ESLO 10 (Escitalopram Tablets 10 mg): Each film coated tablet contains Escitalopram 10 mg.
Escitalopram oxalate 12.775 mg, Equivalent to Escitalopram 10 mg.
ESLO 20 (Escitalopram Tablets 20 mg): Each film coated tablet contains Escitalopram 20 mg.
Escitalopram oxalate 25.550 mg, Equivalent to Escitalopram 20 mg.
Pharmacology: Pharmacodynamics: Escitalopram Oxalate is an orally administered selective serotonin reuptake inhibitor (SSRI). Escitalopram is the pure S-enantiomer (single isomer) of the racemic bicyclic phthalane derivative citalopram. The mechanism of antidepressant action of Escitalopram, the S-enantiomer of racemic citalopram, is presumed to be linked to potentiation of serotonergic activity in the central nervous system resulting from its inhibition of CNS neuronal reuptake of serotonin (5-HT). Escitalopram is at least 100 fold more potent than the R-enantiomer with respect to inhibition of 5-HT reuptake and inhibition of 5-HT neuronal firing rate.
Escitalopram has no or very low affinity for serotonergic (5-HT1-7) or other receptors including alpha- and beta-adrenergic, dopamine (D1-5), histamine (H1-3), muscarinic (M1-5) and benzodiazepine receptors. Escitalopram also does not bind to or has low affinity for various ion channels including Na+, K+, Cl- and Ca++ channels. Antagonism of muscarinic, histaminergic and adrenergic receptors has been hypothesized to be associated with various anticholinergic, sedative and cardiovascular side effects of other psychotropic drugs.
Pharmacokinetics: The single and multiple dose pharmacokinetics of Escitalopram are linear and dose-proportional in a dose range of 10 to 30 mg/day. Biotransformation of Escitalopram is mainly hepatic, with a mean terminal hall-life of about 27-32 hours. With once daily dosing, steady state plasma concentrations are achieved within approximately one week. At steady state, the extent of accumulation of Escitalopram in plasma in young healthy subjects was 2.2-2.5 times the plasma concentrations observed after a single dose.
Absorption and Distribution: Following a single oral dose (20 mg tablet) of Escitalopram, the mean Tmax was 5 ± 1.5 hours.
Absorption of Escitalopram is not affected by food.
The absolute bioavailability of citalopram is about 80% relative to an intravenous dose, and the volume of distribution of citalopram is about 12L/kg. Data specific to Escitalopram are unavailable. The binding of Escitalopram to human plasma proteins is approximately 56%.
Metabolism and Elimination: Following oral administrations of Escitalopram, the fraction of drug recovered in the urine as Escitalopram and S-demethycitalopram (S-DCT) is about 8% and 10% respectively. The oral clearance of the Escitalopram is 600 ml/min, with approximately 7% of that due to renal clearance.
Escitalopram is metabolized to S-DCT and S-didemethylcitalopram (S-DDCT). In humans, unchanged Escitalopram is the predominant compound in plasma. At steady state, the concentration of Escitalopram metabolite S-DCT in plasma is approximately one-third that of Escitalopram. CYP3A4 and CYP2C19 are the primary isozymes involved in the N-demethylation of Escitalopram.
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.
Escitalopram 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 10mg daily. The dose may be further increased, up to a maximum of 20mg daily, dependent on individual patient's response.
Maximum effectiveness is reached after about 3 months. The treatment lasts several months.
Social Anxiety Disorder: Usual dosage is 10 mg once daily. Depending on individual patients' response, the dose may be increased to a maximum of 20 mg daily.
Usually 2-4 weeks are necessary to obtain symptom relief. Treatment for 3 months is recommended to consolidate response. Long-term treatment of responders for 6 month has been shown to prevent relapse and can be considered on an individual basis, treatment benefits should be re-evaluated at regular intervals.
Obsessive Compulsive Disorder (OCD): Usual dosage 10 mg once daily. Depending on individual patient's response, the dose may be increased to 20 mg daily.
As OCD is a chronic disease, patients should be treated for a sufficient period to ensure that they are symptom free. This period may be several months or even longer.
Elderly patient (>65years of age): Initial treatment with half the usually recommended dose and a lower maximum dose should be considered.
Children and Adolescents (<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. Depending on individual patient response, the dose may be increased to 10 mg daily.
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 10mg daily.
Discontinuation symptoms: When stopping treatment with Escitalopram the dose should be gradually reduced over a period of at least one to two weeks in order to avoid possible discontinuation symptoms.
Mode of Administration: Oral.
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 over dose 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 prolongation and arrhythmia) and electrolyte/fluid balance conditions (hypokalaemia, hyponatraemia).
Treatment: 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.
Hypersensitivity to Escitalopram or any of the excipient.
Concomitant treatment with non-selective, irreversible monoamine oxidase inhibitors (MAO-inhibitors).
Concomitant treatment with pimozide.
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 the first two weeks of treatment. A low starting dose is advised to reduce the likelihood of an anxiogenic effect.
