СТИМУЛОТОН®

General characteristics. Structure:

Active ingredient: each tablet, coated, contains respectively 50 or 100 mg of active agent - sertraline in the form of hydrochloride sertraline, and also excipients: magnesium stearate, hydroxypropyl cellulose, sodium of starch glikolit (type A), hydrophosphate calcium a dihydrate, cellulose microcrystallic. The cover contains a gipromelloza 2910, a macrogoal 6000, titanium dioxide. 

Description: Tablets on 50 mg: white or almost white biconvex tablets, coated, an oval form, inodorous, on one party of a tablet an engraving - E 271 on another - dividing risk. Tablets on 100 mg: white or almost white, biconvex tablets coated, an oval form, inodorous, on one party of a tablet an engraving E 272, on other party - dividing risk. On a break: kernel and outside ring of a cover of white or almost white color.

Pharmacological properties:

Pharmacodynamics. Action mechanism. Sertraline - selective serotonin reuptake inhibitor (5-HT). It exerts very weak impact on the return capture of noradrenaline and a dopamine. In therapeutic doses sertraline blocks serotonin reuptake by thrombocytes of the person. It has no the stimulating, sedative or anticholinergic effect. Sertraline has no affinity to muskarinovy (cholinergic), serotonergic, dopaminergic, adrenergic, gistaminergichesky, to GAMK-or benzodiazepine receptors. The antidepressive effect is noted by the end of the second week of regular reception of sertraline whereas the maximum effect is reached only in 6 weeks. Unlike tricyclic antidepressants, at purpose of sertraline there is no increase in body weight. Sertraline does not cause mental or physical medicinal dependence.

Pharmacokinetics. Absorption of sertraline from digestive tract considerable, but happens slowly. The concentration maximum in a blood plasma is reached in 4,5-8,4 hours after administration of drug inside. Equilibrium concentration of sertraline in a blood plasma is reached within a week at single daily dose. Bioavailability during meal increases by 25%, at the same time time of achievement of the maximum concentration is shortened. Distribution. The general linkng of sertraline with proteins of plasma makes 98%. Distribution volume> 20 l/kg. Metabolism and removal. Sertraline is exposed to intensive metabolism at the first passing through a liver, being exposed to N-demethylation. Its main metabolite - N-desmetilsertralin is less active in comparison with initial connection. Metabolites are allocated with urine and a stake in equal quantities. About 0,2% of sertraline are removed by kidneys in not changed look. Time of semi-removal of drug makes 22-36 hours and does not depend on age or a floor. For N-desmetilsertralina this indicator makes 62-104 hours. Time of semi-removal of sertraline and the area under a concentration curve in a blood plasma (AUC) increase at an abnormal liver function. Irrespective of expressiveness of a renal failure the sertraline pharmacokinetics at its constant use does not change. Sertraline gets into breast milk. There are no data on its ability to pass through a gemato-placental barrier. Sertraline is not dialyzed.

Indications to use:

• Depressions of various etiology (treatment and prevention),
• Obsessivno-kompulsivnye Frustration (OKF)
• Panic frustration (with an agarofobiya or without).
• Posttraumatic stressful frustration (PTSR).

Route of administration and doses:

Depressions and ROC
Adults
The initial dose makes 50 mg of STIMULOTONA once a day, in the morning or in the evening. A day dose it is possible gradually, not earlier, than in a week to increase from 50 mg, to the maximum daily dose in 200 mg.
At patients with obsessivno-compulsive frustration for achievement of good result 8-12 weeks can be required. The minimum dose providing medical action remains further as supporting.

Panic frustration and PTSR
The initial dose makes 25 mg of STIMULOTONA once a day, in the morning or in the evening. In a week the doctor can increase a dose to 50 mg of sertraline once a day, and then gradually, not earlier, than in a week, the day dose can be increased gradually from 50 mg to the maximum daily dose in 200 mg.
The satisfactory therapeutic result is achieved usually in 7 days from an initiation of treatment. However achievement of full therapeutic effect requires regular administration of drug within 2-4 weeks.

