Золофт®

General characteristics. Structure:

International unlicensed name: Sertraline/Sertraline
The chemical name – tsis-4-(3,4 dichlorophenyl) -1,2,3,4-тетрагидро-N-метил-1-нафталенамин
Dosage form: tablets, coated.

Active component: sertraline a hydrochloride in the dose corresponding of 50 mg or 100 mg of sertraline.
Excipients: calcium phosphate, cellulose microcrystallic, hydroxypropyl cellulose, sodium starch glycollate, magnesium stearate, gidroksipropilmetiltsellyuloz, polyethyleneglycol, polysorbates, titanium dioxide (E171).
Description: white oblong tablets of a tablet. On a surface of a tablet "Pfizer", on the other hand for a dosage of 50 mg of "ZLT-50" (from risky), for a dosage of 100 mg - "ZLT-100" is squeezed out on the one hand.

Pharmacological properties:

Pharmakodinamichesky properties. Sertraline – antidepressant, powerful specific inhibitor of the return serotonin reuptake (5-HT) in neurons. It exerts very weak impact on the return capture of noradrenaline and a dopamine. In therapeutic doses sertraline blocks serotonin reuptake in thrombocytes of the person. It has no the stimulating, sedative or anticholinergic effect. Thanks to the selection oppression of capture 5-HT, sertraline does not increase adrenergic activity. Sertraline has no affinity to muskarinovy (cholinergic), serotonergic, dopaminergic, adrenergic, gistaminergichesky, to GAMK-or benzodiazepine receptors.
Sertraline does not cause medicinal dependence, does not cause increase in body weight at long reception.

Pharmacokinetic properties. Absorption – high (but with a slow speed). Bioavailability increases during meal by 25%. Food increases the maximum concentration (Cmax) by 25% and shortens time of achievement of the maximum concentration (Tcmax). At the person at treatment by sertraline in a dose from 50 mg to 200 mg once a day within 14 days concentration of drug in plasma reached peak (Cmax) in 4,5 - 8,4 hours after reception. Cmax and the area under a curve concentration time (AUC) are proportional to a dose within 50-200 mg of sertraline of 1 times a day within 14 days, at the same time the linear nature of pharmacokinetic dependence comes to light. A pharmacokinetic profile at teenagers and elderly people do not differ from those at patients aged from 18 up to 65 years. The average elimination half-life (T1/2) of sertraline at young and elderly men and women makes 22-36 h. According to final T1/2 approximately twofold cumulation of drug before equilibrium concentration in 1 week of treatment is observed (reception of a dose once a day). Linkng with proteins of plasma is equal to about 98%. It is shown that the sertraline pharmacokinetics at children with ROC (see below) is similar to that at adults (though at children metabolism of sertraline is a little more active). However, considering lower body weight at children (especially at the age of 6-12 years), drug is recommended to be used in a smaller dose to avoid excessive levels it in plasma.
Sertraline is exposed to active biotransformation at the first passing through a liver. The main metabolite found in plasma, N-desmetilsertralin considerably concedes (approximately by 20 times) to sertraline on activity of in vitro and actually is not active on in vivo depression models. T1/2 of N-desmetilsertralina varies within 62 - 104 hours. Sertraline and N-desmetilsertralin biotransformirutsya actively; the formed metabolites are removed in equal quantities with a stake and urine. Not changed sertraline is removed with urine in insignificant quantity (<0,2%). At patients with cirrhosis T1/2 of drug and AUC in comparison with those at healthy people increase.

Indications to use:

- Depressions of various etiology (treatment and prevention),
- Obsessivno-kompulsivnye Frustration (OKF)
- Panic frustration.
- Posttraumatic stressorny frustration (PTSR).
- Social phobia.

Route of administration and doses:

Sertraline is appointed inside, once a day in the morning or in the evening. A pill of sertraline can be taken irrespective of meal.

Initial dose
Depression and ROC: treatment it is necessary to begin with sertraline with a dose 50 mg/days.
Panic frustration, PTSR and social phobia: treatment begin 25 mg/days which is increased in one week to 50 mg/days with a dose. Use of drug according to such scheme allows to reduce the frequency of the early undesirable effects of treatment characteristic of panic frustration.

