Sertraloft 100

INSTRUCTION FOR MEDICAL USE of the medicinal product SERTRALOFT 25, SERTRALOFT 50, SERTRALOFT 100 (SERTRALOFT 25, SERTRALOFT 50, SERTRALOFT 100)

Composition:

Active substance: sertraline;

1 tablet contains sertraline hydrochloride equivalent to 25 mg, 50 mg, or 100 mg of sertraline;

Excipients:

25 mg dosage – microcrystalline cellulose, maize starch, povidone, lactose monohydrate, magnesium stearate, colloidal anhydrous silicon dioxide, dry mixture "Opadry II yellow" containing titanium dioxide (E 171), talc, polyethylene glycol, polyvinyl alcohol, yellow iron oxide (E 172), tartrazine (E 102) (as aluminum lake);

50 mg dosage – microcrystalline cellulose, povidone, lactose monohydrate, magnesium stearate, colloidal anhydrous silicon dioxide, indigo carmine (E 132), dry mixture "Opadry II white" containing titanium dioxide (E 171), talc, polyethylene glycol, polyvinyl alcohol;

100 mg dosage – microcrystalline cellulose, potato starch, povidone, celactose [a mixture of lactose monohydrate and powdered cellulose (75:25)], stearic acid, hypromellose, titanium dioxide (E 171), talc.

Pharmaceutical form. Film-coated tablets.

Main physicochemical properties: film-coated tablets with a biconvex surface, light yellow to yellow (25 mg dosage), blue (50 mg dosage), or white (100 mg dosage). Two layers are visible in cross-section. Marbling and speckles may be present on the surface of the tablets (100 mg dosage).

Pharmacotherapeutic group. Antidepressants. Selective serotonin reuptake inhibitors (SSRIs). ATC code N06AB06.

Pharmacological Properties

Pharmacodynamics

Mechanism of action. 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 inhibits serotonin uptake in human platelets. The drug does not exhibit stimulant, sedative, anticholinergic, or cardiotoxic effects in animal experiments, does not cause sedation, and does not affect psychomotor functions in healthy volunteers. Since sertraline selectively inhibits 5-HT reuptake, it does not stimulate catecholaminergic activity. The drug has no affinity for muscarinic (cholinergic), serotonergic, dopaminergic, adrenergic, histaminergic, GABA-, or benzodiazepine receptors. Long-term administration of sertraline in animals resulted in decreased activity of brain norepinephrine receptors, a phenomenon also observed with other clinically effective antidepressants and antiobsessional agents. Sertraline does not cause drug dependence, stimulant effects, or anxiety.

Data indicate that the relapse rate in patients with major depressive episodes taking sertraline was statistically significantly lower compared to patients receiving placebo. It is known that in patients with post-traumatic stress disorder (PTSD), the response rate to sertraline therapy was lower in men compared to women. In pediatric patients with obsessive-compulsive disorder (OCD) treated with sertraline, statistically more significant improvement was observed compared to patients receiving placebo.

Pharmacokinetics

Absorption. The pharmacokinetics of sertraline in the dose range of 50 to 200 mg is dose-dependent. After 14 days of sertraline administration at doses of 50–200 mg (orally, once daily), peak plasma concentrations of sertraline are reached within 4.5–8.4 hours after daily dosing. Food does not significantly alter the bioavailability of sertraline tablets.

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

Biotransformation. 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 to 36 hours). Consistent with this terminal half-life, accumulation of the drug (with plasma levels increasing about twofold) occurs at steady-state, which is 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 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 OCD. At steady-state following 200 mg dosing, plasma concentrations of sertraline in children aged 6–12 years are significantly higher compared to those in adolescents aged 13–17 years and adults. 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 is recommended, with dose titration in 25 mg increments. Adolescents may receive the same doses as adults.

Adolescents and elderly patients. The pharmacokinetic profile of sertraline in adolescents and elderly individuals 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 pharmacokinetic curve (AUC) increases threefold (see sections "Dosage and Administration" and "Special Warnings").

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

Clinical characteristics.

Indications. Major depressive episodes (MDE), prevention of MDE recurrence, 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 the active substance or to any of the excipients.

