Selectra (Tablets) Instructions for Use

Marketing Authorization Holder

Abbott Products Operations, AG (Switzerland)

Manufactured By

Actavis, Ltd. (Malta)

Contact Information

ABBOTT LABORATORIES LLC (Russia)

ATC Code

N06AB10 (Escitalopram)

Active Substance

Escitalopram (Rec.INN registered by WHO)

Dosage Forms

	Selectra	Film-coated tablets, 5 mg: 10, 14, 20, 28, 30 or 56 pcs.
		Film-coated tablets, 10 mg: 10, 14, 20, 28, 30 or 56 pcs.
		Film-coated tablets, 15 mg: 10, 14, 20, 28, 30 or 56 pcs.
		Film-coated tablets, 20 mg: 10, 14, 20, 28, 30 or 56 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets white, round, biconvex, with an engraving “E” on one side.

Excipients: Prosolv SMCC^®90/HD90 – 73.71 mg (microcrystalline cellulose – 72.24 mg + colloidal silicon dioxide – 1.47 mg), croscarmellose sodium – 4.5 mg, talc – 4.5 mg, magnesium stearate – 0.9 mg.

Film coating composition Opadry white (Opadry 03F28446 White) – about 2.7 mg: hypromellose 6cP – 1.64 mg, titanium dioxide – 0.66 mg, macrogol 6000 – 0.4 mg.

10 pcs. – blisters (1) – cardboard packs^×.
10 pcs. – blisters (2) – cardboard packs^×.
10 pcs. – blisters (3) – cardboard packs^×.
14 pcs. – blisters (1) – cardboard packs^×.
14 pcs. – blisters (2) – cardboard packs^×.
14 pcs. – blisters (4) – cardboard packs^×.

Film-coated tablets white, oval, biconvex, with an engraving “E” on one side, a score on the other side and side scores.

Excipients: Prosolv SMCC^®90/HD90 – 147.42 mg (microcrystalline cellulose – 144.47 mg + colloidal silicon dioxide – 2.95 mg), croscarmellose sodium – 9 mg, talc – 9 mg, magnesium stearate – 1.8 mg.

Film coating composition Opadry white (Opadry 03F28446 White) – about 5.4 mg: hypromellose 6cP – 3.29 mg, titanium dioxide – 1.31 mg, macrogol 6000 – 0.8 mg.

10 pcs. – blisters (1) – cardboard packs^×.
10 pcs. – blisters (2) – cardboard packs^×.
10 pcs. – blisters (3) – cardboard packs^×.
14 pcs. – blisters (1) – cardboard packs^×.
14 pcs. – blisters (2) – cardboard packs^×.
14 pcs. – blisters (4) – cardboard packs^×.

Film-coated tablets white, oval, biconvex, with an engraving “E-” on one side, a score on the other side and side scores.

Excipients: Prosolv SMCC^®90/HD90 – 221.13 mg (microcrystalline cellulose – 216.71 mg + colloidal silicon dioxide – 4.42 mg), croscarmellose sodium – 13.5 mg, talc – 13.5 mg, magnesium stearate – 2.7 mg.

Film coating composition Opadry white (Opadry 03F28446 White) – about 8.1 mg: hypromellose 6cP – 4.93 mg, titanium dioxide – 1.97 mg, macrogol 6000 – 1.2 mg.

10 pcs. – blisters (1) – cardboard packs^×.
10 pcs. – blisters (2) – cardboard packs^×.
10 pcs. – blisters (3) – cardboard packs^×.
14 pcs. – blisters (1) – cardboard packs^×.
14 pcs. – blisters (2) – cardboard packs^×.
14 pcs. – blisters (4) – cardboard packs^×.

Film-coated tablets white, oval, biconvex, with an engraving “E” on one side, a score on the other side and side scores.

Excipients: Prosolv SMCC^®90/HD90 – 294.84 mg (microcrystalline cellulose – 288.94 mg + colloidal silicon dioxide – 5.9 mg), croscarmellose sodium – 18 mg, talc – 18 mg, magnesium stearate – 3.6 mg.

