Escitalopram Tablets USP 10mg Taj Pharma

Escitalopram Tablets USP 10mg Taj Pharma

1. Name of the medicinal product

Escitalopram 5mg Film-coated Tablets
Escitalopram 10mg Film-coated Tablets
Escitalopram 20mg Film-coated Tablets

2. Qualitative and quantitative composition

a) Each film-coated tablet contains:
Escitalopram Oxalate USP
equivalent to Escitalopram                      5mg
Excipients                                                  q.s
Colour: Titanium Dioxide USP.

b) Each film-coated tablet contains: 
Escitalopram Oxalate USP 
equivalent to Escitalopram                      10mg
Excipients                                                  q.s 
Colour: Titanium Dioxide USP.

c) Each film-coated tablet contains:
Escitalopram Oxalate USP
equivalent to Escitalopram                      20mg
Excipients                                                  q.s
Colour: Titanium Dioxide USP.

For the full list of excipients, see section 6.1.

3. Pharmaceutical form

Film-coated tablet

4. Clinical particulars

4.1 Therapeutic indications

Treatment of

– major depressive episodes

– panic disorder with or without agoraphobia

– social anxiety disorder (social phobia)

– generalised anxiety disorder

– obsessive-compulsive disorder

4.2 Posology and method of administration

Method of administration

Safety of daily doses above 20mg has not been demonstrated.

Escitalopram is administered as a single daily dose and may be taken with or without food.

Posology

Major depressive episodes

Usual dosage is 10mg once daily. Depending on individual patient response, the dose may be increased to a maximum of 20mg daily.

Usually 2-4 weeks are necessary to obtain antidepressant response. After the symptoms resolve, treatment for at least 6 months is required for consolidation of the response.

Panic disorder with or without agoraphobia

An initial dose of 5mg is recommended for the first week before increasing the dose to 10mg daily. The dose may be further increased, up to a maximum of 20mg daily, dependent on individual patient response.

Maximum effectiveness is reached after about 3 months. The treatment lasts several months.

Social anxiety disorder

Usual dosage is 10mg once daily. Usually 2-4 weeks are necessary to obtain symptom relief. The dose may subsequently, depending on individual patient response, be decreased to 5mg or increased to a maximum of 20mg daily.

Social anxiety disorder is a disease with a chronic course, and treatment for 12 weeks is recommended to consolidate response. Long-term treatment of responders has been studied for 6 months and can be considered on an individual basis to prevent relapse; treatment benefits should be re-evaluated at regular intervals.

Social anxiety disorder is a well-defined diagnostic terminology of a specific disorder, which should not be confounded with excessive shyness. Pharmacotherapy is only indicated if the disorder interferes significantly with professional and social activities.

The place of this treatment compared to cognitive behavioural therapy has not been assessed. Pharmacotherapy is part of an overall therapeutic strategy.

Generalised anxiety disorder

Initial dosage is 10mg once daily. Depending on the individual patient response, the dose may be increased to a maximum of 20mg daily.

Long-term treatment of responders has been studied for at least 6 months in patients receiving 20mg daily. Treatment benefits and dose should be re-evaluated at regular intervals (see Section 5.1).

Obsessive-Compulsive Disorder

Initial dosage is 10mg once daily. Depending on the individual patient response, the dose may be increased to a maximum of 20mg daily.

As OCD is a chronic disease, patients should be treated for a sufficient period to ensure that they are symptom free.

Treatment benefits and dose should be re-evaluated at regular intervals (see section 5.1).

Elderly patients (> 65 years of age)

Initial dosage is 5mg once daily. Depending on individual patient response the dose may be increased to 10mg daily (see section 5.2).

The efficacy of Escitalopram in social anxiety disorder has not been studied in elderly patients.

Paediatric population (<18 years)

Escitalopram should not be used in the treatment of children and adolescents under the age of 18 years (see section 4.4).

Reduced renal function

Dosage adjustment is not necessary in patients with mild or moderate renal impairment. Caution is advised in patients with severely reduced renal function (CL_CR less than 30 ml/min) (see section 5.2).

Reduced hepatic function

An initial dose of 5mg daily for the first two weeks of treatment is recommended in patients with mild or moderate hepatic impairment. Depending on individual patient response, the dose may be increased to 10mg daily. Caution and extra careful dose titration is advised in patients with severely reduced hepatic function (see section 5.2).

Poor metabolisers of CYP2C19

For patients who are known to be poor metabolisers with respect to CYP2C19, an initial dose of 5mg daily during the first two weeks of treatment is recommended. Depending on individual patient response, the dose may be increased to 10mg daily (see section 5.2).

Discontinuation symptoms seen when stopping treatment

Abrupt discontinuation should be avoided. When stopping treatment with Escitalopram the dose should be gradually reduced over a period of at least one to two weeks in order to reduce the risk of discontinuation symptoms (see section 4.4 and 4.8). If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. Subsequently, the physician may continue decreasing the dose, but at a more gradual rate.

For the different dosages, film-coated tablets of 5mg, 10mg, 15mg and 20mg are available.

4.3 Contraindications

– Hypersensitivity to the active substance or to any of the excipients listed in section 6.1

– Concomitant treatment with non-selective, irreversible monoamine oxidase inhibitors (MAO-inhibitors) is contraindicated due to the risk of serotonin syndrome with agitation, tremor, hyperthermia etc. (see section 4.5)

– The 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 onset of a serotonine syndrome (see section 4.5)

– Escitalopram is contraindicated in patients with known QT-interval prolongation or congenital long QT syndrome

– Escitalopram is contraindicated together with medicinal products that are known to prolong the QT-interval (see section 4.5)

4.4 Special warnings and precautions for use

The following special warnings and precautions apply to the therapeutic class of SSRIs (Selective Serotonin Re-uptake Inhibitors).

Paediatric Population

Escitalopram should not be used in the treatment of children and adolescents under the age of 18 years. Suicide related behaviours (suicide attempt and suicidal thoughts), and hostility (predominately aggression, oppositional behaviour and anger) were more frequently observed in clinical trials among children and adolescents treated with antidepressants compared to those treated with placebo. If, based on clinical need, a decision to treat is nevertheless taken, the patient should be carefully monitored for the appearance of suicidal symptoms. In addition, long-term safety data in children and adolescents concerning growth, maturation and cognitive and behavioural development are lacking.

Paradoxical anxiety

Some patients with panic disorder may experience increased anxiety symptoms at the beginning of treatment with antidepressants. This paradoxical reaction usually subsides within two weeks during continued treatment. A low starting dose is advised to reduce the likelihood of an anxiogenic effect (see section 4.2).

