Asentra, 50 mg, film-coated tablets, 28 pcs.

Composition and release form

in contour cell packages of 7 pcs.; 4 packs in a cardboard box.

Use of Asentra

Orally 1 time per day in the morning or evening. Depression The usual starting dose is 50 mg sertraline once daily. If necessary, the daily dose can be gradually increased by 50 mg (at intervals of at least 1 week) to a maximum daily dose of 200 mg. Obsessive states The initial dose is 50 mg of sertraline per day. If necessary, the daily dose can be gradually increased by 50 mg (at intervals of at least 1 week) to a maximum daily dose of 200 mg. Children aged 6 to 12 years are prescribed an initial dose of 25 mg 1 time per day. After a week, the dose can be increased to 50 mg of sertraline once a day. Doses in children over 12 years of age are similar to those in adults. Panic states The initial dose is 50 mg of sertraline per day. If necessary, the daily dose can be gradually increased by 50 mg (at intervals of at least 1 week) to a maximum daily dose of 200 mg. It is advisable to take the drug daily, at the same time, with or without food, with water. Tablets should not be crushed or chewed.

Pharmacodynamics

Mechanism of action. Sertraline is a specific serotonin (5-HT) reuptake inhibitor. It has a very weak effect on the reuptake of norepinephrine and dopamine. At therapeutic doses, sertraline blocks the uptake of serotonin into human platelets. It does not have stimulant, sedative or anticholinergic effects. Sertraline has no affinity for muscarinic (cholinergic), serotonergic, dopaminergic, adrenergic, histaminergic, GABA or benzodiazepine receptors.

The antidepressant effect is observed by the end of the second week of regular use of sertraline, while the maximum effect is achieved only after 6 weeks. Unlike tricyclic antidepressants, sertraline does not cause weight gain. Sertraline does not cause mental or physical drug dependence.

Pharmacokinetics

Absorbed into the gastrointestinal tract to a large extent, but slowly. Cmax in blood plasma is achieved 4.5–8.4 hours after taking the drug orally. The equilibrium concentration of sertraline in blood plasma is achieved within a week with a single daily dose. Bioavailability when taken with food increases by 25%, while the time to reach maximum concentration is shortened.

Distribution. The total protein binding of sertraline is 98%. Volume of distribution - >20 l/kg.

Metabolism and excretion. Sertraline undergoes extensive metabolism during its first passage through the liver, undergoing N-demethylation. Its main metabolite, N-desmethylsertraline, is less active than the parent compound.

Metabolites are excreted in urine and feces in equivalent quantities. About 0.2% of sertraline is excreted unchanged by the kidneys. T1/2 of the drug is 22–36 hours and does not depend on age or gender. For N-desmethylsertraline this figure is 62–104 hours.

T1/2 of sertraline and the area under the plasma concentration-time curve (AUC) increase with impaired liver function. Regardless of the severity of renal failure, the pharmacokinetics of sertraline does not change with its continuous use. Sertraline passes into breast milk. There is no data on its ability to pass through the hematoplacental barrier.

Sertraline is not dialysable.

Pharmacological properties of the drug Asentra

Antidepressant. Selective serotonin reuptake inhibitor in brain neurons. The uptake of norepinephrine and dopamine by neurons is practically not affected. The drug has no affinity for serotonin, dopamine, histamine, benzodiazepine, GABA, M-cholinergic and adrenergic receptors. When sertraline is taken orally in doses of 50–200 mg once a day for 14 days, the maximum plasma concentration is achieved after 4.5–8.5 hours. The average half-life in young and elderly individuals is 22–36 hours. Binding with blood plasma proteins - 98%, volume of distribution - 20 l/kg. Intensively metabolized during the first passage through the liver. The main metabolite found in the blood plasma (N-desmethylsertraline) is pharmacologically inactive. The half-life of N-desmethylsertraline ranges from 62 to 104 hours. It is excreted primarily in the form of metabolites through the intestines and urine in approximately equal amounts; less than 0.2% of the drug is excreted unchanged in the urine.

Contraindications

hypersensitivity to the active substance or other ingredients included in the drug;

combined use of sertraline and MAO inhibitors (monoamine oxidase). When replacing one drug with another, you should refrain from taking antidepressants for 14 days;

combined use of sertraline with tryptophan or fenfluramine;

unstable epilepsy;

pregnancy;

lactation period;

children under 6 years of age.

