Instructions Asentra film-coated tablets 50 mg blister No. 28
Composition
active ingredient: sertraline;
1 film-coated tablet contains 50 mg or 100 mg of sertraline as sertraline hydrochloride;
excipients: calcium hydrogen phosphate, microcrystalline cellulose, sodium starch glycolate (type A), hydroxypropyl cellulose, talc, magnesium stearate;
shell: Opadry 03H28758 white (hypromellose, titanium dioxide (E 171), talc, propylene glycol).
Dosage form
Film-coated tablets.
Main physicochemical properties: round, film-coated tablets, white in color, with beveled edges and a score line on one side.
Pharmacotherapeutic group
Antidepressants. Selective serotonin reuptake inhibitors. ATC code N06A B06.
Pharmacological properties
Pharmacodynamics
Sertraline is a potent and specific inhibitor of serotonin (5-HT) neuronal 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. In accordance with its inherent selective inhibition of 5-HT reuptake, sertraline does not stimulate catecholaminergic activity. The agent has no affinity for muscarinic (cholinergic), serotonergic, dopaminergic, adrenergic, histaminergic, GABA or benzodiazepine receptors. Long-term use of sertraline in animals led to a decrease in the activity of brain noradrenaline receptors, which is also observed with the use of other clinically effective antidepressants and anti-obsessional drugs.
Sertraline does not cause drug abuse. Sertraline does not produce the stimulant effects or anxiety characteristic of d-amphetamine, or the sedative effects and psychomotor impairment characteristic of alprazolam. Sertraline does not act as a positive incentive in rhesus macaques trained to self-administer cocaine, nor does it substitute for the recognition incentive of d-amphetamine or phenobarbital in rhesus macaques.
Pharmacokinetics
Absorption
The pharmacokinetics of sertraline in the dose range from 50 to 200 mg are dose-dependent. During 14 days of sertraline administration at a dosage of 50-200 mg (orally 1 time per day) in humans, the maximum concentration of sertraline in the blood plasma is reached 4.5-8.4 hours after daily administration of the drug. Food intake does not significantly change the bioavailability of sertraline in 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) is observed when reaching equilibrium concentrations, which are observed after once-daily dosing for 1 week. The elimination half-life for 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 (
Pharmacokinetics in specific patient groups
Children with obsessive-compulsive disorder (OCD)
For use in children, especially those with low body weight, a low initial dose is recommended, which is increased by titrating the dose 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 the elderly does not differ significantly from that in adults aged 18-65 years.
Liver dysfunction
In patients with hepatic impairment, the half-life of sertraline is prolonged and the area under the pharmacokinetic concentration-time curve (AUC) is increased threefold (see sections 4.2 and 4.4).
Kidney dysfunction
No significant accumulation of sertraline was observed in patients with moderate or severe renal impairment.
Indication
Sertraline is indicated for the treatment of the following disorders:
Major depressive episodes (MDE). Prevention of recurrence of MDE. 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 of the drug.
The use of sertraline together 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 should be discontinued at least 7 days before starting treatment with irreversible MAO inhibitors (see section "Interaction with other medicinal products and other types of interactions").
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
MAO inhibitors
Irreversible MAO inhibitors (e.g., selegiline)
Sertraline is contraindicated in combination with irreversible MAO inhibitors such as selegiline. Sertraline should not be administered for at least 14 days after discontinuation of treatment with an irreversible MAO inhibitor. Sertraline should be discontinued at least 7 days before initiating treatment with an irreversible MAO inhibitor (see section 4.3).
Selective MAO-A reverse-action inhibitor (moclobemide)
Due to the risk of serotonin syndrome, the combination of sertraline with selective MAO inhibitors, such as moclobemide, should not be used. After discontinuation of MAO inhibitors, the period before starting sertraline therapy may be shorter than 14 days, but it is recommended to stop taking sertraline at least 7 days before starting treatment with MAO inhibitors (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 MAO inhibitors (e.g. methylene blue) and started taking sertraline, or who have discontinued sertraline shortly before starting MAO inhibitors. These reactions included tremor, myoclonus, hyperhidrosis, nausea, vomiting, flushing, dizziness, and hyperthermia with features resembling neuroleptic malignant syndrome, convulsions, and death.
