Expiration date: 02/2025

Pharmacokinetics:

Absorption is independent of food intake. The bioavailability of escitalopram is approximately 80%. Mean Tmax in the blood plasma is about 4 hours. Vd apparent after oral administration of 12 to 26 l / kg. The binding of escitalopram and its main metabolites in the blood plasma proteins for about 80%. Escitalopram is metabolised in the liver to the demethylated and didemetilirovannogo metabolites. Both are pharmacologically active. Main ingredient and its metabolites in the form of partially allocated glucuronides.

After repeated use and the average concentration demethyl didemetilmetabolitov typically 28-31% and less than 5%, respectively, the concentration of escitalopram. Biotransformation of escitalopram to the demethylated metabolite occurs primarily via the cytochrome CYP2C19. Perhaps some part of isozymes CYP3A4 and CYP2D6. In persons with a weak activity of CYP2C19 escitalopram concentration may be twice higher than in the case of the high activity of this isoenzyme. Significant changes in the concentration of the drug in cases with weak CYP2D6 isoenzyme activity was found.

T1 / 2, after repeated use is about 30 hours. The clearance when administered orally is about 0.6 l / min. In the main metabolites of escitalopram T1 / 2 is longer. Escitalopram and major metabolites are excreted by the liver (metabolic pathway) and kidneys.

Kinetics of escitalopram is linear. Css achieved in about 1 week. The mean Css - 50 nmol / l (20 to 125 nmol / L) is achieved at a daily dose of 10 mg.

In the elderly (over 65 years) Escitalopram appears slower compared to younger patients. The amount of substance in the systemic circulation, via the calculated AUC, elderly 50% more than in young healthy volunteers.

Description of the pharmacological actions:

Escitalopram is an antidepressant SSRIs. Inhibition of reuptake of serotonin leads to increasing the concentration of the neurotransmitter in the synaptic cleft, amplifies and prolong its effect on post-synaptic receptor sites.

Escitalopram has no or has a very weak ability to bind to a number of receptors, including serotonin 5-HT1A and 5-HT2 receptors, dopamine D1 and D2 receptors, & alpha1-, & alpha2-, & beta-adrenergic receptors, the histamine H1, muscarinic cholinergic, benzodiazepine and opiate receptors.

Testimony:

• depressive disorders of any severity
  
• panic disorder with / without agoraphobia.
  

Contraindications:

• hypersensitivity to the drug or its components
  
• children's age (15 years)
  
• concomitant use with MAO inhibitors
  
• pregnancy
  
• during breastfeeding.
  

Precautions: renal impairment (Cl creatinine <30 ml / min), hypomania, mania disorder pharmacologically uncontrolled epilepsy, depression with suicidal attempts diabetes old age cirrhosis bleeding tendency concomitant use with drugs that reduce the seizure threshold, causing hyponatremia ethanol drugs metabolized involving CYP2C19 system adolescence from 15 to 18 years.

Side effect:

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

CNS: dizziness, weakness, insomnia or drowsiness, seizures, tremor, movement disorders, serotonin syndrome (agitation, tremor, myoclonus, hyperthermia), hallucinations, manic disorder, confusion, agitation, anxiety, depersonalisation, panic attacks, irritability , visual disturbances.

From the digestive system: nausea, vomiting, dry mouth, taste disturbance, loss of appetite, diarrhea, constipation.

From the CCC: orthostatic hypotension.

From endocrine system: reduction of ADH secretion, galactorrhea.

With the genitourinary system: loss of libido, impotence, ejaculation disorder, anorgasmia (in women), urinary retention.

For the skin: skin rash, pruritus, ecchymosis, purpura, angioedema.

Allergic reactions: anaphylactic reactions.

Laboratory findings: hyponatremia, changes in laboratory parameters of liver function.

Other: increased sweating, hyperthermia, sinusitis, arthralgia, myalgia.

Also, after prolonged use of abrupt cessation of therapy with selectors in some patients may result in a withdrawal syndrome. In a dramatic admission of escitalopram may experience adverse reactions such as dizziness, headaches and nausea, the severity of which is small, and the duration - limited.

