Citalopram-ALSI, 10 mg 30 pcs

Pharmacotherapeutic group: Antidepressant.

ATX code: N06AB04.

Pharmacological properties

Citalopram is an antidepressant, a selective serotonin reuptake inhibitor (SSRI).

Pharmacodynamics:

Biochemical and behavioral studies have shown that citalopram is a potent serotonin reuptake inhibitor (5-HT).

The duration of citalopram treatment has no effect on 5-HT reuptake inhibition habituation. Tolerance to serotonin reuptake inhibition does not occur with long-term use of citalopram.

Citalopram is a superselective serotonin reuptake inhibitor (SSRI) with little or no effect on noradrenaline, dopamine and GABA.

Citalopram has no or very weak ability to bind to a number of receptors, including 5-HT_1A-, 5-HT₂-serotonin, D₁– and D₂-dopamine, α1-, α2- and
β-adrenergic, H₁-histamine, muscarinic cholinoreceptors, benzodiazepine and opioid receptors.

The major metabolites of citalopram are all SSRIs, although their activity-selectivity ratios are lower than those of citalopram. However, the selectivity ratios of these metabolites are higher than those of many next-generation SSRIs. The metabolites are not involved in the overall antidepressant effect.

While citalopram does not bind to opioid receptors, it potentiates the antinociceptive effects of commonly used opioid analgesics.

In humans, citalopram does not impair cognitive or psychomotor function and has virtually no sedative properties, even in combination with alcohol.

In a double-blind, placebo-controlled ECG study in healthy volunteers, the change in QTc (Friedericia formula correction) from baseline was 7.5 (90% confidence interval 5.9-9.1) ms for the
20 mg/day dose and 16.7 (90% confidence interval 15.0-18.4) ms for the 60 mg/day dose.

Pharmacokinetics:

Absorption

The absorption of the drug is almost complete and independent of food intake (mean time to reach maximum plasma concentration (Tmax) about 3 hours). Bioavailability when taken orally is approximately 80%.

Distribution

The apparent volume of distribution (Vd)β is approximately 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, citalopram-N-oxide and an inactive derivative of deaminated propionic acid. All of the active metabolites are also SSRIs, although their effects are weaker than those of the parent compound. The predominant component in plasma is unchanged citalopram. The concentrations of demethylcitalopram and didemethylcitalopram are typically 30-50% and 5-10% of the citalopram concentration, respectively. The biotransformation of citalopram to demethylcitalopram is mediated by CYP2C19 (approximately 38%), CYP3A4 (approximately 31%) and CYP2D6 (approximately 31%) isoenzymes.

Evolution

The half-life (T_1/2) is approximately 1¹/₂ days. The systemic plasma clearance (Cls) of citalopram is approximately 0.3-0.4 L/min, and the oral clearance (Cl_oral) is approximately 0.4 L/min.

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

Linearity

The kinetics of citalopram are linear. Equilibrium plasma concentration is reached within 1-2 weeks. The average equilibrium concentration is about 300 nmol/L (165-405 nmol/L) at a daily dose of 40 mg.

Elderly patients (> 65 years)

The elderly patients have been shown to have a longer half-life of the drug (1.5-3.75 days) and lower clearance rates (0.08-0.3 L/min) due to lower metabolic rate. The equilibrium concentration is approximately twice as high in elderly patients than in younger patients receiving the same dose.

Disordered liver function

Citalopram is more slowly excreted in patients with impaired liver function. The half-life of citalopram is about twice as long and the equilibrium concentration is about twice as high compared to patients with normal liver function at the same dose.

Decreased renal function

Citalopram is more slowly excreted in patients with mild to moderate impaired renal function, which, however, does not significantly affect the pharmacokinetics of citalopram. There is currently no information regarding the treatment of patients with severe renal impairment (creatinine clearance < 30 ml/min).

Polymorphism

Studies in vivo

Indications

Moderate to severe depressive episodes and prevention of their recurrence. Panic disorder with/without agoraphobia.

