Serlift tab. of p/o of 50 mg No. 28

Pharmacological properties

Pharmacodynamics. sertraline — powerful selective serotonin reuptake inhibitor. almost does not influence the return capture of noradrenaline and dopamine. sertraline has no affinity to cholinergic, dopamine, histamine, benzodiazepine and adrenergic receptors. sertraline has no sedative, stimulating and anticholinergic effect, does not strengthen katekholaminergichesky stimulation. sertraline does not cause physical and mental dependence.

Pharmacokinetics: sertraline is slowly absorbed in a GIT. Meal has no significant effect on bioavailability of drug. Sertraline is exposed to active metabolism at the first passing through a liver. The main metabolite — N-desmetilsertralin — considerably concedes on activity to sertraline and practically does not show antidepressive effect. Average C _max in blood plasma is reached in 4.5-8.4 h after administration of drug. Equilibrium concentration is reached in 1 week of therapy (at reception of 1 times a day). Extent of linking with proteins of blood plasma makes 98%. T _½ sertraline makes about 26 h (22–36 h), N-desmetilsertralina — 62–104 h. Sertraline and N-desmetilsertralin biotransformirutsya actively, and the formed metabolites are removed with a stake and urine in equal quantities. The medicament pharmacokinetics at patients of advanced and young age has no essential differences.

Indication

Depression, including its form which is followed by feeling of alarm at existence or absence of a mania in the anamnesis.

Obsessivno-kompulsivnoye disorder at adults and children.

Panic disorders with existence or absence of an agoraphobia.

Post-traumatic stress disorder.

Sociophobia (social anxiety disorder).

At satisfactory treatment response the therapy continuation by sertraline is an effective remedy of prevention of a recurrence of an initial episode of a depression and its emergence in the future; recurrence of an initial episode of obsessivno-compulsive disorder; panic disorder, initial episode of post-traumatic stress disorder, sociophobia.

Use

Sertraline is accepted 1 time a day (in the morning if there is an opportunity, or in the evening), irrespective of consumption of food.

Initiation of treatment. Depression and obsessivno-compulsive disorder. Treatment it is necessary to begin with sertraline with a dose 50 mg/days

Panic disorders, post-traumatic stress disorder and sociophobia. Treatment it is necessary to begin 25 mg/days with use of the corresponding dose of sertraline of a hydrochloride. In 1 week the dose is raised to 50 mg of 1 times a day. Such dose mode reduces the frequency of development of side effects at the initial stage of treatment of panic disorders.

Titration of a dose. Depression, obsessivno-compulsive disorder, panic disorders, post-traumatic stress disorder and sociophobia. If the effect of use of a dose of 50 mg is not enough, the dose can be raised. Begin to adjust a dose not earlier than in 1 week of treatment, the titrated dose makes 50 mg/week

Dose should not exceed 200 mg/days. Dose adjustment should be carried out not more often than once a week, in view of T _½ sertraline which makes 24 h

First manifestations of clinical effect note for 7 days of treatment. However its full development requires more long period, especially in obsessivno-compulsive disorder.

Maintenance dose. Dosing at long therapy needs to be held at the low effective level with the following correction depending on treatment response.

Use for children. Safety and efficiency of use of sertraline are shown at children with obsessivno-compulsive disorder aged from 13 up to 18 years. Experience concerning hydrochloride sertraline use for children under 6 years and also in other pathologies is absent. At children with obsessivno-compulsive disorder (at the age of 13–18 years) it is necessary to apply 50 mg of sertraline a day. In case of lack of effect at administration of medicament in a dose of 50 mg/days if necessary its further increase to 200 mg/days is possible. During clinical trials children at the age of 13–18 years with a depression or obsessivno-compulsive disorder had the same pharmacokinetic characteristic of sertraline, as at adults. However at increase in a dose of 50 mg/days in pediatrics it is necessary to consider the small body weight of children in comparison with adults.

Titration of a dose for children. T _½ sertraline — about 1 days. It is not necessary to carry out dose adjustment more often than once a week.

