Sertraline 100mg Tablets
Out of date information, search anotherSUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Sertraline 100 mg Tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains sertraline hydrochloride equivalent to 100 mg sertraline. For full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Film-coated tablets
White to off-white biconvex film-coated tablets.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Sertraline Tablets are indicated for the treatment of symptoms of depressive illness, including accompanying symptoms of anxiety. Following satisfactory response, continuation with Sertraline Tablets therapy is effective in preventing relapse of the initial episode of depression or recurrence of further depressive episodes, including accompanying symptoms of anxiety.
Sertraline Tablets are also indicated for the treatment of obsessive compulsive disorder (OCD). Following initial response, Sertraline Tablets have been associated with sustained efficacy, safety and tolerability in up to two years treatment of OCD.
Sertraline Tablets are also indicated for the treatment of paediatric patients with OCD.
Clinical trials in Post-Traumatic Stress Disorder (PTSD) demonstrated efficacy in female patients but no evidence of efficacy was seen in males. Treatment with Sertraline Tablets is not be recommended for male patients with PTSD.
Sertraline Tablets are not indicated for use in children and adolescents under the age of 18 years with Major Depressive Disorder.
In particular, 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).
4.2 Posology and method of administration
Sertraline Tablets should be given as a single daily dose.
Sertraline Tablets can be administered with or without food.
Initial treatment
Depression and OCD:
Sertraline treatment should be started at a dose of 50 mg/day.
Panic Disorder, PTSD, and Social Anxiety Disorder:
Therapy should be initiated at 25 mg/day. After one week, the dose should be increased to 50 mg once daily.
This dosage regimen has been shown to reduce the frequency of early treatment emergent side effects characteristic of panic disorder.
Titration
Depression, OCD, Panic Disorder, Social Anxiety Disorder and PTSD:
Patients not responding to a 50 mg dose may benefit from dose increases. Dose changes should be made in steps of 50 mg at intervals of at least one week, up to a maximum of 200 mg/day. Changes in dose should not be made more frequently than once per week given the 24-hour elimination half life of sertraline.
The onset of therapeutic effect may be seen within 7 days. However, longer periods are usually necessary to demonstrate therapeutic response, especially in OCD.
Maintenance
Dosage during long term therapy should be kept at the lowest effective level, with subsequent adjustment depending on therapeutic response.
Depression:
Longer-term treatment may also be appropriate for prevention of recurrence of major depressive episodes (MDE). In most of the cases, the recommended dose in prevention of recurrence of MDE is the same as the one used during current episode. Patients with depression should be treated for a sufficient period of time of at least 6 months to ensure they are free from symptoms.
Panic disorder and OCD:
Continued treatment in panic disorder and OCD should be evaluated regularly, as relapse prevention has not been shown for these disorders.
Paediatric patients
Children and adolescents with obsessive compulsive disorder:
• Age 13-17 years: Initially 50 mg once daily.
• Age 6-12 years: Initially 25 mg once daily. The dosage may be increased to 50 mg once daily after one week.
Subsequent doses may be increased in case of less than desired response in 50 mg increments over a period of some weeks, as needed. The maximum dosage is 200 mg daily. However, the generally lower body weights of children compared to those of adults should be taken into consideration when increasing the dose from 50 mg. Dose changes should not occur at intervals of less than one week.
Efficacy is not shown in paediatric major depressive disorder.
No data is available for children under 6 years of age (see also section 4.4).
Use in 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).
Sertraline Tablets are for oral administration only.
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 Special Warnings and Precautions for Use and 4.8 Undesirable Effects). 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.
4.3 Contraindications
Sertraline Tablets are contra-indicated in patients with a known hypersensitivity to sertraline.
Monoamine oxidase inhibitors: Cases of serious and sometimes fatal reactions have been reported in patients receiving an SSRI in combination with an monoamine oxidase inhibitor (MAOI), including the selective MAOI selegiline and the reversible MAOI (RIMA) moclobemide and in patients who have recently discontinued an SSRI and have been started on a MAOI.
