Estazil

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT ESTAZIL (ESTAZIL)

Composition:

Active substance: escitalopram;

1 tablet contains escitalopram 10 mg or 20 mg (as escitalopram oxalate 12.77 mg or 25.54 mg).

Excipients: lactose monohydrate; colloidal anhydrous silicon dioxide; sodium croscarmellose; sodium carboxymethylcellulose; propyl gallate; talc; magnesium stearate.

Coating: Opadry White 03B28796/Instacoat Universal White A05G12130;

Coating composition: hypromellose, titanium dioxide (E 171), macrogol 400.

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties:

10 mg tablets – white or almost white, round, biconvex, film-coated tablets, engraved on one side with "ML 60", a break line on the other side, and notches on both edges of the break line;

20 mg tablets – white or almost white, round, biconvex, film-coated tablets, engraved on one side with "ML 61", a break line on the other side, and notches on both edges of the break line.

Pharmacotherapeutic group. Antidepressants. Selective serotonin reuptake inhibitors. ATC code N06AB10.

Pharmacological properties.

Pharmacodynamics. Escitalopram is a selective serotonin reuptake inhibitor (SSRI) 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-HT_1A-, 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 using Fridericia's formula) prolongation from baseline was 4.3 ms (90% CI: 2.2, 6.4) with a dose of 10 mg/day and 10.7 ms (90% CI: 8.6, 12.8) with a dose higher than therapeutic – 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 treatment of major depressive episodes during the acute phase 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 treatment with escitalopram at a dose of 10 or 20 mg/day during the 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 showed 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 three short-term (12-week) studies and in a 6-month relapse prevention study. In a 24-week optimal dose 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 a total of 421 patients receiving escitalopram and 419 patients receiving placebo, treatment response was observed in 47.5% and 28.9% of patients, respectively, and remission occurred in 37.1% and 20.8% of patients, respectively. A sustained effect was observed from the first week of treatment.

The maintenance effect of escitalopram at a dose of 20 mg/day was demonstrated in a 24–76-week randomized maintenance treatment study involving 373 patients who responded to the drug during the initial 12-week open-label treatment.

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 Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score after 12 weeks of treatment. At 24 weeks, advantages of escitalopram treatment were observed both at 10 mg/day and 20 mg/day compared to 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 enrolled 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 (T_max) 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 (V_d,β/F) after oral administration is approximately 12 to 26 L/kg. The bioavailability of escitalopram is approximately 80%. Plasma 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 dosing, 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 enzymes to this process is possible.

Elimination

The elimination half-life (T_1/2β) of the drug is approximately 30 hours. Oral clearance (Cl_oral) is approximately 0.6 L/min. The main metabolites have longer 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 concentrations are 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 elderly healthy 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 impaired renal function (Cl_cr 10–53 mL/min), administration of racemic citalopram resulted in a longer elimination half-life and slightly greater exposure. Plasma concentrations of metabolites have not been studied but may be increased (see section «Dosage and administration»).

Polymorphism

Patients with poor CYP2C19 metabolic function had plasma escitalopram concentrations twice as high as those with normal CYP2C19 function. No significant changes in exposure were observed with reduced CYP2D6 function (see section «Dosage and administration»).

Clinical characteristics.

Indications.

Treatment:

¬ major depressive episodes;

¬ panic disorders with/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 treatment with non-selective, irreversible monoamine oxidase inhibitors (MAOIs) is contraindicated due to the risk of developing serotonin syndrome with agitation, tremor, hyperthermia, and other symptoms (see section "Interaction with other medicinal products and other forms of interaction"). Combined use of escitalopram with reversible MAO-A inhibitors (e.g., moclobemide) or the reversible non-selective MAOI 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.

Escitalopram must not be used concomitantly with medicinal products capable of prolonging the QT interval (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, as well as in patients who recently discontinued SSRIs and started MAOI treatment (see section "Contraindications"). In some cases, serotonin syndrome developed (see section "Adverse reactions"). The combination of escitalopram with non-selective irreversible MAOIs is contraindicated. Escitalopram treatment should be initiated no earlier than 14 days after discontinuation of irreversible MAOIs. Non-selective irreversible MAOI treatment 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, the combination of escitalopram with the MAO-A inhibitor moclobemide is contraindicated (see section "Contraindications"). If combination therapy is necessary, treatment should be initiated with the lowest recommended doses and intensified clinical monitoring.

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 possible doses of both drugs 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 combined use of escitalopram 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 capable of lowering 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, these agents should be prescribed concomitantly 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

Changes in the effects of anticoagulants may occur with concomitant use of escitalopram. If patients are taking oral anticoagulants, careful monitoring of the coagulation system is required before and after initiation of escitalopram treatment (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 interactions with alcohol. However, as with all psychotropic medicinal products, combination with alcohol is not recommended.