Film coating composition Opadry white (Opadry 03F28446 White) – about 10.8 mg: hypromellose 6cP – 6.57 mg, titanium dioxide – 2.63 mg, macrogol 6000 – 1.6 mg.

10 pcs. – blisters (1) – cardboard packs^×.
10 pcs. – blisters (2) – cardboard packs^×.
10 pcs. – blisters (3) – cardboard packs^×.
14 pcs. – blisters (1) – cardboard packs^×.
14 pcs. – blisters (2) – cardboard packs^×.
14 pcs. – blisters (4) – cardboard packs^×.

^× with first opening control.

Clinical-Pharmacological Group

Antidepressant

Pharmacotherapeutic Group

Antidepressant

Pharmacological Action

Escitalopram is an antidepressant, a selective serotonin reuptake inhibitor (SSRI) with high affinity for the primary binding site.

Escitalopram also binds to the allosteric binding site of the transporter protein, with an affinity a thousand times lower.

The allosteric modulation of the transporter protein enhances the binding of escitalopram at the primary binding site, leading to more complete inhibition of serotonin reuptake.

Escitalopram has no or very low ability to bind to a number of receptors, including: serotonin 5-HT_1A, 5-HT₂ receptors, dopamine D₁ and D₂ receptors, α₁-, α₂-, β-adrenergic receptors, histamine H₁ receptors, muscarinic cholinergic receptors, benzodiazepine and opioid receptors.

Pharmacokinetics

Absorption and Distribution

Absorption is almost complete and independent of food intake.

The bioavailability of escitalopram is about 80%.

The mean time to reach C_max in plasma (T_max) is about 4 hours after multiple administration.

The apparent V_d,β/F after oral administration ranges from 12 to 26 L/kg.

The binding of escitalopram and its main metabolites to plasma proteins is about 80%.

The kinetics of escitalopram are linear.

C_ss is reached in about 1 week.

The mean C_ss – 50 nmol/L (range 20 to 125 nmol/L) is achieved at a daily dose of 10 mg.

Metabolism and Excretion

Escitalopram is metabolized in the liver to demethylated and didemethylated metabolites.

Both are pharmacologically active.

The nitrogen may be oxidized to an N-oxide metabolite.

The parent substance and its metabolites are partially excreted as glucuronides.

After multiple administration, the mean concentration of demethyl and didemethyl metabolites is typically 28-31% and less than 5%, respectively, of the escitalopram concentration.

The biotransformation of escitalopram to the demethylated metabolite occurs mainly via the CYP2C19 isoenzyme.

Some involvement of CYP3A4 and CYP2D6 isoenzymes is possible.

In individuals with poor CYP2C19 activity, the concentration of escitalopram may be 2 times higher than in cases with high activity of this isoenzyme.

No significant changes in drug concentration were found in cases with poor CYP2D6 isoenzyme activity.

T_1/2 after multiple administration is about 30 hours.

Oral clearance is about 0.6 L/min.

The main metabolites of escitalopram have a longer T_1/2.

Escitalopram and its main metabolites are excreted by the liver (metabolic pathway) and kidneys; most is excreted as metabolites in the urine.

Pharmacokinetics in Special Clinical Cases

Elderly patients

In elderly patients over 65 years of age, Escitalopram is eliminated more slowly compared to younger patients.

The amount of substance in the systemic circulation, calculated using the pharmacokinetic parameter AUC, is 50% greater in the elderly than in young healthy volunteers.

Hepatic impairment

In patients with mild and moderate hepatic insufficiency (Child-Pugh class A and B), the T_1/2 of escitalopram is almost 2 times longer, and the amount of substance in the systemic circulation is 60% higher than in individuals with normal liver function.

Renal impairment

When using racemic citalopram in patients with renal insufficiency (creatinine clearance 10-53 ml/min), a prolongation of T_1/2 of the drug and a slight increase in the amount of substance in the systemic circulation were noted.

