Emoton
Ukraine
Table of Contents
INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT EMOTON (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.
Pharmaceutical form. Film-coated tablets.
Main physicochemical properties: white, round, convex tablets with a score line.
Pharmacotherapeutic group.
Antidepressants. Selective serotonin reuptake inhibitors. ATC code N06A B06.
Pharmacological Properties.
Pharmacodynamics.
Sertraline is a potent and specific inhibitor of neuronal serotonin (5-HT) reuptake in vitro, which in animal studies leads to potentiation of 5-HT effects. Sertraline has only very weak effects on neuronal reuptake of norepinephrine and dopamine. At clinical doses, sertraline blocks 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 and did not 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 of the abuse potential of sertraline, alprazolam, and d-amphetamine in humans, sertraline did not cause positive subjective effects indicative of abuse potential. In contrast, study participants who received either alprazolam or d-amphetamine showed statistically significantly higher scores for abuse liability, euphoria, and potential for drug dependence compared to those who received placebo. Sertraline does not produce the stimulant effects or anxiety typical of d-amphetamine, nor does it produce the sedative effects and psychomotor impairments characteristic of alprazolam.
Pharmacokinetics.
Absorption
The pharmacokinetics of sertraline in the dose range of 50 to 200 mg is dose-dependent. After 14 days of oral administration of sertraline at doses of 50–200 mg once daily, peak plasma concentrations are 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 protein-bound in plasma.
Biological Transformation
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 reached after once-daily dosing for 1 week. The elimination half-life of N-desmethylsertraline is 62–104 hours. Sertraline and N-desmethylsertraline are extensively metabolized in humans, and their final metabolites are excreted in equal amounts in feces and urine. 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 gradually titrated 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 patients 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, especially 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 significantly differ from that in adults aged 18–65 years.
Hepatic Impairment
In patients with hepatic 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 disorders 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. Sertraline treatment may be initiated no sooner than 14 days after discontinuation of irreversible (non-selective) MAO inhibitors. Sertraline treatment should be discontinued at least 7 days prior to starting 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. Sertraline treatment may be initiated at least 14 days after discontinuation of reversible (selective) MAO inhibitors. Sertraline treatment should be discontinued at least 7 days before starting 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 initiating MAO inhibitors. Adverse reactions observed included tremor, myoclonus, profuse sweating, nausea, vomiting, facial flushing, dizziness, hyperthermia (particularly resembling neuroleptic malignant syndrome), seizures, and death.
Pimozide
In a study with single low-dose administration of pimozide (2 mg), an increase in pimozide levels of 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 agents.
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 recommended when sertraline is used concomitantly with lithium.
Phenytoin
Data from studies in healthy volunteers indicate that long-term administration of sertraline at a dose of 200 mg daily does not result in 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, including 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 when sertraline is used concomitantly with sumatriptan. Serotonin syndrome symptoms may also occur with other drugs in this class (triptans). If concomitant treatment with sertraline and triptans is clinically necessary, appropriate patient monitoring is required.
Warfarin
Concomitant use of sertraline at a dose of 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 initiation of sertraline therapy and upon discontinuation.
Interaction with other medicinal products. Formal drug interaction studies have been conducted with sertraline and other medicinal products. Concomitant use 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 marked reduction in sertraline clearance. The clinical significance of this phenomenon is not established. Sertraline does not affect the beta-blocking properties of atenolol. No interaction was observed with concomitant use of sertraline 200 mg daily and glyburide or digoxin.
Electroconvulsive therapy (ECT). Studies on the risks or benefits of concomitant use of ECT and sertraline have not been conducted.
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.
Drugs metabolized via 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 are possible with other CYP2D6 substrates that have 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 (diazepam), and CYP2C9 (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 resulted in an almost 100% increase in plasma sertraline levels 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 enzyme 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, lansoprazole, pantoprazole, rabeprozole, fluoxetine, and fluvoxamine cannot be excluded.
Special precautions for use.
