Hyacinthis
Ukraine
Table of Contents
INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT GIACINTIA (GIACINTIA)
Composition:
Active substance: escitalopram;
One tablet contains 12.77 mg or 25.54 mg of escitalopram oxalate, equivalent to 10 mg or 20 mg of escitalopram;
Excipients: microcrystalline cellulose, silicified, talc, sodium croscarmellose, magnesium stearate;
Coating: Opadry II White film-coating mixture: hypromellose (hydroxypropylmethylcellulose); lactose monohydrate; polyethylene glycol; titanium dioxide (E 171).
Pharmaceutical form. Film-coated tablets.
Main physicochemical characteristics: white, round, biconvex tablets with a score line on one side, coated with a film coating.
Pharmacotherapeutic group. Antidepressants. Selective serotonin reuptake inhibitors (SSRIs). ATC code N06AB10.
Pharmacological properties.
Pharmacodynamics.
Escitalopram is a selective serotonin reuptake inhibitor (SSRI) antidepressant characterized by high affinity for the primary binding site. It also binds to the allosteric site of the serotonin transporter, although its affinity for this site is 1000 times lower.
Escitalopram has no or very weak affinity for a number of receptors, including serotonin 5-HT1A-, 5-HT2-receptors, dopamine D1- and D2-receptors, α1-, α2-, β-adrenergic receptors, histamine H1, muscarinic cholinergic, benzodiazepine, and opioid receptors.
Inhibition of 5-HT reuptake is the only plausible mechanism of action that can explain the pharmacological and clinical effects of escitalopram.
Pharmacodynamic effects
In one double-blind, placebo-controlled study of ECG parameters in healthy subjects, QTc interval (corrected by Fridericia’s formula) prolongation from baseline was 4.3 ms (90% CI: 2.2, 6.4) with a 10 mg/day dose and 10.7 ms (90% CI: 8.6, 12.8) with a supratherapeutic dose of 30 mg/day (see sections «Contraindications», «Special precautions», «Interaction with other medicinal products and other forms of interaction», «Adverse reactions», «Overdose»).
Clinical efficacy
Major depressive episodes
The efficacy of escitalopram in the acute treatment of major depressive episodes was demonstrated in 3 out of 4 double-blind, placebo-controlled, short-term (8-week) studies. In a long-term relapse prevention study, 274 patients who responded to escitalopram treatment at 10 or 20 mg/day during an initial 8-week open-label phase were randomized to continue escitalopram at the same dose or placebo for up to 36 weeks. In this study, patients continuing escitalopram had a statistically significantly longer time to relapse within the following 36 weeks compared to those receiving placebo.
Social anxiety disorder
Escitalopram was shown to be effective in the treatment of social anxiety disorder in both three short-term (12-week) studies and a 6-month relapse prevention study. In a 24-week dose-ranging study, efficacy of escitalopram was demonstrated at doses of 5, 10, and 20 mg.
Generalized anxiety disorder
Escitalopram at doses of 10 and 20 mg/day was effective in 4 out of 4 placebo-controlled studies.
According to pooled data from three studies with similar design, involving 421 patients in the escitalopram group and 419 patients in the placebo group, response rates were 47.5% and 28.9%, respectively, and remission rates were 37.1% and 20.8%, respectively. A sustained effect was observed from the first week of treatment.
The maintenance effect of escitalopram at 20 mg/day was demonstrated in a 24–76-week randomized maintenance treatment study involving 373 patients who responded to the drug during an initial 12-week open-label treatment period.
Obsessive-compulsive disorder
In a randomized, double-blind clinical trial, escitalopram at a dose of 20 mg/day demonstrated superiority over placebo in the total score on the Y-BOCS scale (Yale-Brown Obsessive Compulsive Scale) after 12 weeks of treatment. At 24 weeks, both 10 mg/day and 20 mg/day doses of escitalopram showed advantages over placebo.
The efficacy of the drug in relapse prevention was demonstrated for escitalopram at doses of 10 and 20 mg/day in patients who responded to escitalopram during a 16-week open-label period and were then included in a 24-week randomized, double-blind, placebo-controlled phase.
Pharmacokinetics.
Absorption is nearly complete and is not affected by food intake. Maximum plasma concentration (Tmax) is reached within 4 hours after administration.
As with racemic citalopram, the absolute bioavailability of escitalopram is expected to be approximately 80%.
