Escitalopram tablets 10 mg

Characteristics of the substance Escitalopram An antidepressant of the SSRI group, the S-enantiomer of citalopram. Escitalopram oxalate is a white or slightly yellow powder. Easily soluble in methanol and dimethyl sulfoxide, hardly soluble in water and ethanol, slightly soluble in ethyl acetate, insoluble in heptane. Molecular weight - 414.40. Pharmacology Pharmacological action - antidepressant. The mechanism of antidepressant action is presumably associated with an increase in serotonergic activity in the central nervous system as a result of inhibition of neuronal serotonin reuptake. In in vitro and in vivo studies on animals, the ability of escitalopram to highly selectively inhibit the neuronal reuptake of serotonin in the central nervous system with a minimal effect on the reuptake of norepinephrine and dopamine has been shown. Escitalopram is at least 100 times more potent serotonin reuptake inhibitor than the R-enantiomer. Tolerance in modeling the antidepressant effect does not develop with prolonged (up to 5 weeks) administration to rats. Escitalopram does not interact or has a very weak ability to bind to serotonin (5-HT1-7) or other receptors, incl. with alpha and beta adrenergic receptors, dopamine (D1–5), histamine (H1–3), muscarinic (M1–5) and benzodiazepine receptors (antagonism to muscarinic, histamine and adrenergic receptors, presumably, causes, various anticholinergic side effects of other psychotropic drugs). Escitalopram also does not bind or has very low affinity for various ion channels, including Na +, K +, Cl- and Ca2 + channels.

Pharmacokinetics The pharmacokinetics of escitalopram is linear and dose-dependent when taken in single and multiple doses (in the range of 10-30 mg / day). Tablets and oral solution containing escitalopram oxalate are bioequivalent. The absorption of escitalopram is independent of food intake. When a single dose of 20 mg is taken orally, Tmax is about 5 hours. The binding of escitalopram to human plasma proteins is about 56%. When taken once a day, the equilibrium plasma concentration is established within approximately 1 week of therapy. In the equilibrium state, the plasma level of escitalopram in young healthy subjects is 2.2–2.5 times higher than the concentration after taking a single dose. It is metabolized mainly in the liver to form S-demethylcitalopram (S-DCT) and S-didemethylcitalopram (S-DDCT). In vitro studies using human liver microsomes indicate the involvement of isoenzymes CYP3A4 and CYP2C19 in the process of N-demethylation of escitalopram. In human blood plasma, escitalopram prevails unchanged. In the equilibrium state, the concentration of S-DCT in plasma is approximately 1/3 of the concentration of escitalopram. S-DDCT levels were undetectable in most subjects. In vitro studies have shown that the pharmacological activity of escitalopram (inhibition of serotonin reuptake) exceeds that of S-DCT by at least 7 times, S-DCT - 27 times, which indicates that metabolites do not significantly contribute to the antidepressant effect of escitalopram ... S-DCT and S-DCT also do not interact or have very weak affinity for serotonin (5-HT1-7) or other receptors, incl. alpha- and beta-adrenergic receptors, dopamine (D1-5), histamine (H1-3), muscarinic (M1-5) and benzodiazepine receptors, do not bind to various ion channels, including Na +, K +, Cl- and Ca2 + channels. It has been shown that after oral administration, escitalopram is determined in the urine unchanged (about 8%) and in the form of S-DCT - 10%. Oral clearance of escitalopram is 600 ml / min, of which approximately 7% is renal. Terminal T1 / 2 about 27–32 h.