Seizures

Escitalopram should be discontinued if a patient develops seizures for the first time, or if there is an increase in seizure frequency (in patients with a previous 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 in any patient entering a manic phase.

Diabetes

In patients with diabetes, treatment with an SSRI may alter glycaemic control (hypoglycaemia or hyperglycaemia). Insulin and/or oral hypoglycaemic dosage may need to be adjusted.

Suicide/suicidal thoughts or clinical worsening

Depression is associated with an increased risk of suicidal thoughts, self harm and suicide (suicide-related events). This risk persists until significant remission occurs. As improvement may not occur during the first few weeks or more of treatment, patients should be closely monitored until such improvement occurs. It is general clinical experience that the risk of suicide may increase in the early stages of recovery.

Other psychiatric conditions for which Escitalopram is prescribed can also be associated with an increased risk of suicide-related events. In addition, these conditions may be co-morbid with major depressive disorder. The same precautions observed when treating patients with major depressive disorder should therefore be observed when treating patients with other psychiatric disorders.

Patients with a history of suicide-related events, or those exhibiting a significant degree of suicidal ideation prior to commencement of treatment, are known to be at greater risk of suicidal thoughts or suicide attempts, and should receive careful monitoring during treatment. A meta analysis of placebo controlled clinical trials of antidepressant drugs in adult patients with psychiatric disorders showed an increased risk of suicidal behaviour with antidepressants compared to placebo in patients less than 25 years old. Close supervision of patients and in particular those at high risk should accompany drug therapy especially in early treatment and following dose changes.

Patients (and caregivers of patients) should be alerted about the need to monitor for any clinical worsening, suicidal behaviour or thoughts and unusual changes in behaviour and to seek medical advice immediately if these symptoms present.

Akathisia/psychomotor restlessness

The use of SSRIs/SNRIs has been associated with the development of akathisia, characterised by a subjectively unpleasant or distressing restlessness and need to move often accompanied by an inability to sit or stand still. This is most likely to occur within the first few weeks of treatment. In patients who develop these symptoms, increasing the dose can be detrimental.

Hyponatraemia

Hyponatraemia, probably due to inappropriate antidiuretic hormone secretion (SIADH), has been reported rarely with the use of SSRIs and generally resolves on discontinuation of therapy. Caution should be exercised in patients at risk, such as the elderly, or patients with cirrhosis, or if used in combination with other medications which may cause hyponatraemia.

Haemorrhage

There have been reports of cutaneous bleeding abnormalities, such as ecchymoses and purpura, with SSRIs. Caution is advised in patients taking SSRIs, particularly in concomitant use with oral anticoagulants, with medicinal products known to affect platelet function (e.g. atypical antipsychotics and phenothiazines, most tricyclic antidepressants, acetylsalicylic acid and non-steroidal anti-inflammatory medicinal products (NSAIDs), ticlopidine and dipyridamole) and in patients with known bleeding tendencies.

ECT (electroconvulsive therapy)

There is limited clinical experience of concurrent administration of SSRIs and ECT, therefore caution is advisable.

Serotonin syndrome

Caution is advisable if escitalopram is used concomitantly with medicinal products with serotonergic effects such as sumatriptan or other triptans, tramadol and tryptophan.

In rare cases, serotonin syndrome has been reported in patients using SSRIs concomitantly with serotonergic medicinal products. A combination of symptoms, such as agitation, tremor, myoclonus and hyperthermia may indicate the development of this condition. If this occurs treatment with the SSRI and the serotonergic medicinal product should be discontinued immediately and symptomatic treatment initiated.

Coronary heart disease

Due to limited clinical experience, caution is advised in patients with coronary heart disease (see section 5.3).

QT interval prolongation

Escitalopram has been found to cause a dose-dependent prolongation of the QT-interval. Cases of QT interval prolongation and ventricular arrhythmia including torsade de pointes have been reported during the post-marketing period, predominantly in patients of female gender, with hypokalemia, or with pre-existing QT interval prolongation or other cardiac diseases (see sections 4.3, 4.5, 4.8, 4.9 and 5.1).

Caution is advised in patients with significant bradycardia; or in patients with recent acute myocardial infarction or uncompensated heart failure.

Electrolyte disturbances such as hypokalemia and hypomagnesaemia increase the risk for malignant arrhythmias and should be corrected before treatment with escitalopram is started.

If patients with stable cardiac disease are treated, an ECG review should be considered before treatment is started.

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

St. John´s Wort

Concomitant use of SSRIs and herbal remedies containing St. John´s Wort (Hypericum perforatum) may result in an increased incidence of adverse reactions (see section 4.5).

Discontinuation symptoms seen when stopping treatment

Discontinuation symptoms when stopping treatment are common, particularly if discontinuation is abrupt (see section 4.8). In clinical trials adverse events seen on treatment discontinuation occurred in approximately 25% of patients treated with escitalopram and 15% of patients taking placebo.

The risk of discontinuation symptoms may be dependent on several factors including the duration and dose of therapy and the rate of the dose reduction. Dizziness, sensory disturbances (including paraesthesia and electric shock sensations), sleep disturbances (including insomnia and intense 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. Generally these symptoms are mild to moderate, however in some patients they may be severe in intensity.

They usually occur within the first few days of discontinuing treatment, but there have been very rare reports of such symptoms in patients who have inadvertently missed a dose.

Generally these symptoms are self-limiting and usually resolve within 2 weeks, though in some individuals they may be prolonged (2-3 months or more). It is therefore advised that escitalopram should be gradually tapered when discontinuing treatment over a period of several weeks or months, according to the patient’s needs (see “Discontinuation symptoms seen when stopping treatment”, section 4.2).

Angle-Closure Glaucoma

SSRIs including escitalopram may have an effect on pupil size resulting in mydriasis. This mydriatic effect has the potential to narrow the eye angle resulting in increased intraocular pressure and angle-closure glaucoma, especially in patients pre-disposed. Escitalopram should therefore be used with caution in patients with angle-closure glaucoma or history of glaucoma.

4.5 Interaction with other medicinal products and other forms of interaction

Pharmacodynamic interactions

Contra-indicated combinations:

Irreversible non-selective MAOIs

Cases of serious reactions have been reported in patients receiving an SSRI in combination with a non-selective, irreversible monoamine oxidase inhibitor (MAOI), and in patients who have recently discontinued SSRI treatment and have been started on MAOI treatment (see section 4.3). In some cases, the patient developed serotonin syndrome (see section 4.8).