Active ingredient

Citalopram

Composition

One film-coated tablet contains:

The active ingredient:

citalopram hydrobromide 12.5 mg, 25.0 mg, and 50.0 mg, corresponding to 10 mg, 20 mg, and 40 mg of citalopram;

Excipients: Microcrystalline cellulose 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, Opadray II [polyvinyl alcohol (1.28/2.56/5.12) mg, titanium dioxide (0.80/1.60/3.20) mg, macrogol (polyethylene glycol) (0.65/1.30/2.60) mg, talc (0.47/0.94/1.88) mg] 3.20 mg/6.40 mg/12.80 mg.

How to take, the dosage

Citalopram is given orally once a day. The drug can be taken at any time of the day, regardless of meals. The tablets must not be divided in half.

Depression:

Citalopram is prescribed once daily with 20 mg. Depending on the patient’s individual response, the dose may be increased to a maximum of 40 mg per day.

The antidepressant effect usually develops 2-4 weeks after the start of treatment. Therapy with antidepressants is symptomatic in nature and should be continued for a sufficient period of time, usually at least 6 months after the complete elimination of symptoms of depression in order to avoid the development of relapses. In patients with recurrent (unipolar) depression, necessary maintenance therapy may 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 is increased to 20 mg daily. Depending on the patient’s individual response, the dose may 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 the start of treatment and is maintained with continued therapy.

Elderly patients (>65 years):

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

Children and adolescents (under 18 years):

Citalopram should not be used in children and adolescents under 18 years of age (see section “Special Indications”). In addition, there are insufficient long-term safety studies of the drug in children and adolescents regarding growth, maturation, cognitive and behavioral development.

Decreased renal function:

Dose adjustment is not necessary in mild to moderate renal insufficiency. Patients with severe renal insufficiency (creatinine clearance below
30 ml/min) should use Citalopram-ALSI with caution.

Disordered liver function:

In mild to moderate hepatic impairment, the recommended initial dose for the first two weeks of treatment is 10 mg/day.

Depending on the patient’s individual response, the dose may be increased to a maximum of 20 mg/day. In patients with significant hepatic insufficiency the drug should be used with caution; careful dosage titration is required.

Disabled CYP2C19 isoenzyme activity:

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

Cessation of treatment:

Abrupt discontinuation of treatment should be avoided. When therapy with Citalopram-ALSI is discontinued, the dose should be gradually reduced over a minimum of 1-2 weeks to avoid the occurrence of withdrawal reactions. If intolerable symptoms occur when reducing the dose or stopping citalopram treatment, a return to the previous dose or resumption of the drug is possible. Dose reduction may continue thereafter, but more gradually.

Interaction

Pharmacodynamic interactions

Cases of serotonin syndrome have been described when citalopram is combined with moclobemide and buspirone.

Controlled combinations

MAO inhibitors

Concomitant use of citalopram and MAOI inhibitors may lead to serious adverse effects, including serotonin syndrome.

Serious and sometimes fatal reactions have been described in patients receiving concomitant SSRIs and monoamine oxidase inhibitors (MAOIs), including the irreversible MAOI selegiline and the reversible MAOIs linezolid and moclobemide, and in patients who have recently stopped taking SSRIs and started an MAOI.

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

The symptoms of citalopram interaction with IMAOs included: hyperthermia, rigidity, myoclonus, autonomic instability with rapid fluctuations in vital signs, and mental status changes that included confusion, irritability and excessive agitation, which progressed to delirium and coma.

Drugs that prolong the QT interval

Pharmacokinetic and pharmacodynamic studies of the interaction between citalopram and QT interval prolonging drugs have not been performed. The summation of the effects of citalopram and these drugs cannot be excluded. Thus, the simultaneous use of citalopram and drugs that prolong the QT interval, such as antiarrhythmics of classes IA and III, antipsychotics (eg, phenothiazine derivatives, pimozide, haloperidol), tricyclic antidepressants, some antimicrobials (e.g., sparfloxacin, moxifloxacin, IV erythromycin, pentamidine, antimalarials, especially halofantrine), some antihistamines (astemizole, misolastine), etc.д., are contraindicated.

