Escitalopram Sandoz

Escitalopram Sandoz

escitalopram

Manufacturer:

Sandoz

Distributor:

Zuellig Pharma
Full Prescribing Info
Contents
Escitalopram.
Description
Each film coated tablet contains 10 mg of Escitalopram.
Each film coated tablet contains 20 mg of Escitalopram.
Excipients/Inactive Ingredients: Tablet core: Lactose monohydrate, Cellulose, Microcrystalline, Croscarmellose sodium, Hypromellose, Magnesium Stearate, Sillica, Colloidal Anhydrous, Water purified.
Tablet film-coating: Hypromellose, Macrogol 6000, Titanium Dioxide, Talcum, Water Purified.
Action
Pharmacotherapeutic Group: Antidepressants, selective serotonin reuptake inhibitors. ATC Code: N06AB10.
Pharmacology: Pharmacodynamics: Mechanism of Action: Escitalopram is a selective inhibitor of serotonin reuptake with little to no effect on norepinephrine or dopamine reuptake.
Escitalopram has no or very low affinity for 5-HT1-7m alpha-and beta-adrenergic, D1-5, H1-3, M1-5, and benzodiazepine receptors. The inhibition of 5-HT reuptake is the only likely mechanism of action explaining the pharmacological and clinical effects of escitalopram.
Pharmacodynamics Effects: In a double-blind, placebo-controlled ECG study in healthy subjects, the change from baseline in QTc (Fridericia-correction) was 4.3 msec (90% CI: 2.2, 6.4) at the 10 mg/day dose and 10.7 msec (90% CI: 8.6, 12.8) at the supratherapeutic dose of 30 mg/day (see Contraindications, Precautions, Interactions, Adverse Reactions and Overdosage).
Clinical Efficacy: Major depressive episodes: In a longer-term study, 274 adults with major depressive disorder who had responded to escitalopram 10 or 20 mg daily during an initial 8-week, open-label, flexible dosage treatment phase were randomized to continue escitalopram at the same dosage or receive placebo for up to 36 weeks of observation for relapse in the double-blind phase. Relapse during the double-blind phase was defined as an increase in the MADRS total score to 22 or greater or discontinuance due to insufficient clinical response. Escitalopram-treated patients experienced a substantially longer time to relapse of depression compared with those receiving placebo.
Social anxiety disorder: Escitalopram was effective in both three short-term (12- week) studies and in responders in a 6-month relapse prevention study in social anxiety disorder. In a 24-week dose-finding study, efficacy of 5, 10 and 20 mg escitalopram has been demonstrated.
Generalised anxiety disorder: Escitalopram in doses of 10 and 20 mg/day was effective in four out of four placebo-controlled studies.
In pooled data from three studies with similar design comprising 421 escitalopram-treated patients and 419 placebo-treated patients there were 47.5% and 28.9% responders respectively and 37.1% and 20.8% remitters. Sustained effect was seen from week 1.
Maintenance of efficacy of escitalopram 20mg/day was demonstrated in a 24 to 76 week, randomised, maintenance of efficacy study in 373 patients who had responded during the initial 12-week open-label treatment.
Obsessive-compulsive disorder: In a randomised, double-blind, clinical study, 20 mg/day escitalopram separated from placebo on the Y-BOCS total score after 12 weeks. After 24 weeks, both 10 and 20 mg/day escitalopram were superior as compared to placebo.
Prevention of relapse was demonstrated for 10 and 20 mg/day escitalopram in patients who responded to escitalopram in a 16-week open-label period and who entered a 24-week, randomised, double-blind, placebo controlled period.
Pharmacokinetics:
Absorption: Time to peak: Escitalopram : ~ 5 hours
Distribution: The volume of distribution (Vd,) is about 20l/kg. Protein binding: ~ 56% to plasma proteins.
