Escitalopram-teva
Ukraine
Table of Contents
INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT Escitalopram-Teva
Composition:
Active substance: escitalopram;
One tablet contains escitalopram 5 mg, 10 mg, 15 mg, or 20 mg;
Excipients: core: microcrystalline cellulose, anhydrous colloidal silicon dioxide, sodium croscarmellose, stearic acid, magnesium stearate;
coating: hypromellose, titanium dioxide (E 171), polyethylene glycol 400.
Pharmaceutical form. Film-coated tablets.
Main physicochemical properties:
Escitalopram-Teva, 5 mg: white, round, biconvex, film-coated tablets with the imprint "5" on one side of the tablet and smooth on the other side. Cracks or chips are not observed.
Escitalopram-Teva, 10 mg: white, round, biconvex, film-coated tablets with the imprint "10" on one side of the tablet and a break line on the other side. Cracks or chips are not observed.
Escitalopram-Teva, 15 mg: white, round, biconvex, film-coated tablets with a break line on one side, the imprint "S" to the left and "C" to the right of the break line. On the reverse side, the imprint "15" is present, without visible cracks or chips.
The break line is not intended for dividing the tablet into two equal doses, but to facilitate swallowing.
Escitalopram-Teva, 20 mg: white, round, biconvex, film-coated tablets with a break line on one side, the imprint "9" to the left and "3" to the right of the break line. On the reverse side, the imprint "7463" is present, without visible cracks or chips. The tablet can be divided along the break line into two equal parts.
Pharmacotherapeutic group. Antidepressants. Selective serotonin reuptake inhibitors (SSRIs). ATC code N06AB10.
Pharmacological properties.
Pharmacodynamics.
Escitalopram is an antidepressant, a selective serotonin reuptake inhibitor (SSRI), with high affinity for the primary binding site. It also binds to the allosteric site of the serotonin transporter with 1000 times lower affinity.
Escitalopram has no or very weak affinity for a number of receptors, including 5-HT1A-, 5-HT2-, dopamine D1- and D2-receptors, α1-, α2-, β-adrenergic receptors, histamine H1, muscarinic cholinergic, benzodiazepine, and opioid receptors.
Inhibition of serotonin (5-HT) reuptake is considered the likely mechanism of action that may explain the pharmacological and clinical effects of escitalopram.
Pharmacokinetics.
Absorption is almost complete and is not affected by food intake. The median time to reach maximum concentration (median Tmax) is approximately 4 hours. The absolute bioavailability of escitalopram is expected to be 80%.
The apparent volume of distribution (Vd, β/F) after oral administration ranges from 12 to 26 L/kg. Protein binding of escitalopram and its major metabolites to plasma proteins is less than 80%.
Escitalopram is metabolized in the liver to demethylated and didemethylated metabolites. Both are pharmacologically active. Nitrogen may also be oxidized to form an N-oxide metabolite. Both metabolites and the parent compound are partially excreted as glucuronides. After multiple dosing, the average concentrations of the demethyl and didemethyl metabolites are typically 28–31% and <5%, respectively, of the escitalopram concentration. The biotransformation of escitalopram to its demethylated metabolite occurs primarily via the CYP2C19 enzyme. A possible contribution of CYP3A4 and CYP2D6 enzymes is also considered.
The elimination half-life (t1/2) after multiple dosing is approximately 30 hours. The plasma clearance after oral administration is 0.6 L/min. The major metabolites of escitalopram have a longer half-life. Escitalopram and its major metabolites are believed to be eliminated via the liver (metabolic pathway) and kidneys. The majority is excreted in urine as metabolites.
The pharmacokinetics of escitalopram are linear. Steady-state concentration is reached after approximately 1 week. A mean steady-state concentration of 50 nmol/L (range 20–125 nmol/L) is achieved with a daily dose of 10 mg.
Elderly patients (aged 65 years and older)
In elderly patients, escitalopram is eliminated more slowly than in younger patients. The amount of drug in systemic circulation, measured by the pharmacokinetic parameter "area under the curve" (AUC), is 50% higher in elderly patients compared to younger healthy volunteers.
