Emoton

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT EMOCTON (EMOTON)

Composition:

Active substance: sertraline;

One film-coated tablet contains sertraline hydrochloride 50 mg or 100 mg;

Excipients: calcium hydrogen phosphate dihydrate, microcrystalline cellulose, sodium starch glycolate, colloidal anhydrous silicon dioxide, magnesium stearate;

Film coating contains: polyvinyl alcohol, titanium dioxide (E 171), polyethylene glycol 300, talc.

Dosage form. Film-coated tablets.

Main physicochemical properties: white, round, convex tablets with a score line.

Pharmacotherapeutic group.

Antidepressants. Selective serotonin reuptake inhibitors. ATC code N06AB06.

Pharmacological Properties.

Pharmacodynamics.

Sertraline is a potent and specific inhibitor of neuronal serotonin (5-HT) reuptake in vitro, which in animal models leads to potentiation of 5-HT effects. Sertraline has only a very weak effect on neuronal reuptake of norepinephrine and dopamine. At clinical doses, sertraline inhibits serotonin uptake in human platelets. The drug does not exhibit stimulant, sedative, anticholinergic, or cardiotoxic effects in animal experiments. During administration, sertraline did not produce sedative effects or impair psychomotor functions. Due to its selective inhibition of serotonin reuptake, sertraline does not stimulate catecholaminergic activity. The medicinal product has no affinity for muscarinic (cholinergic), serotonergic, dopaminergic, adrenergic, histaminergic, GABA, or benzodiazepine receptors.

Sertraline does not lead to drug dependence. In a comparative study assessing the abuse potential of sertraline, alprazolam, and d-amphetamine in humans, sertraline did not cause positive subjective effects indicative of abuse potential. In contrast, participants receiving either alprazolam or d-amphetamine showed statistically significantly higher scores for abuse liability, euphoria, and potential for drug dependence compared to those receiving placebo. Sertraline lacks the stimulant effects and anxiety-inducing properties characteristic of d-amphetamine, as well as the sedative effects and psychomotor impairments typical of alprazolam.

Pharmacokinetics.

Absorption

The pharmacokinetics of sertraline in the dose range of 50 to 200 mg is dose-dependent. After 14 days of once-daily oral administration of sertraline at doses of 50–200 mg, maximum plasma concentration is reached within 4.5–8.4 hours after daily dosing. Food does not significantly alter the bioavailability of sertraline in tablet form.

Distribution

Approximately 98% of circulating sertraline is bound to plasma proteins.

Metabolism

Sertraline undergoes extensive presystemic metabolism (first-pass effect) in the liver.

Elimination

The mean elimination half-life of sertraline is approximately 26 hours (range: 22–36 hours). Due to this terminal half-life, accumulation of the drug (with plasma levels increasing about twofold) occurs at steady-state concentrations, which are achieved after one week of once-daily dosing. The elimination half-life of N-desmethylsertraline is 62–104 hours. Sertraline and N-desmethylsertraline are extensively metabolized in the human body, and their final metabolites are excreted in feces and urine in equal amounts. Only a very small fraction (<0.2%) of sertraline is excreted unchanged in urine.

Pharmacokinetics in Specific Patient Populations

Children with Obsessive-Compulsive Disorder (OCD)

The pharmacokinetics of sertraline were studied in 29 children aged 6–12 years and 32 adolescents aged 13–17 years. Patients were titrated gradually to a daily dose of 200 mg over 32 days, starting from either 25 mg or 50 mg. Tolerability was similar at doses of 25 mg and 50 mg. At steady-state with a 200 mg dose, plasma concentrations of sertraline in children aged 6–12 years were approximately 35% higher than in those aged 13–17 years and 21% higher than in the reference adult group. No significant differences in clearance were observed between boys and girls. Therefore, for pediatric use, particularly in children with low body weight, a low initial dose and dose titration in 25 mg increments are recommended. Adolescents may be given the same doses as adults.

Adolescents and Elderly Patients

The pharmacokinetic profile of sertraline in adolescents and elderly patients does not differ significantly from that in adults aged 18–65 years.

Hepatic Impairment

In patients with liver impairment, the elimination half-life of sertraline is prolonged, and the area under the plasma concentration-time curve (AUC) increases threefold.

Renal Impairment

In patients with moderate to severe renal impairment, no significant accumulation of sertraline was observed.

Clinical characteristics.

Indications.

• Major depressive episodes. Prevention of relapse of major depressive episodes.
• Panic disorder with or without agoraphobia.
• Obsessive-compulsive disorder (OCD) in adults and children aged 6–17 years.
• Social anxiety disorder.
• Post-traumatic stress disorder (PTSD).

Contraindications.

Hypersensitivity to sertraline or to any of the excipients. Severe hepatic impairment; uncontrolled epilepsy. Concomitant use of monoamine oxidase inhibitors (MAOIs). Concomitant use of sertraline and pimozide is contraindicated.

Interaction with other medicinal products and other forms of interaction.