Biotransformation: Metabolism: Hepatic via CYP2C19 and 3A4 to S-desmethylcitalopram (S-DCT); S-DCT is metabolized to S-didesmethylcitalopram (S-DDCT) via CYP2D6; in vitro data suggest metabolites do not contribute significantly to the antidepressant effects of escitalopram.
Elimination: Half-life elimination: ~ 27-32 hours (increased ~50% in the elderly and doubled in patients with hepatic impairement).
Excretion: Urine(8% as unchanged drug; S-DCT 10%).
Elderly patients (> 65 years of age): 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 (see Dosage & Administration).
Reduced hepatic function: In patients with mild or moderate hepatic impairment (Child-Pugh Criteria A and B), the halflife of escitalopram was about twice as long and higher than in subjects with normal liver function (see Dosage & Administration).
Reduced renal function: Escitalopram should be used with caution in patient with severe renal impairment (ie., creatinine clearance less than 20 ml/minute).
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 congestive heart failure, after treatment for some weeks, when using dosages that caused general toxicity. The cardiotoxicity seemed to correlate with peak plasma concentrations rather than to systemic exposures (AUC). Peak plasma concentrations at no-effect-level were in excess (8-fold) of those achieved in clinical use, while AUC for escitalopram was only 3- to 4-fold higher than the exposure achieved in clinical use. For citalopram AUC values for the S-enantiomer were 6- to 7-fold higher than exposure achieved in clinical use. The findings are probably related to an exaggerated influence on biogenic amines i.e. secondary to the primary pharmacological effects, resulting in haemodynamic effects (reduction in coronary flow) and ischaemia. However, the exact mechanism of cardiotoxicity in rats is not clear. Clinical experience with citalopram, and the clinical trial experience with escitalopram, do not indicate that these findings have a clinical correlate.
Increased content of phospholipids has been observed in some tissues e.g. lung, epididymides and liver after treatment for longer periods with escitalopram and citalopram in rats. Findings in the epididymides and liver were seen at exposures similar to that in man. The effect is reversible after treatment cessation. Accumulation of phospholipids (phospholipidosis) in animals has been observed in connection with many cationic amphiphilic medicines. It is not known if this phenomenon has any significant relevance for man.
In the developmental toxicity study in the rat embryotoxic effects (reduced foetal weight and reversible delay of ossification) were observed at exposures in terms of AUC in excess of the exposure achieved during clinical use. No increased frequency of malformations was noted. A pre- and postnatal study showed reduced survival during the lactation period at exposures in terms of AUC in excess of the exposure achieved during clinical use.
Animal data have shown that citalopram induces a reduction of fertility index and pregnancy index, reduction in number in implantation and abnormal sperm at exposure well in excess of human exposure. No animal data related to this aspect are available for escitalopram.
Indications/Uses
Treatment of major depressive episodes.
Treatment of panic disorder with or without agoraphobia.
Treatment of social anxiety disorder (social phobia).
Treatment of generalised anxiety disorder.
Treatment of obsessive-compulsive disorder.
Dosage/Direction for Use
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, after at least a week.
Usually 2-4 weeks are necessary to obtain antidepressant response. After the symptoms resolve, treatment for at least 6 months is required for consolidation of the response.
Panic disorder with or without agoraphobia: An initial dose of 5 mg is recommended for the first week before increasing the dose to 10 mg daily. The dose may be further increased, up to a maximum of 20 mg daily, dependent on individual patient response.
Maximum effectiveness is reached after about 3 months. The treatment lasts several months.
Social anxiety disorder: Usual dosage is 10 mg once daily. Usually 2-4 weeks are necessary to obtain symptom relief. The dose may subsequently, depending on individual patient response, increased to a maximum of 20 mg daily.
Treatment for 3 months is recommended to consolidate response. Long-term treatment of responders for 6 months has been shown to prevent relapse and can be considered on an individual basis; treatment benefits should be re-evaluated at regular intervals.