Distribution
The apparent volume of distribution (Vd,β/F) after oral administration is approximately 12 to 26 L/kg. The bioavailability of escitalopram is approximately 80%. Protein binding of escitalopram and its main metabolites is less than 80%.
Biological transformation
Metabolism occurs in the liver to demethylated and didemethylated metabolites. Both are pharmacologically active. Alternatively, nitrogen oxidation may occur, forming an N-oxide metabolite. Both the parent compound and metabolites are partially excreted as glucuronides. With repeated administration, mean concentrations of the demethylated and didemethylated metabolites typically amount to 28–31% and < 5%, respectively, of escitalopram concentration. The biotransformation of escitalopram to the demethylated metabolite is primarily mediated by CYP2C19. Some contribution of CYP3A4 and CYP2D6 isoenzymes to this process is possible.
Elimination
The elimination half-life (t½β) of the drug is approximately 30 hours. Oral clearance (Cloral) is approximately 0.6 L/min. The main metabolites have longer elimination half-lives. Escitalopram and its main metabolites are eliminated via the liver (metabolic pathway) and kidneys. The majority of the dose is excreted in urine as metabolites.
Linearity
The pharmacokinetics of escitalopram are linear. Steady-state concentration is reached after approximately 1 week. Mean steady-state concentrations of 50 nmol/L (range 20–125 nmol/L) are achieved with a daily dose of 10 mg.
Elderly patients
In patients aged 65 years and older, escitalopram is eliminated more slowly than in younger patients. Systemic exposure (AUC) in healthy elderly volunteers is approximately 50% higher than in younger healthy volunteers (see section «Dosage and administration»).
Hepatic impairment
In patients with mild to moderate hepatic dysfunction (Child-Pugh classes A and B), elimination half-life was twice as long and exposure was 60% higher compared to individuals with normal liver function (see section «Dosage and administration»).
Renal impairment
In patients with reduced renal function (CLcr 10–53 mL/min), prolonged elimination half-life and slightly increased exposure were observed with racemic citalopram. Plasma concentrations of metabolites have not been studied but may be elevated (see section «Dosage and administration»).
Polymorphism
Patients with poor CYP2C19 metabolic function had twice the plasma concentration of escitalopram compared to patients with normal CYP2C19 function. No significant changes in exposure were observed with reduced CYP2D6 function (see section «Dosage and administration»).
Clinical characteristics.
Indications.
Treatment of major depressive episodes, panic disorders with or without agoraphobia, social anxiety disorders (social phobia), generalized anxiety disorders, obsessive-compulsive disorders.
Contraindications.
Hypersensitivity to escitalopram or to any of the excipients of the medicinal product.
Concomitant use with non-selective irreversible monoamine oxidase inhibitors (MAOIs) is contraindicated due to the risk of developing serotonin syndrome, characterized by agitation, tremor, hyperthermia, and other symptoms (see section "Interaction with other medicinal products and other forms of interaction").
Combination of escitalopram with reversible MAO-A inhibitors (e.g., moclobemide) or the reversible non-selective MAO inhibitor linezolid is contraindicated due to the risk of serotonin syndrome (see section "Interaction with other medicinal products and other forms of interaction").
Escitalopram is contraindicated in patients with known QT interval prolongation or congenital long QT syndrome.
Concomitant use of escitalopram with medicinal products capable of prolonging the QT interval is contraindicated (see section "Interaction with other medicinal products and other forms of interaction").
Interaction with other medicinal products and other forms of interaction.
Pharmacodynamic interactions
Contraindicated combinations
Non-selective irreversible MAOIs
Serious reactions have been reported in patients taking SSRIs in combination with non-selective irreversible MAOIs, and in patients who recently discontinued SSRIs and started MAOIs (see section "Contraindications"). In some cases, serotonin syndrome developed (see section "Adverse reactions"). Combination of escitalopram with non-selective irreversible MAOIs is contraindicated. Treatment with escitalopram should be initiated no earlier than 14 days after discontinuation of irreversible MAOIs. Treatment with non-selective irreversible MAOIs should not be initiated earlier than 7 days after discontinuation of escitalopram.
Combinations requiring caution
Reversible selective MAO-A inhibitor (moclobemide)
Due to the risk of serotonin syndrome, combination of escitalopram with the MAO-A inhibitor moclobemide is contraindicated (see section "Contraindications"). If combination is deemed necessary, treatment should begin with the lowest recommended doses and enhanced clinical monitoring is required.
