Debitum - sanovel: detailed information

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT DEBITUM-SANOVEL (DEBITUM-SANOVEL)

Composition:

Active substance: sertraline;

One film-coated tablet contains 27.975 mg or 55.95 mg or 111.9 mg of sertraline hydrochloride, equivalent to 25 mg or 50 mg or 100 mg of sertraline;

Excipients: calcium hydrogen phosphate anhydrous, microcrystalline cellulose, hydroxypropylcellulose, sodium starch glycolate (type A), magnesium stearate;

For 25 mg tablets: Opadry Green 20A21200 (FD&C Blue No. 2 aluminum lake (E 132), FD&C Yellow No. 6 aluminum lake (E 110), hydroxypropylcellulose, hypromellose, quinoline yellow aluminum lake (E 104), titanium dioxide (E 171));

For 50 mg tablets: Opadry II Blue OY-L-20906 (polyethylene glycol, FD&C Blue No. 2 aluminum lake (E 132), hypromellose, lactose monohydrate, titanium dioxide (E 171));

For 100 mg tablets: Opadry White Y-1-7000 (titanium dioxide (E 171), hypromellose, polyethylene glycol).

Pharmaceutical form. Film-coated tablets.

Main physicochemical characteristics:
25 mg tablets – elongated film-coated tablets of green color;
50 mg tablets – elongated film-coated tablets of blue color, with a score on one side;
100 mg tablets – elongated film-coated tablets of white color, with a score on one side.

Pharmacotherapeutic group. Antidepressants. Selective serotonin reuptake inhibitors. ATC code: N06AB06.

Pharmacological Properties.

Pharmacodynamics.

Mechanism of action

Sertraline is a potent and specific inhibitor of neuronal serotonin reuptake in vitro, which in animal systems enhances the effects of 5-HT. 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. In controlled studies involving healthy volunteers, sertraline did not produce sedative effects and did not affect psychomotor functions. Due to its selective inhibition of 5-HT reuptake, sertraline does not increase catecholaminergic activity. The drug has no affinity for muscarinic (cholinergic), serotonergic, dopaminergic, adrenergic, histaminergic, GABA, or benzodiazepine receptors. Chronic administration of sertraline in animals was associated with a reduction in the number of brain norepinephrine receptors, a phenomenon also observed with other antidepressants and antiobsessional agents effective in clinical practice.

Sertraline does not cause medication abuse. In a placebo-controlled, double-blind, randomized study comparing the abuse potential of sertraline, alprazolam, and d-amphetamine in humans, sertraline did not produce positive subjective effects indicative of abuse potential. In contrast, participants receiving either alprazolam or d-amphetamine showed significantly higher ratings of abuse liability, euphoria, and potential for medication dependence compared to those receiving placebo. Sertraline did not produce the stimulant effects or anxiety associated with d-amphetamine, nor the sedative effects or psychomotor impairment associated with alprazolam. Sertraline did not produce a positive reinforcing stimulus in rhesus monkeys trained to self-administer cocaine, nor did it substitute as a discriminative stimulus for either d-amphetamine or pentobarbital in rhesus monkeys.

Clinical efficacy and safety

Major depressive disorder

Studies were conducted in outpatients with depression who responded to treatment during an initial 8-week open-label phase of sertraline therapy at doses of 50–200 mg/day. These patients (n=295) were then randomized to either continue sertraline at 50–200 mg/day or switch to placebo in a double-blind study lasting 44 weeks. The relapse rate was statistically significantly lower in the group receiving sertraline compared to the placebo group. The mean dose among participants who completed the study was 70 mg/day. The percentage of patients who responded to treatment (defined as those without relapse) in the sertraline and placebo groups was 83.4% and 60.8%, respectively.

Post-traumatic stress disorder (PTSD)

Pooled data from a total number of PTSD patients in three studies indicate a lower response rate in men compared to women. In two clinical trials with a positive overall population, the percentage of patients responding to therapy among women and men in the sertraline and placebo groups was similar (women: 57.2% vs. 34.5%; men: 53.9% vs. 38.2%). The number of men and women in the pooled study population was 184 and 430, respectively. Results were more consistent in women, while men had greater baseline variability (e.g., higher substance abuse, longer duration of illness, trauma etiology, etc.), which correlated with reduced drug efficacy.

Cardiac electrophysiology

In a thorough QTc interval study at steady state under supratherapeutic exposures in healthy volunteers (receiving a dose of 400 mg/day, twice the maximum recommended daily dose), the upper bound of the two-sided 90% CI for the time-matched mean difference in QTcF between sertraline and placebo, obtained by least squares method (11.666 ms), exceeded the pre-specified threshold of 10 ms at the 4-hour post-dose time point. Exposure-response analysis indicated a weak positive relationship between QTcF and plasma sertraline concentration [0.036 ms/(ng/mL); p < 0.0001]. Based on the exposure-response model, the threshold for clinically significant QTcF prolongation (i.e., >10 ms for the predicted 90% CI) was exceeded at least 2.6-fold higher than at the mean Cmax (86 ng/mL) following administration of the highest recommended dose of sertraline (200 mg/day) (see sections "Special precautions for use", "Interaction with other medicinal products and other forms of interaction", "Adverse reactions", and "Overdose").