Generalised anxiety disorder: Initial dosage is 10 mg once daily. Depending on the individual patient response, the dose may be increased to a maximum of 20 mg daily.
Treatment for 3 months is recommended to consolidate response. Long-term treatment of responders for 6 months 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: Initial dosage is 10 mg once daily. Depending on the individual patient response, the dose may be increased to a maximum of 20 mg daily.
As OCD is a chronic disease, patients should be treated for a sufficient period to ensure that they are symptom free.
Treatment benefits and dose should be re-evaluated at regular intervals (see Pharmacology: Pharmacodynamics under Actions).
Elderly patients (> 65 years of age): Initial dosage is 5 mg once daily. Depending on individual patient response the dose may be increased to 10 mg daily (see Pharmacology: Pharmacokinetics under Actions).
Children and adolescents (< 18 years of age): Escitalopram should not be used in children and adolescents under the age of 18 years (see Precautions).
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) (see Pharmacology: Pharmacokinetics under Actions).
Reduced hepatic function: An initial dose of 5 mg daily for the first two weeks of treatment is recommended in patients with mild to moderate hepatic impairment. Depending on the individual patient response, the dose may be increased to 10 mg daily. Caution and extra careful dose titration is advised in patients with severely reduced hepatic function (see Pharmacology: Pharmacokinetics under Actions).
Poor metabolisers of CYP2C19: For patients who are known to be poor metabolisers with respect to CYP2C19, an initial dose of 5 mg daily during the first two weeks of treatment is recommended. Depending on individual patient response, the dose may be increased to 10 mg daily (see Pharmacology: Pharmacokinetics under Actions).
Discontinuation symptoms seen when stopping treatment: Abrupt discontinuation should be avoided. When stopping treatment with escitalopram the dose should be gradually reduced over a period of at least one to two weeks in order to reduce the risk of discontinuation symptoms (see Precautions and Adverse Reactions). 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.
Overdosage
Toxicity: Clinical data on escitalopram overdose are limited and many cases involve concomitant overdoses of other drugs. In the majority of cases mild or no symptoms have been reported. Fatal cases of escitalopram overdose have rarely been reported with escitalopram alone; the majority of cases have involved overdose with concomitant medications. Doses between 400 and 800 mg of escitalopram alone have been taken without any severe symptoms.
Symptoms: Symptoms seen in reported overdose of escitalopram include symptoms mainly related to the central nervous system (ranging from dizziness, tremor, and agitation to rare cases of serotonin syndrome, convulsion, and coma), the gastrointestinal system (nausea/vomiting), and the cardiovascular system (hypotension, tachycardia, QT prolongation, and arrhythmia) and electrolyte/fluid balance conditions (hypokalaemia, hyponatraemia).
Management: There is no specific antidote. Establish and maintain an airway, ensure adequate oxygenation and respiratory function. Gastric lavage and the use of activated charcoal should be considered. Gastric lavage should be carried out as soon as possible after oral ingestion. Cardiac and vital signs monitoring are recommended, along with general symptomatic supportive measures.
ECG monitoring is advisable in case of overdose, in patients with congestive heart failure/bradyarrhythmias, in patients using concomitant medications that prolong the QT interval, or in patients with altered metabolism, e.g. liver impairment.
Contraindications
Hypersensitivity to escitalopram or any of the excipients.
Concomitant treatment with non-selective, irreversible monoamine oxidase inhibitors (MAO-inhibitors) is contraindicated due to the risk of serotonin syndrome with agitation, tremor, hyperthermia etc. (see Interactions).
The combination of escitalopram with reversible MAO-A inhibitors (e.g. moclobemide) or the reversible non-selective MAO-inhibitor linezolid is contraindicated due to the risk of onset of a serotonin syndrome (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).
Special Precautions
The following special warnings and precautions apply to the therapeutic class of SSRIs (Selective Serotonin Re-uptake Inhibitors).
