Misol

General characteristics. Structure:

Active ingredient: 55,954 mg or 111,908 mg of sertraline of a hydrochloride that 50 mg or 100 mg of sertraline respectively are equivalent.

Excipients: lactoses monohydrate (38.830 mg or 77.660 mg), sodium of a kroskarmelloz (3.000 mg or 6.000 mg), PVP K30 (Povidone) (2.625 mg or 5.250 mg), aerosil 200 (1.556 mg or 3.112 mg), cellulose microcrystallic PH 102 (46.535 mg or 93.070 mg), magnesium stearate (1.500 mg or 3.000 mg).

Structure of a film cover No. 1 (5.000 or 10.000 mg): Sepifilm LP 770: gidroksipropilmetiltsellyuloz (E464), cellulose microcrystallic (E460), stearic acid (E570), titanium dioxide (E171).

Pharmacological properties:

Pharmacodynamics. The mechanism of effect of drug MISOL is connected with inhibition of neyronalny serotonin reuptake (5HT). In clinical doses sertraline blocks serotonin reuptake in thrombocytes of the person. Drug is specific inhibitor of neyronalny serotonin reuptake and exerts very weak impact on the return capture of noradrenaline and dopamine.

Has no affinity to adrenergic (an alpha - 1, an alpha - 2, a beta), cholinergic, GAMK-ergichesky, dofaminergichesky, gistaminergichesky, serotonergic (5HT 1A, 5HT 1B, 5HT 2) or to benzodiazepine receptors. Prolonged use leads to decrease of the activity of noradrenalinovy receptors of a brain; other clinically effective antidepressive and antiobsessivny drugs give similar effect. Sertraline does not inhibit a monoaminooxidase.

Does not cause physical and mental dependence.

Pharmacokinetics. At sertraline reception to a dose from 50 to 200 mg once a day within 14 days concentration of sertraline in plasma reaches peak (Cmax) in 4,5 - 8,4 h after reception. The average elimination half-life of sertraline makes about 26 h. Constant level of sertraline in a blood plasma is reached approximately in 1 week of treatment by drug (reception of a dose once a day). Cmax and the area under curve (AUC) of sertraline are proportional to a dose from 50 to 200 mg. According to an elimination half-life at repeated reception of sertraline in a dose from 50 to 200 mg approximately twofold cumulation of drug in comparison with a single dose is observed.

At administration of drug during food the area under a curve slightly increases, and Cmax – increases by 25% before achievement of time of peak plasma concentration (Tmax), and then decreases from 8 h to 5,5 h.
Sertraline biotransformirutsya actively at the first passing through a liver. Main way of metabolism of N-desmetilirovaniye sertraline. N-desmetilsertralin – the main metabolite found in plasma with an elimination half-life of 62 h to 104 h  N-desmetilsertralin considerably concedes on activity to sertraline.

Sertraline and N-desmetilsertralin are exposed to oxidizing deamination and consecutive recovery, a hydroxylation and glyukuronidny conjugation.  About 40 - 45% of the entered radioactive sertraline are removed with urine in 9 days. Invariable sertraline is not found in urine. About 40 - 45% of the entered radioactive sertraline are removed with a stake, including 12 - 14% of invariable sertraline.

Sertraline contacts proteins (98%) in concentration from 20 to 500 ng/ml. The plasma clearance at elderly patients is 40% lower, than at young people.

Indications to use:

- treatment of big depressive episodes, prevention of a recurrence of big depressive episodes;
- the obsessivno-compulsive frustration (OCF) at adults and children since 6 years;
- panic frustration with or without agarofobiya;
- posttraumatic stressorny frustration (PTSR);
- social alarming frustration.

Route of administration and doses:

MISOL is appointed inside, once a day in the morning or in the evening. Pill MISOL can be taken irrespective of meal.

Initial dose. Depression and ROC: treatment of MISOLOM it is necessary to begin 50 mg/days with a dose.

Panic frustration, PTSR and social alarming frustration: 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 alarming frustration: at insufficient effect of use of MISOLA 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 of MISOLOM it is necessary to begin 50 mg/days with a dose. 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 MISOLA pharmacokinetic profile was 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. MISOL 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.

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.

