Instructions Stimuloton film-coated tablets 50 mg blister No. 30
Composition
active ingredient: sertraline;
1 tablet contains 50 mg of sertraline (as 55.95 mg of sertraline hydrochloride);
excipients: magnesium stearate, hydroxypropyl cellulose, sodium starch glycolate
(type A), calcium hydrogen phosphate dihydrate, microcrystalline cellulose;
shell: hypromellose, macrogol 6000, titanium dioxide (E 171).
Dosage form
Film-coated tablets.
Main physicochemical properties: white or almost white biconvex, film-coated tablets, oval in shape, with stylized engraving "E 271" on one side and a score on the other side, odorless.
Pharmacotherapeutic group
Antidepressants. Selective serotonin reuptake inhibitors. ATX code N06A B06.
Pharmacological properties
Pharmacodynamics.
Mechanism of action
Sertraline is a potent and specific inhibitor of neuronal serotonin (5-HT) uptake in vitro, which in animals leads to potentiation of the effects of 5-HT. Sertraline has only a very weak effect on the processes of neuronal reuptake of noradrenaline and dopamine. At clinical doses, sertraline blocks the uptake of serotonin in human platelets. The drug does not show any stimulant, sedative, anticholinergic or cardiotoxic effects in animal experiments. In controlled studies with healthy volunteers, sertraline did not show any sedative effects and did not affect psychomotor functions. Since sertraline is characterized by selective inhibition of 5-HT uptake, it does not increase catecholaminergic activity. The drug has no affinity for muscarinic (cholinergic), serotonergic, dopaminergic, adrenergic, histaminergic, GABA or benzodiazepine receptors. Long-term use of sertraline in animals was associated with a decrease in the number of brain noradrenaline receptors, which is also observed with the use of other clinically effective antidepressants and anti-obsessional drugs.
Sertraline is not a drug of 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 that would indicate abuse potential. In contrast, subjects taking both alprazolam and d-amphetamine had significantly higher rates of abuse, euphoria, and drug dependence than subjects taking placebo. Sertraline did not produce the stimulant effects and anxiety associated with d-amphetamine or the sedation and psychomotor impairment associated with alprazolam. Sertraline does not induce positive incentive salience in rhesus macaques trained to self-administer cocaine, and does not substitute for the reward salience of either d-amphetamine or pentobarbital in rhesus macaques.
Clinical efficacy and safety
Major Depressive Disorder. A study was conducted in outpatients with depression who had responded to treatment by the end of an initial 8-week open-label phase of sertraline 50–200 mg/day. These patients (n = 295) were randomized to either continue sertraline 50–200 mg/day or placebo for 44 weeks in a double-blind study. The rate of relapse in the sertraline group was statistically significantly lower than in the placebo group. The mean dose in participants who completed the study was 70 mg/day. The percentage of patients who responded to treatment (defined as patients who did not relapse) in the sertraline and placebo groups was 83.4% and 60.8%, respectively.
Cardiac Electrophysiology/ In a robust study of the steady-state QTc interval at supratherapeutic exposures in healthy volunteers (given a dose of 400 mg/day, which was twice the maximum recommended daily dose), the upper limit of the 2-sided 90% CI for the time-matched least squares mean difference in QTcF between sertraline and placebo (11.666 ms) exceeded the pre-specified cut-off value of 10 ms at the 4-hour post-dose time point. Exposure-response analysis indicated a weak positive relationship between QTcF and plasma sertraline concentrations [0.036 ms/(ng/mL); p < 0.0001]. Based on the exposure-response model, the threshold for clinically significant prolongation of the QTcF interval (i.e. greater than 10 ms for the predicted 90% CI) was at least 2.6-fold higher than the mean Cmax (86 ng/ml) after the highest recommended dose of sertraline (200 mg/day) (see sections 4.4, 4.5, 4.8 and 4.9).