Paradoxical anxiety: Some patients with panic disorder may experience increased anxiety symptoms at the beginning of treatment with antidepressants. This paradoxical reaction usually subsides within two weeks during continued treatment. A low starting dose is advised to reduce the likelihood of an anxiogenic effect (see Dosage & Administration).
Seizures: Escitalopram should be discontinued if a patient develops seizures for the first time, or if there is an increase in seizure frequency (in patients with a previous diagnosis of epilepsy). SSRIs should be avoided in patients with unstable epilepsy, and patients with controlled epilepsy should be closely monitored.
Mania:
SSRIs should be used with caution in patients with a history of mania/hypomania. SSRIs should be discontinued in any patient entering a manic phase.
Diabetes: In patients with diabetes, treatment with an SSRI may alter glycaemic control (hypoglycaemia or hyperglycaemia). Insulin and/or oral hypoglycaemic dosage may need to be adjusted.
Suicide/suicidal thoughts or clinical worsening: Depression is associated with an increased risk of suicidal thoughts, self harm and suicide (suicide related events). This risk persists until significant remission occurs. As improvement may not occur during the first few weeks or more of treatment, patients should be closely monitored until such improvement occurs. It is general clinical experience that the risk of suicide may increase in the early stages of recovery.
Other psychiatric conditions for which escitalopram is prescribed can also be associated with an increased risk of suicide-related events. In addition, these conditions may be co-morbid with major depressive disorder. The same precautions observed when treating patients with major depressive disorder should therefore be observed when treating patients with other psychiatric disorders.
Patients with a history of suicide-related events, or those exhibiting a significant degree of suicidal ideation prior to commencement of treatment, are known to be at greater risk of suicidal thoughts or suicide attempts, and should receive careful monitoring during treatment. A meta analysis of placebo-controlled clinical trials of antidepressant drugs in adult patients with psychiatric disorders showed an increased risk of suicidal behaviour with antidepressants compared to placebo in patients less than 25 years old. Close supervision of patients and in particular those at high risk should accompany drug therapy especially in early treatment and following dose changes.
Patients (and caregivers of patients) should be alerted about the need to monitor for any clinical worsening, suicidal behaviour or thoughts and unusual changes in behaviour and to seek medical advice immediately if these symptoms present.
Akathisia/psychomotor restlessness: The use of SSRIs/SNRIs has been associated with the development of akathisia characterised by a subjectively unpleasant or distressing restlessness and need to move, often accompanied by an inability to sit or stand still. This is most likely to occur within the first few weeks of treatment. In patients who develop these symptoms, increasing the dose may be detrimental.
Hyponatraemia: Hyponatraemia, probably due to inappropriate antidiuretic hormone secretion (SIADH), has been reported rarely with the use of SSRIs and generally resolves on discontinuation of therapy. Caution should be exercised in patients at risk, such as the elderly, or patients with cirrhosis or if used in combination with other medications which may cause hyponatraemia.
Haemorrhage: There have been reports of cutaneous bleeding abnormalities, such as ecchymoses and purpura, with SSRIs. Caution is advised in patients taking SSRIs, particularly in concomitant use with oral anticoagulants, with medicinal products known to affect platelet function (e.g. atypical antipsychotics and phenothiazines, most tricyclic antidepressants, acetylsalicylic acid and 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.
Serotonin syndrome: Caution is advisable if escitalopram is used concomitantly with medicinal products with serotonergic effects such as sumatriptan or other triptans, tramadol and tryptophan.
In rare cases, serotonin syndrome has been reported in patients using SSRIs concomitantly with serotonergic medicinal products. A combination of symptoms, such as agitation, tremor, myoclonus and hyperthermia may indicate the development of this condition. If this occurs, treatment with the SSRI and the serotonergic medicinal product should be discontinued immediately and symptomatic treatment initiated.