Hepatic impairment
In patients with mild to moderate hepatic insufficiency (Child–Pugh classes A and B), the half-life of escitalopram is nearly doubled, and drug exposure is 60% higher than in individuals with normal liver function.
Renal impairment
In patients with reduced renal function (CLcr 10–53 mL/min), an increased half-life of racemic citalopram and a slight increase in exposure have been observed. Plasma concentrations of metabolites have not been studied, but an increase can be assumed.
In patients with poor CYP2C19 isoenzyme activity, plasma drug concentrations are doubled compared to those with normal escitalopram metabolism.
No significant changes in exposure have been observed in patients with CYP2D6 deficiency.
Clinical characteristics.
Indications.
Treatment:
- Major depressive episodes;
- Panic disorders with or without agoraphobia;
- Social anxiety disorders (social phobia);
- Generalized anxiety disorders;
- Obsessive-compulsive disorders.
Contraindications.
Hypersensitivity to the active substance or to any other component of the medicinal product. Concomitant use of non-selective irreversible monoamine oxidase inhibitors (MAOIs) due to the risk of developing serotonin syndrome, which manifests as agitation, tremor, and hyperthermia.
Combination therapy with escitalopram and reversible MAO-A inhibitors (e.g., moclobemide) or reversible non-selective MAO inhibitors (e.g., linezolid), due to the risk of serotonin syndrome.
Concomitant use of escitalopram with medicinal products that prolong the QT interval is contraindicated in patients known to have QT interval prolongation or congenital long QT syndrome.
Concomitant use with pimozide.
Interaction with other medicinal products and other forms of interaction.
Pharmacodynamic interactions.
Contraindicated combinations
Prolongation of QT interval
Pharmacokinetic and pharmacodynamic studies of escitalopram in combination with other medicinal products that prolong the QT interval have not been conducted. An additive effect of escitalopram and these medicinal products 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), and certain antihistamines (astemizole, mizolastine), is contraindicated.
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 therapy with such MAOIs. In some cases, serotonin syndrome occurred. The combination of escitalopram with non-selective irreversible MAOIs is contraindicated. Escitalopram therapy may be initiated no earlier than 14 days after the last dose of an irreversible MAOI. Conversely, MAOI therapy may be initiated only 7 days after discontinuation of escitalopram.
The combination of pimozide and racemic citalopram resulted in QT interval prolongation of approximately 10 msec. Due to the interaction between escitalopram and low doses of pimozide, and the potentiation of the latter's adverse effects, concomitant use of these drugs is contraindicated.
Reversible non-selective MAOI (linezolid)
The antibiotic linezolid is not recommended for administration to patients receiving escitalopram therapy. If such a combination is necessary, treatment should be initiated at the lowest recommended dose with mandatory close clinical monitoring.
Reversible selective MAOI type A (moclobemide)
Concomitant use of escitalopram with a reversible selective MAOI type A (moclobemide) is not recommended due to the risk of serotonin syndrome. If such a combination is necessary, treatment should be initiated at the lowest recommended dose with mandatory close clinical monitoring. Escitalopram therapy may be initiated no earlier than 1 day after discontinuation of the reversible MAOI moclobemide.
Irreversible selective MAO-B inhibitor (selegiline)
Due to the risk of serotonin syndrome, caution is required when using escitalopram concomitantly with selegiline. For concomitant use with racemic citalopram, selegiline doses up to 10 mg per day are considered safe.
Combinations requiring caution
Serotonergic medicinal products
Concomitant use with serotonergic medicinal products (e.g., opioids such as tramadol and buprenorphine; sumatriptan and other triptans) may lead to the development of serotonin syndrome.
Medicinal products that lower the seizure threshold
SSRIs may lower the seizure threshold. Caution is required when prescribing escitalopram concomitantly with other medicinal products that may reduce the seizure threshold [e.g., antidepressants (tricyclics, SSRIs), neuroleptics (phenothiazines, thioxanthenes, and butyrophenones), mefloquine, bupropion, and tramadol].
Lithium, tryptophan
Cases of enhanced serotonergic effects have been reported when SSRIs are used in combination with lithium or tryptophan. Therefore, caution is recommended when using escitalopram concomitantly with these medicinal products, and regular monitoring of lithium and tryptophan levels is mandatory.