Obsessive-compulsive disorder (OCD) in pediatric patients

The safety and efficacy of sertraline (50–200 mg/day) were evaluated in the treatment of children (6–12 years) and adolescents (13–17 years) without depression, treated as outpatients for obsessive-compulsive disorder (OCD). After a 1-week initial period of single-blind placebo administration, patients were randomized to receive either sertraline or placebo for 12 weeks with flexible dosing. Children (6–12 years) initiated treatment at 25 mg. Patients randomized to sertraline showed significantly greater improvement compared to those receiving placebo, as assessed by the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) (p=0.005), the National Institute of Mental Health Global Obsessive-Compulsive Scale (NIMH) (p=0.019), and the Clinical Global Impression-Improvement scale (p=0.002). Additionally, patients in the sertraline group showed a trend toward greater improvement on the Clinical Global Impression-Severity scale (p=0.089). Mean baseline CY-BOCS scores and mean change from baseline in the placebo group were 22.25 ± 6.15 and -3.4 ± 0.82, respectively, while in the sertraline group, mean baseline score and mean change from baseline were 23.36 ± 4.56 and -6.8 ± 0.87, respectively. In a post-hoc analysis, the percentage of patients who responded to therapy, defined as those with a ≥25% reduction in CY-BOCS score (primary efficacy parameter) from baseline to endpoint, was 53% in the sertraline group compared to 37% in the placebo group (p=0.03).

Data on long-term clinical studies evaluating efficacy in pediatric patients are lacking.

Children

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

Post-marketing safety study SPRITES

An observational post-marketing study involving 941 patients aged 6 to 16 years was conducted to evaluate the long-term safety of sertraline therapy (with and without psychotherapy) compared to psychotherapy alone, with follow-up up to 3 years, assessing cognitive, emotional, physical, and pubertal development. This study was conducted under real-world clinical practice conditions in children and adolescents with primary diagnoses of OCD, depression, or other anxiety disorders, and evaluated cognition (assessed by Trails B test and BRIEF index), behavioral/emotional regulation (assessed by BRIEF behavioral regulation index), and physical/pubertal maturation (assessed by standardized height/weight/body mass index (BMI) and Tanner stage). Sertraline is approved for pediatric use only in patients aged 6 years and older with OCD (see section "Indications"). Standardization of each primary outcome measure based on age- and sex-specific norms showed that overall results were consistent with normal development. No statistically significant differences from baseline were observed except for body weight. Comparative analyses showed statistically significant changes in body weight, although the magnitude of change was minimal.

Pharmacokinetics.

Absorption

During 14-day administration of sertraline 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 protein-bound in plasma.

Biological transformation

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

Based on clinical and in vitro study data, sertraline is metabolized via multiple pathways, including those involving CYP3A4, CYP2C19, and CYP2B6 enzymes (see section "Interaction with other medicinal products and other forms of interaction"). Sertraline and its major metabolite, desmethylsertraline, are also substrates of P-glycoprotein in vitro.

Elimination

The mean elimination half-life of sertraline is approximately 26 hours (range: 22–36 hours). Due to the terminal elimination half-life, there is accumulation of the drug (approximately doubling in concentration) until steady-state concentrations are reached after about 1 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.

Linearity/non-linearity

The pharmacokinetics of sertraline in the dose range of 50–200 mg is dose-dependent.

Pharmacokinetics in specific patient populations

Children with OCD

The pharmacokinetics of sertraline were studied in 29 children aged 6–12 years and 32 adolescents aged 13–17 years. Doses were gradually increased by titration to a daily dose of 200 mg over 32 days, starting from either 25 mg or 50 mg with gradual increments. Tolerability was similar at 25 mg and 50 mg doses. At steady state with 200 mg dosing, plasma sertraline concentrations 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, especially in children with low body weight, a low initial dose and gradual 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 pharmacokinetic curve (AUC) increases threefold (see sections "Dosage and administration" and "Special precautions for use").

Renal impairment

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

Pharmacogenomics

Individuals with slow CYP2C19 metabolism have plasma sertraline levels approximately 50% higher than those with rapid CYP2C19 metabolism. The clinical significance of this finding is not fully established; therefore, dose titration should be based on individual clinical response.

Clinical characteristics.

Indications.

Sertraline is indicated for the treatment of the following disorders:

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 the active substance or to any of the excipients listed in the section "Composition".

Concomitant use of sertraline with irreversible monoamine oxidase inhibitors (MAOIs) is contraindicated due to the risk of developing serotonin syndrome, with symptoms such as agitation, tremor, and hyperthermia. Sertraline therapy must not be initiated within at least 14 days of discontinuation of treatment with an irreversible MAOI. Sertraline must be discontinued at least 7 days before starting 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.

Contraindicated

Monoamine oxidase inhibitors (MAOIs)

Irreversible MAOIs (e.g., selegiline)

Concomitant use of sertraline with irreversible MAOIs such as selegiline is contraindicated. Sertraline therapy may be initiated no sooner than 14 days after discontinuation of treatment with an irreversible MAOI. Sertraline must be discontinued at least 7 days before starting therapy with an irreversible MAOI (see section "Contraindications").

Selective reversible inhibitor of MAO-A (moclobemide)

Due to the risk of serotonin syndrome, sertraline should not be used in combination with a selective reversible MAOI such as moclobemide. The interval between discontinuation of a reversible MAOI and initiation of sertraline therapy may be shorter than 14 days. It is recommended to discontinue sertraline at least 7 days before starting therapy with a reversible MAOI (see section "Contraindications").