Concomitant use of sertraline with irreversible monoamine oxidase inhibitors (MAOIs) is contraindicated due to the risk of developing serotonin syndrome, characterized by symptoms such as agitation, tremor, and hyperthermia. Sertraline therapy must not be initiated within at least 14 days after discontinuation of irreversible MAOI treatment. Sertraline treatment should be discontinued at least 7 days prior to initiating therapy with an irreversible MAOI. Concomitant use of sertraline and pimozide is contraindicated (see section "Interaction with other medicinal products and other forms of interaction").

Interaction with other medicinal products and other forms of interaction.

Concomitant use with sertraline is contraindicated.

Monoamine oxidase inhibitors (MAO).

Irreversible MAO inhibitors (e.g., selegiline). Concomitant use of sertraline with irreversible MAO inhibitors such as selegiline is contraindicated. Sertraline must not be administered within at least 14 days after discontinuation of treatment with irreversible MAO inhibitors. Sertraline treatment should be discontinued at least 7 days prior to initiating therapy with irreversible MAO inhibitors (see section "Contraindications").

Selective reversible MAO-A inhibitor (moclobemide). Due to the risk of serotonin syndrome, sertraline should not be used in combination with reversible selective MAO inhibitors such as moclobemide. The interval between discontinuation of these agents and initiation of sertraline therapy may be shorter than 14 days, while the interval between discontinuation of sertraline and initiation of therapy with reversible MAO inhibitors should be at least 7 days (see section "Contraindications").

Reversible non-selective MAO inhibitors (linezolid). The antibiotic linezolid is a weak, reversible, non-selective MAO inhibitor and should not be used in patients taking sertraline (see section "Contraindications").

Pimozide. Following a single low dose (2 mg) of pimozide, an increase in pimozide levels was observed without 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 (see section "Contraindications").

Concomitant use with sertraline is not recommended.

Central nervous system depressants and alcohol. Concomitant administration of sertraline at a dose of 200 mg/day did not potentiate the effects of alcohol, carbamazepine, haloperidol, or phenytoin on cognitive and psychomotor functions in healthy study participants. However, concomitant use of sertraline with alcohol is not recommended.

Other serotonergic medicinal products (see section "Special precautions for use").

Caution is required when co-administering sertraline with fentanyl (commonly used during general anesthesia and for chronic pain management), other serotonergic agents (including other serotonergic antidepressants, triptans), and other opioid agents.

Special precautions are required when used concomitantly with sertraline.

Medicinal products that prolong the QT interval. The risk of QTc interval prolongation and/or ventricular arrhythmias (e.g., torsades de pointes) is increased when sertraline is used concomitantly with other medicinal products that prolong the QTc interval (e.g., certain antipsychotics and antibiotics) (see section "Special precautions for use").

Lithium. Data indicate that concomitant use of sertraline and lithium does not significantly alter lithium pharmacokinetics, but may enhance tremor, suggesting a possible pharmacodynamic interaction. Appropriate monitoring is required when sertraline and lithium are used concomitantly.

Phenytoin. Long-term administration of sertraline at 200 mg/day does not cause clinically significant inhibition of phenytoin metabolism. Nevertheless, monitoring of plasma phenytoin concentrations is recommended during the initial phase of sertraline therapy, with appropriate dose adjustments of phenytoin. Additionally, concomitant use with phenytoin may reduce plasma sertraline concentrations. A decrease in sertraline plasma levels under the influence of other CYP3A4 inducers, including phenobarbital, carbamazepine, St. John’s wort, and rifampicin, cannot be excluded.

Triptans. Isolated reports have described the development of weakness, hyperreflexia, coordination disturbances, confusion, anxiety, and agitation with concomitant use of sertraline and sumatriptan. Serotonin syndrome symptoms may also occur with other drugs in this class (triptans). If concomitant therapy with sertraline and triptans is clinically necessary, appropriate patient monitoring is required (see section "Special precautions for use").

Warfarin. Concomitant use of sertraline at a dose of 200 mg/day and warfarin resulted in a slight but statistically significant increase in prothrombin time, which may rarely lead to disturbances in the international normalized ratio (INR). Therefore, prothrombin time should be closely monitored at the initiation of sertraline therapy and upon discontinuation.

Interaction with other medicinal products, digoxin, atenolol, cimetidine. Concomitant use with cimetidine resulted in a significant reduction in sertraline clearance. The clinical significance of these changes is not established. Sertraline does not affect the beta-blocking properties of atenolol. No interaction was observed with concomitant administration of sertraline at 200 mg/day and digoxin.

