Lustral 50, 100 mg

/ Dexcel Pharma Technologies Ltd

Initial treatment: Sertraline treatment should be started at a dose of 50 mg/day.
Titration: 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.
Maintenance: Dosage during long-term therapy should be kept at the lowest effective level, with subsequent adjustment depending on therapeutic response. 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.
Paediatric patients: Efficacy is not shown in paediatric major depressive disorder.
Use in elderly: Elderly should be dosed carefully, as elderly may be more at risk for hyponatraemia.
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. Sertraline should not be used in cases of severe hepatic impairment as no clinical data are available.
Use in renal insufficiency: No dosage adjustment is necessary in patients with renal insufficiency.
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. 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 is indicated for the treatment of symptoms of depression in patients with or without a history of mania. Following satisfactory response, continuation with sertraline therapy is effective in prevention relapse of the initial episode of depression or recurrence of further depressive episodes.

Hypersensitivity to the active substance or any of the excipients. .
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 MAOI.
Concomitant intake of pimozide is contraindicated.

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 other serotonergic drugs (including other serotonergic antidepressants, amphetamines, triptans), with drugs which impair metabolism of serotonin (including MAOIs e.g. methylene blue), antipsychotics and other dopamine antagonists, and with opiate drugs. Patients should be monitored for the emergence of signs and symptoms of SS or NMS syndrome.
Switching from Selective Serotonin Reuptake Inhibitors (SSRIs), antidepressants or anti-obsessional 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 amphetamines, 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.
QTc Prolongation/Torsade de Pointes (TdP): Cases of QTc prolongation and TdP have been reported during post-marketing use of sertraline. The majority of reports occurred in patients with other risk factors for QTc prolongation/TdP. Effect on QTc prolongation was confirmed in a thorough 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 hypomagnesemia, familial history of QTc prolongation, bradycardia and concomitant use of medications which prolong QTc interval.
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.
Seizures: Seizures may occur with sertraline therapy: sertraline should be avoided in patients with unstable epilepsy and patients with controlled epilepsy should be carefully monitored. Sertraline should be discontinued in any patient who develops seizures.
Suicide/suicidal thoughts/suicide attempts or clinical worsening: 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 until such improvement occurs. It is general clinical experience that the risk of suicide may increase in the early stages of recovery. 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.
Sexual dysfunction: Selective serotonin reuptake inhibitors (SSRIs) may cause symptoms of sexual dysfunction. There have been reports of long-lasting sexual dysfunction where the symptoms have continued despite discontinuation of SSRIs.
Paediatric population: Sertraline should not be used in the treatment of children and adolescents under the age of 18 years. 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.
Abnormal bleeding/Haemorrhage: There have been reports of bleeding abnormalities with SSRIs including cutaneous bleeding (ecchymoses and purpura) and other haemorrhagic events such as gastrointestinal or gynaecological bleeding, including fatal haemorrhages. SSRIs/SNRIs may increase the risk of postpartum haemorrhage. Caution is advised in patients taking SSRIs, particularly in concomitant use with drugs known to affect platelet function (e.g. anticoagulants, atypical antipsychotics and phenothiazines, most tricyclic antidepressants, acetylsalicylic acid and non-steroidal anti-inflammatory 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 110mmol/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. 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 treatment: Withdrawal symptoms when treatment is discontinued are common, particularly if discontinuation is abrupt. 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.
Akathisia/psychomotor restlessness: The 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.
Hepatic 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 to normal subjects. There were no significant differences in plasma protein binding observed between the two groups.
Renal impairment: Sertraline is extensively metabolised, and excretion of unchanged drug in urine is a minor route of elimination. In studies of 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), 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.
Use in elderly: Over 700 elderly patients (>65 years) have participated in clinical studies. The pattern and incidence of adverse reactions in the elderly was 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.
Diabetes: In patients with diabetes, treatment with an SSRI may alter glycaemic control. Insulin and/or oral hypoglycaemic dosage may need to be adjusted.
Electroconvulsive therapy: There are no clinical studies establishing the risks or benefits of the combined use of ECT and sertraline.
Grapefruit juice: The administration of sertraline with grapefruit juice is not recommended.
Interference with urine screening tests: False-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 glaucoma: SSRIs 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.
Excipient information
This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially
‘sodium-free’.
See prescribing information or full details.