Non-selective reversible MAO inhibitor (linezolid)
The antibiotic linezolid is a non-selective reversible MAO inhibitor and should not be administered to patients receiving escitalopram. If such a combination is necessary, the lowest recommended doses of both agents should be used under close clinical supervision (see section "Contraindications").
Selective irreversible MAO-B inhibitor (selegiline)
Combination with selegiline (an irreversible MAO-B inhibitor) requires caution due to the risk of serotonin syndrome.
Selegiline at doses up to 10 mg/day has been safely used concomitantly with racemic citalopram.
QT interval prolongation
Pharmacokinetic and pharmacodynamic studies of escitalopram in combination with other medicinal products that prolong the QT interval have not been conducted. When escitalopram is used concomitantly with such agents, an additive effect cannot be excluded. Therefore, concomitant use of escitalopram with medicinal products that prolong the QT interval, such as Class IA and III antiarrhythmics, antipsychotics (e.g., phenothiazine derivatives, pimozide, haloperidol), tricyclic antidepressants, certain antimicrobial agents (e.g., sparfloxacin, moxifloxacin, intravenous erythromycin, pentamidine, antimalarials including halofantrine), certain antihistamines (astemizole, hydroxyzine, mizolastine), is contraindicated.
Serotonergic medicinal products
Concomitant use with serotonergic agents (e.g., tramadol, sumatriptan, and other triptans) may lead to serotonin syndrome.
Medicinal products that lower seizure threshold
SSRIs may lower the seizure threshold. Caution is recommended when co-administering agents that may lower the seizure threshold (e.g., antidepressants (tricyclics, SSRIs), neuroleptics (phenothiazines, thioxanthenes, butyrophenones), mefloquine, bupropion, and tramadol).
Lithium, tryptophan
Cases of enhanced effects have been reported with concomitant use of SSRIs and lithium or tryptophan. Therefore, co-administration of these agents with escitalopram should be done with caution.
St. John’s wort
Concomitant use of SSRIs and herbal preparations containing St. John’s wort may increase the frequency of adverse reactions.
Anticoagulants
The effects of anticoagulants may be altered when used concomitantly with escitalopram. If patients are taking oral anticoagulants, careful monitoring of the coagulation system before and after initiation of escitalopram is required (see section "Special precautions for use").
Concomitant use of non-steroidal anti-inflammatory drugs (NSAIDs) may increase the risk of bleeding (see section "Special precautions for use").
Alcohol
Escitalopram does not exhibit pharmacodynamic or pharmacokinetic interaction with alcohol. However, as with other psychotropic medicinal products, combination with alcohol is not recommended.
Medicinal products causing hypokalaemia/hypomagnesaemia
Caution should be exercised when using concomitantly medicinal products that may cause hypokalaemia/hypomagnesaemia, as this may increase the risk of developing malignant arrhythmias (see section "Special precautions for use").
Pharmacokinetic interactions
Effect of other agents on escitalopram pharmacokinetics
Metabolism of escitalopram is primarily mediated by CYP2C19. Enzymes CYP3A4 and CYP2D6 may also play a minor role in its metabolism. The metabolism of the main metabolite S-DCT (desmethyl escitalopram) appears to be partially catalyzed by CYP2D6.
Concomitant administration of escitalopram and omeprazole 30 mg once daily (a CYP2C19 inhibitor) results in a moderate (approximately 50%) increase in plasma escitalopram concentrations.
Concomitant use of escitalopram and cimetidine 400 mg twice daily (a moderate general enzyme inhibitor) leads to a moderate (approximately 70%) increase in plasma escitalopram concentrations. Caution should be exercised when combining escitalopram with cimetidine. Dose adjustment may be necessary (see section "Special precautions for use").
Therefore, caution is advised when escitalopram is used concomitantly with CYP2C19 inhibitors (e.g., omeprazole, esomeprazole, fluconazole, fluvoxamine, lansoprazole, ticlopidine) or cimetidine, particularly when prescribing the upper limit doses of escitalopram. Dose reduction of escitalopram may be necessary depending on clinical assessment.
