Esidep

Esidep

escitalopram

Manufacturer:

Ranbaxy

Distributor:

DKLL
Full Prescribing Info
Contents
Escitalopram oxalate.
Description
Each film coated tablet contains: Escitalopram oxalate equivalent to Escitalopram 10 mg.
ESIDEP (TABLETS 10 MG) (contains 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 of citalopram. Escitalopram oxalate is designated as S-(+)-1-[3-(dimethyl-amino)propyl]-1-(p-fluorophenyl)-5-phthalancarbonitrile oxalate. Its molecular formula and the molecular weight is C20H21FN2O•C2H2O4 and 414.40 respectively.
Excipients/Inactive Ingredients: Each film coated tablet contains microcrystalline cellulose, lactose monohydrate, copovidone, maize starch, silicified MCC, croscarmellose sodium, purified talc/talc, colloidal anhydrous silica, magnesium stearate and opadry OY-S-58910 (white).
Action
Pharmacology: Mechanism of action: Escitalopram is a selective serotonin reuptake inhibitor (SSRI).
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 (CNS) resulting from its inhibition of CNS neuronal reuptake of serotonin (5-HT). It is a highly selective SSRI with minimal effects on norepinephrine and dopamine neuronal reuptake.
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. Tolerance to a model of antidepressant effect in rats was not induced by long-term (up to 5 weeks) treatment with escitalopram. 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 half-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 is 2.2-2.5 times the plasma concentrations observed after a single dose.
Absorption and Distribution: Following a single oral dose (20 mg tablet or solution) of escitalopram, peak blood levels occur at about 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 12 L/kg. Data specific on 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-demethylcitalopram (S-DCT) is about 8% and 10%, respectively. The oral clearance of 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 the escitalopram metabolite S-DCT in plasma is approximately one-third that of escitalopram. The level of S-DDCT was not detectable in most subjects. It has been reported that escitalopram is at least 7 and 27 times more potent than S-DCT and S-DDCT, respectively, in the inhibition of serotonin reuptake, suggesting that the metabolites of escitalopram do not contribute significantly to the antidepressant actions of escitalopram. S-DCT and S-DDCT also have 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. S-DCT and S-DDCT also do not bind to various ion channels including Na+, K+, Cl-, and Ca++ channels.
CYP3A4 and CYP2C19 are the primary isozymes involved in the N-demethylation of escitalopram.
Population Subgroups: Age: Adolescents: Following single dose of 10 mg escitalopram, AUC of escitalopram decreased by 19%, and Cmax increased by 26% in healthy adolescent (12 to 17 years of age) compared to adults. Following multiple dosing of 40 mg/day citalopram, escitalopram elimination half-life, steady-state Cmax and AUC were similar in patients with MDD (12 to 17 years of age) compared to adult patients. No adjustment of dosage is needed in adolescent patients.
Elderly: Compared with younger subjects, AUC and half-life of escitalopram were increased by approximately 50% in elderly subjects (≥ 65 years of age), and Cmax was unchanged. 10 mg is the recommended dose for elderly patients (see Dosage & Administration).
Gender: No dosage adjustment on the basis of gender is needed.
Reduced hepatic function: Citalopram oral clearance was reduced by 37% and half-life was doubled in patients with reduced hepatic function. 10 mg is the recommended dose of escitalopram for most hepatically impaired patients (see Dosage & Administration).
Reduced renal function: In patients with mild to moderate renal function impairment, oral clearance of citalopram was reduced by 17% compared to normal subjects. No adjustment of dosage for such patients is recommended. No information is available about the pharmacokinetics of escitalopram in patients with severely reduced renal function (creatinine clearance <20 mL/min).
Drug-Drug Interactions: Reported literature on in vitro enzyme inhibition has revealed no inhibitory effect escitalopram on CYP3A4, -1A2, -2C9, -2C19, and -2E1. Based on in vitro data, escitalopram would be expected to have little inhibitory effect on in vivo metabolism mediated by these cytochromes. While in vivo information to address this question are limited, results from clinical literature suggest that escitalopram, at a dose of 20 mg, has no 3A4 inhibitory effect and a modest 2D6 inhibitory effect (see Interactions).
Toxicology: Preclinical Safety Data: Carcinogenicity/Mutagenicity/Impairment of Fertility: Carcinogenesis: No evidence for carcinogenicity of racemic citalopram has been reported in mice receiving up to 240 mg/kg/day for 18 months. An increased incidence of small intestine carcinoma has been reported in rats receiving 8 or 24 mg/kg/day racemic citalopram for 24 months. A no-effect dose for this finding was not established. The relevance of these findings to humans is unknown.