Obsessive-compulsive disorder in pediatric patients. The safety and efficacy of sertraline (50–200 mg/day) were studied in non-depressed children (6–12 years) and adolescents (13–17 years) receiving outpatient treatment for obsessive-compulsive disorder (OCD). After a 1-week initial single-blind placebo period, patients were randomized to receive sertraline or placebo for 12 weeks of flexible dosing. Children (6–12 years) were started on 25 mg. Patients randomized to sertraline showed significantly greater improvement than patients randomized to placebo on the Yale-Brown Children's Obsessive-Compulsive Scale (CY-BOCS) (p = 0.005), the National Institute of Mental Health (NIMH) Global Obsessive-Compulsive Scale (p = 0.019), and the Clinical Global Assessment - Improvement (p = 0.002). In addition, patients in the sertraline group showed a trend toward greater improvement than those in the placebo group on the Clinical Global Assessment - Severity of Illness (p = 0.089). The mean baseline CY-BOCS score and mean change from baseline in the placebo group were 22.25 ± 6.15 and -3.4 ± 0.82, respectively, while the mean baseline score and mean change from baseline in the sertraline group were 23.36 ± 4.56 and -6.8 ± 0.87, respectively. In the retrospective analysis, the percentage of patients who responded to treatment, defined as patients with at least a 25% decrease in CY-BOCS score (primary efficacy parameter) from baseline to endpoint, was 53% in the sertraline group compared with 37% in the placebo group (p = 0.03).
There are no data on long-term clinical studies of the effectiveness of the drug in pediatric patients.
Children: There are no data on the use of sertraline in children under 6 years of age.
Postmarketing Safety Study SPRITES: An observational postmarketing study was conducted in 941 patients aged 6 to 16 years to evaluate the long-term safety of sertraline therapy (with and without psychotherapy) compared to psychotherapy on cognitive, emotional, physical, and pubertal maturation for up to 3 years. This study was conducted in a clinical setting in children and adolescents with primary diagnoses of obsessive-compulsive disorder, depression, or other anxiety disorders, assessing cognition (assessed by the Trails B test and the BRIEF index), behavioral/emotional regulation (assessed by the 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 6 years of age and older with OCD (see section 4.4). Standardization of each primary outcome measure based on sex-age norms showed that overall outcomes were consistent with normal development. No statistically significant differences from baseline were observed, except for body weight. In comparative analyses, statistically significant results were observed for body weight, but the magnitude of the change was small.
Pharmacokinetics.
Absorption: During 14 days of oral administration of sertraline at doses of 50-200 mg once daily in humans, peak plasma concentrations of sertraline are reached 4.5-8.4 hours after 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 first-pass metabolism in the liver.
Elimination. The mean elimination half-life of sertraline is approximately 26 hours (range 22 to 36 hours). In accordance with the terminal elimination half-life, accumulation of the drug (with an increase in its level by approximately twofold) to equilibrium concentrations is observed, which are achieved after 1 week of once-daily administration. The elimination half-life of N-desmethylsertraline is 62–104 hours. Sertraline and N-desmethylsertraline are extensively metabolized in humans, their final metabolites are excreted in feces and urine in equal amounts. Only a very small part (< 0.2%) of sertraline is excreted in urine unchanged.
Linearity/non-linearity: The pharmacokinetics of sertraline are dose-dependent over the dose range of 50 to 200 mg.
Pharmacokinetics in specific patient groups
Children with OCD. The pharmacokinetics of sertraline were studied in 29 children aged 6-12 years and 32 adolescents aged 13-17 years. These patients were titrated to a daily dose of 200 mg over 32 days, starting at either 25 mg or 50 mg with gradual increases. Tolerability was similar at 25 mg and 50 mg. At steady state, plasma sertraline concentrations in children aged 6-12 years at 200 mg were approximately 35% higher than in patients aged 13-17 years and 21% higher than in adult controls. There were no significant differences in clearance between boys and girls. Therefore, for use in children, especially those with low body weight, a low initial dose is recommended and titrated in 25 mg increments. The same doses as for adults can be used in adolescents.
Adolescents and elderly patients: The pharmacokinetic profile of sertraline in adolescents and elderly patients does not differ significantly from that in adults aged 18-65 years.
Hepatic impairment: In patients with hepatic impairment, the half-life of sertraline is prolonged and the area under the pharmacokinetic curve (AUC) is increased threefold (see sections 4.2 and 4.4).
Renal impairment: No significant accumulation of sertraline was observed in patients with moderate or severe renal impairment.
Pharmacogenomics: Sertraline plasma levels were approximately 50% higher in CYP2C19 poor metabolizers compared to CYP2C19 extensive metabolizers. The clinical significance of this is unknown and dose titration should be based on the patient's clinical response.