Drug Interactions:

MAO inhibitors

You may experience serious adverse reactions while taking the drug Celektra and MAO inhibitors as well as when taking MAO inhibitors, patients who had recently stop taking the drug. In such cases, serotonin syndrome may develop.

Escitalopram should not be administered concurrently with MAO inhibitors. Escitalopram may be appointed 14 days after discontinuation of treatment irreversible MAO inhibitors and at least 1 day after discontinuing therapy reversible inhibitor of MAO type A - moclobemide. At least 7 days should elapse after stopping escitalopram before you can start treatment of non-selective MAO inhibitors.

Serotonergic drugs

The combined use of serotonergic drugs (eg tramadol, sumatriptan and other triptans) may lead to serotonin syndrome.

Drugs that reduce the seizure threshold

Celektra may lower the seizure threshold. It requires caution with concomitant administration with other drugs that reduce the seizure threshold (tricyclic antidepressants, other SSRI neuroleptics - phenothiazines, thioxanthene and butyrophenone derivatives and mefloquine, tramadol).

Lithium, tryptophan

Escitalopram enhances the pharmacological effects of tryptophan (increased serotonergic effect) and toxic effects of drugs lithium.

St. John's wort (Hypericum perforatum)

Co-administration of escitalopram and products containing St. John's wort (Hypericum perforatum), may lead to an increase in side effects.

Anticoagulants and other drugs that affect blood clotting

A bleeding disorder may occur with concomitant administration of escitalopram with oral anticoagulants and other drugs that affect blood clotting (eg atypical antipsychotics and phenothiazines, most tricyclic antidepressants, acetylsalicylic acid and NSAIDs, ticlopidine and dipyridamole). In such cases, the need to control blood clotting parameters.

ethanol

Escitalopram does not come with ethanol in pharmacodynamic or pharmacokinetic interaction. However, as is the case with other psychotropic drugs, the simultaneous use of escitalopram and alcohol is not recommended.

The influence of other drugs on the pharmacokinetics of escitalopram

Co-administration with drugs inhibiting cytochrome CYP2C19, escitalopram can increase the concentration in plasma. Care should be taken while using escitalopram with similar drugs, such as omeprazole. You may need to reduce the dose of escitalopram.

Precautions should be prescribed higher doses of escitalopram at the same time with high doses of cimetidine, which is a potent inhibitor of cytochrome CYP2D6, CYP3A4 and CYP1A2.

Effect of escitalopram on the pharmacokinetics of other drugs

Escitalopram is an inhibitor of the isoenzyme CYP2D6. Caution must be exercised with concomitant administration of escitalopram and drugs metabolized by this isoenzyme, and having a small therapeutic index, eg flecainide, propafenone and metoprolol (in cases of heart failure), or medicines, mainly metabolized by CYP2D6 and acting on the central nervous system, for example antidepressant - desipramine, clomipramine, nortriptyline, or antipsychotics - risperidone, thioridazine, haloperidol. In these cases, dose adjustment may be required, as escitalopram increases the concentration in the blood plasma.

Co-administration of escitalopram and desipramine or metoprolol resulting in a doubling of the concentration of the latter two drugs that should be considered when selecting the dose.

Escitalopram may slightly inhibit isoenzyme CYP2C19. Therefore, caution is advised during simultaneous use of escitalopram and medications metabolized CYP2C19.

Dosage and administration:

Inside.

The drug is prescribed for adults and children over 15 years once a day regardless of the meal.

Depressive disorders

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

Antidepressant effect usually develops within 2-4 weeks after starting treatment. After the disappearance of the symptoms of depression, at least for another 6 months, it is necessary to continue treatment for fixing the resulting effect.

Panic disorder with / without agoraphobia

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

The maximum therapeutic effect is reached after about 3 months after initiation of treatment. The therapy lasts several months.

Elderly patients (over 65 years)

It is recommended to use half the usual recommended dose (ie, a total of 5 mg / day) and a lower maximum dose (10 mg / day).

