Composition, form of production and packaging
The tablets covered with a film shell of white color, oval, biconcave, with engraving "E" on the one hand, risk on the other hand and lateral risks.
1 tab.
escitalopram oxalate 12.78 mg,
which corresponds to the content of escitalopram 10 mg
[PRING] SMCC В® 90 / HD90 - 147.42 mg (microcrystalline cellulose 144.47 mg, silicon dioxide - 2.95 mg), croscarmellose sodium 9 mg, talc 9 mg, magnesium stearate 1.8 mg.
Composition of the film shell: opadriy white (Opadry 03F28446 White) ~ 5.4 mg: hypromellose 6cP - 3.29 mg, titanium dioxide - 1.31 mg, macrogol 6000 - 0.8 mg.
10 pieces. - blisters (1) - packs of cardboard.
14 pcs. - blisters (2) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2012.
PHARMACHOLOGIC EFFECT
Antidepressant, selective serotonin reuptake inhibitor (SSRI). Inhibition of reuptake of serotonin leads to an increase in the concentration of this neurotransmitter in the synaptic cleft, enhances and prolongs its effect on postsynaptic receptor sites.
Escitalopram has no or very little ability to bind to a number of receptors, including: serotonin 5-HT 1A- , 5-HT 2 -receptors, dopamine D 1 and D 2 receptors,? 1 -,? 2-,? -adrenoceptors, histamine H 1 -receptors, m-cholinergic receptors, benzodiazepine and opioid receptors.
PHARMACOKINETICS
Suction and distribution
Absorption is not dependent on food intake. Bioavailability of escitalopram is about 80%. The average time to reach C max in blood plasma is about 4 hours.
The kinetics of escitalopram are linear. C ss is reached after about 1 week. The average C ss - 50 nmol / l (from 20 to 125 nmol / l) is achieved with a daily dose of 10 mg.
After ingestion, the apparent V d is 12 to 26 l / kg. The binding of escitalopram and its major metabolites to plasma proteins is about 80%.
Metabolism
Escitalopram is metabolized in the liver to demethylated and demodetylated metabolites. They are both pharmacologically active. The basic substance and its metabolites are partially isolated in the form of glucuronides.
After repeated use, the average concentration of demethyl- and didemetylmetabolites is usually 28-31% and less than 5%, respectively, of the concentration of escitalopram. Biotransformation of escitalopram to the demethylated metabolite occurs mainly with cytochrome CYP2C19. Some participation of CYP3A4 and CYP2D6 isoenzymes is possible. In persons with a weak activity of CYP2C19, the concentration of escitalopram can be twice as high as in cases with high activity of this isoenzyme. Significant changes in drug concentration in cases with a weak activity of the isoenzyme CYP2D6 were not detected.
Excretion
T 1/2 after repeated use is about 30 hours. Clearance for oral use is about 0.6 l / min. The main metabolites of escitalopram T 1/2 are longer. Escitalopram and its major metabolites are excreted by the liver (the metabolic pathway) and the kidneys.
Pharmacokinetics in special clinical cases
In elderly (over 65 years) escitalopram is excreted more slowly compared to young patients. AUC in the elderly is 50% greater than in young healthy volunteers.
INDICATIONS
- Depressive disorders of any severity;
- panic disorder with / without agoraphobia.
DOSING MODE
The drug is prescribed for adults and children over 15 years 1 time / day inside, regardless of food intake.
With depressive disorders, 10 mg 1 time / day are prescribed. Depending on the individual reaction of the patient, the dose may be increased to a maximum of 20 mg / day.
The antidepressant effect usually develops in 2-4 weeks after the start of treatment. After the disappearance of the symptoms of depression, at least for another 6 months, it is necessary to continue therapy to fix the effect.
In panic disorders with / without agoraphobia , a dose of 5 mg / day is recommended during the first week of treatment, which is then increased to 10 mg / day.Depending on the individual reaction of the patient, 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. The therapy lasts for several months.
Elderly patients (over 65 years) are recommended to prescribe half of the usually recommended dose (ie, only 5 mg / day) and a lower maximum dose (10 mg / day).
With renal failure of mild to moderate severity, dose adjustments are not required. Patients with severe renal insufficiency (QC below 30 ml / min) should be prescribed the drug with minimal therapeutic doses, gradually increasing them taking into account the tolerability and effectiveness of the drug.
If the liver function is disturbed, the recommended initial dose during the first two weeks of treatment is 5 mg / day. Depending on the individual reaction of the patient, the dose may be increased to 10 mg / day.
For patients with a weak activity of the CYP 2C19 isoenzyme, the recommended initial dose for the first two weeks of treatment is 5 mg / day. Depending on the individual reaction of the patient, the dose may be increased to 10 mg / day.
At the termination of treatment by a drug the dose should gradually decrease within 1-2 weeks in order to avoid occurrence of a withdrawal syndrome.