Indications

• Depressive disorders of any severity;
• Panic disorder with/without agoraphobia;
• Social anxiety disorder (social phobia);
• Generalized anxiety disorder;
• Obsessive-compulsive disorder.

ICD codes

Dosage Regimen

Orally. The drug is prescribed to adults once a day, regardless of meals.

Depressive disorders

Usually prescribed 10 mg once a day. Depending on the individual patient response, the dose may be increased to a maximum of 20 mg/day.

The antidepressant effect usually develops after 2-4 weeks of treatment. After the symptoms of depression disappear, therapy should be continued for at least another 6 months to consolidate the achieved effect.

Panic disorder with/without agoraphobia

During the first week of treatment, a dose of 5 mg/day is recommended, which is then increased to 10 mg/day. Depending on the individual patient response, the dose may be increased to a maximum of 20 mg/day.

The maximum therapeutic effect is achieved approximately 3 months after the start of treatment. Therapy lasts for several months.

Social anxiety disorder (social phobia)

Usually prescribed 10 mg once a day. Depending on the individual patient response, the dose may be increased to a maximum of 20 mg/day. Symptom relief usually develops after 2-4 weeks of treatment. Since social anxiety disorder is a chronic condition, the minimum recommended duration of the therapeutic course is 3 months.

To prevent relapse of the disease, the drug may be prescribed for 6 months or longer depending on the individual patient response. Regular assessment of the ongoing treatment is recommended.

Generalized anxiety disorder

Usually prescribed 10 mg once a day. Depending on the individual patient response, the dose may be increased to a maximum of 20 mg/day. The minimum recommended duration of the therapeutic course is 3 months. To prevent relapse of the disease, long-term use of the drug (6 months or longer) is allowed. Regular assessment of the ongoing treatment is recommended.

Obsessive-compulsive disorder

Usually prescribed 10 mg once a day. Depending on the individual patient response, the dose may be increased to a maximum of 20 mg/day. Since obsessive-compulsive disorder is a chronic condition, the course of treatment should be sufficiently long to ensure complete relief from symptoms and last for at least 6 months. To prevent relapse, treatment for at least 1 year is recommended.

Elderly patients (over 65 years)

It is recommended to use half the usually recommended dose (i.e., only 5 mg/day) and a lower maximum dose (10 mg/day).

Children and adolescents (under 18 years)

Should not be used in children and adolescents under 18 years of age (see section “Special Instructions”). Furthermore, there is insufficient data from long-term safety studies on the use of the drug in children and adolescents concerning growth, maturation, and cognitive and behavioral development.

Renal impairment

In mild and moderate renal impairment, dose adjustment is not required. Patients with severe renal impairment (creatinine clearance below 30 ml/min) should be prescribed the drug with caution.

Hepatic impairment

The recommended initial dose during the first 2 weeks of treatment is 5 mg/day. Depending on the individual patient response, the dose may be increased to 10 mg/day.

Reduced CYP2C19 isoenzyme activity

For patients with poor CYP2C19 isoenzyme activity, the recommended initial dose during the first 2 weeks of treatment is 5 mg/day. Depending on the individual patient response, the dose may be increased to 10 mg/day.

Discontinuation of treatment

When discontinuing treatment with the drug, the dose should be gradually reduced over 1-2 weeks to avoid the occurrence of “withdrawal” syndrome.

Adverse Reactions

Side effects most often occur in the 1st or 2nd week of treatment, then usually become less intense and occur less frequently with continued therapy.

Below are the side effects that occur when taking drugs belonging to the SSRI class and noted when taking escitalopram. Information is based on data from placebo-controlled clinical studies and spontaneous reports.

Frequency is defined according to the following gradation: very common (≥1/10), common (from ≥1/100 to <1/10), uncommon (from ≥1/1000 to <1/100), rare (from ≥1/10000 to <1/1000), very rare (<1/10000), or unknown (frequency cannot be estimated from existing data).

¹ Cases of suicidal thoughts and behavior have been reported during escitalopram use and immediately after therapy discontinuation (see section “Special Instructions”).