Pimozide

. In a study, a single dose of 2 mg of pimozide taken by subjects taking the racemic form of citalopram at a dose of 40 mg/day for 11 days resulted in increased AUC (area under the curve) and Cmax (maximum concentration) values of pimozide, although not always. Co-administration of pimozide and citalopram resulted in an average prolongation of the QTc interval by approximately 10 msec. Given the development of interactions at low doses of pimozide, concomitant use of citalopram and pimozide is contraindicated.

Combinations requiring caution

Selegyline (selective MAO B inhibitor)

Pharmacokinetic and pharmacodynamic interaction studies of concomitant use of citalopram (20 mg/day) and selegiline (10 mg/day) (MAO B selective dose) showed no clinically significant interactions. Simultaneous use of citalopram and selegiline (at a dose greater than 10 mg/day) is not recommended.

Serotonergic drugs

Lithium and tryptophan

. No pharmacodynamic interactions have been found in clinical studies of concomitant use of lithium and citalopram. However, enhanced effects have been reported with concomitant administration of SSRIs with lithium or tryptophan, so the use of such combinations should be used with caution.

Lithium blood levels are monitored routinely.

The co-administration with serotonergic drugs such as tramadol and sumatriptan may lead to increased serotonergic effects. Until definitive data on possible interactions are available, combining citalopram with 5-NT receptor agonists such as sumatriptan and other triptans is not recommended.

Hypericum perforatum

The dynamic interaction of SSRIs with herbal preparations containing St. John’s Wort (Hypericum perforatum) may result in an increased frequency of adverse reactions. Pharmacokinetic interaction has not been studied.

Anticoagulants and agents affecting blood clotting

. Caution should be used when prescribing citalopram for patients treated with anticoagulants, drugs that affect platelet function, such as non-steroidal anti-inflammatory drugs (NSAIDs), acetylsalicylic acid, dipyridamole, and ticlopidine, or other drugs (e.g., atypical antipsychotics, phenothiazines, tricyclic antidepressants), which may increase the risk of bleeding.

Electroconvulsive therapy (ECT)

There are no clinical trial data demonstrating the risks or benefits of concomitant use of ECT and citalopram.

Alcohol

No pharmacodynamic or pharmacokinetic interactions have been found between citalopram and alcohol. However, co-administration of citalopram and alcohol is not recommended.

Drugs that decrease seizure threshold

SIOZS may decrease seizure threshold. Caution is advised when using concomitantly with other drugs that can lower the seizure threshold (e.g., antidepressants [tricyclics, SSRIs], neuroleptics [phenothiazines, thioxanthenes and butyrophenones], mefloquine, bupropion and tramadol).

Neuroleptics

The experience with citalopram showed no clinically significant interactions with neuroleptics. However, as with other SSRIs, the possibility of pharmacodynamic interactions cannot be ruled out.

Pharmacokinetic interactions

. Biotransformation of citalopram to demethylcitalopram is mediated by cytochrome P450 system isoenzymes 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 may be compensated by the others.

Hence, concomitant administration of citalopram with other medications has a very low likelihood of pharmacokinetic interactions.

Food

It has not been reported that food intake affects the absorption and other pharmacokinetic properties of citalopram.

Influence of other drugs on the pharmacokinetics of citalopram

Ketoconazole (a strong CYP3A4 isoenzyme inhibitor) did not alter the pharmacokinetics of citalopram when used together.

Pharmacokinetic studies of interactions between lithium and citalopram showed no interactions.

Cimetidine (a strong inhibitor of the CYP2D6, CYP3A4 and CYP1A2 isoenzymes) caused a moderate increase in the equilibrium concentration of citalopram.

We recommend caution when prescribing citalopram in combination with cimetidine. Dose adjustment may be necessary.

Influence of citalopram on the pharmacokinetics of other drugs

Studies of the pharmacokinetic/pharmacodynamic interaction between citalopram and metoprolol (a substrate of the CYP2D6 isoenzyme) showed a 2-fold increase in metoprolol concentration, but no statistically significant increase in metoprolol effect on blood pressure and heart rate was noted in healthy volunteers. Caution should be exercised when coadministering metoprolol and citalopram. Dose adjustment may be required.