Escitalopram is contraindicated in combination with non-selective, irreversible MAOIs.

Escitalopram may be started 14 days after discontinuing treatment with an irreversible MAOI and at least one day after discontinuing treatment with the reversible MAOI (RIMA), moclobemide. At least 7 days should elapse after discontinuing escitalopram treatment, before starting a non-selective, irreversible MAOI.

Reversible, selective MAO-A inhibitor (moclobemide) Due to the risk of serotonin syndrome, the combination of escitalopram with a MAO-A inhibitor such as moclobemide is contraindicated (see section 4.3). If the combination proves necessary, it should be started at the minimum recommended dosage and clinical monitoring should be reinforced.

Reversible, non-selective MAO-inhibitor (linezolid)

The antibiotic linezolid is a reversible non-selective MAO-inhibitor and should not be given to patients treated with escitalopram. If the combination proves necessary, it should be given with minimum dosages and under close clinical monitoring (see section 4.3).

Irreversible, selective MAO-B inhibitor (selegiline)

In combination with selegiline (irreversible MAO-B inhibitor), caution is required due to the risk of developing serotonin syndrome. Selegiline doses up to 10mg/day have been safely co-administered with racemic citalopram.

QT interval prolongation

Pharmacokinetic and pharmacodynamic studies of escitalopram combined with other medicinal products that prolong the QT interval have not been performed. An additive effect of escitalopram and these medicinal products cannot be excluded. Therefore, co-administration of escitalopram with medicinal products that prolong the QT interval, such as Class IA and III antiarrhythmics, antipsychotics (e.g. phenotiazine derivatives, pimozide, haloperidol), tricyclic antidepressants, certain antimicrobial agents (e.g. sparfloxacin, moxifloxacin, erythromycin IV, pentamidine, anti-malarian treatment particularly halofantrine), certain antihistamines (astemizole, mizolastine), is contraindicated.

Combinations requiring special precautions for use:

Serotonergic medicinal products

Co-administration with serotonergic medicinal products (e.g. tramadol, sumatriptan and other triptans) may lead to serotonin syndrome.

Medicinal products lowering the seizure threshold

SSRIs can lower the seizure threshold. Caution is advised when concomitantly using other medicinal products capable of lowering the seizure threshold (e.g antidepressants (tricyclics, SSRIs), neuroleptics (phenothiazines, thioxanthenes and butyrophenones), mefloquin, bupropion and tramadol).

Lithium, tryptophan

There have been reports of enhanced effects when SSRIs have been given together with lithium or tryptophan, therefore concomitant use of SSRIs with these medicinal products should be undertaken with caution.

St. John’s Wort

Concomitant use of SSRIs and herbal remedies containing St. John´s Wort (Hypericum perforatum) may result in an increased incidence of adverse reactions (see section 4.4).

Haemorrhage

Altered anti-coagulant effects may occur when escitalopram is combined with oral anticoagulants. Patients receiving oral anticoagulant therapy should receive careful coagulation monitoring when escitalopram is started or stopped (see section 4.4).

Concomitant use of non-steroidal anti-inflammatory drugs (NSAIDs) may increase bleeding-tendency (see section 4.4).

Alcohol

No pharmacodynamic or pharmacokinetic interactions are expected between escitalopram and alcohol. However, as with other psychotropic medicinal products, the combination with alcohol is not advisable.

Medicinal products inducing hypokalemia/hypomagnesaemia

Caution is warranted for concomitant use of hypokalaemia/hypomagnesaemia inducing medicinal products as these conditions increase the risk of malignant arrhythmias (see section 4.4).

Pharmacokinetic interactions

Influence of other medicinal products on the pharmacokinetics of escitalopram

The metabolism of escitalopram is mainly mediated by CYP2C19. CYP3A4 and CYP2D6 may also contribute to the metabolism although to a smaller extent. The metabolism of the major metabolite S-DCT (demethylated escitalopram) seems to be partly catalysed by CYP2D6.

Co-administration of escitalopram with omeprazole 30mg once daily (a CYP2C19 inhibitor) resulted in moderate (approximately 50%) increase in the plasma concentrations of escitalopram.

Co-administration of escitalopram with cimetidine 400mg twice daily (moderately potent general enzyme-inhibitor) resulted in a moderate (approximately 70%) increase in the plasma concentrations of escitalopram. Caution is advised when administering escitalopram in combination with cimetidine. Dose adjustment may be warranted.

Thus, caution should be exercised when used concomitantly with CYP2C19 inhibitors (e.g. omeprazole, esomeprazole, fluvoxamine, lansoprazole, ticlopidine) or cimetidine. A reduction in the dose of escitalopram may be necessary based on monitoring of side-effects during concomitant treatment.

Effect of escitalopram on the pharmacokinetics of other medicinal products

Escitalopram is an inhibitor of the enzyme CYP2D6. Caution is recommended when escitalopram is co-administered with medicinal products that are mainly metabolised by this enzyme, and that have a narrow therapeutic index, e.g. flecainide, propafenone and metoprolol (when used in cardiac failure), or some CNS acting medicinal products that are mainly metabolised by CYP2D6, e.g. antidepressants such as desipramine, clomipramine and nortriptyline or antipsychotics like risperidone, thioridazine and haloperidol. Dosage adjustment may be warranted.

Co-administration with desipramine or metoprolol resulted in both cases in a twofold increase in the plasma levels of these two CYP2D6 substrates.

In vitro studies have demonstrated that escitalopram may also cause weak inhibition of CYP2C19. Caution is recommended with concomitant use of medicinal products that are metabolised by CYP2C19.

4.6 Fertility, pregnancy and lactation

Pregnancy

For escitalopram only limited clinical data are available regarding exposed pregnancies.

In reproductive toxicity studies performed in rats with escitalopram, embryo-fetotoxic effects, but no increased incidence of malformations, were observed (see section 5.3).

Escitalopram should not be used during pregnancy unless clearly necessary and only after careful consideration of the risk/benefit.

Neonates should be observed if maternal use of escitalopram continues into the later stages of pregnancy, particularly in the third trimester. Abrupt discontinuation should be avoided if SSRIs are used during pregnancy.

The following symptoms may occur in the neonate after maternal SSRI/SNRI use in later stages of pregnancy: respiratory distress, cyanosis, apnoea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycaemia, hypertonia, hypotonia, hyperreflexia, tremor, jitteriness, irritability, lethargy, constant crying, somnolence, difficulty sleeping. These symptoms could be due to either serotonergic effects or discontinuation symptoms. In a majority of instances the complications begin immediately or soon (<24 hours) after delivery.