² This adverse event has been registered as a class-effect for drugs of the SSRI/SNRI groups (see sections “Special Instructions” and “Pregnancy and Lactation”).

In the post-registration period, cases of QT interval prolongation have been reported, mainly in patients with pre-existing heart disease. In double-blind placebo-controlled ECG studies in healthy volunteers, the change from baseline QTc (Fridericia’s correction) was 4.3 msec at a dose of 10 mg/day and 10.7 msec at 30 mg/day.

Epidemiological studies involving patients aged 50 years and older have shown an increased risk of bone fractures in patients taking SSRIs and tricyclic antidepressants.

The mechanism for this risk has not been established.

Discontinuation of SSRI/SNRI (serotonin and norepinephrine reuptake inhibitors) drugs (especially abrupt) often leads to the occurrence of withdrawal symptoms. The most frequently occurring are dizziness, sensory disturbances (including paresthesia and electric shock sensations), sleep disorders (including insomnia and intense dreams), agitation or anxiety, nausea and/or vomiting, tremor, confusion, increased sweating, headache, diarrhea, palpitations, emotional lability, irritability, visual disturbances. Typically, these effects are mild or moderate and resolve quickly, but in some patients they may be more acute and/or prolonged. Gradual discontinuation of the drug by reducing its dose is recommended.

Contraindications

• Hypersensitivity to escitalopram and other components of the drug;
• Concomitant use of non-selective irreversible MAO inhibitors;
• Concomitant use of pimozide;
• Childhood and adolescence under 18 years (efficacy and safety not confirmed) (see section “Special Instructions”).

With caution

Severe renal impairment (creatinine clearance less than 30 ml/min), mania and hypomania, pharmacologically uncontrolled epilepsy, marked suicidal behavior, diabetes mellitus, liver cirrhosis, bleeding tendency, concomitant use with MAO A inhibitor (moclobemide) and MAO B inhibitor (selegiline); serotonergic drugs; drugs that lower the seizure threshold; lithium, tryptophan derivatives; medicinal products containing St. John’s wort; oral anticoagulants and drugs affecting blood clotting; drugs that can cause hyponatremia; drugs metabolized with the participation of the CYP2C19 isoenzyme; ethanol; electroconvulsive therapy; elderly age; pregnancy, breastfeeding period.

Use in Pregnancy and Lactation

Pregnancy

There are limited data on the use of escitalopram during pregnancy.

Animal studies of escitalopram have demonstrated reproductive toxicity.

Escitalopram during pregnancy should be used only in cases of extreme necessity and after careful assessment of the benefit/risk ratio.
If escitalopram was continued in late pregnancy, especially in the third trimester, the newborn should be monitored. If escitalopram was continued until delivery or discontinued shortly before delivery, the newborn may develop withdrawal symptoms.

When SSRIs/SNRIs are taken by the mother during late pregnancy, the following symptoms may develop in the newborn: respiratory depression, cyanosis, apnea, seizure disorders, temperature fluctuations, feeding difficulties, vomiting, hypoglycemia, hypertension, muscle hypotonia, hyperreflexia, tremor, increased neuro-reflex excitability, irritability, lethargic sleep, persistent crying, drowsiness, poor sleep. These symptoms may arise due to the development of withdrawal syndrome or serotonergic effects. In most cases, such complications occur within 24 hours after birth.

Epidemiological study data suggest that the use of SSRIs during pregnancy, especially in the later stages, may increase the risk of persistent pulmonary hypertension in newborns (PPHN). The observed risk was about 5 cases per 1000 pregnancies. In the general population, 1-2 cases of PPHN per 1000 pregnancies are observed.

Observational data indicate an increased (less than 2-fold) risk of postpartum hemorrhage after the use of SSRIs/SNRIs within one month before delivery (see the “Special Precautions” section).

Breastfeeding period

Escitalopram is expected to be excreted in breast milk, therefore breastfeeding is not recommended during treatment with escitalopram.

Fertility

Animal study data have shown that some SSRIs may affect sperm quality. There are no animal study data on this aspect for escitalopram. Reports on the use of some SSRIs in humans have shown that the effect of these drugs on sperm quality is reversible. So far, no effect of escitalopram on human fertility has been observed.