Carefully:

neurological disorders (including mental retardation);

manic states;

epilepsy;

liver and/or kidney failure;

weight loss;

children over 6 years of age.

Asentra, 50 mg, film-coated tablets, 28 pcs.

MAO inhibitors

. Severe complications have been observed with the simultaneous use of sertraline and MAO inhibitors (including selectively acting MAO inhibitors with a reversible type of action - selegiline and moclobemide). Serotonin syndrome may develop. Similar complications, sometimes fatal, occur when MAO inhibitors are prescribed during treatment with antidepressants that inhibit the neuronal uptake of monoamines or immediately after their withdrawal.

With the simultaneous use of selective neuronal reuptake inhibitors of serotonin and MAO inhibitors, the following occur: hyperthermia, rigidity, convulsions, myoclonus, lability of the autonomic nervous system (rapid fluctuations in the parameters of the respiratory and cardiovascular system), changes in mental status, including increased irritability, severe agitation, confusion consciousness, which in some cases can turn into a delirious state or coma.

Drugs that depress the central nervous system and ethanol.

The combined use of sertraline and substances that depress the central nervous system requires close attention, and the consumption of alcoholic beverages is also prohibited during treatment with sertraline.

Coumarin derivatives.

When they are co-administered with sertraline, a significant increase in PT is observed. In these cases, it is recommended to monitor PT at the beginning of treatment with sertraline and after its discontinuation.

Pharmacokinetic interaction

Sertraline binds to plasma proteins. Therefore, the possibility of its interaction with other protein-binding drugs (eg diazepam, tolbutamide and warfarin) must be taken into account.

Cimetidine.

Concomitant use significantly reduces the clearance of sertraline.

Drugs metabolized by isoenzyme 2D6 of cytochrome P450.

Long-term treatment with sertraline at a dose of 50 mg/day is accompanied by an increase in the concentration of desipramine.

Drugs metabolized by other cytochrome P450 enzyme systems.

Experiments to study the interaction
in vitro
showed that the beta-hydroxylation of endogenous cortisol carried out by the isoenzyme CYP 3A3/4, as well as the metabolism of carbamazepine and terfenadine, do not change with long-term administration of sertraline at a dose of 200 mg/day. The plasma concentrations of tolbutamide, phenytoin and warfarin also do not change with long-term administration of sertraline at the same dose. Thus, we can conclude that sertraline does not inhibit the CYP2C9 isoenzyme.

Sertraline does not affect the concentration of diazepam in the blood serum, which indicates the absence of inhibition of the CYP 2C19 isoenzyme. According to in vitro studies,

Sertraline has virtually no effect or minimal inhibition of the CYP 1A2 isoenzyme.

Lithium.

The pharmacokinetics of lithium does not change with concomitant administration of sertraline. However, when they are used together, tremor is observed more often. As well as the prescription of other selective inhibitors of neuronal serotonin reuptake, the combined use of sertraline with drugs that affect serotonergic transmission (for example, lithium) requires increased caution.

Drugs affecting serotonergic transmission.

When replacing one neuronal serotonin uptake inhibitor with another, there is no need for a washout period. However, caution is required when changing the course of treatment. Co-administration of tryptophan or fenfluramine with sertraline should be avoided.

Induction of microsomal enzymes in the liver.

Sertraline causes minimal induction of liver enzymes. The simultaneous administration of sertraline and antipyrine at a dose of 200 mg leads to a significant decrease in T1/2 of antipyrine (differs in only 5% of observations).

Atenolol.

When administered together, sertraline does not alter its beta-blocking effect.

Glibenclamide and digoxin.

When sertraline was administered in a daily dose of 200 mg, no drug interactions with these drugs were detected.

Use during pregnancy and breastfeeding

There are no controlled results of using sertraline in pregnant women, so the drug should be prescribed to them only if the expected benefit to the mother outweighs the potential risk to the fetus.

Sertraline is found in breast milk and therefore treatment with this drug during breastfeeding is not recommended. There is no reliable data on the safety of its use in this case. If treatment is still necessary, it is better to stop breastfeeding.

Side effects

From the digestive system: dry mouth, decreased appetite (rarely increased), up to anorexia, dyspeptic disorders (flatulence, nausea, vomiting, diarrhea or unstable stool, constipation), stomach cramps, abdominal pain, pancreatitis, hepatitis, jaundice or liver failure.

