Prescribing Information SEROQUEL XL (quetiapine prolonged release)

Consult Summary of Product Characteristics before prescribing.

Use:
Treatment of schizophrenia including preventing relapse in stable schizophrenic patients who have been maintained on Seroquel XL. Treatment of bipolar disorder including manic episodes, major depressive episodes, and preventing recurrence in bipolar disorder.

Presentation:
Prolonged-release tablets containing 50mg, 200mg, 300mg or 400mg of quetiapine (as fumarate).

Dosage and administration:
Seroquel XL should be administered orally, once daily without food (at least one hour before a meal). Adults: For the treatment of schizophrenia: the total daily dose is 300mg on day one, 600mg on day two. Enhanced efficacy at doses higher than 600mg has not been demonstrated, however doses greater than 600mg and up to 800mg daily may benefit some patients and should be initiated by a specialist. The dose should be adjusted within the effective dose range of 400mg to 800mg/day depending on clinical response and tolerability. For the treatment of bipolar mania: the total daily dose is 300mg on day one, 600mg on day two and up to 800mg/day after day two. The dose should be adjusted within the effective dose range of 400mg to 800mg/day. For the treatment of depressive episodes in bipolar disorder: Seroquel XL should be administered once daily at bedtime. The total daily dose for the first four days of therapy is 50mg (Day 1), 100mg (Day 2), 200mg (Day 3) and 300mg (Day 4). The recommended daily dose is 300mg. In clinical trials, no additional benefit was seen in the 600mg group compared to the 300mg group. Individual patients may benefit from a 600mg dose. In individual patients, in the event of tolerance concerns, clinical trials have indicated that dose reduction to a minimum of 200mg could be considered. When treating depressive episodes in bipolar disorder, treatment should be initiated by physicians experienced in treating bipolar disorder. For preventing recurrence in bipolar disorder (manic, mixed or depressive episodes): Patients who have responded to Seroquel XL for acute treatment of bipolar disorder should continue therapy at the same dose administered at bedtime. The dose may be adjusted depending on clinical response and tolerability of the individual patient within the dose range of 300mg to 800mg/day. It is important that the lowest effective dose is used for maintenance therapy. Switching from Seroquel: Patients may be switched to Seroquel XL at the equivalent total daily dose taken once daily. To ensure the maintenance of clinical response, a period of dose titration may be required. Elderly patients: Use with caution. Start with 50mg/day increasing daily by 50mg to an effective dose. Efficacy and safety have not been evaluated in patients over 65 years with depressive episodes in the framework of bipolar disorder. Children and adolescents: Seroquel XL is not recommended for use in children and adolescents below 18 years of age. Hepatic impairment: Use with caution. Start with 50mg/day increasing daily by 50mg to an effective dose depending on the clinical response and tolerability of the individual patient.

Contraindications:
Hypersensitivity to any component of the product. Concomitant administration of cytochrome P450 3A4 inhibitors, such as HIV-protease inhibitors, azole-antifungal agents, erythromycin, clarithromycin and nefazodone.