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 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)
Life-threatening reactions 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 changes in mental status (e.g., agitation, hallucinations, coma), autonomic instability (tachycardia, blood pressure fluctuations, hyperthermia), neuromuscular abnormalities (hyperreflexia, incoordination), and/or gastrointestinal symptoms (nausea, vomiting, diarrhea). Some features of serotonin syndrome, including hyperthermia, muscle rigidity, autonomic instability, and altered mental status, resemble those of NMS. Patients should be monitored for symptoms of SS or NMS.
Transition 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 is advised when changing treatments, particularly when switching to sertrine 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. Sertraline therapy should be discontinued if signs of a manic episode occur.
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 of sertraline in patients with controlled epilepsy requires careful monitoring. Sertraline should be discontinued in patients who develop 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 occurs. Since improvement may take several weeks or longer, patients should be closely monitored until such improvement occurs. Clinical experience suggests 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 precautions 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, are at higher risk of developing suicidal thoughts or attempts during treatment and therefore require close monitoring during therapy. 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.
Careful monitoring of patients at high risk of suicide is recommended during Emoton therapy, especially at the beginning of treatment and after any dosage adjustments. Patients (and caregivers) should be advised to monitor for any signs of clinical worsening, emergence of suicidal behavior or suicidal thoughts, or any unusual behavioral changes, 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 higher rates 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, only limited clinical evidence is available 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 have not yet been established. Long-term therapy in pediatric patients requires physician monitoring for deviations from normal growth and development.
Abnormal bleeding/hemorrhage
Pathological hemorrhagic events, including skin hemorrhages (ecchymosis and purpura), and other hemorrhagic events such as gastrointestinal or gynecological bleeding, some with fatal outcomes, have been reported with the use of SSRIs. SSRIs should be used cautiously 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 occur during therapy with SSRIs or serotonin-norepinephrine reuptake inhibitors (SNRIs), including sertraline. In many cases, hyponatremia is due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Serum sodium levels below 110 mmol/L have been reported. Elderly patients may be at higher 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. For patients with symptomatic hyponatremia, discontinuation of sertraline therapy and appropriate treatment should be considered. 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 clinical trial 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 frequently 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, and 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 taper the dose of sertraline when discontinuing treatment over a period of several weeks or months, depending on the patient's needs.
Akathisia/psychomotor agitation
Sertraline use has been associated with the development of akathisia, characterized by a subjective feeling of unpleasant or uncontrollable restlessness and an urge to move, often accompanied by an inability to sit or stand still. 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 a prolonged elimination half-life and approximately threefold increases in AUC and Cmax compared to individuals with normal liver function. No significant differences in plasma protein binding were observed between these two groups. Caution is advised when administering sertraline to patients with hepatic pathology. 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 drug 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 the degree of renal impairment is not necessary.
Elderly patients
Over 700 elderly patients (aged >65 years) participated in clinical trials. 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 clinically significant hyponatremia in elderly patients, who may be at higher risk of developing this adverse effect (see "Hyponatremia" in the "Special precautions for use" section).
Diabetes mellitus
New-onset diabetes mellitus has been reported in patients receiving SSRIs, 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 carefully monitored for changes in glucose levels, as insulin and/or other oral hypoglycemic agents may require dosage adjustments.
Electroconvulsive therapy (ECT)
Clinical studies evaluating the risks or benefits of combining ECT with sertraline have not been conducted.
Grapefruit juice
Concomitant use of sertraline with grapefruit juice is not recommended.
Interaction with urine screening tests
False-positive immunological urine tests for benzodiazepine metabolites have been reported in patients taking sertraline. These false-positive results are due to the low specificity of the laboratory test and may persist for several days after discontinuation of sertraline. 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, causing mydriasis. This effect may lead to narrowing of the eye angle, resulting in increased intraocular pressure and the 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, with symptoms continuing 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 indicate evidence of congenital malformations due to sertraline use. Use of sertraline during pregnancy has been reported to cause in some newborns (whose mothers took sertraline) symptoms resembling withdrawal reactions. 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 in late pregnancy, particularly in 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 occur per 1000 pregnancies.