Use for patients of advanced age. At patients of advanced age (65 years) it is possible to apply the same doses, as at patients of younger age (up to 65 years). The range and frequency of side effects in this population were similar to that at patients of younger age.

Use in a liver failure. The care at use of sertraline for patients with liver pathology is required. In abnormal liver functions it is necessary to lower a dose or to take the medicament less often.

Use in a renal failure. Sertraline biotransformirutsya intensively in an organism. With urine in not changed look only the insignificant amount of medicament is removed. In view of low indicators of discharge of sertraline kidneys, the dose of medicament can be not adjusted in renal failures.

Contraindication

Hypersensitivity to sertraline, a concomitant use with Mao's inhibitors; simultaneous use of sertraline and Pimozidum. the period for 14 days after cancellation of inhibitors of Mao. sertraline should be cancelled in 7 days prior to treatment by Mao's inhibitors.

Side effects

from a GIT: diarrhea/incontinence a calla, dryness in a mouth, dyspepsia, nausea, an abdominal pain, a constipation, pancreatitis, vomiting, an esophagitis, a dysphagy, the increased salivation, stomatitis, ulcers of language, lips, a glossitis, an eructation, a melena, bloody excrements, a gastroenteritis;

metabolic disturbances: anorexia, increase in appetite, hyponatremia, hypoglycemia;

from central nervous system: dizziness, drowsiness, a tremor, a coma, spasms, a headache, a hypesthesia, migraine, motive disorders (including extrapyramidal symptoms, including a hyperkinesia, hypertension, spasms of a jaw or disturbance of gait), involuntary muscular contractures, paresthesias, a faint, depersonalization, a bruxism, apathy, abnormal thinking, paranoia, the suicide ideas and behavior, circulation in a dream, disturbance of flavoring feelings, attention, coordination, amnesia, disturbance of the speech, migraine, a coma, a choreoathetosis, a hyperesthesia, disturbance of sensitivity, an akathisia. Development of the manifestations of a serotonergic syndrome in certain cases connected with reception of serotonergic means is also recorded namely: agitation, confusion of consciousness, the increased sweating, diarrhea, fever, AG, rigidity and tachycardia;

from mentality: insomnia, aggressive reactions, agitation, uneasiness, depressive symptoms, euphoria, hallucinations, psychomotor excitement, decrease in a libido at men and women, nightmares, psychoses;

from a reproductive system: sexual dysfunctions (first of all an ejaculation delay at men); a galactorrhoea, a gynecomastia, an irregular menstrual cycle and a priapism, a menorrhagia, an atrophic vulvovaginitis, a balanoposthitis, disturbance of sexual function at women;

from skin and hypodermic fabric: the increased sweating, an alopecia, angionevrotichny hypostasis, a face edema, periorbitalny hypostasis, skin reactions of photosensitivity, an itching, skin rash (including isolated cases of exfoliative injuries of skin — Stephens's syndrome — Johnson and an epidermal necrolysis), urticaria, a purpura, xeroderma, disturbance of structure of hair, change of a smell of skin;

from the system of blood: leukopenia and thrombocytopenia, lymphadenopathy;

from a cardiovascular system: palpitations and tachycardia; pathological bleedings (for example nasal bleeding, gastrointestinal bleeding or hamaturia), blood inflows (sudden erubescence), AG, myocardial infarction, bradycardia;

from an organ of hearing: a ring in ears, ear pain, average otitis;

from an endocrine system: giperprolaktinemiya, hypothyroidism, hypoaldosteronism syndrome;

from an organ of sight: mydriasis, disorder of vision, glaucoma, scotoma, diplopia, photophobia;

organism in general: asthenia, stethalgia, peripheral hypostasis, fatigue, fever, indisposition, hemorrhoids, medicamentous dependence, syndrome of inadequate producing antidiuretic hormone, peripheral ischemia, thirst, new growths, injury, abnormal semen;