Medicinal products affecting platelet function. The risk of bleeding may increase when SSRIs are used concomitantly with medicinal products affecting platelet function (nonsteroidal anti-inflammatory drugs, acetylsalicylic acid, and ticlopidine) or other medicinal products that may increase bleeding risk (see section "Special precautions for use").

Neuromuscular blocking agents. SSRIs may reduce plasma cholinesterase activity, leading to prolonged neuromuscular blockade with mivacurium or other neuromuscular blocking agents.

Medicinal products metabolized via cytochrome P450. Sertraline may act as a weak or moderate inhibitor of the CYP2D6 isoenzyme. Long-term administration of sertraline at 50 mg/day resulted in a moderate increase in steady-state plasma concentrations of desipramine (a marker of CYP2D6 activity). Clinically significant interactions may occur with other CYP2D6 substrates having narrow therapeutic ranges, such as class 1C antiarrhythmics (propafenone, flecainide), tricyclic antidepressants, and typical antipsychotics, especially when sertraline is used at higher doses. Sertraline is not a clinically significant inhibitor of CYP3A4, CYP2C9, CYP2C19, or CYP1A2 isoenzymes. This is supported by in vivo drug interaction studies using CYP3A4 substrates (endogenous cortisol, carbamazepine, terfenadine, alprazolam), CYP2C19 substrate (diazepam), and CYP2C9 substrates (tolbutamide, glyburide, and phenytoin). In vitro studies indicate that sertraline has very low or no potential to inhibit CYP1A2.

Data indicate that consumption of three glasses of grapefruit juice daily increases plasma sertraline levels by nearly 100%. Therefore, grapefruit juice should be avoided during sertraline therapy (see section "Special precautions for use"). A greater increase in sertraline exposure cannot be excluded when 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. Consumption of potent CYP3A4 inhibitors should be avoided during sertraline therapy.

In individuals with slow CYP2C19 metabolism, plasma sertraline levels are approximately 50% higher compared to those with rapid CYP2C19 metabolism (see section "Pharmacokinetics"). Drug interactions with potent CYP2C19 inhibitors such as omeprazole, lansoprazole, pantoprazole, rabeprazole, 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. Therapeutic regimen modification or discontinuation of the medicinal product should be considered 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 gradually as quickly as possible, but considering the potential for withdrawal syndrome upon abrupt discontinuation. Prior to initiating therapy, patients should be evaluated for risk of bipolar disorder, including a thorough psychiatric history, including family history of suicide, bipolar disorder, and depression. The drug is not intended for the treatment of bipolar depression.

Serotonin syndrome (SS) or neuroleptic malignant syndrome (NMS). Life-threatening syndromes such as SS or NMS have been reported with SSRIs, including sertraline therapy. The risk increases with concomitant use of other serotonergic agents (including other serotonergic antidepressants, triptans, and fentanyl), agents affecting serotonin metabolism (including MAO inhibitors such as methylene blue), antipsychotics, other dopamine antagonists, and opioids. SS may include mental status changes (e.g., agitation, hallucinations, coma), autonomic dysfunction (tachycardia, blood pressure fluctuations, hyperthermia), neuromuscular disturbances (hyperreflexia, incoordination), and/or gastrointestinal symptoms (nausea, vomiting, diarrhea). Symptoms of SS such as hyperthermia, muscle rigidity, autonomic dysfunction, 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. Data on the optimal timing for switching from SSRIs, antidepressants, or anti-obsessive agents to sertraline are limited. Appropriate medical monitoring is required during such treatment changes, 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 enhancing 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 (due to possible pharmacodynamic interaction).

QTc interval prolongation/ventricular tachycardia of the torsades de pointes type. Cases of QTc interval prolongation and torsades de pointes ventricular tachycardia have been reported. Most cases occurred in patients with other risk factors for QTc prolongation/torsades de pointes. Therefore, sertraline should be used cautiously in patients with risk factors for QTc interval prolongation.

Exacerbation of hypomania or mania. Symptoms of mania/hypomania have been reported in a small percentage of patients receiving approved antidepressants and anti-obsessive agents, including sertraline. Therefore, sertraline should be used cautiously in patients with a history of such symptoms. Close physician monitoring is required. Sertraline therapy should be discontinued if signs of a manic episode are observed.

Schizophrenia. Psychotic symptoms may worsen in patients with schizophrenia during sertraline treatment.