Very Common: insomnia, dizziness, headache, somnolence, nausea, diarrhoea, dry mouth, ejaculation failure, fatigue.
Common: upper respiratory tract infection, pharyngitis, rhinitis, decreased appetite, increased appetite, anxiety, depression, agitation, libido decreased, nervousness, depersonalisation, nightmare, bruxism, tremor, movement disorders (including extrapyramidal symptoms such as hyperkinesia, hypertonia, dystonia, teeth grinding or gait abnormalities), paraesthesia, hypertonia, disturbance in attention, dysgeusia, visual disturbance,
tinnitus, palpitations, hot flush, yawning, dyspepsia, constipation, abdominal pain, vomiting, flatulence, hyperhidrosis, rash, back pain, arthralgia, myalgia, menstruation irregular, erectile dysfunction, malaise, chest pain, asthenia, pyrexia, weight increased, injury.
See prescribing information or full details.

Contraindicated Monoamine Oxidase Inhibitors 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 14 days before starting treatment with an irreversible MAOI.
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 14 days before starting treatment with a reversible MAOI.
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. Severe adverse reactions have been reported in patients who have recently been discontinued from an MAOI (e.g. methylene blue) 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, and hyperthermia with features resembling neuroleptic malignant syndrome, seizures, and death.
Pimozide: Increased pimozide levels of approximately 35% have been demonstrated in a study of a single low dose pimozide (2 mg). 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 sertraline and pimozide is contraindicated.
Co-administration with sertraline is not recommended
CNS depressants and alcohol: The co-administration of sertraline 200 mg daily did not potentiate the effects of alcohol, carbamazepine, haloperidol, or phenytoin on cognitive and psychomotor performance in healthy subjects; however, the concomitant use of sertraline and alcohol is not recommended.
Other serotonergic drugs: Caution is also advised with fentanyl (used in general anaesthesia or in the treatment of chronic pain), other serotonergic drugs (including other serotonergic antidepressants, amphetamines, triptans), and with other opiate drugs.
Special Precautions
Drugs that Prolong the QT Interval: The risk of QTc prolongation and/or ventricular arrhythmias (e.g. TdP) may be increased with concomitant use of other drugs which prolong the QTc interval.
Metamizole: Co-administration of sertraline with metamizole, which is an inducer of metabolising enzymes including CYP2B6 and CYP3A4, may cause a reduction in plasma concentrations of sertraline with potential decrease in clinical efficacy. Therefore, caution is advised when metamizole and sertraline are administered concurrently; clinical response and/or drug levels should be monitored as appropriate.
Warfarin: Co-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.
Drugs affecting platelet function: The 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.
Drugs Metabolized by Cytochrome P450: Sertraline may act as a mild-moderate inhibitor of CYP 2D6. 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. 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. 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. Interaction with strong inhibitors of CYP2C19, cannot be excluded.
See prescribing information for full details.

Pregnancy: There are no well controlled studies in pregnant women. However, a substantial amount of data did not reveal evidence of induction of congenital malformations by sertraline.
Breast-feeding: To date, no adverse effects on the health of infants nursed by mothers using sertraline have been reported, but a risk cannot be excluded. Use in nursing mothers is not recommended unless, in the judgment of the physician, the benefit outweighs the risk.
See prescribing information for full details.      

Toxicity: Sertraline has a margin of safety dependent on patient population and/or concomitant medication. Deaths have been reported involving overdoses of sertraline, alone or in combination with other drugs and/or alcohol. Therefore, any overdosage should be medically 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. Coma has been reported although less frequently. QTc prolongation/Torsade de Pointes has been reported following sertraline overdose; therefore, ECG-monitoring is recommended in all ingestions of sertraline overdoses.
Management: There are no specific antidotes to sertraline. It is recommended to establish and maintain an airway and , if necessary, ensure adequate oxygenation and ventilation,. Activated charcoal, which may be used with a cathartic, may be as or more effective than lavage, and should be considered in treating overdose. Induction of emesis is not recommended. Cardiac (e.g. ECG) and vital sign monitoring is also 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.

Storage: Store below 25°C.