Lexapro

Lexapro

escitalopram

Manufacturer:

Lundbeck

Distributor:

Metro Drug
Full Prescribing Info
Contents
Escitalopram oxalate.
Action
Pharmacology: Mechanism of Action: Escitalopram is a selective inhibitor of serotonin (5-HT) re-uptake. The inhibition of 5-HT re-uptake is the only likely mechanism of action explaining the pharmacological and clinical effects of escitalopram. Escitalopram has no or low affinity for a number of receptors including 5-HT1A, 5-HT2, DA D1 and D2 receptors, α1-, α2-, β-adrenoceptors, histamine H1, muscarine cholinergic, benzodiazepine and opioid receptors.
Pharmacokinetics: Absorption: Absorption is almost complete and independent of food intake (mean Tmax is 4 hrs 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,b/F) after oral administration is about 12-26 L/kg. The plasma protein-binding is <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 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 β) after multiple dosing is about 30 hrs and the oral plasma clearance (Cloral) is about 0.6 L/min. The major metabolites have a significantly longer t½. Escitalopram and major metabolites are assumed to be eliminated by both the hepatic (metabolic) and 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 20-125 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 Renal Function: In patients with mild to moderate hepatic impairment (Child-Pugh Criteria A and B), the t½ of escitalopram was about twice as long and the exposure was about 60% higher than in subjects with normal liver function.
Polymorphism: It has been observed that poor metabolizers with respect to CYP2C19 have twice as high a plasma concentration of escitalopram as extensive metabolizers. No significant change in exposure was observed in poor metabolizers with respect to CYP2D6.
Toxicology: Preclinical Safety Data: No complete conventional battery of preclinical studies was performed with escitalopram since the bridging toxicokinetic and toxicological studies conducted in rats with escitalopram and citalopram showed a similar profile. Therefore, all the citalopram information can be extrapolated to escitalopram.
In comparative toxicological studies in rats, escitalopram and citalopram caused cardiac toxicity including CHF after treatment for some weeks, when using dosages that caused general toxicity. 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. These findings are probably related to an exaggerated influence on biogenic amines ie, secondary to the primary pharmacological effects. However, the exact mechanism of cardiotoxicity is not clear. Clinical experience with citalopram and clinical trial experience with escitalopram do not indicate that these findings have a clinical implication.
Increased content of phospholipids has been observed in some tissues eg, 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 fetal 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. Pre- and postnatal studies showed reduced survival during the lactation period at exposures in terms of AUC in excess of the exposure achieved during clinical use.
Indications/Uses
Treatment of major depressive episodes, panic disorder with or without agoraphobia, social anxiety disorder (social phobia), generalized anxiety disorder and obsessive-compulsive disorder.
Dosage/Direction for Use
Safety of daily doses >20 mg has not been demonstrated.
Lexapro is administered as a single daily dose and may be taken with or without food.
Major Depressive Episodes: Usual Dosage: 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 1st week before increasing the dose to 10 mg daily. The dose may be further increased, up to a maximum of 20 mg daily, depending on individual patient response.
Maximum effectiveness is reached after about 3 months. The treatment lasts several months.
Social Anxiety Disorder (SAD): Usual Dosage: 10 mg once daily. Depending on individual patient response, the dose may be increased to a maximum of 20 mg daily. SAD is a disease with a chronic course and long-term treatment is therefore warranted to consolidate response and prevent relapse.
Generalized Anxiety Disorder (GAD): Usual Dose: 10 mg once daily. Depending on individual patient response, the dose may be increased to a maximum of 20 mg daily. GAD is a disease with a chronic course and long-term treatment is therefore warranted to consolidate response and prevent relapse.
Obsessive-Compulsive Disorder (OCD): Usual dosage is 10 mg once daily. Depending on individual patient response, the dose may be increased to 20 mg daily. Long-term treatment of patients responding to a 16-week open treatment phase has been studied for at least 24 weeks in patients receiving 10 or 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 (>65 years): Initial treatment with ½ the usually recommended dose and a lower maximum dose should be considered.
Children and Adolescents (<18 years): Not recommended, since efficacy has not been investigated in this population.
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 <30 mL/min).
Reduced Hepatic Function: An initial dose of 5 mg daily for the first 2 weeks of treatment is recommended. Depending on individual patient response, the dose may be increased to 10 mg daily.
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 2 weeks of treatment is recommended. Depending on individual patient response, the dose may be increased to 10 mg daily.