Indication
Sertraline is indicated for the treatment of the following disorders:
· major depressive episodes. Prevention of recurrence of major depressive episodes;
Panic disorders with or without agoraphobia;
· obsessive-compulsive disorder (OCD) in adults and children aged 6-17 years;
· social anxiety disorder;
· post-traumatic stress disorder (PTSD).
Contraindication
Hypersensitivity to the active substance or to any of the excipients listed in the "Composition" section.
Concomitant use of sertraline with irreversible monoamine oxidase (MAO) inhibitors is contraindicated due to the risk of serotonin syndrome with symptoms such as agitation, tremor and hyperthermia. Sertraline therapy should not be initiated for at least 14 days after discontinuation of treatment with an irreversible MAO inhibitor. Sertraline should be discontinued at least 7 days before initiation of treatment with an irreversible MAO inhibitor.
The concomitant use of sertraline and pimozide is contraindicated (see section “Interaction with other medicinal products and other types of interactions”).
Interaction with other medicinal products and other types of interactions
Contraindicated
Monoamine oxidase inhibitors (MAOIs)
Irreversible MAOIs (e.g. selegiline). The use of sertraline with irreversible MAOIs such as selegiline is contraindicated. Sertraline therapy should not be initiated until 14 days after discontinuation of the irreversible MAOI. Sertraline should be discontinued at least 7 days before initiation of treatment with an irreversible MAOI (see section 4.3).
Selective reversible MAO-A inhibitor (moclobemide). Due to the risk of serotonin syndrome, sertraline should not be used in combination with selective reversible MAOIs such as moclobemide. After discontinuation of a reversible MAOI, the period before starting sertraline therapy may be shorter than 14 days. It is recommended to stop taking sertraline at least 7 days before starting treatment with a reversible MAOI (see section "Contraindications").
Non-selective reversible MAO inhibitors (linezolid). The antibiotic linezolid is a weak non-selective reversible MAOI that should not be used in patients taking sertraline (see Contraindications).
Serious adverse reactions have been reported in patients who have recently discontinued MAOIs (e.g., methylene blue) and started taking sertraline, or who have discontinued sertraline shortly before starting an MAOI. These reactions included tremor, myoclonus, hyperhidrosis, nausea, vomiting, flushing, dizziness, and hyperthermia with features resembling neuroleptic malignant syndrome, seizures, and death.
In a single low-dose pimozide (2 mg) study, 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 4.3).
Concomitant use with sertraline is not recommended.
Central nervous system depressants and alcohol
Co-administration of sertraline 200 mg/day did not potentiate the effects of alcohol, carbamazepine, haloperidol, or phenytoin on cognitive and psychomotor performance in healthy subjects. However, co-administration of sertraline with alcohol is not recommended.
Other serotonergic drugs
(See section "Features of use").
It is recommended that sertraline be prescribed with caution with opioids (such as fentanyl, which is used mainly during general anesthesia and in the treatment of chronic pain) and other serotonergic drugs (including other serotonergic antidepressants, amphetamines and triptans).
Special precautions for use
Drugs that prolong the QT interval
The risk of QTc prolongation and/or ventricular arrhythmias (e.g. torsades de pointes) is increased when co-administered with other drugs that prolong the QTc interval (e.g. some antipsychotics and antibiotics) (see sections 4.4 and 5.1).
Lithium
In a placebo-controlled study in healthy volunteers, concomitant administration of sertraline and lithium did not significantly alter the pharmacokinetics of lithium, but resulted in increased tremor compared to placebo, suggesting a possible pharmacodynamic interaction. Appropriate monitoring of the patient should be ensured when sertraline and lithium are used concomitantly.
Phenytoin
The results of a placebo-controlled study in healthy volunteers indicate that long-term administration of sertraline at a dose of 200 mg/day does not lead to clinically significant inhibition of phenytoin metabolism. However, some case reports indicate high phenytoin exposures in patients taking sertraline; it is recommended to monitor phenytoin plasma concentrations during the initial phase of sertraline therapy with appropriate adjustments to the phenytoin dose. In addition, concomitant use of the drug with phenytoin may lead to a decrease in sertraline plasma concentrations. The possibility of a decrease in sertraline plasma levels under the influence of other CYP3A4 inducers, such as phenobarbital, carbamazepine, St. John's wort, and rifampicin, cannot be excluded.
