The instruction for medical use
of MISOL 50 medicine
the Trade name
of MISOL 50
of MISOL 100
the International unlicensed
name Sertraline Dosage Form
of the Tablet, film coated 50 mg, 100 mg
One tablet contains
active agent – sertraline a hydrochloride of 55.954 mg or 111.908 mg, 50.00 mg and 100.000 mg of sertraline respectively,
excipients are equivalent: lactoses monohydrate, sodium of a kroskarmelloz, PVP K30 (povidone), aerosil 200, cellulose microcrystalline PH 102, magnesium stearate,
structure of film cover No. 1:
Sepifilm LP 770: hydroksipropilmetiltsellyuloz (E464), microcrystalline cellulose (E460), stearic acid (E570), titan dioxide (E171).
OpisanieTabletki, film coated white color, an oval form, biconvex and with risky on one party (for a dosage of 50 mg).
Tablets, film coated white color, oblong shape, biconvex and with risky on one party
(for a dosage of 100 mg).
of Serotonin of the return capture inhibitors selection.
The code of automatic telephone exchange N06AB06
Pharmacokinetics At properties administration of drug of MISOL in a dose from 50 to 200 mg once a day within 14 days the concentration of sertraline in plasma reaches peak (Cmax) in 4.5 – 8.4 h after reception. Average elimination half-life of sertraline makes about 26 h. Constant level of sertraline in blood plasma is reached approximately in 1 week of drug treatment (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 elimination half-life at repeated intake of sertraline in a dose from 50 to 200 mg approximately twofold cumulation of drug in comparison with single dose is observed. At administration of drug at meal time 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 sertraline-N-desmetilirovaniye. N-desmetilsertralin – the main metabolite found in plasma with 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 restoration, 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.
the Mechanism of effect of drug MISOL is connected with inhibition of neuronalny serotonin reuptake (5HT). In clinical doses of MISOL blocks serotonin reuptake in thrombocytes of the person. MISOL is powerful and specific inhibitor of neuronalny serotonin reuptake and has 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 1 of A, 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. MISOL does not inhibit a monoaminooxidase.
Sertraline does not cause physical and mental dependence.
– depressions of various etiology
– the obsessivno-compulsive disorders (OCD)
– panic disorders
– posttraumatic stressorny disorders (PTSD)
– premenstrual dysphoric disorders (PMDR)
– a social phobia
the Route of administration and a dosage
of the Depression of various etiology and obsessivno-compulsive disorders
the Recommended initial dose of 50 mg/days.
Panic disorders, posttraumatic stressorny disorders and a social phobia
the Recommended initial dose of 25 mg/days which is increased in 1 week up to 50 mg/days. In spite of the fact that the interrelation between a dosage of drug and its efficiency in depressions of various etiology, ROC, panic disorders, a PTSD or a social phobia is not established yet, at the patients taking the drug in a dose from 50 mg to 200 mg a day at conduct of clinical trials the efficiency of the MISOL drug treatment at therapy of the above-stated states was observed. Therefore the dosage of drug of 50 mg accepted once a day is recommended as an initial therapeutic dose. At insufficient effect of use of MISOL in a dose of 50 mg/days it is possible to increase a daily dose to 200 mg/days.
Premenstrual dysphoric disorders
Therapy usually begin with a dose 50 mg/days as throughout a menstrual cycle, and being interrupted during a lyutealny phase of a menstrual cycle, depending on a medical prescription. At insufficient effect of use of drug in a dose of 50 mg/days it is possible to increase a daily dose to 150 mg/days throughout a menstrual cycle or up to 100 mg/days during a lyutealny phase of a menstrual cycle. MISOL needs to be accepted once a day, in the morning or in the evening.
For achievement of optimum therapeutic effect the dose of drug has to be reduced to the minimum effective level. During long maintenance therapy the dose has to remain at the minimum effective level with the subsequent adjustment depending on therapeutic effect.
Use for children
safety and efficiency of drug at children with ROC Is established (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 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 up to 200 mg/days as required. In clinical trials at patients with a depression and ROC aged from 6 up to 17 years it was shown that the pharmacokinetic profile of sertraline 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.
Elimination half-life of the MISOL active agent – sertraline makes about 1 day therefore change of a dose has to happen to an interval not less than 1 week.