Pimozide
In a single low-dose pimozide (2 mg) study, an increase in pimozide levels of approximately 35% was observed. This increase was not accompanied by any changes in ECG parameters. Although the mechanism of this interaction is unknown, concomitant use of sertraline and pimozide is contraindicated due to the narrow therapeutic range of pimozide (see section 4.3).
Concomitant use with sertraline is not recommended.
Alcohol and CNS depressants
Concomitant use of sertraline at a dose of 200 mg per day did not potentiate the effects of alcohol, carbamazepine, haloperidol, or phenytoin on cognitive and psychomotor functions in healthy volunteers, however, concomitant use of sertraline with alcohol is not recommended.
Other serotonergic drugs
(see section "Features of use").
It is recommended to prescribe sertraline with caution with fentanyl, which is used mainly during general anesthesia and in the treatment of chronic pain, other serotonergic drugs (including other serotonergic antidepressants, triptans) and other opioids.
Special precautions for use
Drugs that prolong the QT interval
The risk of QTc prolongation and/or ventricular arrhythmias (e.g. torsades de pointes) may be increased when co-administered with other drugs that prolong the QTc interval (e.g. some antipsychotics and antibiotics) (see section 4.4).
Lithium
In a placebo-controlled study in healthy volunteers, co-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 per day does not lead to clinically significant inhibition of phenytoin metabolism. However, there have been reports of high phenytoin exposures in patients taking sertraline; monitoring of phenytoin plasma concentrations is recommended during the initial phase of sertraline therapy with appropriate adjustment of 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 inducers of the CYP3A4 enzyme, 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 when sertraline and sumatriptan were administered concomitantly. 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 should be ensured (see section 4.4).
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 does not affect the beta-blocking properties of atenolol. No interaction was observed with the simultaneous use of sertraline at a dose of 200 mg/day and digoxin.
Drugs that affect platelet function
The risk of bleeding may be increased by concomitant use of selective serotonin reuptake inhibitors (SSRIs), including sertraline, with medicinal products that affect platelet function (non-steroidal anti-inflammatory drugs (NSAIDs), acetylsalicylic acid and ticlopidine), or with other medicinal products that may increase the risk of bleeding (see section 4.4).
Neuromuscular transmission blockers
SSRIs may reduce plasma cholinesterase activity, leading to prolonged neuromuscular blockade by mivacurium or other neuromuscular blocking agents.
Drugs metabolized by cytochrome P450
Sertraline may act as a weak to moderate inhibitor of the CYP2D6 isoenzyme. Chronic administration of sertraline at a dose of 50 mg per 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 CYP 3A4, CYP 2C9, CYP 2C19 and CYP 1A2 isoenzymes. This is confirmed by the results of in vivo drug interaction studies using CYP 3A4 substrates (endogenous cortisol, carbamazepine, terfenadine, alprazolam), CYP2C19 substrate (diazepam) and CYP 2C9 substrates (tolbutamide, glibenclamide and phenytoin). The results of in vitro studies indicate that sertraline has very little or no potential to inhibit CYP 1A2.
Application features
Serotonin syndrome (SS) or neuroleptic malignant syndrome (NMS)
With the use of SSRIs, including sertraline therapy, the development of syndromes that can be life-threatening, such as SSRIs or NMS, has been recorded. The risk of developing SSRIs or NMS with SSRIs is increased by the simultaneous use of other serotonergic agents (including other serotonergic antidepressants, triptans) with drugs that disrupt serotonin metabolism (including MAOIs, e.g. methylene blue), with antipsychotics and other dopamine antagonists and opiates. Serotonin syndrome may include changes in mental status (e.g. agitation, hallucinations, coma), autonomic disorders (e.g. tachycardia, blood pressure fluctuations, hyperthermia), neuromuscular disorders (e.g. hyperreflexia, impaired coordination) and/or digestive disorders (nausea, vomiting, diarrhea). Some manifestations of serotonin syndrome, including hyperthermia, muscle rigidity, autonomic changes, and mental status changes, are similar to those of neuroleptic malignant syndrome. Patients should be monitored for signs and symptoms of SS or CNS depression (see Contraindications).
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. Caution should be exercised when switching from such treatments, especially when switching to sertraline from long-acting drugs such as fluoxetine.