Features of use:

MISOL should not be applied in a combination with MAO inhibitors or within 14 days after the treatment termination by MAO inhibitor. Similarly, it is possible to appoint MAO inhibitor not earlier, than, at least, in 14 days after cancellation МИСОЛа.

Other serotonergic means – it is necessary to be careful at co-administration of sertraline with other drugs strengthening serotonergic neurotransmission such as, tryptophane, фенфлюрамин or 5-NT-agonisty. Similar joint appointment at an opportunity has to be excluded, considering probability of pharmakodinamichesky interaction.

During treatment drug MISOL forbids alcohol intake and other alcohol-containing drugs.

In the researches conducted at children and adults with a depression and other mental disturbances it is established that antidepressants increase risk of development of suicidal thoughts and behavior. In this regard all patients accepting antidepressants have to be carefully inspected regarding clinical deterioration, tendency to suicides and unusual changes in behavior, especially within the first several months of a course of medicinal therapy or during correction of a dose of drug both increase, and reduction. The decision which is usually made in that case leads to change of the therapeutic mode up to drug withdrawal, especially at such patients at whom considerable deterioration in a depression is observed.

Such symptoms as concern, agitation, acute alarming state with reaction of panic, sleeplessness, irritability, hostile aggression, impulsiveness, an akathisia (psychomotor concern), a hypomania, a mania were found in the patients with a depression and other mental disorders accepting antidepressants. Though the causal relationship between manifestations of these symptoms and deterioration in a depression or suicidal impulses is not established yet, such symptoms can already be predecessors of suicidal manifestations.

The family and the personnel which are looking after patients with a depression or other mental disorders, accepting antidepressants, have to be in advance warned about need to watch carefully patients, especially at manifestation of symptoms of agitation, irritability, unusual changes in behavior and the symptoms stated above and immediately to note them.

During therapy of the patients with a depression inclined to a suicide, within the first several weeks it can not be observed noticeable improvement in this connection such patients need to be observed carefully. The recipe on MISOL has to be written out in the minimum quantity in order to avoid risk of overdose.

If the decision to stop treatment was made, medicinal therapy has to be minimized so quickly as far as it is possible, but with confidence that such sudden cancellation will not be connected with development of certain somatic and psychopathological symptoms.

Depressions of various etiology can be initial display of bipolar disorders. It is usually observed (though it is not established in check tests) when therapy by antidepressants of separate frustration can lead to increase in probability of development of the mixed / maniacal frustration in the patients inclined to bipolar psychoses. In this regard before an initiation of treatment antidepressants patients with symptoms of a depression have to be carefully inspected for definition of existence of risk of development of bipolar disorders; such inspection has to include the detailed psychiatric anamnesis, including data on family cases of a suicide, bipolar disorders and depressions. MISOL is not shown for treatment of bipolar disorders.

The safety profile at treatment by drug MISOL is identical at patients with a depression of various etiology, ROC, panic frustration, PTSR and social phobia.

Drug MISOL was not studied at patients with a convulsive syndrome therefore it is necessary to avoid its use for patients with unstable epilepsy, and patients with controlled epilepsy should be observed carefully during treatment. At emergence of spasms in all cases drug needs to be cancelled. 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.

MISOL promotes reduction in serum of uric acid approximately for 7%. The clinical importance of such weak uricosuric effect is unknown.

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, rigidity of muscles, 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.

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 with it is long the operating 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.

Activation of a mania/hypomania. 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.

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 symptomatic 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.

Withdrawal. At the treatment termination by sertraline development of a withdrawal, especially is possible if the termination is sharp. The risk of development of a withdrawal can depend on several factors, including duration of therapy and a dose, the period of reduction of a dose. It was reported about cases of development of the following symptoms after the termination of treatment of SIOZS: dizziness, touch disturbances, including paresthesias, sleep disorders, including sleeplessness, concern, nausea and/or vomiting, a tremor, the increased perspiration, a headache, diarrhea, emotional instability, irritability and visual frustration. Generally some patients had symptoms of moderate weight, however, they were serious intensity. Symptoms usually pass during the first several days after the treatment termination. Patients who carelessly missed reception of the next dose of drug have very rare messages of signs of a withdrawal. In order to avoid a withdrawal the dose of sertraline has to decrease gradually within several weeks or months.