Symptoms of a drug interaction with a MAOI include: hyperthermia, rigidity, myoclonus, autonomic instability with possible rapid fluctuations of vital signs, mental status changes that include confusion, irritability and extreme agitation progressing to delirium and coma.
Sertraline Tablets should not be used in combination with a MAOI. Sertraline Tablets may be started 14 days after discontinuing treatment with an irreversible MAOI and at least one day after discontinuing treatment with the reversible MAOI (RIMA), moclobemide. At least 14 days should elapse after discontinuing Sertraline Tablets before starting a MAOI or RIMA.
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 -Interaction with Other Medicaments and Other Forms of Interaction).
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).
4.4 Special warnings and precautions for use
Monoamine oxidase inhibitors. See "Contra-indications".
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 drugs:
There is limited controlled experience regarding the optimal timing of switching from SSRIs, antidepressants or anti-obsessional 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 agonists:
Co-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 mania:
Manic/hypomanic symptoms have been reported to emerge in a small proportion of patients treated with marketed antidepressant and anti-obsessional 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.
Schizophrenia:
Psychotic symptoms might become aggravated in schizophrenic patients.
Use in patients with renal or hepatic impairment: As with many other medications, sertraline should be used with caution in patients with renal and hepatic impairment (see "Contra-indications").
Since sertraline is extensively metabolised, excretion of unchanged drug in urine is a minor route of elimination. However, steady state pharmacokinetics of sertraline have not been adequately studied in patients with renal impairment and although no significant change in pharmacokinetics was observed in the studies reported, caution is advised when treating patients with renal impairment.
Sertraline 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.
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.
Psychomotor restlessness: The use of Sertraline has been associated with the development of psychomotor restlessness, which clinically may be very similar to 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 and it may be necessary to review the use of Sertraline.
Electroconvulsive therapy (ECT): Since there is little clinical experience of concurrent administration of Sertraline Tablets and ECT, caution is advisable.
Mania: Sertraline Tablets should be used with caution in patients with a history of mania/hypomania. Sertraline Tablets should be discontinued in any patient entering a manic phase.
Suicide/suicidal thoughts: Depression 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 during this period.
It is general clinical experience that the risk of self harm is highest shortly after presentation and the risk of suicide may increase again in the early stages of recovery. Furthermore, there is evidence that in a small group of people, antidepressants may increase the risk of suicidal thoughts and self-harm.
Other psychiatric conditions for which Sertraline 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, those exhibiting a significant degree of suicidal ideation prior to commencement of treatment, and young adults, are at a greater risk of suicidal thoughts or suicide attempts, and should receive careful monitoring during treatment.
Patients, (and caregivers of patients) should be alerted about the need to monitor for the emergence of suicidal thoughts and to seek medical advice immediately if these symptoms present.
Abnormal bleeding/Haemorrhage: There have been reports of cutaneous bleeding abnormalities such as ecchymoses and purpura 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 antiinflammatory drugs (NSAIDs)) as well as in patients with a history of bleeding disorders.
Hyponatraemia:
Hyponatraemia 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: are common when treatment is discontinued, particularly if discontinuation is abrupt (see section 4.8 Undesirable effects).
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 "Withdrawal Symptoms seen on discontinuation of Sertraline” Section 4.2 Posology and Method of Administration).
Use in the elderly: The pattern and incidence of adverse reactions in the elderly is similar to that in younger patients.
SSRIs or SNRIs including sertraline have however been associated with cases of clinically significant hyponatraemia in elderly patients, who may be at greater risk for this adverse event (see Hyponatraemia in section 4.4).
Use in children and adolescents under 18 years of age: More than 250 paediatric OCD patients have been exposed to Sertraline in completed and ongoing studies. The safety profile of Sertraline in these paediatric studies is comparable to that observed in the adult OCD studies. The efficacy of Sertraline 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.
Sertraline should not be used in the treatment of children and adolescents under the age of 18 years, except for patients with OCD. 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 the appearance of suicidal symptoms. In addition, longterm safety data in children and adolescents concerning growth, maturation and cognitive and behavioural development are lacking.