Other serotonergic agents, such as tryptophan, fenfluramine, and 5-HT agonists
The concomitant use of sertraline and other agents that enhance serotonergic neurotransmission, including tryptophan, fenfluramine, 5-HT agonists or herbal preparations containing St. John's wort (Hypericum perforatum), should be undertaken with caution and, if possible, such combination therapy should be avoided due to possible pharmacodynamic interactions.
QTc prolongation/torsades de pointes
Cases of QTc prolongation and torsades de pointes have been reported in post-marketing experience with sertraline. The majority of cases occurred in patients with other risk factors for QTc prolongation/torsades de pointes. Therefore, sertraline should be used with caution in patients with risk factors for QTc prolongation.
Exacerbation of mania/hypomania has 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 signs of a manic phase appear.
Schizophrenia
Psychotic symptoms may worsen.
Convulsions
Sertraline therapy may cause seizures, so sertraline should not be prescribed to patients with unstable epilepsy, and patients with controlled epilepsy should be closely monitored when using sertraline. Sertraline should be discontinued in patients who develop seizures.
Suicide/suicidal thoughts/suicidal attempts or clinical signs of worsening
Depression is characterized by an increased risk of suicidal thoughts, self-harm, and suicide attempts (suicidality). This risk exists until significant remission is achieved. Since improvement may occur during the first few weeks or longer of therapy, patients should be closely monitored until improvement occurs. In general, clinical experience suggests that the risk of suicide may be increased in the early stages of recovery.
Other psychiatric conditions for which sertraline is prescribed may also be associated with a risk of suicidal behaviour. These conditions may also be co-morbid with major depressive disorder. Therefore, the same precautions should be taken when treating patients with major depressive disorder as when treating patients with other psychiatric disorders.
Patients with a history of suicidal behaviour or who are significantly suicidal prior to initiation of therapy are at greater risk of suicidal thoughts or suicide attempts during treatment and should receive careful monitoring while taking the drug. There is an increased risk of suicidal behaviour when antidepressants are used in patients with psychiatric disorders under the age of 25.
Close monitoring of patients at high risk of suicidality is indicated, particularly at the beginning of therapy and after any dose changes. Patients (and caregivers of patients) should be alerted to the need to monitor for any clinical worsening, the emergence of suicidal behaviour or suicidal thoughts, or any unusual changes in behaviour and to seek medical advice immediately if these symptoms present.
Abnormal bleeding/hemorrhage
Cases of pathological cutaneous haemorrhagic events, such as ecchymoses and purpura, and other haemorrhagic events, such as gastrointestinal or gynaecological haemorrhages, including fatal haemorrhages, have been reported with SSRIs. Caution is advised when SSRIs are used in patients, particularly when used concomitantly with medicinal products known to 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).
Hyponatremia
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. Serum sodium levels below 110 mmol/L have been reported. Elderly patients may be at greater risk of developing hyponatraemia with SSRIs and SNRIs. The risk of this complication may also be increased in patients taking diuretics or in patients with hypovolaemia from any other source. Discontinuation of sertraline therapy should be considered and appropriate medical intervention should be initiated in patients with symptomatic hyponatraemia. Signs and symptoms of hyponatraemia include headache, difficulty concentrating, memory impairment, confusion, weakness and loss of balance, which may lead to falls. Signs and symptoms caused by more severe and/or acute episodes of hyponatremia include hallucinations, syncope, seizures, coma, respiratory arrest, and death.
Withdrawal symptoms are common when treatment is discontinued, particularly if treatment is stopped abruptly (see section 4.8). The risk of developing a withdrawal syndrome may depend on several factors, including duration of treatment, dose and rate of dose reduction. The most commonly reported reactions are 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 after discontinuation of treatment, and in very rare cases, such symptoms have been observed in patients who have accidentally missed a dose. In most cases, these symptoms resolve spontaneously within 2 weeks, although in some patients they may persist for longer (2-3 months or more). It is therefore 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 two weeks of therapy. In patients who develop these symptoms, increasing the dose may be harmful.
Liver failure
Sertraline is extensively metabolized in the liver. In patients with stable mild cirrhosis, a prolongation of the half-life and an increase in AUC and Cmax approximately threefold compared with those 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. Caution should be exercised when using sertraline in 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").