Effect of escitalopram on the pharmacokinetics of other agents
Escitalopram is an inhibitor of the CYP2D6 enzyme. Caution is recommended when escitalopram is used concomitantly with medicinal products that are primarily metabolized by this enzyme and have a narrow therapeutic index, such as flecainide, propafenone, and metoprolol (in heart failure), or with certain centrally acting agents primarily metabolized by CYP2D6, such as antidepressants (e.g., desipramine, clomipramine, nortriptyline) and antipsychotics (e.g., risperidone, thioridazine, haloperidol). Dose adjustment may be required.
Combination with desipramine or metoprolol resulted in a doubling of plasma levels of these two CYP2D6 substrates.
In vitro studies have demonstrated that escitalopram may also cause slight inhibition of CYP2C19.
Caution is recommended when escitalopram is used concomitantly with medicinal products metabolized by CYP2C19.
Special precautions for use.
The following special precautions apply to the therapeutic class of selective serotonin reuptake inhibitors (SSRIs).
Paradoxical anxiety
Some patients with panic disorders may experience increased anxiety at the beginning of treatment with antidepressants. This paradoxical reaction usually resolves within two weeks of treatment. To reduce the likelihood of an anxiogenic effect, a low initial dose is recommended (see section "Dosage and administration").
Seizures
Escitalopram should be discontinued if a patient develops a first seizure or if seizures increase in frequency (in patients with a confirmed diagnosis of epilepsy). SSRIs should be avoided in patients with unstable epilepsy, and patients with controlled epilepsy should be closely monitored.
Mania
SSRIs should be used with caution in patients with a history of mania/hypomania. If a manic state develops, SSRIs should be discontinued.
Diabetes
In patients with diabetes mellitus, treatment with SSRIs may alter glycaemic control. The dose of insulin and/or oral hypoglycaemic agents may require adjustment.
Suicide, suicidal thoughts or clinical worsening
Depression is associated with a risk of suicidal thoughts, self-harm and suicide. This risk persists until sustained remission occurs. Since improvement may not occur during the first few weeks of treatment or longer, patients should be carefully monitored until their condition improves. It is known that the risk of suicide may increase in the early stages of recovery.
Other conditions for which escitalopram is used may also be associated with a risk of suicidal behaviour. In addition, these conditions may be comorbid with major depressive disorder. These warnings also apply to the treatment of patients with other psychiatric disorders.
Patients with a history of suicidal behaviour prior to the start of treatment are at the highest risk of suicidal thoughts or attempts and require close monitoring during treatment. A meta-analysis of clinical trials revealed an increased risk of suicidal behaviour in patients under 25 years of age treated with antidepressants compared to those receiving placebo. Close monitoring of high-risk patients is particularly necessary at the beginning of treatment and when the dose is changed.
Patients and their caregivers should be advised to monitor for any worsening of symptoms, suicidal behaviour or thoughts, and unusual changes in behaviour, and to seek immediate medical advice if such symptoms develop.
Akathisia/psychomotor agitation
The use of SSRIs/serotonin-norepinephrine reuptake inhibitors (SNRIs) has been associated with the development of akathisia—a condition characterised by an unpleasant, distressing sense of restlessness and a need to move, often accompanied by an inability to sit or stand still. This condition is most likely to occur during the first few weeks of treatment. Dose increases may worsen symptoms in patients who develop such symptoms.
Hyponatraemia
Hyponatraemia, possibly related to impaired secretion of antidiuretic hormone (SIADH), has been reported rarely with SSRIs and usually resolves after discontinuation of therapy. SSRIs should be prescribed with caution in patients at risk (elderly patients, patients with liver cirrhosis, or those receiving concomitant medications that may cause hyponatraemia).
Bleeding
Skin haemorrhage, ecchymosis and purpura may occur during treatment with SSRIs. SSRIs/SNRIs may increase the risk of postpartum haemorrhage (see sections "Use in pregnancy or breastfeeding" and "Adverse reactions"). SSRIs should be used with caution in patients receiving concomitant anticoagulants, drugs affecting platelet function (e.g. atypical antipsychotics, phenothiazines, tricyclic antidepressants, acetylsalicylic acid and non-steroidal anti-inflammatory drugs, dipyridamole and ticlopidine), and in patients with a predisposition to bleeding.
Electroconvulsive therapy (ECT)
Clinical experience with the concomitant use of SSRIs and ECT is limited; therefore, caution is recommended.