Discontinuation: When stopping treatment with Lexapro, the dose should be gradually reduced over a period of 1 or 2 weeks in order to avoid possible withdrawal reactions.
Overdosage
Toxicity: Clinical data on escitalopram overdose are limited. However, it has been observed that doses of 190 mg of escitalopram have been taken without any serious symptoms being reported.
Symptoms: Symptoms of overdose with racemic citalopram (>600 mg): Dizziness, tremor, agitation, somnolence, unconsciousness, seizures, tachycardia, changes in the ECG with ST-T changes, broadening of the QRS complex, prolonged QT interval, arrhythmias, respiratory depression, vomiting, rhabdomyolysis, metabolic acidosis, hypokalemia. It is anticipated that overdoses with escitalopram would result in similar symptoms.
Treatment: There is no specific antidote. Establish and maintain an airway, ensure adequate oxygenation and respiratory function. 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.
Contraindications
Hypersensitivity to escitalopram or any of the excipients of Lexapro. Concomitant treatment with nonselective, irreversible MAO inhibitors.
Special Precautions
The following precautions apply to the therapeutic class of selective serotonin re-uptake inhibitors (SSRIs).
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 2 weeks of starting treatment. A low starting dose is advised to reduce the likelihood of an anxiogenic effect.
Seizures: Lexapro 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 patient 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: The possibility of suicide attempt is inherent in depression and may persist until significant improvement occurs, either spontaneously or following treatment.
Patients being treated with antidepressants should be monitored carefully especially at the beginning of treatment for clinical worsening and/or the emergence of suicidality (suicidal ideation and behavior).
This precaution should also be observed when treating other psychiatric disorders because of the possibility of co-morbidity with major depressive disorder.
Hyponatremia: 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 eg, elderly, cirrhotic patients or patients concomitantly treated with medications known to cause hyponatremia.
Hemorrhage: There have been reports of cutaneous bleeding abnormalities eg, ecchymoses and purpura, with SSRIs. Caution is advised in patients taking SSRIs, particularly with concomitant use of oral anticoagulants, with medicinal products known to affect platelet function [eg, 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.
Electroconvulsive Therapy (ECT): 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. Concomitant treatment with nonselective, irreversible MAO inhibitors.
Serotonin Syndrome: Caution is advisable if escitalopram is used concomitantly with medicinal products with serotonergic effects eg, 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 eg, 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.
Withdrawal Reactions: When stopping therapy with Lexapro, the dose should be gradually reduced over a period of 1 or 2 weeks in order to avoid possible withdrawal reactions.
Effects on the Ability to Drive or Operate Machinery: Although escitalopram has been shown not to affect intellectual function or psychomotor performance, any psychoactive medicinal product may impair judgment or skills. Patients should be cautioned about the potential risk of an influence on their ability to drive a car and operate machinery.
Use in Pregnancy: For escitalopram, only limited clinical data are available regarding exposures in pregnancy. Escitalopram should not be used during pregnancy unless clearly necessary and only after careful consideration of the risk/benefit ratio.
In reproductive toxicity studies performed in rats with escitalopram, embryo-fetotoxic effects were observed, but no increased incidence of malformations. Using SSRIs in the 3rd trimester may result in effects, including neurobehavioral disturbances in the newborn infant.
The following effects were reported in neonates with SSRIs administered to pregnant women until date of birth: Irritability, tremor, hypertonia, increased muscle tone, constant crying, difficulty in suckling or in sleeping.
They may either indicate serotonergic effects or withdrawal syndrome. If used during pregnancy, SSRIs should never be stopped abruptly.
Use in Lactation: It is expected that escitalopram will be excreted into human milk, and breastfeeding is not recommended during treatment.
Use in Children: Use in children and adolescents (<18 years) is not recommended since efficacy has not been investigated in this population.
Use In Pregnancy & Lactation
Use in Pregnancy: For escitalopram, only limited clinical data are available regarding exposures in pregnancy. Escitalopram should not be used during pregnancy unless clearly necessary and only after careful consideration of the risk/benefit ratio.
In reproductive toxicity studies performed in rats with escitalopram, embryo-fetotoxic effects were observed, but no increased incidence of malformations. Using SSRIs in the 3rd trimester may result in effects, including neurobehavioral disturbances in the newborn infant.