Kidney failure
Sertraline is extensively metabolized, with urinary excretion of unchanged compound being 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) after 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
In elderly patients (aged >65 years), the nature and frequency of adverse reactions are 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 the subsection “Hyponatremia” in the “Special Instructions” section).
Diabetes mellitus
In patients with diabetes mellitus, the use of SSRIs may affect glycemic control. The dosage of insulin and/or oral hypoglycemic agents may need to be adjusted.
Electroconvulsive therapy (ECT)
The benefits and risks of the combined use of ECT and sertraline have not been studied.
Grapefruit juice
The simultaneous use of sertraline with grapefruit juice is not recommended (see section "Interaction with other medicinal products and other types of interactions").
Impact on urine screening test results
False-positive results of immunological urine screening tests for benzodiazepines have been reported in patients taking sertraline. False-positive results are due to the low specificity of this laboratory test and may occur for several days after discontinuation of sertraline treatment. Differentiation of sertraline from benzodiazepines in urine can be achieved by performing confirmatory tests such as gas chromatography/mass spectrometry.
Angle-closure glaucoma
SSRIs, including sertraline, may affect pupil size with the development of mydriasis. This effect may lead to narrowing of the angle of the eye with subsequent increase in intraocular pressure and the development of angle-closure glaucoma, especially in patients with a corresponding predisposition. Therefore, sertraline should be used with caution in patients with angle-closure glaucoma or a history of glaucoma.
Use during pregnancy or breastfeeding
There are no well-controlled studies of sertraline in pregnant women. However, a substantial amount of data does not indicate any evidence of congenital malformations due to sertraline. Animal studies have shown effects on reproductive function, probably due to maternal toxicity caused by the pharmacodynamic effects of sertraline and/or a direct pharmacodynamic effect of the drug on the fetus.
Epidemiological studies suggest that the use of SSRIs during pregnancy, particularly in late pregnancy, may increase the risk of persistent pulmonary hypertension of the newborn. The risk associated with SSRI use is estimated to be approximately 5 cases per 1000 pregnancies. In the general population, the incidence of persistent pulmonary hypertension of the newborn is 1-2 cases per 1000 pregnancies.
Sertraline has been reported to cause withdrawal-like symptoms in some newborns when used during pregnancy. This phenomenon has also been observed with other SSRI antidepressants. Sertraline is not recommended for use during pregnancy unless the clinical condition of the woman is such that the expected benefit to the mother outweighs the potential risk to the fetus.
Newborns should be monitored if the mother continues to take sertraline later in pregnancy, especially in the third trimester. The following symptoms may occur in newborns after use of sertraline late in pregnancy: respiratory distress syndrome, cyanosis, apnea, seizures, temperature instability, feeding difficulties, vomiting, hypoglycemia, hypertonia, hypotonia, hyperreflexia, tremor, hyperexcitability, irritability, lethargy/apathy, constant crying, drowsiness and difficulty falling asleep. These symptoms may be due to other serotonergic effects or withdrawal symptoms. In most cases, these complications develop immediately after delivery or in the near future (within 24 hours).
Breastfeeding period
Published data on sertraline levels in breast milk indicate that sertraline and its metabolite N-desmethylsertraline are excreted in breast milk in small amounts. In general, negligible or undetectable drug concentrations were found in the serum of infants, except in one case where the drug concentration in the infant's serum was approximately 50% of the maternal serum concentration (but without any noticeable effect on the health of the infant). To date, no adverse effects of the drug on the health of infants breastfed by women taking sertraline have been reported, but such a risk cannot be excluded. The use of the drug during breastfeeding is not recommended unless, in the opinion of the physician, the benefit of taking the drug outweighs the possible risk.
Reproductive function
Animal studies have not shown any effect of sertraline on reproductive function.
In humans, reports have shown reversible effects on sperm. Effects on human reproductive function have not yet been evaluated.
Ability to influence reaction speed when driving vehicles or other mechanisms
Clinical and pharmacological studies indicate that sertraline has no effect on psychomotor functions. However, patients should be cautious because the drug may impair mental or physical reactions required for performing potentially hazardous activities, such as driving a car or operating other mechanisms.
Method of administration and doses
Starting treatment
Depression and OCD
Sertraline treatment should be initiated at a dose of 50 mg per day.
Panic Disorder, 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/day. This dosage regimen has been shown to reduce the incidence of side effects typical of panic disorder in the early stages of treatment.
