Cipramil
Use 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, children and adolescents taking antidepressants were more likely to experience suicidal behavior (suicide attempts and suicidal thoughts) and hostility (with a predominance of aggressive behavior, confrontational behavior, and irritation) than those in the placebo group.
When using drugs belonging to the SSRI therapeutic group, including citalopram, the following should be considered.
Paradoxical anxiety
Some patients with panic disorder may experience increased anxiety when starting antidepressant therapy. This paradoxical reaction usually resolves within the first two weeks after starting treatment. To reduce the likelihood of anxiogenic effects, low initial doses are recommended.
Hyponatremia
Rare cases of hyponatremia, apparently due to inadequate secretion of antidiuretic hormone (ADH), have been reported with the use of SSRIs. This reaction was generally reversible if treatment with the drug was discontinued. The risk was higher in older women.
Suicide/suicidal ideation or clinical worsening
Depression is associated with an increased risk of suicidal ideation, self-harm and suicide (suicidal events). This risk persists until stable remission develops. Since improvement may not be observed during the first few weeks of treatment or even a longer period of time, patients should be closely monitored to ensure that such improvement is detected in a timely manner. 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 a comorbidity in relation to a depressive episode. When treating patients with other mental disorders, the same precautions should be taken as when treating patients with a depressive episode.
Patients with a history of suicidal tendencies or patients with a significant level of suicidal thoughts before treatment are at greater risk for suicidal ideation or suicide attempts and should be closely monitored during treatment. A meta-analysis of placebo-controlled clinical trials of antidepressants in adult patients with mental disorders found that there is an increased risk of suicidal behavior in patients under 25 years of age when taking antidepressants compared with placebo. Drug treatment of these patients, and in particular those at high suicidal risk, should be accompanied by careful monitoring, especially early in treatment and during dose changes. Patients (and caregivers) should be warned to monitor for any signs of clinical worsening, suicidal behavior or ideation, or unusual changes in behavior, and to seek immediate medical advice if these symptoms occur.
Akathisia/psychomotor restlessness
The use of drugs from the SSRI/SNRI group is associated with the development of akathisia, characterized by a feeling of subjectively unpleasant or unbearable motor restlessness, restlessness and the need to move. Often patients in this condition cannot sit or stand quietly. Most often this condition occurs during the first weeks of treatment. In patients with such symptoms, increasing the dose may cause a sharp deterioration of the condition.
Mania
Patients with bipolar affective disorder may develop a manic phase. If a manic state develops, citalopram should be discontinued.
Seizures
There is a risk of seizures when taking antidepressants. In any patient who experiences a seizure, citalopram should be discontinued. Citalopram should not be used in patients with unstable epilepsy; Controlled seizures require careful monitoring. If the frequency of seizures increases, citalopram should be discontinued.
Diabetes
In patients with diabetes, the use of SSRIs may change the concentration of glucose in the blood. In this case, dose adjustment of insulin and/or oral hypoglycemic drugs may be required.
Serotonin syndrome
In rare cases, the development of serotonin syndrome has been reported when taking SSRIs. The development of this condition may be indicated by a combination of symptoms such as agitation, myoclonus and hyperthermia. If such phenomena occur, citalopram should be immediately discontinued and symptomatic treatment should be started.
Serotonergic drugs
Citalopram should not be used in combination with drugs that have serotonergic effects, such as sumatriptan or other triptans, tramadol, oxytriptan and tryptophan.
Bleeding
There are reports of the development of skin hemorrhages, such as ecchymosis, gynecological, gastrointestinal bleeding and other hemorrhagic complications of the skin or mucous membranes while taking SSRIs. Caution should be exercised when using SSRIs concomitantly with drugs that affect platelet function or drugs that may increase the risk of bleeding, as well as when treating patients with a history of bleeding disorders.
Electroconvulsive therapy (ECT)
Because clinical experience with the concomitant use of SSRIs and electroconvulsive therapy (ECT) is limited, caution should be used when citalopram and ECT are used concomitantly.
