Instructions for Zoloft film-coated tablets 50 mg blister No. 28
Composition
active ingredient: sertraline;
One film-coated tablet contains sertraline hydrochloride equivalent to 50 mg of sertraline;
excipients: calcium hydrogen phosphate dihydrate, microcrystalline cellulose, hydroxypropyl cellulose, sodium starch glycolate, magnesium stearate, Opadry white (hydroxypropyl methylcellulose, titanium dioxide (E 171), polyethylene glycol, polysorbate 80), Opadry transparent (hydroxypropyl methylcellulose, polyethylene glycol).
Dosage form
Film-coated tablets.
Main physicochemical properties: white, film-coated, capsule-shaped tablets, embossed with “Pfizer” on one side and “ZLT 50” on the other. The tablets have a functional score line between the inscriptions “ZLT” and “50”.
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. In accordance with its inherent selective inhibition of 5-HT uptake, sertraline 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 of the comparative 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, nor does it 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 design. 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.
Post-traumatic stress disorder (PTSD)
The pooled data from the total number of PTSD patients in the 3 studies suggest a lower response rate among men than women. In the two clinical trials with positive outcomes in the general population, the percentage of patients who responded to treatment was similar for women and men in the sertraline groups compared to placebo (women: 57.2% vs. 34.5%; men: 53.9% vs. 38.2%). The number of men and women in the pooled number of studies was 184 and 430, respectively, with more consistent results in women, and men had other variables at baseline (more substance abuse, longer duration of illness, cause of trauma, etc.) that correlated with less efficacy.
In a robust study of the steady-state QTc interval at supratherapeutic exposures in healthy volunteers (treated with 400 mg/day, 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 sertraline plasma 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 administration of the highest recommended dose of sertraline (200 mg/day) (see sections 4.4, 4.5, 4.8 and 4.9).
Obsessive-compulsive disorder (OCD) 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 a post-hoc analysis, the percentage of patients who responded to treatment, defined as patients with a 25% or greater 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 the long-term safety and efficacy of the drug in this pediatric patient population.
Children
There are no data on the use of sertraline in children under 6 years of age.
Pharmacokinetics.
Absorption
During 14 days of oral administration of sertraline at a dosage of 50–200 mg once daily in humans, peak plasma concentrations of sertraline are reached 4.5–8.4 hours after daily dosing. Food does not significantly alter the bioavailability of sertraline tablets.
Distribution
Approximately 98% of circulating sertraline is bound to plasma proteins.
Biotransformation
Sertraline undergoes extensive presystemic metabolism ("first-pass effect") in the liver.
Based on clinical and in vitro data, sertraline is metabolized by multiple pathways, including CYP3A4, CYP2C19 and CYP2B6 (see Interactions 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 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 until steady-state concentrations are reached 1 week after once-daily dosing. The elimination half-life of N-desmethylsertraline is 62–104 hours. Sertraline and N-desmethylsertraline are extensively metabolized in humans, and their final metabolites are excreted in feces and urine in equal amounts. Only a very small part (< 0.2%) of sertraline is excreted in urine unchanged.
Linearity/nonlinearity
The pharmacokinetics of sertraline in the dose range of 50 to 200 mg are dose-dependent.
Pharmacokinetics in specific patient groups
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 with either 25 mg or 50 mg with gradual increases. Tolerability was similar between the 25 mg and 50 mg doses. At steady state, plasma sertraline concentrations in the 200 mg group of children aged 6–12 years were approximately 35% higher than those in the 13–17 year old group and 21% higher than those in the adult reference group. No significant differences in clearance were observed between boys and girls. Therefore, a low starting dose and titration in 25 mg increments are recommended for children, especially those with low body weight. The same doses as adults can be used for 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 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.
Pharmacogenomics
In CYP2C19 poor metabolizers, sertraline plasma levels were approximately 50% higher than in 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:
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 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)
Sertraline is contraindicated in combination with irreversible MAOIs such as selegiline. Sertraline therapy should not be initiated until 14 days after discontinuation of irreversible MAOI therapy. Sertraline should be discontinued at least 7 days before initiation of irreversible MAOI therapy (see Contraindications).