Use in Hepatic Impairment

The recommended initial dose during the first 2 weeks of treatment is 5 mg/day. Depending on the individual patient response, the dose may be increased to 10 mg/day.

Use in Renal Impairment

In mild to moderate renal impairment, dose adjustment is not required. Patients with severe renal impairment (creatinine clearance below 30 ml/min) should be prescribed the drug at the minimum therapeutic doses, gradually increasing them based on the drug’s tolerability and efficacy.

Pediatric Use

Antidepressants should not be prescribed to children and adolescents under the age of 18 due to an increased risk of suicidal behavior (suicide attempts and suicidal thoughts), hostility (with a predominance of aggressive behavior, confrontational tendencies, and irritability). If a decision to initiate antidepressant therapy is made based on clinical assessment, the patient should be under close supervision.

Geriatric Use

It is recommended to use half the usual recommended dose (i.e., only 5 mg/day) and a lower maximum dose (10 mg/day).

Special Precautions

Use in children and adolescents under 18 years of age

Antidepressants should not be prescribed to children and adolescents under the age of 18 due to an increased risk of suicidal behavior (suicide attempts and suicidal thoughts), hostility (with a predominance of aggressive behavior, confrontational tendencies, and irritability). If a decision to initiate antidepressant therapy is made based on clinical assessment, the patient should be under close supervision.

Paradoxical anxiety

In some patients with panic disorder, increased anxiety may be observed at the beginning of treatment with antidepressants. Such a paradoxical reaction usually disappears within 2 weeks of treatment. To reduce the likelihood of an anxiogenic effect, it is recommended to use low initial doses.

Seizures

The drug should be discontinued if seizures develop for the first time or if their frequency increases (in patients with previously diagnosed epilepsy). SSRIs should not be used in patients with unstable epilepsy; in cases of controlled seizures, careful monitoring is necessary.

Mania/hypomania

Escitalopram should be used with caution in patients with a history of mania/hypomania. If a manic state develops, Escitalopram should be discontinued.

Diabetes mellitus

In patients with diabetes mellitus, treatment with escitalopram may alter blood glucose concentrations. Therefore, adjustment of insulin and/or oral hypoglycemic drug doses may be required.

Suicide/suicidal thoughts or clinical worsening

Depression is associated with an increased risk of suicidal thoughts, self-harm, and suicide (suicidal events). This risk persists until significant remission occurs. Since improvement may not be observed during the first few weeks of therapy or even longer, patients should be under constant supervision until their condition improves.

General clinical experience shows that the risk of suicide may increase in the early stages of recovery.

Other mental conditions for which Escitalopram is prescribed may also be associated with an increased risk of suicidal events and phenomena. Furthermore, these conditions may be comorbid with a depressive episode. When treating patients with other mental disorders, the same precautions should be observed as when treating patients with a depressive episode.

Patients with a history of suicidal behavior or patients with a significant level of suicidal ideation prior to treatment are at greater risk of suicidal thoughts or suicide attempts; therefore, they should be closely monitored during treatment. A meta-analysis of placebo-controlled clinical trials of antidepressants involving adult patients with mental disorders showed that there is an increased risk of suicidal behavior in patients under 25 years of age taking antidepressants compared with placebo. Drug treatment of these patients, and in particular patients at high risk of suicide, should be accompanied by careful monitoring, especially in the early stages of treatment and during dose changes.

Patients and caregivers should be warned to monitor for any signs of clinical worsening, suicidal behavior or thoughts, and unusual changes in behavior, and to seek immediate medical advice if these symptoms appear.

Akathisia/psychomotor agitation

The use of SSRIs/SNRIs is associated with the development of akathisia, characterized by the development of subjectively unpleasant or distressing restlessness and a need to move constantly, often combined with an inability to sit or stand still. This most often manifests during the first few weeks of treatment. In patients with such symptoms, increasing the dose may lead to worsening.