Mutagenesis: Racemic citalopram has been reported to be 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 has also been reported to be clastogenic in the 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: Decreased mating and decreased fertility have been reported in rats at oral doses of racemic citalopram 32, 48, and 72 mg/kg/day and at oral doses of racemic citalopram ≥ 32 mg/kg/day, respectively. Increased gestation duration has also been reported at 48 mg/kg/day of racemic citalopram.
Animal Toxicology and/or Pharmacology: Retinal Changes in Rats: Pathologic changes (degeneration/atrophy) have been reported in the retinas of albino rats in the 2-year carcinogenicity study with racemic citalopram. An increase in both incidence and severity of retinal pathology has been reported in both male and female rats receiving 80 mg/kg/day. Similar findings have not been reported in rats receiving 24 mg/kg/day of racemic citalopram for two years, in mice receiving up to 240 mg/kg/day of racemic citalopram for 18 months, or in dogs receiving up to 20 mg/kg/day of racemic citalopram for one year.
Additional studies to investigate the mechanism for this pathology have not been reported, and the potential significance of this effect in humans has not been established.
Cardiovascular Changes in Dogs: Sudden deaths have been reported in beagle dogs between week 17 and week 31 following initiation of oral racemic citalopram (8 mg/kg/day). Sudden deaths have not been reported in rats at doses of racemic citalopram up to 120 mg/kg/day, which produced plasma levels of citalopram and its metabolites demethylcitalopram and didemethylcitalopram (DDCT) similar to those reported in dogs at 8 mg/kg/day. QT prolongation (a known risk factor for the reported outcome in dogs) has been reported in beagle dogs with intravenous administration of racemic DDCT.
Indications/Uses
Esidep Tablets are indicated for: Treatment of major depressive episodes.
Dosage/Direction for Use
ESIDEP are available as 10 mg tablet.
The general dosage recommendations of escitalopram are presented in the following text: ESIDEP Tablets are administered as a single daily dose and may be taken with or without food.
Major Depressive Disorder: Initial Treatment: Adults: The recommended dose of escitalopram is 10 mg once daily. A fixed-dose trial of escitalopram demonstrated the effectiveness of both 10 mg and 20 mg of escitalopram, but failed to demonstrate a greater benefit of 20 mg over 10 mg. If the dose is increased to 20 mg, this should occur after a minimum of one week.
Maintenance Treatment: It is generally agreed that acute episodes of major depressive disorder require several months or longer of sustained pharmacological therapy beyond response to the acute episode. Systematic evaluation of continuing escitalopram 10 or 20 mg/day in adults patients with major depressive disorder who responded while taking escitalopram during an 8-week, acute-treatment phase demonstrated a benefit of such maintenance treatment. Nevertheless, the physician who elects to use escitalopram for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual patient. Patients should be periodically reassessed to determine the need for maintenance treatment.
Special Populations: 10 mg/day is the recommended dose for most elderly patients and patients with hepatic impairment.
No dosage adjustment is necessary for patients with mild or moderate renal impairment. Escitalopram should be used with caution in patients with severe renal impairment.
Discontinuation of Treatment with Escitalopram: Symptoms associated with discontinuation of escitalopram and other SSRIs and SNRIs have been reported (see Precautions). Patients should be monitored for these symptoms when discontinuing treatment. A gradual reduction in the dose rather than abrupt cessation is recommended whenever possible. 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.
Switching Patients To or From a Monoamine Oxidase Inhibitor:
At least 14 days should elapse between discontinuation of an MAOI and initiation of escitalopram therapy. Similarly, at least 14 days should be allowed after stopping escitalopram before starting an MAOI (see Contraindications and Precautions).
Overdosage
Human Experience: In clinical studies of escitalopram, there were reports of escitalopram overdose, including overdoses of up to 600 mg, with no associated fatalities. During the postmarketing evaluation of escitalopram, escitalopram overdoses involving overdoses of over 1000 mg have been reported. As with other SSRIs, a fatal outcome in a patient who has taken an overdose of escitalopram has been rarely reported.
Symptoms most often accompanying escitalopram overdose, alone or in combination with other drugs and/or alcohol, included convulsions, coma, dizziness, hypotension, insomnia, nausea, vomiting, sinus tachycardia, somnolence, and ECG changes (including QT prolongation and very rare cases of torsade de pointes). Acute renal failure has been very rarely reported accompanying overdose.