Dose titration
Depression, OCD, panic disorder, social anxiety disorder, and PTSD
Patients who do not respond to the 50 mg dose may need to have their dose increased. The dose should be titrated in 50 mg increments at intervals of at least 1 week to a dose not to exceed 200 mg/day. Dose adjustments should be made no more frequently than once per week, taking into account the 24-hour half-life of sertraline.
The onset of therapeutic effect can be observed within 7 days of treatment. However, a longer period of time is usually required to observe a therapeutic response, especially in patients with OCD.
Maintenance dose
Dosage during long-term therapy should be maintained at the lowest effective level with appropriate adjustment depending on the therapeutic response.
Depression
Long-term treatment can also be used to prevent recurrence of major depressive episodes. In most cases, the recommended dose for the prevention of recurrence of MDE is the same as the dose used during the treatment of that depressive episode. Patients with depression should be treated for a sufficient period of time, at least 6 months, to ensure complete resolution of symptoms.
With long-term therapy in patients with panic disorder and OCD, regular evaluation of therapy should be performed, as relapse prevention has not been demonstrated for these disorders.
Use in elderly patients
The drug should be used with caution in elderly patients, as these patients may be at increased risk of developing hyponatremia (see section "Special warnings and precautions for use").
Use in liver failure
Sertraline should be used with caution in patients with liver disease. In case of hepatic insufficiency, the dose or frequency of administration should be reduced (see section "Special warnings and precautions for use"). Sertraline should not be used in patients with severe hepatic insufficiency, as clinical data on the use of the drug in such patients are lacking (see section "Special warnings and precautions for use").
Use in renal failure
In case of impaired renal function, dose adjustment of the drug is not required (see section "Special instructions").
Use in children
Children and adolescents with OCD
Age 13-17 years: the initial dose is 50 mg once a day.
Age 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 the absence of the desired effect when taking the drug in the dose
50 mg per day, it can be further increased by increasing the dose by 50 mg per day at a time over several weeks. The maximum dose is up to 200 mg per day.
However, when increasing the dose above 50 mg in pediatrics, the generally lower body weight of children compared to adults should be taken into account. The dose should not be changed more often than once a week.
The drug's effectiveness in children with major depressive disorder has not been observed.
There are no data on the use of the drug in children under 6 years of age (see section "Special instructions for use").
Withdrawal symptoms observed upon discontinuation of sertraline therapy
Abrupt discontinuation of the drug should be avoided. When discontinuing sertraline treatment, the dose should be gradually reduced over at least 1-2 weeks to reduce the risk of withdrawal reactions (see sections "Special instructions" and "Adverse reactions"). If intolerable symptoms occur after dose reduction or discontinuation, resuming the drug at the previously prescribed dose may be considered. The doctor may then continue to reduce the dose, but more gradually.
Children.
Sertraline should not be used in children, except in patients with OCD aged 6-17 years. If, based on clinical need, a decision is made to prescribe the drug, careful monitoring for signs of suicidal symptoms is necessary. In addition, long-term safety data on the effects of treatment on growth, maturation, and cognitive and behavioral development are lacking in children and adolescents. During long-term therapy of pediatric patients, physicians should monitor for abnormalities in the body's developmental systems.
Overdose
Toxicity
Sertraline has a wide safety margin for overdose, depending on the patient population and/or concomitant medications. Overdoses of up to 13.5 g have been reported as monotherapy. Fatalities have been reported with sertraline overdose, both alone and in combination with other drugs and/or alcohol. Therefore, any overdose should be managed with intensive care.
Symptoms
Symptoms of overdose include serotonin-mediated side effects, including drowsiness, gastrointestinal disturbances (including nausea and vomiting), tachycardia, tremor, agitation, and dizziness. Coma has been reported less frequently.
QTc prolongation/torsades de pointes has been reported following sertraline overdose, therefore ECG monitoring is recommended in all cases of sertraline overdose.
Therapy
There is no specific antidote for sertraline. It is recommended to establish and maintain (if necessary) a patent airway and adequate oxygenation and ventilation. Activated charcoal, which can be used in conjunction with a laxative, may be as effective as gastric lavage, which should be considered in the treatment of overdose. Induction of vomiting is not recommended. Cardiovascular monitoring is recommended.
