- sertraline hydrochloride
POM: Prescription only medicine
This information is intended for use by health professionals
AdultsDepression (including accompanying symptoms of anxiety): The starting dose is 50mg daily and the usual antidepressant dose is 50mg daily. In some patients, doses higher than 50mg may be required. Obsessive Compulsive Disorder: The starting dose is 50mg daily, and the therapeutic dose range is 50-200mg daily.Post-Traumatic Stress Disorder: Treatment for PTSD should be initiated at 25mg/day. After one week, the dose should be increased to 50mg once daily.PTSD is a heterogeneous illness and some patient groups fulfilling the criteria for PTSD do not appear to be responsive to treatment with Sertraline Tablets. Dosing should be reviewed periodically by the prescribing physician to determine response to therapy and treatment should be withdrawn if there is no clear evidence of efficacy.Depression (including accompanying symptoms of anxiety), OCD and PTSD: In some patients doses higher than 50mg daily may be required. In patients with incomplete response but good toleration at lower doses, dosage adjustments should be made in 50mg increments over a period of weeks to a maximum of 200mg daily. Once optimal therapeutic response is achieved the dose should be reduced, depending on therapeutic response, to the lowest effective level. Dosage during prolonged maintenance therapy should be kept at the lowest effective level, with subsequent adjustments depending on therapeutic response. The onset of therapeutic effect may be seen within 7 days, although 2-4 weeks (and even longer in OCD) are usually necessary for full activity. A longer treatment period, even beyond 12 weeks in some cases, may be required in the case of a therapeutic trial in PTSD.Use in children aged 6-17 years Treatment should only be initiated by specialists. The safety and efficacy of Sertraline Tablets has been established in paediatric OCD patients (aged 6-17). The administration of Sertraline Tablets to paediatric OCD patients (aged 13-17) should commence at 50 mg/day. Therapy for paediatric OCD patients (aged 6-12) should commence at 25mg/day increasing to 50mg/day after 1 week. Subsequent doses may be increased in case of lack of response in 50mg/day increments up to 200mg/day as needed.However, the generally lower body weights of children compared to adults should be taken into consideration in advancing the dose from 50mg, in order to avoid excessive dosing. Given the 24 hour elimination half-life of sertraline, dose changes should not occur at intervals of less than 1 week.The efficacy and safety of Sertraline Tablets in children and adolescents under the age of 18 years with Major Depressive Disorder have not been established. Controlled clinical studies failed to demonstrate efficacy and do not support the use of Sertraline Tablets in the treatment of children and adolescents with Major Depressive Disorder (See sections 4.3, Contra-Indications and 4.8, Undesirable effects).Children aged less than six years Sertraline Tablets is not recommended in children under six years of age since safety and efficacy have not been established. See also 'Pharmacological Properties'. Use in the elderly Elderly should be dosed carefully, as elderly may be more at risk for hyponatraemia (see section 4.4). Use in hepatic insufficiency The use of sertraline in patients with hepatic disease should be approached with caution. A lower or less frequent dose should be used in patients with hepatic impairment (see section 4.4). Sertraline should not be used in cases of severe hepatic impairment as no clinical data are available (see section 4.4). Use in renal insufficiency No dosage adjustment is necessary in patients with renal insufficiency (see section 4.4).Withdrawal symptoms seen on discontinuation of sertraline Abrupt discontinuation should be avoided. When stopping treatment with sertraline the dose should be gradually reduced over a period of at least one to two weeks in order to reduce the risk of withdrawal reactions (see sections 4.4 and 4.8). If intolerable symptoms occur following a decrease in the dose or upon discontinuation of treatment, then resuming the previously prescribed dose may be considered. Subsequently, the physician may continue decreasing the dose, but at a more gradual rate.Sertraline Tablets are for oral administration only.
Monoamine oxidase inhibitors:Concomitant treatment with irreversible monoamine oxidase inhibitors (MAOIs) is contraindicated due to the risk of serotonin syndrome with symptoms such as agitation, tremor and hyperthermia. Sertraline must not be initiated for at least 14 days after discontinuation of treatment with an irreversible MAOI. Sertraline must be discontinued for at least 7 days before starting treatment with an irreversible or reversible MAOI (see section 4.5). Use in hepatic impairment: There is insufficient clinical experience in patients with significant hepatic dysfunction and accordingly Sertraline Tablets should not be used in such patients. Concomitant use in patients taking pimozide is contra-indicated (see section 4.5). - Sertraline Tablets should not be used in children and adolescents under the age of 18 years with Major Depressive Disorder. (See section 4.8, Undesirable effects).