Precautions: Depression in bipolar disorder is associated with an increased risk of suicidal thoughts, self-harm and suicide. This risk persists until significant remission occurs and patients should be closely monitored until such improvement occurs. In clinical studies of patients with major depressive episodes in bipolar disorder an increased risk of suicide-related events was observed in young adult patients less than 25 years of age who were treated with quetiapine as compared to those treated with placebo. Quetiapine treatment has been associated with somnolence and related symptoms, such as sedation. Bipolar depression 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. Caution in patients with cardiovascular disease, cerebrovascular disease or other conditions predisposing to hypotension. Quetiapine may induce orthostatic hypotension, especially during the initial dose-titration period. Dose reduction or more gradual titration should be considered if this occurs. Caution in patients with a history of seizures. In placebo controlled clinical trials quetiapine was associated with an increased incidence of extrapyramidal symptoms (EPS) compared to placebo in patients treated for major depressive episodes in bipolar disorder. If signs and symptoms of tardive dyskinesia appear, consider dosage reduction or discontinuation of Seroquel XL. In cases of neuroleptic malignant syndrome, discontinue Seroquel XL and give appropriate medical treatment. Severe neutropenia (neutrophil count <0.5 X 109/L) has been uncommonly reported in quetiapine clinical trials. Patients should be observed for signs and symptoms of infection and neutrophil counts followed (until they exceed 1.5 X 109/L). Hyperglycaemia or exacerbation of pre-existing diabetes reported during treatment with quetiapine. Appropriate clinical monitoring is advisable in diabetic patients and in patients with risk factors for the development of diabetes mellitus. Increases in triglycerides, LDL and total cholesterol and decreases in HDL cholesterol have been observed in clinical trials with quetiapine, lipid changes should be managed as clinically appropriate. Caution in patients with a family history of QT prolongation, and in combination with drugs known to prolong the QTc interval, especially in the elderly, in patients with congenital long QT syndrome, congestive heart failure, heart hypertrophy, hypokalaemia or hypomagnesaemia. Acute withdrawal symptoms have been described after abrupt cessation of high doses of antipsychotic drugs. Therefore, gradual withdrawal over a period of at least one to two weeks is advisable. Caution in patients with risk factors for stroke. Seroquel XL is not approved for the treatment of dementia-related psychosis and may increase the risk of stroke and death in these patients. If jaundice develops, Seroquel XL should be discontinued. Dysphagia and aspiration have been reported with Seroquel XL. Use with caution in patients at risk for aspiration pneumonia. Cases of venous thromboembolism have been reported with antipsychotic drugs. All possible risk factors for VTE should be identified before and during treatment with quetiapine and preventive measures undertaken. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption should not take Seroquel XL. Caution in combination with other centrally acting drugs and alcohol, and on coadministration with thioridazine, phenytoin, carbamazepine or other hepatic enzyme inducers. It is not recommended to take quetiapine together with grapefruit juice. Seroquel XL should only be used during pregnancy if benefits justify the potential risks. Avoid breastfeeding whilst taking Seroquel XL. Patients should be cautioned about operating hazardous machines, including motor vehicles. In post-marketing experience, there have been very rare reports of overdose of quetiapine alone resulting in death or coma or QT-prolongation.

Undesirable events:
Very common: Dizziness and somnolence (may lead to falls), headache, dry mouth, withdrawal symptoms such as nausea, vomiting, insomnia, headache, diarrhoea, dizziness and irritability, elevations in serum triglyceride levels and total cholesterol (predominantly LDL cholesterol), decreases in HDL cholesterol, weight gain. Common: Leucopenia, hyperprolactinaemia, increased appetite, abnormal dreams and nightmares, syncope and orthostatic hypotension (may lead to falls), extrapyramidal symptoms, dysarthria, tachycardia, blurred vision, rhinitis, constipation, dyspepsia, mild asthenia, peripheral oedema, irritability, elevations in serum transaminases (ALT, AST), decreased neutrophil count, increased blood glucose to hyperglycaemic levels. Uncommon: Eosinophilia, thrombocytopenia, hypersensitivity, seizures, restless leg syndrome, tardive dyskinesia, dysphagia, elevations in gamma-GT levels, platelet count decreased. Rare: Jaundice, priapism, galactorrhoea, neuroleptic malignant syndrome, elevations in blood creatine phosphokinase, venous thromboembolism. Very rare: Anaphylactic reaction, diabetes mellitus, hepatitis, angioedema, Stevens-Johnson syndrome. QT prolongation, ventricular arrhythmia, sudden death, cardiac arrest and torsades de pointes have been reported very rarely. Decreases in thyroid hormone levels, particularly total T4 and free T4 are usually reversible on cessation of therapy.

Legal category:
POM.

Marketing Authorisation numbers:
50mg tablet: 17901/0249; 200mg tablet: 17901/0250; 300mg tablet: 17901/0251; 400mg tablet: 17901/0252

Basic NHS cost: 60 x 50mg tablets £67.66; 60 x 200mg tablets £113.10; 60 x 300mg tablets £170.00; 60 x 400mg tablets £226.20.

Further information is available from the Marketing Authorisation Holder:
AstraZeneca UK Limited, 600 Capability Green, Luton, LU1 3LU, UK.

Date of Prep 01/2010.

Seroquel XL is a trade mark of the AstraZeneca group of companies.