Management of Overdose: Establish and maintain an airway to ensure adequate ventilation and oxygenation. Gastric evacuation by lavage and use of activated charcoal should be considered. Careful observation and cardiac and vital sign monitoring are recommended, along with general symptomatic and supportive care. Due to the large volume of distribution of escitalopram, forced diuresis, dialysis, hemoperfusion, and exchange transfusion are unlikely to be of benefit. There are no specific antidotes for escitalopram.
In managing overdosage, consider the possibility of multiple-drug involvement. The physician should consider contacting a poison control center for additional information on the treatment of any overdose.
Contraindications
Escitalopram is contraindicated in patients with a hypersensitivity to escitalopram or citalopram or any of the inactive ingredients in escitalopram.
Concomitant use in patients taking monoamine oxidase inhibitors (MAOIs) is contraindicated (see Precautions).
Concomitant use in patients taking pimozide is contraindicated (see Interactions).
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 Interactions).
Warnings
SUICIDALITY AND ANTIDEPRESSANT DRUGS: Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of escitalopram or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Reported short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Escitalopram is not approved for use in pediatric patients less than 12 years of age (see Clinical Worsening and Suicide Risk, and Use in Children under Precautions).
Special Precautions
Antidepressants are not recommended in children and adolescents less than 18 years old. The clinical study showed an increase of suicidal thinking and behavior with antidepressants compared to placebo in children and adolescents. If an antidepressant is needed, the patient should be monitored appropriately and observed closely for suicidality.
Clinical worsening and suicide risk: Patients with major depressive disorder (MDD), both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide. There has been a long-standing concern, however, that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment. Pooled analyses of short-term placebo-controlled trials of Antidepressant drugs (SSRIs and others) showed that these drugs increase the risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (ages 18-24) with major depressive disorder (MDD) and other psychiatric disorders. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction with antidepressants compared to placebo in adults aged 65 and older.
The pooled analyses of placebo-controlled trials In children and adolescents with MDD, obsessive compulsive disorder (OCD), or other psychiatric disorders included a total of 24 short-term trials of 9 antidepressant drugs in over 4400 patients. The pooled analyses of placebo-controlled trials in adults with MDD or other psychiatric disorders included a total of 295 short-term trials (median duration of 2 months) of 11 antidepressant drugs in over 77,000 patients. There was considerable variation in risk of suicidality among drugs, but a tendency toward an increase in the younger patients for almost all drugs studied. There were differences in absolute risk of suicidality across the different indications, with the highest incidence in MDD. The risk differences (drug vs. placebo), however, were relatively stable within age strata and across indications. These risk differences (drug-placebo difference in the number of cases of suicidality per 1000 patients treated) are provided in Table 1. (See Table 1.)

Click on icon to see table/diagram/image

No suicides occurred in any of the pediatric trials. There were suicides in the adult trials, but the number was not sufficient to reach any conclusion about drug effect on suicide.
It is unknown whether the suicidality risk extends to longer-term use, i.e., beyond several months. However, there is substantial evidence from placebo-controlled maintenance trials in adults with depression that the use of antidepressants can delay the recurrence of depression.
All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases.
The following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have been reported in adult and pediatric patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and nonpsychiatric. Although a causal link between the emergence of such symptoms and either the worsening of depression and/or the emergence of suicidal impulses has not been established, there is concern that such symptoms may represent precursors to emerging suicidality.
Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse, or who are experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality, especially if these symptoms are severe, abrupt in onset, or were not part of the patient's presenting symptoms.
If the decision has been made to discontinue treatment, medication should be tapered, as rapidly as is feasible, but with recognition that abrupt discontinuation can be associated with certain symptoms (see Dosage & Administration).
Families and caregivers of patients being treated with antidepressants for major depressive disorder or other indications, both psychiatric and nonpsychiatric, should be alerted about the need to monitor patients for the emergence of agitation, irritability, unusual changes in behavior, and the other symptoms described above, as well as the emergence of suicidality, and to report such symptoms immediately to health care providers. Such monitoring should include daily observation by families and caregivers. Prescriptions for escitalopram should be written for the smallest quantity of tablets consistent with good patient management, in order to reduce the risk of overdose.
Screening patients for bipolar disorder: A major depressive episode may be the initial presentation of bipolar disorder. It is generally believed (though not established in controlled trials) that treating such an episode with an antidepressant alone may increase the likelihood of precipitation of a mixed/manic episode in patients at risk for bipolar disorder. Whether any of the symptoms described above represent such a conversion is unknown. However, prior to initiating treatment with an antidepressant, patients with depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression. It should be noted that escitalopram is not approved for use in treating bipolar depression.
