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

Excipients: cellulose microcrystalline 46.90 / 93.80 / 187.60 mg, pregelatinized starch 20.20 / 40.40 / 80.80 mg, magnesium stearate 0.40 / 0.80 / 1.60 mg, Opadrai II [polyvinyl alcohol (1.28 / 2.56 / 5.12) mg, macrogol (0.65 / 1.30 / 2.60) mg, talc (0.47 / 0.94 / 1.88) mg, titanium dioxide 0.80 / 1.60 / 3.20) mg] 3.20 mg / 6.40 mg / 12.80 mg.

Description:Round tablets of biconvex form, covered with a film coat of white color. On the cross-section, the inner layer is white or white with a yellowish tint of color.

Pharmacotherapeutic group:antidepressant

ATX: & nbsp

N.06.A.B.04 Citalopram

Pharmacodynamics:

Citalopram is an antidepressant belonging to the group of selective serotonin reuptake inhibitors (SSRIs). Has a strong ability to inhibit serotonin reuptake, has or has a very weak ability to bind to a variety of receptors, including gamma-aminobutyric acid (GABA) receptors, H₁-gistaminovye, D₁- and D₂-dophamine, alpha1-, alpha2-, beta-adrenergic; benzodiazepine and m-cholinergic receptors, which causes a virtually complete absence of such undesirable effects as negative chrono-, dromo- and inotropic effects, orthostatic hypotension, sedation, and dry mouth. Citalopram only to a very small extent inhibits the isoenzyme CYP2D6, and, therefore, practically does not interact with drugs metabolized by this enzyme. Thus, side effects and toxic effects are manifested to a much lesser extent. The antidepressant effect usually develops after 2-4 weeks of treatment.

Citalopram has no effect on serum levels of prolactin and growth hormone. Citalopram does not impair cognitive / intellectual functions and psychomotor function and has practically no sedative effect.

Citalopram in doses exceeding 40 mg per day can cause abnormal changes in the electrical activity of the heart (lengthening of the interval QT on the ECG).

Pharmacokinetics:

Bioavailability of citalopram is 80% and practically does not depend on food intake. Maximum concentration (FROM_mOh) in plasma is achieved on average through 3 hours. Pharmacokinetics has a linear dose-dependent character with single and multiple doses (doses in the range of 10-60 mg per day). When taking 1 time per day, the equilibrium concentration in the plasma is established after 7-14 days of therapy. The volume of distribution is about 12-17 l / kg. Binding to plasma proteins - no more than 80%. The plasma is present unchanged. Penetrates into breast milk.

Metabolized by demethylation, deamination and oxidation involving cytochrome P450 (isoenzymes CYP3A4 and CYP2C19, to a lesser degree CYP2D6) with the formation of pharmacologically less active metabolites. Inhibition of one of these enzymes can be compensated by other enzymes.Half-life (T_1/2) citalopram is 1.5 days (36 hours). Excretion is performed by the kidneys (15%) and the liver (85%). 12-23% of citalopram is excreted unchanged through the kidneys. Hepatic clearance is about 0.3 l / min, renal clearance is 0.05-0.08 l / min.

Patients over the age of 65:

There is a longer half-life and lower clearance due to a decrease in metabolism.

Lack of liver function:

In patients with reduced liver function citalopram output more slowly. The half-life of citalopram is almost doubled and the equilibrium concentrations citalopram in plasma is almost twice as high as in patients with normal liver function after taking a similar dose.

Lack of kidney function:

In patients with mild to moderate renal dysfunction, excretion of citalopram proceeds more slowly without a significant effect on pharmacokinetics. Care should be taken in patients with severe renal insufficiency (creatinine clearance below 30 ml / min).

Indications:

Depressive episodes of moderate to severe severity.

Panic disorders.

Contraindications:

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

- Citalopram should not be used in combination with monoamine oxidase (MAO) inhibitors, including selegiline, moclobemide, linezolid (antibiotic), and within 14 days after discontinuation. Treatment with MAO inhibitors can be initiated no earlier than 7 days after stopping citalopram;

- Citalopram is contraindicated with simultaneous use with drugs that extend the interval QT on the ECG (in particular, with pimozide), as well as with the innate lengthening of the interval QT;

- Children under the age of 18 are a contraindication for the use of citalopram, since the efficacy and safety of its use at this age is not established.