Serotonin Syndrome (SS) or Neuroleptic Malignant Syndrome (NMS)The development of potentially life-threatening syndromes like serotonin syndrome (SS) or Neuroleptic Malignant Syndrome (NMS) has been reported with SSRIs, including treatment with sertraline. The risk of SS or NMS with SSRIs is increased with concomitant use of serotonergic drugs (including triptans), with drugs which impair metabolism of serotonin (including MAOIs), antipsychotics and other dopamine antagonists. Patients should be monitored for the emergence of signs and symptoms of SS or NMS syndrome (see section 4.3 Contraindications).
Switching from Selective Serotonin Reuptake Inhibitors (SSRIs), antidepressants or antiobsessional drugsThere is limited controlled experience regarding the optimal timing of switching from SSRIs, antidepressants or antiobsessional drugs to sertraline. Care and prudent medical judgment should be exercised when switching, particularly from long-acting agents such as fluoxetine.
Other serotonergic drugs e.g. tryptophan, fenfluramine and 5-HT agonistsCo-administration of sertraline with other drugs which enhance the effects of serotonergic neurotransmission such as tryptophan or fenfluramine or 5-HT agonists, or the herbal medicine, St John's Wort (hypericum perforatum), should be undertaken with caution and avoided whenever possible due to the potential for a pharmacodynamic interaction.
Activation of hypomania or maniaManic/hypomanic symptoms have been reported to emerge in a small proportion of patients treated with marketed antidepressant and antiobsessional drugs, including sertraline. Therefore sertraline should be used with caution in patients with a history of mania/hypomania. Close surveillance by the physician is required. Sertraline should be discontinued in any patient entering a manic phase.
SchizophreniaPsychotic symptoms might become aggravated in schizophrenic patients. Monoamine oxidase inhibitors See 'Contra-indications' and interactions.
Renal ImpairmentSince sertraline is extensively metabolised, excretion of unchanged drug in urine is a minor route of elimination. In patients with mild to moderate renal impairment (creatinine clearance 30-60ml/min) or moderate to severe renal impairment (creatinine clearance 10-29ml/min), multiple-dose pharmacokinetic parameters (AUC0-24 or Cmax) were not significantly different compared with controls. Sertraline dosing does not have to be adjusted based on the degree of renal impairment. However, steady state pharmacokinetics of sertraline have not been adequately studied in this patient population and caution is advised when treating patients with renal impairment.
Hepatic ImpairmentSertraline is extensively metabolised by the liver. A multiple dose pharmacokinetic study in subjects with mild, stable cirrhosis demonstrated a prolonged elimination half-life and approximately three-fold greater AUC and Cmax in comparison with normal subjects. There were no significant differences in plasma protein binding observed between the two groups. The use of sertraline in patients with hepatic disease should be approached with caution. A lower or less frequent dose should be used in patients with hepatic impairment. Sertraline should not be used in patients with severe hepatic impairment (see section 4.2). Diabetes In patients with diabetes, treatment with an SSRI may alter glycaemic control, possibly due to improvement of depressive symptoms. Insulin and/or oral hypoglycaemic dosage may be needed to be adjusted. Seizures Seizures are a potential risk with antidepressant or antiobsessional drugs. The drug should be discontinued in any patient who develops seizures. Sertraline Tablets should be avoided in patients with unstable epilepsy and patients with controlled epilepsy should be carefully monitored. Sertraline Tablets should be discontinued if there is an increase in seizure frequency. Electroconvulsive therapy (ECT) Since there is little clinical experience of concurrent administration of Sertraline Tablets and ECT, caution is advisable.Grapefruit juice The administration of sertraline with grapefruit juice is not recommended (see section 4.5)
