopram concentration, respectively. Biotransformation of citalopram in demethyl citalopram is mediated by isoenzymes CYP2C19 (approximately 38%), CYP3A4 (approximately 31%) and CYP2D6 (approximately 31%).

Excretion

Half-life (T_1/2) is approximately 1.5 days. Systemic plasma clearance (Cl_s) citalopram is approximately 0.3-0.4 l / min, and the clearance for oral administration (Cl_oral) of about 0.4 l / min.

Citalopram is excreted mainly through the liver (85%) and through the kidneys (15%); 12-23% of the daily dose is excreted in the urine as unchanged citalopram. The hepatic (residual) clearance is approximately 0.3 l / min, and the renal clearance is about 0.05-0.08 l / min.

Linearity

The kinetics of citalopram is linear. The equilibrium concentration in plasma is reached within 1-2 weeks. The average equilibrium concentration is about 300 nmol / l (165-405 nmol / L) against the background of a daily dose of 40 mg.

Elderly patients (> 65 years)

It is shown that in elderly patients, due to a decrease in metabolic rate, a longer half-life of the drug (1.5-3.75 days) and lower clearance (0.08-0.3 l / min) is observed.The equilibrium concentration is approximately twice as high in the elderly than in young patients receiving the same dose.

Decreased liver function

Citalopram is slower in patients with impaired hepatic function. The half-life of citalopram is approximately twice as large, and the equilibrium concentration is approximately twice as high as in patients with normal liver function with the same dose.

Decreased kidney function

Citalopram is more slowly excreted in patients with moderate or moderate renal dysfunction, which, however, does not significantly affect the pharmacokinetics of citalopram. Currently, there is no information on the treatment of patients with severe renal impairment (creatinine clearance <30 mL / min).

Polymorphism

Research in vivo showed that the metabolism of citalopram is not distinguished by a clinically significant polymorphism of oxidation of sparteine / debrisoquine (CYP2D6). In patients with a weak isoenzyme activity CYP2C19 as a precautionary measure the recommended initial dose should not exceed 10 mg per day.

Indications:

Depressive episodes of moderate to severe severity and prevention of their recurrence.

Panic disorder with or without agoraphobia.

Contraindications:

Hypersensitivity to citalopram or any of the excipients.

Simultaneous reception with monoamine oxidase (MAO) inhibitors (including selegilin in 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 the medical use of these drugs. Treatment with MAO inhibitors can be started no earlier than 7 days after stopping citalopram.

Simultaneous reception with linezolid, if it is impossible to monitor the patient carefully and monitor blood pressure.

Simultaneous reception with pimozide.

Specified interval lengthening QT or congenital elongated interval QT.

Simultaneous reception with drugs that extend the interval QT.

Children and adolescence (up to 18 years of age) (efficacy and safety of use not confirmed).

Hereditary intolerance to galactose, insufficiency of lactase or impaired absorption of glucose and galactose.

Carefully:

- Haveinterval spacing QT in the anamnesis; ventricular arrhythmia, including torsade de pointes;

- Significant bradycardia;

- recently suffered acute myocardial infarction;

Decompensated heart failure;

- hypokalemia and / or hypomagnesemia (electrolyte disturbances should be corrected before treatment with citalopram);

- marked renal failure (creatinine clearance below 30 ml / min);

- severe hepatic impairment (a careful dose selection is recommended);

- pronounced suicidal behavior (careful monitoring of patients is required before the onset of improvement in a few weeks after the start of treatment);

- diabetes mellitus (it may be necessary to adjust the dose of insulin and / or oral hypoglycemic drugs);

- a tendency to bleeding (especially when used simultaneously with drugs that affect platelet function or drugs that may increase the risk of bleeding);

- simultaneous administration with an MAO inhibitor in selegiline, serotonergic drugs; drugs,

reducing the threshold of convulsive readiness; cimetidine (increase

the equilibrium concentration of citalopram), metoprolol (increasing the concentration of metoprolol), lithium and tryptophan (increasing action), pharmaceutical preparations containing St. John's wort (increased side effects); oral anticoagulants and drugs that affect blood coagulability (increased risk of bleeding); drugs that are weak metabolites of isoenzyme CYP2C19 (it is necessary to lower the initial dose);

- ethanol;

- electroconvulsive therapy;

- elderly age over 65 years (dose reduction required);

- pregnancy, the period of breastfeeding.