St. John's wort
Citalopram and preparations containing St. John's wort (Hypericum perforatum) should not be used simultaneously, because this may increase the risk of adverse reactions (see section “Interaction with other medicinal products and other forms of interaction”).
Psychosis
Treatment of psychotic patients with a depressive episode may increase the manifestation of psychotic symptoms.
Symptoms "oooMethod of administration and dosage").
QT prolongation
Citalopram has been found to cause dose-dependent prolongation of the QT interval. Cases of QT prolongation and ventricular arrhythmias, including torsade de pointes, have been reported post-marketing, predominantly in female patients with hypokalemia or pre-existing QT prolongation or other cardiac disease.
The drug is recommended to be used with caution in patients with significant bradycardia, in patients who have recently suffered a myocardial infarction, or with decompensated heart failure.
Electrolyte disturbances, 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 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 performed.
Excipients
The tablets contain lactose monohydrate. Patients with hereditary galactose intolerance, lactase deficiency or glucose-galactose malabsorption should not be treated with this drug.
Cipramil 20 mg 28 pcs. film-coated tablets
pharmachologic effect
Antidepressant.
Composition and release form Tsipramil 20 mg 28 pcs. film-coated tablets
Tablets - 1 tablet:
- Active ingredient: citalopram hydrobromide 24.98 mg, which is equivalent to citalopram 20 mg;
- Excipients: corn starch 46.1 mg, lactose monohydrate 23.1 mg, copovidone 6.25 mg, glycerol 85% 2.5 mg, microcrystalline cellulose 18.8 mg, croscarmellose sodium 2.5 mg, magnesium stearate 0.87 mg;
- Shell: hypromellose 5 2.04 mg, macrogol 400 0.408 mg, titanium dioxide (E 171) 0.679 mg.
14 tablets per blister made of PVC/PVDC and aluminum foil. 1 or 2 blisters with instructions for use in a cardboard box.
Description of the dosage form
Oval, white, film-coated tablets with a score, marked “C” and “N” symmetrically around the score.
Directions for use and doses
Cipramil is prescribed orally once a day. The drug can be taken at any time of the day, regardless of meals. The tablets can be divided in half into two equal parts.
Depression
Cipramil is prescribed once a day 20 mg. Depending on the patient's individual response, the dose can be increased to a maximum of 40 mg per day.
The antidepressant effect usually develops 2-4 weeks after the start of treatment. Antidepressant therapy is symptomatic and should be continued for a sufficient period of time, usually at least 6 months after complete elimination of depressive symptoms, to avoid relapse. In patients with recurrent (unipolar) depression, the necessary maintenance therapy may be continued 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/day. Depending on the patient's individual response, the dose can be increased to a maximum of 40 mg/day.
When treating panic disorder, the maximum therapeutic effect of citalopram is achieved approximately 3 months after the start of treatment and persists with continued therapy.
Elderly patients (over 65 years old)
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 teenagers (up to 18 years old)
Cipramil should not be used in children and adolescents under 18 years of age. In addition, there is insufficient long-term data from long-term studies on the safety of the drug in children and adolescents regarding growth, maturation, cognitive and behavioral development.
Decreased kidney function
For mild to moderate renal failure, no dose adjustment is required. Patients with severe renal failure (creatinine clearance below 30 ml/min) should use Cipramil with caution.
Decreased liver function
For mild to moderate liver failure, the recommended initial dose during the first two weeks of treatment is 10 mg/day. Depending on the patient’s individual response, the dose can be increased to a maximum of 20 mg/day. Patients with severe liver failure should use the drug with caution; careful dose titration is required.
Reduced activity of the CYP2C19 isoenzyme
For patients with weak activity of the CYP2C19 isoenzyme, the recommended initial dose during the first two weeks of treatment is 10 mg/day. Depending on the patient’s individual response, the dose can be increased to a maximum of 20 mg/day.
