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Active ingredients
Citalopram
Release form
Pills
Composition
Citalopram (in the form of hydrobromide) 20 mg; Auxiliary substances: microcrystalline cellulose 93.80 mg, pregelatinized starch 40.40 mg, magnesium stearate 0.80 mg.; Film coating composition: Opadry II 6.40 mg, including polyvinyl alcohol 2.56 mg, macrogol 1.30 mg , talc 0.94 mg, titanium dioxide 1.60 mg.
Pharmacological effect
Citalopram is an antidepressant, belonging to the group of selective serotonin reuptake inhibitors (SSRIs). It has a pronounced ability to inhibit serotonin reuptake, does not have or has a very weak ability to bind to a number of receptors, including gamma-aminobutyric acid receptors (GABA), H1-histamine, D1- and D2-dopamine; 1-, 2-, beta-adrenergic; benzodiazepine and m-cholinergic receptors, which accounts for the almost complete absence of such undesirable effects as negative chrono-, dromo- and inotropic effects, orthostatic hypotension, sedation and dry mouth. Citalopram inhibits CYP2D6 isoenzyme only to a very small extent, and, therefore, practically does not interact with drugs metabolized by this enzyme. Thus, side effects and toxic effects are significantly less.; The antidepressant effect usually develops after 2-4 weeks of treatment.; Citalopram does not affect serum levels of prolactin and growth hormone.; Citalopram does not impair cognitive / intellectual functions and psychomotor function and practically does not have a sedative effect.; Citalopram in doses exceeding 40 mg per day can cause abnormal changes in the electrical activity of the heart (prolongation of the QT interval on an ECG).
Pharmacokinetics
The bioavailability of citalopram is 80% and is almost independent of food intake. Cmax in plasma is achieved after an average of 3 hours. Pharmacokinetics is linear dose-dependent in the administration of single and multiple doses (doses in the range of 10-60 mg per day). When taken 1 time per day Css in plasma is set after 7-14 days of therapy. Vd - about 12-17 l / kg. Plasma protein binding - no more than 80%. In the plasma is present unchanged. Penetrates into breast milk. Metabolized by demethylation, deamination and oxidation with the participation of cytochrome P450 (CYP3A4 and CYP2C19 isoenzymes, to a lesser extent CYP2D6) with the formation of pharmacologically less active metabolites.Inhibition of one of these enzymes can be compensated by other enzymes. T1 / 2 citalopram is 1.5 days (36 hours). Excretion is carried out by the kidneys (15%) and the liver (85%). 12-23% of citalopram is excreted unchanged through the kidneys. Hepatic clearance - about 0.3 l / min, renal clearance - 0.05-0.08 l / min; Patients over the age of 65 years; There is a longer T1 / 2 and lower clearance values due to a decrease in metabolism; Insufficiency of liver function; Y in patients with reduced liver function, citalopram is eliminated more slowly. T1 / 2 citalopram is almost twice as high and the equilibrium plasma concentrations of citalopram are almost two times higher than in patients with normal liver function after taking a similar dose.; Kidney function deficiency; proceeds more slowly without significant effect on pharmacokinetics. Patients with severe renal insufficiency (creatinine clearance below 30 ml / min) require caution.
Indications
- depressive episodes of moderate and severe; - panic disorders.
Contraindications
- Hypersensitivity to citalopram or to any of the excipients that make up this drug; - Citalopram should not be used in combination with monoamine oxidase inhibitors (MAO), including selegiline, moclobemide, linezolid (antibiotic), and also for 14 days after discontinuation of their administration. Treatment with MAO inhibitors can be started no earlier than 7 days after discontinuation of citalopram; - Citalopram is contraindicated in case of simultaneous use with drugs that prolong the QT interval on the ECG (in particular, with pimozide), as well as with congenital prolongation of the QT interval; - Children under the age of 18 is a contraindication for the use of citalopram, since the efficacy and safety of its use at this age has not been established.
Use during pregnancy and lactation
Pregnant and lactating women should not be given to citalopram if the potential clinical benefit does not prevail over the theoretical risk, since the safety of the drug during pregnancy and lactation in a woman has not been established. The use of citalopram in the third trimester of pregnancy may adversely affect the psychophysical development of the newborn.The following disorders are possible in newborns whose mothers took selective serotonin reuptake inhibitors right up to delivery: respiratory failure, cyanosis, shortness of breath, convulsions, temperature instability, feeding difficulties, vomiting, hypoglycemia, muscle hypertension or hypotension, hyperreflexia, tremor, nervousness, irritability, lethargy, constant crying, drowsiness and insomnia. Epidemiological data suggest that the use of SSRIs during pregnancy, especially in late pregnancy, can It 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 is from 1 to 2 cases of persistent pulmonary hypertension in newborns per 1000 pregnancies. Such violations may indicate serotonergic effects or the occurrence of the "cancellation" syndrome. In the case of citalopram during pregnancy, its reception should not be abruptly interrupted.