St. John’s wort
Concomitant use of escitalopram and herbal preparations containing St. John’s wort (Hypericum perforatum) may increase the frequency of adverse reactions; therefore, their concomitant use is not recommended.
Anticoagulants and medicinal products affecting blood coagulation
The effects of anticoagulants may be altered when used concomitantly with escitalopram. Concomitant use of escitalopram and oral anticoagulants requires careful monitoring of blood coagulation parameters, especially before and after discontinuation of escitalopram. Concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDs) may increase the risk of bleeding.
Ethanol
Escitalopram does not exhibit pharmacodynamic or pharmacokinetic interaction with ethanol; however, as with other psychotropic medicinal products, concomitant use of escitalopram with medicinal products containing ethanol is not recommended.
Medicinal products causing hypokalemia/hypomagnesemia
Caution is required when concomitantly using medicinal products that cause hypokalemia/hypomagnesemia, as this increases the risk of developing malignant arrhythmias.
Pharmacokinetic interactions.
Effect of other medicinal products on the pharmacokinetics of escitalopram
The metabolism of escitalopram occurs primarily via CYP2C19, although CYP3A4 and CYP2D6 are also involved to a lesser extent. The isoenzyme CYP2D6 is considered a partial catalyst in the metabolism of the main metabolite S-DCT (demethylated escitalopram).
Concomitant administration of escitalopram and omeprazole 30 mg once daily (a CYP2C19 inhibitor) results in a moderate increase (approximately 50%) in plasma concentration of escitalopram.
Concomitant administration of escitalopram and cimetidine 400 mg twice daily (a moderate general enzyme inhibitor) results in a moderate increase (approximately 70%) in plasma concentration of escitalopram.
Therefore, escitalopram should be prescribed with caution when used concomitantly with inhibitors of cytochrome CYP2C19 (e.g., omeprazole, esomeprazole, fluoxetine, fluconazole, fluvoxamine, lansoprazole, ticlopidine) or cimetidine. When used concomitantly with the above-mentioned medicinal products, adverse effects may necessitate a reduction in the dose of escitalopram.
Effect of escitalopram on the pharmacokinetics of other medicinal products
Escitalopram is an inhibitor of the CYP2D6 isoenzyme. Caution is required when prescribing escitalopram concomitantly with medicinal products metabolized by this isoenzyme and having a narrow therapeutic index, such as flecainide, propafenone, metoprolol (in heart failure), or with CNS-acting drugs primarily metabolized by CYP2D6, such as antidepressants (e.g., desipramine, clomipramine, nortriptyline) and antipsychotics (e.g., risperidone, thioridazine, haloperidol). In such cases, dose adjustment may be necessary.
Concomitant use with desipramine or metoprolol results in a doubling of plasma levels of these two CYP2D6 substrates. Escitalopram causes weak inhibition of CYP2C19 in in vitro studies; therefore, caution is recommended when co-administering medicinal products whose metabolism is mediated by CYP2C19.
Special precautions for use.
The special warnings and precautions listed below apply to the entire therapeutic class of 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 the first two weeks of treatment. To reduce the likelihood of an anxiogenic effect, a low initial dose is recommended.
Seizures
Treatment with escitalopram should be discontinued if a patient develops a first seizure or experiences increased seizure frequency (in patients with established epilepsy diagnosis). SSRIs should be avoided in patients with unstable epilepsy, and patients with controlled epilepsy require careful monitoring.
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 affect glycaemic control (hypoglycaemia or hyperglycaemia). Doses of insulin and/or oral hypoglycaemic agents may require adjustment.
Suicide, suicidal thoughts, or clinical worsening
Depression is associated with an increased risk of suicide, suicidal thoughts, and self-harm (suicidal behaviour). This risk persists until remission is achieved. Since improvement may not occur during the first few weeks of treatment or longer, patients should be closely monitored until their condition improves. It is known that the risk of suicide may increase in the early stages of recovery.
Other psychiatric disorders for which escitalopram is used may also be associated with an increased risk of suicidal behaviour. In addition, these conditions may be comorbid with major depressive disorder. Similar caution is required when treating other psychiatric disorders.