The following effects were reported in neonates with SSRIs administered to pregnant women until date of birth: Irritability, tremor, hypertonia, increased muscle tone, constant crying, difficulty in suckling or in sleeping.
They may either indicate serotonergic effects or withdrawal syndrome. If used during pregnancy, SSRIs should never be stopped abruptly.
Use in Lactation: It is expected that escitalopram will be excreted into human milk, and breastfeeding is not recommended during treatment.
Adverse Reactions
Adverse reactions are most frequent during the 1st or 2nd week of treatment and usually decrease in intensity and frequency with continued treatment.
After prolonged administration, abrupt cessation of SSRIs may produce withdrawal reactions in some patients. Although withdrawal reactions may occur on stopping therapy, the available preclinical and clinical evidence does not suggest that SSRIs cause dependence.
Withdrawal symptoms (dizziness, headache and nausea) have been observed in some patients after abrupt discontinuation of escitalopram treatment.
Most symptoms were mild and self-limiting. In order to avoid withdrawal reactions, tapered discontinuation over 1-2 weeks is recommended.
The following adverse reactions have occurred more frequently with escitalopram than with placebo in double-blind placebo-controlled studies. The frequencies listed are not placebo-corrected (uncommon: >1/1000, <1/100; common >1/100, <1/10; very common >1/10).
Metabolism and Nutrition Disorders: Common: Decreased appetite.
Psychiatric Disorders: Common: Decreased libido, anorgasmia (female).
Nervous System Disorders: Common: Insomnia, somnolence, dizziness. Uncommon: Taste disturbance, sleep disorder.
Respiratory, Thoracic and Mediastinal Disorders: Common: Sinusitis, yawning.
Gastrointestinal Disorders: Very common: Nausea. Common: Diarrhea, constipation.
Skin and Subcutaneous Tissue Disorders: Common: Increased sweating.
Reproductive System and Breast Disorders: Common: Ejaculation disorder, impotence.
General Disorders and Administration Site Conditions: Common: Fatigue, pyrexia.
The following adverse reactions apply to the therapeutic class of SSRIs.
Cardiovascular Disorders: Postural hypotension.
Disorders of Metabolism and Nutrition: Hyponatremia, inappropriate ADH secretion.
Disorders of the Eye: Abnormal vision.
Gastrointestinal Disorders: Nausea, vomiting, dry mouth, diarrhea, anorexia.
General Disorders: Insomnia, dizziness, fatigue, drowsiness, anaphylactic reactions.
Hepatobiliary Disorders: Abnormal liver function tests.
Musculoskeletal Disorders: Arthralgia, myalgia.
Neurological Disorders: Seizures, tremor, movement disorders, serotonin syndrome.
Psychiatric Disorders: Hallucinations, mania, confusion, agitation, anxiety, depersonalization, panic attacks, nervousness.
Renal and Urinary Disorders: Urinary retention.
Reproductive Disorders: Galactorrhea, sexual dysfunction terms including impotence, ejaculation disorder, anorgasmia.
Skin Disorders: Rash, ecchymoses, pruritus, angioedema, sweating.
Drug Interactions
Pharmacodynamic Interactions: Contraindicated Combinations: Nonselective MAOIs: Cases of serious reactions have been reported in patients receiving an SSRI in combination with a nonselective 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 contraindicated in combination with nonselective MAOIs. Escitalopram may be started 14 days after discontinuing treatment with an irreversible MAOI and at least 1 day after discontinuing treatment with the reversible MAOI (RIMA), moclobemide. At least 7 days should elapse after discontinuing escitalopram treatment, before starting a nonselective MAOI.
Inadvisable Combinations: 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.
Combinations Requiring Precautions for Use: 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 co-administered with racemic citalopram.
Serotonergic Medicinal Products: Co-administration with serotonergic medicinal products (eg, 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.
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.
Hemorrhage: Altered anticoagulant 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.
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.
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 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 thus be exercised at the upper end of the dose range of escitalopram when used concomitantly with CYP2C19 inhibitors (eg, fluoxetine, fluvoxamine, lansoprazole, ticlopidine) or cimetidine. A reduction in the dose of escitalopram may be necessary based on clinical judgment.
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 metabolized by this enzyme, and that have a narrow therapeutic index eg, flecainide, propafenone and metoprolol (when used in cardiac failure), or some CNS-acting medicinal products that are mainly metabolized by CYP2D6 eg, antidepressants eg, desipramine, clomipramine and nortryptyline or antipsychotics eg, risperidone, thioridazine and haloperidol. Dosage adjustment may be warranted.
Co-administration with desipramine or metoprolol resulted in both cases in a 2-fold 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 metabolized by CYP2C19.
Storage
Store at temperatures not exceeding 30°C.
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 5 mg x 28's. 10 mg x 14's. 20 mg x 28's.
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