Citalopram and demethylcitalopram are minor inhibitors of the CYP2C9, CYP2E1 and CYP3A4 isoenzymes and only weak inhibitors of CYP1A2, CYP2C19 and CYP2D6 compared to other SSRIs considered significant inhibitors.

Levomepromazine, digoxin, carbamazepine

No or only very small clinically significant changes were observed when citalopram was used concomitantly with CYP1A2 substrates (clozapine and theophylline), CYP2C9 (warfarin), CYP2C19 (imipramine and mefenitoin), 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 (indicating that citalopram neither induces nor inhibits P-glycoprotein).

Desipramine, imipramine

In pharmacokinetic studies, no changes in the levels of either citalopram or imipramine were found, although levels of desipramine, the main metabolite of imipramine, were increased. When citalopram and desipramine were used concomitantly, plasma levels of the latter were elevated. A reduction in the dose of desipramine may be required.

Special Instructions

Application in children and adolescents under 18 years of age

Antidepressants should not be prescribed to children and adolescents under 18 years of age. In clinical studies, suicidal behavior (suicide attempts and suicidal ideation) and hostility (with a predominance of aggressive behavior, confrontational tendencies, and irritability) were more common among children and adolescents who took antidepressants than in the placebo group.

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

Paradoxical anxiety

In some patients with panic disorder, increased anxiety may be observed at the beginning of antidepressant therapy. This paradoxical reaction usually subsides within the first two weeks of starting treatment. Low initial doses are recommended to reduce the likelihood of anxiogenic effects.

Hyponatremia

In the use of SSRIs, rare cases of hyponatremia have been reported, apparently due to inadequate secretion of antidiuretic hormone (ADH). This reaction was generally reversible when treatment with the drug was discontinued. The risk of occurrence was higher in older women.

Suicidal ideation/suicidal thoughts or clinical deterioration

Depression is associated with an increased risk of suicidal ideation, self-harm and suicide (suicidality). This risk persists until stable remission develops.

Since no improvement may be seen during the first few weeks of treatment or even longer, patients should be monitored for timely detection of such improvement. Clinical experience suggests that the risk of suicide increases in the early stages of recovery.

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

Patients with a history of suicidal tendencies or patients with significant levels of suicidal ideation prior to treatment are at greater risk for suicidal thoughts or suicide attempts, so they should be monitored closely during treatment. A meta-analysis of placebo-controlled clinical trials of antidepressants involving adult patients with psychiatric disorders found that there is an increased risk of suicidal behavior when taking antidepressants in patients younger than 25 years compared to taking a placebo. Medication treatment of these patients and, in particular, those at high suicidal risk should be accompanied by close monitoring, especially in the early phase of treatment and during dose changes. Patients (and caregivers) should be warned to monitor for any signs of clinical deterioration, suicidal behavior or thoughts, and unusual behavioral changes, and to seek medical advice immediately if these symptoms occur.

Akathisia/psychomotor restlessness

The use of SSRI/SIOSS drugs is associated with the development of akathisia, characterized by feelings of subjectively unpleasant or unbearable motor restlessness, restlessness and need to move. Often patients in this condition cannot sit or stand quietly. This condition most often occurs during the first weeks of treatment. In patients with these symptoms, increasing the dose may cause a sudden worsening of the condition.

Mania

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

Convulsive seizures

There is a risk of seizures when taking antidepressants. In any patient, citalopram should be stopped if a seizure occurs. Citalopram should not be used in patients with unstable epilepsy; if seizures are controlled, close monitoring is necessary. If seizure frequency increases, citalopram should be discontinued.

Diabetes mellitus

In patients with diabetes mellitus, use of SSRIs may alter blood glucose concentrations. In this case, it may be necessary to adjust the dose of insulin and/or oral hypoglycemic drugs.

Serotonin Syndrome

In rare cases, the development of serotonin syndrome has been reported while taking SSRIs. The development of this condition may be indicated by a combination of symptoms such as agitation, myoclonus and hyperthermia. If these phenomena occur, citalopram should be discontinued immediately and symptomatic treatment should be initiated.