SIDE EFFECT
Side effects most often occur at 1 or 2 weeks of treatment, then usually become less intense and occur less frequently with continued therapy.
From the side of the central nervous system: dizziness, weakness, insomnia or drowsiness, convulsions, tremor, motor disorders, serotonin syndrome (agitation, tremor, myoclonus, hyperthermia), hallucinations, manic disorders, confusion, agitation, anxiety, depersonalization, panic attacks, increased irritability , a disorder of vision.
On the part of the digestive system: nausea, vomiting, dry mouth, taste disorders, decreased appetite, diarrhea, constipation.
From the cardiovascular system: orthostatic hypotension.
On the part of the endocrine system: a decrease in the secretion of ADH, galactorrhea.
From the genitourinary system: decreased libido, impotence, ejaculation, anorgasmia (in women), urinary retention.
Dermatological reactions: skin rash, itching, ecchymosis, purpura.
Allergic reactions: angioedema, anaphylactic reactions.
On the part of laboratory indicators: hyponatremia, changes in laboratory parameters of liver function.
Other: increased sweating, hyperthermia, sinusitis, arthralgia, myalgia.
In addition, after a prolonged use, a sharp discontinuation of therapy with the Selektra drug in some patients can lead to the onset of withdrawal syndrome. With a sharp discontinuation of escitalopram, unwanted reactions such as dizziness, headaches and nausea, which are not significant, and duration - are limited.
CONTRAINDICATIONS
- simultaneous administration with MAO inhibitors;
- Children's age (up to 15 years);
- Pregnancy;
- the period of lactation (breastfeeding);
- Hypersensitivity to the drug or its components.
Caution should be given to the drug with renal failure (QC below 30 ml / min), hypomania, manic disorders, pharmacologically uncontrolled epilepsy, depression with suicidal attempts, diabetes, cirrhosis, tendency to bleeding, while taking medication that lower the threshold convulsive readiness, causing hyponatremia, with ethanol, with drugs metabolized with CYP2C19, as well as elderly patients and adolescents aged 15 about 18 years.
PREGNANCY AND LACTATION
The drug is contraindicated for use in pregnancy and lactation.
APPLICATION FOR FUNCTIONS OF THE LIVER
With renal failure of mild to moderate severity, dose adjustments are not required. Patients with severe renal insufficiency (QC below 30 ml / min) should be prescribed the drug with minimal therapeutic doses, gradually increasing them taking into account the tolerability and effectiveness of the drug.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
If the liver function is disturbed, the recommended initial dose during the first two weeks of treatment is 5 mg / day. Depending on the individual reaction of the patient, the dose may be increased to 10 mg / day.
APPLICATION FOR CHILDREN
Contraindication: children's age (up to 15 years).
APPLICATION IN ELDERLY PATIENTS
Elderly patients (over 65 years) are recommended to prescribe half of the usually recommended dose (ie, only 5 mg / day) and a lower maximum dose (10 mg / day).
SPECIAL INSTRUCTIONS
Some patients with panic disorder at the beginning of SSRI treatment may experience increased anxiety. A similar paradoxical reaction usually disappears within two weeks of treatment. To reduce the likelihood of anxiogenic effect, it is recommended to use the drug in a low initial dose.
It is necessary to cancel the drug in case of convulsive seizures. It is not recommended to use in patients with uncontrolled epilepsy; with controlled seizures careful monitoring is necessary. With an increase in the frequency of convulsive seizures, SSRIs, including escitalopram, should be abolished.
Escitalopram should be used with caution in patients with a history of mania / hypomania. With the development of the manic state, escitalopram should be abolished.
In patients with diabetes, treatment with escitalopram can alter blood glucose levels (both hypoglycemia and hyperglycemia are possible). Therefore, the dosage of insulin and / or oral hypoglycemic agents may need to be adjusted.
The risk of committing suicide is inherent in depression and can persist until a significant improvement in the condition occurs spontaneously or due to ongoing therapy. Careful observation of patients on antidepressant medication is necessary, especially at the beginning of treatment because of the possibility of clinical deterioration and / or the appearance of suicidal manifestations (thoughts and behavior). This precaution should be followed in the treatment of other mental disorders due to the possibility of simultaneous development of depression.
In some cases, in the treatment of SSRIs with antidepressants, there has been an increased risk of developing suicidal thoughts and behavior in children, adolescents and young people younger than 24 years, compared with placebo.
Hyponatremia, possibly associated with a violation of ADH secretion, against the background of taking escitalopram occurs rarely and usually disappears when therapy is withdrawn. Caution should be manifested in the appointment of escitalopram and other SSRIs to persons at risk of developing hyponatremia: the elderly, the patient with cirrhosis of the liver and taking drugs that can cause hyponatremia.
When taking escitalopram, subcutaneous hemorrhage (ecchymosis and purpura) may develop. Escitalopram should be used with caution in patients with a tendency to bleeding, and also taking oral anticoagulants and other drugs that affect blood clotting.