– hypoglycemic reactions (dizziness, sonitus, pallor, cold sticky skin, trembling, the increased perspiration, nausea, vomiting, hyperaemia, a syncope), the increased salivation, dryness in a mouth, thirst, loss of appetite, a hiccups, a glossitis, a hyperplasia of gums, stomatitis, including aphthous stomatitis, the aggravated caries, dyspepsia, a dysphagy, an esophagitis, a gastroenteritis, a melena
– decrease in body weight
– insomnia, drowsiness, fever
– a mydriasis, an exophthalmos, a ptosis, glaucoma, conjunctivitis, ear pain
– a gynecomastia, disturbances of a menstrual cycle, a dysmenorrhea, intermenstrual bleeding, disturbance of sexual function at men, a priapism
– a stethalgia, hypertensia, tachycardia, hypotension, a peripheral ischemic syndrome
– a gipoesteziya, a hyperesthesia, convulsive movements, confusion of consciousness, a hyperkinesia, an ataxy, migraine, abnormal coordination, a systremma, unusual gait, a nystagmus, a hypokinesia, a dysphonia (hoarseness), dyskinesia, hypotonia, a choreoathetosis, hyporeflexia
– the itching, an acne, urticaria, swelled, an alopecia, xeroderma, erythematic rash, reaction of photosensitivity, papular rash, follicular rash, eczema, dermatitis, contact dermatitis, bullous rash, a hypertrichosis (hypertrichosis), decolouration of skin, pustulous rash
– a hyperacusia
– an abnormal liver function
– myalgia, an arthralgia, dystonia, arthrosis, a spasm of muscles, muscle
weakness, a dorsodynia
– unusual dreams, amnesia, apathy, an asthenia, euphoria, paranoid reaction, hallucinations, aggressive reaction, nonsense, suicidal thoughts, illusion, a hypomania and a mania
– rhinitis, cough, dispnoe, upper respiratory tract infections
is rare (about 0.8%)
– reversible symptomatic increase in activity of plasma transaminases (nuclear heating plant and ALT) and other liver enzymes: it is usually observed within the first from 1 to 9 weeks of treatment and at once decreases after drug withdrawal
– insignificant increase in the general cholesterol (about 3%), triglycerides (about 5%) and reduction of uric acid in serum (about 7%), however these changes are not of clinical importance
of the Contraindication
– hypersensitivity to sertraline or other components of drug
– the patients receiving inhibitors of a monoaminooxidase (MAO)
– neurologic disturbances (including a delay of intellectual
– maniacal states
– decrease in body weight
– pregnancy and the period of a lactation
– children’s age up to 6 years
Combined use of drug MISOL with:
– the drugs contacting proteins of 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 blood plasma. In researches of comparison of a prothrombin time and AUC (the area under a curve) (0-120 h) at intake of warfarin (in a dose of 0.75 mg/kg) to and on the expirations of 21 days after intake of sertraline (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 (r
– Cimetidinum, causes significant increase in AUC (50%), Cmax (24%) and elimination half-life (26%) of sertraline at their combined use. The clinical value of these changes is unknown,
– the means influencing central nervous system (for example, diazepam) observe reduction of clearance of sertraline by 32% of rather basic line of diazepam. The 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 trials which purpose was a definition of the optimum time necessary for the translation of patients from reception of other antidepressive means effective at treatment of depressions of various etiology, ROC, panic disorders, a PTSD, premenstrual dysphoric disorders and a social phobia on sertraline is limited. It is necessary to be careful upon such transition, especially from drugs of long action. The necessary interval between cancellation of one selective serotonin reuptake inhibitor (SSRI) and the beginning of intake 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 propafenon and flekainid), 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 sumatriptan are celebrated. Observation of patients who have corresponding clinical bases for a concomitant use of a sumatriptan and SIOZS (to tsitalopra, fluoxetine, fluvoksamin, paroksetin) is recommended,
– tricyclic antidepressants, extent of interaction of SIOZS with tricyclic antidepressants (TCA) 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 TCA and drug MISOL as the last can suppress metabolism of TCA. At a concomitant use of TCA and MISOL it is necessary to control plasma concentration of TCA and to reduce TCA dose,
– tolbutamide, MISOL causes considerable reduction (to 16% of the basic line) clearance of tolbutamide. MISOL slightly influences linking with plasma proteins or tolbutamide distribution volume, assuming that the lowered clearance – result of change of metabolism of drug. The clinical value of lowering of clearance of tolbutamide is unknown,
– atenolol, drug MISOL at single dose in a dose of 100 mg
does not affect beta and adrenoceptor blocking activity of atenolol,
– digoxin, reception of MISOL does not influence a plasma kontsen-
a tration of digoxin and its renal clearance.
instructions 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 MISOLA.