St. John's Wort: Concomitant use of SSRIs and herbal remedies containing St. John's Wort (Hypericum perforatum) may result in an increased incidence of adverse reactions (see Interactions).
Discontinuation symptoms seen when stopping treatment: Discontinuation symptoms when stopping treatment are common, particularly if discontinuation is abrupt (see Adverse Reactions). In clinical trials adverse events seen on treatment discontinuation occurred in approximately 25% of patients treated with escitalopram and 15% of patients taking placebo.
The risk of discontinuation symptoms may be dependent on several factors including the duration and dose of therapy and the rate of dose reduction. Dizziness, sensory disturbances (including paraesthesia and electric shock sensations), sleep disturbances (including insomnia and intense dreams), agitation or anxiety, nausea and/or vomiting, tremor, confusion, sweating, headache, diarrhoea, palpitations, emotional instability, irritability, and visual disturbances are the most commonly reported reactions. Generally these symptoms are mild to moderate, however, in some patients they may be severe in intensity.
They usually occur within the first few days of discontinuing treatment, but there have been very rare reports of such symptoms in patients who have inadvertently missed a dose.
Generally these symptoms are self-limiting and usually resolve within 2 weeks, though in some individuals they may be prolonged (2-3 months or more). It is therefore advised that escitalopram should be gradually tapered when discontinuing treatment over a period of several weeks or months, according to the patient's needs (see Discontinuation symptoms seen when stopping treatment under Dosage & Administration).
Coronary heart disease: Due to limited experience, caution is advised in patients with coronary heart disease (see Pharmacology: Toxicology: Preclinical Safety Data under Actions).
QT interval prolongation: Escitalopram has been found to cause a dose-dependent prolongation of the QT interval. Cases of QT interval prolongation and ventricular arrhythmia including torsade de pointes have been reported during the post-marketing period, predominantly in patients of female gender, with hypokalaemia, or with pre-existing QT interval prolongation or other cardiac diseases (see Contraindications, Interactions, Adverse Reactions, Overdose and Pharmacology: Pharmacodynamics under Actions).
Caution is advised in patients with significant bradycardia; or in patients with recent acute myocardial infarction or uncompensated heart failure.
Electrolyte disturbances such as hypokalaemia and hypomagnesaemia increase the risk for malignant arrhythmias and should be corrected before treatment with escitalopram is started.
If patients with stable cardiac disease are treated, an ECG review should be considered before treatment is started.
If signs of cardiac arrhythmia occur during treatment with escitalopram, the treatment should be withdrawn and an ECG should be performed.
Angle-Closure Glaucoma: SSRIs including escitalopram may have an effect on pupil size resulting in mydriasis. This mydriatic effect has the potential to narrow the eye angle resulting in increased intraocular pressure and angle-closure glaucoma, especially in patients pre-disposed. Escitalopram should therefore be used with caution in patients with angle-closure glaucoma or history of glaucoma.
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. Patients should be cautioned about the potential risk of an influence on their ability to drive a car and operate machinery.
Fertility: Animal data have shown that citalopram may affect sperm quality (see Pharmacology: Toxicology: Preclinical Safety Data under Actions). Human case reports with some SSRIs have shown that an effect on sperm quality is reversible. Impact on human fertility has not been observed so far.
Use in Children: Children and adolescents under 18 years of age: Escitalopram should not be used in the treatment of children and adolescents under the age of 18 years. Suicide related behaviours (suicide attempt and suicidal thoughts), and hostility (predominantly aggression, oppositional behaviour and anger) were more frequently observed in clinical trials among children and adolescents treated with antidepressants compared to those treated with placebo. If, based on clinical need, a decision to treat is nevertheless taken, the patient should be carefully monitored for the appearance of suicidal symptoms. In addition, long-term safety data in children and adolescents concerning growth, maturation and cognitive and behavioural development are lacking.