Due to the high risk of suicidal thoughts and behaviours during treatment, close monitoring is essential for patients with a history of suicidal ideation or behaviour, or with significant levels of suicidal thinking prior to treatment initiation. A meta-analysis of placebo-controlled clinical trials of antidepressants in adult patients with psychiatric disorders showed an increased risk of suicidal behaviour with antidepressant use in patients under 25 years of age compared to placebo. Pharmacological therapy should be accompanied by close monitoring of patients, particularly those at increased risk, especially at the beginning of treatment and after dose changes.
Patients (and their caregivers) should be advised to monitor for any worsening of symptoms, suicidal thoughts or behaviours, or unusual changes in behaviour, and to seek immediate medical advice if such symptoms occur.
Akathisia and psychomotor agitation
The use of SSRIs/SNRIs (selective serotonin and norepinephrine reuptake inhibitors) is associated with the development of akathisia – a condition characterized by unpleasant, distressing 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. Increasing the dose may worsen symptoms in patients who develop such reactions.
Hyponatraemia
Isolated cases of hyponatraemia have been reported during SSRI treatment, probably due to syndrome of inappropriate antidiuretic hormone secretion (SIADH), which usually resolves after discontinuation of therapy. Particular caution is required when treating patients at risk (elderly patients, patients with liver cirrhosis, or those taking concomitant medications with hyponatraemic potential).
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 NSAIDs, ticlopidine, and dipyridamole), and in patients with a predisposition to bleeding.
The use of SSRIs/SNRIs may increase the risk of postpartum haemorrhage (see sections "Use during pregnancy or breastfeeding" and "Adverse reactions").
Electroconvulsive therapy (ECT)
Clinical experience with concomitant use of SSRIs and ECT is limited; therefore, caution is recommended.
Reversible selective MAO-A inhibitors
Combining escitalopram with MAO-A inhibitors is contraindicated due to the risk of serotonin syndrome.
Serotonin syndrome
Caution is required when escitalopram is used concomitantly with serotonergic agents such as sumatriptan or other triptans, opioids (e.g. tramadol and buprenorphine), and tryptophan.
Isolated cases of serotonin syndrome have been reported in patients taking SSRIs concomitantly with serotonergic drugs. Symptoms indicating the onset of this condition may include agitation, tremor, myoclonus, and hyperthermia. In such cases, escitalopram and the serotonergic drug should be discontinued immediately, and symptomatic treatment initiated.
St. John’s wort
Concomitant use of SSRIs and herbal preparations containing St. John’s wort (Hypericum perforatum) may increase the frequency of adverse reactions.
Withdrawal symptoms
Withdrawal symptoms usually occur upon discontinuation of treatment (especially abrupt discontinuation). In clinical trials, adverse reactions associated with discontinuation were observed in approximately 25% of patients in the escitalopram group and 15% in the placebo group.
The risk of withdrawal symptoms depends on several factors, including duration of therapy, dose, and the 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, increased sweating, headache, diarrhoea, palpitations, emotional instability, irritability, and visual disturbances have been reported as the most common reactions. These symptoms are generally mild to moderate in severity, but may be severe in some patients. They usually occur within the first few days after discontinuation, although isolated reports describe symptoms occurring after unintentional omission of just one dose. These symptoms are usually self-limiting and resolve within 2 weeks, although in some patients they may persist for longer periods (2–3 months or more). In such cases, it is recommended to discontinue escitalopram gradually over several weeks to several months, depending on the patient's condition.
Coronary heart disease
Due to limited clinical experience, caution is required when treating patients with coronary heart disease.
QT interval prolongation
Escitalopram has been shown to cause dose-dependent QT interval prolongation. During the post-marketing period, cases of QT interval prolongation, including torsades de pointes, have been reported, primarily in female patients with hypokalaemia, pre-existing QT prolongation, or other cardiac conditions.
The drug should be used with caution in patients with marked bradycardia, or in those who have recently experienced acute myocardial infarction or have uncompensated heart failure.