Serotonin syndrome or neuroleptic malignant syndrome (NMS)-like reactions: The development of a potentially life-threatening serotonin syndrome or Neuroleptic Malignant Syndrome (NMS)-like reactions have been reported with SNRIs and SSRIs alone, including escitalopram treatment, but particularly with concomitant use of serotonergic drugs (including triptans) with drugs which impair metabolism of serotonin (including MAOIs), or with antipsychotics or other dopamine antagonists. Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination) and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). Serotonin syndrome, in its most severe form can resemble neuroleptic malignant syndrome, which includes hyperthermia, muscle rigidity, autonomic instability with possible rapid fluctuation of vital signs, and mental status changes. Patients should be monitored for the emergence of serotonin syndrome or NMS-like signs and symptoms.
The concomitant use of escitalopram with MAOIs intended to treat depression is contraindicated. If concomitant treatment of escitalopram with a 5-hydroxytryptamine receptor agonist (triptan) is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases.
The concomitant use of escitalopram with serotonin precursors (such as tryptophan) is not recommended. Treatment with escitalopram and any concomitant serotonergic or antidopaminergic agents, including antipsychotics, should be discontinued immediately if the above events occur and supportive symptomatic treatment should be initiated.
Discontinuation of treatment with escitalopram: During marketing of escitalopram and other SSRIs and SNRIs (serotonin and norepinephrine reuptake inhibitors), there have been spontaneous reports of adverse events occurring upon discontinuation of these drugs, particularly when abrupt, including the following: dysphoric mood, irritability, agitation, dizziness, sensory disturbances (e.g., paresthesias such as electric shock sensations), anxiety, confusion, headache, lethargy, emotional lability, insomnia, and hypomania. While these events are generally self-limiting, there have been reports of serious discontinuation symptoms.
Patients should be monitored for these symptoms when discontinuing treatment with escitalopram. A gradual reduction in the dose rather than abrupt cessation is recommended whenever possible. 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 (see Dosage & Administration).
Seizures: Although anticonvulsant effects of racemic citalopram have been reported in animal, escitalopram has not been systematically evaluated in patients with a seizure disorder. Cases of convulsion have been reported in association with escitalopram treatment. Like other drugs effective in the treatment of major depressive disorder, escitalopram should be introduced with care in patients with a history of seizure disorder.
Activation of mania/hypomania: Activation of mania/hypomania was reported in 0.1% patients with MDD treated with escitalopram. One additional case of hypomania has been reported in association with escitalopram treatment. Activation of mania/hypomania has also been reported in a small proportion of patients with major affective disorders treated with racemic citalopram and other marketed drugs effective in the treatment of major depressive disorder. As with all drugs effective in the treatment of major depressive disorder, escitalopram should be used cautiously in patients with a history of mania.
Hyponatremia: Hyponatremia may occur as a result of treatment with SSRIs and SNRIs, including escitalopram. In many cases, this hyponatremia appears to be the result of the syndrome of inappropriate antidiuretic hormone secretion (SIADH), and was reversible when escitalopram was discontinued.
Cases with serum sodium lower than 110 mmol/L have been reported. Elderly patients may be at greater risk of developing hyponatremia with SSRIs and SNRIs. Also, patients taking diuretics or who are otherwise volume depleted may be at greater risk. Discontinuation of escitalopram should be considered in patients with symptomatic hyponatremia and appropriate medical intervention should be instituted.
Signs and symptoms of hyponatremia include headache, difficulty concentrating, memory impairment, confusion, weakness, and unsteadiness, which may lead to falls. Signs and symptoms associated with more severe and/or acute cases have included hallucination, syncope, seizure, coma, respiratory arrest, and death.
Abnormal bleeding: SSRIs and SNRIs, including escitalopram, may increase the risk of bleeding events. Concomitant use of aspirin, non-steroidal antiinflammatory drugs, warfarin, and other anticoagulants may add to the risk. Case reports and epidemiological data have reported an association between use of drugs that interfere with serotonin reuptake and the occurrence of gastrointestinal bleeding. Bleeding events related to SSRIs and SNRIs use have ranged from ecchymoses, hematomas, epistaxis, and petechiae to life-threatening hemorrhages.
Patients should be cautioned about the risk of bleeding associated with the concomitant use of escitalopram and NSAIDs, aspirin, or other drugs that affect coagulation.
Interference with cognitive and motor performance: Escitalopram 10 mg/day has not reported impairment of intellectual function or psychomotor performance. Because any psychoactive drug may impair judgment, thinking, or motor skills, however, patients should be cautioned about operating hazardous machinery, including automobiles, until they are reasonably certain that escitalopram therapy does not affect their ability to engage in such activities.