Contraindicated

Irreversible (non-selective) MAO inhibitors (selegiline)

Sertraline should not be used in combination with irreversible (non-selective) MAO inhibitors such as selegiline. Treatment with sertraline may be initiated at least 14 days after discontinuation of irreversible (non-selective) MAO inhibitors. Sertraline treatment should be discontinued 7 days prior to starting treatment with irreversible (non-selective) MAO inhibitors.

Reversible selective MAO inhibitors (moclobemide)

Due to the risk of serotonin syndrome when sertraline is used concomitantly with reversible selective MAO inhibitors such as moclobemide, such combination is not recommended. Treatment with sertraline may be initiated at least 14 days after discontinuation of reversible (selective) MAO inhibitors. Sertraline treatment should be discontinued 7 days prior to starting treatment with reversible (selective) MAO inhibitors.

Reversible non-selective MAO inhibitors (linezolid)

The antibiotic linezolid is a weak reversible non-selective MAO inhibitor and should not be administered to patients receiving sertraline.

Severe adverse reactions have been reported in patients who recently discontinued MAO inhibitors (e.g., methylene blue) and started sertraline, or who discontinued sertraline shortly before starting MAO inhibitors. Adverse reactions observed include tremor, myoclonus, profuse sweating, nausea, vomiting, facial flushing, dizziness, hyperthermia (particularly resembling neuroleptic malignant syndrome), seizures, and fatal outcomes.

Pimozide

In a study with single low-dose administration of pimozide (2 mg), an increase in pimozide levels by approximately 35% was observed. This increase was not accompanied by any changes in ECG parameters. Although the mechanism of this interaction is unknown, concomitant use of sertraline and pimozide is contraindicated due to the narrow therapeutic index of pimozide.

Concomitant use with sertraline not recommended

Central nervous system (CNS) depressants, alcohol

Concomitant administration of sertraline at a dose of 200 mg daily did not potentiate the effects of alcohol, carbamazepine, haloperidol, or phenytoin on cognitive and psychomotor functions in healthy volunteers; however, concomitant use of sertraline with alcohol is not recommended.

Other serotonergic medicinal products

Caution is advised when co-administering sertraline with fentanyl (used primarily during general anesthesia and chronic pain therapy), other serotonergic agents (including other serotonergic antidepressants, triptans), and other opioid medications.

Special precautions for use

Lithium

In a study involving healthy volunteers, concomitant administration of sertraline and lithium did not significantly alter the pharmacokinetics of lithium, but resulted in increased tremor compared to placebo, suggesting a possible pharmacodynamic interaction. Appropriate monitoring is required when sertraline and lithium are used concomitantly.

Phenytoin

Data from studies in healthy volunteers indicate that long-term administration of sertraline at a dose of 200 mg daily does not cause clinically significant inhibition of phenytoin metabolism. However, there are reports of high phenytoin exposure in patients taking sertraline; monitoring of plasma phenytoin concentrations is recommended during the initial phase of sertraline therapy, with appropriate dose adjustment of phenytoin. Additionally, concomitant use of sertraline with phenytoin may lead to decreased plasma concentrations of sertraline. A reduction in sertraline plasma levels under the influence of other CYP3A4 inducers, such as phenobarbital, carbamazepine, St. John’s wort, and rifampicin, cannot be excluded.

Triptans

There have been isolated reports of weakness, hyperreflexia, incoordination, confusion, anxiety, and agitation with concomitant use of sertraline and sumatriptan. Serotonin syndrome symptoms may also occur with other drugs of this class (triptans). If concomitant treatment with sertraline and triptans is clinically necessary, appropriate patient monitoring should be ensured.

Warfarin

Concomitant use of sertraline 200 mg daily and warfarin resulted in a small but statistically significant increase in prothrombin time, which may in rare cases lead to disturbances in the international normalized ratio (INR). Therefore, prothrombin time should be carefully monitored at the beginning of sertraline therapy and upon its discontinuation.

Interaction with other medicinal products. Formal drug interaction studies have been conducted with sertraline and other medicinal products. Concomitant administration of sertraline 200 mg daily with diazepam or tolbutamide resulted in minor but statistically significant changes in some pharmacokinetic parameters. Concomitant use with cimetidine causes a significant reduction in sertraline clearance. The clinical significance of this phenomenon has not been established. Sertraline does not affect the beta-blocking properties of atenolol. No interaction was observed with concomitant administration of sertraline 200 mg daily and glyburide or digoxin.

Electroconvulsive therapy (ECT). No studies have been conducted on the risks or benefits of concomitant use of ECT and sertraline.

MEDICINAL PRODUCTS AFFECTING PLATELET FUNCTION

The risk of bleeding may be increased when selective serotonin reuptake inhibitors (SSRIs), including sertraline, are used concomitantly with medicinal products affecting platelet function (e.g., non-steroidal anti-inflammatory drugs (NSAIDs), acetylsalicylic acid, and ticlopidine), or with other medicinal products that may increase the risk of bleeding.