Pregnancy and lactation:

Do not assign citalopram pregnant and breastfeeding women, if the potential clinical benefit does not prevail over the theoretical risk, because the safety of the drug during pregnancy and lactation in women is not established.

The use of citalopram in the third trimester of pregnancy can adversely affect the psychophysical development of the newborn.The following abnormalities are possible in newborns whose mothers have taken selective serotonin reuptake inhibitors up to the time of delivery: respiratory failure, cyanosis, dyspnea, convulsions, temperature instability, feeding difficulties, vomiting, hypoglycemia, muscle hypertension or hypotension, hyperreflexia, tremor, nervousness, irritability, lethargy, constant crying, drowsiness and insomnia.

Epidemiological evidence suggests that the use of SSRIs during pregnancy, especially late in pregnancy, may increase the risk of persistent pulmonary hypertension in newborns. The observed risk was in 5 cases per 1000 pregnancies. In the general population, the risk of 1 to 2 cases of persistent pulmonary hypertension of newborns per 1000 pregnancies.

Such violations may indicate serotonergic effects or the occurrence of the "withdrawal" syndrome. In case of using citalopram during pregnancy, its reception should not be abruptly interrupted.

Dosing and Administration:

Citalopram is taken orally once a day (not liquid, squeezed with a small amount of liquid).The drug can be used at any time of the day, regardless of food intake, it is desirable to take the drug at the same time of day.

Depression:

Therapy of depression begins with the administration of 20 mg of citalopram per day. Depending on the individual reaction of the patient and the severity of depression, the dose may be increased to a maximum of 40 mg per day.

Panic disorder:

For panic disorders within 1 week, the recommended dose is 10 mg per day, then the dose rises to 20 mg per day. The daily dose, depending on the individual reaction of the patient, can be further increased to 40 mg per day.

Patients aged 65 years older:

The recommended daily dose for the elderly is 10-20 mg. Depending on the individual reaction and severity of depression, the dose may be increased to a maximum of 20 mg per day.

Impaired renal function:

In chronic renal failure, a moderate and moderate degree of correction of the dosing regimen is not required. In patients with severe renal failure (creatinine clearance below 30 ml / min) caution in choosing a dose is required.

Disrupted liver function:

In patients with mild and moderate hepatic insufficiency, the initial dose is 10 mg per day for the first two weeks.Depending on the reaction, the dose can be increased to 20 mg per day. In patients with severe hepatic insufficiency, extreme caution is required in choosing a dose.

Patients with low isoenzyme activity CYP2C19:

In patients with low isoenzyme activity CYP2C19 The initial dose is 10 mg per day for two weeks. Depending on the reaction, the dose can be increased to 20 mg per day.

Duration of treatment:

The effect manifests itself in 2-4 weeks, the duration of the course of treatment is determined by the patient's condition, the effectiveness and tolerability of the therapy and an average of 6 months.

Features of the drug when it is canceled:

Symptomatology, which can be noted with a sharp abolition of citalopram, is not characteristic. This is most often dizziness, headache, paresthesia, sleep disturbance, asthenia, nervousness, tremor, nausea and / or vomiting.

If treatment is completed citalopram It is necessary to cancel gradually over several weeks in order to avoid the "withdrawal" syndrome. In most cases, it takes about 2 weeks, but in each case the doctor solves this question individually: for some patients it may take 2-3 months or more.

Side effects:

As in the case of the use of other SSRI drugs, undesirable side reactions are noted while using citalopram, but they are transient and weakly expressed.

Adverse reactions with the use of citalopram are observed during the first one or two weeks of treatment and usually significantly weaken as the patients improve.

Frequency of adverse reactions: very often - ≥ 10%; often -≥1%, but <10%; infrequently - ≥ 0,1%, but <1%; rarely - ≥ 0.01%, but <0.1%; very rarely - <0.01%.

The following adverse reactions may occur:

Allergic reactions: infrequently - hypersensitivity; very rarely - anaphylactic reactions.

From the central nervous system: very often - drowsiness, headache, tremor, dizziness; often - migraine, paresthesia, sleep disorder; infrequently - extrapyramidal disorders, convulsions; rarely - serotonin syndrome (combination of excitation, tremor, myoclonus and hyperthermia); frequency unknown - psychomotor agitation, akathisia.