More detailed information about the instructions and safety precautions listed in the "Interaction with other medicinal products and other forms of interaction", "Cautions", "Pregnancy and lactation".

Pregnancy and lactation:

Published data on pregnant women (more than 2500 cases completed) showed the formation of any malformations and feto / neonatal toxicity under the influence of citalopram. Nevertheless, citalopram should not be used during pregnancy without extreme necessity and careful evaluation of potential risks and benefits.

If the use of citalopram continues in late pregnancy, especially in the third trimester, newborns should be monitored. Avoid abrupt discontinuation of the drug during pregnancy.

If the mother of SSRIs / SSRIs receives a late pregnancy, the following symptoms can occur in newborns: respiratory distress, cyanosis, apnea, convulsive seizures, instability of body temperature, feeding difficulties, vomiting, hypoglycemia, muscle hypertension, muscle hypotension, hyperreflexia, tremor, increased nervous reflex excitability, irritability, lethargy, constant crying, drowsiness and restless sleep. These symptoms can occur due to the development of the syndrome of "withdrawal" or serotonergic action. In most cases, complications develop immediately after or soon (<24 hours) after delivery. Epidemiological data suggest that the use of SSRIs during pregnancy, especially in later life,may increase the risk of developing persistent pulmonary hypertension in newborns. The observed risk was approximately 5 cases per 1000 pregnancies. In the general population, the risk of this disorder is 1-2 cases per 1000 pregnancies.

Citalopram penetrates into breast milk. It is believed that infants receive about 5% maternal daily dose of citalopram, calculated by weight (in mg / kg). Virtually no consequences for children were observed. However, the available information is not sufficient to assess the risks to the child. Therefore, during citalopram treatment, breast-feeding is not recommended.

Dosing and Administration:

Cipramil is given orally once a day. The drug can be taken at any time of the day, regardless of food intake.

Tablets of 20 and 40 mg can be divided in half.

Depression

Cipramil is prescribed once a day for 20 mg. Depending on the individual response of the patient, the dose can be increased to a maximum of 40 mg per day.

The antidepressant effect usually develops in 2-4 weeks after the start of treatment. Therapy with antidepressants is symptomatic and should continue for a sufficient period of time,usually at least 6 months after the complete elimination of the symptoms of depression in order to avoid the development of relapses. In patients with recurrent (unipolar) depression, the necessary supportive therapy can continue for several years to prevent the development of new episodes.

Panic disorder

During the first week of treatment, the recommended single dose is 10 mg / day orally, then the dose rises to 20 mg per day. Depending on the individual response of the patient, the dose can be increased to a maximum of 40 mg / day.

In the treatment of panic disorder, the maximum therapeutic effect of citalopram is achieved approximately 3 months after initiation of treatment and is maintained with continued therapy.

Elderly patients (over 65 years of age)

The daily dose for elderly patients should be reduced to half the recommended dose, i.e. up to 10-20 mg. The recommended maximum dose for elderly patients is 20 mg / day.

Children and adolescents (under 18 years of age)

Cipramil should not be used in children and adolescents under the age of 18 (see "SPECIAL INSTRUCTIONS"). In addition, there is insufficient evidence of long-term safety studies in children and adolescents regarding growth, maturation,cognitive and behavioral development.

Decreased kidney function

With mild and moderate renal failure, dose adjustments are not required. Patients with severe renal insufficiency (creatinine clearance below 30 ml / min) should be used with caipramil caution.

Decreased liver function

With mild and moderate hepatic impairment, the recommended initial dose for the first two weeks of treatment is 10 mg / day. Depending on the individual reaction of the patient, the dose may be increased to a maximum of 20 mg / day. Patients with severe hepatic insufficiency should use the drug with caution, requires a thorough titration of the dose.

Reduced isoenzyme activity CYP2C19

For patients with a weak isoenzyme activity CYP2C19 The recommended initial dose for the first two weeks of treatment is 10 mg / day. Depending on the individual reaction of the patient, the dose may be increased to a maximum of 20 mg / day.