Medicinal products metabolized by cytochrome P450

Sertraline may act as a weak or moderate inhibitor of the CYP2D6 isoenzyme. Long-term administration of sertraline at a dose of 50 mg daily resulted in a moderate increase (on average by 23–37%) in steady-state plasma concentrations of desipramine (a marker of CYP2D6 activity). Clinically significant interactions may occur with other CYP2D6 substrates having a narrow therapeutic index, such as class 1C antiarrhythmics (e.g., propafenone and flecainide), tricyclic antidepressants, and typical antipsychotics, particularly when sertraline is used at higher doses.

Sertraline is not a clinically significant inhibitor of the CYP3A4, CYP2C9, CYP2C19, or CYP1A2 isoenzymes. This is supported by results from in vivo drug interaction studies using substrates of CYP3A4 (endogenous cortisol, carbamazepine, terfenadine, alprazolam), CYP2C19 substrate (diazepam), and CYP2C9 substrates (tolbutamide, glyburide, and phenytoin). In vitro study results indicate that sertraline has very low or no potential to inhibit CYP1A2.

Daily consumption of three glasses of grapefruit juice increased plasma sertraline levels by nearly 100% in a crossover study in healthy Japanese volunteers. Interaction with other CYP3A4 inhibitors has not been studied. Therefore, grapefruit juice should be avoided during sertraline therapy.

Given the results of the grapefruit juice interaction study, a substantially greater increase in sertraline exposure cannot be excluded when sertraline is used concomitantly with potent CYP3A4 inhibitors, including protease inhibitors, ketoconazole, itraconazole, posaconazole, voriconazole, clarithromycin, telithromycin, and nefazodone. This also applies to moderate CYP3A4 inhibitors – aprepitant, erythromycin, fluconazole, verapamil, and diltiazem. The use of potent CYP3A4 inhibitors should be avoided during sertraline therapy.

In individuals with slow CYP2C19 metabolism, plasma levels of sertraline are increased by 50% compared to individuals with rapid CYP2C19 metabolism. Drug interactions with potent CYP2C19 inhibitors such as omeprazole, lanoprazole, pantoprazole, rabeprazole, fluoxetine, and fluvoxamine cannot be excluded.

Special precautions.

Symptoms such as restlessness, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, psychomotor agitation, hypomania, and mania have been observed in adults and children treated with antidepressants. These symptoms may precede the emergence of suicidal ideation. Consideration should be given to changing the therapeutic regimen or discontinuing Emoton if depressive symptoms worsen, suicidal ideation emerges, or symptoms of worsening suicidality occur. If a decision is made to discontinue treatment, the drug should be tapered off as rapidly as possible, but it should be remembered that abrupt discontinuation may be accompanied by withdrawal syndrome. Prior to initiating treatment, patients should be evaluated for the risk of developing bipolar disorder. This includes a thorough psychiatric history, including family history of suicide, bipolar disorders, and depression. Emoton is not indicated for the treatment of bipolar depression.

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

Cases of potentially life-threatening syndromes such as serotonin syndrome (SS) or neuroleptic malignant syndrome (NMS) have been reported with the use of SSRIs, including sertraline therapy. The risk of developing SS or NMS with SSRIs increases when used concomitantly with other serotonergic agents (including other serotonergic antidepressants, triptans, and fentanyl), drugs that impair serotonin metabolism (including MAO inhibitors, e.g., methylene blue), antipsychotics, other dopamine antagonists, and opioids. Serotonin syndrome may include mental status changes (e.g., agitation, hallucinations, coma), autonomic dysfunction (tachycardia, fluctuations in blood pressure, hyperthermia), neuromuscular abnormalities (hyperreflexia, incoordination), and/or gastrointestinal symptoms (nausea, vomiting, diarrhea). Some manifestations of serotonin syndrome, including hyperthermia, muscle rigidity, autonomic instability, and mental status changes, resemble those of NMS. Patients should be monitored for symptoms of SS or NMS.

Switching from SSRIs, antidepressants, or anti-obsessive agents

There are limited data on the optimal timing for switching from SSRIs, antidepressants, or anti-obsessive agents to sertraline. Caution should be exercised when changing treatments, especially when switching to sertraline from long-acting agents such as fluoxetine.

Other serotonergic agents, e.g., tryptophan, fenfluramine, and 5-HT agonists

Concomitant use of sertraline with other agents that enhance serotonergic neurotransmission, including tryptophan, fenfluramine, fentanyl, 5-HT agonists, or herbal preparations containing St. John’s wort (Hypericum perforatum), should be done with caution, and such combination therapy should be avoided (if possible) due to potential pharmacodynamic interactions.

Exacerbation of hypomania or mania

Exacerbation of manic/hypomanic symptoms has been reported in a small percentage of patients receiving approved antidepressants and anti-obsessive agents, including sertraline. Therefore, sertraline should be used with caution in patients with a history of mania/hypomania. Close medical monitoring is required. If signs of a manic episode occur, sertraline should be discontinued.