from a gepatobiliarny system: heavy abnormal liver functions (hepatitis, jaundice, a liver failure), asymptomatic increase in level of transaminases in blood plasma;

from the immune system: allergic reactions, anaphylactic reactions;

laboratory indicators: wrong results of clinical laboratory analyses, change of function of thrombocytes, increase in concentration of cholesterol in blood serum, increase or degrowth of a body;

from a musculoskeletal system: arthralgia, muscular spasms, osteoarthritis, weakness of muscles, dorsodynia;

from an urinary system: urine incontinence, ischuria, nocturia, polyuria, pollakiuria, urination disturbance;

from a respiratory system: infections of ENT organs and upper airways, bronchospasm, yawning, asthma, laryngospasm, dysphonia, hiccups, pharyngitis, rhinitis, diverticulitis.

revealed in clinical trials at patients with a depression.

Manifestation of a withdrawal at the treatment termination by sertraline — agitation, uneasiness, dizziness, a headache, nausea, paresthesias.

Special instructions

Mao's Inhibitors. cases of development of serious side effects, sometimes deadly, at the patients applying sertraline combined with Mao's inhibitors, in particular with selection inhibitor of Mao — selegiliny and with reversible inhibitor of Mao — moklobemidy are recorded. in certain cases the serotonergic syndrome with manifestations of such symptoms as a hyperthermia, rigidity, a myoclonus, vegetative dysfunction with a possibility of sudden disturbances of vital signs developed. mental disorders at the same time are shown by nonsense, irritability and the significant agitation progressing to a condition of a delirium and a coma. therefore sertraline cannot be applied combined with Mao's inhibitors or for 14 days after the termination of a course of treatment Mao's inhibitors. also treatment by Mao's inhibitors should not be begun earlier than in 14 days after the end of treatment with sertraline.

Other serotonergic means. The combined use of sertraline and other means stimulating serotonergic neuromediation, in particular tryptophane, a fenfluramin or 5-NT-agonistov needs to be carried out with care and if there is an opportunity, it should be excluded (in view of risk of pharmakodinamichesky interaction).

Transition from selective serotonin reuptake inhibitors, antidepressants or antiobsessivny drugs. There is a limited controlled experience of calculations of optimum time of switching from selective serotonin reuptake inhibitors, antidepressants or antiobsessivny medicaments to sertraline. The care is required upon transition, in particular from such for a long time operating medicaments as fluoxetine. Washing away period duration for transition from one selective serotonin reuptake inhibitor to another is not established.

Strengthening of maniacal/hypomaniacal manifestations. According to dolitsenzionny data, strengthening of maniacal/hypomaniacal manifestations was noted approximately at 0.4% of the patients accepting sertraline and in insignificant quantity — at the patients with big affective disorders applying other licensed antidepressants and antiobsesivny means.

Convulsive attacks. Spasms are a potential complication of therapy by antidepressants and antiobsessivny means. Spasms were noted approximately at 0.08% of the patients accepting sertraline within therapy of a depression. At treatment by sertraline of panic disorders of cases of a spasm it is not recorded. In all these cases the causal interrelation with therapy by sertraline is improbable. As use of sertraline was not investigated at patients with convulsive pathology, patients should not appoint it with unstable epilepsy; at patients with controlled epilepsy it is required to apply sertraline with care and under control. It is necessary to cancel use of medicament at development of spasms.

Suicide. Patients with a depression are inclined to attempts of a suicide which can restrain before emergence of significant remission. Therefore at early stages of treatment the patients have to be under fixed observation of the doctor.

Considering an established fact of frequent simultaneous development of obsessivno-compulsive disorders and a depression, panic disorders and depression, post-traumatic stress disorders and depression, similar cautions should be considered at treatment of patients with obsessivno-compulsive disorder, panic disorders and post-traumatic stress disorders.