4.5 Interaction with other medicinal products and other forms of interaction Monoamine oxidase inhibitors: see "Contra-indications".
Centrally active medication: Caution is advised if Sertraline Tablets are 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. There is variability among the SSRIs in the extent to which they inhibit the activity of CYP2D6. The clinical significance of this depends on the extent of inhibition and the therapeutic index of the co-administered drug. In formal interaction studies, chronic dosing with sertraline 50 mg daily showed minimal elevation (mean 23-37 %) of steady state plasma desipramine levels (a marker of CYP2D6 isoenzyme activity).
Pimozide - Increased pimozide levels have been demonstrated in a study of a single low dose pimozide (2 mg) with sertraline co-administration. These increased levels were not associated with any changes in ECG. While the mechanism of this interaction is unknown, due to the narrow therapeutic index of pimozide, concomitant of pimozide and sertraline is contra-indicated.
Alcohol: In 11 healthy subjects administered Sertraline Tablets (200 mg daily) for 9 days, there was no adverse effect on cognitive or psychomotor performance relative to placebo, following a single dose of 500 mg/kg alcohol. However, the concomitant use of Sertraline Tablets and alcohol in depressed patients is not recommended.
Lithium and Tryptophan: In placebo-controlled trials in normal volunteers, the coadministration 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. 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.
Serotonergic drugs: There is limited controlled experience regarding the optimal timing of switching from other antidepressant or antiobsessional drugs to Sertraline Tablets. Care and prudent medical judgement 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 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. Coadministration of Sertraline Tablets (200 mg 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 (200 mg daily) was observed with glibenclamide or digoxin.
Co-administration of Sertraline Tablets (200 mg 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 (200 mg daily), did not potentiate the effects of carbamazepine, haloperidol or phenytoin on cognitive and psychomotor performance in healthy subjects.
4.6 Fertility, pregnancy and lactation
Fertility: Animal data did not show an effect of sertraline on fertility parameters (see section 5.3). Human case reports with some SSRIs have shown that an effect on sperm quality is reversible. Impact on human fertility has not been observed so far.
Pregnancy: Although animal studies did not provide any evidence of teratogenicity, the safety of Sertraline Tablets during human pregnancy has not been established. As with all drugs Sertraline Tablets should only be used in pregnancy if the potential benefits of treatment to the mother outweigh the possible risks to the developing foetus.
Use of sertraline during pregnancy has been reported to cause symptoms, compatible with withdrawal reactions, in some neonates, whose mothers had been on sertraline. This phenomenon has also been observed with other SSRI antidepressants. Sertraline is not recommended in pregnancy, unless the clinical condition of the woman is such that the benefit of the treatment is expected to outweigh the potential risk.
Neonates should be observed if maternal use of sertraline continues into the later stages of pregnancy, particularly the third trimester. The following symptoms may occur in the neonate after maternal sertraline use in later stages of pregnancy: respiratory distress, cyanosis, apnoea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycaemia, hypertonia, hypotonia, hyperreflexia, tremor, jitteriness, irritability, lethargy, constant crying, somnolence and difficulty in sleeping. These symptoms could be due to either serotonergic effects or withdrawal symptoms. In a majority of instances the complications begin immediately or soon (<24 hours) after delivery.
Lactation: Sertraline is known to be excreted in breast milk. Its effects on the nursing infant have not yet been established. If treatment with Sertraline Tablets is considered necessary, discontinuation of breast feeding should be considered.
4.7 Effects on ability to drive and use machines
Sertraline has no effect on psychomotor performance. However, since antidepressant or antiobsessional drugs may impair the abilities required to perform potentially hazardous tasks such as driving a car or operating machinery, the patient should be cautioned accordingly. Sertraline Tablets should not be administered with benzodiazepines or other tranquillizers in patients who drive or operate machinery.