Discontinuation of treatment

Avoid sudden cessation of treatment. When cipramil therapy is discontinued, the dose should gradually decrease for a minimum of 1-2 weeks in order to avoid the occurrence of "cancellation" reactions.If, with a decrease in the dose or discontinuation of citalopram treatment, intolerable symptoms occur, it is possible to return to the previous dose or resume the drug. Subsequently, the dose reduction can be continued, but more gradually.

Side effects:

The undesirable effects observed with Cipramil are usually poorly expressed and transient. Most often they occur in the first or second week of treatment and usually significantly weaken as the therapy continues.

The following reactions were found to be dependent on the dose used: increased sweating, dry mouth, insomnia, drowsiness, diarrhea, nausea, and weakness.

Below are the data on the incidence of adverse reactions associated with the use of SSRIs and / or citalopram observed in ≥ 1% of patients who participated in double-blind placebo-controlled studies, and in the post-registration period. The frequency is indicated as follows: very often (≥1/10), often (from ≥1/100 to <1/10), infrequently (from ≥1/1000 to <1/100), rarely (from≥1/10000 to <1/1000), very rarely (<1/10000), is unknown (can not be estimated based on existing data).

From the side of the kroen and lymphatic system: unknown - thrombocytopenia.

From the immune system: unknown - increased sensitivity, anaphylactic reactions.

From the endocrine system: unknown - insufficient secretion of anti diuretic hormone (ADH).

Metabolic disorders and eating disorders: often - decreased appetite, weight loss; infrequently - increased appetite, weight gain; rarely - hyponatremia; unknown - hypokalemia.

From the side of the psyche: often - agitation, decreased libido, anxiety, nervousness, confusion, anorgasmia (in women), unusual dreams; infrequently - aggression, depersonalization, hallucinations, mania; unknown - panic attacks, bruxism, anxiety, suicidal thoughts, suicidal behavior. Cases of the appearance of suicidal thoughts and behavior were noted during the therapy with citalopram and immediately after the withdrawal of treatment.

From the nervous system: very often - drowsiness, insomnia; often - tremor, paresthesia, dizziness, violation of attention; rarely - a syncope; rarely - large convulsive seizures, dyskinesia, taste disorders; unknown - convulsive disorders, serotonin syndrome, extrapyramidal disorders, akathisia, motor disorders.

On the part of the organs of vision: infrequently - mydriasis (dilated pupils); unknown - visual impairment.

From the side of the hearing organ and labyrinthine disorders: often - noise in the ears.

From the cardiovascular system: very often - a feeling of palpitations; infrequently bradycardia, tachycardia; rarely bleeding; unknown - interval lengthening QT on an electrocardiogram, ventricular arrhythmia, including the type of "pirouette" (torsade de pointes), orthostatic hypotension.

From the respiratory system, chest and mediastinum: often - yawning; unknown - epistaxis.

From the gastrointestinal tract: very often - dry mouth, nausea; often diarrhea, vomiting, constipation; unknown - gastrointestinal bleeding (including rectal bleeding).

From the liver and bile ducts: rarely - hepatitis; unknown - violations of the liver's functional parameters.

From the skin and subcutaneous tissues: very often - excessive sweating; often itching; infrequently - hives, alopecia, rash, purpura, photosensitization; unknown - ecchymosis, angioedema.

From the musculoskeletal and connective tissue: often - myalgia, arthralgia.

From the side of the kidneys and urinary tract: unknown - urinary retention.

On the part of the reproductive system and mammary glands: often - impotence, ejaculation, lack of ejaculation; infrequently - menorrhagia (in women); unknown - galactorrhea, metrorrhagia (uterine bleeding), priapism (in men).

On the part of the body as a whole and violations at the site of administration: often - weakness; infrequently - swelling; rarely - hyperthermia.

Epidemiological studies, predominantly involving patients aged 50 years and older, have shown the existence of an increased risk bone fractures in patients taking SSRIs and tricyclic antidepressants. The mechanism that leads to this risk is unknown.

Cases lengthening interval QT and ventricular arrhythmias, including arrhythmias of the "pirouette" type (torsade de pointes), It was reported in the Post-registration period, predominantly in female patients with hypokalemia or existing elongation interval QT and other heart diseases.