Use in a liver failure. Sertraline biotransformutsya intensively in a liver. The multidosed pharmacokinetic research at patients with moderate stable cirrhosis showed lengthening of T _½ and approximately three times the big sizes AUC and C _max in blood plasma in comparison with healthy patients. Reliable divergences in parameters of linking with proteins of blood plasma at these two groups it is not established. The care at use of sertraline for patients with liver pathology is required. In abnormal liver functions it is necessary to lower a dose or to take the medicament less often.

Use in a renal failure. Sertraline biotransformutsya intensively in an organism. With urine in an invariable look only the insignificant amount of medicament is removed. In researches at patients with degree of a renal failure from easy to average (clearance of creatinine — 30–60 ml/min.) or from average to heavy (clearance of creatinine — 10–29 ml/min.) multidose pharmacokinetic parameters (AUC _0-24 and the C _max ) essentially did not differ from control. Half-life periods were similar and any differences in linking with proteins of blood plasma in all studied groups is not revealed. Data of researches demonstrate that, in view of low indicators of removal of sertraline kidneys, the dose of medicament can be not adjusted depending on degree of a renal failure.

Use during pregnancy and feeding a breast

due to the lack of clinical data medicament is appointed during pregnancy only when the expected advantage for mother exceeds potential risk for a fruit.

due to the lack of data on use of medicament during feeding by a breast for treatment breastfeeding should be stopped.

to Women of reproductive age at intake of sertraline needs to apply appropriate means of contraception.

Children

Data relatively of use of sertraline for children under 6 years are absent therefore it is not necessary to appoint Serlift to patients of this age group.

Ability to influence speed of response at control of vehicles or work with other mechanisms

At use of medicament needs to refrain from control of vehicles and work with potentially dangerous mechanisms

Interaction

Mao's Inhibitors. contraindicated combined use of sertraline together with Mao's inhibitors (see special instructions).

Other serotonergic means (see. Special INSTRUCTIONS).

Transition from selective serotonin reuptake inhibitors, antidepressants or antiobsessivny medicaments (see. Special INSTRUCTIONS).

Pimozidum. The increased concentration of Pimozidum is shown in a research of the combined use of a single low dose of Pimozidum (2 mg) and sertraline. This indicator was not followed by changes on the ECG.

Considering that the mechanism of this interaction is unknown, and a narrow framework of the therapeutic index of Pimozidum, the combined use of sertraline and Pimozidum it is contraindicated.

Depressants of central nervous system and ethanol. The combined use of sertraline (200 mg/days) did not exponentiate influence of ethanol, carbamazepine, a haloperidol or Phenytoinum on cognitive and psychomotor activity at healthy faces, however the concomitant use of sertraline and alcohol intake is not recommended.

Lities. The combined intake of sertraline and lithium authentically does not change lithium pharmacokinetics, however raises a tremor in comparison with placebo that demonstrates possible pharmakodinamichesky interaction. At simultaneous use of sertraline and medicaments of lithium which can influence serotonergic neuromediation it is necessary to provide the corresponding control.

Phenytoinum. Long intake of sertraline of 200 mg/days does not cause clinically significant oppression of metabolism of Phenytoinum. Despite this, it is necessary to recommend carrying out monitoring of concentration of Phenytoinum in blood plasma throughout the initial stage of therapy by sertraline with the corresponding dose adjustment of Phenytoinum. Besides, the combined use of Phenytoinum can cause decrease in concentration of sertraline in blood plasma.

Sumatriptan. There are data of single observations at a post-license stage concerning development of weakness, hyperreflexia, a diskoordination, nonsense, uneasiness and agitation in patients at the combined use of sertraline and a sumatriptan. If simultaneous treatment by sertraline and sumatriptany is necessary, it is necessary to provide the corresponding control.

Means, contacting proteins of blood plasma. As sertraline contacts proteins of blood plasma, it is necessary to consider a possibility of interaction with other means which also contact proteins of blood plasma. However in three formal researches of interaction with diazepam, tolbutamide and warfarin of influence of sertraline on linking of these means with proteins of plasma noted.