During the MISOL drug treatment the intake of alcohol and other alcohol-containing drugs is forbidden.
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 examined 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 disturbing condition with reaction of panic, insomnia, 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 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.
The prescription on MISOL has to be written during therapy of the patients with a depression inclined to a suicide, within the first several weeks can not be observed noticeable improvement in this connection such patients need to be observed carefully. The prescription on MISOL has to be written 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 manifestation of bipolar disorders. It is usually observed (though it is not established in check tests) when therapy by antidepressants of separate disorders can lead to increase in a likelihood of developing the mixed / maniacal disorders at 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 examined for definition of presence of risk of developing 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.
Safety profile at the MISOL drug treatment is identical at patients with a depression of various etiology, ROC, panic disorders, a PTSD, premenstrual dysphoric disorders and a 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 appearance of spasms in all cases drug needs to be cancelled.
MISOL promotes reduction in serum of uric acid approximately for 7%. The clinical importance of such weak uricosuric effect is unknown.
In a liver failure
of MISOL it biotransformirutsya actively in a liver. At patients with a chronic liver failure of an easy course at administration of drug of MISOL the decrease in clearance leading to increase in 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 from the liver broken by function, it is necessary to discuss expediency of a dose decline or increase in an interval between administration of drug.
In a renal failure
Drug MISOL is exposed to active biotransformation therefore in not changed view with urine he is brought in insignificant quantity. At patients with an initial and moderate renal failure (clearance of creatinine of 20-50 ml/min.) and patients with a heavy renal failure (clearance of creatinine
Use in pediatrics
of ROC the only indication at which appoint MISOL to children. The efficiency of use of sertraline for children with ROC was proved when carrying out multicenter placebos – controlled researches. At the same time the profile of safety is comparable to that at treatment of adult patients with SURROUNDING. The efficiency of administration of drug of MISOL at children with a depression or panic disorders is not established in controlled researches. The same as at reception of other SIOZS, reception MISOLA 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 trials 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 a lactation
of Controlled results of use of drug MISOL for pregnant women are not present 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 prescribing of drug is necessary, then breastfeeding should be stopped.
Features of influence on ability to run vehicles or other potentially dangerous mechanisms
of the Research showed that drug MISOL does not affect psychomotor function. Nevertheless, antidepressive or antiobsessivny means can worsen the intellectual or physical activity necessary for performance of potentially dangerous functions of type of 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 operating potentially dangerous mechanisms.
overdose cases at monotherapy by drug MISOL in a dose up 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 the ECG, a mydriasis, nausea, vomiting, tachycardia.
Treatment: there is no specific antidote. Ensuring normal passability of airways (oxygenation and ventilation of the lungs), gastric lavage, purpose of emetic HP, activated carbon with sorbitol is required. Control of function of heart, liver and other vitals and performing symptomatic and maintenance therapy are necessary.
The artificial diuresis, dialysis, hemoperfusion and exchange blood transfusion are ineffective.
Form of release and packing
of the Tablet, film coated 50 mg: in blister strip packaging on 10 or 14 tablets, on 1 or 2 blister strip packagings on 14 tablets or 3 blister strip packagings on 10 tablets in a cardboard pack together with the instruction for use.
Tablets, film coated 100 mg: in blister strip packaging on 5 or 7 tablets, on 2 or 4 blister strip packagings on 7 tablets or 6 blister strip packagings on 5 tablets in a cardboard pack together with the instruction for use.
To Store storage conditions at a temperature not above 25 °C in the dry, protected from light place in own packing.
A period of storage
According to the prescription
by NOBEL Ilach Sanai ve A.Sh. Tidzharet, Turkey
JSC Nobel Almatinskaya Pharmatsevticheskaya Fabrika
the Republic of Kazakhstan
Almaty, Shevchenko St. 162 E Is packed.