MEDICINAL PRODUCTS CAUSING HYPOKALEMIA/HYPOMAGNESEMIA

Caution should be exercised when using medicinal products capable of causing hypokalemia/hypomagnesemia concomitantly, as this increases the risk of developing malignant arrhythmias (see section "Special precautions for use").

Pharmacokinetic interactions

Effect of other agents on escitalopram pharmacokinetics

The metabolism of escitalopram is primarily mediated by CYP2C19. CYP3A4 and CYP2D6 enzymes may also play a minor role in its metabolism. The metabolism of the main metabolite S-DCIT (demethylated 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) led 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").

Thus, caution is advised when combining escitalopram with CYP2C19 inhibitors (e.g., omeprazole, esomeprazole, fluconazole, fluvoxamine, lansoprazole, ticlopidine) and 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 minor inhibition of CYP2C19.

Caution is recommended when using escitalopram 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 anxiogenic effects, a low initial dose is recommended (see section "Dosage and administration").

Seizures

Esitalopram should be discontinued if a patient develops a first seizure or experiences an increase in seizure 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. SSRIs should be discontinued if a manic state develops.

Diabetes mellitus

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 a sustained remission is achieved. 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, such 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 have 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 taking antidepressants compared to those receiving placebo. Close monitoring of patients at high risk is particularly necessary at the beginning of treatment and when the dose is changed.

Patients and their caregivers should be warned to monitor for any worsening of symptoms, suicidal behaviour or thoughts, or unusual changes in behaviour, and to seek immediate medical advice if such symptoms develop.

Akathisia/psychomotor agitation

The use of SSRIs/SSRIs is associated with the development of akathisia—a condition characterized by an unpleasant, distressing sense of restlessness and a compelling 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 escalation may be harmful in patients who develop such symptoms.

Hyponatraemia

Hyponatraemia, possibly related to syndrome of inappropriate antidiuretic hormone secretion (SIADH), is rarely observed during SSRI therapy and usually resolves after discontinuation of treatment. SSRIs should be used with caution in patients at risk (elderly patients, patients with liver cirrhosis, or those receiving concomitant medications that can cause hyponatraemia).

Bleeding

Skin haemorrhages, ecchymoses, and purpura may occur during SSRI treatment. 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 nonsteroidal 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.

Serotonin syndrome has been reported in isolated cases in patients taking SSRIs concomitantly with serotonergic agents. Caution is advised when using escitalopram concomitantly with medicinal products having serotonergic activity. A 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 should be initiated.

Concomitant use of SSRIs and herbal preparations containing St. John's wort may lead to an increased frequency of adverse reactions (see section "Interaction with other medicinal products and other forms of interaction").

Discontinuation symptoms

Discontinuation symptoms upon stopping treatment, especially abrupt discontinuation, are common. In clinical trials, adverse reactions during discontinuation occurred in approximately 25% of patients receiving escitalopram and in 15% of patients receiving placebo.

The risk of discontinuation symptoms may depend on several factors, including duration and dose of treatment, and the rate of dose reduction. 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, excessive sweating, headache, diarrhea, palpitations, emotional instability, irritability, and visual disturbances are the most commonly reported reactions. These symptoms are usually mild to 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 of similar symptoms have occurred in patients who inadvertently missed a dose. These discontinuation symptoms usually resolve within 2 weeks, but may be prolonged (2–3 months or longer) in some patients. Therefore, it is recommended to gradually discontinue treatment with escitalopram 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 continued despite discontinuation of SSRIs/SNRIs.

Ischaemic heart disease

Due to limited clinical experience, caution is recommended when administering the drug to 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 torsade de pointes, have been reported, primarily in women, patients with hypokalaemia, and patients with pre-existing QT interval 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 who have recently experienced 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 initiating treatment with escitalopram.

In patients with stable cardiac disease, a thorough assessment of ECG parameters should be performed before initiating treatment with escitalopram.

If signs of cardiac arrhythmia occur during treatment with escitalopram, the drug should be discontinued and an ECG should be performed.

Angle-closure glaucoma

SSRIs, including escitalopram, may affect pupil size, leading to mydriasis. This mydriatic effect may potentially narrow the eye angle, resulting in increased intraocular pressure and angle-closure glaucoma, particularly in predisposed patients. Therefore, escitalopram should be used with caution in patients with angle-closure glaucoma or a history of glaucoma.

SSRIs/SNRIs may increase the risk of postpartum haemorrhage (see sections "Use during pregnancy or breastfeeding" and "Adverse reactions").

Excipients

This medicinal product contains less than 1 mmol sodium (23 mg) per tablet, i.e. it is essentially "sodium-free".

Use during pregnancy or breastfeeding.

Pregnancy.

Clinical data on the use of escitalopram in pregnant women are limited.