Triptans
During post-marketing surveillance, there have been isolated reports of weakness, hyperreflexia, incoordination, confusion, anxiety and agitation following concomitant use of sertraline and sumatriptan. Symptoms of serotonin syndrome may also occur with other drugs of the same class (triptans). If concomitant treatment with sertraline and triptans is clinically necessary, appropriate monitoring of the patient is recommended (see section 4.4).
Warfarin
Concomitant use of sertraline 200 mg/day and warfarin resulted in a small but statistically significant increase in prothrombin time, which may in some rare cases lead to abnormalities in the international normalized ratio (INR). Therefore, prothrombin time should be carefully monitored when initiating and discontinuing sertraline therapy.
Interaction with other drugs, with digoxin, atenolol, cimetidine
Concomitant use with cimetidine resulted in a significant decrease in sertraline clearance. The clinical significance of these changes is unknown. Sertraline did not affect the beta-blocking properties of atenolol. No interaction was observed when sertraline 200 mg/day was co-administered with digoxin.
Drugs that affect platelet function
The risk of bleeding increases with the concomitant use of selective serotonin reuptake inhibitors (SSRIs), including sertraline, with drugs that affect platelet function (e.g. non-steroidal anti-inflammatory drugs (NSAIDs), acetylsalicylic acid and ticlopidine) or other drugs that increase the risk of bleeding (see section "Special warnings and precautions for use").
Neuromuscular transmission blockers
SSRIs may reduce plasma cholinesterase activity, leading to prolonged neuromuscular blockade by mivacurium or other neuromuscular blocking agents.
Sertraline may act as a weak to moderate inhibitor of the CYP2D6 isoenzyme. Long-term administration of sertraline at a dose of 50 mg/day resulted in a moderate increase (on average by 23-37%) in the steady-state plasma concentrations of desipramine (an indicator of CYP2D6 isoenzyme activity). Clinically significant interactions may occur with other CYP2D6 substrates with narrow therapeutic ranges, such as class 1C antiarrhythmics, including propafenone and 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 and CYP1A2 isoenzymes. This is supported by the results of in vivo drug interaction studies using CYP3A4 substrates (endogenous cortisol, carbamazepine, terfenadine, alprazolam), CYP2C19 substrate (diazepam) and CYP2C9 substrates (tolbutamide, glibenclamide and phenytoin). The results of in vitro studies indicate that sertraline has very little or no potential to inhibit CYP1A2.
Daily consumption of three glasses of grapefruit juice increased sertraline plasma levels by almost 100% in a cross-over study in 8 healthy Japanese subjects. Therefore, grapefruit juice should be avoided during treatment with sertraline (see section 4.4).
Based on the results of the grapefruit juice interaction study, it cannot be excluded that even a significantly greater increase in sertraline exposure may occur when co-administered with potent CYP3A4 inhibitors, such as the protease inhibitors ketoconazole, itraconazole, posaconazole, voriconazole, clarithromycin, telithromycin and nefazodone. This also applies to moderate CYP3A4 inhibitors, such as aprepitant, erythromycin, fluconazole, verapamil and diltiazem. Potent CYP3A4 inhibitors should be avoided during sertraline therapy.
In CYP2C19 poor metabolisers, plasma levels of sertraline are increased by approximately 50% compared to CYP2C19 extensive metabolisers (see section 5.2). Drug interactions with potent CYP2C19 inhibitors, such as omeprazole, lansoprazole, pantoprazole, rabeprazole, fluoxetine, fluvoxamine, cannot be excluded.
Application features
Serotonin syndrome (SS) or neuroleptic malignant syndrome (NMS)
Syndromes that may be life-threatening, such as SSRIs or NMS, have been reported with SSRIs, including sertraline. The risk of SSRIs or NMS with SSRIs is increased by concomitant use of other serotonergic agents (including other serotonergic antidepressants, amphetamines, triptans) with agents that disrupt serotonin metabolism (including MAOIs, e.g. methylene blue), antipsychotics, other dopamine antagonists and opioids. Patients should be monitored for signs and symptoms of SSRIs or NMS (see section 4.3).