Non-selective reversible MAOIs (linezolid)

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

Severe adverse reactions have been reported in patients who recently discontinued an MAOI (e.g., methylene blue) and started sertraline, or who discontinued sertraline shortly before starting an MAOI. These reactions included tremor, myoclonus, excessive sweating, nausea, vomiting, flushing, dizziness, and hyperthermia with features resembling neuroleptic malignant syndrome, seizures, and fatal outcomes.

Pimozide

In a single-dose study with a low dose of pimozide (2 mg), an increase in pimozide levels of approximately 35% was observed. This increase in levels was not associated with 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 not recommended

CNS 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 function in healthy study participants; however, concomitant use of sertraline with alcohol is not recommended.

Other serotonergic medicinal products

See section "Special precautions for use".

Sertraline should be used with caution when co-administered with opioids (such as fentanyl, primarily used during general anesthesia and for chronic pain management), tramadol, and other serotonergic agents (including other serotonergic antidepressants, amphetamines, and triptans).

Special precautions for use

Medicinal products that prolong the QT interval

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

Lithium

In a placebo-controlled study in healthy volunteers, concomitant administration of sertraline and lithium did not significantly alter the pharmacokinetics of lithium but was associated with increased tremor compared to placebo, suggesting a possible pharmacodynamic interaction. Appropriate monitoring of patients is recommended when sertraline and lithium are used concomitantly.

Phenytoin

Results from a placebo-controlled study in healthy volunteers indicate that prolonged administration of sertraline at a dose of 200 mg/day does not lead to clinically significant inhibition of phenytoin metabolism. However, case reports suggest high phenytoin exposure in patients taking sertraline; monitoring of plasma phenytoin concentrations is recommended during the initial phase of sertraline therapy, with appropriate dose adjustments of phenytoin. Additionally, concomitant use of sertraline with phenytoin, a known inducer of CYP3A4, may lead to decreased plasma concentrations of sertraline.

Metamizole

Concomitant use of sertraline with metamizole, an inducer of metabolizing enzymes including CYP2B6 and CYP3A4, may lead to decreased plasma concentrations of sertraline with a potential reduction in clinical efficacy. Therefore, caution is recommended when using metamizole and sertraline concomitantly; clinical response and/or drug levels should be monitored as necessary.

Triptans

During the post-marketing period, isolated reports have been received of weakness, hyperreflexia, incoordination, confusion, anxiety, and agitation following concomitant use of sertraline and 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 recommended (see section "Special precautions for use").

Warfarin

Concomitant use of sertraline at a dose of 200 mg/day 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, digoxin, atenolol, cimetidine

Concomitant use with cimetidine led to a significant reduction in sertraline clearance. The clinical significance of these changes is not established. Sertraline did not affect the beta-blocking properties of atenolol. No interaction was observed when sertraline at a dose of 200 mg/day was used concomitantly with digoxin.

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., NSAIDs, acetylsalicylic acid, ticlopidine) or other medicinal products that may increase the risk of bleeding (see section "Special precautions for use").

Neuromuscular blocking agents

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

Anesthetics

Concomitant use with the anesthetic suxamethonium should not be used.

Medicinal products metabolized by cytochrome P450

Sertraline may act as a weak or moderate inhibitor of the CYP2D6 isoenzyme. Prolonged administration of sertraline at a dose of 50 mg/day led to 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 that have narrow therapeutic ranges, such as class 1C antiarrhythmics (particularly propafenone and flecainide), tricyclic antidepressants, and typical antipsychotics, especially 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 CYP3A4 substrates (endogenous cortisol, carbamazepine, terfenadine, alprazolam), the CYP2C19 substrate diazepam, and CYP2C9 substrates (tolbutamide, glipizide, 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 levels of sertraline by nearly 100% in a crossover study in 8 healthy Japanese subjects. Therefore, grapefruit juice should be avoided during sertraline therapy (see section "Special precautions for use").

Based on the results of the grapefruit juice interaction study, a potentially even greater increase in sertraline exposure cannot be excluded when sertraline is used concomitantly with potent inhibitors of the CYP3A4 enzyme, such as protease inhibitors, ketoconazole, itraconazole, posaconazole, voriconazole, fluconazole, clarithromycin, telithromycin, and nefazodone. This also applies to moderate CYP3A4 inhibitors such as aprepitant, erythromycin, fluconazole, verapamil, and diltiazem. The use of potent CYP3A4 inhibitors should be avoided during sertraline therapy. Concomitant use with medicinal products used to treat high blood pressure, chest pain, and to regulate heart rate and rhythm (such as flecainide and propafenone) should not be used.

A potential decrease in plasma levels of sertraline cannot be excluded under the influence of other inducers of the CYP3A4 enzyme, such as phenobarbital, carbamazepine, St. John's wort, and rifampicin.

In individuals with slow CYP2C19 metabolism, plasma levels of sertraline are increased by approximately 50% compared to individuals with rapid CYP2C19 metabolism (see section "Pharmacokinetics"). A potential drug interaction with potent inhibitors of CYP2C19, such as omeprazole, lansoprazole, pantoprazole, rabeprazole, fluoxetine, and fluvoxamine, cannot be excluded.

Depression

Concomitant use with medicinal products for the treatment of depression (e.g., amitriptyline, nortriptyline, nefazodone, fluoxetine, fluvoxamine) should not be used.

Schizophrenia

Debitum-sanovel should not be used concomitantly with medicinal products for the treatment of schizophrenia and other psychiatric disorders (e.g., perphenazine, levomepromazine, olanzapine).