Since the clinical experience of simultaneous use of escitalopram and electroconvulsive therapy is limited, caution should be exercised in such cases.
Combining escitalopram and MAO inhibitors type A is not recommended because of the risk of developing a serotonin syndrome.
In patients taking escitalopram and other SSRIs concomitantly with serotonergic drugs, in rare cases, a serotonin syndrome may develop. It is necessary to use caution with escitalopram simultaneously with drugs that have a serotonergic effect. The combination of such symptoms as agitation, tremor, myoclonus, hyperthermia, may indicate the development of serotonin syndrome. If this occurs, SSRIs and serotonergic drugs should be immediately withdrawn and symptomatic treatment is prescribed.
Impact on the ability to drive vehicles and manage mechanisms
During the treatment of the drug, patients should avoid performing potentially dangerous activities requiring high rates of psychomotor reactions, such as driving a car or controlling machinery.
OVERDOSE
Symptoms: dizziness, tremor, agitation, drowsiness, darkening of consciousness, convulsive attacks, tachycardia, ECG changes (ST segment change, T wave, QRS complex expansion, QT interval prolongation), arrhythmias, respiratory depression, vomiting, rhabdomyolysis, metabolic acidosis, hypokalemia, very rarely - acute renal failure.
Treatment: symptomatic and supportive: gastric lavage, adequate oxygenation. Monitoring the function of the cardiovascular and respiratory systems. There is no specific antidote.
DRUG INTERACTION
Serious adverse reactions may occur with the simultaneous use of the preparation of Selectra and MAO inhibitors , as well as with the administration of MAO inhibitors to patients who have recently stopped taking the drug. In such cases, a serotonin syndrome may develop.
Escitalopram can not be administered simultaneously with MAO inhibitors. Escitalopram can be prescribed 14 days after discontinuation of treatment with irreversible MAO inhibitors and at least 1 day after discontinuation of therapy with a reversible MAO inhibitor of type A-moclobemide. At least 7 days must pass after the end of taking escitalopram before treatment with non-selective MAO inhibitors can begin.
Joint use with serotonergic drugs (eg tramadol, sumatriptan and other triptans) may lead to the development of serotonin syndrome.
Sepect can lower the threshold of convulsive readiness. Care should be taken when concomitantly with other drugs that reduce the threshold of convulsive readiness(tricyclic antidepressants, other SSRIs, neuroleptics (phenothiazines, thioxanthene derivatives and butyrophenone), mefloquine and tramadol).
Escitalopram enhances the pharmacological effects of tryptophan (increased serotonergic effect) and the toxic effects of lithium preparations.
Simultaneous administration of escitalopram and preparations containing St. John's wort (Hypericum perforatum) may lead to an increase in the number of side effects.
Violation of blood clotting can occur with the simultaneous administration of escitalopram with oral anticoagulants and other drugs that affect blood clotting (for example, atypical antipsychotics and phenothiazines, most tricyclic antidepressants, acetylsalicylic acid and NSAIDs, ticlopidine and dipyridamole). In such cases, control of blood clotting parameters is necessary.
Escitalopram does not enter with pharmacodynamic or pharmacokinetic interaction with ethanol . However, as with other psychotropic drugs, simultaneous use of escitalopram and alcohol is not recommended.
The effect of other drugs on the pharmacokinetics of escitalopram
Co-administration with drugs that inhibit CYP2C19 can increase the concentration of escitalopram in the blood plasma. Caution should be exercised while using escitalopram with similar drugs, for example, omeprazole. A decrease in the dose of escitalopram may be required.
Caution should be given to escitalopram in high doses concomitantly with cimetidine, which is a potent inhibitor of the isoenzymes CYP2D6, CYP3A4 and CYP1A2, in high doses.
The effect of escitalopram on the pharmacokinetics of other drugs
Escitalopram is an inhibitor of the CYP2D6 isoenzyme. Care should be taken when concomitantly administering escitalopram and drugs metabolized by this isoenzyme and having a small therapeutic index, for example, flecainide, propafenone and metoprolol (in cases of heart failure) or medications that are mainly metabolized by CYP2D6 and acting on the CNS , for example, antidepressants - desipramine, clomipramine, nortriptyline or antipsychotic agents - risperidone, thioridazine, haloperidol. In these cases, dose adjustment may be required, because the concentration of escitalopram in the blood plasma increases.
Simultaneous administration of escitalopram and desipramine or metoprolol leads to a twofold increase in the concentration of the last two drugs, which should be taken into account when choosing doses.
Escitalopram can slightly inhibit the isoenzyme CYP2C19. Therefore, caution should be exercised while using escitalopram and medications that are metabolized by CYP2C19.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
The drug should be stored out of reach of children at a temperature of no higher than 25 В° C. Shelf life - 24 months.