Stopping treatment
Abrupt cessation of treatment should be avoided. When discontinuing treatment with Cipramil, the dose should be gradually reduced over a period of at least 1-2 weeks in order to avoid the occurrence of torsade de pointes reactions; significant bradycardia; recent acute myocardial infarction; decompensated heart failure; hypokalemia and/or hypomagnesemia (electrolyte imbalances should be corrected before starting treatment with citalopram); severe renal failure (creatinine clearance below 30 ml/min); severe liver failure (careful dose selection is recommended); severe suicidal behavior (careful monitoring of patients is required until the condition improves several weeks after the start of treatment); diabetes mellitus (dosage adjustment of insulin and/or oral hypoglycemic drugs may be required); tendency to bleeding (especially when used simultaneously with drugs that affect platelet function or drugs that may increase the risk of bleeding); simultaneous use with the MAO B inhibitor selegiline, serotonergic drugs; drugs that lower the seizure threshold; cimetidine (increased equilibrium concentration of citalopram), metoprolol (increased concentration of metoprolol), lithium and tryptophan (increased effect), drugs containing St. John's wort (increased side effects); oral anticoagulants and medications that affect blood clotting (increasing the risk of bleeding); drugs that are weak metabolites of the CYP2C19 isoenzyme (it is necessary to reduce the initial dose); ethanol; electroconvulsive therapy; elderly people over 65 years of age (dose reduction required); pregnancy, breastfeeding period.
Application of Cipramil 20 mg 28 pcs. film-coated tablets during pregnancy and breastfeeding
Pregnancy
Published data on pregnant women (more than 2500 completed cases) did not show the formation of any malformations and feto-/neonatal toxicity under the influence of citalopram. However, citalopram should not be used during pregnancy unless absolutely necessary and a careful assessment of the potential risks and benefits.
If citalopram use is continued late in pregnancy, especially in the third trimester, neonates should be monitored. Abrupt withdrawal of the drug during pregnancy should be avoided.
If the mother takes SSRIs/SNRIs during late pregnancy, the newborn may experience the following symptoms: respiratory distress, cyanosis, apnea, seizures, instability of body temperature, feeding difficulties, vomiting, hypoglycemia, muscle hypertension, muscle hypotonia, hyperreflexia, tremor, increased neuro-reflex excitability, irritability, lethargy, constant crying, drowsiness and restless sleep. These symptoms may occur due to the development of the syndrome "oooopirouette", stupor, sweating, cyanosis, hyperventilation, as well as atrial and ventricular arrhythmias.
Treatment.
There is no specific antidote. Treatment is symptomatic and supportive. Gastric lavage should be performed and activated charcoal and osmotic laxatives (eg, sodium sulfate) given. If consciousness is impaired, the patient should be intubated. 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 drugs that prolong the QT interval, or in patients with metabolic disorders such as liver failure.
Side effects Tsipramil 20 mg 28 pcs. film-coated tablets
The undesirable effects observed when taking Cipramil are usually mild and transient in nature. They most often occur in the first or second week of treatment and usually subside significantly as therapy continues.
For the following reactions, a dependence on the dose used was found: increased sweating, dry mouth, insomnia, drowsiness, diarrhea, nausea and weakness.
Below are data on the incidence of adverse reactions associated with taking SSRIs and/or citalopram, observed in ≥1% of patients participating in double-blind, placebo-controlled studies and during the post-marketing period. The frequency is indicated as follows: very often (≥1/10), often (≥1/100 to
Blood and lymphatic system disorders: unknown - thrombocytopenia.
Immune system disorders: unknown - hypersensitivity, anaphylactic reactions.
Endocrine system disorders: unknown - insufficient secretion of antidiuretic hormone (ADH).
Metabolic and nutritional disorders: often - loss of appetite, loss of body weight; infrequently - increased appetite, weight gain; rarely - hyponatremia; unknown - hypokalemia.
Mental disorders: 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 suicidal thoughts and behavior have been reported during treatment with citalopram and immediately after discontinuation of treatment.
Nervous system disorders: very often - drowsiness, insomnia; often - tremor, paresthesia, dizziness, impaired attention; infrequently - fainting; rarely - grand mal seizures, dyskinesia, taste disturbances; unknown - seizure disorders, serotonin syndrome, extrapyramidal disorders, akathisia, movement disorders.