Suicide/suicidal thoughts or clinical worseningDepression is associated with an increased risk of suicidal thoughts, self harm and suicide (suicide-related events). This risk persists until significant remission occurs. As improvement may not occur during the first few weeks or more of treatment, patients should be closely monitored until such improvement occurs. It is general clinical experience that the risk of suicide may increase in the early stages of recovery.Other psychiatric conditions for which Sertraline Tablets is prescribed can also be associated with an increased risk of suicide-related events. In addition, these conditions may be co-morbid with major depressive disorder. The same precautions observed when treating patients with major depressive disorder should therefore be observed when treating patients with other psychiatric disorders.Patients with a history of suicide-related events, or those exhibiting a significant degree of suicidal ideation prior to commencement of treatment 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 antidepressant drugs in adult patients with psychiatric disorders showed an increased risk of suicidal behaviour with antidepressants compared to placebo in patients less than 25 years old. Close supervision of patients and in particular those at high risk should accompany drug therapy especially in early treatment and following dose changes. Patients (and caregivers of patients) should be alerted about the need to monitor for any clinical worsening, suicidal behaviour or thoughts and unusual changes in behaviour and to seek medical advice immediately if these symptoms present. Haemorrhage There have been reports of cutaneous bleeding abnormalities such as ecchymoses and purpura and other hemorrhagic events such as gastrointestinal or gynaecological bleeding with SSRIs. Caution is advised in patients taking SSRIs, particularly in concomitant use with drugs known to affect platelet function (e.g. atypical antipsychotics and phenothiazines, most tricyclic antidepressants, aspirin and non-steroidal anti-inflammatory drugs (NSAIDs) and anticoagulants) as well as in patients with a history of bleeding disorders (see section 4.5). Use in the elderly Over 700 elderly patients (>65 years) have participated in clinical studies with Sertraline Tablets. The pattern and incidence of adverse reactions in the elderly is similar to that in younger patients. SSRI's or SNRIs including sertraline have however been associated with cases of clinically significant hyponatreamia in elderly patients, who may be at greater risk for this adverse event (see Hyponatreamia in section 4.4). Use in Children and adolescents under 18 years of age Sertraline should not be used in the treatment of children and adolescents under the age of 18 years, except for patients with obsessive compulsive disorder aged 6-17 years old. Suicide-related behaviours (suicide attempt and suicidal thoughts), and hostility (predominantly aggression, oppositional behaviour and anger) were more frequently observed in clinical trials among children and adolescents treated with antidepressants compared to those treated with placebo. If, based on clinical need, a decision to treat is nevertheless taken; the patient should be carefully monitored for appearance of suicidal symptoms. In addition, long-term safety data in children and adolescents concerning growth, maturation and cognitive and behavioural development are lacking. Physicians must monitor paediatric patients on long term treatment for abnormalities in these body systems. More than 250 paediatric OCD patients have been exposed to Sertraline Tablets in completed and ongoing studies. The safety profile of Sertraline Tablets in these paediatric studies is comparable to that observed in the adult OCD studies. The efficacy of Sertraline Tablets in paediatric patients with depression or panic disorder has not been demonstrated in controlled trials. Safety and effectiveness in paediatric patients below the age of 6 have not been established. There is limited knowledge with respect to an effect on sexual development in children.
HyponatraemiaHyponatraemia may occur as a result of treatment with SSRIs or SNRIs including sertraline. In many cases, hyponatraemia appears to be the result of a syndrome of inappropriate antidiuretic hormone secretion (SIADH). Cases of serum sodium levels lower than 110 mmol/l have been reported. Elderly patients may be at greater risk of developing hyponatraemia with SSRIs and SNRIs. Also patients taking diuretics or who are otherwise volume-depleted may be at greater risk (see Use in elderly). Discontinuation of sertraline should be considered in patients with symptomatic hyponatraemia and appropriate medical intervention should be instituted. Signs and symptoms of hyponatraemia include headache, difficulty concentrating, memory impairment, confusion, weakness and unsteadiness which may lead to falls. Signs and symptoms associated with more severe and/or acute cases have included hallucination, syncope, seizure, coma, respiratory arrest, and death.