Dosage and administration
Citalopram is taken orally once a day (without chewing, with a small amount of liquid). The drug can be used at any time of the day, regardless of the meal, it is advisable to take the drug at the same time of day.; Depression; Depression therapy begins with taking 20 mg of citalopram per day. Depending on the patient's individual response and the severity of depression, the dose may be increased to a maximum of 40 mg per day. Panic disorder; For panic disorders, the recommended dose for 1 week is 10 mg per day, then the dose is increased to 20 mg per day. The daily dose, depending on the individual response of the patient, may 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 response and the severity of depression, the dose may be increased to a maximum of 20 mg per day. Impaired renal function; In chronic renal failure, mild to moderate severity of correction of the dosing regimen is not required. Patients with severe renal insufficiency (creatinine clearance below 30 ml / min) require caution in dose selection. Liver dysfunction; 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 may be increased to 20 mg per day.Patients with severe hepatic insufficiency require extreme caution in dose selection.; Patients with low CYP2C19 isoenzyme activity; In patients with low CYP2C19 isoenzyme, the initial dose is 10 mg per day for two weeks. Depending on the response, the dose can be increased up to 20 mg per day.; Duration of treatment; The effect manifests itself after 2-4 weeks, the duration of the course of treatment is determined by the patient’s condition, the effectiveness and tolerability of the therapy being administered and averages 6 months. its abolition; Symptomatology, which may be noted with a sharp abolition of citalopram, is not characteristic. This is most often dizziness, headache, paresthesia, insomnia, asthenia, nervousness, tremor, nausea and / or vomiting. If treatment is completed, citalopram must be discontinued gradually over several weeks to avoid the "cancellation" syndrome. In most cases, about 2 weeks are enough for this, but in each case the doctor decides this question individually: for some patients it may take 2-3 months or more.
Side effects
As with the use of other drugs of the SSRI group, undesirable side reactions are noted against the use of citalopram, but they are transient in nature and weakly expressed.; Adverse reactions against the use of citalopram are observed during the first one to two weeks of treatment and usually weaken significantly improve the condition of patients.; The 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, increased sensitivity; very rarely - anaphylactic reactions. From the side of the central nervous system: very often - drowsiness, headache, tremor, dizziness; often - migraine, paresthesia, sleep disorder; infrequently - extrapyramidal disorders, convulsions; rarely, serotonin syndrome (a combination of arousal, tremor, myoclonus, and hyperthermia); frequency is unknown - psychomotor agitation, akathisia. From the mental 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 is unknown - panic attacks, bruxism, suicidal thoughts. From the digestive system: very often - dry mouth, nausea, constipation; often - vomiting, flatulence, diarrhea, abdominal pain, hepatitis; frequency is unknown - gastrointestinal bleeding.; From the side of the cardiovascular system: very often - a sensation of heartbeat; often - tachycardia, arterial hypertension, orthostatic hypotension; rarely - bradycardia, lower blood pressure, arrhythmia; unknown frequency - prolongation of the QT interval on the ECG often - a violation of taste, visual disturbances, infrequently - ringing in the ears. From the respiratory system: often - rhinitis, sinusitis; infrequently - cough; rarely - dyspnea. On the part of the reproductive system: often - a violation of sexual function, namely a violation of ejaculation, decreased libido, impotence, menstrual disorders; rarely - galactorrhea.; From the urinary system: often - painful urination, polyuria.; Metabolic disorders: often - loss of 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 - photosensitivity, urticaria, alopecia, purpura; frequency is unknown - angioedema, bruising. From the musculoskeletal system: infrequently - myalgia, arthralgia, increased risk of injuries and fractures. Laboratory indicators: often - changes in laboratory indicators of liver function; infrequently - increased activity of liver enzymes, changes in the electrocardiogram (prolongation of the QT interval), hyponatremia.; Other: rarely - hyperthermia, yawning, increase or decrease in body weight.