Electrolyte imbalances such as hypokalaemia and hypomagnesaemia increase the risk of malignant arrhythmias and should be corrected before initiating escitalopram treatment.
An ECG should be performed before starting treatment in patients with stable cardiac disease.
If signs of cardiac arrhythmia occur during escitalopram treatment, therapy should be discontinued and an ECG performed.
Alcoholic beverages should not be consumed during treatment with Escitalopram-Teva.
Closed-angle glaucoma
SSRIs, including escitalopram, may affect pupil size, resulting in mydriasis. In turn, pupil dilation may lead to narrowing of the anterior chamber angle and, consequently, increased intraocular pressure and precipitation of 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.
Sexual dysfunction
The use of SSRIs/SNRIs may lead to symptoms of sexual dysfunction. Cases of persistent sexual dysfunction have been reported, in which symptoms persisted even after discontinuation of SSRIs/SNRIs.
Use during pregnancy or breastfeeding.
Pregnancy
Data on the use of escitalopram during pregnancy are limited. Reproductive toxicity studies in animals have shown embryofetotoxic effects without an increased incidence of developmental malformations. Escitalopram is contraindicated during pregnancy except in cases where a careful evaluation of risks and benefits clearly justifies its use. Newborns of mothers who took escitalopram during pregnancy, particularly in the third trimester, should be carefully monitored.
Treatment with the drug during pregnancy should not be discontinued abruptly.
The following complications have been observed in newborns whose mothers took SSRIs/SNRIs late in pregnancy: respiratory distress syndrome, cyanosis, apnoea, seizures, temperature instability, feeding difficulties, vomiting, hypoglycaemia, arterial hypertension, arterial hypotension, hyperreflexia, tremor, jitteriness, nervousness, irritability, somnolence, persistent crying, lethargy, and sleep disturbances. These complications may represent serotonergic effects or withdrawal syndrome. In most cases, complications began immediately or shortly (<24 hours) after delivery.
Use of SSRIs during pregnancy has been associated with an increased risk of persistent pulmonary hypertension in the newborn (PPHN), with an estimated risk of approximately 5 cases per 1000 pregnancies, compared to 1–2 cases per 1000 pregnancies in the general population. Observational data suggest an increased risk (less than 2-fold) of postpartum haemorrhage after use of SSRIs/SNRIs within one month before delivery (see sections "Special precautions for use" and "Adverse reactions").
Breastfeeding
Since escitalopram passes into breast milk, breastfeeding is not recommended during treatment.
Fertility
Animal studies have shown that some SSRIs may affect sperm quality. Reports on the use of certain SSRIs indicate that effects on human sperm quality are reversible. No effect on human fertility has been observed to date.
Ability to affect reaction speed when driving or operating machinery.
Although it has been established that escitalopram does not impair cognitive function or psychomotor performance, any psychoactive drug may impair the ability to think rationally or perform skilled tasks. 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 has not been demonstrated.
The medicinal product Escitalopram-Teva is administered orally once daily, independent of food intake.
Major Depressive Episode
The usual dose is 10 mg daily. Depending on individual patient response, the dose may be increased to a maximum of 20 mg daily. Antidepressant effect usually develops within 2–4 weeks after initiation of treatment. After resolution of depressive symptoms, treatment should be continued for at least 6 months to consolidate the therapeutic response.
Panic Disorders with or without Agoraphobia
A dose of 5 mg daily is recommended during the first week of treatment, which is then increased to 10 mg daily. Depending on individual patient response, the dose may be further increased to a maximum of 20 mg daily.
Maximum therapeutic effect is achieved approximately within 3 months. Treatment continues for several months.
Social Anxiety Disorders
The usual dose is 10 mg daily. Symptom improvement typically occurs within 2–4 weeks. Depending on individual patient response, the dose may be reduced to 5 mg daily or increased to a maximum of 20 mg daily. Since social anxiety disorder is a chronic condition, a minimum recommended treatment duration of 12 weeks is advised to consolidate the achieved effect. To prevent relapse, the medicinal product may be prescribed for up to 6 months, depending on individual patient response. Therapeutic benefit should be regularly evaluated.