Switching from SSRIs, antidepressants, or anti-obsessional medications
There are limited data from controlled trials investigating the optimal timing of switching from SSRIs, antidepressants, or antiobsessional drugs to sertraline. Appropriate medical evaluation should be performed when such changes in treatment are made, especially when switching to sertraline from long-acting drugs such as fluoxetine.
Other serotonergic agents, such as tryptophan, fenfluramine, and 5-HT agonists
Concomitant use of sertraline and other agents that enhance the effect of serotonergic neurotransmission, such as amphetamines, tryptophan, fenfluramine, 5-HT agonists or herbal preparations, St. John's wort (Hypericum perforatum), should be undertaken with caution and such combination therapy should be avoided (due to possible pharmacodynamic interactions).
QTc prolongation/torsades de pointes
During the post-marketing period, cases of QTc prolongation and torsades de pointes have been reported, mostly in patients with risk factors. The effect on QTc prolongation was confirmed in a QTc study in healthy volunteers with a statistically significant positive 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, and concomitant use of medicinal products known to prolong the QTc interval (see sections 4.5 and 5.1).
Worsening of hypomania or mania
Symptoms of mania/hypomania have been reported in a small percentage of patients treated with licensed antidepressants and anti-obsessional drugs, including sertraline. Therefore, sertraline should be used with caution in patients with a history of mania/hypomania. Close medical supervision is required. Sertraline should be discontinued if a patient develops signs of a manic phase.
Schizophrenia
Psychotic symptoms may be exacerbated in patients with schizophrenia.
Sertraline therapy may cause seizures: sertraline should not be prescribed to patients with unstable epilepsy; in patients with controlled epilepsy, the use of sertraline requires careful supervision. Patients who develop seizures should discontinue the drug.
Suicide/suicidal thoughts/suicidal attempts or clinical signs of worsening
Depression is associated with an increased risk of suicidal ideation, self-harm and suicide attempts (suicidal acts and manifestations). This risk exists until significant remission is achieved. As improvement may not occur within the first few weeks or longer of therapy, patients should be closely monitored until such improvement occurs. In general, clinical experience suggests that the risk of suicide is increased in the early stages of recovery.
Other psychiatric conditions for which sertraline is prescribed may also be associated with an increased risk of suicidal behaviour and suicidal thoughts. In addition, these conditions may be co-morbid with major depressive disorder. Therefore, similar precautions that apply to the treatment of patients with major depressive disorder should be taken when treating patients with other psychiatric disorders.
Patients with a history of suicidal ideation or behavior, or those showing a significant degree of suicidal ideation prior to initiation of therapy, are known to be at greater risk of suicidal thoughts or suicide attempts and should receive careful monitoring during treatment. A meta-analysis of placebo-controlled clinical trials of antidepressants in adult patients with psychiatric disorders has shown an increased risk of suicidal behavior with antidepressants in patients under 25 years of age compared with placebo.
Patients, particularly those at high risk of suicidality, should be closely monitored, particularly at the beginning of therapy and after any dose changes. Patients (and caregivers of patients) should be warned about the need to monitor for any clinical worsening, the emergence of suicidal behaviour or suicidal thoughts, as well as any unusual changes in behaviour and to seek medical advice immediately if these symptoms present.
Use in children
Sertraline should not be used in children and adolescents, except in patients with obsessive-compulsive disorder aged 6 to 17 years. In clinical trials, suicidal behaviour (suicidal attempts and suicidal thoughts) and hostility (predominantly aggression, oppositional behaviour and anger) were more frequently observed in children and adolescents treated with antidepressants compared to patients treated with placebo. If, based on clinical need, a decision is nevertheless made in favor of prescribing this drug, the patient should be closely monitored for signs of suicidal symptoms, especially at the beginning of treatment. Long-term safety in terms of cognitive, emotional, physical and pubertal maturation in children and adolescents aged 6 to 16 years was evaluated in a long-term observational study of up to 3 years duration (see section "Pharmacological properties"). In the post-marketing period, several cases of growth retardation and delayed puberty have been reported. The clinical significance and causality are not yet clear. During long-term therapy of pediatric patients, physicians should monitor for abnormalities in growth and development.