Schizophrenia. At the patients having schizophrenia psychotic signs can worsen.

Diabetes mellitus. At patients with diabetes at use of SIOZS it is regularly necessary to check glucose level in blood. If necessary dose adjustment of insulin or peroral hypoglycemic means has to be carried out.

Akathisia / psychomotor concern. Use of sertraline was connected with development of psychomotor concern which can clinically be similar to the akathisia which is characterized subjectively unpleasant or the disturbing restlessness and requirement to move, often accompanied inability to sit or stop. These symptoms are most probable within the first several weeks after administration of drug. To patients at whom these signs, increase in a dose of drug develop can be dangerous.

Liver failure. 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. At patients with a chronic liver failure of an easy current at administration of drug of MISOL the decrease in clearance leading to increase in an elimination half-life was observed. Therefore it is necessary to use drug MISOL at patients with liver diseases with care. If drug is appointed 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.

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 with a renal failure (clearance of creatinine of 10-29 ml/min.) pharmacokinetic parameters (AUC0-24 and Cmax) drug 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 excretion of sertraline, correction of its dose depending on expressiveness of a renal failure is not required. 

Use in pediatrics. ROC the only indication at which appoint MISOL to children. The profile of safety is comparable to that at treatment of adult patients with SURROUNDING. Efficiency of administration of drug of MISOL at children with a depression or panic frustration is not established in controlled researches. The same as at reception of other SIOZS, reception МИСОЛа causes a loss of appetite and loss of weight. At long purpose of SIOZS children need to control periodically during treatment the body weight and growth of patients. Safety and efficiency of administration of drug at children are younger than 6 years is not established.

Use for elderly people. About 800 elderly people took part in clinical tests of sertraline 65 or 75 years are more senior. Patients of elderly and younger age had an identical profile and frequency of side reactions.

Pregnancy and lactation. There are no controlled results of use of drug MISOL for pregnant women therefore it is possible to appoint drug at pregnancy only if the expected advantage for mother exceeds potential risk for a fruit.

It is unknown whether it is found and if it is found out, then in what quantity, sertraline or its metabolites in breast milk. If purpose of drug is necessary, then breastfeeding should be stopped.

Features of influence on ability to manage vehicles or other potentially dangerous mechanisms. Researches showed that drug MISOL does not exert impact on psychomotor function. Nevertheless, antidepressive or antiobsessivny means can worsen the intellectual or physical activity necessary for performance of potentially dangerous functions like driving of the car or control of mechanisms what it is necessary to warn the patient about. MISOL should not be appointed with benzodiazepines or other tranquilizers to the drivers or persons managing potentially dangerous mechanisms.

Side effects:

Very often:
- sleeplessness, drowsiness, dizziness, headache;
- nausea, dryness in a mouth, diarrhea;
- disturbance of an ejaculation;
- fatigue.
Often:
- pharyngitis;
- appetite loss, increase in appetite;
- depression, depersonalization, nightmares, alarm, agitation, decrease libido, bruxism, paresthesia, tremor, hypertension, dysgeusia, disturbance of attention;
- visual disturbances, tinnit;
- heartbeat, inflows, yawning;
- abdominal pain, vomiting, dyspepsia, meteorism, lock;
- skin rash, hyperhidrosis;
- mialgiya;
- sexual dysfunction, erectile dysfunction.
Infrequently:
- upper respiratory tract infections, rhinitis;
- hallucinations, euphoria, apathy, disturbance of thinking;
- spasms, involuntary muscular contractions, incoordination, hyperkinesia, amnesia, hypesthesia, alalias, confusion of consciousness hypokinesia, hypotonia, hyporeflexia;
- postural dizziness, migraine, ear pain;
- tachycardia, hypertensia;
- bronchospasm, диспноэ, cough, эпистаксис;
- esophagitis, dysphagy, hypersalivation, eructation;
- periorbital hypostasis, purpura, alopecia, cold sweat, xeroderma, small tortoiseshell;
- osteoarthritis, muscular weakness, dorsodynia, convulsive twitchings of muscles;
- nocturia, ischuria, polyuria, pollakiuria, frustration of an urination;
- vaginal bleeding, disturbance of sexual function at women;
- indisposition, fever, temperature increase, thirst;
- increase in body weight, decrease in body weight.
Seldom:
- diverticulitis, gastroenteritis;
- average otitis;
- neoplasm;
- limfoadenopatiya;
- hypercholesterolemia, hypoglycemia;
- medicinal dependence, psychotic frustration, aggression, paranoid reaction, suicide thoughts / behavior, hypomania, mania, premature ejaculation;
- coma, choreoathetosis, dyskinesia, hyperesthesia;
- disturbance of a slezootdeleniye, scotoma, diplopia, photophobia, hyphema, mydriasis, exophthalmos, ptosis, conjunctivitis, nystagmus;
- myocardial infarction, bradycardia, cardial frustration, peripheral ischemia;
- laryngospasm, hyperventilation, hypoventilation, stridor, dysphonia, hiccups;
- stomatitis, language ulcers, a hyperplasia of gums, disturbances from teeth, the aggravated caries, a glossitis, a melena;
- abnormal liver functions;
- dermatitis, violent dermatitis, follicular rash, disturbance of structure of hair, abnormal smell of skin, acne, eczema, hypertrichosis, decolouration of skin, pustular rash;
- hyperacusia;
- disturbances from bones;
- urine incontience;
- menorrhagia, atrophic vulvovaginitis, balanoposthitis, genital allocations, priapism, galactorrhoea;
- hernia;
- decrease in medicinal tolerance, gait disturbance;
- increase in activity of ALT, nuclear heating plant;
- vazodilatation.
With an unknown frequency:
- leukopenia, thrombocytopenia, anemia;
- anaphylactoid reactions, allergic reactions;
- giperprolaktinemiya;
- hypothyroidism, syndrome of inadequate secretion of antidiuretic hormone;
- hyponatremia, diabetes mellitus, hyperglycemia;
- paranoia, motive frustration, including extrapyramidal symptoms, such as a hyperkinesia, a hypertension, a gnash teeth, gait disturbance, синкопэ;
- a serotonergic syndrome or the malignant antipsychotic syndrome in certain cases connected with combined use of serotonergic medicines that includes agitation, concern, sweating, diarrhea, fever, hypertensia, tachycardia, rigidity, an akathisia, psychomotor disturbances, a bespokoynost, vision disorders;
- gastrointestinal bleedings, hamaturia;
- pancreatitis;
- jaundice, liver failure;
- Stephens-Johnson's syndrome, epidermal necrolysis, Quincke's disease, face edema, photosensitivity, itch;
- arthralgia, muscular spasms;
- gynecomastia, disturbances of a menstrual cycle;
- peripheral hypostases;
- dysfunction of thrombocytes.

Interaction with other medicines:

Combined use of drug MISOL with:
- the drugs contacting proteins of a blood plasma (for example, warfarin, digitoxin), can lead to shift in plasma concentration, shown in the form of side reaction in view of the fact that MISOL also strongly contacts proteins of a blood plasma. In researches of comparison of a prothrombin time and AUC (the area under a curve) (0-120 h) at warfarin reception (in a dose of 0,75 mg/kg) to and on the expirations of 21 days after sertraline reception (50-200 mg/days) or placebo, increase in a prothrombin time by 8% of rather basic line for the sertraline compared to 1% reduction for placebo was observed (р <0,02). In this regard it is necessary to watch carefully an indicator of a prothrombin time at the beginning of therapy by drug MISOL or after its cancellation;
- Cimetidinum, causes essential increase in AUC (50%), Cmax (24%) and an elimination half-life (26%) of sertraline at their combined use. Clinical value of these changes is unknown;
- with diazepam reduction of clearance of sertraline by 32% of rather basic line of diazepam is observed. Clinical value is unknown;
- lithium drugs, it is recommended to control plasma concentration of lithium at a concomitant use of sertraline and, if necessary, to adjust a dose of drugs of lithium.