Use In Pregnancy & Lactation
Use in Pregnancy: For escitalopram only limited clinical data are available regarding exposed pregnancies. In reproductive toxicity studies performed in rats with escitalopram, embryo-fetotoxic effects, but no increased incidence of malformations, were observed (see Pharmacology: Toxicology: Preclinical Safety Data under Actions). Escitalopram should not be used during pregnancy unless clearly necessary and only after careful consideration of the risk/benefit.
Neonates should be observed if maternal use of escitalopram continues into the later stages of pregnancy, particularly in the third trimester. Abrupt discontinuation should be avoided during pregnancy.
The following symptoms may occur in the neonate after maternal SSRI/SNRI use in later stages of pregnancy: respiratory distress, cyanosis, apnoea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycaemia, hypertonia, hypotonia, hyperreflexia, tremor, jitteriness, irritability, lethargy, constant crying, somnolence and difficulty sleeping. These symptoms could be due to either serotonergic effects or discontinuation symptoms. In a majority of instances the complications begin immediately or soon (< 24 hours) after delivery.
Epidemiological data have suggested that the use of SSRIs in pregnancy, particular in late pregnancy, may increase the risk of persistent pulmonary hypertension in the newborn (PPHN). The observed risk was approximately 5 cases per 1000 pregnancies. In the general population 1 to 2 cases of PPHN per 1000 pregnancies occur.
Use in Lactation: It is expected that escitalopram will be excreted into human milk. Consequently, breast-feeding is not recommended during treatment.
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.
Adverse drug reactions known for SSRIs and also reported for escitalopram in either placebo controlled clinical studies or as spontaneous post-marketing events are listed below by system organ class and frequency.
Frequencies are taken from clinical studies; they are not placebo-corrected. Frequencies are defined as: Very common (≥ 1/10); Common (≥ 1/100 to < 1/10); Uncommon (≥ 1/1,000 to < 1/100); Rare (≥ 1/10,000 to < 1/1,000); Very rare (< 1/10,000); Not known (cannot be estimated from the available data).
Blood and lymphatic system disorders: Not known: Thrombocytopenia.
Immune system disorders: Rare: Anaphylactic reaction.
Endocrine disorders: Not known: Inappropriate ADH secretion.
Metabolism and nutrition disorders: Common: Decreased appetite, increased appetite, weight increased.
Uncommon: Weight decreased.
Not known: Hyponatraemia, anorexia.2
Psychiatric disorders: Common: Anxiety, restlessness, abnormal dreams: Female and male: libido decreased.
Female: anorgasmia.
Uncommon: Bruxism, agitation, nervousness, panic attack, confusional state.
Rare: Aggression, depersonalisation, hallucination.
Not known: Mania, suicidal ideation and suicidal behaviour1.
Nervous system disorders: Very common: Headache.
Common: Insomnia, somnolence, dizziness, paraesthesia, tremor.
Uncommon: Taste disturbance, sleep disorder, syncope.
Rare: Serotonine syndrome.
Not known: Dyskinesia, movement disorder, convulsion, psychomotor restlessness/akathisia2.
Eye disorders: Uncommon: Mydriasis, visual disturbance.
Ear and labyrinth disorders: Uncommon: Tinnitus.
Cardiac disorders: Uncommon: Tachycardia.
Rare: Bradycardia.
Not known: Electrocardiogram QT prolonged, ventricular arrhythmia including torsade de pointes.
Vascular disorders: Not known: Orthostatic hypotension.
Respiratory, thoracic and mediastinal disorders: Common: Sinusitis, yawning.
Uncommon: Epistaxis.
Gastrointestinal disorders: Very common: Nausea.
Common: Diarrhoea, constipation, vomiting, dry mouth.
Uncommon: Gastrointestinal haemorrhages (including rectal haemorrhage).
Hepatobiliary disorders: Not known: Hepatitis, liver function test abnormal.
Skin and subcutaneous tissue disorders: Common: Sweating increased.