Reversible, selective MAO-A inhibitors
Combining escitalopram with MAO-A inhibitors is not recommended due to the risk of serotonin syndrome.
Serotonin syndrome
Caution is advised when escitalopram is used concomitantly with serotonergic agents such as sumatriptan or other triptans, tramadol, and tryptophan.
There have been reports of serotonin syndrome in isolated cases in patients taking SSRIs concomitantly with serotonergic drugs. Escitalopram should be used with caution when combined with other serotonergic drugs. The combination of symptoms such as agitation, tremor, myoclonus, and hyperthermia may indicate the development of this condition. In such cases, the SSRI and the serotonergic agent should be discontinued immediately and symptomatic treatment initiated.
St. John's wort
Concomitant use of SSRIs and herbal preparations containing St. John's wort may increase the frequency of adverse reactions (see section "Interaction with other medicinal products and other forms of interaction").
Withdrawal symptoms
Withdrawal symptoms upon discontinuation of treatment, especially abrupt discontinuation, are common. In clinical trials, adverse reactions during discontinuation occurred in approximately 25% of patients treated with escitalopram and in 15% of patients receiving placebo.
The risk of withdrawal symptoms may depend on several factors, including duration of treatment, dose, and rate of dose reduction. Dizziness, sensory disturbances (including paraesthesia and electric shock sensations), sleep disturbances (including insomnia and vivid dreams), agitation or anxiety, nausea and/or vomiting, tremor, confusion, sweating, headache, diarrhoea, palpitations, emotional instability, irritability, and visual disturbances are the most commonly reported reactions. These symptoms are usually mild or moderate in severity, but may be severe in some patients. They typically occur within the first few days after stopping treatment, although very rare reports describe similar symptoms in patients who accidentally missed a dose. Withdrawal symptoms usually resolve within 2 weeks, but may be prolonged (2–3 months or longer) in some patients. Therefore, it is recommended that escitalopram treatment be gradually discontinued by reducing the dose over several weeks or months, depending on the patient's condition (see section "Dosage and administration").
Sexual dysfunction
Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) may cause symptoms of sexual dysfunction (see section "Adverse reactions"). There have been reports of persistent sexual dysfunction, where symptoms persisted despite discontinuation of SSRIs/SNRIs.
Ischaemic heart disease
Due to limited clinical experience, caution is recommended when using the drug in patients with ischaemic heart disease.
QT interval prolongation
Escitalopram has been shown to cause dose-dependent QT interval prolongation. In the post-marketing period, cases of QT interval prolongation and ventricular arrhythmias, including polymorphic ventricular tachycardia (torsade de pointes), have been reported, primarily in women, patients with hypokalaemia, and patients with pre-existing QT prolongation or other cardiac diseases (see sections "Contraindications", "Interaction with other medicinal products and other forms of interaction", "Adverse reactions", "Overdose", and "Pharmacodynamics").
The drug should be used with caution in patients with marked bradycardia and in patients with recent acute myocardial infarction or decompensated heart failure.
Electrolyte imbalances such as hypokalaemia and hypomagnesaemia increase the risk of developing malignant arrhythmias and should be corrected before starting escitalopram treatment.
In patients with stable cardiac disease, a thorough assessment of ECG parameters should be performed before initiating escitalopram treatment.
If signs of cardiac arrhythmia occur during treatment with escitalopram, the drug should be discontinued and an ECG performed.
Closed-angle glaucoma
SSRIs, including escitalopram, may affect pupil size, leading to mydriasis. This mydriatic effect may potentially narrow the anterior chamber angle of the eye, resulting in increased intraocular pressure and closed-angle glaucoma, particularly in predisposed patients. Therefore, escitalopram should be used with caution in patients with closed-angle glaucoma or a history of glaucoma.
Excipients
This medicinal product contains less than 1 mmol of sodium (23 mg) per tablet, i.e. it is essentially "sodium-free".
The medicine contains lactose. If you have been diagnosed with an intolerance to certain sugars, consult your doctor before taking this medicine.
Use during pregnancy or breastfeeding.
Pregnancy
Clinical data on the use of escitalopram for treatment during pregnancy are limited. Animal studies have shown reproductive toxicity.
Escitalopram is contraindicated during pregnancy except in cases where a careful evaluation of risks and benefits has clearly demonstrated the necessity of treatment. Newborns whose mothers have taken escitalopram during pregnancy, especially in the third trimester, should be carefully monitored. Abrupt discontinuation of the drug during pregnancy should be avoided.