Prescribing Information SEROQUEL* (quetiapine)
*Intensive monitoring is requested only when used for the recently licensed indication of bipolar depression.

Consult Summary of Product Characteristics before prescribing.

Use:
Treatment of schizophrenia. Treatment of bipolar disorder including manic episodes, major depressive episodes, and preventing recurrence in bipolar disorder.

Presentation:
Tablets containing 25mg, 100mg, 150mg, 200mg and 300mg of quetiapine (as fumarate).

Dosage and administration: Adults:
For the treatment of schizophrenia: Seroquel should be administered twice daily. The total daily dose for the first four days of therapy is 50mg (Day 1), 100mg (Day 2), 200mg (Day 3) and 300mg (Day 4). From Day 4 onwards, titrate to usual effective range of 300 to 450mg/day. Dose may be adjusted within the range 150 to 750mg/day according to clinical response and tolerability. For the treatment of manic episodes associated with bipolar disorder: Seroquel should be administered twice daily. As monotherapy or as adjunct therapy to mood stabilizers, the total daily dose for the first four days of therapy is 100mg (Day 1), 200mg (Day 2), 300mg (Day 3) and 400mg (Day 4). Further dosage adjustments up to 800mg/day by Day 6 should be in increments of no greater than 200mg/day. Dose may be adjusted within the range 200 to 800mg/day according to clinical response and tolerability. The usual effective dose is in the range of 400 to 800 mg/day. For the treatment of depressive episodes in bipolar disorder: Seroquel should be administered once daily at bedtime. The total daily dose for the first four days of therapy is 50mg (Day 1), 100mg (Day 2), 200mg (Day 3) and 300mg (Day 4). The recommended daily dose is 300mg. In clinical trials, no additional benefit was seen in the 600mg group compared to the 300mg group. Individual patients may benefit from a 600mg dose. In individual patients, in the event of tolerance concerns, clinical trials have indicated that dose reduction to a minimum of 200mg could be considered. When treating depressive episodes in bipolar disorder, treatment should be initiated by physicians experienced in treating bipolar disorder. For preventing recurrence in bipolar disorder (manic, mixed or depressive episodes): Patients who have responded to quetiapine for acute treatment of bipolar disorder should continue therapy at the same dose. The dose may then be adjusted depending on clinical response and tolerability of the individual patient, within the range of 300 to 800mg/day administered twice daily. It is important that the lowest effective dose is used for maintenance therapy. Elderly patients: Use with caution, starting with 25mg/day and increasing daily by 25 to 50mg to an effective dose. Efficacy and safety have not been evaluated in patients over 65 years with depressive episodes in the framework of bipolar disorder. Children and adolescents: Seroquel is not recommended for use in children and adolescents below 18 years of age. Hepatic impairment: Use with caution. Start with 25mg/day increasing daily by 25 to 50mg to an effective dose depending on the clinical response and tolerability of the individual patient.

Contraindications:
Hypersensitivity to any component of the product. Concomitant administration of cytochrome P450 3A4 inhibitors, such as HIV-protease inhibitors, azole-antifungal agents, erythromycin, clarithromycin and nefazodone.