Reduced kidney function

In mild and moderate renal insufficiency dose adjustment is required. Patients with severe renal impairment (Cl creatinine <30 ml / min) should be prescribed with minimal therapeutic doses, gradually increasing them based on tolerability and efficacy.

Reduced liver function

The recommended starting dose for the first 2 weeks of treatment was 5 mg / day. Depending on the individual patient response, dosage may be increased to 10 mg / day.

Reduced activity of cytochrome CYP2C19

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

Discontinuation of treatment

Upon termination of treatment with the drug dose should be gradually reduced over 1-2 weeks to avoid the occurrence of withdrawal syndrome.

Overdose:

Symptoms. Dizziness, tremor, agitation, somnolence, dizziness, seizures, tachycardia, ECG changes (change of segment ST, T wave, the expansion of the complex the QRS, QT prolongation), arrhythmias, depression of respiratory activity, vomiting, rhabdomyolysis, metabolic acidosis, hypokalemia, very rarely - acute renal failure.

Treatment. There is no specific antidote. Treatment is symptomatic and supportive: gastric lavage, adequate oxygenation. Monitoring the function of the cardiovascular and respiratory systems.

Precautionary measures:

In the application of drugs belonging to the therapeutic group of SSRIs, including escitalopram, should consider the following

Some patients with panic disorder at the beginning of treatment with SSRIs may experience increased anxiety. This paradoxical reaction usually disappears within two weeks of treatment. To reduce the likelihood of anxiogenic effects, it is recommended to use low initial dose.

It is necessary to stop the drug in case of seizures. Not recommended in patients with uncontrolled epilepsy under controlled seizures should be closely monitored. An increase in the frequency of seizures SSRIs, including escitalopram should be repealed.

Escitalopram should be used with caution in patients with mania / hypomania in history. With the development of mania escitalopram should be abolished.

In patients with diabetes treated with escitalopram may change in blood glucose level (possible hypoglycemia and hyperglycemia). Therefore, it may require dose adjustment of insulin and / or oral hypoglycemic drugs.

The risk of suicide is characteristic of depression and may persist until significant improvement, the come spontaneously or as a result of the therapy. Careful monitoring of patients being treated with antidepressants, especially at the beginning of treatment, due to the possibility of clinical deterioration and / or the emergence of suicidal events (thoughts and behavior). This precaution should be observed in the treatment of other psychiatric disorders due to the simultaneous development of depression.

In some cases, the treatment of SSRI antidepressant indicated increased risk of suicidal thoughts and behavior in children, adolescents and young adults under the age of 24 years compared with placebo.

Hyponatremia may be associated with impaired secretion of ADH, while taking escitalopram is rare and usually disappears when you cancel therapy. Caution should be manifested in the appointment of escitalopram and other SSRIs to persons at risk of hyponatremia: the elderly, patients with liver cirrhosis and receiving drugs that can cause hyponatremia.

When receiving escitalopram may develop bruising (ecchymosis and purpura). It should be used with caution in patients with escitalopram with a tendency to bleeding, as well as taking oral anticoagulants and other medicines that affect blood clotting.

Since clinical experience of concurrent use of escitalopram and electroconvulsive therapy is limited, in such cases, caution should be exercised.

Combine escitalopram and MAO inhibitors type A is not recommended due to the risk of serotonin syndrome.

In patients taking escitalopram and other SSRIs together with serotonergic agents, serotonin syndrome may develop in rare cases. Caution should be used in conjunction with drug escitalopram having serotonergic activity. A combination of symptoms such as agitation, tremor, myoclonus, hyperthermia may indicate the development of serotonin syndrome. If this happens, the SSRI and the serotonergic drugs should be stopped immediately and symptomatic treatment is scheduled.

Effects on ability to drive or to perform work requiring higher rate of physical and mental reactions

In the process of treatment, patients should avoid the performance of potentially hazardous activities that require high speed of psychomotor reactions, such as driving a car or operating machinery.