From the nervous system: drowsiness, headache, dizziness, tremor, insomnia, anxiety, agitation, hypomania, mania, akathisia, paresthesia, symptoms of depression, hallucinations, aggressiveness, agitation, anxiety, psychosis, gait disturbances, extrapyramidal disorders, dyskinesia, tremor , convulsions. Motor disorders were more often observed in patients with indications of their presence in the anamnesis or with concomitant use of antipsychotic drugs.

From the genitourinary system: delayed ejaculation, decreased libido, erectile dysfunction, anorgasmia, menstrual irregularities, gynecomastia, priapism, hyperprolactinemia, galactorrhea.

From the respiratory system: suffocation or a feeling of chest compression.

From the cardiovascular system: palpitations, chest pain, arterial hypertension, arterial hypotension, swelling, fainting and tachycardia (very rare).

From the senses: visual impairment (including blurred vision).

Allergic reactions: redness of the skin, urticaria, swelling of the eyelids, face or lips, skin rash, generalized itching, erythema multiforme.

Laboratory data: reversible increase in transaminase activity, thrombocytopenia, leukopenia, transient hyponatremia (syndrome of inadequate secretion of antidiuretic hormone, more often in elderly patients, as well as when taking diuretics or a number of other drugs).

Other: sporadic bleeding (including nosebleeds), hypothyroidism, increased sweating, weight loss, weakness, yawning, flushing. When treatment with sertraline is stopped, withdrawal syndrome may occur.

Asentra

With the simultaneous use of sertraline and MAO inhibitors (including selectively acting MAO inhibitors with a reversible type of action - selegiline and moclobemide), the development of serotonin syndrome is possible: hyperthermia, rigidity, myoclonus, lability of the autonomic nervous system (rapid fluctuations in parameters of the respiratory and cardiovascular system), changes mental status, including increased irritability, severe agitation, confusion, which in some cases can develop into a delirious state or coma (this combination is contraindicated). Similar complications (sometimes fatal) occur when MAO inhibitors are prescribed during treatment with antidepressants that inhibit the neuronal uptake of monoamines or immediately after their withdrawal.

In healthy volunteers, the use of sertraline at a dose of 200 mg / day does not affect the effect of ethanol, carbamazepine or haloperidol, as well as mental activity and psychomotor activity (however, the combined administration of sertraline and drugs that depress the central nervous system requires close attention, and simultaneous use with ethanol and ethanol-containing drugs is contraindicated).

When indirect anticoagulants (coumarin derivatives) are co-administered with sertraline, a significant increase in prothrombin time is observed (monitoring of prothrombin time is required at the beginning of sertraline use and after its discontinuation).

Pharmacokinetic interaction

When used together, sertraline may interact with other drugs that bind to plasma proteins (diazepam, tolbutamide and warfarin).

Concomitant use of the drug with cimetidine significantly reduces the clearance of sertraline.

Long-term use of sertraline at a dose of 50 mg/day with desipramine (a drug metabolized by the CYP2D6 isoenzyme) is accompanied by an increase in the concentration of desipramine in the blood plasma.

In vitro experiments have shown that the beta-hydroxylation of endogenous cortisol carried out by the CYP3A3/4 isoenzyme, as well as the metabolism of carbamazepine and terfenadine, do not change with long-term administration of sertraline at a dose of 200 mg/day.

The plasma concentrations of tolbutamide, phenytoin and warfarin do not change with long-term administration of sertraline at a dose of 200 mg/day, therefore, we can conclude that sertraline does not inhibit the CYP2C9 isoenzyme.

Sertraline does not affect the concentration of diazepam in the blood serum, which indicates the absence of inhibition of the CYP2C19 isoenzyme.

According to in vitro studies, sertraline has virtually no effect or minimal inhibition of the CYP1A2 isoenzyme.

The pharmacokinetics of lithium do not change statistically significantly with concomitant administration of sertraline; but tremor is observed more frequently, suggesting the possibility of a pharmacodynamic interaction (this combination requires caution). Sertraline should also be administered with caution with other drugs that affect serotonergic transmission.

When replacing one neuronal uptake inhibitor with another, there is no need for a washout period. However, caution is required when changing the course of treatment. Co-administration of tryptophan or fenfluramine with sertraline should be avoided.

Clinical studies have shown that sertraline causes minimal induction of liver enzymes. Simultaneous administration of sertraline at a dose of 200 mg and antipyrine leads to a significant decrease in T1/2 of antipyrine (this change is detected in only 5% of observations).

When administered together, sertraline does not affect the beta-blocking effect of atenolol.

