Escitalopram - instructions for use, dose, side effects, contraindications

Antidepressant. Selectively inhibits the reuptake of serotonin; increases the concentration of the neurotransmitter in the synaptic cleft, enhances and prolongs the action of serotonin on postsynaptic receptors. Escitalopram practically does not bind to serotonin (5-HT), dopamine (D₁ and D₂) receptors, α-adreno, m-cholinergic receptors, as well as with benzodiazepine and opioid receptors.

The antidepressant effect usually develops in 2-4 weeks after the start of treatment. The maximum therapeutic effect of treatment of panic disordersis reached approximately in 3 months after the beginning of treatment.

Pharmacokinetics:

Absorption is not dependent on food intake. Bioavailability - 80%. The time to reach the maximum concentrationin plasma - 4 hours. The kinetics of escitalopram is linear. The equilibrium concentrationis achieved after 1 week. The average equilibrium concentration is 50 nmol / L (20 to 125 nmol / L) and is achieved at a dose of 10 mg per day. Apparent volume of distribution- from 12 to 26 l / kg. Binding to plasma proteins - 80%. Metabolized in the liver to active demethylated and demodetylated metabolites. After repeated use, the average concentration of demethyl- and didemetilmetabolites is 28-31% and less than 5%, respectively, of the concentration of escitalopram. Metabolism of escitalopram with the formation of a demethylated metabolite occurs mainly with the participation of isoenzymes CYP2C19, CYPZA4 and CYP2D6. In persons with a weak activity of the isoenzyme CYP2C19, the concentration of escitalopram can be 2 times higher than in persons with a high activity of this isoenzyme. Significant changes in the concentration of the drug with a weak activity of the isoenzyme CYP2D6 is not observed. The half-life after repeated use is 30 hours. In the main metabolites of escitalopram, the elimination half-lifemore prolonged.Clearance - 0,6 l / min. Escitalopram and its major metabolites are excreted by the liver and most of it by the kidneys, partially excreted in the form of glucuronides. Half-lifeand AUC is increased in elderly patients.

Indications:

Escitalopram is indicated for the treatment of depression, panic disorders (including agoraphobia).

ICD-10

V.F40-F48.F41.2 Mixed anxiety and depressive disorder

V.F40-F48.F41.0 Panic disorder [episodic paroxysmal anxiety]

V.F40-F48.F40 Phobic anxiety disorders

V.F30-F39.F33 Recurrent depressive disorder

V.F30-F39.F31 Bipolar affective disorder

Contraindications:

Simultaneous administration of MAO inhibitors, childhood and adolescence up to 15 years, pregnancy, lactation, increased sensitivity to escitalopram.

Carefully:

Caution should be used in patients with renal insufficiency (creatinine clearance less than 30 ml / min), hypomania, mania, with pharmacologically uncontrolled epilepsy, with depression with suicide attempts, diabetes, in elderly patients, with cirrhosis, with a tendency to bleeding ,simultaneously with taking medications that reduce the threshold of convulsive readiness, causing hyponatremia, with ethanol, with drugs metabolized with the participation of isoenzymes of the CYP2C19 system.

Pregnancy and lactation:

Action category for the fetus by FDA - C. Adequate and strictly controlled studies of the safety of the use of escitalopram in pregnant women have not been conducted. Do not apply.

In newborns who have been exposed to escitalopram and other selective serotonin reuptake inhibitors or serotonin reuptake inhibitors and norepinephrine at the end of the third trimester of the mother's pregnancy, complications that require prolongation of hospitalization, maintenance of breathing, and feeding through the probe have developed. Such complications can occur immediately after delivery. The noted clinical symptoms included: breathing disorder, cyanosis, apnea, convulsions, unstable temperature, feeding difficulties, vomiting, hypoglycemia, hypotension, hyperreflexia, tremor, nervous excitement, irritability, constant crying. These symptoms are associated either with direct toxic effects of selective serotonin reuptake inhibitors or serotonin and noradrenaline reuptake inhibitors, or, possibly,are manifestations of the reaction of withdrawal in a newborn. In some cases, the clinical picture was similar to the development of serotonin syndrome.

If the patient takes escitalopram During the third trimester of pregnancy, the physician should carefully evaluate the risk / benefit ratio, while taking into account the possibility of developing a drug discontinuation syndrome in a newborn. The doctor may decide to phase out treatment with escitalopram in the third trimester.

The effect of escitalopram oxalate on labor and delivery in humans is not known.

Lactation. Breastfeeding women should stop breastfeeding, or taking escitalopram oxalate.