Seizures. Seizures may occur during sertraline therapy; sertraline should not be prescribed to patients with unstable epilepsy. In patients with controlled epilepsy, sertraline use requires careful monitoring. The drug 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 not occur during the first few weeks or longer periods of therapy, patients should be closely monitored until improvement occurs. Clinical experience generally 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 precautions required for treating patients with major depressive disorder are necessary when treating patients with other psychiatric disorders.

Patients with a history of suicidal behaviors or manifestations or with pronounced suicidal ideation have a higher risk of developing suicidal thoughts or suicide attempts during treatment and should be closely monitored, especially at the beginning of therapy and after any dosage adjustments. Patients and caregivers should be informed of the need to monitor for any clinical worsening, emergence of suicidal behavior or suicidal thoughts, or any unusual behavioral changes and to seek immediate medical attention if these symptoms occur. Data indicate an increased risk of suicidal behavior in adult patients under 25 years of age when using antidepressants compared to placebo.

Use in children. Sertraline should not be used to treat children and adolescents except for patients with OCD aged 6–17 years. In children receiving antidepressants, suicidal behavior (suicide attempts and suicidal thoughts) and hostility (mainly aggression, oppositional behavior, anger) were observed more frequently compared to placebo. Careful monitoring for signs of suicidal symptoms is required when prescribing the drug. Long-term safety data in children regarding the impact of treatment on growth, sexual maturation, cognitive, and behavioral development are lacking. There have been reports of several cases of delayed growth and sexual maturation. Physicians should monitor for deviations from normal growth and development.

Abnormal bleeding/bleeding events. Cases of pathological hemorrhagic events, including skin hemorrhages (ecchymoses and purpura) and other hemorrhagic events such as gastrointestinal or gynecological bleeding, including fatal bleeding, have been reported with SSRIs. Caution is recommended when using SSRIs concomitantly with medicinal products affecting platelet function (e.g., anticoagulants, atypical antipsychotics, phenothiazines, most tricyclic antidepressants, acetylsalicylic acid, and nonsteroidal anti-inflammatory drugs) and in patients with a history of hemorrhagic disorders (see section "Interaction with other medicinal products and other forms of interaction").

SSRIs/SSRIs may increase the risk of postpartum hemorrhage (see sections "Use during pregnancy or breastfeeding" and "Adverse reactions").

Hyponatremia. Hyponatremia may develop during SSRI or serotonin-norepinephrine reuptake inhibitor (SNRI) therapy, often as a result of the syndrome of inappropriate antidiuretic hormone secretion. Elderly patients, patients taking diuretics, and patients with hypovolemia of any origin are at increased risk of hyponatremia. Serum sodium levels below 110 mmol/L have been reported. Consideration should be given to discontinuing therapy and appropriate medical intervention in patients with symptomatic hyponatremia, including 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 death.

Discontinuation symptoms observed upon cessation of sertraline therapy. Discontinuation symptoms are common upon stopping the drug, especially with abrupt discontinuation (see section "Adverse reactions"). The risk of discontinuation syndrome depends on several factors, including duration of therapy, dosage, and rate 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. Generally, these symptoms are mild to moderate in severity, but may be severe in some patients. They usually occur within the first few days after discontinuation, and very rarely in patients who 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 sertraline dose over a period of several weeks or months according to patient needs when discontinuing therapy (see section "Dosage and administration").

Akathisia/psychomotor agitation. Sertraline use is associated with akathisia, characterized by subjectively unpleasant or uncontrollable restlessness and a need to move, often accompanied by inability to sit or stand still, with the highest risk of such complications occurring during the first few weeks of therapy. For patients who develop these symptoms, increasing the dose may be harmful.

Use in hepatic impairment. Sertraline is extensively metabolized in the liver. With repeated administration in patients with stable mild cirrhosis, elimination half-life was prolonged, and AUC and Cmax increased approximately threefold compared to individuals with normal liver function, without significant differences in plasma protein binding. Caution is required when administering sertraline to patients with hepatic pathology, and dose reduction or less frequent dosing should be considered. Sertraline should not be used in patients with severe hepatic impairment (see section "Dosage and administration").

Use in renal impairment. Sertraline is extensively metabolized; excretion of unchanged compound in urine is a minor elimination pathway. In patients with mild to severe renal impairment, AUC0-24 and Cmax values after repeated administration were not statistically significantly different from those in the control group. Dose adjustment based on the degree of renal impairment is not necessary.