When sertraline was administered in a daily dose of 200 mg, no drug interactions with glibenclamide and digoxin were detected.

Interaction

MAO inhibitors. Severe complications have been observed with the simultaneous use of sertraline and MAO inhibitors (including selectively acting MAO inhibitors with a reversible type of action - selegiline and moclobemide). Serotonin syndrome may develop. Similar complications, sometimes fatal, occur when MAO inhibitors are prescribed during treatment with antidepressants that inhibit the neuronal uptake of monoamines or immediately after their withdrawal.

With the simultaneous use of selective neuronal reuptake inhibitors of serotonin and MAO inhibitors, the following occur: hyperthermia, rigidity, convulsions, myoclonus, lability of the autonomic nervous system (rapid fluctuations in the parameters of the respiratory and cardiovascular system), changes in mental status, including increased irritability, severe agitation, confusion consciousness, which in some cases can turn into a delirious state or coma.

Drugs that depress the central nervous system and ethanol. The combined use of sertraline and substances that depress the central nervous system requires close attention, and the consumption of alcoholic beverages is also prohibited during treatment with sertraline.

Coumarin derivatives. When they are co-administered with sertraline, a significant increase in PT is observed. In these cases, it is recommended to monitor PT at the beginning of treatment with sertraline and after its discontinuation.

Pharmacokinetic interaction

Sertraline binds to plasma proteins. Therefore, the possibility of its interaction with other protein-binding drugs (eg diazepam, tolbutamide and warfarin) must be taken into account.

Cimetidine. Concomitant use significantly reduces the clearance of sertraline.

Drugs metabolized by isoenzyme 2D6 of cytochrome P450. Long-term treatment with sertraline at a dose of 50 mg/day is accompanied by an increase in the concentration of desipramine.

Drugs metabolized by other cytochrome P450 enzyme systems. Experiments to study the interaction in vitro showed that the beta-hydroxylation of endogenous cortisol carried out by the isoenzyme CYP 3A3/4, as well as the metabolism of carbamazepine and terfenadine, do not change with long-term administration of sertraline at a dose of 200 mg/day. The plasma concentrations of tolbutamide, phenytoin and warfarin also do not change with long-term administration of sertraline at the same dose. Thus, we can conclude that sertraline does not inhibit the CYP2C9 isoenzyme.

Sertraline does not affect the concentration of diazepam in the blood serum, which indicates the absence of inhibition of the CYP 2C19 isoenzyme. According to in vitro studies, sertraline has virtually no effect or minimal inhibition of the CYP 1A2 isoenzyme.

Lithium. The pharmacokinetics of lithium does not change with concomitant administration of sertraline. However, when they are used together, tremor is observed more often. As well as the prescription of other selective inhibitors of neuronal serotonin reuptake, the combined use of sertraline with drugs that affect serotonergic transmission (for example, lithium) requires increased caution.

Drugs affecting serotonergic transmission. When replacing one neuronal serotonin uptake inhibitor with another, there is no need for a washout period. However, caution is required when changing the course of treatment. Co-administration of tryptophan or fenfluramine with sertraline should be avoided.

Induction of microsomal enzymes in the liver. Sertraline causes minimal induction of liver enzymes. The simultaneous administration of sertraline and antipyrine at a dose of 200 mg leads to a significant decrease in T1/2 of antipyrine (differs in only 5% of observations).

Atenolol. When administered together, sertraline does not alter its beta-blocking effect.

Glibenclamide and digoxin. When sertraline was administered in a daily dose of 200 mg, no drug interactions with these drugs were detected.

Asentra®

Monoamine oxidase inhibitors (MAOIs).

Severe complications have been observed with the simultaneous use of sertraline and MAOIs (including selective MAOIs with a reversible type of action - selegiline and moclobemide). Serotonin syndrome may develop. Similar complications, sometimes fatal, occur when MAOIs are prescribed during treatment with antidepressants that inhibit the neuronal uptake of monoamines or immediately after their withdrawal.

With the simultaneous use of selective serotonin reuptake inhibitors and MAOIs, the following occurs:

hyperthermia, rigidity, convulsions, myoclonus, lability of the autonomic nervous system (rapid fluctuations in parameters of the respiratory and cardiovascular system), changes in mental status, including increased irritability, severe agitation, confusion, which in some cases can develop into a delirious state or coma.

Medicines that depress the central nervous system and ethanol.