4.8 Undesirable effects
Side-effects which occurred significantly more frequently with sertraline than placebo in multiple dose studies were: nausea, diarrhoea/loose stools, anorexia, dyspepsia, tremor, dizziness, insomnia, somnolence, increased sweating, dry mouth and sexual dysfunction (principally ejaculatory delay in males).
The side-effect profile commonly observed in patients with OCD and PTSD is similar to that observed in patients with depression.
In paediatric OCD patients, side-effects which occurred significantly more frequently with sertraline than placebo were: headache, insomnia, agitation, anorexia, tremor. Most were of mild to moderate severity.
Post-marketing spontaneous reports include the following:
Cardiovascular: Blood pressure disturbances including postural hypotension, tachycardia.
Eye disorders: Abnormal vision.
Gastro-intestinal: Vomiting, abdominal pain.
Nervous system: Amnesia, headache, drowsiness, movement disorders, parathesia, hypoaesthesia, depressive symptoms, hallucinations, aggressive reaction, agitation, anxiety, psychosis, depersonalisation, nervousness, panic reaction and signs and symptoms associated with serotonin syndrome which include fever, rigidity, confusion, agitation, diaphoresis, tachycardia, hypertension and diarrhoea.
There have also been reports of manic reaction, although this phenomenon may be part of the underlying disease.
Convulsions (Seizures): Sertraline Tablets should be discontinued in any patient who develops seizures (See " Special warnings and special precautions for use ").
Psychomotor restlessness/akathisia: Rare (see section 4.4 Special Warnings and Precautions for Use)
Musculoskeletal: Arthralgia, myalgia.
Hepatic / pancreatic: Rarely, pancreatitis and serious liver events (including hepatitis, jaundice and liver failure). Asyrnptomatic elevations in serum transaminases (SGOT and SGPT) have been reported in association with sertraline administration (0.8 -1.3 %), with an increased risk associated with the 200 mg daily dose. The abnormalities usually occurred within the first 1 to 9 weeks of drug treatment and promptly diminished upon drug discontinuation.
Renal urinary disorders: Urinary retention.
Reproductive: Hyperprolactinemia, galactorrhoea, menstrual irregularities, anorgasmy.
Skin and allergic reactions: Rash (including rare reports of erythema multiforme, photosensitivity), angioedema, ecchymoses, pruritus and anaphylactoid reactions.
Metabolic: Rare cases of hyponatremia have been reported and appeared to be reversible when sertraline was discontinued. Some cases were possibly due to the syndrome of inappropriate antidiuretic hormone secretion. The majority of reports were associated with older patients, and patients taking diuretics or other medications.
Haematiological: There have been rare reports of altered platelet function and/or abnormal clinical laboratory results in patients taking sertraline. While there have been reports of thrombocytopenia, abnormal bleeding or purpura in several patients taking sertraline, it is unclear whether sertraline had a causative role. See also "Special warnings and special precautions for use".
General: Malaise.
Withdrawal symptoms have been reported on discontinuation of Sertraline treatment.
Discontinuation 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 reactions. 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 Posology and Method of Administration and 4.4 Special Warnings and Precautions for use).
Adverse events from paediatric clinical trials:
In paediatric clinical trials in depression the following adverse events were reported at a frequency of at least 2 % of patients and occurred at a rate of at least twice that of placebo: dry mouth (2.1 % vs 0.5 %), hyperkinesia (2.6 % vs 0.5 %), tremor (2.1 % vs 0 %), diarrhoea (9.5 % vs 1.6 %), vomiting (4.2 % vs 1.1 %), agitation (6.3 % vs 1.1 %), anorexia (5.3 % vs 1.1 %) and urinary incontinence (2.1 % vs 0 %).
Suicidal thoughts and suicide attempts were mainly observed in clinical trials with Major Depressive Disorder.
4.9 Overdose Toxicity:
On the evidence available, Sertraline has a wide margin of safety in overdose. Overdoses of Sertraline alone of up to 8 g have been reported. Deaths involving overdoses of Sertraline in combination with other drugs and/or alcohol have been reported. Therefore, any overdosage should be treated aggressively.