Seizures: The medicinal product should be discontinued in any patient who develops seizures. SSRIs should be avoided in patients with unstable epilepsy and patients with controlled epilepsy should be carefully monitored. SSRIs should be discontinued if there is an increase in seizure frequency.
Mania: SSRIs should be used with caution in patients with a history of mania/hypomania. SSRIs should be discontinued in any patients entering a manic phase.
Diabetes: In patients with diabetes, treatment with an SSRI may alter glycemic control, Insulin and/or oral hypoglycemic dosage may need to be adjusted.
Suicide/Suicidal thought: 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 in 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 at greater risk of suicidal thoughts or suicidal attempts, and should receive careful monitoring during treatment. In addition, there is a possibility of an increased risk of suicidal behaviour in young adults. Patients (and caregivers of patients) should be alerted about the need to monitor for the emergence of such events 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, characterized by a subjective unpleasant or distressing restlessness and 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: Hyponatremia, 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 elderly, cirrhotic patients or patients concomitantly treated with medications known to 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 with concomitant use of oral anticoagulants, medicinal products known to affect platelet function (e.g. atypical antipsychotic 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.
Reversible Selective MAO A inhibitors: The combination of Escitalopram with MAO A inhibitors is generally not recommended due to the risk of onset of a serotonin syndrome.
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 indicated.
Potential for interaction with Monoamine Oxidase Inhibitors: In patients receiving serotonin reuptake inhibitor drugs in combination with a Monoamine Oxidase Inhibitors (MAOI) there have been reports of serious, sometimes fatal reactions including hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations of vital signs and mental status changes that include extreme agitation progressing to delirium and coma. These reactions have also been reported in patients who have recently discontinued SSRI treatment and have been started on a MAOI. Some cases presented with features resembling neuroleptic malignant syndrome. Furthermore limited animal data on the effects of combined use of SSRIs and MAOIs suggest that these drugs may act synergistically to elevate blood pressure and evoke behavioral excitation therefore it is recommended that ESLO should not be used in combination with a MAOI or within 14 days of discontinuing treatment with a MAOI. Similarly at least 7 days should be allowed after stopping ESLO before starting a MAOI.
St. John's Wort: Concomitant use of SSRI 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 seen when stopping treatment are common, particularly if discontinuation is abrupt.
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, diarrhea, palpitations, emotional instability, irritability and visual disturbances are the most commonly reported reactions. Generally those reactions 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.
Special warning - Suicidality in Children and Adolescents: Escitalopram should not be used in the treatment of children and adolescents under the age of 18 years. Antidepressants increase the risk of suicidal thinking and behavior (suicidality) in children and adolescents with major depressive disorder (MDD) and other psychiatric disorder. Anyone considering the use of an antidepressant in a child or adolescent for any clinical use must balance the risk of an increased suicidality with the clinical need. If, based on clinical need, a decision to treat is nevertheless taken, patients who are started on therapy should be observed closely for clinical worsening, suicidality, or unusual change in behavior. Families and caregivers should be advised to closely observe the patient and to communicate with the prescriber.
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. Patient should be cautioned about the potential risk of an influence on their ability to drive a car and operate machinery.
Antidepressants should not be used in the treatment of children and adolescents under age at 18 years. Suicide related behaviors (suicide attempt and suicidal thoughts) and hostility (predominantly aggression oppositional behavior and anger) were more frequently observed in children and adolescent treated with antidepressants compared to those treated with placebo. If based on clinical need, a decision to treat nevertheless taken, the patient should be carefully monitored for the appearance of suicidal symptoms.
The following special warnings and precautions apply to the therapeutic class of SSRIs (Selective Serotonin Reuptake inhibitors).
Carcinogenesis: Racemic citalopram was administered in the diet to NMRI/BOM strain mice and COBS WI strain rats for 18 and 24 months, respectively. There was no evidence for carcinogenicity of racemic citalopram in mice receiving up to 240 mg/kg/day. There was an increased incidence of small intestine carcinoma in rats receiving 8 or 24 mg/kg/day racemic citalopram. A no-effect dose for this finding was not established. The relevance of these findings to humans is unknown.
Mutagenesis: Racemic citalopram was mutagenic in the in vitro bacterial reverse mutation assay (Ames test) in 2 of 5 bacterial strains (Salmonella TA98 and TA1537) in the absence of metabolic activation. It was clastogenic in elhe in vitro Chinese hamster lung cell assay for chromosomal aberrations in the presence and absence of metabolic activation. Racemic Citalopram was not mutagenic in the in vitro mammalian forward gene mutation assay (HPRT) in mouse lymphoma cells or in a coupled in vitro/in vivo unscheduled DNA synthesis (UDS) assay in rat liver. It was not clastogenic in the in vitro chromosomal aberration assay in human lymphocytes or in two in vivo mouse micronucleus assays.
Impairment of Fertility: When racemic citalopram was administered orally to 16 male and 24 female rats prior to and throughout mating and gestation at doses of 32, 48, and 72 mg/kg/day, mating was decreased at all doses and fertility was decreased at doses ≥32 mg/kg/day. Gestation duration was increased at 48 mg/kg/day.
Use in Children: Safety and effectiveness in pediatric patients have not been established.
