Description of the active substance: Sertraline

Characteristics:
Antidepressant, a specific serotonin reuptake inhibitor, enhances its effects has little effect on the reuptake of norepinephrine and dopamine, in therapeutic doses, blocks the uptake of serotonin into human platelets. Inhibition of serotonin reuptake increases serotonergic transmission, which leads to subsequent inhibition of adrenergic activity in the locus ceruleus (locus ceruleus). Sertraline inhibits the initiation of serotonin neurons in the weld area (the middle line of the medulla oblongata), which leads to an initial increase in activity of bluish place with subsequent reduction in the activity of postsynaptic beta-adrenergic receptors and presynaptic alpha2-adrenergic receptors. There is no drug dependence, has no psihoostimuliruyuschego, sedation, anticholinergic and m-cardiotoxic action does not alter the psychomotor activity. Due to the selective serotonin reuptake inhibition does not increase the activity of the sympathetic nervous system. Has no affinity for m-choline-, serotonin (5-HT1A, 5-HT1B, 5-HT2), dopamine, adrenergic, histamine, GABA or benzodiazepine receptors, does not inhibit MAO. Unlike tricyclic antidepressants in treating depression or obsessive-compulsive disorder (obsessive-compulsive disorder) does not increase body weight. The initial effect develops within 7 days, the full develops within 2-4 weeks.

Uses:
Depressive states (including the accompanying anxiety), prevention of initial or chronic episodes of depression, obsessive-compulsive disorder, panic disorder.

Contraindications:
Hypersensitivity, pregnancy, lactation, concomitant use of inhibitors MAO. Neurological disorders (including mental retardation), manic state, epilepsy, liver and / or renal failure, weight loss, childhood.

Side effects:
Allergic reactions, bleeding (including nose), palpitations, dry mouth, loss of appetite. Rarely - increased appetite (perhaps as a consequence of eliminating of depression), nausea, vomiting, unstable stool, diarrhea, stomach cramps or abdominal bloating or pain, weight loss, headache, dizziness, insomnia, somnolence, tremor, movement disorders (extrapyramidal symptoms, change of gait), akathisia, muscle cramps, paresthesias, symptoms of depression, hallucinations, aggression, agitation, anxiety, psychosis, skin flushing or "tides" of blood to the face, impaired vision (including blurred vision), yawning, sweating, sexual violation function (delayed ejaculation, decreased potency and / or libido, anorgasmia), dysmenorrhea, galactorrhea, hypomania, mania, hyponatremia (syndrome of inappropriate secretion of ADH), hyperprolactinemia syndrome "cancel", erythema multiforme, rash and zud. Overdose. Symptoms: Anxiety, drowsiness, ECG changes, mydriasis, nausea, vomiting, tachycardia. Treatment: To ensure the normal airway (oxygenation and ventilation of the lungs), gastric lavage, emesis drug assignment, activated charcoal with sorbitol. Necessary to monitor the heart and liver. Ineffective forced diuresis, dialysis, hemoperfusion and exchange transfusion (taking into account the large volume of distribution).

Dosage and direction:
Inside, 50 mg, 1 time per day in the morning or evening, with or without food. In the absence of effect may gradually (over several weeks) increase the dose to 200 mg / day (50 mg / week). Some clinicians recommend at first to appoint a dose of 25 mg / day for 1-2 days. Panic disorder: initial dose - 25 mg / day increasing to 50 mg / day for 1 week. When conducting long-term maintenance therapy is prescribed in the lowest effective dose, which subsequently changed depending on the effect. Obsessive-compulsive disorder: children and adolescents 13-17 years of the initial dose - 50 mg / day in children 6-12 years of the initial dose - 25 mg / day, followed by an increase within 1 week to 50 mg / day. With little effect dose can be increased stepwise to 50 mg / day to 200 mg / day, with an interval of at least 1 week. For elderly patients the initial dose - 25 mg / day (morning or evening), followed by a gradual increase.