The combined use of sertraline and substances that depress the central nervous system requires close attention, and the consumption of alcoholic beverages is prohibited during treatment with sertraline.

Coumarin derivatives

- when they are co-administered with sertraline, a significant increase in prothrombin time is observed - in these cases it is recommended to monitor the prothrombin time at the beginning of treatment with sertraline and after its discontinuation.

Pharmacokinetic interaction

Sertraline binds to plasma proteins. Therefore, the possibility of its interaction with other protein-bound drugs (eg diazepam, tolbutamide and warfarin) must be taken into account.

Cimetidine:

simultaneous use significantly reduces the clearance of sertraline.

Drugs metabolized by isoenzyme
2 D 6 of cytochrome P450:
long-term treatment with sertraline at a dose of 50 mg per day is accompanied by an increase in the concentration of desipramine.

Drugs metabolized by other cytochrome P450 enzyme systems.

Experiments to study the interaction in vitro showed that the beta-hydroxylation of endogenous cortisol carried out by the isoenzyme CYP 3A3/4, as well as the metabolism of carbamazepine and terfenadine, do not change with long-term administration of sertraline at a dose of 200 mg per day. The plasma concentrations of tolbutamide, phenytoin and warfarin also do not change with long-term administration of sertraline at the same dose. Thus, we can conclude that sertraline does not inhibit the CYP2C9 isoenzyme.

Sertraline does not affect the concentration of diazepam in the blood serum, which indicates the absence of inhibition of the CYP 2C19 isoenzyme. According to in vitro studies, sertraline has virtually no effect or minimal inhibition of the CYP 1A2 isoenzyme.

Lithium:

The pharmacokinetics of lithium do not change with concomitant administration of sertraline. However, tremor is observed more often when they are used together. As with the administration of other selective neuronal serotonin reuptake inhibitors, the combined use of sertraline with drugs that affect serotonergic transmission (for example, lithium) requires increased caution.

Drugs affecting serotonergic transmission.

When replacing one neuronal serotonin uptake inhibitor with another, there is no need for a washout period. However, caution is required when changing the course of treatment. Co-administration of tryptophan or fenfluramine with sertraline should be avoided.

Induction of microsomal enzymes in the liver.

Sertraline causes minimal induction of liver enzymes. The simultaneous administration of sertraline and antipyrine at a dose of 200 mg leads to a significant decrease in the half-life of antipyrine, although this occurs in only 5% of cases.

Atenolol:

when administered together, sertraline does not change its β-adrenergic blocking effect.

Glibenclamide and digoxin

: When sertraline was administered in a daily dose of 200 mg, no drug interactions with these drugs were detected.

Directions for use and doses

Inside.

For depression and OCD in adults, the average starting dose is 50 mg once a day, in the morning or evening. The daily dose can be gradually, no earlier than a week later, increased from 50 mg to a maximum daily dose of 200 mg.

For panic and post-traumatic stress disorders, the initial dose of Asentra is 25 mg once a day, in the morning or evening. After a week, you can increase the dose to 50 mg once a day, and then gradually, no earlier than a week later, increase to a maximum daily dose of 200 mg.

A satisfactory therapeutic result is usually achieved within 7 days from the start of treatment. However, to achieve the full therapeutic effect, regular use of the drug is required for 2–4 weeks. In patients with OCD, it may take 8–12 weeks to achieve good results. The minimum dose that provides a therapeutic effect is subsequently maintained as a maintenance dose.

The starting dose of Asentra for children aged 6 to 12 years is 25 mg sertraline once a day, in the morning or evening. After a week, you can increase the dose to 50 mg 1 time per day. For children aged 12 to 17 years, the initial dose is 50 mg 1 time per day in the morning or evening. If necessary, the daily dose can be gradually, no earlier than a week later, increased from 50 mg to a maximum daily dose of 200 mg. To avoid overdose, the lower body weight of children compared to adults should be taken into account, and when increasing the dose to more than 50 mg/day, careful monitoring of this category of patients is necessary and the drug should be discontinued at the first signs of overdose.

In elderly patients there is no need for special dose selection.

In case of liver dysfunction, the drug should be prescribed with caution. In case of severe liver dysfunction, the dose of the drug should be reduced or the intervals between doses increased.

In patients with impaired renal function, no special adjustment of the dosage regimen is required.