Hyponatremia

Hyponatremia, possibly associated with impaired secretion of antidiuretic hormone (ADH), rarely occurs with the use of SSRIs and usually resolves upon discontinuation of therapy. Caution should be exercised when prescribing escitalopram and other SSRIs to individuals at risk of developing hyponatremia: the elderly, patients with liver cirrhosis, and those taking drugs that can cause hyponatremia.

Bleeding

Cases of skin hemorrhages (ecchymoses and purpura) have been reported with the use of SSRIs. Escitalopram should be used with caution in patients with a tendency to bleeding, as well as in those taking oral anticoagulants and medications that affect blood clotting.

ECT (electroconvulsive therapy)

Since clinical experience with the simultaneous use of SSRIs and electroconvulsive therapy (ECT) is limited, caution should be exercised when using escitalopram and ECT concomitantly.

Reversible selective MAO-A inhibitors

Combining Escitalopram and MAO-A inhibitors is not recommended due to the risk of serotonin syndrome.

Serotonin syndrome

Caution should be exercised when using Escitalopram concomitantly with drugs that have serotonergic effects, for example, sumatriptan or other triptans, tramadol, and tryptophan. In rare cases, serotonin syndrome has developed in patients taking Escitalopram and other SSRIs simultaneously with serotonergic drugs. Its development may be indicated by a combination of symptoms such as agitation, tremor, myoclonus, and hyperthermia. If this occurs, simultaneous treatment with SSRIs and serotonergic drugs should be discontinued immediately and symptomatic treatment initiated.

Closed-angle glaucoma

SSRIs, including Escitalopram, may affect pupil size, causing mydriasis (pupil dilation). Due to this effect, the viewing angle may decrease, and subsequently, intraocular pressure may increase and closed-angle glaucoma may develop; this is especially characteristic for patients predisposed to this condition. Therefore, Escitalopram should be used with particular caution in patients with closed-angle glaucoma or a history of glaucoma.

Alcohol

Escitalopram does not interact pharmacodynamically or pharmacokinetically with alcohol. However, as with other psychotropic drugs, the concomitant use of escitalopram and alcohol is not recommended.

Effect on ability to drive and operate machinery

Although Escitalopram does not affect intellectual function and psychomotor activity, patients are not recommended to drive a car or operate machinery during treatment.

Overdose

Data on escitalopram overdose are limited, and in many such cases, there was also an overdose of other drugs. In most cases, symptoms of overdose are absent or mild. Cases of fatal overdose with escitalopram (without taking other drugs) are rare; in most cases, there is also an overdose of other drugs.

Symptoms of escitalopram overdose mainly involve the CNS (from dizziness, tremor, and agitation to rare cases of serotonin syndrome, seizure disorders, and coma), the gastrointestinal tract (nausea/vomiting), the cardiovascular system (arterial hypotension, tachycardia, QT interval prolongation, and arrhythmia), and electrolyte imbalances (hypokalemia, hyponatremia).

Treatment: there is no specific antidote. Ensure normal airway patency, oxygenation, and ventilation. Gastric lavage should be performed and activated charcoal administered. Gastric lavage should be performed as soon as possible after drug intake. It is recommended to monitor cardiac function and other vital signs and to provide symptomatic and supportive therapy.

Drug Interactions

Pharmacodynamic interactions

Non-selective irreversible MAO inhibitors

Serious adverse reactions have been reported with the concomitant use of SSRIs and non-selective irreversible MAO inhibitors, as well as when starting MAO inhibitors in patients who have recently discontinued SSRIs. In some cases, patients developed serotonin syndrome.

Concomitant use of Escitalopram with non-selective irreversible MAO inhibitors is contraindicated. Escitalopram may be started 14 days after discontinuation of irreversible MAO inhibitors. At least 7 days should elapse after stopping escitalopram before starting non-selective irreversible MAO inhibitors.