Cautions:
In the period of treatment should closely monitor the behavior of patients with depression (risk of suicide attempts) until there will come a significant improvement as a result of the treatment. Sertraline administered no earlier than 14 days after discontinuation of MAO inhibitors. Women of childbearing age during treatment should use appropriate methods of contraception. During the period of treatment must be careful when driving and occupation of other potentially hazardous activities that require your full attention and psychomotor speed of reaction.

Interaction:
Is able to displace from its association with plasma proteins other drugs. Enhances the effect of indirect anticoagulants (increased prothrombin time), blocks cytochrome CYP2D6, increasing the plasma concentration of both drugs used in the metabolism of which involved the enzyme (tricyclic antidepressants, antiarrhythmic drugs of class Ic - propafenone, flecainide). Reduces the clearance of tolbutamide (requires monitoring of blood glucose, while the application). MAO inhibitors increase the risk of side effects (hyperthermia, rigidity, seizures, altered mental status, confusion, irritability, excessive stimulation with the development of delirium and coma). Incompatible with ethanol. Cimetidine decreases the AUC, Cmax and T1 / 2 of sertraline for 50, 24 and 26% respectively. While the use of drugs Li+ increases the risk of tremors.

Description of Zoloft is not intended to assign treatment without a doctor and based on the approved instructions for use of the drug Zoloft ® for specialists and approved by the manufacturer to editions of 2011.

Pharmacokinetics

Absorption
Absorption is high, but at a slow speed. While taking the drug together with food increases bioavailability by 25%, C max increased by 25% and T max decreases.

In humans at a dose of sertraline from 50 to 200 mg 1 time / within 14 days, C max was reached after 4.5-8.4 h after administration. C max and AUC proportional to dose within the 50-200 mg sertraline 1 time / within 14 days, with the detected linear pharmacokinetic dependence.

Distribution

Plasma protein binding is about 98%.
Prior to the equilibrium state after 1 week of treatment (dose of 1 X / ) is approximately two-fold drug accumulation.

Metabolism
Sertraline undergoes biotransformation in the active "first pass" through the liver. The main metabolite found in plasma, - N-desmetilsertralin - far below (about 20 times) of sertraline on the activity in vitro, and in fact is not active in models of depression in vivo.
Sertraline and N-desmetilsertralin actively biotransformed.

Breeding
The average T 1 / 2 of sertraline in young and elderly men and women is 22-36 h. T 1 / 2 N-desmetilsertralina varies from 62-104 h. The metabolites are excreted in the feces and urine in equal amounts. Only a small fraction of the drug (less than 0.2%) is excreted in the urine in unchanged form.

Pharmacokinetics in special clinical situations

The pharmacokinetic profile in adolescents and the elderly is not significantly different from that in patients aged 18 to 65 years.
ÏIt is shown that the pharmacokinetics of sertraline in children with OCD is similar to that in adults (although the metabolism of sertraline in children is somewhat more active). However, due to a lower body weight in children (especially those aged 6-12 years), the drug recommended for use in a smaller dose to avoid excessive levels in plasma.
Patients with liver cirrhosis increased T 1 / 2 and AUC of the drug compared with those in healthy people.
According to the pharmacokinetic study, with multiple receiving sertraline in patients with stable cirrhosis of easy flow, an increase in T 1 / 2 of the drug and almost three-fold increase in AUC (area under the concentration / time) and C max of the drug compared with those in healthy people. There were no significant differences in the binding to plasma proteins in the 2 groups was not.
In patients with mild renal insufficiency and moderate (creatinine clearance 30-60 ml / min) and patients with severe renal insufficiency (creatinine clearance 10-29 ml / min) pharmacokinetic parameters (AUC 0-24 and C max) of sertraline with repeated his admission were not significantly different from controls. In all groups, T 1 / 2 drugs was similar, as there were no differences in binding to plasma proteins.