Withdrawal symptoms seen on discontinuation of sertraline treatmentWithdrawal symptoms when treatment is discontinued are common, particularly if discontinuation is abrupt (see section 4.8). In clinical trials, among patients treated with sertraline, the incidence of reported withdrawal reactions was 23% in those discontinuing sertraline compared to 12% in those who continued to receive sertraline treatment.The risk of withdrawal symptoms may be dependent on several factors including the duration and dose of therapy and the rate of dose reduction. Dizziness, sensory disturbances (including paraesthesia), sleep disturbances (including insomnia and intense dreams), agitation or anxiety, nausea and/or vomiting, tremor and headache are the most commonly reported reactions. Generally these symptoms are mild to moderate; however, in some patients they may be severe in intensity. They usually occur within the first few days of discontinuing treatment, but there have been very rare reports of such symptoms in patients who have inadvertently missed a dose. Generally these symptoms are self-limiting and usually resolve within 2 weeks, though in some individuals they may be prolonged (2-3 months or more). It is therefore advised that sertraline should be gradually tapered when discontinuing treatment over a period of several weeks or months, according to the patient's needs (see section 4.2).
Akathisia/psychomotor restlessnessThe use of sertraline has been associated with the development of akathisia, characterised by a subjectively unpleasant or distressing restlessness and need to move often accompanied by an inability to sit or stand still. This is most likely to occur within the first few weeks of treatment. In patients who develop these symptoms, increasing the dose may be detrimental.
Interference with urine screening testsFalse-positive urine immunoassay screening tests for benzodiazepines have been reported in patients taking sertraline. This is due to lack of specificity of the screening tests. False-positive test results may be expected for several days following discontinuation of sertraline therapy. Confirmatory tests, such as gas chromatography/mass spectrometry, will distinguish sertraline from benzodiazepines.
Angle-Closure GlaucomaSSRIs including sertraline may have an effect on pupil size resulting in mydriasis. This mydriatic effect has the potential to narrow the eye angle resulting in increased intraocular pressure and angle-closure glaucoma, especially in patients pre-disposed. Sertraline should therefore be used with caution in patients with angle-closure glaucoma or history of glaucoma.
Irreversible MAOIs (e.g. selegiline)Sertraline must not be used in combination with irreversible MAOIs such as selegiline. Sertraline must not be initiated for at least 14 days after discontinuation of treatment with an irreversible MAOI. Sertraline must be discontinued for at least 7 days before starting treatment with an irreversible MAOI (see section 4.3).
Reversible, selective MAO-A inhibitor (moclobemide)Due to the risk of serotonin syndrome, the combination of sertraline with a reversible and selective MAOI, such as moclobemide, should not be given. Following treatment with a reversible MAO-inhibitor, a shorter withdrawal period than 14 days may be used before initiation of sertraline treatment. It is recommended that sertraline should be discontinued for at least 7 days before starting treatment with a reversible MAOI (see section 4.3).
Reversible, non-selective MAOI (linezolid)The antibiotic linezolid is a weak reversible and non-selective MAOI and should not be given to patients treated with sertraline (see section 4.3).Severe adverse reactions have been reported in patients who have recently been discontinued from an MAOI and started on sertraline, or have recently had sertraline therapy discontinued prior to initiation of an MAOI. These reactions have included tremor, myoclonus, diaphoresis, nausea, vomiting, flushing, dizziness, fluctuations of vital signs and hyperthermia with features resembling neuroleptic malignant syndrome, seizures, and death. Centrally active medication Caution is advised if Sertraline Tablets is administered with other centrally active medication. In particular, SSRIs have the potential to interact with tricyclic antidepressants leading to an increase in plasma levels of the tricyclic antidepressant. A possible mechanism for this interaction is the inhibitory effect of SSRIs on the CYP2D6 isoenzyme. Pimozide Increased pimozide levels of approximately 35% have been demonstrated in a study of a single low dose pimozide (2mg) with sertraline co administration. These increased levels were not associated with any changes in EKG. While the mechanism of this interaction is unknown, due to the narrow therapeutic index of pimozide, concomitant administration of pimozide and sertraline is contra-indicated (see section 4.3). CNS depressants and Alcohol The co-administration of sertraline 200mg daily did not potentiate the effects of alcohol, carbamazapine, haloperidol, or phenytoin on cognitive and psychomotor performance in healthy subjects; however, the concomitant use of Sertraline Tablets and alcohol in depressed patients is not recommended.