Use in elderly patients. The nature and frequency of adverse reactions in elderly patients (>65 years) were similar to those observed in younger patients. However, the risk of clinically significant hyponatremia is higher (see "Hyponatremia" in section "Special precautions for use").

Diabetes mellitus. In patients with diabetes mellitus, SSRI use may affect glycemic control. Insulin and/or oral hypoglycemic agent dosing may require adjustment.

Electroconvulsive therapy (ECT). Clinical studies evaluating the risks or benefits of combined ECT and sertraline use have not been conducted.

Grapefruit juice. Concomitant use of sertraline with grapefruit juice is not recommended (see section "Interaction with other medicinal products and other forms of interaction").

Urine screening tests. Reports have been received of false-positive immunoassay screening tests for benzodiazepines in urine of 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. Differentiation of sertraline from benzodiazepines in urine can be achieved by confirmatory testing—gas chromatography/mass spectrometry.

Closed-angle glaucoma. SSRIs, including sertraline, may affect pupil size, potentially leading to mydriasis. This effect may cause narrowing of the eye angle, resulting in increased intraocular pressure and development of closed-angle glaucoma, especially in patients with predisposition. Sertraline should be used with caution in patients with closed-angle glaucoma or a history of glaucoma.

Sexual dysfunction. SSRIs may cause symptoms of sexual dysfunction (see section "Adverse reactions"). Reports of persistent sexual dysfunction, where symptoms persisted despite discontinuation of SSRIs, have been received.

The product contains lactose; therefore, if the patient has been diagnosed with intolerance to certain sugars, consultation with a physician is required before taking this medicinal product.

Tartrazine (E 102) may cause allergic reactions.

Use during pregnancy or breastfeeding.

Pregnancy. Well-controlled studies of the drug in pregnant women have not been conducted. However, there is a substantial amount of data indicating no evidence of congenital malformations due to sertraline use. Animal studies revealed effects on reproductive function, likely due to the toxic effect of the drug on the maternal organism and/or direct pharmacodynamic effect on the fetus. Use of sertraline during pregnancy has been reported to cause in some newborns symptoms similar to withdrawal reactions. Sertraline is not recommended during pregnancy except when the woman's clinical condition is such that the expected benefits outweigh the potential risks. Women of reproductive age taking sertraline should use appropriate contraceptive methods. Newborns should be monitored if the mother continued sertraline use in late pregnancy, especially in the third trimester, due to possible occurrence of 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 and usually develop immediately after birth or shortly thereafter (within less than 24 hours). Use of SSRIs during pregnancy, especially in late pregnancy, is expected to increase the risk of persistent pulmonary hypertension in newborns—approximately 5 cases per 1000 pregnancies.

Observational data indicate an increased risk (less than 2-fold) of postpartum hemorrhage following SSRI/SSRI use within one month before delivery (see sections "Special precautions for use" and "Adverse reactions").

Breastfeeding. Sertraline and its metabolite N-desmethylsertraline are excreted in breast milk in small amounts. Generally, negligible or undetectable concentrations of the drug were found in infant serum, except in one case where the infant serum concentration was approximately 50% of the maternal serum concentration (but without any noticeable effect on the infant's health). To date, no adverse effects of the drug on the health of breastfed infants of women taking sertraline have been reported, but this risk cannot be excluded. Use of the drug during breastfeeding is not recommended except when, in the physician's opinion, the benefits of taking the drug outweigh the potential risks.

Fertility. No effect of sertraline on fertility parameters was observed in animal studies, and effects on sperm quality were reversible. No effect on human fertility has been observed.

Ability to affect reaction speed when driving or operating machinery. No effect of sertraline on psychomotor functions was observed. However, patients should exercise caution, as the drug may impair mental or physical reactions required for performing potentially hazardous tasks such as driving a car or operating machinery.

Dosage and administration. The drug should be taken once daily, in the morning or evening, independent of food intake.

Initiation of therapy

Depression and OCD. Therapy should be initiated at a dose of 50 mg/day.

Panic disorders, PTSD, and social anxiety disorder. Therapy should be initiated at a dose of 25 mg/day. After 1 week, the dose should be increased to 50 mg once daily. This dosing regimen reduces the frequency of adverse effects at the beginning of therapy, typical for panic disorders.