Cancel citalopram (especially sharp) often leads to the appearance of withdrawal symptoms. The most common are dizziness, sensitivity disorders (including paresthesia),sleep disorders (including insomnia and intense dreams), agitation or anxiety, nausea and / or vomiting, tremors, confusion, sweating, headache, diarrhea, palpitations, emotional instability, irritability, visual disturbances. Typically, these effects are mild or moderate and quickly pass, however, in some patients, they may manifest themselves in a more acute form and / or longer. In the event that citalopram therapy is no longer required, it is recommended to gradually phase out the drug by lowering its dose.

Overdose:

Clinical data on the overdose of citalopram are limited and in many cases are associated with concomitant overdose of other drugs or alcohol. Cases of overdose of citalopram with a fatal outcome have been reported, however, the majority of lethal cases were associated with concomitant overdose of other drugs.

Symptoms

In case of an overdose, the following symptoms were witnessed: convulsions, tachycardia, drowsiness, lengthening of the interval QT, coma, vomiting, tremor, hypotension, cardiac arrest, nausea, serotonin syndrome, agitation, bradycardia, dizziness, bundle blockade, lengthening of the complex QRS, hypertension, mydriasis, arrhythmia of the type "pirouette", stupor, sweating, cyanosis, hyperventilation, as well as atrial and ventricular rhythm disturbances.

Treatment

There is no specific antidote. Treatment is symptomatic and supportive. Gastric lavage should be performed and given Activated carbon and osmotic laxatives (for example, sodium sulfate). In case of a violation of consciousness, the patient must be intubated. It is necessary to monitor the ECG and indicators of vital functions.

ECG monitoring is recommended in case of an overdose in patients with congestive heart failure / bradyarrhythmias, in patients receiving concomitant treatment with drugs that extend the interval QT, or in patients with metabolic disorders, for example, with hepatic insufficiency.

Interaction:

Pharmacodynamic interaction

There have been described cases of the development of serotonin syndrome in the joint use of citalopram with moclobemide and buspirone.

Contraindicated combinations

MAO inhibitors

Simultaneous use of citalopram and MAO inhibitors can lead to serious undesirable consequences, including serotonin syndrome.

Cases of serious and sometimes lethal reactions in patients receiving SSRIs and a monoamine oxidase inhibitor (MAOI), including irreversible MAOI selegiline and reversible MAOIs linezolid and moclobemide, as well as in patients who recently stopped taking SSRIs and started taking MAOI.

In some of the cases presented, there were signs resembling serotonin syndrome.

Symptoms of citalopram interaction with MAOI included: hyperthermia, rigidity, myoclonus, autonomic instability with rapid fluctuations in vital signs, changes in mental status, which included confusion, irritability and excessive agitation, progressing to delirium and to whom.

Drugs that extend the interval QT

Pharmacokinetic and pharmacodynamic studies of the interaction between citalopram and drugs extending the interval QT, were not conducted. Summation of the effect of citalopram and these drugs can not be ruled out. Thus, simultaneous application of citalopram and drugs extending the interval QT, such as antiarrhythmics of classes IA and III, antipsychotics (eg, phenothiazine derivatives, pimozide, haloperidol), tricyclic antidepressants, some antimicrobial agents (for example, sparfloxacin, moxifloxacin, erythromycin IV, pentamidine, antimalarials, especially halofantrine), some antihistamines (astemizole, misolastine), etc., is contraindicated.

Pimozide

In the study, a single dose of pimozide in a dose of 2 mg to subjects taking the racemic form of citalopram at a dose of 40 mg / day for 11 days resulted in an increase in the values AUC and C_mOh pimozide, although not always. The combined use of pimozide and citalopram led to an average interval elongation QTc approximately 10 msec. Given the development of interaction with a low dose of pimozide, simultaneous administration of citalopram and pimozide is contraindicated.

Combinations that require caution

Selegiline (selective MAO B inhibitor)

Studies of pharmacokinetic and pharmacodynamic interaction with concurrent use of citalopram (20 mg / day) and selegiline (10 mg / day) (dose selective for MAO B) revealed no clinically significant interactions. The simultaneous use of citalopram and selegiline (at a dose exceeding 10 mg per day) is not recommended.

