Seroquel XL 50 mg prolonged-release tablets
Seroquel XL 150 mg prolonged-release tablets
Seroquel XL 200 mg prolonged-release tablets
Seroquel XL 300 mg prolonged-release tablets
Seroquel XL 400 mg prolonged-release tablets
Seroquel XL 50 mg contains 50 mg quetiapine (as quetiapine fumarate)
Excipient : 119 mg lactose (anhydrous) per tablet
Seroquel XL 150 mg contains 150 mg quetiapine (as quetiapine fumarate)
Excipient : 71 mg lactose (anhydrous) per tablet
Seroquel XL 200 mg contains 200 mg quetiapine (as quetiapine fumarate)
Excipient : 50 mg lactose (anhydrous) per tablet
Seroquel XL 300 mg contains 300 mg quetiapine (as quetiapine fumarate)
Excipient : 47 mg lactose (anhydrous) per tablet
Seroquel XL 400 mg contains 400 mg quetiapine (as quetiapine fumarate)
Excipient : 15 mg lactose (anhydrous) per tablet
For a full list of excipients, see Section 6.1.
Prolonged-release tablet
Seroquel XL 50 mg tablets are peach-coloured and engraved with “XR 50” on one side
Seroquel XL 150 mg tablets are white and engraved with “XR 150” on one side
Seroquel XL 200 mg tablets are yellow and engraved with “XR 200” on one side
Seroquel XL 300 mg tablets are pale yellow and engraved with “XR 300” on one side
Seroquel XL 400 mg tablets are white and engraved with “XR 400” on one side
Seroquel XL is indicated for:
• treatment of Schizophrenia
• treatment of bipolar disorder:
o For the treatment of moderate to severe manic episodes in bipolar disorder
o For the treatment of major depressive episodes in bipolar disorder
o For the prevention of recurrence of manic or depressed episodes in patients with bipolar disorder who previously responded to quetiapine treatment.
• add-on treatment of major depressive episodes in patients with Major Depressive Disorder (MDD) who have had sub-optimal response to antidepressant monotherapy (seeSection 5.1). Prior to initiating treatment, clinicians should consider the safety profile of Seroquel XL (see Section 4.4).
Different dosing schedules exist for each indication. It must therefore be ensured that patients receive clear information on the appropriate dosage for their condition.
Seroquel XL should be administered once daily, without food. The tablets should be swallowed whole and not split, chewed or crushed.
Adults:
For the treatment of schizophrenia and moderate to severe manic episodes in bipolar disorder
Seroquel XL should be administrated at least one hour before a meal. The daily dose at the start of therapy is 300 mg on Day 1 and 600 mg on Day 2. The recommended daily dose is 600 mg, however if clinically justified the dose may be increased to 800 mg daily. The dose should be adjusted within the effective dose range of 400 mg to 800 mg per day, depending on the clinical response and tolerability of the patient. For maintenance therapy in schizophrenia no dosage adjustment is necessary.
For the treatment of major depressive episodes in bipolar disorder
Seroquel XL should be administered at bedtime. The total daily dose for the first four days of therapy is 50 mg (Day 1), 100 mg (Day 2), 200 mg (Day 3) and 300 mg (Day 4). The recommended daily dose is 300 mg. In clinical trials, no additional benefit was seen in the 600 mg group compared to the 300 mg group (see Section 5.1). Individual patients may benefit from a 600 mg dose. Doses greater than 300 mg should be initiated by physicians experienced in treating bipolar disorder. In individual patients, in the event of tolerance concerns, clinical trials have indicated that dose reduction to a minimum of 200 mg could be considered
For preventing recurrence in bipolar disorder
For preventing recurrence of manic, mixed or depressive episodes in bipolar disorder, patients who have responded to Seroquel XL for acute treatment of bipolar disorder should continue on Seroquel XL at the same dose administered at bedtime. Seroquel XL dose can be adjusted depending on clinical response and tolerability of the individual patient within the dose range of 300 mg to 800 mg/day. It is important that the lowest effective dose is used for maintenance therapy.
For add-on treatment of major depressive episodes in MDD
Seroquel XL should be administered prior to bedtime. The daily dose at the start of therapy is 50 mg on Day 1 and 2, and 150 mg on Day 3 and 4. Antidepressant effect was seen at 150 and 300 mg/day in short-term trials as add-on therapy (with amitriptyline, bupropion, citalopram, duloxetine, escitalopram, fluoxetine, paroxetine, sertraline and venlafaxine - see Section 5.1) and at 50 mg/day in short-term monotherapy trials. There is an increased risk of adverse events at higher doses. Clinicians should therefore ensure that the lowest effective dose, starting with 50 mg/day, is used for treatment. The need to increase the dose from 150 to 300 mg/day should be based on individual patient eva luation.
Switching from Seroquel immediate-release tablets:
For more convenient dosing, patients who are currently being treated with divided doses of immediate-release Seroquel tablets may be switched to Seroquel XL at the equivalent total daily dose taken once daily. Individual dosage adjustments may be necessary.
Elderly:
As with other antipsychotics and antidepressants, Seroquel XL should be used with caution in the elderly, especially during the initial dosing period. The rate of dose titration of Seroquel XL may need to be slower, and the daily therapeutic dose lower, than that used in younger patients. The mean plasma clearance of quetiapine was reduced by 30% to 50% in elderly patients when compared to younger patients. Elderly patients should be started on 50 mg/day. The dose can be increased in increments of 50 mg/day to an effective dose, depending on the clinical response and tolerability of the individual patient.