Other serotonergic drugsSee section 4.4 Caution is also advised with fentanyl used in general anaesthesia or in the treatment of chronic pain.
Special Precautions:Lithium In placebo-controlled trials in normal volunteers, the co-administration of Sertraline Tablets and lithium did not significantly alter lithium pharmacokinetics. Co-administration of Sertraline Tablets with lithium did result in an increase in tremor relative to placebo, indicating a possible pharmacodynamic interaction. When co-administering sertraline with lithium, patients should be appropriately monitored. There have been other reports of enhanced effects when SSRIs have been given with lithium or tryptophan and therefore the concomitant use of SSRIs with these drugs should be undertaken with caution.Phenytoin A placebo-controlled trial in normal volunteers suggests that chronic administration of sertraline 200 mg/day does not produce clinically important inhibition of phenytoin metabolism. Nonetheless, as some case reports have emerged of high phenytoin exposure in patients using sertraline, it is recommended that plasma phenytoin concentrations be monitored following initiation of sertraline therapy, with appropriate adjustments to the phenytoin dose. In addition, co-administration of phenytoin may cause a reduction of sertraline plasma levels. It cannot be excluded that other CYP3A4 inducers, e.g. phenobarbital, carbamazepine, St John´s Wort, rifampicin may cause a reduction of sertraline plasma levels.
TriptansThere have been rare post-marketing reports describing patients with weakness, hyperreflexia, incoordination, confusion, anxiety and agitation following the use of sertraline and sumatriptan. Symptoms of serotonergic syndrome may also occur with other products of the same class (triptans). If concomitant treatment with sertraline and triptans is clinically warranted, appropriate observation of the patient is advised (see section 4.4).
WarfarinCo-administration of sertraline 200 mg daily with warfarin resulted in a small but statistically significant increase in prothrombin time, which may in some rare cases unbalance the INR value.Accordingly, prothrombin time should be carefully monitored when sertraline therapy is initiated or stopped.
Other drug interactions, digoxin, atenolol, cimetidineCo-administration with cimetidine caused a substantial decrease in sertraline clearance. The clinical significance of these changes is unknown. Sertraline had no effect on the beta-adrenergic blocking ability of atenolol. No interaction of sertraline 200 mg daily was observed with digoxin.
Drugs affecting platelet functionThe risk of bleeding may be increased when medicines acting on platelet function (e.g. NSAIDs, acetylsalicylic acid and ticlopidine) or other medicines that might increase bleeding risk are concomitantly administered with SSRIs, including sertraline (see section 4.4).
Drugs Metabolized by Cytochrome P450Sertraline may act as a mild-moderate inhibitor of CYP 2D6. Chronic dosing with sertraline 50 mg daily showed moderate elevation (mean 23%-37%) of steady-state desipramine plasma levels (a marker of CYP 2D6 isozyme activity). There is variability among the SSRIs in the extent to which they inhibit the activity of CYP2D6. Clinical relevant interactions may occur with other CYP 2D6 substrates with a narrow therapeutic index like class 1C antiarrhythmics such as propafenone and flecainide, TCAs and typical antipsychotics, especially at higher sertraline dose levels. Sertraline does not act as an inhibitor of CYP 3A4, CYP 2C9, CYP 2C19, and CYP 1A2 to a clinically significant degree. This has been confirmed by in-vivo interaction studies with CYP3A4 substrates (endogenous cortisol, carbamazepine, terfenadine, alprazolam), CYP2C19 substrate diazepam, and CYP2C9 substrates tolbutamide, glibenclamide and phenytoin. In vitro studies indicate that sertraline has little or no potential to inhibit CYP 1A2.Intake of three glasses of grapefruit juice daily increased the sertraline plasma levels by approximately 100% in a cross-over study in eight Japanese