Serotonergic drugs

Lithium and tryptophan

In clinical trials of simultaneous use of lithium and citalopram, no pharmacodynamic interactions were identified. However, it has been reported that the effect is enhanced with the simultaneous administration of SSRIs with lithium or tryptophan, so the use of such combinations should be done with caution. Monitoring of the level of lithium in the blood is carried out as usual. Joint use with such serotonergic drugs as tramadol and sumatriptan, can lead to an increase in serotonergic effects. Until there is accurate data on possible interactions, the combination of citalopram with 5-HT receptor agonists, such as sumatriptan and other triptans, is not recommended.

St. John's wort perforated

Dynamic interaction of SSRIs with herbal preparations containing St. John's wortHypericum perforatum), can lead to an increase in the frequency of adverse reactions. Pharmacokinetic interaction has not been studied.

Anticoagulants and agents that affect blood coagulability

Caution should be exercised in appointing citalopram to patients,who receive treatment with anticoagulants, drugs that affect the function of platelets, such as non-steroidal anti-inflammatory drugs (NSAIDs), acetylsalicylic acid, dipyridamole and ticlopidine, or other drugs (eg, atypical antipsychotics, phenothiazines, tricyclic antidepressants) that may increase the risk of bleeding.

Electroconvulsive therapy (ECT)

Data from clinical trials demonstrating the risks or benefits of concurrent use of ECT and citalopram are not available.

Alcohol

There were no pharmacodynamic or pharmacokinetic interactions between citalopram and alcohol. Nevertheless, a joint intake of citalopram and alcohol is not recommended.

Drugs that reduce the threshold of convulsive readiness SSRIs can reduce the threshold of convulsive alertness. It is advisable to use caution when combined with other drugs that can reduce the threshold of convulsive readiness (for example, antidepressants [tricyclics, SSRIs], neuroleptics [phenothiazines, thioxanthenes and butyrophenones], mefloquine, bupropion and tramadol).

Desipramine, imipramine

In pharmacokinetic studies, there was no change in the level of either citalopram or imipramine, although the level of desipramine, the main metabolite of imipramine, was increased. With the simultaneous use of citalopram and desipramine, the level of the latter in plasma was elevated. You may need to reduce the dose of desipramine.

Neuroleptics

The experience of using citalopram did not reveal clinically significant interactions with neuroleptics. However, as in the case of other SSRIs, the possibility of pharmacodynamic interaction is not excluded.

Pharmacokinetic interactions

Biotransformation of citalopram to demethylcitalopram is mediated by isoenzymes of the cytochrome P450 system CYP2C19 (about 38%), CYP3A4 (about 31%) and CYP2D6 (about 31%). The fact that citalopram is metabolized by more than one isoenzyme, suggests that inhibition of its biotransformation is unlikely, since the degree of inhibition of one of the enzymes can be compensated by others. Therefore, the simultaneous administration of citalopram with other drugs has a very low probability of pharmacokinetic interactions.

Food

It has not been reported that eating influences the absorption and other pharmacokinetic properties of citalopram.

The effect of other drugs on the pharmacokinetics of citalopram

When combined ketoconazole (strong inhibitor of isoenzyme CYP3A4) did not change the pharmacokinetics of citalopram.

Pharmacokinetic studies of the interaction of lithium and citalopram did not reveal any interactions.

Cimetidine (a strong inhibitor of isoenzymes CYP2D6, 3A4 and 1A2) caused a moderate increase in the level of equilibrium concentration of citalopram. It is advisable to use caution in the administration of citalopram in combination with cimetidine. Dose adjustment may be required.

Effect of citalopram on the pharmacokinetics of other drugs

Pharmacokinetic / pharmacodynamic studies the interaction of citalopram and metoprolol (the substrate of the isoenzyme CYP2D6) showed a 2-fold increase in the concentration of metoprolol, but there was no statistically significant increase in the effect of metoprolol on blood pressure and heart rhythm in healthy volunteers. Care must be taken when using metoprolol and citalopram together.Dose adjustment may be required.

Citalopram and demethylcitalopram are insignificant inhibitors of isoenzymes CYP2C9, CYP2E1 and CYP3A4 and only weak inhibitors of CYP1A2, CYP2C19 and CYP2D6 in comparison with other SSRIs considered to be significant inhibitors.