Schizophrenia

Psychotic symptoms may be exacerbated in patients with schizophrenia during treatment.

Seizures

Seizures may occur during sertraline therapy: sertraline should not be prescribed to patients with unstable epilepsy; use in patients with controlled epilepsy requires careful monitoring. The drug should be discontinued in patients who experience seizures.

Suicide/suicidal thoughts/suicide attempts or clinical worsening

Patients with depression have an increased risk of suicidal thoughts, self-harm, and suicide attempts (suicidal behaviors and manifestations). This risk persists until significant remission is achieved. Since improvement in patients may take several weeks or longer, patients should be closely monitored until such improvement occurs. Clinical experience indicates that the risk of suicide may increase in the early stages of recovery.

Other psychiatric disorders for which sertraline is prescribed may also be associated with an increased risk of suicidal behaviors and manifestations. Additionally, these conditions may coexist with major depressive disorder. Therefore, similar precautionary measures applicable to patients with major depressive disorder are necessary when treating patients with other psychiatric disorders.

It is known that patients with a history of suicidal behaviors or manifestations, or those who exhibit pronounced suicidal ideation prior to treatment initiation, have a higher risk of developing suicidal thoughts or suicide attempts during treatment and therefore require close monitoring during drug administration. A meta-analysis of data from clinical trials of antidepressants in adult patients with psychiatric disorders showed an increased risk of suicidal behavior in patients under 25 years of age treated with antidepressants compared to placebo.

Close monitoring of patients at high risk of suicide is recommended during treatment with Emoton, especially at the beginning of therapy and after any dosage adjustments. Patients (and caregivers) should be warned to monitor for any signs of clinical worsening, emergence of suicidal behavior or suicidal thoughts, or any unusual changes in behavior, and to seek immediate medical attention if these symptoms occur.

Use in children

Sertraline should not be used for the treatment of children and adolescents, except for patients with OCD aged 6–17 years. In clinical trials, children receiving antidepressants showed a higher incidence of suicidal behavior (suicide attempts and suicidal thoughts) and hostility (mainly aggression, oppositional behavior, and anger) compared to those receiving placebo. If, based on clinical need, a decision is made to prescribe this medication, careful monitoring for suicidal symptoms is required. Additionally, there is limited clinical evidence on the long-term safety of the drug in children and adolescents, including its effects on growth, sexual maturation, and cognitive and behavioral development. There have been reports of several cases of delayed growth and delayed sexual maturation. The clinical significance and causal relationship remain unclear. Long-term therapy in pediatric patients requires physician monitoring for deviations in normal growth and development.

Abnormal bleeding/bleeding events

Cases of pathological bleeding events, including skin hemorrhagic manifestations (ecchymosis and purpura), and other hemorrhagic events such as gastrointestinal or gynecological bleeding, including fatal bleeding, have been reported with the use of SSRIs. SSRIs should be used with caution in patients, especially when used concomitantly with drugs known to affect platelet function (e.g., anticoagulants, atypical antipsychotics, phenothiazines, most tricyclic antidepressants, acetylsalicylic acid, and NSAIDs), as well as in patients with a history of bleeding disorders.

The use of SSRIs and SNRIs (serotonin-norepinephrine reuptake inhibitors) may increase the risk of postpartum hemorrhage (see sections "Use during pregnancy and breastfeeding" and "Adverse reactions").

Hyponatremia

Hyponatremia may develop during treatment with SSRIs or serotonin-norepinephrine reuptake inhibitors (SNRIs), including sertraline. In many cases, hyponatremia is due to the syndrome of inappropriate antidiuretic hormone secretion. Serum sodium levels below 110 mmol/L have been reported. Elderly patients may have an increased risk of developing hyponatremia when treated with SSRIs and SNRIs. The risk of this complication may also be increased in patients taking diuretics or those with hypovolemia of any origin. Discontinuation of sertraline therapy and initiation of appropriate treatment should be considered in patients with symptomatic hyponatremia. Symptoms of hyponatremia include headache, difficulty concentrating, memory impairment, confusion, weakness, and loss of physical balance, which may lead to falls. Symptoms associated with more severe and/or acute episodes of hyponatremia include hallucinations, syncope, seizures, coma, respiratory arrest, and fatal outcome.

Withdrawal symptoms observed upon discontinuation of sertraline therapy

Withdrawal symptoms are common upon discontinuation of the drug, especially with abrupt cessation. According to study data, the incidence of withdrawal reactions in patients who discontinued sertraline was 23% compared to 12% in patients who continued sertraline therapy.