healthy subjects. Therefore, the intake of grapefruit juice should be avoided during treatment with sertraline (see section 4.4).Based on the interaction study with grapefruit juice, it cannot be excluded that the concomitant administration of sertraline and potent CYP3A4 inhibitors, e.g. protease inhibitors, ketoconazole, itraconazole, posaconazole, voriconazole, clarithromycin, telithromycin and nefazodone, would result in even larger increases in exposure of sertraline. This also concerns moderate CYP3A4 inhibitors, e.g. aprepitant, erythromycin, fluconazole, verapamil and diltiazem. The intake of potent CYP3A4 inhibitors should be avoided during treatment with sertraline.Sertraline plasma levels are enhanced by about 50% in poor metabolizers of CYP2C19 compared to rapid metabolizers (see section 5.2). Interaction with strong inhibitors of CYP2C19, e.g. omeprazole, lansoprazole, pantoprazole, rabeprazole, fluoxetine, fluvoxamine cannot be excluded. Serotonergic drugs There is limited controlled experience regarding the optimal timing of switching from other antidepressant or anti-obsessional drugs to Sertraline Tablets. Care and prudent medical judgment should be exercised when switching, particularly from long-acting agents. The duration of washout period which should intervene before switching from one selective serotonin reuptake inhibitor (SSRI) to another has not been established. Until further data are available, serotonergic drugs, such as tramadol, sumatriptan or fenfluramine, should not be used concomitantly with Sertraline Tablets, due to a possible enhancement of 5-HT associated effects. St John's Wort Concomitant use of the herbal remedy St John's wort (Hypericum perforatum) in patients receiving SSRIs should be avoided since there is a possibility of serotonergic potentiation. Drugs that affect platelet function, such as NSAIDs See 'Special warnings and special precautions for use (Haemorrhage)'. Other drug interactions Since Sertraline Tablets is bound to plasma proteins, the potential of Sertraline Tablets to interact with other plasma protein bound drugs should be borne in mind. Formal drug interaction studies have been performed with Sertraline Tablets. Co-administration of Sertraline Tablets (200mg daily) with diazepam or tolbutamide resulted in small, statistically significant changes in some pharmacokinetic parameters. Co-administration with cimetidine caused a substantial decrease in sertraline clearance. The clinical significance of these changes is unknown. Sertraline Tablets had no effect on the beta-adrenergic blocking ability of atenolol. No interaction with Sertraline Tablets (200mg daily) was observed with glibenclamide or digoxin. Co-administration of Sertraline Tablets (200mg daily) with warfarin resulted in a small but statistically significant increase in prothrombin time, the clinical significance of which is unknown. Accordingly, prothrombin time should be carefully monitored when Sertraline Tablets therapy is initiated or stopped. Sertraline Tablets (200mg daily), did not potentiate the effects of carbamazepine, haloperidol or phenytoin on cognitive and psychomotor performance in healthy subjects.
Table 1: Adverse ReactionsFrequency of adverse reactions observed from placebo-controlled clinical trials in depression, OCD, panic disorder, PTSD and social anxiety disorder. Pooled analysis and postmarketing experience (frequency not known).
|Very Common (≥1/10)||Common (≥1/100 to <1/10)||Uncommon (≥1/1000 to <1/100)||Rare (≥1/10000 to <1/1000)||Very rare (<1/10000)||Frequency not Known|
|Infections and Infestations|
|Pharyngitis||Upper Respiratory Tract Infection, Rhinitis||Diverticulitis, Gastroenteritis, Otitis Media|
|Neoplasms benign, malignant (including cysts and polyps)|
|Blood and lymphatic system disorders|
|Immune system disorders|
|Anaphylactoid Reaction, Allergic Reaction, Allergy|
|Hyperprolactinaemia, Hypothyroidism and syndrome of inappropriate ADH secretion|
|Metabolism and Nutrition Disorders|
|Anorexia, Increased Appetite*||Hypercholesterolaemia, Hypoglycaemia||Hyponatremia, Diabetes Mellitus, Hyperglycaemia|