Dosing and Administration:

Is taken orally, regardless of food intake. Depending on the indications, a single dose of 10-20 mg per day. The maximum daily dose is 20 mg. Duration of treatment is several months. At the end of treatment, the dose should gradually decrease within 1-2 weeks in order to avoid the occurrence of the "withdrawal" syndrome.

For elderly patients (over 65 years), the recommended dose is 5 mg per day, the maximum daily dose is 10 mg.

If the liver function is disturbed, the recommended initial dose for the first 2 weeks of treatment is 5 mg per day. Depending on the individual reaction, the dose can be increased to 10 mg per day.

For patients with a weak activity of the CYP2C19 isoenzyme, the recommended initial dose for the first 2 weeks of treatment is 5 mg per day. Depending on the individual reaction, the dose can be increased to 10 mg per day.

Side effects:

From the side CNS and peripheral nervous system: dizziness, weakness, insomnia or drowsiness, convulsions, tremor, motor disorders, serotonin syndrome (agitation, tremor, myoclonus, hyperthermia), hallucinations, mania, confusion, agitation, anxiety, depersonalization, panic attacks, increased irritability, visual disturbances.

From the side digestive system: nausea, vomiting, dryness of the oral mucosa, taste disorders, decreased appetite, diarrhea, constipation, changes in laboratory parameters of liver function.

From the side of cardio-vascular system: orthostatic hypotension.

From the side endocrine system: decrease in secretion of ADH, galactorrhea.

From the side reproductive system: decreased libido, impotence, violation of ejaculation, anorgasmia (in women).

From the side urinary system: retention of urine.

Dermatological reactions: skin rash, itching, ecchymosis, purpura, increased sweating.

Allergic reactions: angioedema, anaphylactic reactions.

From the side metabolism: hyponatremia, hyperthermia.

From the side musculoskeletal system: arthralgia, myalgia.

Other: sinusitis, withdrawal syndrome (dizziness, headaches and nausea).

Overdose:

When conducting clinical trials of escitalopram, there were reports of an overdose (up to 600 mg) without a lethal outcome.

Treatment: maintenance and maintenance of airway patency for adequate ventilation and oxygenation, gastric lavage and the use of activated charcoal. It is recommended to closely monitor and monitor vital functions, including heart function, symptomatic and supportive therapy. Due to the large volume of distribution of escitalopram, the effectiveness of such activities as forced diuresis, dialysis, hemoperfusion and exchange blood transfusion is unlikely.There is no specific antidote.

Interaction:

When used simultaneously with MAO inhibitors, the risk of developing serotonin syndrome and serious adverse reactions increases.

Joint application with serotonergic drugs (including tramadol, triptans) may lead to the development of serotonin syndrome.

With simultaneous use with drugs that reduce the threshold of convulsive readiness, increases the risk of seizures.

Escitalopram enhances the effects of tryptophan and lithium preparations, increases the toxicity of St. John's wort preparations, the effects of drugs that affect blood clotting (monitoring of blood coagulation indices is necessary).

Drugs metabolized with the participation of the isoenzyme CYP2S19 (including omeprazole), and are also potent inhibitors of CYPZA4 and CYP2D6 (including flecainide, propafenone, metoprolol, desipramine, clomipramine, nortriptyline, risperidone, thioridazine, haloperidol), increase the concentration of escitalopram in blood plasma.

Escitalopram increases the plasma concentration of desipramine and metoprolol by a factor of 2.

Special instructions:

Escitalopram should be administered only 2 weeks after the cancellation of irreversible MAO inhibitors and 24 hours after discontinuation of therapy with a reversible MAO inhibitor. Non-selective MAO inhibitors can be prescribed no earlier than 7 days after the withdrawal of escitalopram.

In some patients with panic disorder, early on with the treatment with escitalopram, anxiety may increase, which usually disappears during the next 2 weeks of treatment. To reduce the likelihood of an alarm, it is recommended to use low initial doses.

It should be canceled escitalopram in the case of epileptic seizures or their increase in pharmacologically uncontrolled epilepsy.

With the development of the manic state escitalopram should be canceled.

Escitalopram is able to increase the concentration of glucose in the blood in diabetes mellitus, which may require correction of doses of hypoglycemic drugs.

The clinical experience of using escitalopram indicates a possible increase in the risk of suicide attempts in the first weeks of therapy, which is why it is very important to carefully monitor patients during this period.

Hyponatremia, associated with a decrease in ADH secretion, against the background of escitalopram is rare and usually disappears when it is withdrawn.

With the development of serotonin syndrome escitalopram should be immediately withdrawn and symptomatic treatment should be prescribed.

During the period of treatment, patients should avoid driving motor vehicles and other activities that require a high concentration of attention and speed of psychomotor reactions.

Instructions

Escitalopram (Escitalopramum)