Instructions for use ASENTRA® (ASENTRA)

Serotonin syndrome (SS) or neuroleptic malignant syndrome (NMS)

The development of potentially life-threatening syndromes such as SS or NMS may be associated with selective serotonin reuptake inhibitors, including treatment with sertraline. The risk of CVD and NCD increases with concomitant use of serotonergic drugs (including triptans), drugs that reduce serotonin metabolism (including irreversible MAO inhibitors), antipsychotic drugs and other dopamine antagonists. Patients should be monitored for symptoms of SS and NMS.

Switching from selective serotonin reuptake inhibitors (SSRIs), antidepressants, or anti-obsessive medications

There are a limited number of controlled trials examining the optimal timing of switching from SSRIs, antidepressants, or anti-obsessive medications to sertraline. Reasonable and careful medical investigation should be performed, especially when switching from long-acting drugs such as fluoxetine.

Other serotonergic drugs, such as tryptophan, fenfluramine and 5-HT agonists

Concomitant use of sertraline with other drugs that enhance the effect of serotonergic nerve transmission, such as tryptophan or fenfluramine or 5-HT agonists, or with the herbal medicine St. John's wort (St. John's wort), should be cautious or avoided if possible due to the risk of pharmacodynamic interactions.

QT prolongation /TdP: QT prolongation and torsade de pointes ( TdP )
have been reported during post-marketing use of sertraline. The majority of reports were in patients with other concomitant risk factors for QT prolongation/TdP. Therefore, sertraline should be used with caution in patients with risk factors for QT prolongation.

Stimulation of manic/hypomanic state

Manic/hypomanic symptoms may occur in a small number of patients treated with antidepressants and anti-obsessive medications, including sertraline. Therefore, sertraline should be used with caution in patients with a history of mania/hypomania. Careful medical supervision is necessary. Sertraline should be discontinued in any patient entering a manic phase.

Schizophrenia

Psychiatric symptoms may be worse in patients with schizophrenia.

Epileptic seizures

Epileptic seizures may occur during sertraline therapy:

• Sertraline should be avoided in patients with unstable epilepsy;
• Patients with controlled epilepsy require careful monitoring. Sertraline should be discontinued if epileptic seizures develop.

Suicide/suicidal ideation or clinical worsening

Depression is associated with an increased risk of suicidal ideation, self-harm and suicide (suicide-related events). The risk is present until final remission. Improvement may not be observed during the first few weeks or more of treatment; patients should be closely monitored until improvement occurs. General clinical experience suggests that the risk of suicide may increase during the early stages of recovery.

Other psychiatric conditions for which sertraline is recommended may also be associated with an increased risk of suicide-related events. In addition, these conditions may co-occur with major depressive disorders. The same precautions are necessary when treating patients with major depressive disorder and when treating patients with other psychiatric disorders.

Patients with a history of suicide-related events or patients who express a high level of suicidal ideation before treatment are at higher risk for suicidal ideation or suicide attempts and should receive close monitoring during treatment. A meta-analysis of placebo-controlled clinical trials of antidepressants in adult patients with mental disorders showed an increased risk of suicidal behavior in the antidepressant group compared with placebo in patients under 25 years of age.

Careful monitoring of patients, especially those at high risk, should accompany drug therapy, especially in the early stages of treatment and with subsequent dose changes. Patients (caregivers) should be advised to look for any clinical worsening, suicidal behavior or thoughts, and unusual changes in behavior and to seek medical attention promptly if such symptoms occur.

Abnormal bleeding/hemorrhages

There is evidence of abnormal cutaneous hemorrhages such as ecchymosis and purpura and other hemorrhages such as gastrointestinal or gynecological bleeding associated with SSRIs. Caution should be exercised when treating patients taking SSRIs concomitantly with drugs that affect platelet function (for example, anticoagulants, atypical antipsychotics and phenothiazines, most tricyclic antidepressants, acetylsalicylic acid and NSAIDs), as well as in patients with a history of bleeding.

Hyponatremia

Hyponatremia may occur as a result of treatment with SSRIs or SNRIs, including sertraline. In many cases, hyponatremia occurs as a result of syndrome of inappropriate ADH secretion (SIADH). Serum sodium levels below 110 mmol/L have been reported. Elderly patients are at higher risk of developing hyponatremia due to use of SSRIs or SNRIs. The risk of developing hyponatremia is higher in patients taking diuretics or in patients with hypovolemia. If symptomatic hyponatremia develops, sertraline should be discontinued and appropriate therapeutic measures taken. Signs and symptoms of hyponatremia include headache, difficulty concentrating, memory loss, confusion, weakness and unsteadiness, which can lead to falls. Signs and symptoms associated with more severe and/or acute cases include hallucinations, fainting, seizures, coma, respiratory arrest, and death.