Use of medicinal products for pain/arthritis

Concomitant use with medicinal products for the treatment of pain/arthritis (e.g., metamizole, nonsteroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, aspirin) should not be used.

Use in patients with increased gastric acidity

Concomitant use with medicinal products for the treatment of excess stomach acid, ulcers, and heartburn (cimetidine, omeprazole, lansoprazole, pantoprazole, rabeprazole) should not be used.

Diabetes

Concomitant use with medicinal products for the treatment of diabetes, such as tolbutamide, should not be used.

Sedative medicinal products

Concomitant use with sedative medicinal products such as diazepam should not be used.

Use of medicinal products for the treatment of bacterial infections

Concomitant use with medicinal products for the treatment of bacterial infections (e.g., rifampicin, clarithromycin, telithromycin, erythromycin) should not be used.

Treatment of HIV/AIDS and hepatitis C

Concomitant use with medicinal products for the treatment of HIV/AIDS and hepatitis C, such as protease inhibitors (e.g., ritonavir, telaprevir), should not be used.

Chemotherapy

Concomitant use with medicinal products for the prevention of nausea and vomiting after surgery or chemotherapy (e.g., aprepitant) should not be used.

Special precautions for use.

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

Life-threatening syndromes such as serotonin syndrome (SS) or neuroleptic malignant syndrome (NMS) have been reported during treatment with 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, amphetamines, triptans), agents that impair serotonin metabolism (including MAOIs, e.g., methylene blue), antipsychotics and other dopamine antagonists, and opioids. Patients should be monitored for signs and symptoms of SS or NMS (see section "Contraindications").

Switching from SSRIs, antidepressants, or anti-obsessive agents

There are limited data from controlled studies on the optimal timing for switching from SSRIs, antidepressants, or anti-obsessive agents to sertraline. Appropriate medical evaluation should be conducted when making such treatment changes, especially when switching 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, such as amphetamines, tryptophan, fenfluramine, 5-HT agonists, or herbal preparations such as St. John's wort (Hypericum perforatum), should be undertaken with caution, and such combination therapy should be avoided if possible due to potential pharmacodynamic interactions.

QTc interval prolongation/ventricular tachycardia of the torsades de pointes type

Cases of QTc interval prolongation and ventricular tachycardia of the torsades de pointes type have been reported during post-marketing use of sertraline. Most cases occurred in patients with other risk factors for QTc prolongation or torsades de pointes. The effect on QTc prolongation has been confirmed in a QTc study in healthy volunteers, with a statistically significant exposure-response relationship. Therefore, sertraline should be used with caution in patients with additional risk factors for QTc prolongation, such as cardiac disease, hypokalemia or hypomagnesemia, family history of QTc prolongation, bradycardia, or concomitant use of drugs that prolong the QTc interval (see sections "Interaction with other medicinal products and other forms of interaction" and "Pharmacodynamics").

Exacerbation of hypomania or mania

A small percentage of patients receiving approved antidepressants and anti-obsessive agents, including sertraline, have experienced manic/hypomanic episodes. Therefore, sertraline should be used cautiously in patients with a history of mania/hypomania. Close physician monitoring is required. If signs of a manic episode occur, sertraline should be discontinued.

Schizophrenia

Psychotic symptoms may worsen in patients with schizophrenia.

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 experience seizures.

Suicide/suicidal thoughts/suicide attempts or clinical worsening

Depression is associated with an increased risk of suicidal thoughts, self-harm, and suicide attempts (suicidal behaviors and manifestations). This risk persists until significant remission occurs. Since improvement in patients may not occur during the first few weeks or longer of treatment, 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 conditions 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 the treatment of patients with major depressive disorder are necessary when treating patients with other psychiatric disorders.

Patients with a history of suicidal behaviors or manifestations, or those with pronounced suicidal ideation prior to treatment initiation, are at higher risk of developing suicidal thoughts or attempts; thus, they require close monitoring during treatment. A meta-analysis of data from placebo-controlled clinical trials of antidepressants in adult patients with psychiatric disorders showed an increased risk of suicidal behavior with antidepressants in patients under 25 years of age compared to placebo.

Close monitoring of patients, particularly those at high risk of suicidality, is essential, especially at the beginning of therapy and after any dosage adjustments. Patients (and caregivers) should be advised to monitor for any clinical worsening, emergence of suicidal behavior or 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 aged 6–17 years with obsessive-compulsive disorder. In clinical trials involving children and adolescents receiving antidepressants, suicidal behavior (suicide attempts and suicidal thoughts) and hostility (predominantly aggression, oppositional behavior, and anger) were observed more frequently compared to placebo recipients. If, based on clinical need, the decision is made to prescribe this medication, careful monitoring for suicidal symptoms is required, especially at the beginning of treatment. Long-term safety regarding cognitive, emotional, physical, and pubertal development in children and adolescents aged 6 to 16 years was evaluated in a long-term observational study lasting up to 3 years (see section "Pharmacological properties"). In the post-marketing period, there have been reports of several cases of delayed growth and delayed sexual maturation. The clinical significance and causal relationship remain unclear. Physicians should monitor for deviations from normal growth and development in children undergoing long-term therapy.