Precautions:
Depression in bipolar disorder is associated with an increased risk of suicidal thoughts, self-harm and suicide. This risk persists until significant remission occurs and patients should be closely monitored until such improvement occurs. In clinical studies of patients with major depressive episodes in bipolar disorder an increased risk of suicide-related events was observed in young adult patients less than 25 years of age who were treated with quetiapine as compared to those treated with placebo. Quetiapine treatment has been associated with somnolence and related symptoms, such as sedation. Bipolar depression 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. Caution in patients with cardiovascular disease, cerebrovascular disease or other conditions predisposing to hypotension. Quetiapine may induce orthostatic hypotension, especially during the initial dose-titration period. Dose reduction or more gradual titration should be considered if this occurs. Caution in patients with a history of seizures. In placebo controlled clinical trials quetiapine was associated with an increased incidence of extrapyramidal symptoms (EPS) compared to placebo in patients treated for major depressive episodes in bipolar disorder. If signs and symptoms of tardive dyskinesia appear, consider dosage reduction or discontinuation of Seroquel. In cases of neuroleptic malignant syndrome, discontinue Seroquel and give appropriate medical treatment. Severe neutropenia (neutrophil count <0.5 X 109/L) has been uncommonly reported in Seroquel clinical trials. Patients should be observed for signs and symptoms of infection and neutrophil counts followed (until they exceed 1.5 X 109/L). Hyperglycaemia or exacerbation of pre-existing diabetes reported during treatment with quetiapine. Appropriate clinical monitoring advisable in diabetic patients and in patients with risk factors for the development of diabetes mellitus. Increases in triglycerides, LDL and total cholesterol and decreases in HDL cholesterol have been observed in clinical trials with quetiapine, lipid changes should be managed as clinically appropriate. Caution in patients with a family history of QT prolongation, and in combination with drugs known to prolong the QTc interval, especially in the elderly, in patients with congenital long QT syndrome, congestive heart failure, heart hypertrophy, hypokalaemia or hypomagnesaemia. Acute withdrawal symptoms have been described after abrupt cessation of antipsychotic drugs. Therefore, gradual withdrawal over a period of at least one to two weeks is advisable. Caution in patients with risk factors for stroke. Seroquel is not approved for the treatment of dementia-related psychosis and may increase the risk of stroke and death in these patients. If jaundice develops, Seroquel should be discontinued. Dysphagia and aspiration have been reported with Seroquel. Use with caution in patients at risk for aspiration pneumonia. Cases of venous thromboembolism have been reported with antipsychotic drugs. All possible risk factors for VTE should be identified before and during treatment with quetiapine and preventive measures undertaken. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption should not take Seroquel. Caution in combination with other centrally acting drugs and alcohol, and on coadministration with thioridazine, phenytoin, carbamazepine or other hepatic enzyme inducers. It is not recommended to take quetiapine together with grapefruit juice. Seroquel should only be used during pregnancy if benefits justify the potential risks. Avoid breastfeeding whilst taking Seroquel. Patients should be cautioned about operating hazardous machines, including motor vehicles. In post-marketing experience, there have been very rare reports of overdose of quetiapine alone resulting in death or coma or QT-prolongation.

Undesirable events:
Very common: Dizziness and somnolence (may lead to falls), headache, dry mouth, withdrawal symptoms such as nausea, vomiting, insomnia, headache, diarrhoea, dizziness and irritability, elevations in serum triglyceride levels and total cholesterol (predominantly LDL cholesterol), decreases in HDL cholesterol, weight gain. Common: Leucopenia, hyperprolactinaemia, increased appetite, abnormal dreams and nightmares, syncope and orthostatic hypotension (may lead to falls), extrapyramidal symptoms, dysarthria, tachycardia, blurred vision, rhinitis, constipation, dyspepsia, mild asthenia, peripheral oedema, irritability, elevations in serum transaminases (ALT, AST), decreased neutrophil count, increased blood glucose to hyperglycaemic levels. Uncommon: Eosinophilia, thrombocytopenia, hypersensitivity, seizures, restless leg syndrome, tardive dyskinesia, dysphagia, elevations in gamma-GT levels, platelet count decreased. Rare: Jaundice, priapism, galactorrhoea, neuroleptic malignant syndrome, elevations in blood creatine phosphokinase, venous thromboembolism. Very rare: Anaphylactic reaction, diabetes mellitus, hepatitis, angioedema, Stevens-Johnson syndrome. QT prolongation, ventricular arrhythmia, sudden death, cardiac arrest and torsades de pointes have been reported very rarely. Decreases in thyroid hormone levels, particularly total T4 and free T4 are usually reversible on cessation of therapy.

Legal category: POM.

Marketing Authorisation numbers: 25mg tablet: 17901/0038; 100mg tablet: 17901/0039; 150mg tablet: 17901/0041; 200mg tablet: 17901/0040; 300mg tablet: 17901/0088

Basic NHS cost: 60 x 25mg tablets £33.83; 60 x 100mg tablets £113.10; 60 x 150mg tablets £113.10; 60 x 200mg tablets £113.10; 60 x 300mg tablets £170.00.

Further information is available from the Marketing Authorisation Holder:
AstraZeneca UK Limited, 600 Capability Green, Luton, LU1 3LU, UK. Seroquel is a trade mark of the AstraZeneca group of companies.

Date of Prep 01/2010.