Pregnancy: There are no adequate and well-controlled studies in pregnant women; therefore, Escitalopram should be used during pregnancy only if the potential benefit justifies the potential risk to the foetus.
Labor and Delivery: The effect of Escitalopram on labor and delivery in humans is unknown.
Lactation: It is expected that Escitalopram will be excreted into human milk and breast feeding is not recommended during the treatment.
Adverse reaction are most frequent during the first or second week of treatment and usually decrease in intensity and frequency with continued treatment.
Adverse drug reaction known for SSRIs and also reported for Escitalopram.
Frequencies are defined as: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to ≤1/100), rare (≥1/10000 to ≤1/1000), very rare (≤1/10000), or not known (cannot be estimated from the available data). (See table.)
Click on icon to see table/diagram/image
The following adverse drug reactions have been reported for the therapeutic class of SSRIs: psychomotor restlessness/akathisia and anorexia.
Cases of QT-prolongation have been reported, predominantly in patients with pre-existing cardiac disease. No causal relationship has been established.
Discontinuation symptoms seen when stopping treatment.
Discontinuation of SSRIs/ SNRIs (particular when abrupt) commonly lead to and discontinuation symptoms. Dizziness, sensory disturbance (including paresthesia and electric shock sensations), sleep disturbances (including insomnia and intense dream), agitation or anxiety, nausea, and or vomiting, tremor, confusion, sweating, headache, diarrhea, 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 that when Escitalopram treatment is no longer required, gradual discontinuation by dose tapering and should be carried out.
Contra-indicated MAOIs: Cases of serious reactions have been reported in patients receiving an SSRI in combination with a non-selective monoamine oxidase inhibitor (MAOI), and in patients who have recently discontinued SSRI treatment and have been started on MAOI treatment. In some cases, the patient developed serotonin syndrome.
Escitalopram is contra-indicated in combination with non-selective 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 MAOI.
Inadvisable combination: Reversible, selective MAO A inhibitor (moclobemide): Due to the risk of serotonin syndrome, the combination of Escitalopram with a MAO A inhibitor is not recommended. If the combination proves necessary, it should be started at the minimum recommended dosage and clinical monitoring is strongly recommended.
Combination requiring precautions for use: Selegiline: In combination with selegiline (irreversible MAO B inhibitor), caution is required due to the risk of developing serotonin syndrome.
Serotonergic medicinal products: Co-administration with serotonergic medicinal products (e.g. tramadol, sumatriptan and other triptans) may lead to serotonin syndrome.
Medicinal product lowering the seizure threshold: SSRIs can lower the seizure threshold. Caution is advised when concomitantly using other medicinal product capable of lowering the seizure threshold (e.g. antidepressants tricyclics, SSRIs) neuroleptics (phenothiazines, thioxanthenes, butyrophenones) mefloquine, 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 coagulations monitoring when Escitalopram is started or stopped.
Alcohol: No pharmacodynamics or pharmacokinetics interactions are expected between Escitalopram and alcohol. However, as with other psychotropic medicinal products the combination with alcohol is not advisable.
NSAIDs: Concomitant use of non-steroidal anti-inflammatory drugs (NSAIDs) may increase bleeding-tendency.
Pharmacokinetics 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 catalyzed by CYP2D6.
Co-administration of Escitalopram with omeprazole (a CYP2C19 inhibitor) resulted in moderate (approximately 50%) increase in the plasma concentrations of Escitalopram.
Co-administration of Escitalopram with cimetidine (moderately potent general enzyme-inhibitor) resulted in moderate (approximately 70%) increase in the plasma concentrations of Escitalopram.
Caution should be thus be exercised at the upper end of the dose range of Escitalopram when used concomitantly with CYP2C19 inhibitors (e.g. Omeprazole, fluoxetine, fluvoxamine, lansoprazole, ticlopidine) and with cimetidine.
A reduction in the dose of Escitalopram may be necessary based on clinical judgement.
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 are mainly by this enzyme, and that have a narrow therapeutics index, e.g. flecainide, propafenone and metoprolol (when used in cardiac failure), or some CNS acting medicinal products that are mainly metabolized by CYP2D6, e.g. antidepressants such as desipramine, clomipramine and nortriptyline or antipsychotics like risperidone, thioridazine and haloperidol. Dosage adjustments may be warranted.
Co-administered with desipramine or metoprolol resulted in a two-fold increase in the plasma levels of these two CYP2D6 substrates.
Escitalopram may also cause weak inhibition of CYP2C19. Caution is recommended with concomitant use of medicinal products that are metabolized by CYP2C19.
Store below 30ºC and protect from moisture.
Shelf-Life: 24 months.
N06AB10 - escitalopram ; Belongs to the class of selective serotonin reuptake inhibitors. Used in the management of depression.
FC tab 10 mg (white to off white, oval, scored, biconvex, debossed with 'J' on one side and '2' on the other side) x 3 x 10's, 10 x 10's. 20 mg (white to off white, oval, scored, biconvex, debossed with 'J' on one side and '4' on the other side) 3 x 10's, 10 x 10's.