Serotonergic drugs

Citalopram should not be used together with drugs that have serotonergic effects, such as sumatriptan or other triptans, tramadol, oxytriptan and tryptophan.

Bleeding

There have been reports of skin bleeding such as ecchymosis, gynecological, gastrointestinal bleeding and other hemorrhagic complications of the skin or mucous membranes while taking SSRIs. Caution should be exercised when concomitant use of SSRIs and drugs that affect platelet function or drugs that may increase the risk of bleeding, as well as when treating patients with a history of hemorrhagic disorders.

Electroconvulsive therapy (ECT)

Because clinical experience with concomitant use of SSRIs and electroconvulsive therapy (ECT) is limited, caution should be used with citalopram and ECT.

Selective selective MAO A inhibitors

The concomitant use of citalopram and MAO A inhibitors is not recommended because of the risk of serotonin syndrome.

Hypericum perforatum

The simultaneous use of citalopram and preparations containing St. John’s Wort (Hypericum perforatum) should be avoided because it may increase the risk of adverse effects.This may increase the risk of adverse reactions.

Psychosis

The treatment of psychotic patients with a depressive episode may exacerbate psychotic symptoms.

Withdrawal symptoms when discontinuing SSRI therapy

The withdrawal symptoms occur quite often, especially when therapy is stopped abruptly.

The likelihood of withdrawal symptoms may depend on a number of factors, including the length of treatment, the dose of the medication, and the rate of withdrawal.

The most commonly reported manifestations are dizziness, sensory disturbances (including paresthesias), sleep disturbances (including insomnia and vivid dreams), agitation or anxiety, nausea and/or vomiting, tremor, confusion, sweating, headache, diarrhea, palpitations, emotional lability, irritability and visual disturbances. Usually, these manifestations are mild to moderate in severity, but in some patients they may be severe.

In general, these effects usually occur within the first few days of withdrawal, but there have been isolated reports of these conditions occurring in patients who have accidentally missed their next dose.

In most cases, these complications resolve within 2 weeks, although in some patients the symptoms may persist for 2-3 months or longer. Therefore, it is recommended that the dose of citalopram be reduced gradually over a period of weeks to months, depending on the patient’s condition (see section “Dosage and administration”).

QT interval prolongation

Citalopram has been found to cause dose-dependent prolongation of the QT interval. In the post-registration period, cases of QT interval prolongation and ventricular arrhythmias, including torsade de pointes, have been reported predominantly in female patients with hypokalemia or pre-existing QT interval prolongation or other cardiac conditions.

The drug is recommended with caution in patients with significant bradycardia, recent myocardial infarction, or decompensated heart failure.

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

In patients with compensated heart disease, an ECG study should be performed before starting treatment.

If any signs of cardiac arrhythmias occur during treatment with citalopram, the latter should be discontinued and an ECG study should be performed.

Influence on the ability to drive vehicles and operate machinery

Citalopram has minimal or moderate ability to affect the ability to drive vehicles and operate machinery.

Psychoactive medications may affect decision-making and the ability to respond to emergencies. Patients should be advised of potential effects on their ability to drive and operate machinery.

Synopsis

Round biconvex tablets with white film coating. On cross section the inner layer is white or white with a yellowish tint.

Contraindications

Hypersensitivity to citalopram or any of the excipients.

Simultaneous use with monoamine oxidase inhibitors (MAOIs) (including selegiline at a dose above 10 mg/day). The time interval between the end of taking irreversible MAO inhibitors and the beginning of citalopram administration should be at least 14 days. In case of use of reversible MAO A inhibitors, the duration of the break is determined in accordance with the instructions for medical use of these drugs. Treatment with MAO inhibitors can be started not earlier than 7 days after citalopram cessation.

Simultaneous use with linezolid if close patient monitoring and blood pressure monitoring are not possible.

Concomitant use with pimozide.

An established prolonged QT interval or congenital prolonged QT interval.

Concomitant use with drugs that prolong the QT interval.

Childhood and adolescence (under 18 years of age) (efficacy and safety of use have not been confirmed).