Selective MAO-A reverse-action inhibitor (moclobemide)
Due to the risk of serotonin syndrome, sertraline should not be used in combination with a selective, reversible MAOI such as moclobemide. After discontinuation of a reversible MAOI, the period before starting sertraline therapy may be shorter than 14 days. It is recommended that sertraline be discontinued at least 7 days before starting treatment with a reversible MAOI (see section 4.3).
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.
Pimozide
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.
CNS depressants and alcohol
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 subjects, however, concomitant use of sertraline with alcohol is not recommended.
Other serotonergic drugs
It is recommended that sertraline be prescribed with caution with opioids (such as fentanyl (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) may be increased by concomitant use 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 patients 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; monitoring of phenytoin plasma concentrations is recommended 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 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 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 may be increased when selective serotonin reuptake inhibitors (SSRIs), including sertraline, are used concomitantly with medicinal products that affect platelet function (e.g. NSAIDs, acetylsalicylic acid and ticlopidine) or 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. 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.
Based on the results of the grapefruit juice interaction study, the possibility of an even greater increase in sertraline exposure cannot be excluded 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 such as methylene blue), antipsychotics, and 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 studies investigating the optimal timing of switching from SSRIs, antidepressants, or anti-obsessional 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 if possible (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 with sertraline. The majority of cases occurred in patients with other risk factors for QTc prolongation/torsades de pointes. 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, hypokalaemia or hypomagnesaemia, a 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.
Convulsions
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 events). This risk exists until significant remission is achieved. Because improvement may not occur during the first few weeks or longer of therapy, patients should be closely monitored until such improvement occurs. Overall, clinical experience suggests that the risk of suicide may be increased in the early stages of recovery.
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 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 for patients with obsessive-compulsive disorder aged 6-17 years. In clinical trials involving children and adolescents treated with antidepressants, suicidal behaviour (suicidal attempts and suicidal thoughts) and hostility (predominantly aggression, oppositional behaviour and anger) were more frequently observed 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 carefully monitored for signs of suicidal symptoms. In addition, only limited clinical evidence is available on the long-term safety of the drug in children and adolescents, including effects on their growth, puberty, and cognitive and behavioural development. In the post-marketing period, a few cases of growth retardation and puberty retardation 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 the use of SSRIs. SSRIs/NSAIDs may increase the risk of postpartum haemorrhage (see sections 4.8 and 4.8). Caution is advised when using SSRIs in patients, particularly when concomitantly administered with medicinal products known to affect platelet function (e.g. anticoagulants, atypical antipsychotics and phenothiazines, most tricyclic antidepressants, acetylsalicylic acid and non-steroidal anti-inflammatory drugs (NSAIDs)), and in patients with a history of haemorrhagic disorders (see section 4.5).
Hyponatremia
Hyponatremia may occur as a result of treatment with SSRIs or serotonin norepinephrine reuptake inhibitors (SNRIs), including sertraline. In many cases, hyponatremia is the result of the syndrome of inappropriate antidiuretic hormone secretion. Cases of serum sodium levels falling 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 or in patients with hypovolaemia from any other source (see information on use in elderly patients in 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 hyponatraemia include headache, difficulty concentrating, memory impairment, confusion, weakness and loss of physical balance, which may lead to falls. Signs and symptoms associated with more severe and/or acute episodes of hyponatraemia include hallucinations, syncope, convulsions, coma, respiratory arrest and death.
Withdrawal symptoms observed upon discontinuation of sertraline therapy
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 after 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 longer (2-3 months or more). 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 "Dosage and administration").
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. A multiple-dose pharmacokinetic study in patients with stable mild cirrhosis showed a prolongation of the elimination half-life and an increase in AUC or Cmax approximately threefold compared to those in subjects with normal liver function. There were no significant differences in the degree of binding of the drug to plasma proteins between these two groups of study participants. Caution should be exercised when prescribing sertraline 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 may be at greater risk of developing this adverse event (see Hyponatremia in the Precautions 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)
No clinical trials have been conducted to examine the risks or benefits of the combined use of ECT and sertraline.
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
SSRI class drugs, including sertraline, may