Social anxiety disorder has clearly defined diagnostic criteria for a specific condition and should not be confused with exaggerated shyness. Pharmacotherapy is indicated only for disorders significantly affecting professional and social functioning. The efficacy of this treatment compared to cognitive-behavioral therapy has not been studied. Pharmacotherapy should be part of an overall therapeutic strategy.
Generalized Anxiety Disorders
The recommended initial dose is 10 mg daily. Depending on individual patient response, the dose may be increased to a maximum of 20 mg daily. Treatment should be continued for at least 3 months. Long-term use (up to 6 months) at a dose of 20 mg daily is permitted to prevent relapse. The therapeutic benefit and dosage should be regularly evaluated.
Obsessive-Compulsive Disorder (OCD)
The usual dose is 10 mg daily. Depending on individual sensitivity, the dose may be increased to 20 mg daily. OCD is a chronic disorder; treatment should continue for a sufficient duration to ensure complete symptom remission, which may take several months or longer. The therapeutic benefit and dosage should be regularly assessed.
Elderly Patients (aged 65 years and older)
Initial dose: 5 mg daily. Depending on the individual patient's response, the dose may be increased to 10 mg daily. The lowest effective dose should be used.
The efficacy of Escitalopram-Teva in elderly patients with social anxiety disorder has not been studied.
Renal Impairment
Dose adjustment is not required in patients with mild to moderate renal impairment. The medicinal product should be administered with caution in patients with severe renal impairment (CLcr < 30 ml/min).
Hepatic Impairment
In patients with mild to moderate hepatic impairment, the recommended initial dose for the first two weeks is 5 mg daily. Depending on individual patient response, the dose may be increased to 10 mg daily. Caution and careful dose titration are required in patients with severe hepatic impairment.
Reduced CYP2C19 Isoenzyme Activity
For patients with known low CYP2C19 isoenzyme activity, the recommended initial dose of Escitalopram-Teva for the first two weeks is 5 mg daily. Depending on individual patient response, the dose may be increased to 10 mg daily.
Withdrawal Symptoms after Discontinuation
Abrupt discontinuation of this medication should be avoided. The dose of escitalopram should be gradually reduced over 1–2 weeks to minimize potential withdrawal symptoms. If withdrawal symptoms occur during dose reduction, the previous prescribed dose may be reinstated. The physician may then continue to reduce the dose, but more gradually.
Children
Antidepressants are contraindicated for the treatment of children (under 18 years of age). Suicidal behavior (suicide attempts and suicidal thoughts) and hostility (predominantly aggression, oppositional behavior, and anger) have been observed more frequently in 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 the emergence of suicidal symptoms is essential.
Furthermore, there are no data on the long-term safety of antidepressants in children and adolescents regarding growth, sexual maturation, and cognitive and behavioral development.
Overdose
Toxicity. Data on escitalopram overdose are limited and, in many cases, involve concomitant overdose with other medicinal products. In most cases, symptoms were mild or absent. Fatal cases following escitalopram overdose have been rarely reported, and most of these involved concomitant overdose with other drugs. Single doses of escitalopram up to 400–800 mg have not caused severe symptoms.
Symptoms. Signs of escitalopram overdose generally involve the CNS (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), as well as fluid and electrolyte imbalances (hypokalemia, hyponatremia).
Treatment. There is no specific antidote. Supportive care and maintenance of airway patency, respiratory function, and adequate oxygenation are required. Gastric lavage and administration of activated charcoal should be performed as soon as possible after oral ingestion. Continuous monitoring of cardiovascular function and vital signs, combined with general symptomatic and supportive measures, is recommended.
ECG monitoring is recommended in cases of overdose in patients with congestive heart failure/bradyarrhythmia, in patients concurrently taking drugs that prolong the QT interval, or in patients with impaired metabolism, such as those with hepatic impairment.
Adverse reactions.
Adverse reactions most commonly occur during the first and second weeks of treatment and subsequently become less intense, with their frequency decreasing during continued treatment.
The adverse effects typical for all SSRIs and escitalopram, observed during placebo-controlled studies and in clinical practice, are listed below by organ systems and frequency of occurrence.
Frequency classification: 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 available data).
Blood and lymphatic system disorders.