In elderly patients with major depressive episodes in MDD, dosing should begin with 50 mg/day on Days 1-3, increasing to 100 mg/day on Day 4 and 150 mg/day on Day 8. The lowest effective dose, starting from 50 mg/day should be used. Based on individual patient eva luation, if dose increase to 300 mg/day is required this should not be prior to Day 22 of treatment.
Efficacy and safety has not been eva luated in patients over 65 years with depressive episodes in the framework of bipolar disorder.
Paediatric Population:
Seroquel XL is not recommended for use in children and adolescents below 18 years of age, due to a lack of data to support use in this age group. The available evidence from placebo-controlled clinical trials is presented in Sections 4.4, 4.8, 5.1 and 5.2.
Renal impairment:
Dosage adjustment is not necessary in patients with renal impairment.
Hepatic impairment:
Quetiapine is extensively metabolised by the liver. Therefore, Seroquel XL should be used with caution in patients with known hepatic impairment, especially during the initial dosing period. Patients with hepatic impairment should be started on 50 mg/day. The dose can be increased in increments of 50 mg/day to an effective dose, depending on the clinical response and tolerability of the individual patient.
Hypersensitivity to the active substance or to any of the excipients of this product.
Concomitant administration of cytochrome P450 3A4 inhibitors, such as HIV-protease inhibitors, azole-antifungal agents, erythromycin, clarithromycin and nefazodone, is contraindicated. (see Section 4.5).
As Seroquel XL has several indications, the safety profile should be considered with respect to the individual patient's diagnosis and the dose being administered.
Long-term efficacy and safety in patients with MDD has not been eva luated as add-on therapy, however long-term efficacy and safety has been eva luated in adult patients as monotherapy (see Section 5.1).
Paediatric population:
Quetiapine is not recommended for use in children and adolescents below 18 years of age, due to a lack of data to support use in this age group. Clinical trials with quetiapine have shown that in addition to the known safety profile identified in adults (see Section 4.8), certain adverse events occurred at a higher frequency in children and adolescents compared to adults (increased appetite, elevations in serum prolactin, vomiting, rhinitis and syncope), or may have different implications for children and adolescents (extrapyramidal symptoms and irritability) and one was identified that has not been previously seen in adult studies (increases in blood pressure). Changes in thyroid function tests have also been observed in children and adolescents.
Furthermore, the long-term safety implications of treatment with quetiapine on growth and maturation have not been studied beyond 26 weeks. Long-term implications for cognitive and behavioural development are not known.
In placebo-controlled clinical trials with children and adolescent patients, quetiapine was associated with an increased incidence of extrapyramidal symptoms (EPS) compared to placebo in patients treated for schizophrenia, bipolar mania and bipolar depression (see Section 4.8).
Suicide/suicidal thoughts 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.
In addition, physicians should consider the potential risk of suicide-related events after abrupt cessation of quetiapine treatment, due to the known risk factors for the disease being treated.
Other psychiatric conditions for which quetiapine 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 episodes. The same precautions observed when treating patients with major depressive episodes 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.
In shorter-term placebo controlled clinical studies of patients with major depressive episodes in bipolar disorder an increased risk of suicide-related events was observed in young adult patients (younger than 25 years of age) who were treated with quetiapine as compared to those treated with placebo (3.0% vs. 0%, respectively). In clinical studies of patients with MDD the incidence of suicide-related events observed in young adult patients (younger than 25 years of age) was 2.1% (3/144) for quetiapine and 1.3% (1/75) for placebo.
Metabolic Risk:
Given the observed risk for worsening of their metabolic profile, including changes in weight, blood glucose (see hyperglycemia) and lipids, which was seen in clinical studies, patient's metabolic parameters should be assessed at the time of treatment initiation and changes in these parameters should be regularly controlled for during the course of treatment. Worsening in these parameters should be managed as clinically appropriate (see also Section 4.8).
Extrapyramidal symptoms:
In placebo controlled clinical trials of adult patients quetiapine was associated with an increased incidence of extrapyramidal symptoms (EPS) compared to placebo in patients treated for major depressive episodes in bipolar disorder and major depressive disorder (see Sections 4.8 and 5.1).
The use of quetiapine 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.
Tardive Dyskinesia:
If signs and symptoms of tardive dyskinesia appear, dose reduction or discontinuation of quetiapine should be considered. The symptoms of tardive dyskinesia can worsen or even arise after discontinuation of treatment (see Section 4.8).
Somnolence and dizziness:
Quetiapine treatment has been associated with somnolence and related symptoms, such as sedation (see Section 4.8). In clinical trials for treatment of patients with bipolar depression and major depressive disorder, onset was usually within the first 3 days of treatment and was predominantly of mild to moderate intensity. Patients experiencing somnolence of severe intensity may require more frequent contact for a minimum of 2 weeks from onset of somnolence, or until symptoms improve and treatment discontinuation may need to be considered.
Orthostatic Hypotension:
Quetiapine treatment has been associated with orthostatic hypotension and related dizziness (see Section 4.8) which, like somnolence has onset usually during the initial dose-titration period. This could increase the occurrence of accidental injury (fall), especially in the elderly population. Therefore, patients should be advised to exercise caution until they are familiar with the potential effects of the medication.
Quetiapine should be used with caution in patients with known cardiovascular disease, cerebrovascular disease, or other conditions predisposing to hypotension. Dose reduction or more gradual titration should be considered if orthostatic hypotension occurs, especially in patients with underlying cardiovascular disease.
Seizures:
In controlled c