Experience of clinical tests which purpose was a definition of the optimum time necessary for transfer of patients from reception of other antidepressive funds for sertraline is limited. It is necessary to be careful upon such transition, especially from drugs of long action, for example, from fluoxetine: the necessary interval between cancellation of one selective serotonin reuptake inhibitor (SSRI) and the beginning of reception of other similar drug is not established;
- with the drugs which are metabolized P450 2D6 (tricyclic antidepressants and antiarrhytmic drugs 1C of a class, such as пропафенон and флекаинид), MISOL, as well as many other antidepressants, inhibits biochemical activity of enzyme P450 2D6 cytochrome (debrizokvingidroksilaza) and at the expense of it can increase concentration in plasma of other drugs which biotransformirutsya by this enzyme;
- sumatriptany, 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 SIOZS and суматриптан are celebrated. Observation of patients who have corresponding clinical bases for a concomitant use of a sumatriptan and SIOZS is recommended (to tsitalopra, fluoxetine, флувоксамин, пароксетин);
- tricyclic antidepressants, extent of interaction of SIOZS with tricyclic antidepressants (TTsA) can cause the clinical problems depending on degree of inhibition and pharmacokinetics of SIOZS. However it is necessary to be careful at co-administration of TTsA and drug MISOL as the last can suppress metabolism of TTsA. At a concomitant use of TTsA and MISOL it is necessary to control plasma concentration of TTsA and to reduce TTsA dose;
- Tolbutamidum, MISOL causes considerable reduction (to 16% of the basic line) clearance of Tolbutamidum. MISOL slightly influences linkng with plasma proteins or the volume of distribution of Tolbutamidum, assuming that the lowered clearance – result of change of metabolism of drug. Clinical value of decrease in clearance of Tolbutamidum is unknown;
- atenololy, drug MISOL at a single dose in a dose of 100 mg does not exert impact on beta and adrenoceptor blocking activity of an atenolol;
- digoxin, reception of MISOL does not influence plasma concentration of digoxin and its renal clearance;
- with 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.
- with 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.
- with selective inhibitors of the return neyronalny 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.
- with medicines, oppressing the central nervous system and ethanol requires close attention, and also the use of the alcoholic drinks and drugs containing alcohol during treatment by sertraline is forbidden;
- with 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.
- with 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 an elimination half-life of antipyrine;
- with glibenclamide and digoxin: at administration of sertraline in a daily dose of 200 mg of medicinal interaction with these drugs it is not revealed.
- with Phenytoinum: prolonged use of sertraline in a dose of 200 mg/days does not make clinically significant impact 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.

Contraindications:

- hypersensitivity to sertraline or other components of drug;
- neurologic disturbances (including delay of intellectual development);
- maniacal states;
- epilepsy;
- decrease in body weight;
- simultaneous use with inhibitors of a monoaminooxidase (IMAO) and with Pimozidum;
- intolerance of a galactose, insufficiency of lactase of Lapp, malabsorption of a glucose/galactose;
- pregnancy and period of a lactation;
- children's age up to 6 years.

Overdose:

Overdose cases at monotherapy by drug MISOL in a dose to 6 g were reported. Death cases at overdose of drug MISOL in combination with other medicines and/or alcohol are known.

Symptoms: uneasiness, drowsiness, changes on an ECG, a mydriasis, nausea, vomiting, tachycardia.

Treatment: there is no specific antidote. Ensuring normal passability of respiratory tracts (oxygenation and ventilation of the lungs), a gastric lavage, purpose of emetic HP, absorbent carbon with sorbitol is required. Control of function of heart, liver and other vitals and carrying out a symptomatic and maintenance therapy are necessary.

The artificial diuresis, dialysis, hemoperfusion and exchange hemotransfusion are ineffective.

Storage conditions:

To store at a temperature not above 25 °C, in the dry, protected from light place. Period of storage 2 years.

Issue conditions:

According to the recipe

Packaging:

Tablets, film coated 50 mg, 100 mg. On 10 or 14 tablets (for a dosage of 50 mg) and 5 or 7 tablets (for a dosage of 100 mg) in a blister strip packaging from a film of white not transparent PVH/PE/PVDH and aluminum foil.

On 3 (on 10 tablets) or 1 or 2 (on 14 tablets) planimetric packaging (for a dosage of 50 mg); 2 or 4 (on 7 tablets) or 6 planimetric packagings (on 5 tablets) (for a dosage of 100 mg) together with the instruction on a medical use in the state and Russian languages place in a pack cardboard with the hologram of firm – producer.