Each film coated tablet contains: Escitalopram oxalate eq. to Escitalopram 10 mg.
Excipients/Inactive Ingredients: Silicified microcrystalline cellulose (Prosolv SMCC 90), Croscarmellose sodium, Sodium metabisulfite, Talc, Magnesium stearate, Hypromellose (HPMC 2910), Titanium dioxide, Butylated hydroxytoluene (BHT), and Polyethylene glycol (PEG 400).
Pharmacology: 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-adrenoreceptors, 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.
Pharmacokinetics: 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, 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 metabolized in the liver to the demethylated and didemethylated metabolites. Both of these are pharmacologically active. Alternatively, the Nitrogen may be oxidized 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 enzymez CYP3A4 and CYP2D6 is possible.
Elimination: The elimination half-life (t½β) after multiple dosing is about 30 hours and the oral plasma clearance (CIoral) is about 0.6 mL/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 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 metabolizers with respect to CYP2C19 have twice as high as plasma concentration of Escitalopram as extensive metabolizers. No significant change in exposure was observed in poor metabolizers with respect to CYP2D6.
Indicated for the treatment of: major depressive episodes, panic disorders with or without agoraphobia, social anxiety disorder (social phobia), generalized anxiety disorder, obsessive-compulsive disorder.
"If the dose of 5 mg is necessary, an Escitalopram 5 mg strength is available on the market from other brands."
Safety of daily doses above 20 mg has not been demonstrated.
ESOPAM is administered as a single daily dose and may be taken with or without food.
Posology: Major depressive espisodes: 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.
Generalized 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 inidvidual 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.
Pediatric population (< 18 years): Escitalopram 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 metabolizers of CYP2C19: For patients who are known to be poor metabolizers 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.
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.
Hypersensitivity to the active substance or to any of the excipients.
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.
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.
Serotonergic psychiatric drugs should not be started in a patient receiving Linezolid. Wait until 24 hours after the last dose of Linezolid before starting the serotonergic psychiatric drugs.
QT interval prolongation: Escitalopram has been found to cause a dose-dependent prolongation of the QT interval.
10 mg per day is the maximum recommended dose for patients who are 65 years of age or older, or have liver problems, or are taking the heartburn drugs Omeprazole or Cimetidine which can increase the blood level of Escitalopram. 20 mg per day is the maximum recommended dose for most patients.
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.
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, breastfeeding 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.
Common or very common:
Abnormal dreams; fatigue; paraesthesia; pyrexia; restlessness; sinusitis; yawning.
Alopecia; bruxism; confusion; epistaxis; menstrual disturbances; mydriasis; edema; pruritus; syncope; tachycardia; taste disturbances; tinnitus.
Aggression; bradycardia; depersonalization.
Frequency not known:
Hepatitis; paradoxical increased anxiety during initial treatment of panic disorder (reduce dose); postural hypotension; QT interval prolongation; thrombocytopenia.
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 have a clear QT interval prolonging effect, such as Class IA and III antiarrhythmics, certain antipsychotics (e.g. Ziprasidone), tricyclic antidepressants, opioids (e.g. Methadone), certain antimicrobial agents (e.g. Moxifloxacin), is discouraged. The concomitant use of Escitalopram with drugs that can disrupt electrolyte levels is discouraged. Drugs that decrease electrolyte levels include, but are not limited to, the following: loop, thiazide, and related diuretics; laxatives and enemas; Amphotericin B; high dose corticosteroids. The previously mentioned lists of potentially interacting drugs are not comprehensive.
Store at temperature not more than 30°C.
N06AB10 - escitalopram ; Belongs to the class of selective serotonin reuptake inhibitors. Used in the management of depression.