|Insomnia (19%)||Depression*, Depersonalisation, Nightmare, Anxiety*, Agitation*, Nervousness, Libido Decreased*, Bruxism||Hallucination*, Euphoric Mood*, Apathy, Thinking Abnormal||Conversion Disorder, Drug Dependence, Psychotic disorder*, Aggression*, Paranoia, Suicidal Ideation/behaviour***, Sleep Walking, Premature Ejaculation||Paroniria|
|Nervous System Disorders|
|Dizziness (11%), Somnolence (13%), Headache (21%)*||Paraesthesia*, Tremor, Hypertonia, Dysgeusia, Disturbance in Attention,||Convulsion*, Muscle Contractions Involuntary*, Coordination Abnormal, Hyperkinesia, Amnesia, Hypoaesthesia*, Speech Disorder, Dizziness Postural, Migraine*||Coma*, Choreoathetosis, Dyskinesia, Hyperaesthesia, Sensory Disturbance||Movement Disorders (including extrapyramidal symptoms such as hyperkinesia, hypertonia, dystonia, teeth grinding or gait abnormalities), Syncope. Also reported were signs and symptoms associated with Serotonin Syndrome or Neuroleptic Malignant Syndrome: In some cases associated with concomitant use of serotonergic drugs that included agitation, confusion, diaphoresis, diarrhoea, fever, hypertension, rigidity and tachycardia. Akathisia and pyschomotor restlessness (see section 4.4), Cerebrovascular Spasm (including reversible cerebral vasconstriction syndrome and call-fleming syndrome).|
|Visual Disturbance||Glaucoma, Lacrimal Disorder, Scotoma, Diplopia, Photophobia, Hyphaema, Mydriasis*||Vision Abnormal, Pupils Unequal|
|Ear and Labyrinth Disorders|
|Palpitations*||Tachycardia||Myocardial Infarction, Bradycardia, Cardiac Disorder|
|Hot flush*||Hypertension*, Flushing||Peripheral Ischaemia||Abnormal Bleeding (such as epistaxis, gastrointestinal bleeding or haematuria)|
|Respiratory, Thoracic, and Mediastinal Disorders|
|Yawning*||Bronchospasm*, Dyspnoea, Epistaxis||Laryngospasm, Hyperventilation, Hypoventilation, Stridor, Dysphonia, Hiccups||Interstitial Lung Disease|
|Diarrhoea (18%), Nausea (24%), Dry Mouth (14%)||Abdominal Pain* Vomiting*, Constipation* Dyspepsia, Flatulence||Oesophagitis, Dysphagia, Haemorrhoids, Salivary Hypersecretion, Tongue Disorder, Eructation||Melaena, Haematochezia, Stomatitis, Tongue ulceration, Tooth Disorder, Glossitis, Mouth Ulceration||Pancreatitis|
|Hepatic Function Abnormal||Serious liver events (including hepatitis, jaundice and liver failure)|
|Skin and Subcutaneous Tissue Disorders|
|Rash*, Hyperhidrosis||Periorbital Oedema*, Purpura*, Alopecia*, Cold Sweat, Dry skin, Urticuria*||Dermatitis, Dermatitis Bullous, Rash Follicular, Hair Texture Abnormal, Skin Odour Abnormal||Rare reports of severe cutaneous adverse reactions (SCAR): e.g. Stevens-Johnson syndrome and epidermal necrolysis, Angioedema, Face Oedema, Photosensitivity, Skin Reaction, Pruritus|
|Musculoskeletal and Connective Tissue Disorders|
|Myalgia||Osteoarthritis, Muscular Weakness, Back Pain, Muscle Twitching||Bone Disorder||Arthralgia, Muscle Cramps|
|Renal and Urinary Disorders|
|Nocturia, Urinary Retention*, Polyuria, Pollakiura, Micturition disorder||Oliguria, Urinary Incontinence*, Urinary Hesitation|
|Reproductive System and Breast Disorders**|
|Ejaculation Failure (14%)||Sexual Dysfunction, Erectile Dysfunction||Vaginal Haemorrhage, Female Sexual Dysfunction||Menorrhagia, Atrophic Vulvuvaginitis, Balanoposthitis, Genital Discharge, Priapism*, Galactorrhoea*||Gynaecomastia, Menstrual Irregularities|
|General Disorders and Administration Site Conditions|
|Fatigue (10%)*||Chest Pain*||Malaise*, Chills, Pyrexia*, Asthenia*,Thirst||Hernia, Drug Tolerance Decreased, Gait Disturbance||Oedema Peripheral|
|Weight Decreased*, Weight Increased*||Alanine Aminotransferarase Increased*, Aspartate Aminotransferase Increased*, Semen Abnormal||Abnormal Clinical Laboratory Results, Altered Platelet Function, Increased Serum Cholesterol|
|Injury and poisoning|
|Surgical and medical procedures|