Epidemiological data have suggested that the use of SSRIs in pregnancy, particular in late pregnancy, may increase the risk of persistent pulmonary hypertension in the newborn (PPHN). The observed risk was approximately 5 cases per 1000 pregnancies. In the general population 1 to 2 cases of PPHN per 1000 pregnancies occur.

Breastfeeding

It is expected that escitalopram will be excreted into human milk.

Consequently, breast-feeding is not recommended during treatment.

Fertility

Animal data have shown that citalopram may affect sperm quality (see section 5.3).Human case reports with some SSRIs have shown that an effect on sperm quality is reversible.

Impact on human fertility has not been observed so far.

4.7 Effects on ability to drive and use machines

Although escitalopram has been shown not to affect intellectual function or psychomotor performance, any psychoactive medicinal product may impair judgement or skills. Patients should be cautioned about the potential risk of an influence on their ability to drive a car and operate machinery.

4.8 Undesirable effects

Adverse reactions are most frequent during the first or second week of treatment and usually decrease in intensity and frequency with continued treatment.

Tabulated list of adverse reactions Adverse reactions known for SSRIs and also reported for escitalopram in either placebo-controlled clinical studies or as spontaneous post-marketing events are listed below by system organ class and frequency.

Frequencies are taken from clinical studies; they are not placebo-corrected.

Frequencies are defined as:

Very common (≥1/10)

Common (≥1/100 to <1/10)

Uncommon (≥1/1,000 to <1/100)

Rare (≥1/10,000 to <1/1,000)

Very rare (<1/10,000), or not known (cannot be estimated form the available data).

¹Cases of suicidal ideation and suicidal behaviours have been reported during escitalopram therapy or early after treatment discontinuation (see section 4.4).

²These events have been reported for the therapeutic class of SSRIs.

QT interval prolongation

Cases of QT interval prolongation and ventricular arrhythmia including torsade de pointes have been reported during the post-marketing period, predominantly in patients of female gender, with hypokalemia, or with pre-existing QT interval prolongation or other cardiac diseases (see sections 4.3, 4.4, 4.5, 4.9 and 5.1).

Class effects

Epidemiological studies, mainly conducted in patients 50 years of age and older, show an increased risk of bone fractures in patients receiving SSRIs and TCAs. The mechanism leading to this risk is unknown.

Discontinuation symptoms seen when stopping treatment

Discontinuation of SSRIs/SNRIs (particularly when abrupt) commonly leads to discontinuation symptoms. Dizziness, sensory disturbances (including paraesthesia and electric shock sensations), sleep disturbances (including insomnia and intense 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. Generally these events are mild to moderate and are self-limiting, however, in some patients they may be severe and/or prolonged. It is therefore advised that when escitalopram treatment is no longer required, gradual discontinuation by dose tapering should be carried out (see section 4.2 and 4.4).

4.9 Overdose

Toxicity

Clinical data on escitalopram overdose are limited and many cases involve concomitant overdoses of other drugs. In the majority of cases mild or no symptoms have been reported. Fatal cases of escitalopram overdose have rarely been reported with escitalopram alone; the majority of cases have involved overdose with concomitant medications. Doses between 400 and 800mg of escitalopram alone have been taken without any severe symptoms.

Symptoms

Symptoms seen in reported overdose of escitalopram include symptoms mainly related to the central nervous system (ranging from dizziness, tremor, and agitation to rare cases of serotonin syndrome, convulsion, and coma), the gastrointestinal system (nausea/vomiting), and the cardiovascular system (hypotension, tachycardia, QT interval prolongation, and arrhythmia) and electrolyte/fluid balance conditions (hypokalaemia, hyponatraemia).

Managment

There is no specific antidote. Establish and maintain an airway, ensure adequate oxygenation and respiratory function. Gastric lavage and the use of activated charcoal should be considered. Gastric lavage should be carried out as soon as possible after oral ingestion. Cardiac and vital signs monitoring are recommended along with general symptomatic supportive measures.

ECG monitoring is advised in case of overdose, in patients with congestive heart failure/bradyarrhythmias, in patients using concomitant medications that prolong the QT interval, or in patients with altered metabolism, e.g. liver impairment.

5. Pharmacological properties

5.1 Pharmacodynamic properties

Pharmacotherapeutic group:

Antidepressants, selective serotonin reuptake inhibitors

Mechanism of action

Escitalopram is a selective inhibitor of serotonin (5-HT) re-uptake with high affinity for the primary binding site. It also binds to an allosteric site on the serotonin transporter, with a 1000 fold lower affinity.

Escitalopram has no or low affinity for a number of receptors including 5-HT1A, 5-HT2, DA D1 and D2 receptors, α1-, α2-, β-adrenoceptors, histamine H1, muscarine cholinergic, benzodiazepine, and opioid receptors.

The inhibition of 5-HT re-uptake is the only likely mechanism of action explaining the pharmacological and clinical effects of escitalopram.

Pharmacodynamic effects

In a double-blind, placebo-controlled ECG study in healthy subjects, the change from baseline in QTc (Fridericia-correction) was 4.3 msec (90% CI: 2.2, 6.4) at the 10mg/day dose and 10.7 msec (90% CI: 8.6, 12.8) at the supratherapeutic dose of 30mg/day (see sections 4.3, 4.4, 4.5, 4.8 and 4.9).

Clinical efficacy and safety

Major Depressive Episodes

Escitalopram has been found to be effective in the acute treatment of major depressive episodes in three out of four double-blind, placebo controlled short-term (8-weeks) studies. In a long-term relapse prevention study, 274 patients who had responded during an initial 8-week open label treatment phase with escitalopram 10 or 20mg/day, were randomised to continuation with escitalopram at the same dose, or to placebo, for up to 36 weeks. In this study, patients receiving continued escitalopram experienced a significantly longer time to relapse over the subsequent 36 weeks compared to those receiving placebo.

Social Anxiety Disorder

Escitalopram was effective in both three short-term (12- week) studies and in responders in a 6 months relapse prevention study in social anxiety disorder. In a 24-week dose-finding study, efficacy of 5, 10 and 20mg escitalopram has been demonstrated.

Generalised anxiety disorder

Escitalopram in doses of 10 and 20mg/day was effective in four out of four placebo-controlled studies.

In pooled data from three studies with similar design comprising 421 escitalopram-treated patients and 419 placebo-treated patients there were 47.5% and 28.9% responders respectively and 37.1% and 20.8% remitters. Sustained effect was seen from week 1.