Dose titration

Depression, OCD, panic disorders, social anxiety disorder, and PTSD. For patients who do not respond to the 50 mg dose, the dose may be increased, but not earlier than 1 week after initiation of therapy, increasing by 50 mg increments with intervals of at least 1 week. The maximum dose should not exceed 200 mg/day. Dose adjustments should be made no more frequently than once a week, considering the 24-hour elimination half-life of sertraline. Initial signs of therapeutic effect may be observed within 7 days of therapy. However, a longer period is usually required to achieve therapeutic response, especially in patients with OCD.

Maintenance dose

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

Depression. Long-term therapy may be used to prevent MDE recurrence. The recommended dose for prevention of MDE recurrence is generally the same as the dose used for its treatment. Therapy should be continued for a sufficient duration, at least 6 months, to ensure complete absence of symptoms.

Panic disorders and OCD. For long-term therapy in patients with panic disorders and OCD, regular evaluation of therapy is required, as efficacy in preventing recurrence has not been demonstrated.

Use in children

Children with OCD. For children aged 13–17 years, the initial dose is 50 mg once daily; for children aged 6–12 years, the initial dose is 25 mg once daily, with possible increase by 50 mg/day after 1 week. If necessary and in the absence of desired effect, further dose increases by 50 mg/day may be considered, no more frequently than once a week, considering the lower body weight of children compared to adults. The maximum dose is 200 mg/day. Efficacy of the drug in children with MDE has not been demonstrated. Data on use in children under 6 years of age are lacking (see section "Special precautions for use").

Use in elderly patients

The drug should be used with caution in elderly patients due to their increased risk of hyponatremia (see section "Special precautions for use").

Use in hepatic impairment

Caution is required when administering sertraline to patients with hepatic pathology. In cases of hepatic dysfunction, the dose or frequency of administration should be reduced. Sertraline should not be used in patients with severe hepatic impairment due to lack of clinical data on use in such patients (see section "Special precautions for use").

Use in renal impairment

Dose adjustment is not required in cases of renal impairment (see section "Special precautions for use").

Discontinuation symptoms observed upon cessation of therapy

Abrupt discontinuation of the drug should be avoided. To reduce the risk of discontinuation syndrome, the dose should be gradually reduced over at least 1–2 weeks (see sections "Special precautions for use" and "Adverse reactions"). If intolerable symptoms occur after dose reduction or discontinuation, resumption of the drug at the previously prescribed dose may be considered. Subsequently, the physician may continue to reduce the dose but more gradually.

Children. Sertraline should not be used to treat children except for children with OCD aged 6 years and older (see section "Dosage and administration").

Overdose.

Toxicity. Sertraline has a safety margin dependent on the patient population and/or concomitant use of medicinal products. Fatal cases of sertraline overdose have been reported both with sertraline alone (without concomitant drugs) and in combination with other agents and/or alcohol. Therefore, each case of overdose requires intensive therapy.

Symptoms: serotonin-mediated adverse effects, including somnolence, gastrointestinal disturbances (e.g., nausea and vomiting), tachycardia, tremor, agitation, and dizziness; less frequently, coma. QTc interval prolongation/torsades de pointes ventricular tachycardia has been reported after sertraline overdose; therefore, ECG monitoring is recommended in all cases of sertraline overdose.

Treatment. There are no specific antidotes for sertraline. Airway patency, adequate oxygenation, and ventilation should be ensured and maintained if necessary. Administration of activated charcoal with a laxative may be as effective as gastric lavage. Induction of emesis is not recommended. Recommended monitoring includes cardiac monitoring (e.g., ECG) and other vital signs, along with symptomatic and supportive therapy. Due to the large volume of distribution of sertraline, forced diuresis, dialysis, hemoperfusion, or exchange transfusion are unlikely to be beneficial.

Adverse Reactions

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 during continued therapy.

Some of the adverse reactions listed below may decrease in intensity and frequency with prolonged treatment and do not necessarily require discontinuation of therapy.

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

Benign and malignant neoplasms (including cysts and polyps): One case of a new tumor 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: hyperprolactinemia, hypothyroidism, syndrome of inappropriate antidiuretic hormone secretion (SIADH).