With caution

History of QT interval prolongation; ventricular arrhythmias, including torsade de pointes; significant bradycardia; recent acute myocardial infarction; decompensated heart failure; hypokalemia and/or hypomagnesemia (electrolyte disturbances should be corrected before treatment with citalopram); severe renal insufficiency (creatinine clearance
30 ml/min); severe hepatic insufficiency (careful dosage adjustment is recommended); severe suicidal behavior (close monitoring of patients until improvement in several weeks after treatment start is required); diabetes (adjustment of insulin dose and/or oral hypoglycemic agents may be required); susceptibility to bleeding (especially when concomitant use with drugs that affect platelet function or drugs that may increase the risk of bleeding); concomitant use with MAO inhibitor B selegiline, serotonergic drugs drugs that lower the seizure threshold; cimetidine (increased citalopram equilibrium concentration), metoprolol (increased metoprolol concentration), lithium and tryptophan (increased effect), drugs containing St. John’s Wort (increased side effects); oral anticoagulants and drugs that affect blood clotting (increased risk of bleeding); drugs that are weak CYP2C19 isoenzyme metabolites (initial dose should be reduced); ethanol; electroconvulsive therapy; elderly people over 65 (dose should be reduced); pregnancy, breast-feeding.

There is more detailed information about the indications and precautions in the sections “Interaction with other medicinal products”, “Cautions”, “Administration during pregnancy and breastfeeding”.

Side effects

The undesirable effects observed when taking Citalopram-ALSI are usually mild and transient in nature. They occur most frequently in the first or second week of treatment and usually subside considerably as therapy continues.

The following reactions have been found to be dose dependent: increased sweating, dry mouth, insomnia, somnolence, diarrhea, nausea and weakness.

The incidence of adverse reactions associated with taking SSRIs and/or citalopram observed in ≥1% of patients who participated in double-blind, placebo-controlled trials and in the post-registration period is presented below. Frequency is indicated as follows: very common (≥1/10), common (≥1/100 to < 1/10), infrequent (≥1/1000 to < 1/100), rare (≥1/10000 to < 1/1000), very rare (< 1/10000), unknown (cannot be estimated from existing data).

Blood and lymphatic system: unknown – thrombocytopenia.

From the immune system: unknown – hypersensitivity, anaphylactic reactions.

From the endocrine system: unknown – insufficient secretion of antidiuretic hormone (ADH).

Metabolic disorders and eating disorders: often – decreased appetite, decreased body weight; infrequently – increased appetite, increased body weight; rarely – hyponatremia; unknown – hypokalemia.

Mental side: frequent – agitation, decreased libido, anxiety, nervousness, confusion, anorgasmia (in women), unusual dreams; infrequent – aggression, depersonalization, hallucinations, mania; unknown – panic attacks, bruxism, anxiety, suicidal thoughts, suicidal behavior. Cases of suicidal thoughts and behavior have been reported during citalopram therapy and immediately after treatment withdrawal.

Nervous system disorders: very common – somnolence, insomnia; common – tremor, paresthesias, dizziness, impaired attention; infrequent – fainting; rare – grand mal seizures, dyskinesia, taste disorders; unknown – seizure disorders, serotonin syndrome, extrapyramidal disorders, akathisia, movement disorders.

Visual organs: infrequent – mydriasis (dilation of the pupils); unknown – visual disturbances.

Hearing organ and labyrinth disorders: often – tinnitus.

Cardiovascular system: very common – palpitations; infrequent – bradycardia, tachycardia; rare – bleeding; unknown – QT interval prolongation on electrocardiogram, ventricular arrhythmia, including “torsade de pointes” type, orthostatic hypotension.

As for the respiratory system, thorax and mediastinum: frequently – yawning; unknown – nose bleed.

Gastrointestinal tract: very common – dry mouth, nausea; common – diarrhea, vomiting, constipation; unknown – gastrointestinal bleeding (including rectal bleeding).

Hepatic and biliary tract disorders: rare – hepatitis; unknown – disorders of liver function parameters.

Skin and subcutaneous tissue: very common – increased sweating; common – itching; infrequent – urticaria, alopecia, rash, purpura, photosensitization; unknown – ecchymosis, angioedema.