Overdose
Overdose symptoms: convulsions, drowsiness, 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 arrhythmia, ventricular arrhythmia, coma.; Coma and lethal cases of overdose with citalopram are extremely rare, most of them include a simultaneous overdose with other drugs and.; Treatment of overdose: there is no specific antidote. In case of overdose, gastric lavage should be carried out as soon as possible. Treatment is symptomatic and supportive. Medical observation is recommended, with loss of consciousness and respiratory failure - intubation, as well as careful monitoring of ECG and other vital functions, since there is a high risk of fatal arrhythmias accompanied by sinus tachycardia, nodal rhythm, prolongation of the QT interval, in particular, pirouette arrhythmias may develop , ventricular arrhythmias.
Interaction with other drugs
Combined use; with MAO inhibitors; Concomitant treatment with MAO inhibitors is contraindicated (both non-selective and selective) due to the risk of serious side effects, including serotonin syndrome. Citalopram should not be used in combination, incl. with selegilin, moclobemide, linezolid (antibiotic), etc., as well as within 14 days after stopping their intake. Treatment with MAO inhibitors can be started no earlier than 7 days after discontinuation of citalopram. With drugs that extend the QT interval; Use with drugs that prolong the QT interval, such as antiarrhythmics (procainamide, amiodarone, etc.), antipsychotic drugs / neuroleptics (for example, phenothiazine derivatives, pimozide, haloperidol), tricyclic antidepressants and SSRIs (fluoxetine), antimicrobial drugs (macrolide antibiotics and their analogues, for example, erythromycin, clarithromycin; quinolone and fluoroquinolone: sparfloxacin, moxifloxacin, pentamidine), blockers of H1-histamine receptors (astemizole, mizolastin), antifungal agents of the azole series (ketoconazole, fluconazole), domperidone, ondansetron, and using maritime patterns, as well as mar- ters, as well as one of the most important sources of maritime patterns, such as the use of marts electrical activity of the heart (prolongation of the QT interval on the ECG) and lead to a heart rhythm disorder (includingdevelopment of arrhythmias of the type "pirouette"), which can be fatal.; Pimozide; Simultaneous use of pimozide and citalopram is contraindicated because their combined use lengthens the QT interval. This also applies to such agents as amitriptyline, maprotiline, venlafaxine, terfenadine, haloperidol, droperidol, chlorpromazine, thioridazine. The combined use of Citalopram should be carried out with caution:; Citalopram can reduce the threshold of convulsive readiness. It is necessary to exercise caution while taking other means of reducing the threshold of convulsive readiness (tricyclic antidepressants, SSRIs, neuroleptics - derivatives of phenothiazine, thioxanthene and butyrophenone; meflokhina and tramadol); With the simultaneous use of citalopram and tryptophan, cases of increased activity of the drug have been reported. It is advisable not to combine serotonergic drugs such as sumatriptan or other triptans, as well as tramadol with citalopram.; Simultaneous use of citalopram and preparations containing St. John's wort (Hypericum perforatum) can lead to an increase in side effects. blood concentrations of citalopram. Therefore, it is recommended to exercise caution when prescribing maximum doses of citalopram simultaneously with the use of high doses of cimetidine. While using citalopram with indirect anticoagulants and other agents that affect blood clotting (atypical neuroleptics and phenothiazine derivatives, most tricyclic anti-depressants, acetylles, and the use of adjectives, it is necessary to use adipozymes, you can use the same timeframes, you should use the same time formulas, and you should also use one of one of the same time formidytotoytocrostoc ants). ticlopidine and dipyridamole) coagulation disorders may occur. In such cases, at the beginning or end of treatment with citalopram, regular monitoring of blood clotting is necessary. With simultaneous administration with warfarin, the prothrombin time increases by 5%; there is no interaction of citalopram with alcohol. However, as in the case of other psychotropic drugs, simultaneous use of citalopram and alcohol is not recommended.; In vitro studies have revealed that citalopram is converted to its demethylated derivatives with the participation of CYP2C19 and CYP3A4 isoenzymes, as well as with a small contribution from the CYP2D6 isoenzyme. It has been proven that inhibition of one of the enzymes can be compensated by other enzymes.The inhibitory effect of citalopram on these and other cytochrome P450 isoenzymes is weak or insignificant, therefore citalopram has a low ability for clinically significant drug interactions known for this situation. However, caution is needed if citalopram is prescribed in conjunction with drugs that are metabolized mainly by the CYP2D6 isoenzyme and have a low therapeutic index. Although clinical data on multiple-dose pharmacokinetic studies are not available, there is in vitro data (a model of human liver microsomes) that show a slower formation of demethylated citalopram derivatives by 45–60% and 75–85% compared to control after adding ketoconazole and omeprazole , respectively. It may prove necessary in these cases, care in assignment together with citalopram such strong inhibitors of CYP3A4, as ketoconazole, itraconazole, fluconazole, or such strong inhibitors of CYP2C19, as omeprazole, esomeprazole, fluvoxamine, ticlopidine, lansoprazole, as their co-administration with citalopram may significantly reduce clearance of citalopram. Therefore, the maximum recommended dose of citalopram for patients taking together drugs-inhibitors of the CYP2C19 isoenzyme should not exceed 20 mg / day, incl. and because the risk of prolongation of the QT interval increases. The combined use of citalopram with imipramine or desipramine does not affect the concentration of imipramine and citalopram, but increases the concentration of desipramine; dose adjustment of desipramine may be necessary.
