Citalopram

When ATH:
N06AB04

Characteristic.

Citalopram hydrobromide - white or almost white powder. It is soluble in water, soluble in ethanol.

Pharmacological action.
Antidepressant.

Application.

Depression different etiology.

Contraindications.

Hypersensitivity, simultaneous MAO inhibitors.

Restrictions apply.

Pregnancy, lactation, childhood (safety and effectiveness in children have not identified).

Pregnancy and breast-feeding.

Maybe, if the effect of therapy outweighs the potential risk to the fetus and child (adequate and well-controlled studies of the safety of use in pregnant and lactating women have not been conducted).

Category actions result in FDA - C. (The study of reproduction in animals has revealed adverse effects on the fetus, and adequate and well-controlled studies in pregnant women have not held, However, the potential benefits, associated with drugs in pregnant, may justify its use, in spite of the possible risk.)

Side effects.

Side effects, associated with discontinuation of treatment in the short-term, placebo-controlled trials. According to the results of placebo-controlled trials of up to 6 Sun 16% from 1063 patients, receiving dosages of citalopram 10 to 80 mg per day, discontinued treatment because of side effects, compared to 8% from 446 patients, placebo. Side effects, associated with the termination of treatment, and recognizes the consequent citalopram (ie. observed in at least 1% patients, poluchavshih citalopram, in 2 times more likely to placebo), include: asthenia 1%(<1%), nausea 4%(0%), dry mouth 1%(<1%), vomiting 1%(0%), dizziness 2%(<1%), insomnia 3%(1%), drowsiness 2%(1%), ažitaciâ 1%(<1%).

Side effects, observed in placebo-controlled clinical trials. The table below shows adverse effects, were observed in patients, receiving dosages of citalopram 10 to 80 mg daily for 6 Sun (specified adverse effects, marked at least 2% patients and greater than placebo in frequency).

* Fixed only for women: N=638 (citalopram), N=252 (placebo).
** Fixed only in men: N=425 (citalopram), N=194 (placebo)

Adverse effects, noted in these clinical trials, 2% patients and less common, than placebo: headache, asthenia, dizziness, constipation, heartbeat, pharyngitis, violation of urination, backache.

Evaluation of frequency of side effects was conducted on the dose at fixed doses in patients with depression, receiving placebo or citalopram doses 10, 20, 40 and 60 mg. Using Jonckheer's test positive correlation (p<0,05) the following effects: fatiguability, impotence, insomnia, drowsiness, zevota.

Changes in vital signs. There were no clinically significant changes in vital signs (pulse, USA, DAD), incl. orthostatic changes when you change the position of the body during treatment with citalopram compared to placebo.

Changes in body weight. In controlled trials of weight loss was about 0,5 kg (changes in the placebo group was).

Changes in laboratory parameters. No clinically significant changes in laboratory test was not observed.

ECG changes. Comparison of ECG in patients, poluchavshih citalopram (n=802) placebo (n=241), found, statistically significant difference was only a decrease in heart rate in patients receiving citalopram.

Cooperation.

Concomitant use with MAO inhibitors may increase the pressure and excitement. Citalopram may enhance the effects of sumatriptan and other serotonergic agents, Increases metoprolol in plasma (result of the interaction is not clinically significant) and plasma concentration (on 50%) aktivnogo imipramine metabolites (the clinical significance of the effect is unknown).

Cimetidine AUC povыshaet (on 43%) and C_max (on 39%) citalopram. There were no clinically significant interaction with digoxin, varfarinom, karʙamazepinom, triazolamom, ketoconazole, pour (In a joint application should be careful, tk. lithium may increase serotonergic effects of citalopram) and alcohol.

Overdose.

In clinical trials, an overdose of citalopram (to 2000 mg) deaths were observed. In post-marketing reports of drug overdose, including as citalopram, fixed 12 deaths, 10 of which - in combination with other drugs and / or alcohol and 2 - when taking only citalopram (3920 mg 2800 mg); It has also been reported 1 case of overdose without fatal outcome when taking 6000 mg.

Symptoms: dizziness, increased perspiration, nausea, vomiting, tremor, drowsiness, sinus tachycardia. In more rare cases, amnesia, confusion, coma, convulsions, hyperventilation, cyanosis, raʙdomioliz, ECG changes (including lengthening of QT c nodal rhythm and ventricular arrhythmia and 1 eventuality torsades de pointes).

Treatment: Gastric lavage and the use of activated carbon. Keeping the airway to ensure adequate ventilation and oxygenation. It is recommended that careful observation and monitoring of vital functions, incl. cardiac function, symptomatic and supportive therapy. Because of the large volume of distribution of citalopram is unlikely the effectiveness of such measures, as a forced diuresis, dialysis, hemoperfusion and exchange transfusion. The specific antidote is absent.

Dosing and Administration.

Inside, once a day, Anytime, regardless of the meal. The initial dose - 20 mg / day, maximum - 60 mg / day. For patients older 65 years and patients with impaired liver function, the recommended dose is 20 mg, maximum - 40 mg / day (if necessary).

Precautions.

When mild to moderate severity renal impairment dose adjustment is not required, in severe renal impairment requires careful.

When co-administered drugs from the group of serotonin reuptake inhibitors in combination with MAO inhibitors reported to occur in patients serious, sometimes fatal reactions, including hyperthermia, rigidity, unstable vital signs with possible rapid fluctuations, altered mental status (including agitation, up to delirium and coma). It reported the same reactions in patients, initiating MAO inhibitors shortly after discontinuation of treatment with citalopram. Therefore, it should not be combined with MAO inhibitors, citalopram, or assign it within the first two weeks after their withdrawal. At the end of treatment with citalopram should also take a break 2 weeks before receiving MAO inhibitors.

Should consider the possibility of hyponatremia (reported several cases), and the syndrome of inappropriate secretion of ADH, taking place at the termination of treatment and / or medical intervention.

According to the results of placebo-controlled trials, some of which included patients with bipolar disorder, in 0,2% patients 1063, poluchavshih citalopram (compared to 446 patients, placebo), observed activation of mania / hypomania. It should be used with caution citalopram (as well as other antidepressants) patients with a history of mania.

Caution is needed, as when receiving other antidepressants, with a history of seizures.

Due to the possibility of suicide attempts in patients with depression requires careful monitoring of patients in the early treatment and appointment of the minimum effective dose to reduce the risk of overdose.

In studies in healthy volunteers, dosed 40 mg / day, not decreased mental activity and speed of psychomotor reactions. However, patients should be warned to use caution when working with potentially dangerous machinery, incl. while driving.

Clinical experience with citalopram in the presence of comorbidities in patients is limited. Be careful when diseases, associated with impaired metabolism or hemodynamic.

There have been no systematic observations in patients with myocardial infarction or unstable heart disease, tk. these patients were excluded from clinical studies premarketingovyh. However, analysis of the ECG 1116 patients, poluchavshih citalopram, shows, that taking citalopram is not associated with the development of clinically significant ECG abnormalities.

Care must be taken while taking other centrally acting drugs.

In experimental, as well as in clinical studies revealed no cases of abuse, of tolerance, physical dependence. However, these observations were not systematic, therefore require careful monitoring of patients, with a history of drug abuse observed.

Cooperation