Maintenance of efficacy of escitalopram 20mg/day was demonstrated in a 24 to 76 week, randomised, maintenance of efficacy study in 373 patients who had responded during the initial 12-week open-label treatment.

Obsessive-compulsive disorder

In a randomized, double-blind, clinical study, 20mg/day escitalopram separated from placebo on the Y-BOCS total score after 12 weeks. After 24 weeks, both 10 and 20mg/day escitalopram were superior as compared to placebo.

Prevention of relapse was demonstrated for 10 and 20mg/day escitalopram in patients who responded to escitalopram in a 16-week open-label period and who entered a 24 week, randomized, double blind, placebo controlled period.

5.2 Pharmacokinetic properties

Absorption

Absorption is almost complete and independent of food intake. (Mean time to maximum concentration (mean T_max) is 4 hours after multiple dosing). As with racemic citalopram, the absolute bio-availability of escitalopram is expected to be about 80%.

Distribution

The apparent volume of distribution (Vd,β/F) after oral administration is about 12 to 26 L/kg. The plasma protein binding is below 80% for escitalopram and its main metabolites.

Biotransformation

Escitalopram is metabolised in the liver to the demethylated and didemethylated metabolites. Both of these are pharmacologically active. Alternatively, the nitrogen may be oxidised to form the N-oxide metabolite. Both parent substance and metabolites are partly excreted as glucuronides. After multiple dosing the mean concentrations of the demethyl and didemethyl metabolites are usually 28-31% and <5%, respectively, of the escitalopram concentration. Biotransformation of escitalopram to the demethylated metabolite is mediated primarily by CYP2C19. Some contribution by the enzymes CYP3A4 and CYP2D6 is possible.

Elimination

The elimination half-life (t_½ β) after multiple dosing is about 30 hours and the oral plasma clearance (Cl_oral) is about 0.6 L/min. The major metabolites have a significantly longer half-life.

Escitalopram and its major metabolites are assumed to be eliminated by both the hepatic (metabolic) and the renal routes, with the major part of the dose excreted as metabolites in the urine.

There is linear pharmacokinetics. Steady-state plasma levels are achieved in about 1 week. Average steady-state concentrations of 50 nmol/L (range 20 to 125 nmol/L) are achieved at a daily dose of 10mg.

Elderly patients (> 65 years)

Escitalopram appears to be eliminated more slowly in elderly patients compared to younger patients. Systemic exposure (AUC) is about 50 % higher in elderly compared to young healthy volunteers (see section 4.2).

Reduced hepatic function

In patients with mild or moderate hepatic impairment (Child-Pugh Criteria A and B), the half-life of escitalopram was about twice as long and the exposure was about 60% higher than in subjects with normal liver function (see section 4.2).

Reduced renal function

With racemic citalopram, a longer half-life and a minor increase in exposure have been observed in patients with reduced kidney function (CL_cr 10-53 ml/min). Plasma concentrations of the metabolites have not been studied, but they may be elevated (see section 4.2).

Polymorphism

It has been observed that poor metabolisers with respect to CYP2C19 have twice as high a plasma concentration of escitalopram as extensive metabolisers. No significant change in exposure was observed in poor metabolisers with respect to CYP2D6 (see section 4.2).

5.3 Preclinical safety data

No complete conventional battery of preclinical studies was performed with escitalopram since the bridging toxicokinetic and toxicological studies conducted in rats with escitalopram and citalopram showed a similar profile. Therefore, all the citalopram information can be extrapolated to escitalopram.

In comparative toxicological studies in rats, escitalopram and citalopram caused cardiac toxicity, including congestive heart failure, after treatment for some weeks, when using dosages that caused general toxicity. The cardiotoxicity seemed to correlate with peak plasma concentrations rather than to systemic exposures (AUC). Peak plasma concentrations at no-effect-level were in excess (8-fold) of those achieved in clinical use, while AUC for escitalopram was only 3- to 4-fold higher than the exposure achieved in clinical use. For citalopram AUC values for the S-enantiomer were 6- to 7-fold higher than exposure achieved in clinical use. The findings are probably related to an exaggerated influence on biogenic amines i.e. secondary to the primary pharmacological effects, resulting in hemodynamic effects (reduction in coronary flow) and ischemia. However, the exact mechanism of cardiotoxicity in rats is not clear. Clinical experience with citalopram, and the clinical trial experience with escitalopram, do not indicate that these findings have a clinical correlate.

Increased content of phospholipids has been observed in some tissues e.g. lung, epididymides and liver after treatment for longer periods with escitalopram and citalopram in rats. Findings in the epididymides and liver were seen at exposures similar to that in man. The effect is reversible after treatment cessation. Accumulation of phospholipids (phospholipidosis) in animals has been observed in connection with many cationic amphiphilic medicines. It is not known if this phenomenon has any significant relevance for man.

In the developmental toxicity study in the rat embryotoxic effects (reduced foetal weight and reversible delay of ossification) were observed at exposures in terms of AUC in excess of the exposure achieved during clinical use. No increased frequency of malformations was noted. A pre- and postnatal study showed reduced survival during the lactation period at exposures in terms of AUC in excess of the exposure achieved during clinical use.

Animal data have shown that citalopram induces a reduction of fertility index and pregnancy index, reduction in number in implantation and abnormal sperm at exposure well in excess of human exposure.

No animal data related to this aspect are available for escitalopram.

6. Pharmaceutical particulars

6.1 List of excipients

Tablet core:

Cellulose, microcrystalline, Colloidal anhydrous silica, Croscarmellose sodium

Talc, Magnesium stearate

Coating:

Hypromellose 6cP, Titanium dioxide , Macrogol

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

PVC/PVDC/aluminium blister: 3 years

Plastic (polyethylene) container: 3 years

6.4 Special precautions for storage

PVC/PVDC/aluminium blister: Do not store above 25°C.

Plastic (polyethylene) container: Do not store above 30°C.

6.5 Nature and contents of container

PVC/PVDC/aluminium blister with 14, 20, 28, 30, 50, 56, 60, 98, 100, 200 tablets (5, 10, 15, 20mg)

Plastic (polyethylene) container with 100 (5, 10, 15, 20mg) and 200 (5 and 10mg) tablets

Not all pack sizes may be marketed

6.6 Special precautions for disposal and other handling

No special requirements.