Skeletal, muscular and connective tissue: often – myalgia, arthralgia.

Kidney and urinary tract disorders: unknown – urinary retention.

Reproductive system and mammary glands: often – impotence, impaired ejaculation, lack of ejaculation; infrequent – menorrhagia (in women); unknown – galactorrhea, metrorrhagia (uterine bleeding), priapism (in men).

Body in general and disorders at the site of administration: often – weakness; infrequently – edema; rarely – hyperthermia.

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

In cases of QT interval prolongation and ventricular arrhythmias, including torsade de pointes, have been reported in the post-registration period, predominantly in female patients with hypokalemia or with pre-existing QT interval prolongation and other heart disease.

The withdrawal of citalopram (especially abrupt) often results in “withdrawal” symptoms. The most common are dizziness, sensory disturbances (including paresthesias), sleep disturbances (including insomnia and intense dreaming), agitation or anxiety, nausea and/or vomiting, tremors, confusion, sweating, headache, diarrhea, palpitations, emotional instability, irritability, and visual disturbances. As a rule, these effects are mild to moderate and pass quickly, however, in some patients they may appear in a more acute form and/or for a longer time. If citalopram therapy is no longer required, a gradual withdrawal of the drug by reducing its dose is recommended.

Overdose

Clinical data on citalopram overdose are limited and in many cases are associated with concomitant overdose of other drugs or alcohol. Fatal cases of citalopram overdose have been reported, but most fatal cases have been associated with concomitant overdose of other medications.
Symptoms.
The following symptoms have been documented in overdoses: seizures, tachycardia, somnolence, QT interval prolongation, coma, vomiting, tremors, hypotension, cardiac arrest, nausea, serotonin syndrome, agitation, bradycardia, dizziness, Gis bundle block, prolongation of the QRS complex, hypertension, mydriasis, pirouette arrhythmia, stupor, sweating, cyanosis, hyperventilation, and atrial and ventricular rhythm disturbances.
Treatment.
There is no specific antidote. Treatment is symptomatic and supportive. Gastric lavage should be performed and activated charcoal and osmotic laxatives (e.g., sodium sulfate) should be given. The patient should be intubated if unconsciousness is impaired. ECG and vital signs should be monitored.
ECG monitoring is recommended in case of overdose in patients with congestive heart failure/bradyarrhythmias, in patients receiving concomitant treatment with QT interval prolonging drugs, or in patients with metabolic disorders such as liver failure.

Pregnancy use

Published data in pregnant women (over 2500 completed cases) have not shown the formation of any malformations or feto/neonatal toxicity to citalopram. Nevertheless, citalopram should not be used during pregnancy without extreme necessity and a careful assessment of potential risks and benefits.

If citalopram use continues into late pregnancy, especially in the third trimester, newborns should be monitored. Abrupt withdrawal of the drug during pregnancy should be avoided.

The following symptoms may occur in newborns if the mother takes SSRIs/ SSRIs in late pregnancy: Respiratory distress, cyanosis, apnea, seizures, body temperature instability, difficulty feeding, vomiting, hypoglycemia, muscle hypertonia, muscle hypotonia, hyperreflexia, tremor, increased neuroreflex excitability, irritability, lethargy, constant crying, sleepiness and restless sleep. These symptoms may occur due to the development of withdrawal or serotoninergic syndrome. In most cases, complications develop immediately after or shortly (< 24 hours) after delivery.

Epidemiologic evidence suggests that SSRI use during pregnancy, particularly in the late term, may increase the risk of sustained pulmonary hypertension in the neonate. 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. Breastfed infants are thought to receive about 5% of the maternal daily dose of citalopram, calculated by weight (in mg/kg). Virtually no effects on children have been observed. However, the information available is insufficient to assess the risks to the child. Therefore, breastfeeding is not recommended during treatment with citalopram.

Fertility

The data from animal studies have shown that citalopram can affect sperm quality. Reports on the use of some SSRIs in humans have shown that the effects on semen quality are reversible. So far, no effects of citalopram on fertility have been observed in humans.

Similarities

Cipramil, Citalopram