Selection of a dose
Depression, ROC, panic frustration, PTSR and social phobia: at insufficient effect of use of sertraline for patients in a dose of 50 mg/days, its daily dose can be increased. The dose should be raised with an interval not more often than weekly to the maximum recommended dose making 200 mg/days.
The initial therapeutic effect can be shown within 7 days, however the full effect is usually reached in 2 – 4 weeks (or even during longer time at ROC).
Maintenance therapy. The maintenance dose at prolonged treatment has to be minimum effective – with its corresponding changes depending on therapeutic effect.
Use for treatment of children.
Safety and efficiency of sertraline are established at children with ROC (aged from 6 up to 17 years). At the teenagers (at the age of 13-17 years) suffering from ROC treatment it is necessary to begin with sertraline with a dose 50 mg/days. At children (at the age of 6-12 years) therapy of ROC begin 25 mg/days with a dose, in one week increase it to 50 mg/days. In the subsequent, at insufficient effect the dose can be increased in steps on 50 mg/days to 200 mg/days as required. In clinical tests at patients with a depression and ROC aged from 6 up to 17 years it was shown that the pharmacokinetic profile of sertraline is similar to that at adults. However, to avoid overdose, at increase in a dose more than 50 mg it is necessary to take into account smaller body weight at children in comparison with adults.
Selection of a dose at children and teenagers. The elimination half-life of sertraline makes about 1 days therefore change of a dose has to happen to an interval not less than 1 week.
Use for treatment of elderly people. At advanced age drug is used in the same range of doses, as at more young people.
Use for patients with insufficiency of function of a liver. Sertraline should be applied with care at patients with liver diseases. At patients with a liver failure it is necessary to use smaller doses or to increase an interval between administrations of drug (See. Special instructions).
Use for patients with insufficiency of function of kidneys. Sertraline is substantially metabolized in an organism. In not changed view with urine only the insignificant amount of drug is removed. As expected taking into account insignificant renal excretion of sertraline, correction of its dose depending on expressiveness of a renal failure it is not required (See. Special instructions).