Manufactured By:
Taj Pharmaceuticals Ltd.
at: Plot. No. 220, Mahagujarat
Industrial Estate, At & Post-Moraiya,
Tal-Sanand, Dist- Ahmedabad Gujarat (India)

Escitalopram 5mg Film-coated Tablets
Escitalopram 10mg Film-coated Tablets
Escitalopram 20mg Film-coated Tablets

Package leaflet: Information for the user

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

1 What Escitalopram is and what it is used for
2 What you need to know before you take Escitalopram
3 How to take Escitalopram
4 Possible side effects
5 How to store Escitalopram
6 Contents of the pack and other information

1 What Escitalopram is and what it is used for

Escitalopram is an antidepressant which belongs to the ‘SSRI’ group (selective serotonin reuptake inhibitors). These medicines act on the serotonin-system in the brain by increasing the serotonin level. Disturbances in the serotonin-system are considered an important factor in the development of depression and related diseases.

Escitalopram is used to treat:

• Depressive disorders (episodes of a major depression)
• Panic disorder with or without agoraphobia (e.g. fear of leaving the house, entering shops, being in crowds and in public places)
• Social anxiety disorder (social phobia)
• Generalised anxiety disorder
• Obsessive-compulsive disorder

2 What you need to know before you take Escitalopram

Do not take Escitalopram

• if you are allergic to escitalopram or any of the other ingredients of this medicine (listed in section 6)
• if you take other medicines which belong to a group called MAO inhibitors, including selegiline (used in the treatment of Parkinson´s disease), moclobemide (used in the treatment of depression) and linezolid (an antibiotic)
• If you are born with or have had an episode of abnormal heart rhythm (seen at ECG; an examination to evaluate how the heart is functioning)
• If you take medicines for heart rhythm problems or that may affect the heart’s rhythm (see section 2 “Other medicines and Escitalopram”)

Warnings and precautions

Talk to your doctor, pharmacist or nurse before taking Escitalopram.

Please tell your doctor if you have any other condition or illness, as your doctor may need to take this into consideration. In particular, tell your doctor if you:

• have epilepsy. Treatment with Escitalopram should be stopped if seizures occur or if there is an increase in the seizure frequency (see also section 4 “Possible side effects”)
• suffer from impaired liver or kidney function. Your doctor may need to adjust your dosage
• have diabetes. Treatment with Escitalopram may alter glycaemic control. Insulin and/or oral hypoglycaemic dosage may need to be adjusted
• have a decreased level of sodium in the blood
• have low levels of potassium or magnesium in your blood (hypookalemia/ hypomagnesaemia).
• have a tendency to easily develop bleedings or bruises
• are receiving electroconvulsive treatment
• have coronary heart disease
• suffer or have suffered from heart problems or have recently had a heart attack
• suffer from a heart condition called ‘QT-prolongation’ or if the condition runs in your family
• have a low resting heart-rate and/or you know that you may have salt depletion as a result of prolonged severe diarrhoea and vomiting (being sick) or usage of diuretics (water tablets)
• experience a fast or irregular heartbeat, fainting, collapse or dizziness on standing up, which may indicate abnormal functioning of the heart rate
• have or have a history of glaucoma.

Please note

Some patients with manic-depressive illness may enter into a manic phase. This is characterized by unusual and rapidly changing ideas, inappropriate happiness and excessive physical activity. If you experience this, contact your doctor.

Symptoms such as restlessness or difficulty to sit or stand still can also occur during the first weeks of the treatment. Tell your doctor immediately if you experience these symptoms.

Thoughts of suicide and worsening of your depression or anxiety disorder

If you are depressed and/or have anxiety disorders you can sometimes have thoughts of harming or killing yourself. These may be increased when first starting antidepressants, since these medicines all take time to work, usually about two weeks but sometimes longer.

You may be more likely to think like this:

• If you have previously had thoughts about killing or harming yourself
• If you are a young adult. Information from clinical trials has shown an increased risk of suicidal behaviour in adults aged less than 25 years with psychiatric conditions who were treated with an antidepressant

If you have thoughts of harming or killing yourself at any time, contact your doctor or go to a hospital straight away.

You may find it helpful to tell a relative or close friend that you are depressed or have an anxiety disorder, and ask them to read this leaflet. You might ask them to tell you if they think your depression or anxiety is getting worse, or if they are worried about changes in your behaviour.

Children and adolescents

Escitalopram should normally not be used for children and adolescents under 18 years. Also, you should know that patients under 18 have an increased risk of side effects such as suicide attempts, suicidal thoughts and hostility (predominately aggression, oppositional behaviour and anger) when they take this class of medicines. Despite this, your doctor may prescribe Escitalopram for patients under 18 because he/she decides that this is in their best interest. If your doctor has prescribed Escitalopram for a patient under 18 and you want to discuss this, please go back to your doctor. You should inform your doctor if any symptoms listed above develop or worsen when patients under 18 are taking Escitalopram. Also, the long term safety effects concerning growth, maturation and cognitive and behavioural development of Escitalopram in this age group have not yet been demonstrated.

Other medicines and Escitalopram

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.

Do not take Escitalopram if you take medicines for heart rhythm problems or medicines that may affect the heart’s rhythm, such as Class IA and III antiarrhythmics, antipsychotics (e.g. phenothiazine derivatives, pimozide, haloperidol), tricyclic antidepressants, certain antimicrobial agents (e.g. sparfloxacin, moxifloxacin, erythromycin IV, pentamidine, anti-malarian treatment particularly halofantrine), certain antihistamines (astemizole, mizolastine). If you have any further questions about this you should speak to your doctor.

Tell your doctor if you are taking any of the following medicines:

• “Non-selective monoamine oxidase inhibitors (MAOIs)”, containing phenelzine, iproniazid isocarboxazid, nialamide, and tranylcypromine as active ingredients. If you have taken any of these medicines you will need to wait 14 days before you start taking Escitalopram. After stopping Escitalopram you must allow 7 days before taking any of these medicines
• “Reversible, selective MAO-A inhibitors”, containing moclobemide (used to treat depression)
• “Irreversible MAO-B inhibitors”, containing selegiline (used to treat Parkinson’s disease). These increase the risk of side effects
• The antibiotic linezolid
• Lithium (used in the treatment of manic-depressive disorder) and tryptophan
• Sumatriptan and similar medicines (used to treat migraine) and tramadol (used against severe pain) These increase the risk of side effects
• Cimetidine and omeprazole (used to treat stomach ulcers), fluvoxamine (antidepressant) and ticlopidine (used to reduce the risk of stroke). These may cause increased blood levels of Escitalopram
• St. John’s Wort (hypericum perforatum) – a herbal remedy used for depression
• Acetylsalicylic acid and non-steroidal anti-inflammatory drugs (medicines used for pain relief or to thin the blood, so called anti-coagulant)
• Warfarin, dipyridamole, and phenprocoumon (medicines used to thin the blood, so called anti-coagulant). Your doctor will probably check the coagulation time of your blood when starting and discontinuing Escitalopram in order to verify that your dose of anti-coagulant is still adequate
• Mefloquin (used to treat Malaria), bupropion (used to treat depression and to help you quit smoking) and tramadol (used to treat severe pain) due to a possible risk of a lowered threshold for seizures
• Neuroleptics (medicines to treat schizophrenia, psychosis) due to a possible risk of a lowered threshold for seizures, and antidepressants
• Flecainide, propafenone, and metoprolol (used in cardio-vascular diseases) desipramine, clomipramine, and nortriptyline (antidepressants) and risperidone, thioridazine, and haloperidol (antipsychotics). The dosage of Escitalopram may need to be adjusted
• Medicines that prolong the so-called ‘QT interval’ or medicines which lower potassium or magnesium levels in the blood. Ask your doctor for advice on these medicines.