Observational data indicate an increased risk (less than twofold) of postpartum hemorrhage after use of SSRIs and SNRIs within one month before delivery (see sections "Special precautions for use" 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, minimal or undetectable concentrations of the drug have been found in infant plasma, except in one case where the infant's plasma concentration was approximately 50% of the mother's plasma concentration (but without any noticeable effect on the infant's health). No adverse effects of the drug on the health of breastfed children have 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 a vehicle or operating machinery.
Method of Administration and Dosage
The Emoton medication 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 begin no earlier than 1 week after starting treatment, gradually increasing by 50 mg at intervals of at least 1 week. The maximum dose should not exceed 200 mg per day. Dose adjustments should not be made more frequently than once weekly, considering sertraline’s elimination half-life of 24 hours.
Initial signs of therapeutic effect may be observed within 7 days of treatment. However, achieving a full therapeutic response usually requires a longer period, particularly 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 preventing 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 in patients with panic disorders and OCD, regular evaluation of therapy is recommended, as the effectiveness 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, the initial dose of Emoton is 25 mg daily; for children aged 13–18 years, the initial dose is 50 mg daily. 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.
There are no data on the use of the drug in children under 6 years of age.
Geriatric Patients
The drug should be used with caution in elderly patients due to the 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 its 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 Therapy
Abrupt discontinuation of the drug should be avoided. When stopping 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 the previously prescribed dose. Subsequently, the physician may continue tapering 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.
Overdose
Toxicity
Sertraline has a safety margin that depends on the patient population and/or concomitant use of other medications. Fatal cases of 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 management.
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 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. Continuous cardiac monitoring and observation of other vital signs, along with symptomatic and supportive therapy, are recommended. Due to sertraline’s large volume of distribution, 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 during treatment 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 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 with sertraline or shortly after discontinuation in clinical trials lasting 1–12 weeks), somnambulism, premature ejaculation, paraphrenia.
Nervous system disorders: dizziness, somnolence, headache, paresthesia, tremor, hypertonia, dysgeusia, attention disturbance, seizures, involuntary muscle contractions, coordination disorders, 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, belching, melena, hematochezia, stomatitis, tongue ulcers, dental disorders, glossitis, oral mucosal ulcers, pancreatitis; frequency unknown – microscopic colitis.
Hepatobiliary disorders: liver function abnormalities; hepatic failure, rarely leading to fatal outcomes; 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 disorders, muscle spasms.
Renal and urinary disorders: nocturia, urinary retention, polyuria, pollakiuria, micturition disorder, urinary incontinence, oliguria, difficulty in initiating micturition.
Reproductive system and breast disorders: ejaculation disorder, erectile dysfunction, vaginal bleeding, sexual dysfunction, sexual dysfunction in women, 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 warnings and precautions for use" and "Use during pregnancy or breastfeeding").
General disorders and administration site conditions: increased fatigue, chest pain, malaise, peripheral edema, chills, pyrexia, asthenia, thirst, hernia, reduced 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 changes.
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 used to describe adverse events were reclassified according to terms used for patients with depression.
Discontinuation symptoms observed upon stopping sertraline
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 or moderate in severity and resolve spontaneously; however, in some patients, they may be severe and/or prolonged. Therefore, when further treatment with sertraline 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, in whom the risk of developing this adverse effect may be increased.
Use in children
In over 600 children receiving 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 disturbances, 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 disturbances, alopecia, dermatitis, skin disorders, atypical skin odor, urticaria, bruxism, hyperemia, enuresis.
Effects specific to 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 receiving SSRIs and tricyclic antidepressants. The mechanism underlying this increased risk is unknown.
Reporting suspected adverse reactions
Reporting suspected adverse reactions after marketing authorization is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are encouraged to 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 per blister. 3 blisters per cardboard box.
Prescription status. Prescription only.
Manufacturer.
Atlantique Farmá – Produtos Farmacêuticos, S.A.
Manufacturer's address.
Rua Tapada Grande, 2, Abrunheira, Sintra, 2710-228, Portugal.
Marketing Authorization Holder.
LLC "Ersel Pharma Ukraine".
Address of Marketing Authorization Holder.
21000, Vinnytsia, 20/73, Yunosti Ave., Ukraine.