Abnormal bleeding/bleeding events

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 during SSRIs use. SSRIs/SNRIs may increase the risk of postpartum hemorrhage (see sections "Use during pregnancy or breastfeeding" and "Adverse reactions"). Caution is recommended when using SSRIs in patients, especially when used concomitantly with medicinal products known to affect platelet function (e.g., anticoagulants, atypical antipsychotics, phenothiazines, most tricyclic antidepressants, acetylsalicylic acid, and nonsteroidal anti-inflammatory drugs (NSAIDs)), as well as in patients with a history of bleeding disorders (see section "Interaction with other medicinal products and other forms of interaction").

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. Cases of serum sodium levels below 110 mmol/L have been reported.

Elderly patients may be at 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 (see information on use in elderly patients in sections "Dosage and administration" and "Adverse reactions"). In patients with symptomatic hyponatremia, discontinuation of sertraline therapy and appropriate medical intervention should be considered. Signs and symptoms of hyponatremia include headache, difficulty concentrating, memory impairment, confusion, weakness, and loss of physical coordination, which may lead to falls. Signs and symptoms associated with more severe and/or acute episodes of hyponatremia include hallucinations, syncope, seizures, coma, respiratory arrest, and fatal outcome.

Discontinuation symptoms observed upon stopping sertraline therapy

Discontinuation symptoms are common when stopping the medication, particularly in cases of abrupt discontinuation (see section "Adverse reactions"). Clinical trial data show that the rate of discontinuation reactions in patients who stopped sertraline was 23%, compared to 12% in patients who continued sertraline therapy.

The risk of developing a discontinuation syndrome may depend on several factors, including duration of therapy, dosage, and rate of dose reduction. 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 in some patients, they may be severe. They usually occur within the first few days after stopping therapy, although in very rare cases, 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 over a period of several weeks or months, according to patient needs, when discontinuing treatment (see section "Dosage and administration").

Akathisia/psychomotor agitation

Sertraline use has been associated with akathisia, characterized by a subjectively unpleasant or distressing 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 few weeks of therapy. Increasing the dose may be harmful in patients who develop these symptoms.

Use in 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 a threefold increase in AUC or Cmax compared to individuals with normal hepatic function. No significant differences in plasma protein binding between these two groups were observed. Caution should be exercised when prescribing sertraline to patients with hepatic disease. When prescribing sertraline to patients with impaired liver function, consideration should be given to reducing the dose or frequency of administration. Sertraline should not be used in patients with severe hepatic impairment (see section "Dosage and administration").

Use in renal impairment

Sertraline is extensively metabolized; urinary excretion of unchanged compound is a minor elimination pathway. Pharmacokinetic parameters (AUC0–24 and Cmax) after multiple dosing in patients with mild to moderate (creatinine clearance 30–60 mL/min) or moderate to severe (creatinine clearance 10–29 mL/min) renal impairment showed no statistically significant differences compared to the control group. Dose adjustment based on the degree of renal impairment is not necessary.

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

Diabetes mellitus

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

Electroconvulsive therapy (ECT)

No clinical studies have been conducted to evaluate the risks or benefits of combined use of ECT and sertraline.

Grapefruit juice

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

Effect on urine screening test results

False-positive results in immunoassay screening tests for urinary benzodiazepines have been reported in patients taking sertraline. False-positive results are due to the low specificity of the laboratory test and may persist for several days after discontinuation of sertraline therapy. Sertraline can be differentiated from benzodiazepines in urine by confirmatory testing using gas chromatography/mass spectrometry.

Angle-closure glaucoma

SSRIs, including sertraline, may affect pupil size by causing mydriasis. This effect may lead to angle narrowing, increased intraocular pressure, and development of angle-closure glaucoma, particularly in patients predisposed to this condition. Therefore, sertraline should be used with caution in patients with angle-closure glaucoma or a history of glaucoma.

Information on excipients

This medicinal product contains less than 1 mmol sodium (23 mg) per tablet, i.e., essentially "sodium-free."

Sexual dysfunction

Selective serotonin reuptake inhibitors (SSRIs)/serotonin-norepinephrine reuptake inhibitors (SNRIs) may cause symptoms of sexual dysfunction (see section "Adverse reactions"). Reports of persistent sexual dysfunction, where symptoms persist despite discontinuation of SSRIs/SNRIs, have been received.

Use during pregnancy or breastfeeding.

Pregnancy

There are no well-controlled studies of the drug in pregnant women. However, a substantial amount of data has not shown evidence of fetal 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, pharmacodynamic action of the drug, and/or direct pharmacodynamic action on the fetus.

Use of sertraline during pregnancy has been reported to cause in some newborns (whose mothers took sertraline) symptoms similar to withdrawal reactions. This phenomenon has also been observed with other SSRIs antidepressants. Sertraline is not recommended for use during pregnancy, except when the woman's clinical condition justifies the expected benefits of using the drug over the potential risk.

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

Newborns should be monitored if the mother continues sertraline use late in pregnancy, particularly in the third trimester. After sertraline use in late pregnancy, newborns may experience the following symptoms: respiratory distress syndrome, cyanosis, apnea, seizures, temperature instability, feeding difficulties, vomiting, hypoglycemia, hypertonia, hypotonia, hyperreflexia, tremor, syndrome of increased neuromuscular excitability, irritability, lethargy, persistent crying, somnolence, and difficulty sleeping. These symptoms may be due to either serotonergic effects or withdrawal symptoms. In most cases, these complications occur immediately after birth or shortly thereafter (within less than 24 hours).