In newborns whose mothers have taken SSRIs/SNRIs during late pregnancy, the following symptoms may occur: respiratory distress, cyanosis, apnoea, seizures, temperature instability, feeding difficulties, vomiting, hypoglycaemia, hypertension, hypotension, hyperreflexia, tremor, nervous agitation, irritability, apathy, persistent crying, somnolence, and sleep disturbances. These symptoms may be due to either serotonergic effects or withdrawal symptoms. In most cases, such complications occur immediately or shortly (within 24 hours) after delivery.
Epidemiological data indicate that the use of SSRIs during pregnancy may increase the risk of persistent pulmonary hypertension in the newborn (up to 5 cases per 1000 pregnancies, according to observational studies). In the general population, 1 to 2 cases per 1000 pregnancies occur.
Breastfeeding
Since escitalopram passes into breast milk, breastfeeding is not recommended during treatment.
Observational data suggest an increased risk (less than 2-fold) of postpartum haemorrhage after use of SSRIs or SNRIs within one month before delivery (see sections "Adverse reactions" and "Special precautions for use").
Fertility
Animal studies have shown that escitalopram may affect sperm quality. Reports on the use of certain SSRIs in humans suggest that the effect on sperm quality is reversible. No effect on human fertility has been observed to date.
Ability to drive and use machines.
Although escitalopram does not affect intellectual or psychomotor performance, any psychoactive drug may impair skills or the ability to make prudent decisions. Patients should be warned about the potential risk of impaired ability to drive or operate machinery.
Method of Administration and Dosage
The safety of doses exceeding 20 mg per day has not been established.
The medicinal product is administered orally once daily to adults, independent of food intake.
Major Depressive Episode
The usual dose is 10 mg once daily. Depending on individual patient sensitivity, the daily dose may be increased to a maximum of 20 mg.
Antidepressant effect usually occurs within 2–4 weeks. After symptom remission, treatment should be continued for at least 6 months to consolidate the therapeutic effect.
Panic Disorders with or without Agoraphobia
During the first week, an initial dose of 5 mg per day is recommended before increasing to 10 mg per day. Subsequently, the dose may be increased to a maximum of 20 mg per day, depending on individual patient sensitivity.
Maximum therapeutic effect in treating panic disorders is achieved within 3 months. The duration of treatment spans several months and depends on disease severity.
Social Anxiety Disorders (Social Phobia)
The usual dose is 10 mg once daily. Symptom relief typically requires 2–4 weeks of therapy. Thereafter, depending on individual patient response, the dose may be reduced to 5 mg or increased to a maximum of 20 mg per day.
Social anxiety disorder is a chronic condition; therefore, treatment should be continued for at least 12 weeks to consolidate the effect.
Long-term treatment for 6 months has been shown to prevent relapse and may be prescribed individually; benefits of treatment should be regularly evaluated.
Social anxiety disorder is a clearly defined diagnostic term for a specific disorder and should not be confused with excessive shyness. Pharmacotherapy is indicated only when this disorder significantly impairs professional functioning and social activity.
The value of this treatment compared to cognitive-behavioral therapy has not been evaluated. Pharmacotherapy is one component of an overall treatment strategy.
Generalized Anxiety Disorders
The usual dose is 10 mg of the drug once daily. Depending on individual sensitivity, the dose may be increased up to a maximum of 20 mg per day.
Long-term treatment has been studied for at least 6 months in patients receiving a daily dose of 20 mg; benefits of treatment should be regularly evaluated (see section "Pharmacodynamics").
Obsessive-Compulsive Disorders (OCD)
The usual initial dose is 10 mg once daily. Depending on individual patient sensitivity, the dose may be increased to 20 mg per day. OCD is a chronic condition; treatment should continue for a sufficient duration to ensure complete symptom remission, which may take several months or longer. The benefit of treatment and dosage should be evaluated at regular intervals (see section "Pharmacodynamics").
Elderly Patients (aged 65 years and older)
The initial dose is 5 mg per day. Depending on individual patient sensitivity and severity of depression, the daily dose may be increased to a maximum of 10 mg per day (see section "Pharmacokinetics").
The efficacy of Hyacinthia in elderly patients with social anxiety disorder has not been evaluated.