Symptoms:
Symptoms of overdose include serotonin-mediated side-effects such as somnolence, gastrointestinal disturbances (such as nausea and vomiting), tachycardia, tremor, agitation and dizziness. Less frequently reported was coma.
No specific therapy is recommended and there are no specific antidotes to Sertraline. 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 duresis, dialysis, haemoperfusion and exchange transfusion are unlikely to be of benefit.
5.1 Pharmacodynamic properties
ATC Code: N06 AB06
Sertraline is a potent and specific inhibitor of neuronal serotonin (5-HT) uptake in vitro and in vivo, but is without affinity for muscarinic, serotonergic, dopaminergic, adrenergic, histaminergic, GABA or benzodiazepine receptors.
Sertraline is devoid of stimulant, sedative or anticholinergic activity or cardiotoxicity in animals.
Unlike tricyclic antidepressants, no weight gain is observed with treatment for depression.
Sertraline has not been observed to produce physical or psychological dependence.
Sertraline has been evaluated in paediatric OCD patients aged 6 to 17 in a 12 week placebo-controlled study. Therapy for paediatric OCD patients (aged 6-12) commenced at 25 mg/day increasing to 50 mg/day after 1 week. Side-effects which occurred significantly more frequently with sertraline than placebo were: headache, insomnia, agitation [6-12 years]; insomnia, anorexia, tremor [13-17 years]. There is limited evidence of efficacy and safety beyond 12 weeks of treatment
5.2 Pharmacokinetic properties
Sertraline exhibits dose proportional pharmacokinetics over a range of 50-200 mg. After oral administration of sertraline in man, peak blood levels occur at about 4.5 -8.4 hours. Daily doses of sertraline achieve steady state after one week. Sertraline has a plasma half-life of approximately 26 hours with a mean half-life for young and elderly adults ranging from 22-36 hours. Sertraline is approximately 98 bound to plasma proteins. The principal metabolite, N-desmethylsertraline, is inactive in in vivo models of depression and has a half-life of approximately 62-104 hours. Sertraline and N-desmethylsertraline are both extensively metabolised in man and the resultant metabolites excreted in faeces and urine in equal amounts. Only a small amount (< 0.2 %) of unchanged sertraline is excreated in the urine.
The pharmacokinetics of sertraline in paediatric OCD patients have been shown to be comparable with adults (although paediatric patients metabolise sertraline with slightly greater efficiency). However, lower doses may be advisable for paediatric patients given their lower body weights (especially 6-12 years). in order to avoid excessive plasma levels.
A clear relationship between sertraline concentration and the magnitude of therapeutic response has not been established.
The pharmacokinetics of sertraline in elderly patients are similar to younger adults. Food does not significantly change the bioavailability of Sertraline Tablets.
5.3
Preclinical safety data
Extensive chronic safety evaluation studies in animals show that sertraline is generally well tolerated at doses that are appreciable multiples of those that are clinically effective.
Animal data from rodents and non-rodents does not reveal effects on fertility.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Tablet core: Anhydrous colloidal silica, microcrystalline cellulose, croscarmellose sodium, copovidone, lactose, magnesium stearate.
Film-coating: Hypromellose, hydroxypropyl cellulose, titanium dioxide (E171) and macrogol 400.
6.2 Incompatibilities
None known
6.3 Shelf life
The shelf life for this product is 2 years.
6.4 Special precautions for storage
None
6.5 Nature and contents of container
Blister packs of aluminium foil and PVC/PVDC in cartons.
Pack size: 28, 30, 56, 60, 84, 100, 250, 500 & 1000 tablets.
6.6 Special precautions for disposal
No special requirements.
7 MARKETING AUTHORISATION HOLDER
Chatfield Pharmaceuticals Limited Trading as Chatfield Laboratories Kramer Mews London SW5 9JL
8 MARKETING AUTHORISATION NUMBER(S)
PL 02142/0081
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
30/09/2011
10 DATE OF REVISION OF THE TEXT
19/09/2012