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

Breastfeeding

Published data on sertraline levels in breast milk indicate that sertraline and its metabolite N-desmethylsertraline are excreted in small amounts into breast milk. Generally, negligible or undetectable concentrations of the drug were found in infant plasma, except in one case where the drug concentration in infant plasma was approximately 50% of the concentration in maternal plasma (but without any noticeable effect on the infant's health). No adverse effects of the drug on the health of breastfed infants 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 risk.

Fertility

Animal studies did not reveal any effect of sertraline on fertility parameters.

Reports from human studies with some SSRIs suggest that effects on sperm quality are reversible. To date, no effect on human fertility has been identified.

Ability to affect reaction speed when driving or operating machinery.

Clinical pharmacological studies indicate no effect of sertraline on psychomotor functions. However, patients should be warned that psychotropic agents may impair mental or physical reactions required for performing potentially hazardous tasks, such as driving a car or operating machinery.

Method of Administration and Dosage

Method of Administration

Sertaline should be taken once daily (in the morning or evening).

Sertaline tablets may be taken independently of food intake.

Initiation of Treatment

Depression and OCD

Treatment with sertaline should be initiated at a dose of 50 mg/day.

Panic Disorders, PTSD, and Social Anxiety Disorder

Treatment 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 has been shown to reduce the frequency of adverse effects typical of panic disorders at the beginning of treatment.

Dose Titration

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

In patients who do not respond to a 50 mg dose, therapeutic effect may be achieved by increasing the dose. Dose adjustments should be made in 50 mg increments at intervals of not less than one week, up to a maximum dose of 200 mg/day. Dose adjustments should not occur more frequently than once per week, considering the elimination half-life of sertaline, 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 therapeutic response, especially in patients with OCD.

Maintenance Dose

Dosage during long-term therapy should be maintained at the lowest effective level, with subsequent 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

During long-term therapy in patients with panic disorders and OCD, regular assessment of treatment is required, as efficacy of the drug in preventing relapse has not been demonstrated for these disorders.

Use in Children

Children and Adolescents with Obsessive-Compulsive Disorder

Adolescents aged 13–17 years: initial dose is 50 mg once daily.

Children aged 6–12 years: initial dose is 25 mg once daily. After 1 week, the dose may be increased to 50 mg once daily.

If necessary, in cases of insufficient response, further dose increases are possible, increasing by 50 mg at a time over several weeks. The maximum dose is 200 mg/day. However, when increasing the dose beyond 50 mg, the generally lower body weight of children compared to adults should be taken into account. Dose adjustments should not occur more frequently than once per week.

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

Data on use of the drug in children under 6 years of age are lacking (see also section "Special Instructions").

Use in Elderly Patients

Dosage in elderly patients should be selected cautiously, as these patients may have an increased risk of developing hyponatremia (see section "Special Instructions").

Use in Hepatic Impairment

Caution should be exercised when administering sertaline to patients with liver disease. In patients with impaired liver function, the dose or frequency of administration should be reduced. Sertaline should not be used in patients with severe hepatic impairment, as clinical data on use in such patients are lacking (see section "Special Instructions").

Use in Renal Impairment

Dose adjustment is not required in patients with renal impairment (see section "Special Instructions").

Withdrawal Symptoms Observed upon Discontinuation of Sertaline Therapy

Abrupt discontinuation of the drug should be avoided. When stopping sertaline treatment, the dose should be gradually reduced over at least 1–2 weeks to minimize the risk of withdrawal reactions (see sections "Special Instructions" and "Adverse Reactions"). If intolerable symptoms occur after dose reduction or discontinuation, resumption of the previously prescribed dose may be considered. Subsequently, the physician may continue to reduce the dose, but more gradually.

Children

Sertaline should not be used for the treatment of children, except for children with obsessive-compulsive disorder aged 6 years and older (see section "Method of Administration and Dosage").

Overdose

Toxicity

Sertaline has a safety margin that depends on the patient population and/or concomitant use of other medicinal products. Fatal cases of sertaline overdose have been reported, both with sertaline alone and in combination with other agents and/or alcohol. Therefore, every case of overdose requires intensive therapy.

Symptoms

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

Cases of QTc interval prolongation/ventricular tachycardia of the "torsades de pointes" type have been reported after sertaline overdose; therefore, ECG monitoring is recommended in all cases of sertaline overdose (see sections "Special Instructions," "Interaction with Other Medicinal Products and Other Forms of Interaction," and "Pharmacodynamics").

Therapy

There are no specific antidotes for sertaline. Maintenance of airway patency, adequate oxygenation, and ventilation should be ensured and supported as needed. In the management of overdose, administration of activated charcoal (which may be used with a laxative) may be as effective or more effective than gastric lavage. Induced emesis is not recommended. Cardiac monitoring (e.g., ECG) and monitoring of vital signs are recommended, along with general symptomatic and supportive therapy. Due to the large volume of distribution of sertaline, interventions such as forced diuresis, dialysis, hemoperfusion, or exchange transfusion are unlikely to be beneficial.

Adverse Reactions

The most commonly observed adverse effect is nausea. In the treatment of social anxiety disorder, sexual dysfunction (ejaculation disorder) occurred in 14% of men taking sertraline, compared to 0% of patients receiving placebo. These adverse effects are dose-dependent and often resolve spontaneously during continued therapy.

The adverse effect profile observed in double-blind, placebo-controlled studies involving patients with OCD, panic disorders, PTSD, and social anxiety disorders was similar to that observed in patients with depression participating in clinical trials.