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.
Serotoninovy syndrome and malignant antipsychotic syndrome
At use of the selective serotonin reuptake inhibitors (SSRI) cases of development of a serotoninovy syndrome (CC) and the malignant antipsychotic syndrome (MAS) which risk increases at SIOZS combination with other serotonergic means (including triptanes), and also the drugs influencing serotonin metabolism (including monoamine oxidase inhibitors), antipsychotic means and other antagonists of dopamine receptors are described. Changes of the mental status (in particular, agitation, hallucinations, a coma), vegetative lability (tachycardia, fluctuations of arterial pressure, a hyperthermia), changes of neuro and muscular transfer (a hyperreflexia, a lack of coordination of movements) and/or disturbances from digestive tract (nausea, vomiting and diarrhea) can be manifestations of CC. Some manifestations of CC, including, the hyperthermia, muscle tension, vegetative lability with a possibility of bystry fluctuations of parameters of the vital functions, and also changes of the mental status, can remind the symptomatology developing at ZNS. Monitoring of patients regarding development of clinical manifestations of CC and ZNS is necessary.
Other serotonergic means - it is necessary to be careful at co-administration of sertraline with other drugs strengthening serotoninergicheskuyu neurotransmission such as, tryptophane, фенфлюрамин or 5-NT-agonisty. Similar joint appointment at an opportunity has to be excluded, considering probability of pharmakodinamichesky interaction.
Other serotonergic means - it is necessary to be careful at co-administration of sertraline with other drugs strengthening serotoninergicheskuyu neurotransmission such as, tryptophane, фенфлюрамин or 5-NT-agonisty. Similar joint appointment at an opportunity has to be excluded, considering probability of pharmakodinamichesky interaction.
Transition from other selective serotonin reuptake inhibitors (SSRI), antidepressants or antiobsessivny drugs. Experience of clinical trials which purpose was a definition of the optimum time necessary for transfer of patients from reception of other antidepressive and antiobsessivny funds for sertraline is limited. It is necessary to be careful upon such transition, especially from dlitelnodeystvuyushchy drugs, for example, from fluoxetine. The necessary interval between cancellation of one selective serotonin reuptake inhibitor and the beginning of reception of other similar drug is not established. 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. There is no experience of use of sertraline for patients with a convulsive syndrome therefore it is necessary to avoid its use for patients with unstable epilepsy, and patients with controlled epilepsy need to be observed carefully during treatment. At emergence of spasms drug should be cancelled. 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.
Activation of a mania/hypomania. During clinical trials before implementation of sertraline on the market, the hypomania and a mania were observed approximately at 0,4% of the patients receiving sertraline. Cases of activation of a mania/hypomania are described also at a small part of the patients with maniac-depressive psychosis receiving other antidepressive or antiobsessivny means.
Use at insufficiency of function of a liver. Sertraline biotransformirutsya actively in a liver. According to a pharmacokinetic research, at multiple dose of sertraline at patients with stable cirrhosis of an easy current increase in an elimination half-life of drug and almost triple increase in AUC (the area under a curve concentration/time) and the maximum concentration of drug in comparison with those at healthy people was observed. Essential distinctions in linkng with proteins of plasma in two groups were not. It is necessary to apply sertraline at patients with liver diseases with care. At purpose of drug to the patient with the broken function of a liver, it is necessary to discuss expediency of a dose decline or increase in an interval between administration of drug.
Use at a renal failure
Sertraline is exposed to active biotransformation therefore in not changed view with urine he is brought in insignificant quantity. At patients with the slight and moderately expressed renal failure (clearance of creatinine of 30-60 ml/min.) and patients with moderate or heavy degree of a renal failure (clearance of creatinine of 10-29 ml/min.) pharmacokinetic parameters (AUC0-24 and Cmax) sertraline at its multiple dose significantly did not differ from group of control. In all groups the elimination half-life of drug was identical, is equal as there were no distinctions in linkng with proteins of plasma. Results of this research demonstrate to what, as expected taking into account insignificant renal excretion of sertraline, correction of its dose depending on expressiveness of a renal failure is not required.
Pathological bleedings / hemorrhages
It is recommended to be careful at purpose of selective serotonin reuptake inhibitors in combination with the drugs having the established ability to change of functions of thrombocytes and also at patients with hemorrhagic diseases in the anamnesis.
Hyponatremia
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. At development of a simtomatichesky hyponatremia sertraline it is necessary to cancel and appoint the adequate therapy directed to correction of level of sodium in blood. Signs and symptoms of a hyponatremia include a headache, disturbance of concentration of attention, memory disturbance, weakness and instability that can lead to falling. In more hard cases there can be hallucinations, a faint, spasms, a coma, an apnoea and death.
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:

Alimentary system: dispepsichesky frustration (a meteorism, nausea, vomiting, diarrhea, a lock), an abdominal pain, pancreatitis, dryness in a mouth.
Cardiovascular system: tachycardia, tachycardia, arterial hypertension.
Musculoskeletal system: arthralgia, muscular spasms.
Central and peripheral nervous system: extrapyramidal frustration (dyskinesia, akathisias, gnash teeth, gait disturbance), involuntary muscular contractions, paresthesias, faint, drowsiness, headache, migraine, dizziness, tremor, sleeplessness, alarm, agitation, hypomania, mania, hallucinations, euphoria, nightmares, psychosis, decrease libido, suicide, coma.
System of breath: bronchospasm, yawning.
Urinary system: enuresis, incontience or ischuria. Reproductive system and mammary gland: disturbance of sexual function (ejaculation delay, decrease in a potentiality), galactorrhoea, gynecomastia, disturbance of a menstrual cycle, priapism.
Organs of sight: vision disorder, mydriasis.
Endocrine system: giperprolaktinemiya, гипотериоз, syndrome of inadequate secretion of ADG.
Gepatobiliarny system: hepatitis, jaundice, liver failure. Allergic reactions: urticaria, itch, anaphylactoid reaction. Other: weakness, erubescence or "inflows" of blood to the person, a ring in ears, an alopecia, a Quincke's disease, a face edema, periorbital hypostasis, reaction of a fotosensebilization, purple, the increased sweating, a loss of appetite (it is rare – increase), up to anorexia, decrease or increase in body weight, bleeding (including nasal, gastrointestinal or a hamaturia), peripheral hypostasis, occasionally Stephen-Johnson's syndrome and an epidermal necrolysis.
Data of laboratory analyses: seldom, 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. Development of a leukopenia and thrombocytopenia, and also increase in level of cholesterol in blood serum is possible. At the treatment termination sertraline described exceptional cases of a withdrawal. There can be paresthesias, hypesthesias, symptoms of a depression, hallucination, aggressive reactions, psychomotor excitement, concern or symptoms of psychosis which cannot be distinguished from symptoms of a basic disease.