Escitalopram with food, drink and alcohol

Escitalopram can be taken with or without food (see section 3 “How to take Escitalopram”).

As with many medicines, combining Escitalopram with alcohol is not advisable, although Escitalopram is not expected to interact with alcohol.

Pregnancy, breast-feeding and fertility

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before taking this medicine.

Make sure your midwife and/or doctor know you are on Escitalopram. When taken during pregnancy, particularly in the last 3 months of pregnancy, medicines like Escitalopram may increase the risk of a serious condition in babies, called persistent pulmonary hypertension of the new born (PPHN), making the baby breathe faster and appear bluish. These symptoms usually begin during the first 24 hours after the baby is born. If this happens to your baby you should contact your midwife and/or doctor immediately.

If you take Escitalopram during the last 3 months of your pregnancy you should be aware that the following effects may be seen in your newborn baby: trouble with breathing, blue-ish skin, fits, body temperature changes, feeding difficulties, vomiting, low blood sugar, stiff or floppy muscles, vivid reflexes, tremor, jitteriness, irritability, lethargy, constant crying, sleepiness and sleeping difficulties. If your newborn baby has any of these symptoms, please contact your doctor immediately.

If used during pregnancy Escitalopram should never be stopped abruptly.

Do not take Escitalopram if you are breast-feeding unless you and your doctor have discussed the risks and benefits involved.

Ask your doctor or pharmacist for advice before taking any medicine.

Fertility

Citalopram, a medicine like escitalopram, has been shown to reduce the quality of sperm in animal studies. Theoretically, this could affect fertility, but impact on human fertility has not been observed as yet.

Driving and using machines

This medicine can alter reaction times severely enough, even when used as indicated, to impair the ability to drive or use machinery. Do not drive a car or operate machinery until you know how Escitalopram affects you.

3 How to take Escitalopram

Always take this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

Adults

To treat depression

The recommended dose of Escitalopram is 10mg taken as one daily dose. The dose can be increased by your doctor to a maximum of 20mg per day.

To treat panic disorders, with or without agoraphobia

The starting dose of Escitalopram is 5mg as one daily dose for the first week before increasing the dose to 10mg per day. The dose may be further increased by your doctor to a maximum of 20mg per day.

To treat social anxiety disorder (social phobia)

The recommended dose of Escitalopram is 10mg taken as one daily dose. Depending on your response to the treatment, your doctor can either decrease your dose to 5mg per day or increase the dose to a maximum of 20mg daily.

To treat generalised anxiety disorder

The normally recommended dose of Escitalopram is 10mg taken as one daily dose. The dose may be increased by your doctor to a maximum of 20mg per day.

To treat Obsessive-Compulsive Disorder (OCD)

The recommended dose of Escitalopram is 10mg taken as one daily dose. The dose may be increased by your doctor to a maximum of 20mg daily. For long-term treatment, the benefits of treatment should be regularly checked

Elderly patients (above 65 years of age)

The recommended starting dose of Escitalopram is 5mg taken as one daily dose. The dose may be increased by your doctor to 10mg per day.

The efficacy of Escitalopram in social anxiety disorder (social phobia) in elderly patients has not been studied.

Patients with impaired liver function

The recommended starting dose of Escitalopram for patients with impaired liver function should not exceed 5mg daily in the first 14 days. Your doctor can then raise the daily dose, depending on your response, up to 10mg daily. Caution and an especially careful dose titration are indicated in patients with severely impaired liver function.

Patients with impaired kidney function

With mild to moderate impairment of kidney function, no dose adjustment is required. Caution is indicated for patients with severely impaired kidney function.

Use in children and adolescents (below 18 years of age)

Escitalopram should not normally be given to children and adolescents. For further information please see section 2 “What you need to know before you take Escitalopram”.

Escitalopram 5mg Film-coated Tablets:

Please take the film-coated tablets once daily, swallowed whole with sufficient fluid (preferably a glass of water). Escitalopram may be taken with or without food.

Escitalopram 10mg and 20mg Film-coated Tablets:

Please take the film-coated tablets once daily, swallowed whole with sufficient fluid (preferably a glass of water). Escitalopram may be taken with or without food.

If necessary, tablets may be broken by firstly placing the tablet on a flat surface with the score facing upwards. The tablets may then be broken by pressing down on each end of the tablet, using both forefingers as shown in the drawing.

Duration of treatment

It may take a couple of weeks before you start to feel better. Continue to take Escitalopram even if it takes some time before you feel any improvement in your condition. Do not change the dose of your medicine without talking to your doctor first.

Continue to take Escitalopram for as long as your doctor recommends. If you stop your treatment too soon, your symptoms may return. It is recommended that treatment should be continued for at least 6 months after you feel well again.

If you take more Escitalopram than you should.

If you have taken more Escitalopram than you should, or if someone else has taken your medicine by mistake, inform your doctor or go to a hospital straight away. Do this even if you still feel well. Take any remaining tablets as well as the box/container with you, even if this is empty.

Symptoms of overdose might include dizziness, shaking, restlessness, feeling sleepy, falling unconscious, change in heart rhythm, fits, hypoventilation, muscle weakness, tenderness or pain and feeling unwell or have a high temperature (rhabdomyolysis), change in body fluid/salt balance, vomiting and being sick.

If you forget to take Escitalopram.

Do not take a double dose to make up for forgotten doses. If you should forget to take a dose of Escitalopram, just take Escitalopram as usual the next time.

If you stop taking Escitalopram.