Violations of the organ of vision: infrequently - mydriasis (dilation of the pupils); unknown - visual impairment.
Hearing and labyrinthine disorders: often - tinnitus.
Cardiac disorders: uncommon - bradycardia, tachycardia; unknown - prolongation of the QT interval on the electrocardiogram, ventricular arrhythmia, including torsade de pointes.
Vascular disorders: rarely - bleeding; unknown - orthostatic hypotension.
Disorders of the respiratory system, chest and mediastinal organs: often - yawning; unknown - nosebleed.
Gastrointestinal disorders: very often - dry mouth, nausea; often - diarrhea, vomiting, constipation; unknown - gastrointestinal bleeding (including rectal bleeding).
Disorders of the liver and biliary tract: rarely - hepatitis; unknown—impaired liver function parameters.
Disorders of the skin and subcutaneous tissues: very often increased sweating; often - itching; uncommon - urticaria, alopecia, rash, purpura, photosensitivity; unknown - ecchymosis, angioedema.
Musculoskeletal and connective tissue disorders: often - myalgia, arthralgia.
Renal and urinary tract disorders: urinary retention unknown.
Disorders of the reproductive system and mammary glands: often - impotence, ejaculation disorders, lack of ejaculation; infrequently - menorrhagia (in women); unknown - galactorrhea, metrorrhagia (uterine bleeding), priapism (in men).
General disorders and disorders at the injection site: often - weakness; infrequently - swelling; rarely - hyperthermia.
Epidemiological studies primarily involving patients aged 50 years and older have shown an increased risk of bone fractures in patients taking SSRIs and tricyclic antidepressants. The mechanism leading to this risk is unknown.
Cases of QT prolongation and ventricular arrhythmias, including torsades de pointes, have been reported post-marketing, predominantly in female patients with hypokalemia or with pre-existing QT prolongation and other cardiac disease.
Withdrawal from citalopram (especially abruptly) often results in withdrawal symptoms. The most common symptoms include dizziness, sensory disturbances (including paresthesia), sleep disturbances (including insomnia and intense dreams), agitation or anxiety, nausea and/or vomiting, tremor, confusion, sweating, headache, diarrhea, palpitations , emotional instability, irritability, visual disturbances. As a rule, these effects are mild or moderate and disappear quickly, however, in some patients they may occur in a more acute form and/or for a longer period of time. If citalopram therapy is no longer required, it is recommended to gradually discontinue the drug by reducing its dose.
Drug interactions
Pharmacodynamic interaction
Cases of the development of serotonin syndrome have been described with the combined use of citalopram with moclobemide and buspirone.
Contraindicated combinations
MAO inhibitors
Concomitant use of citalopram and MAO inhibitors may lead to serious adverse effects, including serotonin syndrome.
Cases of serious and sometimes fatal reactions have been reported in patients receiving both an SSRI and a monoamine oxidase inhibitor (MAOI), including the irreversible MAOI selegiline and the reversible MAOIs linezolid and moclobemide, as well as in patients who have recently stopped taking an SSRI and started taking an MAOI.
In some of the presented cases, features resembling serotonin syndrome were noted.
Symptoms of interactions between citalopram and MAOIs included pyrexia, rigidity, myoclonus, autonomic instability with rapid fluctuations in vital signs, and mental status changes that included confusion, irritability, and excessive agitation progressing to delirium and coma.
Pimozide
In a study, a single 2 mg dose of pimozide in subjects taking racemic citalopram 40 mg/day for 11 days resulted in an increase in pimozide AUC and Cmax, although not always. Concomitant use of pimozide and citalopram resulted in a mean prolongation of the QTc interval by approximately 10 ms. Given the development of interaction with low doses of pimozide, simultaneous use of citalopram and pimozide is contraindicated.
Combinations requiring caution
Selegiline (selective MAO B inhibitor)
Pharmacokinetic and pharmacodynamic interaction studies with concomitant use of citalopram (20 mg/day) and selegiline (10 mg/day) (MAO B selective dose) did not reveal any clinically significant interactions. The simultaneous use of citalopram and selegiline (at a dose exceeding 10 mg per day) is contraindicated.