Levomepromazine, digoxin, carbamazepine

No changes or only very small clinically significant changes were observed with the simultaneous use of citalopram with substrates CYP1A2 (clozapine and theophylline), CYP2C9 (warfarin), CYP2C19 (imipramine and mephenytoin), CYP2D6 (sparteine, imipramine, amitriptyline, risperidone) and CYP3A4 (warfarin, carbamazepine (and its metabolite carbamazepine-epoxide) and triazolam).

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

Special instructions:

Use in children and adolescents under 18 years of age

Antidepressants should not be given to children and adolescents under the age of 18 years. In clinical trials, among children and adolescents who took antidepressants, more often than inthe placebo group had cases of suicidal behavior (suicide attempts and suicidal thoughts) and hostility (with a predominance of aggressive behavior, a tendency to confrontation and irritation).

When using drugs belonging to the therapeutic group of SSRIs, including citalopram, the following should be considered.

Paradoxical anxiety

Some patients with panic disorder may experience anxiety at the onset of antidepressant therapy. Such a paradoxical reaction usually occurs within the first two weeks after the start of treatment. To reduce the likelihood of anxiogenic action, it is recommended to use low initial doses.

Hyponatremia

When SSRIs were used, there were reports of rare cases of hyponatremia, apparently due to inadequate secretion of antidiuretic hormone (ADH). This reaction was generally reversible in the event of discontinuation of drug treatment. The risk of occurrence was higher in elderly women.

Suicide / suicidal thoughts or clinical worsening

Depression is associated with an increased risk of suicidal thoughts, self-harm and suicide (suicidal events). This risk persists until the development of stable remission.Since there may be no improvement in the first few weeks of treatment or even a longer period of time, patients should be under constant surveillance to detect such an improvement in a timely manner. Clinical experience indicates that the risk of suicide is increased in the early stages of recovery.

Other mental disorders for which treatment is prescribed citalopram, may also be associated with an increased risk of suicidal events. In addition, these conditions can be a concomitant pathology in relation to a depressive episode. When treating patients with other mental disorders, the same precautions should be followed as in the treatment of patients with a depressive episode.

Patients who have a history of suicidal tendencies, or patients with a significant level of meditation on suicidal topics prior to initiation of treatment are more at risk of suicidal thoughts or suicide attempts, so they should be closely monitored during treatment. A meta-analysis of placebo-controlled clinical trials of antidepressants with the participation of adult patients with mental disorders showed,that when taking antidepressants in patients younger than 25 years there is an increased risk of suicidal behavior compared with taking placebo. Drug treatment of these patients, and in particular of patients with a high degree of suicidal risk should be accompanied by careful monitoring, especially at an early stage of treatment and with dose changes. Patients (and caregivers) should be warned about the need to monitor any manifestations of clinical impairment, suicidal behavior or thoughts, and unusual behavioral changes, and seek medical advice immediately if these symptoms appear.

Akathisia / psychomotor anxiety

The use of SSRI / SSRIs drugs is associated with the development of akathisia, characterized by a feeling of subjectively unpleasant or intolerable motor anxiety, restlessness and the need to move. Often patients in this state can not sit or stand still. Most often this condition occurs during the first weeks of treatment. In patients with such symptoms, increasing the dose can cause a sharp deterioration in the condition.

Mania

Patients with bipolar affective disorder may develop a manic phase. When developing a manic state, citalopram should be discontinued.

Convulsive seizures

When taking antidepressants, there is a risk of seizures. Any patient in the event of a convulsive seizure citalopram should be canceled. Citalopram Do not use in patients with unstable epilepsy; with controlled seizures careful monitoring is necessary. In case of an increase in the frequency of seizures citalopram should be canceled.

Diabetes

In patients with diabetes mellitus, the use of SSRIs can alter the concentration of glucose in the blood. In this case, you may need to adjust the dose of insulin and / or oral hypoglycemic drugs.

Serotonin syndrome

In rare cases, when SSRI was taken, the development of serotonin syndrome was reported. The combination of such symptoms as agitation, myoclonus and hyperthermia can indicate the development of this condition. When such phenomena occur citalopram should be immediately withdrawn and symptomatic treatment started.

Serotonergic drugs

Citalopram should not be used in conjunction with drugs that have a serotonergic effect, such as sumatriptan or other triptans, tramadol, oxytryptan and tryptophan.