Warfarin. The combined use of sertraline of 200 mg/days and warfarin led to insignificant, but statistically reliable increase in a prothrombin time. The clinical value of this phenomenon is not found out. Therefore constant control of indicators of a prothrombin time at the beginning or at the end of treatment is required by sertraline.

Interaction with other means. Formal researches of interaction of sertraline with other medicaments are conducted. The combined use of sertraline of 200 mg/days and diazepam or tolbutamide led to insignificant, but statistically reliable changes of some pharmakokinetichny parameters. The combined use with Cimetidinum is the reason of significant decrease in clearance of sertraline. The clinical value of this phenomenon is not found out. Sertraline does not affect the β-blocking properties of atenolol. Any interaction at simultaneous use of sertraline of 200 mg/days and glibenclamide or digoxin is not revealed.

Electroconvulsive therapy. The clinical trials directed to studying possible risk or advantage of the combined use of electroconvulsive therapy and sertraline it was not carried out.

Means which are metabolized with the participation of P450 cytochrome (CYP) 2D6. Drugs of antidepressants have different potential concerning oppression of activity of an isoenzyme of P450 2D6 cytochrome. The clinical value of this phenomenon depends on extent of oppression and therapeutic coefficient of medicaments which are used combined. Substrates of P450 2D6 cytochrome with a narrow framework of the therapeutic index include tricyclic antidepressants and class 1C of antiarrhytmic means, in particular a propafenon and a flekainid. In formal researches of interaction the long intake of sertraline in a dose of 50 mg/days led to the minimum increase (on average for 23–37%) equilibrium concentration of desipramine (a marker of activity of an isoenzyme P450 2D6 cytochrome) in blood plasma.

Means which are metabolized with the participation of other enzymes of P450 cytochrome (CYP 3A3/4, CYP 2C9, CYP 2C19, CYP 1A2):

• P450 3A3/4 cytochrome. The research of interaction in vivo demonstrates that long intake of sertraline of 200 mg/days does not suppress CYP P450 cytochrome 3A3/4-dependent 6-β-гидроксилирование endogenous cortisol or carbamazepine metabolism, or a terfenadina. Besides, long intake of sertraline in a dose of 50 mg/days does not suppress P450 cytochrome 3A3/4-dependent metabolism of an alprazolam. Results of these researches demonstrate that sertraline is not clinically significant inhibitor of P450 3A3/4 cytochrome;
• P450 2C9 cytochrome. The practical lack of clinically significant influence of sertraline in a dose of 200 mg/days on concentration of tolbutamide, Phenytoinum and warfarin in blood plasma demonstrates that sertraline is not clinically significant inhibitor of P450 2C9 cytochrome;
• P450 2C19 cytochrome. The practical lack of clinically significant influence of sertraline in a dose of 200 mg/days on concentration of diazepam in blood plasma demonstrates that sertraline is not clinically significant inhibitor of P450 2C19 cytochrome;
• P450 1A2 cytochrome. The researches in vitro demonstrate that sertraline has very insignificant potential concerning oppression of P450 1A2 cytochrome.

Overdose

Sertraline has a wide range of safety at overdose. cases of overdose of medicament at its reception in a dose to 13.5 g are recorded; death at overdose, mainly in a combination with other means and/or alcohol. thus, each case of overdose needs intensive care. symptoms of overdose include serotoninzavisimy side effects, in particular drowsiness, gastrointestinal disturbances (including nausea and vomiting), tachycardia, a tremor, agitation, dizziness; in isolated cases — to whom.

Treatment: support of passability of airways, adequate level of ventilation and oxygenation. Intake of activated carbon which can be applied as depletive can be more effective, than gastric lavage. It is not recommended to cause vomiting. It is necessary to provide monitoring of vital signs and warm activity and symptomatic and also maintenance therapy. Considering the considerable volume of distribution of sertraline, such measures as stimulation of a diuresis, dialysis, hemoperfusion or a replaceable hemotransfusion are inefficient. Specific antidote does not exist.

Storage conditions

At a temperature up to 25 °C in original packing.