Serotonergic drugs
Lithium and tryptophan
In clinical studies of the simultaneous use of lithium and citalopram, no pharmacodynamic interactions were identified. However, increased effects have been reported when SSRIs are coadministered with lithium or tryptophan, so the use of such combinations should be done with caution. Blood lithium levels are monitored as usual.
Concomitant use with serotonergic drugs such as tramadol and sumatriptan may lead to increased serotonergic effects. Until there is definitive 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
The dynamic interaction of SSRIs with herbal preparations containing St. John's wort (Hypericum perforatum) may lead to an increase in the frequency of adverse reactions. Pharmacokinetic interactions have not been studied.
Anticoagulants and agents affecting blood clotting
Caution should be exercised when prescribing citalopram to patients being treated with anticoagulants, drugs that affect platelet function such as non-steroidal anti-inflammatory drugs (NSAIDs), acetylsalicylic acid, dipyridamole and ticlopidine, or other drugs (for example, 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 were observed between citalopram and alcohol. However, the combined use of citalopram and alcohol is not recommended.
Drugs that lower the seizure threshold
SSRIs may lower the seizure threshold. Caution is recommended when used concomitantly with other drugs that may lower the seizure threshold (eg, antidepressants [tricyclics, SSRIs], antipsychotics [phenothiazines, thioxanthenes, and butyrophenones], mefloquine, bupropion, and tramadol).
QT prolongation
Studies of pharmacokinetic and pharmacodynamic interactions between citalopram and other drugs that also prolong the QT interval have shown that additive effects of citalopram and these drugs cannot be excluded. For this reason, co-administration of citalopram and drugs that prolong the QT interval, such as class IA and III antiarrhythmics, antipsychotics (for example, phenothiazine derivatives, pimozide, haloperidol), tricyclic antidepressants, some antimicrobials (for example, sparfloxacin, moxifloxacin, erythromycin IV, pentamidine , drugs for the treatment of malaria, especially halofantrine), some antihistamines (astemizole, mizolastine), can only be carried out after a thorough clinical assessment of the admissibility of such a combination.
Pharmacokinetic interactions
The biotransformation of citalopram to demethylcitalopram is mediated by the 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 food intake affects the absorption and other pharmacokinetic properties of citalopram.
Effect of other drugs on the pharmacokinetics of citalopram When used together, ketoconazole (a strong inhibitor of the CYP3A4 isoenzyme) did not change the pharmacokinetics of citalopram.
Pharmacokinetic interaction studies between lithium and citalopram did not reveal any interactions.
Cimetidine (a strong inhibitor of CYP2D6, 3A4 and 1A2 isoenzymes) caused a moderate increase in the steady-state concentration of citalopram. Caution is recommended when prescribing citalopram in combination with cimetidine. Dose adjustment may be required.
Effect of citalopram on the pharmacokinetics of other drugs Studies of the pharmacokinetic/pharmacodynamic interaction of citalopram and metoprolol (a substrate of the CYP2D6 isoenzyme) showed a 2-fold increase in the concentration of metoprolol, but a statistically significant increase in the effect of metoprolol on blood pressure and heart rate in healthy volunteers was not noted. Caution must be exercised when using metoprolol and citalopram together. Dose adjustment may be required.
Citalopram and demethylcitalopram are minor inhibitors of CYP2C9, CYP2E1 and CYP3A4 and only weak inhibitors of CYP1A2, CYP2C19 and CYP2D6 compared to other SSRIs considered significant inhibitors.
Levomepromazine, digoxin, carbamazepine
No changes or only very small clinically significant changes were observed when citalopram was co-administered with substrates of 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 (indicating that citalopram does not induce or inhibit P-glycoprotein).
Desipramine, imipramine
Pharmacokinetic studies showed no changes in levels of either citalopram or imipramine, although levels of desipramine, the main metabolite of imipramine, were increased. With the simultaneous use of citalopram and desipramine, the level of the latter in the blood plasma was increased. A dose reduction of desipramine may be required.