The risk of developing withdrawal syndrome may depend on several factors, including duration of therapy, dosage, and speed of dose reduction. The most commonly reported reactions include dizziness, sensory disturbances (including paresthesia), sleep disturbances (including insomnia and vivid dreams), agitation or anxiety, nausea and/or vomiting, tremor, and headache. These symptoms are generally mild to moderate in severity, although they may be severe in some patients. They usually occur within the first few days after discontinuation of therapy; very rarely, such symptoms have been reported in patients who accidentally missed a dose. In most cases, these symptoms resolve spontaneously within 2 weeks, although in some patients they may persist longer (2–3 months or more). Therefore, it is recommended to gradually reduce the dose of sertraline when discontinuing therapy over a period of several weeks or months according to patient needs.

Akathisia/psychomotor agitation

Sertraline use is associated with the development of akathisia, characterized by subjective distress or an inability to remain still, often accompanied by an inability to sit or stand quietly. The risk of such complications is highest during the first two weeks of therapy. Increasing the dose may be harmful in patients who develop these symptoms.

Hepatic impairment

Sertraline is extensively metabolized in the liver. Pharmacokinetic studies with multiple dosing in patients with stable mild cirrhosis showed prolonged elimination half-life and approximately threefold increases in AUC and Cmax compared to individuals with normal liver function. No significant differences in protein binding of the drug between these two groups were observed. Caution should be exercised when administering sertraline to patients with liver disease. When prescribing sertraline to patients with impaired liver function, consideration should be given to reducing the dose or frequency of administration. Sertraline is contraindicated in patients with severe hepatic impairment.

Renal impairment

Sertraline is extensively metabolized; excretion of unchanged compound in urine is a minor elimination pathway. In studies involving patients with mild to moderate (creatinine clearance 30–60 mL/min) or moderate to severe (creatinine clearance 10–29 mL/min) renal impairment, pharmacokinetic parameters (AUC0–24 and Cmax) after multiple dosing were not statistically significantly different from those in the control group. Dose adjustment based on degree of renal impairment is not necessary.

Elderly patients

Over 700 elderly patients (aged >65 years) participated in clinical studies. The nature and frequency of adverse reactions in elderly patients were similar to those observed in younger patients.

However, the use of SSRIs and SNRIs, including sertraline, has been associated with cases of clinically significant hyponatremia in elderly patients, who may have an increased risk of developing this adverse effect (see "Hyponatremia" in the "Special precautions" section).

Diabetes mellitus

New-onset diabetes mellitus has been reported in patients receiving SSRI therapy, including sertraline. Loss of glycemic control, including both hyperglycemia and hypoglycemia, has been reported in patients with and without diabetes. Therefore, patients should be monitored for symptoms of glucose level changes. Patients with diabetes should be especially carefully monitored for changes in glucose levels, as insulin and/or other oral hypoglycemic agents may require dose adjustments.

Electroconvulsive therapy (ECT)

Clinical studies specifically designed to evaluate the risks or benefits of combined use of ECT and sertraline have not been conducted.

Grapefruit juice

Concomitant use of sertraline with grapefruit juice is not recommended.

Interaction with urine screening tests

Reports have been received regarding false-positive immunoassay urine tests for benzodiazepine metabolites in patients taking sertraline. False-positive results are due to the low specificity of the laboratory test and may occur for several days after discontinuation of sertraline therapy. Sertraline can be differentiated from benzodiazepine derivatives in urine by confirmatory testing using gas chromatography/mass spectrometry.

Angle-closure glaucoma

SSRI-class drugs, including sertraline, may affect pupil size, leading to mydriasis. This effect may result in narrowing of the eye angle, increased intraocular pressure, and development of angle-closure glaucoma, particularly in patients predisposed to this condition. Sertraline should be used with caution in patients with angle-closure glaucoma or a history of glaucoma.

Sexual dysfunction

SSRIs and SNRIs may cause sexual dysfunction. There have been reports of persistent sexual dysfunction, where symptoms continued despite discontinuation of SSRIs/SNRIs.

Use during pregnancy or breastfeeding.

Pregnancy

There are no well-controlled studies of the drug in pregnant women. However, a substantial amount of data does not show evidence of congenital malformations due to sertraline use. Use of sertraline during pregnancy has been reported to cause symptoms similar to withdrawal reactions in some newborns (whose mothers took sertraline). This phenomenon has also been observed with other SSRIs. Sertraline is not recommended during pregnancy except when the woman's clinical condition indicates that the expected benefits outweigh the potential risks.

Women of reproductive age taking sertraline should use appropriate contraceptive methods.

Newborns whose mothers used sertraline late in pregnancy, especially during the third trimester, should be closely observed, as they may develop symptoms such as respiratory distress syndrome, cyanosis, apnea, seizures, temperature instability, feeding difficulties, vomiting, hypoglycemia, hypertonia, hypotonia, hyperreflexia, tremor, syndrome of increased neuromuscular excitability, irritability, lethargy/apathy, persistent crying, somnolence, and difficulty falling asleep. These symptoms may be due to other serotonergic effects or withdrawal symptoms. In most cases, such complications occur immediately after birth or shortly thereafter (within less than 24 hours).