Children with ROC
For children from 6 to 12 years the initial dose makes 25 mg of sertraline once a day, in the morning or in the evening. In a week, it is possible to increase a dose to 50 mg once a day.
For children from 12 to 17 years the initial dose makes 50 mg once a day, in the morning or in the evening. A day dose it is possible gradually, not earlier, than in a week to increase from 50 mg, to the maximum daily dose in 200 mg. To avoid overdose, it is necessary to take into account smaller body weight at children in comparison with adults, and at increase in a dose more than 50 mg/days are necessary careful observation of this category of patients and at the first signs of overdose to cancel drug.
Elderly patients have no need for special selection of a dose.
Patients with abnormal liver functions require special attention at treatment by sertraline. At heavy disorder of function of a liver a dose of drug it is necessary to reduce or increase intervals between receptions. At patients with renal failures specially it is not required to select a dose (see Osobyeukazaniya).

Features of use:

It is not necessary to appoint sertraline together with IMAO, and also within 14 days after the termination of treatment of IMAO. Similarly after cancellation of sertraline within 14 days do not appoint IMAO.
It should be noted that at the patients who are exposed to electroconvulsive therapy, sufficient experience of use of sertraline is absent. Possible success or risk of the similar combined treatment is not studied.
The patients having a depression are risk group concerning suicide attempts. This danger remains before remission development. Therefore from an initiation of treatment and before achievement of optimum clinical effect for patients it is necessary to establish constant medical observation.

Pregnancy and breastfeeding:

There are no controlled results of use of sertraline for pregnant women therefore they need to appoint drug if the expected advantage for mother exceeds potential risk for a fruit. Women of reproductive age which is supposed to appoint sertraline should recommend to use effective contraceptive remedies. Sertraline is found in breast milk in this connection treatment by this drug during breastfeeding is not recommended. There are no reliable data about safety of its use in this case. If treatment nevertheless is necessary, then a breast it is better to stop feeding.
Influence on ability to driving of motor transport and to control of mechanisms: Appointment, sertraline, as a rule, is not followed by disturbance of psychomotor functions. However its use along with other drugs can lead to disturbance of attention and coordination of movements. Therefore during treatment by sertraline to manage vehicles, the special equipment or to be engaged in the activity connected with the increased risk it is not recommended.

Side effects:

Dryness in a mouth, the increased sweating, drowsiness, a headache, dizziness, a tremor, sleeplessness, alarm, agitation, a hypomania, a mania, a loss of appetite (it is rare - increase), up to anorexia, dispepsichesky frustration (a meteorism, nausea, vomiting, a diarrhea), an abdominal pain, decrease in body weight, gait disturbance.
Also weakness, erubescence, vision disorders, frustration of an ejaculation, decrease in a libido are possible.
During treatment sertraline noted extrapyramidal frustration, dyskinesia, a tremor, spasms, disturbances of a menstrual cycle, a giperprolaktinemiya, a galactorrhoea, skin rash, occasionally multiformny erythema. Motive disturbances were more often noted at patients with instructions on their existence in the anamnesis or at the accompanying use of antipsychotic means.
At the treatment termination sertraline described exceptional cases of a withdrawal. There can be paresthesias, giposteziya, symptoms of a depression, hallucination, aggressive reactions, psychomotor excitement, concern or symptoms of psychosis which cannot be distinguished from symptoms of a basic disease.
Data of laboratory analyses: seldom - in 0,8% of observations, at prolonged use there is a symptomless increase in activity of transaminases in blood serum. Drug withdrawal in this case leads to normalization of activity of enzymes. During treatment the tranzitorny hyponatremia can arise sertraline. It develops at elderly patients more often, and also at reception of diuretics or some other drugs. The similar side effect is connected with a syndrome of inadequate secretion of antidiuretic hormone.

Interaction with other medicines:

Monoamine oxidase inhibitors (IMAO). Heavy complications at simultaneous use of sertraline and IMAO are noted (including IMAO which are selectively operating (селегилин) and with reversible type of action (моклобемид). Development of a serotoninovy syndrome is possible. Similar complications, sometimes from the death, arise at purpose of IMAO against the background of treatment by the antidepressants oppressing neyronalny capture of monoamines or right after their cancellation.
At simultaneous use of selective inhibitors of the return neyronaljny serotonin reuptake and IMAO arise: a hyperthermia, rigidity, a myoclonus, lability of the autonomic nervous system (bystry fluctuations of parameters of respiratory and cardiovascular system), changes of the mental status, including an acrimony, the expressed excitement, confusion of consciousness which in certain cases can pass into a delirious state or a coma.
Medicines, the oppressing central nervous system and ethanol. The combined use of sertraline and the substances oppressing the central nervous system requires close attention, and also the use of alcoholic drinks is forbidden during treatment by sertraline.
Coumarin derivatives - at their joint appointment with sertraline significant increase in a prothrombin time is noted - in these cases it is recommended to control a prothrombin time in an initiation of treatment sertraline and after its cancellation. Pharmacokinetic interaction
Sertraline contacts proteins of a blood plasma. Therefore it is necessary to consider a possibility of its interaction with other drugs contacting proteins (for example: diazepam, Tolbutamidum and warfarin).
Cimetidinum: simultaneous use substantially reduces clearance of sertraline.
Medicines, metaboliziruyemy isoenzyme 2D6 of P450 cytochrome: prolonged treatment by sertraline in a dose of 50 mg a day is followed by increase in concentration of desipramine.
Medicines, metaboliziruyemy other fermental systems of P450 cytochrome. Experiments on studying of interaction of in vitro showed that the beta hydroxylation of endogenous cortisol which is carried out by CYP 3AZ/4 isoenzyme, and also metabolism of carbamazepine and a terfenadin at long purpose of sertraline in a dose of 200 mg a day do not change. Concentration in a blood plasma of Tolbutamidum, Phenytoinum and warfarin at long purpose of sertraline in the same dose also does not change. Thus, it is possible to make the conclusion that sertraline does not oppress CYP 2C9 isoenzyme.
Sertraline does not influence concentration of diazepam in blood serum that speaks about lack of inhibition of SNZ 2S19 isoenzyme. According to the researches in vitro sertraline practically does not influence or minimum CYP 1A2 isoenzyme oppresses.
Lithium. The pharmacokinetics of lithium does not change at the accompanying administration of sertraline. However, the tremor is observed more often at their combined use. Also as well as purpose of other selective inhibitors of the return neyronalny serotonin reuptake, combined use of sertraline with the medicines influencing serotonergic transfer (for example, with lithium), demands the increased care.
The drugs influencing serotonergic transfer. When replacing one inhibitor of neyronalny serotonin reuptake by another there is no need for "the washing period". However it is required to be careful at treatment changes of course. It is necessary to avoid joint purpose of tryptophane or a fenfluramin with sertraline.
Induction of microsomal enzymes of a liver. Sertraline causes the minimum induction of enzymes of a liver. Co-administration of sertraline and antipyrine in a dose of 200 mg leads to reliable reduction of an elimination half-life of antipyrine though there is it in only 5% of observations.
Atenolol: at joint introduction sertraline does not change its β-adrenoceptor blocking action.
Glibenclamide and digoxin: at administration of sertraline in a daily dose of 200 mg of medicinal interaction with these drugs not vyivleno.

Contraindications:

• Hypersensitivity to the active agent or other ingredients which are a part of drug
• combined use of sertraline and MAO inhibitors (watch the section "Special Instructions" and "Interaction"),
• combined use of sertraline with tryptophane or fenfluraminy
• unstable epilepsy,
• children's age up to 6 years;
• pregnancy and the period of a lactation (see. "Special instructions").

With care: organic diseases of a brain (including a delay of intellectual development), maniacal states, epilepsy, a liver and/or renal failure, decrease in body weight, at children are more senior than 6 years.

Overdose:

Simptomy:tyazhely symptoms at overdose of sertraline it is not revealed even at purpose of drug in high doses. However at simultaneous introduction with other drugs or ethanol there can be a serious poisoning.
The overdose can cause a serotoninovy syndrome with nausea, vomiting, drowsiness, tachycardia, agitation, the dizziness, psychomotor excitement, diarrhea increased by sweating, a myoclonus and a hyperreflexia.
Treatment: there are no specific antidotes. The intensive maintenance therapy and constant observation of the vital functions of an organism is required. It is not recommended to cause vomiting. Administration of absorbent carbon can be more effective, than a gastric lavage. It is necessary to maintain passability of respiratory tracts. At sertraline the large volume of distribution, in this regard strengthening of a diuresis, carrying out dialysis, hemoperfusion or hemotransfusion can be ineffectual.

Storage conditions:

Period of storage 3 years. The period of storage is specified on packaging. Not to use after the date designated on packaging. To store at a temperature of 15-25 °C, in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Tablets coated 50 mg. On 10 tablets in the blister. 1, 2 or 3 blisters are packed into a cardboard pack together with the application instruction. Tablets coated 100 mg. On 14 tablets in the blister. 1 or 2 blisters are packed into a cardboard pack together with the application instruction.