Frequency not known: thrombocytopenia.
Immune system disorders.
Rare: anaphylactic reactions.
Endocrine system disorders.
Frequency not known: disturbance of antidiuretic hormone secretion.
Nutrition and metabolism disorders.
Common: decreased or increased appetite, weight gain.
Uncommon: weight loss.
Frequency not known: hyponatremia, anorexia².
Psychiatric disorders.
Common: anxiety, restlessness, abnormal dreams, decreased libido in men and women, anorgasmia in women.
Uncommon: bruxism, agitation, nervousness, panic attacks, confusion.
Rare: aggression, depersonalization, hallucinations.
Frequency not known: mania, suicidal thoughts, suicidal behavior¹.
Nervous system disorders.
Very common: headache.
Common: insomnia, somnolence, dizziness, paraesthesia, tremor.
Uncommon: taste disturbance, sleep disorders, syncope.
Rare: serotonin syndrome.
Frequency not known: dyskinesia, movement disorders, convulsions, psychomotor restlessness/akathisia².
Eye disorders.
Uncommon: mydriasis, blurred vision.
Ear and labyrinth disorders.
Uncommon: tinnitus.
Cardiac disorders.
Uncommon: tachycardia.
Rare: bradycardia.
Frequency not known: ventricular arrhythmia, including torsade de pointes, QT interval prolongation on ECG, orthostatic hypotension.
Respiratory disorders.
Common: sinusitis, yawning.
Uncommon: epistaxis.
Gastrointestinal disorders.
Very common: nausea.
Common: diarrhea, constipation, vomiting, dry mouth.
Uncommon: gastrointestinal hemorrhage (including rectal).
Hepatobiliary disorders.
Frequency not known: hepatitis, changes in liver function tests.
Skin and subcutaneous tissue disorders.
Common: increased sweating.
Uncommon: skin rash, alopecia, urticaria, pruritus.
Frequency not known: bruising, angioedema.
Musculoskeletal and connective tissue disorders.
Common: arthralgia, myalgia.
Renal and urinary disorders.
Frequency not known: urinary retention.
Reproductive system and breast disorders.
Common: men: ejaculation disorder, impotence.
Uncommon: women: metrorrhagia, menorrhagia.
Frequency not known: galactorrhea; men: priapism; women: postpartum haemorrhage³.
General disorders.
Common: fatigue, pyrexia.
Uncommon: swelling.
¹Cases of suicidal thoughts or behavior were observed both during escitalopram therapy and immediately after discontinuation of treatment.
²These adverse reactions have been reported for the SSRI drug class as a whole.
³This effect has been reported for the SSRI/SNRI drug class as a whole (see sections "Special precautions", "Use during pregnancy or breastfeeding").
QT interval prolongation
During the post-marketing period, cases of QT interval prolongation, including torsade de pointes arrhythmia, have been reported, primarily in female patients with hypokalemia or pre-existing QT interval prolongation or other cardiac conditions.
Class-specific effects of SSRIs
Epidemiological studies, primarily conducted in patients aged 50 years and older, have shown an increased risk of bone fractures in patients receiving SSRIs and tricyclic antidepressants. The mechanism of this phenomenon is unknown.
Withdrawal symptoms upon abrupt discontinuation
Discontinuation of SSRIs/SNRIs (especially abrupt) usually leads to withdrawal symptoms. 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, increased sweating, headache, diarrhea, palpitations, emotional instability, irritability, and visual disturbances have been reported as the most common reactions. These symptoms are usually mild to moderate in severity and transient; however, in some patients, they may be severe and/or prolonged. Therefore, it is recommended to gradually discontinue escitalopram by dose reduction over several weeks or months, depending on the patient's condition.
Shelf life. 3 years.
Storage conditions.
Store at a temperature not exceeding 25°C, in the original packaging to protect from light and moisture, and in a place inaccessible to children.
Packaging.
14 tablets per blister pack, 2 blisters per cardboard box.
Prescription category. Prescription only.
Manufacturer: Teva Operations Poland Sp. z o.o.
Manufacturer's address and place of business.
80 Mogilska Street, 31-546 Kraków, Poland.