Epidemiological data suggest that the use of SSRIs during pregnancy, particularly in late pregnancy, may increase the risk of persistent pulmonary hypertension in newborns. The risk associated with drug use is approximately 5 cases per 1000 pregnancies. In the general population, 1–2 cases of persistent pulmonary hypertension in newborns per 1000 pregnancies are observed.

Observational data indicate an increased risk (less than two-fold) of postpartum hemorrhage after use of SSRIs and SNRIs within one month before delivery (see sections "Special precautions" and "Adverse reactions").

Breastfeeding period

Published data on sertraline levels in breast milk indicate that sertraline and its metabolite N-desmethylsertraline are excreted into breast milk in small amounts. Generally, low or undetectable concentrations of the drug have been found in infant serum, except in one case where the drug concentration in infant serum was approximately 50% of the maternal serum concentration (but without any noticeable effect on the infant's health). Adverse effects of the drug on the health of breastfed infants have not been reported to date, but this risk cannot be excluded. Use of the drug during breastfeeding is not recommended, except when, in the physician’s opinion, the benefit of taking the drug outweighs the potential risk.

Ability to affect reaction speed when driving or operating machinery.

Studies indicate no effect of sertraline on psychomotor functions. However, patients should exercise caution, as the drug may impair mental or physical reactions required for performing potentially hazardous tasks such as driving or operating machinery.

Method of Administration and Dosage

Emotin is taken once daily (in the morning or evening).

Tablets may be taken independently of food intake.

Initiation of Treatment

Depression and OCD

Treatment with sertraline should be initiated at a dose of 50 mg once daily.

Panic Disorders, PTSD, and Social Anxiety Disorder

Treatment should be initiated at a dose of 25 mg once daily. After 1 week, the dose should be increased to 50 mg once daily. This dosing regimen has been shown to reduce the frequency of adverse effects typical for panic disorders during the initial treatment phase.

Dose Titration

Depression, OCD, Panic Disorders, Social Anxiety Disorder, and PTSD

In patients who do not respond to the 50 mg dose, therapeutic effect may be achieved by increasing the dose. Dose adjustments should not begin earlier than 1 week after starting treatment, increasing gradually by 50 mg at intervals of at least 1 week. The maximum dose should not exceed 200 mg per day. Dose adjustments should be made no more frequently than once a week, considering the elimination half-life of sertraline, which is 24 hours.

Initial signs of therapeutic effect may be observed within 7 days of treatment. However, a longer period is usually required to achieve a full therapeutic response, especially in patients with OCD.

Maintenance Dose

Dosage during long-term therapy should be maintained at the lowest effective level, with further adjustments based on therapeutic response.

Depression

Long-term therapy may also be used to prevent relapse of major depressive episodes (MDE). In most cases, the recommended dose for prevention of MDE relapse is the same as the dose used during treatment of the depressive episode. Patients with depression should continue therapy for a sufficient duration, at least 6 months, to ensure complete absence of symptoms.

Panic Disorders and OCD

For long-term use, patients with panic disorders and OCD should undergo regular therapy assessments, as the efficacy of the drug in preventing relapses of these disorders has not been demonstrated.

Use in Children

Children with OCD

The safety and efficacy of sertraline have been established in children aged 6 years and older. For children aged 6–12 years with OCD, Emotin is initiated at a dose of 25 mg per day; for children aged 13–18 years, the initial dose is 50 mg per day. The dose may be increased as needed under close medical supervision, but no more frequently than once every 7 days. The maximum daily dose for adults and children is 200 mg. The treatment course for primary disorders should last at least 6 weeks, and for relapses – at least 3–6 months.

The efficacy of the drug in children with major depressive disorder has not been demonstrated.

Data on the use of the drug in children under 6 years of age are lacking.

Geriatric Patients

Emotin should be used with caution in elderly patients due to an increased risk of hyponatremia.

Hepatic Impairment

Caution should be exercised when administering sertraline to patients with liver disease. In patients with impaired liver function, the dose or frequency of administration should be reduced. Sertraline should not be used in patients with severe hepatic impairment, as clinical data on drug use in such patients are lacking.

Renal Impairment

Dose adjustment is not required in patients with renal impairment.

Withdrawal Symptoms Observed Upon Discontinuation of Sertraline

Abrupt discontinuation of the drug should be avoided. When discontinuing sertraline treatment, the dose should be gradually reduced over at least 1–2 weeks to minimize the risk of withdrawal syndrome. If intolerable symptoms occur after dose reduction or discontinuation, consideration should be given to resuming treatment at the previously prescribed dose. The physician may then continue to reduce the dose, but more gradually.

Children

Sertraline should not be used for the treatment of children, except for children aged 6 years and older with obsessive-compulsive disorder (OCD).

Overdose

Toxicity

Sertraline has a safety margin that depends on the patient population and/or concomitant use of other medications. Fatal outcomes following sertraline overdose have been reported, both with sertraline alone (without concomitant drugs) and in combination with other medications and/or alcohol. Therefore, every case of overdose requires intensive therapy.