Withdrawal symptoms observed when stopping treatment with sertraline

When stopping treatment with sertraline, patients often develop withdrawal symptoms, especially if treatment is stopped suddenly. In clinical studies among patients treated with sertraline, withdrawal reactions were observed in 23% of those who discontinued treatment versus 12% of those who continued treatment with sertraline.

The risk of withdrawal symptoms may depend on several factors, including duration of therapy, dose, and sequence of dose reduction. Dizziness, sensory disturbances (including paresthesia), sleep disturbances (including insomnia and nightmares), agitation and restlessness, nausea and/or vomiting, tremor and headache are the most commonly reported reactions. In general, such symptoms are mild or moderate; however, they may be severe in some patients. They usually occur within the first few days after stopping treatment, but such symptoms have very rarely been reported in patients who accidentally missed taking the drug. In most cases, these symptoms go away on their own within 2 weeks, although in some cases they can be long-lasting (2-3 months or more). Therefore, when stopping treatment, it is recommended to gradually reduce the dose of sertraline over several weeks or months, according to the patient's needs.

Akathisia/psychomotor instability

The use of sertraline can lead to the development of akathisia, characterized by subjective unpleasant or irritating restlessness and the need to move more often, and the inability to sit or stand still. These symptoms most often occur during the first few weeks of treatment. In patients with the development of these symptoms, increasing the dose is undesirable.

Use for liver dysfunction

Sertraline undergoes extensive first-pass metabolism in the liver. Pharmacokinetic studies with repeated doses in patients with mild stabilized cirrhosis revealed an increased T1/2 and approximately 3 times greater AUC and Cmax values ​​compared to healthy individuals. There were no significant changes in plasma protein binding in either group. The use of sertraline in patients with liver disease should be used with caution. If sertraline is used in patients with hepatic impairment, it is necessary to use a lower dose or increase the interval between doses. Sertraline should not be used in patients with severe hepatic impairment.

Use for renal impairment

Sertraline is extensively metabolized and excreted unchanged in the urine. In a study of patients with mild and moderate renal failure (creatinine clearance 30-60 ml/min or 0.5-1 ml/s) and moderate and severe renal failure (creatinine clearance 10-29 ml/min or 0.167-0.483 ml/s) significant changes in pharmacokinetic parameters after repeated doses (AUC0-24 or Cmax) compared to control. Dosing of sertraline does not depend on the degree of kidney damage.

Diabetes

Treatment with SSRIs may impair glycemic control in patients with diabetes, possibly due to an improvement in symptoms of depression. Glycemic control must be carefully monitored in patients taking sertraline, and dosage adjustments of insulin or oral hypoglycemic agents may be necessary.

Use in elderly patients

More than 700 elderly patients (>65 years) took part in clinical studies. The nature and frequency of adverse reactions in elderly patients are approximately equal to those in young patients.

However, SSRIs and SNRIs, including sertraline, are to varying degrees associated with cases of clinical manifestations of hyponatremia in elderly patients; the risk of developing this unfavorable factor is highest in these patients.

Use in pediatrics

Sertraline should not be used to treat children and adolescents under 18 years of age, with the exception of patients with obsessive-compulsive disorder aged 6-17 years. Suicide-related behavior (suicidal attempts or suicidal ideation) and hostility (primarily aggression, contradictory behavior, and anger) were observed more frequently in clinical trials in children and adolescents treated with antidepressants compared with those treated with placebo. If, based on clinical need, a decision to treat is made, the patient should be closely monitored for the emergence of suicidal symptoms. In addition, there are insufficient long-term studies on the safety of sertraline in children and adolescents in relation to growth, puberty, cognitive and behavioral development of patients. Doctors should monitor pediatric patients over a long period of time for abnormalities in growth and development.

Electroconvulsive therapy

There are no clinical studies establishing the risks or benefits of concomitant use of ECT and sertraline.

Grapefruit juice

The use of sertraline with grapefruit juice is not recommended.

Effect on urine screening tests

False-positive immunoscreening tests for benzodiazepines have been reported in patients taking sertraline. This is due to the lack of specificity of screening tests. False-positive test results can be expected for several days after stopping sertraline therapy. Confirmatory techniques such as gas chromatography/mass spectrometry will separate sertraline from benzodiazepines.