From the psychic sphere: very often - agitation, nervousness; often - decreased libido, violation of orgasm (in women), anxiety, confusion, drowsiness, impaired concentration, strange dreams, amnesia; infrequently - aggression, depersonalization, hallucinations, mania, euphoria, increased libido; frequency unknown - panic attacks, bruxism, suicidal thoughts.

From the digestive system: very often - dry mouth, nausea, constipation; often - vomiting, flatulence, diarrhea, abdominal pain, hepatitis; frequency unknown - gastrointestinal bleeding.

From the cardiovascular system: very often - a feeling of palpitations; often - tachycardia, arterial hypertension, orthostatic hypotension; rarely - bradycardia, lowering blood pressure, arrhythmia; frequency unknown - interval elongation QT on the ECG.

On the part of the organs of hematopoiesis: rarely - hemorrhage (eg, gynecological bleeding, bleeding of the gastrointestinal tract, ecchymosis and other forms).

From the sense organs: very often - a violation of accommodation; often - violation of taste, visual impairment, infrequent - ringing in the ears.

From the respiratory system: often - rhinitis, sinusitis; infrequently - cough; rarely - dyspnoea.

On the part of the reproductive system: often - the violation of sexual function, namely the violation of ejaculation, decreased libido, impotence, menstrual irregularities; rarely - galactorrhea.

From the urinary system: often - painful urination, polyuria.

Metabolic disorders: often - decreased appetite, weight loss, increased appetite; rarely - insufficient secretion of antidiuretic hormone (ADH), weight gain, hyponatremia; hypokalemia.

From the skin: very often - excessive sweating, often - skin rash, itching; infrequently - photosensitization, hives, alopecia, purpura; frequency unknown - angioedema, bruising.

From the musculoskeletal system: infrequently - myalgia, arthralgia, increased risk of injuries and fractures.

Laboratory indicators: often - changes in laboratory parameters of liver function; infrequently - increased activity of "hepatic" enzymes, alteration of the electrocardiogram (lengthening of the interval QT), hyponatremia.

Other: rarely - hyperthermia, yawning, increase or decrease in body weight.

Overdose:

Overdose Symptoms: spasms, lethargy, tachycardia, bradycardia, hypotonia or hypertension, nausea, vomiting, tremor, serotonin syndrome, agitation, dizziness, mydriasis, stupor, sweating, cyanosis of the skin, heart failure, bundle branch block, hyperventilation, atrial fibrillation , ventricular arrhythmia, coma.

Coma and fatal cases of citalopram overdose are extremely rare, most of them involve simultaneous overdose with other drugs.

Treatment of overdose: there is no specific antidote. In case of an overdose, gastric lavage should be carried out as soon as possible. Treatment is symptomatic and supportive. Recommended medical surveillance, with loss of consciousness and disturbance of respiration - intubation, as well as careful monitoring of ECG and other vital functions as a high risk of fatal arrhythmias accompanied by sinus tachycardia, nodal rhythm, lengthening the interval QTIn particular, may develop arrhythmias such as "pirouette", ventricular arrhythmia.

Interaction:

Contraindicated joint application:

- With MAO inhibitors

Concomitant treatment with MAO inhibitors is contraindicated (both non-selective and selective) in connection with the risk of serious side effects, including serotonin syndrome. Citalopram should not be used in combination, including with selegiline, moclobemide, linezolid (antibiotic), etc., and also within 14 days after discontinuation of their administration. Treatment with MAO inhibitors can be started no earlier than 7 days after stopping citalopram.

- With funds, extending the interval QT

Do not use with medications that extend the interval QT, such as antiarrhythmics (procainamide, amiodarone and others), antipsychotics / antipsychotics (for example, phenothiazine derivatives, pimozide, haloperidol), tricyclic antidepressants and SSRIs (fluoxetine), antimicrobial agents (macrolide antibiotics and their analogues, for example, erythromycin, clarithromycin; derivatives of quinolone and fluoroquinolone: sparfloxacin, moxifloxacin; pentamidine), blockers H₁-gistaminovyh receptors (astemizole, mizolastin), antifungal agents of the azole series (ketoconazole, fluconazole), domperidone, ondansetron, because the citalopram in doses exceeding 40 mg per day can cause abnormal changes in the electrical activity of the heart (lengthening of the interval QT on the ECG) and lead to a violation of the heart rate (including the development of arrhythmias like "pirouette"), which can be fatal.