Use in patients with concomitant illness: Clinical experience with escitalopram in patients with certain concomitant systemic illnesses is limited. Caution is advisable in using escitalopram in patients with diseases or conditions that produce altered metabolism or hemodynamic responses.
Escitalopram has not been systematically evaluated in patients with a recent history of myocardial infarction or unstable heart disease.
In patients with hepatic impairment, clearance of racemic citalopram was reported to be decreased and plasma concentrations were increased. The recommended dose of escitalopram in hepatically impaired patients is 10 mg/day (see Dosage & Administration).
Because escitalopram is extensively metabolized, excretion of unchanged drug in urine is a minor route of elimination. Until adequate numbers of patients with severe renal impairment have been evaluated during chronic treatment with escitalopram, however, it should be used with caution in such patients (see Dosage & Administration).
Potential for interaction with monoamine oxidase inhibitors: In patients receiving serotonin reuptake inhibitor drugs in combination with a monoamine oxidase inhibitor (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 an MAOI. Some cases presented with features resembling neuroleptic malignant syndrome. Furthermore, limited animal information on the effects of combined use of SSRIs and MAOIs suggests that these drugs may act synergistically to elevate blood pressure and evoke behavioral excitation. Therefore, it is recommended that escitalopram should not be used in combination with an MAOI, or within 14 days of discontinuing treatment with an MAOI. Similarly, at least 14 days should be allowed after stopping escitalopram before starting an MAOI.
Serotonin syndrome has been reported in two patients who were concomitantly receiving linezolid, an antibiotic which is a reversible nonselective MAOI.
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.
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.
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 inpatients 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.
ECT (electroconvulsive therapy): There is limited clinical experience of concurrent administration of SSRIs and ECT, therefore caution is advisable.
Use in Children: Safety and effectiveness of escitalopram has not been established in pediatric patients (less than 12 years of age) with Major Depressive Disorder. Safety and effectiveness of escitalopram has been established in adolescents (12 to 17 years of age) for the treatment of major depressive disorder. Although maintenance efficacy in adolescent patients with Major Depressive Disorder has not been systematically evaluated, maintenance efficacy can be extrapolated from adult data along with comparisons of escitalopram pharmacokinetic parameters in adults and adolescent patients.
Safety and effectiveness of escitalopram has not been established in pediatric patients less than 18 years of age with Generalized Anxiety Disorder.
Decrease appetite and weight loss have been observed in association with the use of SSRIs. Consequently, regular monitoring of weight and growth should be performed in children and adolescents treated with an SSRI such as escitalopram.
Use in Elderly: Clinical experience of efficacy in elderly patients (≥60 years) receiving 10 to 20 mg daily has been reported in published literature. The number of elderly patients was insufficient to adequately assess for possible differential efficacy and safety measures on the basis of age. Nevertheless, greater sensitivity of some elderly individuals to effects of escitalopram cannot be ruled out.
SSRIs and SNRIs, including escitalopram, have been associated with cases of clinically significant hyponatremia in elderly patients, who may be at greater risk for this adverse event.
Half-life of escitalopram has been reported to increase by approximately 50% in elderly subjects as compared to young subjects, whereas Cmax remains unchanged (see Pharmacology under Actions). 10 mg/day is the recommended dose for elderly patients (see Dosage & Administration).
Use In Pregnancy & Lactation
Use in Pregnancy: Pregnancy Category C: Oral administration of escitalopram (56, 112, or 150 mg/kg/day) to pregnant rats during the period of organogenesis resulted in decreased fetal body weight and associated delays in ossification at the two higher doses (approximately ≥ 56 times the maximum recommended human dose [MRHD] of 20 mg/day on a body surface area [mg/m2] basis). Maternal toxicity (clinical signs and decreased body weight gain and food consumption), mild at 56 mg/kg/day, was reported at all dose levels. The developmental no-effect dose of 56 mg/kg/day is approximately 28 times the MRHD on a mg/m2 basis. No teratogenicity has been reported at any of the doses (as high as 75 times the MRHD on a mg/m2 basis).
Slightly increased offspring mortality and growth retardation has been reported in pregnant rats at 48 mg/kg/day which is approximately 24 times the MRHD on a mg/m2 basis. Slight maternal toxicity (clinical signs and decreased body weight gain and food consumption) has been reported at this dose. Slightly increased offspring mortality was also reported at 24 mg/kg/day. The no-effect dose was 12 mg/kg/day which is approximately 6 times the MRHD on a mg/m2 basis.