Abnormal bleeding/hemorrhage
Cases of pathological haemorrhagic events, including cutaneous haemorrhagic events (ecchymoses and purpura), and other haemorrhagic events such as gastrointestinal or gynaecological haemorrhages, including fatal haemorrhages, have been reported with SSRIs. SSRIs/NSAIDs increase the risk of postpartum haemorrhage (see sections 4.8 and 4.8). Caution is advised when using SSRIs, especially in patients receiving concomitant medicinal products that affect platelet function (e.g. anticoagulants, atypical antipsychotics and phenothiazines, most tricyclic antidepressants, acetylsalicylic acid and NSAIDs) and in patients with a history of haemorrhagic disorders (see section 4.5).
Hyponatraemia may occur as a result of treatment with SSRIs or serotonin norepinephrine reuptake inhibitors (SNRIs), including sertraline. In many cases, hyponatraemia is the result of the syndrome of inappropriate antidiuretic hormone secretion. Cases of serum sodium levels below 110 mmol/l have been reported. Elderly patients may be at greater risk of developing hyponatraemia when taking SSRIs and SNRIs. The risk of this complication may also be increased in patients taking diuretics and in patients with hypovolaemia from any other source (for use in elderly patients, see sections 4.2 and 4.8). In patients with symptomatic hyponatraemia, discontinuation of sertraline therapy should be considered and appropriate medical intervention should be initiated. Signs and symptoms of hyponatremia include headache, difficulty concentrating, memory impairment, confusion, weakness, and loss of physical balance, which can lead to falls. More severe and/or acute episodes of hyponatremia may include hallucinations, syncope, seizures, coma, respiratory arrest, and even death.
Withdrawal symptoms observed upon discontinuation of sertraline therapy
Withdrawal symptoms are common when treatment is discontinued, particularly if treatment is discontinued abruptly (see section 4.8). In clinical trials, the incidence of withdrawal reactions was 23% in patients who discontinued sertraline compared to 12% in patients who continued to receive sertraline.
The risk of developing a withdrawal syndrome may depend on several factors, including duration of therapy, dosage and rate of dose reduction. The most commonly reported reactions were dizziness, sensory disturbances (including paraesthesia), sleep disturbances (including insomnia and vivid dreams), agitation or anxiety, nausea and/or vomiting, tremor and headache. These symptoms were generally mild to moderate in severity, but may be severe in some patients. They usually occur within the first few days of discontinuation of therapy, but in very rare cases, such symptoms have been reported in patients who have accidentally missed a dose of the drug. In most cases, these symptoms resolve spontaneously within 2 weeks, although in some patients they may persist for longer (2-3 months or longer). Therefore, it is recommended that the dose of sertraline be gradually reduced when discontinuing therapy over a period of several weeks or months, according to the patient's needs (see section 4.2).
Akathisia/psychomotor restlessness
Sertraline has been associated with the development of akathisia, a subjectively unpleasant or insatiable restlessness and need to move, often accompanied by an inability to sit or stand still. The risk of such complications is greatest during the first few weeks of therapy. In patients who develop these symptoms, increasing the dose may be harmful.
Use in liver failure
Sertraline is extensively metabolized in the liver. In a multiple-dose pharmacokinetic study in patients with stable mild cirrhosis, a prolongation of the half-life and an increase in AUC or Cmax of approximately three times that in subjects with normal liver function were observed. No significant differences in the degree of binding of the drug to plasma proteins were found between these two groups of study participants. Sertraline should be administered with caution to patients with liver pathology. In the case of prescribing sertraline to patients with impaired liver function, it is necessary to consider the feasibility of reducing the dose or frequency of administration of the drug. Sertraline should not be used in patients with severe hepatic insufficiency (see section "Method of administration and dosage").
Use in renal failure
Sertraline is extensively metabolized; urinary excretion of unchanged compound is a minor route of elimination. In studies involving patients with mild to moderate renal impairment (creatinine clearance 30-60 ml/min) or moderate to severe renal impairment (creatinine clearance 10-29 ml/min), pharmacokinetic parameters (AUC0-24 and Cmax) with multiple dosing were not statistically significantly different from those in the control group. No dose adjustment is necessary based on the degree of renal impairment.
Use in elderly patients
Clinical studies have included over 700 elderly patients (aged > 65 years). The nature and frequency of adverse reactions in elderly patients were similar to those observed in younger patients.
However, the use of SSRIs and SNRIs, including sertraline, has been associated with cases of clinically significant hyponatremia in elderly patients, who are at greater risk of developing this adverse event (see “Hyponatremia”).