Dependence of pharmacokinetic parameters on some factors

Age. The pharmacokinetic parameters of escitalopram when taken in single and multiple doses in people over 65 years of age and young people are comparable. When taking the recommended dose (10 mg) in the elderly, AUC and T1 / 2 increased by about 50%, Cmax did not change. Floor. When using multiple doses of escitalopram (10 mg / day for 3 weeks) in 18 men (9 elderly and 9 young) and 18 women (9 elderly and 9 young), no differences were found in the values ​​of AUC, Cmax and T1 / 2. There is no need to adjust the dose depending on gender. Decreased liver function. For most patients with impaired liver function, the recommended dose of escitalopram is 10 mg. Decreased kidney function. There is no information on the pharmacokinetic parameters of escitalopram in patients with severe renal failure (with Cl creatinine less than 20 ml / min). Clinical trials Major depressive disorder The efficacy of escitalopram oxalate in the treatment of depression has been established in 3 placebo-controlled studies of 8 weeks duration in adult outpatients (age 18–65 years) with major depressive disorder (according to DSM-IV criteria). The main criterion for efficacy in all 3 studies was the change in the total Montgomery-Asberg score (MADRS). A fixed-dose study comparing 10 and 20 mg / day escitalopram oxalate, placebo and 40 mg / day citalopram showed that the improvement was significantly more pronounced in the groups of patients taking 10 and 20 mg / day escitalopram, compared with placebo (according to with MADRS score). The efficacy rates in the groups of patients treated with 10 or 20 mg / day of escitalopram were similar. In another study with a fixed dose of escitalopram oxalate 10 mg / day, the improvement was significantly higher in this group compared to placebo (as assessed by MADRS). In a study using different dose ranges of escitalopram titrated between 10 and 20 mg / day, compared with placebo and different doses of citalopram titrated between 20 and 40 mg / day, the improvement in the escitalopram oxalate group was significantly higher in compared with placebo (according to the MADRS score). The efficacy of escitalopram for maintenance therapy in the treatment of depression was evaluated in a placebo-controlled study with a 36-week open phase. The study included 274 patients with major depressive disorder (according to DSM-IV criteria) who were responders after an initial 8-week treatment for an acute condition and were then randomized to continue escitalopram therapy at the same dose (10 or 20 mg / day ), or a placebo. The response to treatment in the open phase of the study was defined as a decrease in scores on the MADRS scale ≤12. Relapse during a double-blind study was defined as an increase in MADRS scores ≥22 or discontinuation of therapy due to an unsatisfactory clinical response. Patients who continued to receive escitalopram for 36 weeks had significantly longer remission times compared with placebo. Adequate controlled studies of the effectiveness of escitalopram in the treatment of hospitalized patients with depression have not been conducted.

Generalized Anxiety Disorder (GAD) The efficacy of escitalopram in the treatment of generalized anxiety disorder has been demonstrated in 3 multicenter, placebo-controlled studies of 8 weeks duration using doses of 10–20 mg / day. The study included patients aged 18 to 80 years with a diagnosis of GAD (in accordance with the DSM-IV criteria). In all 3 studies, the improvement with escitalopram was significantly higher compared to placebo (assessed by the Hamilton Anxiety Scale, HAM-A). In these groups, there were too few patients with ethnic or age characteristics to assess their impact on the effect of therapy. The response to treatment was independent of the gender of the patients. The effectiveness of escitalopram in long-term (more than 8 weeks) treatment of GAD in controlled trials has not been systematically evaluated. Panic Disorder * The efficacy of escitalopram was shown in a 10-week, randomized, double-blind study in 351 patients. Patients after a 2-week induction placebo period were randomized to receive escitalopram (n = 125), placebo (n = 114), or the active comparator citalopram (n = 112).

