Treatment of major depressive episodes.
Treatment of panic disorder with or without agoraphobia.
Treatment of social anxiety disorder (social phobia).
Treatment of generalized anxiety disorder.
Treatment of obsessive-compulsive disorder.

Safety of daily doses above 20 mg has not been demonstrated.
Setapro is administered as a single daily dose and may be taken with or without food.
Major depressive episodes
Usual dosage is 10 mg once daily. Depending on individual patient response, the dose may be
increased to a maximum of 20 mg 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 5 mg is recommended for the first week before increasing the dose to 10 mg
daily. The dose may be further increased, up to a maximum of 20 mg 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 10 mg once daily. Usually 2-4 weeks are necessary to obtain symptom relief. The
dose may subsequently, depending on individual patient response, be decreased to 5 mg or
increased to a maximum of 20 mg 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 behavioral therapy has not been assessed.
Pharmacotherapy is part of an overall therapeutic strategy.

Generalised anxiety disorder
Initial dosage is 10 mg once daily. Depending on the individual patient response, the dose may be
increased to a maximum of 20 mg daily.
Long-term treatment of responders has been studied for at least 6 months in patients receiving 20
mg daily. Treatment benefits and dose should be re-evaluated at regular intervals.
Obsessive-compulsive disorder
Initial dosage is 10 mg once daily. Depending on the individual patient response, the dose may be
increased to a maximum of 20 mg 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.
Elderly patients (> 65 years of age)
Initial dosage is 5 mg once daily. Depending on individual patient response the dose may be
increased to 10 mg daily.
The efficacy of Escitalopram in social anxiety disorder has not been studied in elderly patients.
Children and adolescents (<18 years)
Setapro should not be used in the treatment of children and adolescents under the age of 18 years.
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 (CLCR less than 30 ml/min.).
Reduced hepatic function
An initial dose of 5 mg 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 10 mg daily. Caution and extra careful dose titration is advised in patients with
severely reduced hepatic function.
Poor metabolisers of CYP2C19
For patients who are known to be poor metabolisers with respect to CYP2C19, an initial dose of 5
mg daily during the first two weeks of treatment is recommended. Depending on individual patient
response, the dose may be increased to 10 mg daily.

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. 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.

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 (MAOinhibitors) is contraindicated due to the risk of serotonin syndrome with agitation, tremor, hyperthermia etc. 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 serotonin syndrome. 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.

The following special warnings and precautions apply to the therapeutic class of SSRIs (Selective
Serotonin Re-uptake Inhibitors).
Use in children and adolescents under 18 years of age
Setapro should not be used in the treatment of children and adolescents under the age of 18 years.
Suicide related behaviors (suicide attempt and suicidal thoughts), and hostility (predominately
aggression, oppositional behavior 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 behavioral 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.
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 Setapro 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 may 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 nonsteroidal
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.
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.

Discontinuation symptoms seen when stopping treatment
Discontinuation symptoms when stopping treatment are common, particularly if discontinuation is
abrupt. 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 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”.
Coronary heart disease
Due to limited clinical experience, caution is advised in patients with coronary heart disease.
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
hypokalaemia, or with pre-existing QT interval prolongation or other cardiac diseases.
Caution is advised in patients with significant bradycardia; or in patients with recent acute
myocardial infarction or uncompensated heart failure.
Electrolyte disturbances such as hypokalaemia 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.

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.

Pharmacodynamic interactions
Contraindicated 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 such MAOI treatment. In some
cases, the patient developed serotonin syndrome.
Escitalopram is contraindicated in combination with non-selective, irreversible MAOIs.
Escitalopram may be started 14 days after discontinuing treatment with an irreversible MAOI. At
least 7 days should elapse after discontinuing escitalopram treatment, before starting a nonselective,
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. 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.
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 10 mg/day have been safely coadministered
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. phenothiazine derivatives, pimozide, haloperidol), tricyclic antidepressants,
certain antimicrobial agents (e.g. sparfloxacin, moxifloxacin, erythromycin IV, pentamidine, antimalarial
treatment particularly halofantrine), certain antihistamines (e.g. astemizole, mizolastine),
is contraindicated.
Combinations requiring 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.
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. Concomitant use of non-steriodal anti-inflammatory drugs
(NSAIDs) may increase bleeding-tendency.