Uncommon: Urticaria, alopecia, rash, pruritus.
Not known: Ecchymosis, angioedemas.
Musculoskeletal and connective tissue disorders: Common: Arthralgia, myalgia.
Renal and urinary disorders: Not known: Urinary retention.
Reproductive system and breast disorders: Common: Male: ejaculation disorder, impotence.
Uncommon: Female: metrorrhagia, menorrhagia.
Not known: Galactorrhoea. Male: priapism.
General disorders and administration site conditions: Common: Fatigue, pyrexia.
Uncommon: Oedema.
1Cases of suicidal ideation and suicidal behaviours have been reported during escitalopram therapy or early after treatment discontinuation (see Precautions).
2These events have been reported for the therapeutic class of SSRIs.
QT interval prolongation: Cases of QT interval prolongation and ventricular arrhythmia including torsade de pointes have been reported during the post-marketing period, predominantly in patients of female gender, with hypokalaemia, or with pre-existing QT interval prolongation or other cardiac diseases (see Contraindications, Precautions, Interactions, Overdose and Pharmacology: Pharmacodynamics under Actions).
Class effects: Epidemiological studies, mainly conducted in patients 50 years of age and older, show an increased risk of bone fractures in patients receiving SSRIs and TCAs. The mechanism leading to this risk is unknown.
Discontinuation symptoms seen when stopping treatment: Discontinuation of SSRIs/SNRIs (particularly when abrupt) commonly leads to discontinuation symptoms. Dizziness, sensory disturbances (including paraesthesia and electric shock sensations), sleep disturbances (including insomnia and intense dreams), agitation or anxiety, nausea and/or vomiting, tremor, confusion, sweating, headache, diarrhoea, palpitations, emotional instability, irritability, and visual disturbances are the most commonly reported reactions. Generally these events are mild to moderate and are self-limiting, however, in some patients they may be severe and/or prolonged. It is therefore advised that when escitalopram treatment is no longer required, gradual discontinuation by dose tapering should be carried out (see Dosage & Administration and Precautions).
Drug Interactions
Pharmacodynamic Interactions: Contraindicated combinations: Irreversible non-selective MAOIs: Cases of serious reactions have been reported in patients receiving an SSRI in combination with a non-selective, irreversible monoamine oxidase inhibitor (MAOI), and in patients who have recently discontinued SSRI treatment and have been started on such MAOI treatment (see Contraindications). In some cases, the patient developed serotonin syndrome (see Adverse Reactions).
Escitalopram is contraindicated in combination with non-selective, irreversible MAOIs. Escitalopram may be started 14 days after discontinuing treatment with an irreversible MAOI. At least 7 days should elapse after discontinuing of escitalopram treatment, before starting a non-selective, irreversible MAOI.
Reversible, selective MAO-A inhibitor (moclobemide): Due to the risk of serotonin syndrome, the combination of escitalopram with a MAO-A inhibitor such as moclobemide is contraindicated (see Contraindications). If the combination proves necessary, it should be started at the minimum recommended dosage and clinical monitoring should be reinforced.
Reversible, non-selective MAO-inhibitor (linezolid): The antibiotic linezolid is a reversible non-selective MAO-inhibitor and should not be given to patients treated with escitalopram. Escitalopram should be withheld for at least 2 weeks prior to initiating linezolid. When necessary, escitalopram may be started 24 hours after the last linezolid dose.
Irreversible, selective MAO-B inhibitor (selegiline): In combination with selegiline (irreversible MAO-B inhibitor), caution is required due to the risk of developing a serotonin syndrome.
QT interval prolongation: Pharmacokinetic and pharmacodynamic studies of escitalopram combined with other medicinal products that prolong the QT interval have not been performed. An additive effect of escitalopram and these medicinal products cannot be excluded. Therefore, coadministration of escitalopram with medicinal products that prolong the QT interval, such as Class IA and III antiarrhythmics, antipsychotics (e.g. phenotiazine derivatives, pimozide, haloperidol), tricyclic antidepressants, certain antimicrobial agents (e.g. sparfloxacin, moxifloxacin, erythromycin IV, pentamidine, anti-malarian treatment particularly halofantrine), certain antihistamines (astemizole, mizolastine), is contraindicated.