Bleeding

There are reports of the development of skin hemorrhages, such as ecchymosis, gynecological, gastrointestinal bleeding and other hemorrhagic complications from the skin or mucous membranes on the background of the SSRI. Caution should be exercised when using SSRIs and drugs that affect the function of platelets or drugs that may increase the risk of bleeding and also in the treatment of patients with hemorrhagic disorders in history.

Electroconvulsive therapy (ECT)

Because the clinical experience of the simultaneous use of SSRIs and electroconvulsive therapy (ECT) is limited, caution and caution should be exercised while using citalopram and ECT.

Reversible selective inhibitors of MAO A

Simultaneous administration of citalopram and MAO-A inhibitors is not recommended because of the risk of developing a serotonin syndrome.

St. John's wort perforated

Do not use citalopram and preparations containing St. John's wort (Hypericum perforatum), since this can increase the risk of unwanted reactions.

Psychosis

Treatment of psychotic patients with a depressive episode can intensify the manifestations of psychotic symptoms.

Symptoms of withdrawal upon discontinuation of SSRI therapy

Symptoms of cancellation occur quite often, especially with a sharp cessation of therapy.

The likelihood of withdrawal symptoms may depend on a number of factors, including the duration of treatment, the dose of the drug and the rate of its reduction.

The most common reported development of the following manifestations: dizziness, sensitivity disorders (including paresthesia), sleep disorders (including insomnia and vivid dreams), agitation or anxiety, nausea and / or vomiting, tremor, confusion, sweating, headache, diarrhea, heart palpitations, emotional lability, irritability and visual impairment. Usually these manifestations are of mild or moderate severity, but in some patients they can be severe.

Usually such manifestations develop during the first days after drug withdrawal, but there are some reports of the development of such conditions in patients who accidentally missed the next dose.

In most cases, these complications stop within 2 weeks, although in some patients the symptomatology may persist for 2-3 months or longer. Therefore, before the end of the course of taking citalopram, it is recommended to gradually reduce the dose of the drug for a period of several weeks to several months, depending on the patient's condition (see "DOSAGE AND ADMINISTRATION").

Interval lengthening QT

It was found that citalopram causes dose-dependent lengthening of the interval QT. In the post-marketing period there were reported cases of lengthening the interval QT and ventricular arrhythmias, including torsade de pointes, predominantly in female patients, with hypokalemia or pre-existing interval lengthening QT or other heart diseases.

The drug is recommended for use with caution in patients with significant bradycardia, in patients who have recently had a myocardial infarction, or with decompensated heart failure.

Electrolyte disorders, such as hypokalemia and hypomagnesemia, increase the risk of malignant arrhythmias and should therefore be corrected before initiating citalopram therapy.

In patients with compensated heart disease, an ECG study is necessary before starting treatment.

In case of any signs of cardiac arrhythmias against the background of citalopram treatment, the latter should be abolished and an ECG study performed.

Excipients

Tablets contain lactose monohydrate. Patients with hereditary intolerance to galactose, a deficiency of lactase, or a violation of glucose-galactose absorption should not receive treatment with this drug.

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

Citalopram has a minimal or moderate ability to influence the ability to drive and work with machinery. Psychoactive drugs can influence the decision-making process and the ability to respond to emergencies. Patients should be warned about the potential impact on the ability to drive and work with machinery.

Form release / dosage:

Tablets, film-coated, 20 mg and 40 mg.

Packaging:

20 mg - 14, 28 and 56 pcs.

For 14 tablets in a blister of PVC, Al-Folga. 1, 2 or 4 blisters with instructions for use in a cardboard box.

40 mg - 28 pcs.

For 14 tablets in a blister of PVC, Al-Folga. 2 blisters with instructions for use in a cardboard box.

Storage conditions:

Store at a temperature not exceeding 30 ° C.

Keep out of the reach of children.

Shelf life:

5 years.

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

Terms of leave from pharmacies:On prescription

Registration number:P N014835 / 01-2003

Date of registration:09.02.2009

The owner of the registration certificate:H. Lundbeck A / SH. Lundbeck A / S Denmark

Manufacturer: & nbsp

H.LUNDBECK, A / S Denmark

Representation: & nbspLUNDBEK EXPORT A / C LUNDBEK EXPORT A / C Denmark

Information update date: & nbsp27.09.2015

Illustrated instructions

Instructions

Cipramil (Cipramil)