Reversible selective MAO-A inhibitor (moclobemide)

Due to the risk of serotonin syndrome, it is not recommended to use Escitalopram concomitantly with the MAO-A inhibitor moclobemide. If the use of such a drug combination is deemed clinically necessary, it is recommended to start with the lowest possible doses and conduct constant clinical monitoring of the patient’s condition. Escitalopram can be started at least one day after discontinuation of the reversible MAO-A inhibitor moclobemide.

Irreversible MAO-B inhibitor (selegiline)

Due to the risk of serotonin syndrome, caution is required when taking escitalopram concomitantly with the irreversible MAO-B inhibitor selegiline.

Serotonergic drugs

Concomitant use with serotonergic drugs (e.g., tramadol, sumatriptan and other triptans) may lead to the development of serotonin syndrome.

Drugs that lower the seizure threshold

SSRIs may lower the seizure threshold. Caution is required when using other drugs that lower the seizure threshold concomitantly with escitalopram (tricyclic antidepressants, SSRIs, antipsychotic drugs (neuroleptics) – phenothiazine, thioxanthene, and butyrophenone derivatives, mefloquine, bupropion, and tramadol).

Lithium, tryptophan

Since cases of enhanced effects have been reported with the concomitant use of SSRIs and lithium or tryptophan, caution is recommended when using escitalopram concomitantly with these drugs.

St. John’s wort

Concomitant use of SSRIs and preparations containing St. John’s wort (Hypericum perforatum) may lead to an increased number of side effects.

Anticoagulants and drugs affecting blood clotting

Impaired blood clotting may occur with the concomitant use of escitalopram and oral anticoagulants and drugs affecting blood clotting (for example, atypical antipsychotics and phenothiazine derivatives, most tricyclic antidepressants, acetylsalicylic acid and non-steroidal anti-inflammatory drugs, ticlopidine, and dipyridamole). In such cases, careful monitoring of blood coagulation is necessary.

Concomitant use with NSAIDs may lead to an increased number of bleedings.

Pharmacokinetic interactions

Effect of other drugs on the pharmacokinetics of escitalopram

The metabolism of escitalopram is primarily mediated by the CYP2C19 isoenzyme. To a lesser extent, the CYP3A4 and CYP2D6 isoenzymes may be involved in its metabolism. The metabolism of the main metabolite (demethylated escitalopram) appears to be partially catalyzed by the CYP2D6 isoenzyme.

Concomitant use of escitalopram and omeprazole (a CYP2C19 isoenzyme inhibitor) leads to a moderate (approximately 50%) increase in the plasma concentration of escitalopram.

Concomitant use of escitalopram and cimetidine (an inhibitor of CYP2D6, CYP3A4, and CYP1A2 isoenzymes) leads to an increase (approximately 70%) in the plasma concentration of escitalopram.

Therefore, the maximum possible doses of escitalopram should be used with caution concomitantly with CYP2C19 isoenzyme inhibitors (e.g., omeprazole, fluoxetine, fluvoxamine, lansoprazole, ticlopidine) and cimetidine. When escitalopram is used concomitantly with the aforementioned drugs, a dose reduction of escitalopram may be required based on clinical assessment.

Effect of escitalopram on the pharmacokinetics of other drugs

Escitalopram is an inhibitor of the CYP2D6 isoenzyme. Caution should be exercised when using escitalopram concomitantly with drugs metabolized by this isoenzyme and having a narrow therapeutic index, for example, flecainide, propafenone, and metoprolol (in cases of use for heart failure) or drugs primarily metabolized via CYP2D6 and acting on the CNS, for example, antidepressants – desipramine, clomipramine, nortriptyline, or antipsychotics – risperidone, thioridazine, haloperidol. In these cases, dose adjustment may be required.

Concomitant use of escitalopram and desipramine or metoprolol leads to a twofold increase in the concentration of the latter two drugs.

Escitalopram may slightly inhibit the CYP2C19 isoenzyme. Therefore, caution is recommended when using escitalopram concomitantly with drugs metabolized by the CYP2C19 isoenzyme.

Storage Conditions

At a temperature not exceeding 25°C (77°F). Keep out of reach of children!

Shelf Life

The shelf life is 2 years. Do not use after the expiration date printed on the package.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.