Animal studies have shown reproductive toxicity.

Escitalopram is contraindicated during pregnancy except in cases where, after careful evaluation of risks and benefits, a clear need for treatment has been established. Newborns whose mothers have taken escitalopram during pregnancy, especially during 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 in 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 discontinuation symptoms. In most cases, such complications occur immediately or shortly (within 24 hours) after delivery.

Epidemiological data have shown 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 data). In the general population, the incidence is 1 to 2 cases per 1000 pregnancies.

Breastfeeding

Since escitalopram passes into breast milk, breastfeeding is not recommended during treatment.

Observational data indicate an increased risk (less than 2-fold) of postpartum haemorrhage following the 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 affect reaction speed when driving or operating machinery.

Although Estazil has negligible or moderate influence on the ability to drive, as with other psychotropic drugs, patients should be warned about the potential risk of adverse effects on the ability to drive or operate machinery.

Method of Administration and Dosage

The safety of doses exceeding 20 mg per day has not been established.

Estazil 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.

The 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

A starting dose of 5 mg per day is recommended during the first week before increasing to 10 mg per day. The dose may subsequently be increased to a maximum of 20 mg per day, depending on individual patient sensitivity.

Maximum therapeutic effect in panic disorders is achieved within 3 months. The duration of treatment is several months and depends on disease severity.

Social Anxiety Disorder (Social Phobia)

The usual dose is 10 mg once daily. Usually, 2–4 weeks of therapy are required to alleviate symptoms. 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, and 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 individually prescribed; the benefits of continued 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 if this disorder significantly impairs professional and social functioning.

The value of pharmacotherapy relative to cognitive-behavioral therapy has not been assessed. Medication is one component of an overall treatment strategy.

Generalized Anxiety Disorder

The usual dose is 10 mg 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 20 mg per day; treatment benefits should be regularly evaluated (see section "Pharmacodynamics").

Obsessive-Compulsive Disorder (OCD)

The usual initial dose is 10 mg once daily. Depending on individual sensitivity, the dose may be increased to 20 mg per day. OCD is a chronic condition; treatment should continue for a sufficient period to ensure complete symptom remission, which may take several months or longer. The benefit of treatment and dosage should be regularly evaluated (see section "Pharmacodynamics").

Elderly Patients (aged 65 years and older)

The initial dose is 5 mg per day. Depending on individual 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 Estazil in elderly patients with social anxiety disorder has not been evaluated.

Pediatric Population

Estazil 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 adjustment is 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 in patients with mild or moderate hepatic impairment is 5 mg per day. Depending on individual patient response, the dose may be increased to 10 mg per day. The drug should be used with caution and carefully titrated in patients with severe hepatic impairment (see section "Pharmacokinetics").

Reduced Activity of the CYP2C19 Isoenzyme

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 "Pharmacokinetics").

Discontinuation Symptoms upon Stopping Treatment

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 discontinuation symptoms (see sections "Special Warnings and Precautions for Use" and "Adverse Reactions"). 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, but 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 clinical decision to prescribe is made, careful monitoring for the emergence of suicidal symptoms is essential.

Overdose

Toxicity. Clinical data on escitalopram overdose are limited. Many cases involve concomitant overdose with other drugs. In most cases, symptoms were mild or absent. Reports of fatal outcomes following escitalopram overdose are rare and mostly involved concomitant overdose with other medications. Doses of escitalopram up to 400–800 mg have not caused 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 taking concomitant drugs 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.

Adverse reactions known for SSRIs and escitalopram, observed during placebo-controlled studies and in clinical use, are listed below by organ systems 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 based on available data).

1 Suicidal thoughts and behaviors have been reported during treatment with escitalopram or shortly after its discontinuation.

2 Such cases are known for all drugs within the entire SSRI class.

3 Cases have been reported for the therapeutic class of SSRIs or SNRI-SSRIs (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, in patients with hypokalemia, and in patients with pre-existing QT interval prolongation or other cardiac diseases (see sections "Contraindications", "Special precautions for use", "Interaction with other medicinal products and other forms of interaction", "Overdose", and "Pharmacodynamics").

Class effects

Epidemiological studies, conducted primarily 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 (especially 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, excessive sweating, headache, diarrhea, palpitations, emotional instability, irritability, and visual disturbances are the most commonly reported 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", "Special precautions for use").

Shelf life.

3 years.

Storage conditions.

Store at temperatures not exceeding 30 °C in the original packaging.

Keep out of reach of children.

Packaging.

10 tablets per blister; 3 or 6 blisters per cardboard package.

Prescription status.

Prescription only.

Manufacturer.

MACLEODS PHARMACEUTICALS LIMITED.

Manufacturer's address and site of operations.

Village Thedda, P.O. Lodhiamaira, Tehsil Baddi, District Solan, Himachal Pradesh, 174101, India.