Racemic citalopram has been shown to have adverse effects on embryo/fetal and postnatal development, including teratogenic effects, in pregnant rats at doses greater than human therapeutic doses.
Oral administration of racemic citalopram (32, 56, or 112 mg/kg/day) to pregnant rats during the period of organogenesis resulted in decreased embryo/fetal growth and survival and an increased incidence of fetal abnormalities (including cardiovascular and skeletal defects) at the high dose. This dose was also associated with maternal toxicity (clinical signs, decreased body weight gain). The developmental no-effect dose was 56 mg/kg/day. Also no adverse effects on embryo/fetal development have been reported in pregnant rabbits at doses of racemic citalopram of up to 16 mg/kg/day. Thus, teratogenic effects of racemic citalopram were reported at a maternally toxic dose in the rat and were not reported in the rabbit.
When female rats were treated with racemic citalopram (4.8, 12.8, or 32 mg/kg/day) from late gestation through weaning, increased offspring mortality during the first 4 days after birth and persistent offspring growth retardation were reported at the highest dose. The no-effect dose was 12.8 mg/kg/day. Similar effects on offspring mortality and growth have been reported in dams receiving escitalopram throughout gestation and early lactation at doses ≥ 24 mg/kg/day. A no-effect dose has not been reported.
There are no adequate and well-controlled reported studies in pregnant women; therefore, escitalopram should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Pregnancy-Nonteratogenic Effects:
Neonates exposed to escitalopram and other SSRIs or SNRIs, late in the third trimester, have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. Such complications can arise immediately upon delivery. Reported findings have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying. These features are consistent with either a direct toxic effect of SSRIs and SNRIs or, possibly, a drug discontinuation syndrome. It should be noted that, in some cases, the clinical picture is consistent with serotonin syndrome (see Precautions).
Infants exposed to SSRIs in late pregnancy may have an increased risk for persistent pulmonary hypertension of the newborn (PPHN). The reported risk was approximately 5 cases per 1000 pregnancies. PPHN occurs in 1-2 per 1000 live births in the general population and is associated with substantial neonatal morbidity and mortality.
When treating a pregnant woman with escitalopram during the third trimester, the physician should carefully consider both the potential risks and benefits of treatment (see Dosage & Administration).
Physicians should note that in women with a history of major depression who are euthymic at the beginning of pregnancy, women who discontinue antidepressant medication during pregnancy are more likely to experience a relapse of major depression than women who continue antidepressant medication.
Labor and Delivery:
The effect of escitalopram on labor and delivery in humans is unknown.
Use in Lactation:
Like racemic citalopram, escitalopram is distributed in human breast milk. Potential for serious adverse effects (e.g., excessive somnolence, decreased feeding, weight loss) in nursing infants exists. Discontinue nursing or the drug, taking into account the potential risk in nursing infants and the importance of the drug to the mother.
Adverse Reactions
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 are listed below by system organ class and frequency.
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). (See Table 2.)

Click on icon to see table/diagram/image

Class effects: An increased risk of bone fractures in patients receiving SSRIs and TCAs has been reported in epidemiological literature, mainly in patients 50 years of age and older. 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 Dosage & Administration and Precautions).
QT interval prolongation: Cases of QT interval prolongation and ventricular arrhythmia including torsade de pointes have been reported during the postmarketing period, predominantly in patients of female gender, with hypokalaemia, or with pre-existing QT interval prolongation or other cardiac diseases (see Contraindications, Precautions, Interactions and Overdosage).
In addition to the adverse events presented above, following adverse events have been reported with escitalopram.

Gastrointestinal disorders: Indigestion, abdominal pain, abdominal cramp, flatulence, toothache, heartburn, gastroenteritis, dysphagia, gastroesophageal reflux, pancreatitis.
Reproductive disorders/female: Menstrual cramps, menstrual disorder.
Respiratory, thoracic and mediastinal disorders: Bronchitis, rhinitis, coughing, nasal congestion, sinus congestion, sinus headache, dyspnea, pulmonary embolism, pulmonary hypertension of the newborn.
Blood and lymphatic system disorders: Anaemia, agranulocytis, aplastic anaemia, haemolytic anaemia, idiopathic thrombocytopenia purpura, leukopenia.
Cardiac disorders: Atrial fibrillation, Cardiac failure, myocardial infarction, hypertension, palpitation.
Ear and labyrinth disorders: Vertigo.
Endocrine disorders: Diabetes mellitus, hyperprolactinaemia.
Eye disorders: Diplopia, glaucoma.