Below are data on adverse reactions observed during post-marketing surveillance (frequency unknown) and in placebo-controlled clinical trials (in which a total of 2542 patients received sertraline and 2145 patients received placebo), involving patients with depression, OCD, panic disorders, PTSD, and social anxiety disorders.

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

Immediately inform your doctor if, after taking this medication, the patient experiences any of the symptoms listed below, as they may indicate a serious condition.

If the patient develops a severe blistering rash (multiform erythema) (which may affect the mouth and tongue). This could be a sign of a condition known as Stevens-Johnson syndrome or toxic epidermal necrolysis. In such cases, the doctor will discontinue treatment.

Allergic reaction or allergy, which may include symptoms such as itchy rash, difficulty breathing, wheezing, swollen eyelids, facial or lip swelling.

If agitation, confusion, diarrhea, high body temperature and blood pressure, excessive sweating, and rapid heartbeat are observed. These are symptoms of a condition known as serotonin syndrome. In rare cases, this syndrome may occur if the patient is taking certain other medications concurrently with sertraline. The doctor may instruct to discontinue treatment.

If the skin and eyes turn yellow, this may indicate liver damage.

If the patient develops depressive symptoms with thoughts of self-harm or suicide (suicidal ideation).

If the patient feels restless and unable to sit or stand still after taking Debitum-Sanovel. The patient should inform their doctor if they begin to feel restless.

If the patient experiences a seizure.

If the patient is currently experiencing a manic episode.

Below is the frequency of adverse reactions observed in placebo-controlled clinical trials in patients with depression, OCD, panic disorders, PTSD, and social anxiety disorders. Combined data from studies and post-marketing surveillance (frequency unknown) are presented.

Adverse reaction frequency is categorized as: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1000 to < 1/100); rare (≥ 1/10,000 to < 1/1000); very rare (< 1/10,000); frequency unknown (cannot be estimated from available data).

Infections and infestations. Common: upper respiratory tract infections, pharyngitis, rhinitis; uncommon: gastroenteritis, otitis media; rare: diverticulitis§.

Benign, malignant and unspecified neoplasms (including cysts and polyps). Uncommon: neoplasm.

Blood and lymphatic system disorders. Rare: lymphadenopathy, thrombocytopenia*§, leukopenia*§, enlarged lymph glands.

Immune system disorders. Uncommon: hypersensitivity*, seasonal allergy*; rare: anaphylactoid reaction*.

Endocrine disorders. Uncommon: hypothyroidism*; rare: hyperprolactinemia*§, syndrome of inappropriate antidiuretic hormone secretion*§.

Metabolism and nutrition disorders. Common: decreased appetite, increased appetite*; rare: hypercholesterolemia, diabetes mellitus, hypoglycemia*, hyperglycemia*§, hyponatremia*§.

Psychiatric disorders. Very common: insomnia; common: anxiety*, depression*, agitation*, decreased libido*, restlessness, depersonalization, nightmares, bruxism*; uncommon: suicidal ideation/suicidal behavior, psychotic disorder*, pathological thinking, apathy, hallucinations*, aggression*, euphoric mood*, paranoia; rare: conversion disorder*§, pyromania*§, drug dependence, sleepwalking, premature ejaculation.

Nervous system disorders. Very common: dizziness, headache*, somnolence, fatigue; common: tremor, movement disorders (including extrapyramidal symptoms such as hyperkinesia, hypertonia, dystonia, jaw spasms or gait disturbances, reduced touch sensitivity, tingling), paresthesia*, hypertonia*, attention disturbances, dysgeusia; uncommon: amnesia, hypoesthesia*, involuntary muscle contractions*, syncope*, hyperkinesia*, migraine*, seizures*, postural dizziness, coordination disturbances, speech disorders; rare: trismus of masticatory muscles, coma*, akathisia (see section "Special precautions"), dyskinesia, hyperesthesia, cerebral vasospasm (including transient cerebral vasoconstriction syndrome and Call-Fleming syndrome)*§, psychomotor agitation*§ (see section "Special precautions"), sensory disturbances, choreoathetosis§, nightmares, symptoms associated with serotonin syndrome* or neuroleptic malignant syndrome, sometimes related to concomitant use of serotonergic agents, such as agitation, confusion, excessive sweating, diarrhea, fever, hypertension, rigidity, and tachycardia§.

Eye disorders. Common: visual disturbances*; uncommon: mydriasis*; rare: scotoma, glaucoma, diplopia, photophobia, hyphema*§, anisocoria*§, visual disorders§, lacrimation disorders, maculopathy.

Ear and labyrinth disorders. Common: tinnitus*; uncommon: ear infection, ear pain.

Cardiac disorders. Common: palpitations*; uncommon: tachycardia*, cardiac rhythm disturbances; rare: dyspnea, myocardial infarction*§, torsades de pointes ventricular tachycardia*§ (see sections "Special precautions", "Interaction with other medicinal products and other forms of interaction", and "Pharmacodynamics"), bradycardia, QTc interval prolongation* (see sections "Special precautions", "Interaction with other medicinal products and other forms of interaction", and "Pharmacodynamics").

Vascular disorders. Common: hot flushes*; uncommon: pathological bleeding (such as gastrointestinal bleeding, epistaxis)*, hypertension*, hyperemia, hematuria*; rare: peripheral ischemia, hot flushes.