- Pimozide

Simultaneous use of pimozide and citalopram is contraindicated, as their combined use lengthens the interval QT. This also applies to tools such as amitriptyline, maprotiline, venlafaxine, terfenadine, haloperidol, droperidol, chlorpromazine, thioridazine.

Joint application CItalyama must be performed with caution:

Citalopram can reduce the threshold of convulsive readiness. Care should be taken while taking other drugs that reduce the threshold of convulsive readiness (tricyclic antidepressants, SSRIs, neuroleptics - derivatives of phenothiazine, thioxanthene and butyrophenone, mefloquine and tramadol).

With the simultaneous use of citalopram and tryptophan, cases of increased actionpreparation. It is advisable not to combine with the administration of citalopram serotonergic drugs, such as sumatriptan or other triptans, and tramadol.

Simultaneous use of citalopram and preparations containing St. John's Wort (perforated)Hypericum perforatum) can lead to an increase in side effects.

With simultaneous application cimetidine causes a moderate increase in the equilibrium concentration of citalopram in the blood. Therefore, caution should be exercised when assigning the maximum doses of citalopram simultaneously with the use of high doses of cimetidine.

With the simultaneous use of citalopram with indirect anticoagulants and other means that affect blood clotting (atypical antipsychotics and phenothiazine derivatives, most tricyclic antidepressants, acetylsalicylic acid and non-steroidal anti-inflammatory drugs, ticlopidine and dipyridamole), blood clotting may occur. In such cases, at the beginning or end of citalopram therapy, regular monitoring of blood coagulability is necessary.

With a simultaneous appointment with warfarin, prothrombin time increases by 5%.

There was no interaction between citalopram and alcohol. However, as in the case of other psychotropic drugs, simultaneous use of citalopram and alcohol is not recommended.

In studies in vitro revealed that citalopram is converted into its demethylated derivatives with the participation of isoenzymes CYP2C19 and CYP3A4, and also with a small contribution of the isoenzyme CYP2D6. It has been proved that inhibition of one of the enzymes can be compensated by other enzymes. The inhibitory effect of citalopram on these and other isoenzymes of cytochrome P450 is weak or inessential, therefore citalopram has a low ability for clinically relevant drug interactions known to the situation. However, caution is needed if citalopram is prescribed together with drugs that are metabolized mainly by isoenzyme CYP2D6 n have a low therapeutic index. Although clinical data on multiple-dose pharmacokinetic studies are not available, data are available in vitro (model of human liver microsomes), which show a delay in the formation of demethylated citalopram derivatives by 45-60% and by 75-85% compared with the control after the addition of ketoconazole and omeprazole, respectively.This can justify the necessary caution in these cases when co-administered with citalopram such strong inhibitors CYP3A4, how ketoconazole, itraconazole, fluconazole, or such strong inhibitors CYP2C19, as omeprazole, esomeprazole, fluvoxamine, ticlopidine, lansoprazole, since their joint administration with citalopram can significantly reduce the clearance of citalopram. Therefore, the maximum recommended dose of citalopram for patients taking together isoenzyme inhibitor preparations CYP2C19, should not exceed 20 mg / day, including because it increases the risk of lengthening the interval QT.

The combined use of citalopram with imipramine or desipramine does not affect the concentration of imipramine and citalopram, but increases the concentration of desipramine; correction of dose of desipramine may be necessary.

Special instructions:

Children under 18 years of age are contraindicated for the use of citalopram, since the efficacy and safety of its use at this age is not established.

In connection with the possibility of suicide attempts, patients with depression need careful monitoring of patients at the beginning of treatment and the appointment of minimum effective doses to reduce the risk of overdose.This precaution should be followed in the treatment of other mental disorders due to the possibility of concurrent depressive episode.