Paediatric Population
The medicinal product should not be used to treat children and adolescents (under 18 years of age) (see section "Special Warnings and Precautions for Use").
Renal Impairment
No dosage adjustments are required in patients with mild to moderate renal impairment. The drug should be used with caution in patients with severe renal impairment (CLCR < 30 mL/min) (see section "Pharmacokinetics").
Hepatic Impairment
The recommended initial dose for the first two weeks of treatment is 5 mg per day in patients with mild or moderate hepatic impairment. Depending on individual patient response, the dose may be increased to 10 mg per day. The drug should be used with caution and dose titrated very carefully in patients with severe hepatic impairment (see section "Pharmacokinetics").
Reduced CYP2C19 Isoenzyme Activity
For patients with low CYP2C19 isoenzyme activity, the recommended initial dose for the first two weeks of treatment is 5 mg per day. Depending on individual patient response, the dose may be increased to 10 mg per day (see section "Pharmacokin游戏副本tics").
Withdrawal Symptoms upon Discontinuation
Abrupt discontinuation of the drug should be avoided. When stopping escitalopram treatment, the dose should be gradually reduced over at least 1–2 weeks to minimize the risk of withdrawal symptoms (see sections "Special Warnings and Precautions for Use" and "Side Effects"). If intolerable symptoms occur after dose reduction or discontinuation, consideration should be given to resuming the previously prescribed dose. The physician may then continue tapering the dose more gradually.
Children
Antidepressants should not be used to treat children and adolescents (under 18 years of age). Suicidal behavior (suicide attempts and suicidal thoughts) and hostility (mainly aggression, oppositional behavior, and anger) have been observed more frequently in clinical trials among children and adolescents treated with antidepressants compared to those receiving placebo. If a decision to prescribe is made based on clinical judgment, careful monitoring for emergence of suicidal symptoms is essential.
Overdose
Toxicity. Clinical data on escitalopram overdose are limited. Many cases involve concomitant overdose with other medicinal products. In most cases, mild symptoms or asymptomatic overdose have been reported. Fatal outcomes following escitalopram overdose are rare and mostly involve concomitant overdose with other medications. Doses of escitalopram ranging from 400–800 mg have not caused any severe symptoms.
Symptoms. Signs of escitalopram overdose are primarily related to the central nervous system (from dizziness, tremor, and agitation to rare cases of serotonin syndrome, seizures, and coma), gastrointestinal system (nausea, vomiting), cardiovascular system (hypotension, tachycardia, QT interval prolongation, arrhythmias), and fluid/electrolyte imbalance (hypokalemia, hyponatremia).
Treatment. There is no specific antidote. Maintain adequate respiratory function and ensure proper oxygenation. Gastric lavage and activated charcoal may be used. Continuous monitoring of cardiac and vital functions, along with symptomatic and supportive treatment, is recommended.
In cases of overdose, ECG monitoring is recommended for patients with congestive heart failure/bradyarrhythmias, patients concurrently taking medications that prolong the QT interval, and patients with impaired drug metabolism, such as those with hepatic impairment.
Adverse reactions.
Adverse reactions most commonly occur during the first or second week of treatment, and their frequency and intensity usually gradually decrease with continued treatment.
The adverse reactions known for SSRIs and escitalopram, observed during placebo-controlled studies and post-marketing use, are listed below by system organ class and frequency in the table. Frequency is defined as: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1000 to < 1/100), rare (≥ 1/10000 to < 1/1000), very rare (< 1/10000), or frequency not known (cannot be estimated from the available data).