Respiratory, thoracic and mediastinal disorders. Common: yawning*; sore throat; nasal congestion; uncommon: dyspnea, epistaxis*, bronchospasm*; rare: hyperventilation, interstitial lung disease*§, laryngospasm, dysphonia, stridor*§, hypoventilation, hiccups, labored breathing, wheezing, eosinophilic pneumonia.

Gastrointestinal disorders. Very common: nausea, diarrhea, dry mouth; common: dyspepsia, constipation*, abdominal pain*, vomiting*, flatulence; uncommon: melena, dental disorders, esophagitis, glossitis, hemorrhoids, hypersalivation, dysphagia, belching, tongue changes; rare: gastrointestinal inflammation, oral mucosal ulcers, pancreatitis*§, hematochezia, tongue ulcers, stomatitis; frequency unknown: microscopic colitis*.

Hepatobiliary disorders. Rare: liver function abnormalities, serious liver function abnormalities (including hepatitis, jaundice, and hepatic failure).

Skin and subcutaneous tissue disorders. Common: hyperhidrosis, rash*; uncommon: periorbital edema*, urticaria*, alopecia*, pruritus*, purpura*, dermatitis, dry skin, facial swelling, cold sweat; rare: rare cases of severe skin reactions such as Stevens-Johnson syndrome* and epidermal necrolysis*§, skin reaction*§, photosensitivity§, angioneurotic edema, pathological changes in hair texture, unusual skin odor, bullous dermatitis, vesicular rash.

Musculoskeletal and connective tissue disorders. Common: back pain, arthralgia*, myalgia; uncommon: osteoarthritis, muscle twitching, muscle spasms*, muscle weakness; rare: rhabdomyolysis*§, bone injury; frequency unknown: trismus*.

Renal and urinary disorders. Uncommon: polyuria, micturition disorders, urinary retention, urinary incontinence*, polyuria, nocturia; rare: micturition disorders*, oliguria.

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

General disorders. Very common: increased fatigue*; common: fever, cold, malaise*, chest pain*, asthenia*, pyrexia*; uncommon: peripheral edema*, chills, gait disturbances*, thirst; rare: hernia, decreased drug tolerance.

Investigations. Common: weight gain*; uncommon: increased alanine aminotransferase* (ALT), increased aspartate aminotransferase* (AST), weight loss*; rare: decreased thyroid hormone levels, increased blood cholesterol*, abnormal clinical laboratory test results, impaired sperm quality, platelet function changes*§.

Injury, poisoning and procedural complications. Common: injury.

Surgical and medical procedures. Rare: vasodilation procedure.

* Adverse reactions reported during the post-marketing period.

§ Frequency of adverse reactions estimated using the upper bound of the 95% confidence interval according to the "rule of three".

† This adverse reaction was reported for the therapeutic class SSRIs/SNRIs (see sections "Special precautions" and "Use during pregnancy or breastfeeding").

Withdrawal symptoms observed upon discontinuation of sertraline

Discontinuation of sertraline treatment (especially abrupt discontinuation) usually leads to 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; however, in some patients, they may be severe and/or prolonged. Therefore, when sertraline treatment is no longer 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, has been associated with clinically significant cases of hyponatremia in elderly patients, in whom the risk of developing this adverse effect may be increased (see section "Special precautions").

Use in children

In over 600 children receiving sertraline, the overall adverse reaction profile was generally similar to that observed in studies involving adult patients. The following adverse reactions were recorded in controlled trials (number of patients receiving sertraline was 281):

Very common (≥ 1/10): headache (22%), insomnia (21%), diarrhea (11%), nausea (15%).

Common (≥ 1/100 to < 1/10): chest pain, mania, pyrexia, vomiting, anorexia, affective lability, aggression, agitation, restlessness, attention disturbances, dizziness, hyperkinesia, migraine, somnolence, tremor, visual disturbances, dry mouth, dyspepsia, nightmares, increased fatigue, urinary incontinence, rash, acne, epistaxis, flatulence. Uncommon (≥ 1/1000 to < 1/100): QT interval prolongation on ECG (see sections "Special precautions", "Interaction with other medicinal products and other forms of interaction", and "Pharmacodynamics"), suicide attempts, seizures, extrapyramidal disorder, paresthesia, depression, hallucinations, purpura, hyperventilation, anemia, liver function abnormalities, increased alanine aminotransferase, cystitis, herpes simplex, otitis externa, ear pain, eye pain, mydriasis, malaise, hematuria, pustular rash, rhinitis, injury, weight loss, muscle twitching, unusual dreams, apathy, albuminuria, polyuria, polyuria, breast pain, menstrual cycle disturbances, alopecia, dermatitis, skin lesions, unusual skin odor, bruxism, hot flushes. Frequency unknown: enuresis.

Effects typical of this class of medicinal products

Epidemiological studies, primarily involving 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 of adverse reactions after drug registration is important. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals, pharmacists, patients, and their legal representatives should report all suspected adverse reactions and lack of efficacy through the automated pharmacovigilance information system at: https://aisf.dec.gov.ua.

Shelf life.

2 years.

Storage conditions.

Store in a place inaccessible to children at a temperature not exceeding 25 °C.

Packaging. 14 tablets in a blister; 2 blisters in a cardboard box.

Prescription status. Prescription only.

Manufacturer. Sanovel Ilac Sanai ve Ticaret A.S., Turkey.

Manufacturer's address and location of business activity.

Balaban district, Cihanger Sokagi, No. 10, Istanbul, 34580, Silivri, Turkey.