Use of the substance Escitalopram According to the State Register1, escitalopram is indicated for the treatment of depression, panic disorders (including agoraphobia). According to the Physicians Desk Reference (2009) 2, escitalopram is indicated for the treatment of major depressive disorder, generalized anxiety disorder. Contraindications Hypersensitivity, concomitant use of MAO inhibitors, age up to 18 years (see "Precautions"). Application during pregnancy and lactation During pregnancy, it is possible if the expected effect of therapy outweighs the potential risk to the fetus (adequate and strictly controlled studies of the safety of escitalopram in pregnant women have not been conducted). FDA category of action on the fetus - C. Administration of escitalopram to pregnant rats at doses of 6, 12, 24, or 48 mg / kg / day, from late pregnancy to weaning, led to a slight increase in offspring mortality and growth retardation at a dose of 48 mg / kg / day (approximately 24 times the MRDC, calculated in mg / m2). At the same dose, there was a slight toxicity to the maternal organism (clinical signs, decreased weight gain and food intake). The dose of 12 mg / kg / day, at which no adverse effects were observed, is approximately 6 times higher than the MRSA, when calculated in mg / m2. According to the results of a study of embryo / fetal development in rats, oral administration of escitalopram to pregnant rats at doses of 56, 112, or 150 mg / kg / day during organogenesis was accompanied by a decrease in fetal body weight and delayed ossification at 2 higher doses (approximately 56 times higher than the MRDC - 20 mg / day, calculated in mg / m2). Maternal toxicity (clinical signs, decreased weight gain and food intake), moderate at 56 mg / kg / day, was observed at all dose levels. The dose of 56 mg / kg / day, at which there was no effect on fetal development, was approximately 28 times higher than the MRAF, when calculated in mg / m2. There was no evidence of teratogenicity at any of the tested doses (up to more than 75 times higher than the MRDC, when calculated in mg / m2). Non-teratogenic effects Newborns who were exposed to escitalopram and other SSRIs or serotonin and norepinephrine reuptake inhibitors at the end of the third trimester of the mother's pregnancy developed complications requiring prolonged hospitalization, maintaining breathing, and feeding through a tube. Such complications can appear immediately after delivery. Reported clinical symptoms included: respiratory distress, cyanosis, apnea, seizures, unstable temperature, difficulty feeding, vomiting, hypoglycemia, hypotension, hyperreflexia, tremors, nervous excitement, irritability, and constant crying. These symptoms are either associated with direct toxicity from SSRIs or serotonin and norepinephrine reuptake inhibitors, or may be manifestations of a withdrawal response in the newborn. In some cases, the clinical picture was similar to the development of serotonin syndrome. If the patient is taking escitalopram during the third trimester of pregnancy, the doctor should carefully assess the risk / benefit ratio, while taking into account the possibility of a drug discontinuation syndrome in the newborn. The doctor may decide to gradually stop treatment with escitalopram in the third trimester. The effect of escitalopram oxalate on labor and delivery in humans is not known. L actation. Women who are breastfeeding should stop either breastfeeding or escitalopram oxalate. 

Side effects of the substance Escitalopram

The tables present side effects, the frequency of which is expressed as a percentage and reflects the number of patients who had at least one case of a single side effect during the observation period. Standard WHO terminology has been used to group the side effects noted in various studies. Side effects that led to discontinuation of treatment Major depressive disorder In double-blind, placebo-controlled trials in patients with depression, 6% of 715 patients treated with escitalopram discontinued treatment due to side effects, compared with 2% of 592 patients treated with placebo. In studies with fixed doses, the proportion of patients who received 10 mg / day of escitalopram and discontinued treatment due to side effects did not differ significantly from that of patients who received placebo. The proportion of patients receiving a fixed dose of escitalopram 20 mg / day and discontinuing treatment was 10%, which was significantly different from that among patients receiving 10 mg / day (4%) and placebo (3%). Side effects that caused discontinuation of escitalopram treatment in at least 1% of patients, with a frequency of occurrence 2 times higher than placebo - nausea (2%), ejaculation disorder (2% of male patients). Generalized anxiety disorder

In double-blind, placebo-controlled trials in patients with GAD, 8% of 429 patients who received 10–20 mg / day of escitalopram discontinued treatment due to side effects, compared with 4% of 427 patients who received placebo. Side effects that caused discontinuation of escitalopram treatment in at least 1% of patients, with a frequency of occurrence 2 times higher than placebo - nausea (2%), insomnia (1%), fatigue (1%).