Depression is characterized by the risk of suicidal actions, which can persist until a significant remission is achieved. In this regard, at the beginning of treatment, a combination with drugs from the group of benzodiazepines or neuroleptic drugs and the constant medical control (entrusting the authorized persons with storage and dispensing of drugs) can be shown. In the treatment of panic disorders with the appointment of antidepressants and / or benzodiazepines, anxiety or anxiety is significantly increased in some patients in response to the treatment initiated. This condition (called specialists "pathological disinhibition" or simply "paradoxical anxiety," the term itself has not yet been approved) is regarded as a rare phenomenon, although this pathological reaction has been documented repeatedly in the scientific literature. This "paradoxical anxiety" usually decreases within the first few weeks after the start of treatment. It is recommended to start with a low dose to reduce the risk of paradoxical anxiety.The abolition of the drug in this case is recommended if such a paradoxical reaction does not disappear for a long time, and if such complications of therapy exceed the benefits of the treatment.

In children, adolescents and young people (under 24 years) with depression and other mental disorders, antidepressants, compared with placebo, increase the risk of suicidal thoughts and suicidal behavior. Therefore, the appointment of citalopram or any other antidepressant in this category of patients should correlate the risk of suicide and the benefits of their use. In short-term studies in people over 24 years of age, the risk of suicide did not increase, but in people older than 65 years, it declined slightly. During treatment with antidepressants, all patients should be monitored for early detection of suicidal tendencies.

It should be applied Citalopram with caution in renal insufficiency (creatinine clearance below 30 ml / min), hypomania, mania, pharmacologically uncontrolled epilepsy, depression with suicidal attempts, diabetes, cirrhosis, tendency to bleeding; simultaneous admission with drugs,reducing the threshold of convulsive readiness and causing hyponatremia, with ethanol, as well as with drugs metabolized by isoenzyme CYP2C19.

Citalopram can cause a dose-dependent lengthening interval QT, which can lead to a disturbance of the heart rhythm.

Hyponatremia develops due to impaired secretion of antidiuretic hormone, especially a high level of risk in older women.

Treatment with citalopram can alter glycemic control in patients with diabetes mellitus. The dose of insulin and / or oral hypoglycemic agents should be adjusted.

It is rare to develop akathisia, characterized by a constant or recurring feeling of internal motor anxiety and manifested in the inability to sit quietly in one position for a long time or remain without movement for a long time. It takes place during the first weeks of treatment.

In patients with bipolar a disorder may give rise to mania. Then the citalopram treatment should be stopped.

It is necessary to use caution citalopram in the presence of drug dependence (including in the anamnesis) and epileptic seizures in the anamnesis.

Citalopram should not be used in combination with monoamine oxidase (MAO) inhibitors (see "Contraindications" and "Interactions with other medicines").

With mild to moderate impairment of renal function, dose adjustment is not required, with severe renal dysfunction, caution is required. If the liver function is limited, the drug intake is limited to the minimum recommended doses. In elderly patients, a dose reduction of citalopram is required.

When developing a manic condition, the drug should be discarded.

Clinical experience of simultaneous application of SSRIs and electroconvulsive therapy is inadequate, therefore caution is required.

At the beginning of treatment, insomnia and anxiety can occur, which can be resolved by adjusting the initial dose.

A sharp cessation of therapy with citalopram can lead to the syndrome of "withdrawal". There may be such undesirable reactions, such as dizziness, headaches, nausea. To avoid the occurrence of the "withdrawal" syndrome, a gradual withdrawal of the drug within a few weeks is necessary.

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

Citalopram should be used with caution in persons whose activities are related to mechanisms or the management of moving funds. Citalopram does not reduce the intellectual ability and speed of psychomotor reactions, however, patients may expect some decrease in attention and concentration due to the existing disease, adverse reactions from the treatment or both.

Form release / dosage:

Tablets, film-coated, 10 mg, 20 mg and 40 mg.

Packaging:

For 10 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

1, 2, 3, 4 or 5 contour mesh packages together with the instruction for use are placed in a pack of cardboard.

Storage conditions:

In the dark place 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 expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-001955

Date of registration:25.12.2012

Date of cancellation:2017-12-25

The owner of the registration certificate:ALSI Pharma, ZAO ALSI Pharma, ZAO Russia

Manufacturer: & nbsp

ALSI Pharma, ZAO Russia

Representation: & nbspALSI Pharma CJSC ALSI Pharma CJSC Russia

Information update date: & nbsp27.09.2015

Illustrated instructions

Instructions

Citalopram (Citalopram)