Combinations requiring precautions for use: Serotonergic medicinal products: Co-administration with serotonergic medicinal products (e.g. tramadol, sumatriptan and other triptans) may lead to serotonin syndrome.
Medicinal products lowering the seizure threshold: SSRIs can lower the seizure threshold. Caution is advised when concomitantly using other medicinal products capable of lowering the seizure threshold (e.g. antidepressants (tricyclics, SSRIs), neuroleptics (phenothiazines, thioxanthenes and butyrophenones), 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 (see Precautions).
Haemorrhage: Altered anti-coagulant effects may occur when escitalopram is combined with oral anticoagulants. Patients receiving oral anticoagulant therapy should receive careful coagulation monitoring when escitalopram is started or stopped (see Precautions). Concomitant use of non-steroidal anti-inflammatory drugs (NSAIDs) may increase bleeding tendency (see Precautions).
Alcohol: No pharmacodynamic or pharmacokinetic interactions are expected between escitalopram and alcohol. However, as with other psychotropic medicinal products, the combination with alcohol is not advisable.
Medicinal products inducing hypokalaemia/hypomagnesaemia: Caution is warranted for concomitant use of hypokalaemia/hypomagnesaemia inducing medicinal products as these conditions increase the risk of malignant arrhythmias (see Precautions).
Pharmacokinetic Interactions: Influence of other medicinal products on the pharmacokinetics of escitalopram: The metabolism of escitalopram is mainly mediated by CYP2C19. CYP3A4 and CYP2D6 may also contribute to the metabolism, although to a smaller extent. The metabolism of the major metabolite S-DCT (demethylated escitalopram) seems to be partly catalysed by CYP2D6.
Co-administration of escitalopram with omeprazole 30 mg once daily (a CYP2C19 inhibitor) resulted in moderate (approximately 50%) increase in the plasma concentrations of escitalopram.
Co-administration of escitalopram with cimetidine 400 mg twice daily (moderately potent general enzyme-inhibitor) resulted in a moderate (approximately 70%) increase in the plasma concentrations of escitalopram. Caution is advised when administering escitalopram in combination with cimetidine. Dose adjustment may be warranted.
Thus, caution should be exercised when used concomitantly with CYP2C19 inhibitors (e.g. omeprazole, esomeprazole, fluvoxamine, lansoprazole, ticlopidine) or cimetidine. A reduction in the dose of escitalopram may be necessary based on monitoring of side-effects during concomitant treatment.
Effect of escitalopram on the pharmacokinetics of other medicinal products: Escitalopram is an inhibitor of the enzyme CYP2D6. Caution is recommended when escitalopram is co-administered with medicinal products that are mainly metabolised by this enzyme, and that have a narrow therapeutic index, e.g. flecainide, propafenone and metoprolol (when used in cardiac failure) or some CNS acting medicinal products that are mainly metabolised by CYP2D6, e.g. antidepressants such as desipramine, clomipramine or nortriptyline or antipsychotics like risperidone, thioridazine and haloperidol. Dosage adjustment may be warranted.
Co-administration with desipramine or metoprolol resulted in both cases in a twofold increase in the plasma levels of these two CYP2D6 substrates.
In vitro studies have demonstrated that escitalopram may also cause weak inhibition of CYP2C19. Caution is recommended with concomitant use of medicinal products that are metabolised by CYP2C19.
Caution For Usage
Incompatibilities: Not applicable.
Storage
Do not store above 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 10 mg (white, oval with breaking notch on one side) x 28's. 20 mg (white, round with cross-breaking notch on both sides) x 28's.
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