General disorders and administration site conditions:
Abnormal gait, asthenia, fall, feeling abnormal, malaise, allergy, chest pain, hot flushes, pain in limb, influenza-like symptoms.
Hepatobiliary disorders:
Fulminant hepatitis, hepatic failure, hepatic necrosis.
Immune system disorders: Allergic reaction.
Metabolism and nutrition disorders: Hyperglycaemia, hypoglycaemia.
Musculoskeletal and connective tissue disorders:
Muscle cramp, muscle stiffness, muscle weakness, rhabdomyolysis, jaw stiffness, neck/shoulder pain, back pain.
Nervous system disorders: Amnesia, ataxia, choreoathetosis, cerebrovascular accident, dysarthria, dystonia, extrapyramidal disorders, hypoaesthesia, myoclonus, nystagmus, parkinsonism, restless legs, light-headed feeling, migraine.
Pregnancy, puerperium and perinatal conditions: Spontaneous abortion.
Psychiatric disorders: Anger, apathy, completed suicide, depression aggravated, delirium, delusion, disorientation, feeling unreal, mood swings, nervousness, nightmare, paranoia, self-harm or thoughts of self-harm, suicide attempt, concentration impaired, lethargy.
Renal and urinary disorders: Acute renal failure, dysuria, urinary frequency, urinary tract infection.
Skin and subcutaneous tissue disorders: Dermatitis, erythema multiforme, photosensitivity reaction, Stevens Johnson Syndrome, toxic epidermal necrolysis.
Vascular disorders: Deep vein thrombosis, flushing, hypertensive crisis, orthostatic hypotension, phlebitis, thrombosis.
Investigations:
Bilirubin increased, hypercholesterolemia, INR increased, prothrombin decreased.
Drug Interactions
Serotonergic Drugs: Based on the mechanism of action of SNRIs and SSRIs including escitalopram, and the potential for serotonin syndrome, caution is advised when escitalopram is co-administered with other drugs that may affect the serotonergic neurotransmitter systems, such as triptans, linezolid (an antibiotic which is a reversible non-selective MAOI), lithium, tramadol, or St. John's Wort (see Precautions). The concomitant use of escitalopram with other SSRIs, SNRIs or tryptophan is not recommended.
Triptans: There have been rare postmarketing reports of serotonin syndrome with use of an SSRI and a triptan. If concomitant treatment of escitalopram with a triptan is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases (see Precautions).
CNS Drugs: Given the primary CNS effects of escitalopram, caution should be used when it is taken in combination with other centrally acting drugs.
Alcohol:
Although escitalopram did not potentiate the cognitive and motor effects of alcohol in a clinical trial, as with other psychotropic medications, the use of alcohol by patients taking escitalopram is not recommended.
Monoamine Oxidase Inhibitors (MAOIs):
(see Contraindications and Precautions).
Drugs that Interfere with Hemostasis (NSAIDs, Aspirin, Warfarin, etc.): Serotonin release by platelets plays an important role in hemostasis. An association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding has also shown that concurrent use of an NSAID or aspirin may potentiate the risk of bleeding. Altered anticoagulant effects, including increased bleeding, have been reported when SSRIs and SNRIs are co-administered with warfarin. Patients receiving warfarin therapy should be carefully monitored when escitalopram is initiated or discontinued.
Cimetidine: An increase in citalopram AUC and Cmax of 43% and 39%, respectively, have been reported in patients who had received 21 days of 40 mg/day racemic citalopram and 400 mg/day cimetidine for 8 day. The clinical significance of these findings is unknown.
Digoxin: No significant affect on the pharmacokinetics of either citalopram or digoxin has been reported with combined administration of citalopram (40 mg/day for 21 day) and digoxin (single dose 1 mg).
Lithium:
Co-administration of racemic citalopram (40 mg/day for 10 days) and lithium (30 mmol/day for 5 days) had no significant effect on the pharmacokinetics of citalopram or lithium. Nevertheless, plasma lithium levels should be monitored with appropriate adjustment to the lithium dose in accordance with standard clinical practice. Because lithium may enhance the serotonergic effects of escitalopram, caution should be exercised when escitalopram and lithium are co-administered.
Pimozide: Increased QTc intervals have been reported when pimozide and racemic citalopram have been concurrently administered. Effects on escitalopram have not been evaluated. Pharmacokinetics of racemic citalopram (AUC and peak plasma concentrations) was not affected by pimozide. Concomitant use of pimozide with escitalopram is contraindicated.