| System, organ, class |
Frequency |
Reaction |
| Disorders of blood and lymphatic system |
Unknown |
Thrombocytopenia |
| Immune system disorders |
Rare |
Anaphylactic reactions |
| Endocrine disorders |
Unknown |
Disturbance in antidiuretic hormone secretion |
| Nutritional and metabolic disorders |
Common |
Decreased or increased appetite, weight gain |
| Uncommon |
Weight loss |
|
| Unknown |
Hypotension, anorexia2 |
|
| Psychiatric disorders |
Common |
Anxiety, restlessness, abnormal dreams, decreased libido, Women: anorgasmia |
| Uncommon |
Teeth grinding, excitement, nervousness, panic attacks, confusion |
|
| Rare |
Aggression, depersonalization, hallucinations |
|
| Unknown |
Mania, suicidal thoughts, suicidal behavior1 |
|
| Nervous system disorders |
Very common |
Headache |
| Common |
Insomnia, somnolence, dizziness, paresthesia, tremor |
|
| Uncommon |
Taste disturbance, sleep disorder, loss of consciousness |
|
| Rare |
Serotonin syndrome |
|
| Unknown |
Dyskinesia, movement disorders, seizures, psychomotor agitation/akathisia2 |
|
| Visual disturbances |
Uncommon |
Pupil dilation, blurred vision |
| Ear and labyrinth disorders |
Uncommon |
Tinnitus |
| Cardiac disorders |
Uncommon |
Tachycardia |
| Rare |
Bradycardia |
|
| Unknown |
QT interval prolongation on electrocardiogram, ventricular arrhythmia, including torsade de pointes |
|
| Vascular disorders |
Unknown |
Orthostatic hypotension |
| Respiratory disorders |
Common |
Sinusitis, yawning |
| Uncommon |
Nosebleeds |
|
| Gastrointestinal disorders |
Very common |
Nausea |
| Common |
Diarrhea, constipation, vomiting, dry mouth |
|
| Uncommon |
Gastrointestinal hemorrhage (including rectal) |
|
| Hepatobiliary disorders |
Unknown |
Hepatitis, changes in liver function tests |
| Skin and subcutaneous tissue disorders |
Common |
Increased sweating |
| Uncommon |
Rash, alopecia, urticaria, pruritus |
|
| Unknown |
Ecchymosis, edema |
|
| Musculoskeletal disorders |
Common |
Arthralgia, myalgia |
| Renal and urinary disorders |
Unknown |
Urinary retention |
| Reproductive system and breast disorders |
Common |
Men: ejaculation disorders, impotence |
| Uncommon |
Women: metrorrhagia, menorrhagia |
|
| Unknown |
Galactorrhea Men: priapism Women: postpartum hemorrhage3 |
|
| General disorders |
Common |
Fatigue, pyrexia |
| Uncommon |
Edema |
1 Suicidal thoughts and behaviors have been reported during treatment with escitalopram or shortly after discontinuation.
2 Such cases are known for the entire class of SSRIs.
3 Cases have been reported for the therapeutic class of SSRIs or SNRIs (see sections "Use during pregnancy or breastfeeding", "Special precautions for use").
QT interval prolongation
During the post-marketing period, cases of QT interval prolongation and ventricular arrhythmias, including polymorphic ventricular tachycardia (torsade de pointes), have been reported, primarily in women, patients with hypokalemia, and patients with pre-existing QT prolongation or other cardiac diseases (see sections "Contraindications", "Special precautions for use", "Interaction with other medicinal products and other forms of interactions", "Overdose", and "Pharmacodynamics").
Class effects of medicinal products
Epidemiological studies, conducted predominantly in patients aged 50 years and older, have demonstrated an increased risk of bone fractures in patients receiving selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants. The mechanism leading to this increased risk is currently unknown.
Withdrawal symptoms
Discontinuation of SSRIs (particularly abrupt discontinuation) usually leads to withdrawal symptoms. Dizziness, sensory disturbances (including paresthesia and electric shock sensations), sleep disturbances (including insomnia and vivid dreams), agitation or anxiety, nausea and/or vomiting, tremor, confusion, sweating, headache, diarrhea, palpitations, emotional instability, irritability, and visual disturbances are the most common reactions. These symptoms are usually mild to moderate in severity and transient, but may be severe and/or prolonged in some patients. Therefore, it is recommended to gradually discontinue escitalopram treatment by dose reduction (see sections "Dosage and administration" and "Special precautions for use").
Reporting of adverse reactions
Reporting of adverse reactions after medicinal product registration is of great importance. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy through the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.
Shelf life. 3 years.
Storage conditions.
Store in the original packaging at a temperature not exceeding 25 °C.
Keep out of reach of children.
Packaging.
Tablets 10 mg
10 tablets in a blister; 3 blisters in a carton.
10 tablets in a blister; 6 blisters in a carton.
Tablets 20 mg
10 tablets in a blister; 3 blisters in a carton.
Prescription category. Prescription only.
Manufacturer. JSC "KYIV VITAMIN PLANT".
Manufacturer's address and location of its business activity.
38 Kopilivska Street, Kyiv, 04073, Ukraine.
Web-site: www.vitamin.com.ua