|If adverse experience occurred in depression, OCD, panic disorder, PTSD and social anxiety disorder, body term reclassified by depression studies body term. One case of neoplasm was reported in one patient receiving sertraline compared with no cases in the placebo arm. * these adverse reactions also occurred in postmarketing experience ** the denominator uses the number of patients in that sex group-combined: sertraline (1118 males, 1424 females) placebo (926 males, 1219 females) For OCD, short term, 1-12 week studies only *** Cases of suicidal ideation and suicidal behaviours have been reported during sertraline therapy or early after treatment discontinuation (see section 4.4).|
Withdrawal symptoms seen on discontinuation of sertraline treatmentDiscontinuation of sertraline (particularly when abrupt) commonly leads to withdrawal symptoms. Dizziness, sensory disturbances (including paraesthesia), sleep disturbances (including insomnia and intense dreams), agitation or anxiety, nausea and/or vomiting, tremor and headache are the most commonly reported. Generally these events are mild to moderate and are self-limiting; however, in some patients they may be severe and/or prolonged. It is therefore advised that when sertraline treatment is no longer required, gradual discontinuation by dose tapering should be carried out (see sections 4.2 and 4.4).
Elderly populationSSRIs or SNRIs including sertraline have been associated with cases of clinically significant hyponatraemia in elderly patients, who may be at greater risk for this adverse event (see section 4.4).
Paediatric populationIn over 600 paediatric patients treated with sertraline, the overall profile of adverse reactions was generally similar to that seen in adult studies. The following adverse reactions were reported from controlled trials (n=281 patients treated with sertraline):Very common (≥1/10): Headache (22%), insomnia (21%), diarrhoea (11%) and nausea (15%).Common (≥1/100 to <1/10): Chest pain, mania, pyrexia, vomiting, anorexia, affect lability, aggression, agitation, nervousness, disturbance in attention, dizziness, hyperkinesia, migraine, somnolence, tremor, visual disturbance, dry mouth, dyspepsia, nightmare, fatigue, urinary incontinence, rash, acne, epistaxis, flatulence.Uncommon (≥1/1000 to <1/100): ECG QT prolonged, suicide attempt, convulsion, extrapyramidal disorder, paraesthesia, depression, hallucination, purpura, hyperventilation, anaemia, hepatic function abnormal, alanine aminotransferase increased, cystitis, herpes simplex, otitis externa, ear pain, eye pain, mydriasis, malaise, haematuria, rash pustular, rhinitis, injury, weight decreased, muscle twitching, abnormal dreams, apathy, albuminuria, pollakiuria, polyuria, breast pain, menstrual disorder, alopecia, dermatitis, skin disorder, skin odour abnormal, urticaria, bruxism, flushing.Frequency not known: enuresis
Class effectsEpidemiological studies, mainly conducted in patients 50 years of age and older, show an increased risk of bone fractures in patients receiving SSRIs and TCAs. The mechanism leading to this risk is unknown.
TreatmentNo specific therapy is recommended and there are no specific antidotes to Sertraline Tablets. Establish and maintain an airway, ensure adequate oxygenation and ventilation. Activated charcoal, which may be used with sorbitol, may be as or more effective than emesis or lavage, and should be considered in treating overdose. Cardiac and vital signs monitoring is recommended along with general symptomatic and supportive measures. Due to the large volume of distribution of sertraline, forced diuresis, dialysis, haemoperfusion and exchange transfusion are unlikely to be of benefit. Sertraline overdose may prolong the QT-interval and ECG-monitoring is recommended in all ingestions of sertraline overdoses.
Tablet cores:Calcium hydrogen phosphate anhydrous (E 341) Microcrystalline cellulose (E460) Hydroxypropylcellulose (E463) Sodium starch glycolateMagnesium stearate
Film coating in 100mg:Opadry Yellow Hydroxy Propyl methyl cellulose (E464) Titanium dioxide (E171) Macragol Iron oxide Yellow (E172) Polysorbate 80 (E433)
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+44 (0)1565 751 378
+44 (0)1748 828 380
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