Angle-closure glaucoma

SSRIs, including sertraline, can affect pupil size, leading to mydriasis. This mydriatic effect causes a narrowing of the visual angle, which leads to increased intraocular pressure and angle-closure glaucoma, especially in predisposed patients. Therefore, sertraline should be used with caution in patients with angle-closure glaucoma or a history of glaucoma.

Preclinical Safety Data

Preclinical data have not identified a specific hazard in humans as demonstrated by traditional pharmacological studies of safety, repeated dose toxicity, genotoxicity and carcinogenicity. Reproductive toxicity studies in animals have found no evidence of teratogenicity or adverse effects on male fertility. The observed fetotoxicity was likely related to maternal toxicity. Postpartum survival and fetal weight were reduced only in the first days after birth. It has been proven that early postnatal mortality was caused by intrauterine exposure after the 15th day of pregnancy. Postnatal developmental delays in the litters of treated females were likely due to exposure to females and are therefore not relevant to human risk.

Studies in rodents and other animals have shown no effect on fertility.

Research on juveniles.

A juvenile toxicology study was conducted in rats in which sertraline was administered orally to males and females on postnatal days 21 to 56 (at doses of 10, 40, or 80 mg/kg/day) with a no-dose recovery phase until postnatal day 196. Delayed puberty was observed in females and males at different doses (males at 80 mg/kg and females at ≥10 mg/kg), but despite this, sertraline-associated effects on reproductive endpoints in females and males were not found. In addition, in the postnatal period from days 21 to 56, dehydration, chromorinorrhea and a decrease in average body weight gain were observed. All of the above-mentioned effects associated with sertraline administration disappeared at some point during the non-dosing recovery phase. The clinical significance of the effects observed in rats when administered sertraline has not been established.

Precautions when disposing of a used medicinal product or waste obtained after using or working with a medicinal product

There are no special requirements for disposal of the drug. All remaining medicinal product and waste should be destroyed in an appropriate manner.

Impact on the ability to drive vehicles and machinery

Clinical pharmacological studies have shown that sertraline has no effect on psychomotor functions. However, because psychotropic drugs may impair the mental or physical abilities needed to perform potentially hazardous tasks, such as driving a vehicle or operating equipment, the patient should take appropriate precautions.

Overdose

Symptoms: serotonin syndrome - nausea, vomiting, drowsiness, ECG changes, mydriasis, tachycardia, agitation, dizziness, anxiety, psychomotor agitation, diarrhea, increased sweating, myoclonus and hyperreflexia.

Treatment: symptomatic provision of normal airway patency (oxygenation and ventilation) and monitoring of heart rate and vital organs and systems. Inducing vomiting is not recommended. The administration of activated charcoal and sorbitol may be more effective than gastric lavage. There are no specific antidotes. Sertraline has a large volume of distribution, and therefore increased diuresis, dialysis, hemoperfusion or blood transfusion may not be effective.

special instructions

Sertraline should not be co-administered with MAO inhibitors, or within 14 days after stopping treatment with MAO inhibitors. Similarly, after discontinuation of sertraline, MAO inhibitors are not prescribed for 14 days.

It should be noted that there is no sufficient experience with the use of sertraline in patients undergoing electroconvulsive therapy. The possible success or risk of this combination treatment has not been studied. Patients suffering from depression are at risk for suicide attempts. This danger persists until remission develops. Therefore, from the start of treatment until the optimal clinical effect is achieved, patients should be under constant medical supervision.

Women of childbearing age should use adequate contraception during treatment.

Influence on the ability to drive vehicles and operate machinery. The administration of sertraline, as a rule, is not accompanied by impairment of psychomotor functions. However, its use simultaneously with other drugs can lead to impairment of attention and coordination of movements. Therefore, during treatment with sertraline, driving vehicles, special equipment or engaging in activities associated with increased risk is not recommended.

Special instructions for the use of Asentra

If hypersensitivity reactions or severe sleep disturbances occur, stop taking the drug. Patients with depression are at risk (suicidal behavior), therefore, from the start of treatment until clinical effect is achieved, they should be under constant medical supervision. Sertraline is prescribed to patients with impaired liver function with caution. It is possible to reduce the dose or increase the interval between its increases. Sertraline is not recommended for patients with severe liver dysfunction. The safety of the drug during pregnancy and lactation has not been established. Asentra may affect the patient's psychophysical abilities, so the patient's condition must be carefully assessed before allowing the patient to drive or operate potentially dangerous machinery.