special instructions
Children under 18 years of age are contraindicated for the use of citalopram, since its efficacy and safety have not been established at this age. In connection with the possibility of suicide attempts, patients with depression need careful monitoring of patients at the beginning of treatment and prescribing minimal effective doses to reduce overdose risk. This precaution must also be observed in the treatment of other mental disorders due to the possibility of simultaneous illness of a depressive episode. Severe depressions are characterized by the risk of suicidal acts, which can persist until substantial remission is achieved.In this regard, at the beginning of treatment, a combination with drugs from the group of benzodiazepines or neuroleptic drugs and constant medical supervision (to entrust the storage and distribution of drugs to trusted persons) can be shown. In the treatment of panic disorders with the prescription of antidepressants and / or benzodiazepines, in some patients, anxiety or anxiety is greatly increased in response to the treatment initiated. This condition (called by specialists “pathological disinhibition” or simply “paradoxical anxiety”, the term has not yet been approved) is considered as a rare phenomenon, although this pathological reaction has been repeatedly documented in the scientific literature. This "paradoxical anxiety" usually decreases during 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. In this case, drug withdrawal 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) with depression and other mental disorders, antidepressants are compared with with placebo, increase the risk of suicidal thoughts and suicidal behavior. Therefore, when prescribing citalopram or any other antidepressants in this category of patients, the risk of suicide should be correlated with the benefits of their use. In short-term studies, the risk of suicide was not increased in people over 24 years of age, while in people over 65 years of age it was somewhat reduced. During treatment with antidepressants, all patients should be monitored for early detection of suicidal tendencies.; Citalopram should be used with caution in renal failure (creatinine clearance below 30 ml / min), hypomania, mania, pharmacologically uncontrolled epilepsy, depression with suicidal attempts, diabetes, cirrhosis of the liver, bleeding tendency; simultaneous use with drugs that reduce the threshold of convulsive readiness and causing hyponatremia with ethanol, as well as drugs that are metabolized by the CYP2C19 isoenzyme.; Citalopram can cause a dose-dependent prolongation of the QT interval, which can lead to heart rhythm disturbances. for violations of antidiuretic hormone secretion, especially a high level of risk in older women. Treatment with Citalopram may alter the glycemic control in patients with sugar m diabetes.The dose of insulin and / or oral hypoglycemic agents must be adjusted. Akatizia is rarely possible, characterized by a constant or recurring sense of internal motor anxiety and manifested in the inability to sit still for a long time in one position or remain motionless for a long time. It takes place during the first weeks of treatment. Mania may develop in patients with bipolar disorder. Then treatment with citalopram should be stopped.; It is necessary to use citalopram with caution in the presence of drug dependence (including history) and epileptic seizures in history.; Citalopram should not be used in combination with monoamine oxidase inhibitors (MAO) if severely impaired function kidney care is required. In case of abnormal liver function, taking the drug is limited to the minimum recommended doses. Older patients require a dose reduction of citalopram. With the development of a manic state, the drug should be discontinued. Clinical experience of simultaneous use of SSRIs and electroconvulsive therapy is insufficient, therefore caution is required. At the beginning of treatment, insomnia and anxiety may occur, which can be solved by correcting initial dose. Abrupt cessation of treatment with Citalopram can lead to "withdrawal" syndrome. Such adverse reactions may occur, such as dizziness, headaches, nausea. To avoid the emergence of the syndrome of "cancellation" requires a gradual withdrawal of the drug within a few weeks.; Effect on the ability to drive vehicles and control mechanisms; Citalopram should be used with caution in persons whose activities are related to the mechanisms or control of moving vehicles. Citalopram does not reduce the mental abilities and the speed of psychomotor reactions, however, in patients we can expect some reduction in attention and concentration due to the existing disease, adverse reactions from the treatment being carried out or from both.