Symptoms

Symptoms of overdose include serotonin-mediated adverse effects, such as somnolence, gastrointestinal disturbances (including nausea and vomiting), tachycardia, tremor, agitation, and dizziness. Coma has been reported less frequently.

Treatment

There are no specific antidotes for sertraline. Airway patency, adequate oxygenation, and ventilation must be ensured and maintained. Administration of activated charcoal, which may be used in conjunction with a laxative, may be as effective as gastric lavage and should be considered in the management of overdose. Induction of emesis is not recommended. Recommended measures include continuous cardiac monitoring and monitoring of other vital signs, along with symptomatic and supportive therapy. Due to the large volume of distribution of sertraline, interventions such as forced diuresis, dialysis, hemoperfusion, or exchange transfusion are unlikely to be effective.

Sertraline overdose may lead to QT interval prolongation; therefore, ECG monitoring is recommended in all cases of overdose.

Side effects.

The most commonly observed adverse effect is nausea. Sexual dysfunction (ejaculation disorders) was reported in men treated with sertraline for social anxiety disorder. These adverse effects are dose-dependent and often resolve spontaneously with continued therapy.

Infections and infestations: pharyngitis, upper respiratory tract infections, rhinitis, diverticulitis, gastroenteritis, otitis media.

Benign and malignant neoplasms (including cysts and polyps): neoplasm (one case of neoplasm was reported in a patient receiving sertraline, compared to no such cases in the placebo group).

Blood and lymphatic system disorders: lymphadenopathy, leukopenia, thrombocytopenia.

Immune system disorders: hypersensitivity, anaphylactoid reaction, allergy.

Endocrine disorders: hypothyroidism, hyperprolactinemia, syndrome of inappropriate antidiuretic hormone secretion.

Metabolism and nutrition disorders: decreased appetite, increased appetite, diabetes mellitus, hypercholesterolemia, hypoglycemia, hyponatremia, hyperglycemia.

Psychiatric disorders: insomnia, depression, depersonalization, nightmares, anxiety, agitation, nervousness, decreased libido, bruxism, hallucinations, aggression, euphoric mood, apathy, pathological thinking, conversion disorder, drug dependence, psychotic disorder, paranoia, suicidal ideation/suicidal behavior (in patients with OCD, cases of suicidal thoughts and suicidal behavior were reported during short-term treatment lasting 1–12 weeks with sertraline or shortly after discontinuation of therapy), somnambulism, premature ejaculation, paraphilia.

Nervous system disorders: dizziness, somnolence, headache, paresthesia, tremor, hypertonia, dysgeusia, attention disturbance, seizures, involuntary muscle contractions, coordination abnormalities, hyperkinesia, amnesia, hypoesthesia, speech disorder, postural dizziness, syncope, migraine, coma, choreoathetosis, dyskinesia, hyperesthesia, sensory disturbances, movement disorders (including extrapyramidal symptoms such as hyperkinesia, hypertonia, jaw spasms, or gait disturbances). Symptoms of serotonin syndrome or CNS toxicity have also been reported, sometimes associated with concomitant use of serotonergic agents, namely: agitation, confusion, excessive sweating, diarrhea, elevated body temperature, hypertension, rigidity, tachycardia, akathisia, psychomotor agitation, cerebral vasospasm (including transient cerebral vasoconstriction syndrome or Call-Fleming syndrome).

Eye disorders: visual disturbances, mydriasis, glaucoma, lacrimation disorders, scotoma, diplopia, photophobia, hyphema, visual disorders, anisocoria; frequency unknown – maculopathy.

Ear and labyrinth disorders: tinnitus, ear pain.

Cardiac disorders: palpitations, tachycardia, myocardial infarction, bradycardia, cardiac arrhythmia, flushing, hypertension, hyperemia, peripheral ischemia, hematuria, pathological hemorrhagic events (such as gastrointestinal bleeding).

Respiratory, thoracic and mediastinal disorders: yawning, bronchospasm, dyspnea, epistaxis, laryngospasm, hyperventilation, hypoventilation, stridor, dysphonia, hiccup, interstitial lung disease.

Gastrointestinal disorders: diarrhea, nausea, dry mouth, abdominal pain, vomiting, constipation, dyspepsia, flatulence, esophagitis, dysphagia, hemorrhoids, hypersalivation, tongue changes, eructation, melena, hematochezia, stomatitis, tongue ulcers, dental disorders, glossitis, oral mucosal ulcers, pancreatitis; frequency unknown – microscopic colitis.

Hepatobiliary disorders: liver function abnormalities; hepatic failure, which rarely may lead to fatal outcome; fulminant hepatitis; necrotic hepatitis; cholestatic jaundice.

Skin and subcutaneous tissue disorders: rash, hyperhidrosis, periorbital edema, facial swelling, purpura, alopecia, cold sweat, dry skin, urticaria, pruritus, dermatitis, bullous dermatitis, vesicular rash, pathological changes in hair texture, atypical skin odor; rare cases of severe skin reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis, angioedema, photosensitivity reactions, and skin reactions have been reported.