Interaction with other medicines:

Pimozidum – At combined use of sertraline and Pimozidum increase in levels of Pimozidum at its single appointment in a low dose (2 mg) was noted. Increase in levels of Pimozidum was not connected with any changes in an ECG. As, the mechanism of this interaction is not known, and Pimozidum differs in a narrow therapeutic index, the concomitant use of Pimozidum and sertraline is contraindicated.
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, and also линезолид). Development of a serotoninovy syndrome is possible (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). 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.
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 the alcoholic drinks and drugs containing alcohol during treatment by sertraline is forbidden. Potentiation of effect of ethanol, carbamazepine, a haloperidol or Phenytoinum on cognitive and psychomotor function at healthy people is noted; however combined use of sertraline and alcohol is not recommended.
Anticoagulants of indirect action (warfarin) - at their joint appointment with sertraline not considerable, but statistically reliable 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 and Tolbutamidum).
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 increases concentration in plasma of at the same time applied medicines in which metabolism this enzyme takes part (tricyclic antidepressants, antiarrhytmic Ic medicines of a class - пропафенон, флекаинид).
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 3A3/4 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 Tolbutamidum plasma (but at a concomitant use reduces clearance of Tolbutamidum – control of glucose in blood at simultaneous use is necessary), 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 CYP 2C19 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 brings in a dose of 200 mg and antipyrine to small (5%), but to reliable reduction of the period antipyrine semi-removal.
Atenolol: at joint introduction sertraline does not change it to ß - adrenoceptor blocking action.
Glibenclamide and digoxin: at administration of sertraline in a daily dose of 200 mg of medicinal interaction with these drugs it is not revealed.
Phenytoinum: prolonged use of sertraline in a dose of 200 mg/days renders clinically significant influence and does not suppress metabolism of Phenytoinum. Despite it, careful observation of Phenytoinum level in a blood plasma is recommended from the moment of purpose of sertraline with the corresponding correction of doses of Phenytoinum.
Sumatriptan: extremely exceptional cases of emergence of weakness, increase in tendon jerks, confusion of consciousness, alarm and excitement at the patients who were at the same time accepting sertraline and суматриптан are celebrated. Observation of patients who have corresponding clinical bases for a concomitant use of sertraline and a sumatriptan is recommended.

Contraindications:

The known hypersensitivity to sertraline, children's age up to 6 years, pregnancy and the period of breastfeeding (see the section Pregnancy and breastfeeding). It is impossible to appoint drug the patient who is at the same time receiving inhibitors of a monoaminooxidase (MAO) and Pimozidum. With care: organic diseases of a brain (including a delay of intellectual development) epilepsy, a liver and/or renal failure, the expressed decrease in body weight.
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 supposes to mean 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. In case of use of sertraline during pregnancy and feeding by a breast at some newborns whose mothers accepted antidepressants from group of the selective serotonin reuptake inhibitors (SSRI) including serotonin, the symptoms similar to reaction to drug withdrawal can be observed.

Overdose:

Heavy 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 alcohol there can be a serious poisoning, up to a coma and a lethal outcome. 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:

List B. At a temperature not above 30 °C, in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Blisters from opaque polypropylene and aluminum foil on 14 tablets, coated on 50 mg or 100 mg; on 1 or 2 blisters in a cardboard pack together with the application instruction.