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

Psychiatric disorders: insomnia, depression, depersonalization, nightmares, anxiety, agitation, nervousness, decreased libido, bruxism, hallucinations, euphoric mood, apathy, pathological thinking, conversion disorder, drug dependence, psychotic disorder, aggression, paranoia, suicidal ideation/behavior (only in patients with OCD), somnambulism, premature ejaculation, parasomnia.

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, migraine, coma, choreoathetosis, dyskinesia, hyperesthesia, sensory disturbances, movement disorders (including extrapyramidal symptoms such as hyperkinesia, hypertonia, dystonia, jaw spasms, or gait disturbances); syncope; serotonin syndrome or neuroleptic malignant syndrome, in some cases associated with concomitant use of serotonergic agents (agitation, confusion, excessive sweating, diarrhea, elevated body temperature, hypertension, rigidity, tachycardia); akathisia and psychomotor agitation (see section "Special precautions").

Cerebral vasospasm (including transient cerebral vasoconstriction syndrome and Call-Fleming syndrome).

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

Ear and labyrinth disorders: tinnitus, ear pain.

Cardiac disorders: palpitations, tachycardia, myocardial infarction, bradycardia, cardiac arrhythmias, QTc interval prolongation, torsades de pointes.

Vascular disorders: hot flushes, arterial hypertension, hyperemia, peripheral ischemia, hemorrhagic events (gastrointestinal bleeding), hematuria.

Respiratory, thoracic and mediastinal disorders: yawning, bronchospasm, dyspnea, laryngospasm, hyperventilation, hypoventilation, epistaxis, stridor, dysphonia, hiccups, 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, microscopic colitis.

Hepatobiliary disorders: liver function abnormalities, severe liver function impairment (including hepatitis, jaundice, and liver failure).

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

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

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

Reproductive system and breast disorders: ejaculation disorder, sexual dysfunction, erectile dysfunction, vaginal bleeding, female sexual dysfunction, menorrhagia, atrophic vulvovaginitis, balanoposthitis, genital discharge, priapism, galactorrhea, gynecomastia, irregular menstrual cycle; postpartum hemorrhage*.

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

Injury and poisoning: injury.

Surgical and interventional procedures: vasodilation.

Investigations: weight loss/gain, increased levels of alanine aminotransferase (ALT)/aspartate aminotransferase (AST), sperm quality abnormalities, abnormal clinical laboratory test results, platelet function changes, increased serum cholesterol concentration.

Discontinuation symptoms observed upon stopping sertraline. Adverse events reported upon discontinuation of sertraline 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 and self-limiting; however, they may be severe and/or prolonged. When further treatment with sertraline is not required, gradual discontinuation by stepwise dose reduction is recommended (see sections "Dosage and administration" and "Special precautions").

Use in elderly patients. The use of selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs), including sertraline, in elderly patients increases the risk of clinically significant hyponatremia (see section "Special precautions").

Use in children. The following adverse reactions have been reported: 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 disorders, increased alanine aminotransferase levels, cystitis, herpes simplex, otitis externa, ear pain, eye pain, mydriasis, malaise, hematuria, pustular rash, rhinitis, weight loss, muscle twitching, unusual dreams, apathy, albuminuria, pollakiuria, polyuria, breast pain, menstrual cycle disturbances, alopecia, dermatitis, skin lesions, unusual skin odor, urticaria, bruxism, hyperemia, enuresis.

Effects associated with this class of medicinal products. An increased risk of bone fractures has been observed in patients, primarily aged 50 years and older, receiving SSRIs and tricyclic antidepressants. The mechanism of this 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.

* This event has been reported for the therapeutic class of SSRIs/SNRIs (see sections "Special precautions" and "Use during pregnancy or breastfeeding").

Shelf life. 3 years.

Storage conditions. Store in the original packaging at a temperature not exceeding 25°C. Keep out of the reach of children.

Packaging. Tablets, 10×3 in blisters, in a carton.

Prescription status. Prescription only.

Manufacturer. Limited Liability Company "Pharmaceutical Company "Zdorov'ya".

Limited Liability Company "FARMEKS GROUP".

Manufacturer's address and place of business. Ukraine, 61013, Kharkiv region, Kharkiv, Shevchenko St., 22.

(Limited Liability Company "Pharmaceutical Company "Zdorov'ya")

Ukraine, 08301, Kyiv region, Boryspil, Shevchenko St., 100.

(Limited Liability Company "FARMEKS GROUP")