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 hypokalaemia/hypomagnesaemia
Caution is warranted for concomitant use of hypokalaemia/hypomagnesaemia inducing medicinal
products as these conditions increase the risk of malignant arrhythmias.
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 30 mg once daily (a CYP2C19 inhibitor)
resulted in moderate (approximately 50%) increase in the plasma concentrations of Escitalopram.
Co-administration of Escitalopram with cimetidine 400 mg 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.

Pregnancy Category C
Pregnancy
For Escitalopram only limited clinical data are available regarding exposed pregnancies.
Animal studies have shown reproductive toxicity. Setapro 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 Setapro continues into the later stages of
pregnancy, particularly in the third trimester. Abrupt discontinuation should be avoided 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 and 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, particularly 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.
Breast-feeding
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. 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.

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

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 placebocontrolled
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 from the
available data).

1 These events have been reported for the therapeutic class of SSRIs.
2 Cases of suicidal ideation and suicidal behaviours have been reported during Escitalopram
therapy or early after treatment discontinuation.

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
hypokalaemia, 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.
To report any side effect(s):
• Saudi Arabia:
The National Pharmacovigilance and Drug Safety Centre (NPC)
􀁸 Fax: +966-11-205-7662
􀁸 Call NPC at +966-11-2038222,
Exts: 2317-2356-2353-2354-2334-2340.
􀁸 Toll free phone: 8002490000
􀁸 E-mail: npc.drug@sfda.gov.sa
􀁸 Website: www.sfda.gov.sa/npc

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 800 mg 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).
Management
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.
 

Pharmacotherapeutic group: antidepressants, selective serotonin reuptake inhibitors
ATC-code: N06AB10
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, 􀄮1-, 􀄮2-, 􀈕-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 ms (90% CI: 2.2, 6.4) at the 10 mg/day dose and 10.7 ms
(90% CI: 8.6, 12.8) at the supratherapeutic dose 30 mg/day (see sections 4.3, 4.4, 4.5, 4.8 and 4.9).
Clinical efficacy
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-week) 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 20 mg/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-
month relapse prevention study in social anxiety disorder. In a 24-week dose-finding study,
efficacy of 5, 10 and 20 mg Escitalopram has been demonstrated.
Generalised anxiety disorder
Escitalopram in doses of 10 and 20 mg/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 randomised, double-blind, clinical study, 20 mg/day Escitalopram separated from placebo on
the Y-BOCS total score after 12 weeks. After 24 weeks, both 10 and 20 mg/day Escitalopram were
superior as compared to placebo.
Prevention of relapse was demonstrated for 10 and 20 mg/day Escitalopram in patients who
responded to escitalopram in a 16-week open-label period and who entered a 24-week,
randomised, double-blind, placebo controlled period.

Absorption
Absorption is almost complete and independent of food intake. (Mean time to maximum
concentration (mean Tmax) is 4 hours after multiple dosing).
As with racemic citalopram, the absolute bioavailability of Escitalopram is expected to be about
80%.
Distribution
The apparent volume of distribution (Vd,􀈕/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 Noxide
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 (t½􀈕) after multiple dosing is about 30 hours and the oral plasma
clearance (Cloral) is about 0.6 L/min. The major metabolites have a significantly longer half-life.
Escitalopram and 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.
Linearity
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 10 mg.

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.
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.
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 (CLcr 10-53 ml/min). Plasma concentrations of the
metabolites have not been studied, but they may be elevated.
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.

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 haemodynamic effects (reduction in coronary flow) and ischaemia. 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 preand
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 implantation number and abnormal sperm at exposure well in excess of human
exposure. No animal data related to this aspect are available for Escitalopram.

Core tablet content:
Microcrystalline cellulose, Talc, Colloidal silicon dioxide, Croscarmellose sodium and Magnesium
Stearate.
Coating content:
Opadry white (which contains, Hypromellose, Titanium dioxide, Propylene glycol and Talc).

Not applicable

2 years.

Do not store above 30°C.

Setapro 20 mg Film Coated Tablets are packed as 10 Tablets in Aluminum-PVC/PVDC blister
containing 30 (3x10) film coated tablets in outer carton with Patient Information Leaflet.

No special requirements.