Musculoskeletal and connective tissue disorders: arthralgia, myalgia, osteoarthritis, muscle weakness, back pain, muscle twitching, bone injury, muscle spasms.

Renal and urinary disorders: nocturia, urinary retention, polyuria, pollakiuria, micturition disorder, urinary incontinence, oliguria, difficulty initiating micturition.

Reproductive system and breast disorders: ejaculation disorder, erectile dysfunction, vaginal bleeding, sexual dysfunction, female sexual dysfunction, irregular menstrual cycle, menorrhagia, atrophic vulvovaginitis, balanoposthitis, genital discharge, priapism, galactorrhea, gynecomastia; frequency unknown – postpartum hemorrhage (this event has been reported for the therapeutic class of SSRIs/SNRIs (see sections "Special precautions" and "Use during pregnancy or breastfeeding").

General disorders and administration site conditions: increased fatigue, chest pain, malaise, peripheral edema, chills, pyrexia, asthenia, thirst, hernia, decreased drug tolerance, gait disturbance.

Investigations: increased alanine aminotransferase levels, increased aspartate aminotransferase levels, decreased body weight, increased body weight, impaired sperm quality, increased blood cholesterol levels, abnormal clinical laboratory test results, platelet function abnormalities.

Injury, poisoning and procedural complications: injury.

Surgical and medical procedures: vasodilation.

If an adverse event was observed in patients with depression, OCD, panic disorder, PTSD, or social anxiety disorder, the terms describing adverse events were reclassified according to terms used for patients with depression.

Discontinuation symptoms observed upon stopping sertraline treatment

Discontinuation of sertraline treatment (especially abrupt discontinuation) usually leads to the development of withdrawal symptoms. The most commonly reported adverse events include dizziness, sensory disturbances (including paresthesia), sleep disturbances (including insomnia and vivid dreams), agitation or anxiety, nausea and/or vomiting, tremor, and headache. These adverse events are usually mild to moderate in severity and resolve spontaneously, although in some patients they may be severe and/or prolonged. Therefore, if further sertraline therapy is not required, gradual discontinuation by stepwise dose reduction is recommended.

Use in elderly patients

The use of SSRIs or SNRIs, including sertraline, has been associated with clinically significant cases of hyponatremia in elderly patients, among whom the risk of developing this adverse effect may be increased.

Use in children

In over 600 children treated with sertraline, the overall adverse reaction profile was generally similar to that observed in adult clinical trials. The following adverse reactions were reported during studies: headache, insomnia, diarrhea, nausea, chest pain, mania, pyrexia, vomiting, anorexia, affective lability, aggression, agitation, nervousness, attention disturbance, dizziness, hyperkinesia, migraine, somnolence, tremor, visual disturbance, dry mouth, dyspepsia, nightmares, increased fatigue, urinary incontinence, rash, acne, epistaxis, flatulence, QT interval prolongation on ECG, suicide attempts, seizures, extrapyramidal disorder, paresthesia, depression, hallucinations, purpura, hyperventilation, anemia, liver function abnormalities, increased alanine aminotransferase levels, cystitis, herpes simplex, otitis externa, ear pain, eye pain, mydriasis, malaise, hematuria, pustular rash, rhinitis, injury, weight loss, muscle twitching, unusual dreams, apathy, albuminuria, pollakiuria, polyuria, breast pain, menstrual cycle disturbance, alopecia, dermatitis, skin injury, atypical skin odor, urticaria, bruxism, hyperemia, enuresis.

Effects typical of this class of medicinal products

Epidemiological studies, primarily conducted in patients aged 50 years and older, have shown an increased risk of bone fractures in patients treated with SSRIs and tricyclic antidepressants. The mechanism underlying this increased risk is unknown.

Reporting suspected adverse reactions

Reporting suspected adverse reactions after product authorization is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals should report any suspected adverse reactions via the national reporting system.

Shelf life: 3 years.

Storage conditions.

Store at temperatures not exceeding 30 °C.

Keep out of reach of children.

Packaging.

10 tablets in a blister. 3 blisters in a cardboard box.

Prescription status. Prescription only.

Manufacturer.

Atlantique Farmacêutica – Produtos Farmacêuticos, S.A.

Manufacturer's address.

Rua Tapada Grande, 2, Abrunheira, Sintra, 2710-228, Portugal.

Marketing Authorization Holder.

TOV "Ersel Pharma Ukraine".

Address of Marketing Authorization Holder.

21000, Vinnytsia, Prospekt Yunosti, 20/73, Ukraine.

In case of adverse events, side effects, or lack of therapeutic effect, please contact TOV "Ersel Pharma Ukraine", 21000, Vinnytsia, Prospekt Yunosti, 20/73, Tel./Fax (0432) 65-78-78, e-mail: [email protected]