If you want to interrupt the treatment, please discuss this with your doctor beforehand. He might need to take appropriate measures. Do not stop taking the medicine on your own initiative without discussing this with your doctor. When stopping treatment with Escitalopram, your doctor will gradually reduce your dose over a number of weeks or months. This should help reduce the possibility of withdrawal effects.

When you stop taking Escitalopram, especially if it is abruptly, you may feel discontinuation symptoms. These are common when treatment with Escitalopram is stopped. The risk is higher, when Escitalopram has been used for a long time or in high doses or when the dose is reduced too quickly. Most people find that the symptoms are mild and go away on their own within two weeks. However, in some patients they may be severe in intensity or they may be prolonged (2-3 months or more). If you get severe discontinuation symptoms when you stop taking Escitalopram, please contact your doctor. He or she may ask you to start taking your tablets again and come off them more slowly.

Discontinuation symptoms include: Feeling dizzy (unsteady or off-balance), feelings like pins and needles, burning sensations and (less commonly) electric shock sensations, including in the head, sleep disturbances (vivid dreams, nightmares, inability to sleep), feeling anxious, headaches, feeling sick (nausea) and vomiting, sweating (including night sweats), feeling restless or agitated, tremor (shakiness), feeling confused or disorientated, feeling emotional or irritable, diarrhoea (loose stools), visual disturbances, fluttering or pounding heartbeat (palpitations).

If you have any further questions on the use of this medicine, ask your doctor, pharmacist or nurse.

4 Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody gets them.

Side effects most commonly occur in the first or second week of treatment, and normally become less severe and less frequent as treatment continues.

See your doctor if you get any of the following side effects during treatment:

Uncommon (more than 1 out of 1000 persons and less than 1 out of 100 persons):

• Unusual bleeds, including gastrointestinal bleeds

Rare (more than 1 out of 10000 and less than 1 out of 1000 persons):

• If you experience swelling of skin, tongue, lips, or face, or have difficulties breathing or swallowing (allergic reaction), contact your doctor or go to a hospital straight away
• If you have a high fever, agitation, confusion, trembling and abrupt contractions of muscles these may be signs of a rare condition called serotonin syndrome

If you experience the following side affects you should contact your doctor or go to the hospital straight away:

• Difficulties urinating
• Seizures (fits)
• Yellowing of the skin and the white in the eyes are signs of liver function impairment/ hepatitis
• Fast, irregular heart beat, fainting which could be symptoms of a life-threatening condition known as Torsades de Pointes

In addition to above the following side effects have been reported:

Very common (more than 1 out of 10 persons):

• Feeling sick (nausea)
• Headache

Common (more than 1 out of 100 persons and less than 1 out of 10 persons):

• Generalised fear, restlessness, abnormal dreams, difficulty in sleeping, sleepiness, dizziness, a skin sensation, such as burning, prickling, itching, or tingling, with no apparent physical cause, tremor, yawning
• Sexual disturbances (delayed ejaculation, problem with erection, decreased sexual drive and women may experience difficulties achieving orgasm)
• Diarrhoea, constipation, vomiting, dry mouth
• Blocked or runny nose (sinusitis)
• Increased sweating
• Fatigue, fever
• Joint and muscle pain
• Increased weight
• Decreased or increased appetite

Uncommon (more than 1 out of 1000 persons and less than 1 out of 100 persons):

• Involuntary grinding or clenching of the teeth, agitation, nervousness, panic attack, confusion state
• Taste disturbance, sleep disorder, fainting
• Nosebleed
• Bleeding from the uterus that is not associated with menstruation, abnormally heavy or extended menstrual flow
• Nettle rash (urticaria), rash, itching (pruritus)
• Hair loss
• Swelling of the arms or legs
• Enlarged pupils (mydriasis), blurred vision, ringing in the ears (tinnitus)
• Fast heart beat
• Decreased weight

Rare (more than 1 out of 10000 and less than 1 out of 1000 persons):

• Aggression, depersonalisation, hallucination
• Slow heart beat

Some patients have reported (frequency cannot be estimated from the available data):

• Thoughts of harming yourself or thoughts of killing yourself, see also section “Warnings and precautions”
• Mania
• Movement disorders (involuntary movements of the muscles)
• Flow of milk in women that are not nursing
• Painful erection of the penis
• Bleeding disorders including skin and mucous bleeding (ecchymosis) and low level of blood platelets (thrombycytopenia)
• Dizziness when you stand up due to low blood pressure (orthostatic hypotension)
• Decreased levels of sodium in the blood (the symptoms are feeling sick and unwell with weak muscles or confused)
• Increase in the amount of urine excreted (inappropriate ADH secretion)
• Abnormal liver function test (increased amounts of liver enzymes in the blood)
• Sudden swelling of the skin and mucosa (angioedemas)
• Suicide-related events
• Inability to sit still or remain motionless, feeling of restlessness associated with increased movement*
• Anorexia*
• An increased risk of bone fractures has been observed in patients taking this type of medicine
• Alteration of the heart rhythm (called “prolongation of QT interval”, seen on ECG, electrical activity of the heart)

* These side effects have been reported with drugs that work in a similar way to escitalopram (the active ingredient of Escitalopram).

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any side effects not listed in this leaflet.

By reporting side effects you can help provide more information on the safety of this medicine.

5 How to store Escitalopram

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the blister strips, tablet container and carton after EXP. The expiry date refers to the last day of that month.

Blister packs: Do not store above 25°C

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6 Contents of the pack and other information

What Escitalopram contains:

The active substance is escitalopram.

a) Each film-coated tablet contains:
Escitalopram Oxalate USP
equivalent to Escitalopram                      5mg
Excipients                                                  q.s
Colour: Titanium Dioxide USP.

b) Each film-coated tablet contains: 
Escitalopram Oxalate USP 
equivalent to Escitalopram                      10mg
Excipients                                                  q.s 
Colour: Titanium Dioxide USP.

c) Each film-coated tablet contains:
Escitalopram Oxalate USP
equivalent to Escitalopram                      20mg
Excipients                                                  q.s
Colour: Titanium Dioxide USP.

The other ingredients are:

Tablet core:microcrystalline cellulose, colloidal anhydrous silica, croscarmellose sodium, talc, magnesium stearate

Coating: hypromellose, titanium dioxide, macrogol.

What Escitalopram looks like and contents of the pack:

Escitalopram are available in blister packs of 10, 20, 30, 50, 100 and 500 tablets

Manufactured By:
Taj Pharmaceuticals Ltd.
at: Plot. No. 220, Mahagujarat
Industrial Estate, At & Post-Moraiya,
Tal-Sanand, Dist- Ahmedabad Gujarat (India)