Sumatriptan: There have been rare postmarketing reports describing patients with weakness, hyperreflexia, and incoordination following the use of an SSRI and sumatriptan. If concomitant treatment with sumatriptan and an SSRI (e.g., fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram, escitalopram) is clinically warranted, appropriate observation of the patient is advised.
Theophylline: Combined administration of racemic citalopram (40 mg/day for 21 days) and the CYP1A2 substrate theophylline (single dose of 300 mg) did not affect the pharmacokinetics of theophylline. The effect of theophylline on the pharmacokinetics of citalopram was not evaluated.
Warfarin: Administration of 40 mg/day racemic citalopram for 21 days did not affect the pharmacokinetics of warfarin, a CYP3A4 substrate. Prothrombin time was increased by 5%, the clinical significance of which is unknown.
Carbamazepine: Combined administration of racemic citalopram (40 mg/day for 14 days) and carbamazepine (titrated to 400 mg/day for 35 days) did not significantly affect the pharmacokinetics of carbamazepine, a CYP3A4 substrate. Although trough citalopram plasma levels were unaffected, given the enzyme-inducing properties of carbamazepine, the possibility that carbamazepine might increase the clearance of escitalopram should be considered if the two drugs are coadministered.
Triazolam: Combined administration of racemic citalopram (titrated to 40 mg/day for 28 days) and the CYP3A4 substrate triazolam (single dose of 0.25 mg) did not significantly affect the pharmacokinetics of either citalopram or triazolam.
Ketoconazole: Combined administration of racemic citalopram (40 mg) and ketoconazole (200 mg), a potent CYP3A4 inhibitor, decreased the Cmax and AUC of ketoconazole by 21% and 10%, respectively, and did not significantly affect the pharmacokinetics of citalopram.
Ritonavir: Combined administration of a single dose of ritonavir (600 mg), both a CYP3A4 substrate and a potent inhibitor of CYP3A4, and escitalopram (20 mg) did not affect the pharmacokinetics of either ritonavir or escitalopram.
CYP3A4 and -2C19 Inhibitors: It has been reported that CYP3A4 and -2C19 are the primary enzymes involved in the metabolism of escitalopram. However, co-administration of escitalopram (20 mg) and ritonavir (600 mg), a potent inhibitor of CYP3A4, did not significantly affect the pharmacokinetics of escitalopram. Because escitalopram is metabolized by multiple enzyme systems, inhibition of a single enzyme may not appreciably decrease escitalopram clearance.
Drugs Metabolized by Cytochrome P4502D6: An inhibitory effect of escitalopram on CYP2D6 is not known. In addition, steady state levels of racemic citalopram were not significantly different in poor metabolizers and extensive CYP2D6 metabolizers after multiple-dose administration of citalopram, suggesting that co-administration, with escitalopram, of a drug that inhibits CYP2D6, is unlikely to have clinically significant effects on escitalopram metabolism. However, there are limited in vivo information suggesting a modest CYP2D6 inhibitory effect for escitalopram, i.e., co-administration of escitalopram (20 mg/day for 21 days) with the tricyclic antidepressant desipramine (single dose of 50 mg), a substrate for CYP2D6, resulted in a 40% increase in Cmax and a 100% increase in AUC of desipramine. The clinical significance of this finding is unknown. Nevertheless, caution is indicated in the co-administration of escitalopram and drugs metabolized by CYP2D6.
Metoprolol: A 50% increase in Cmax and 82% increase in AUC of the beta-adrenergic blocker metoprolol (single dose of 100 mg) has been reported after co-administration of 20 mg/day escitalopram for 21 days. Increased metoprolol plasma levels have been associated with decreased cardioselectivity. Co-administration of escitalopram and metoprolol had no clinically significant effects on blood pressure or heart rate.
Electroconvulsive Therapy (ECT):
There are no clinical studies of the combined use of ECT and escitalopram.
Caution For Usage
Special precautions for disposal: Any unused product or waste should be disposed of in accordance with local requirements.
Incompatibilities: Not applicable.
Storage
Store below 30°C, protected from moisture.
Special precautions for storage:
This medicinal product does not require any special storage conditions.
Shelf-Life: 2 years.
MIMS Class
ATC Classification
N06AB10 - escitalopram ; Belongs to the class of selective serotonin reuptake inhibitors. Used in the management of depression.
Presentation/Packing
FC tab 10 mg (white to off-white, oval, biconvex debossed with 'E' and '8' on either side of the eye breakline on one side and plain on the other side) x 4 x 7's.
Register or sign in to continue
Asia's one-stop resource for medical news, clinical reference and education
Sign up for free
Already a member? Sign in