Seroquel XR 50mg. 150mg. 200mg. 300mg. 400mg Tablet

SEROQUEL XR is indicated for the treatment of:

• Schizophrenia
• Preventing relapse in stable schizophrenic patients who have been maintained on SEROQUEL XR
• Bipolar disorder including:
• Manic episodes associated with bipolar disorder
• Depressive episodes associated with bipolar disorder
• Preventing recurrence in the maintenance treatment of bipolar disorder (manic, mixed or depressive episodes) as monotherapy or in combination with mood stabilisers
• Major depressive disorder
• Preventing relapse in stable major depressive disorder patients who have been maintained on SEROQUEL XR.

SEROQUEL XR should be administered once daily, with or without food. The tablets should be swallowed whole and not split, chewed or crushed.

Adults:

For the treatment of schizophrenia:

The daily dose at the start of therapy is 300 mg on Day 1, 600 mg on Day 2 and up to 800 mg after Day 2. The dose should be adjusted within the effective dose range of 400-800 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 manic episodes associated with bipolar disorder:

The daily dose at the start of therapy is 300 mg on Day 1, 600 mg on Day 2 and up to 800 mg after Day 2. The dose should be adjusted within the effective dose range of 400-800 mg per day, depending on the clinical response and tolerability of the patient.

For the treatment of depressive episodes associated with bipolar disorder:

SEROQUEL XR should be administered once daily in the evening. SEROQUEL XR should be titrated as follows: 50 mg (Day 1), 100 mg (Day 2), 200 mg (Day 3) and 300 mg (Day 4). SEROQUEL XR can be titrated to 400 mg on Day 5 and up to 600 mg by Day 8. Antidepressant efficacy was demonstrated with SEROQUEL at 300 mg and 600 mg, however no additional benefit was seen in the 600 mg group during short-term treatment.

For preventing recurrence in maintenance treatment of bipolar disorder:

Patients who have responded to SEROQUEL XR in combination therapy to a mood stabiliser (lithium or valproate) for acute treatment of bipolar disorder should continue on SEROQUEL XR therapy at the same dose. The SEROQUEL XR dose can be re-adjusted depending on clinical response and tolerability of the individual patient within the dose range of 400-800 mg/day. Patients who have responded to SEROQUEL XR for acute treatment of bipolar disorder should continue on SEROQUEL XR therapy at the same dosing regimen.

For the treatment of major depressive disorder:

SEROQUEL XR should be administered once daily in the evening. Initial dosing should begin at 50 mg on Day 1 and 2, increased to 150 mg on Day 3 and 4. Further adjustments can be made upwards or downwards within the recommended dose range of 50-300 mg depending upon the clinical response and tolerability of the patient. For maintenance therapy in major depressive disorder the effective dose during initial treatment should be continued. The dose can be adjusted within the recommended dose range depending upon the clinical response and tolerability of the patient.

Switching from SEROQUEL immediate-release tablets:

For more convenient dosing, patients who are currently being treated with divided doses of SEROQUEL immediate release (SEROQUEL tablets) may be switched to SEROQUEL XR at the equivalent total daily dose taken once daily. Individual dosage adjustments may be necessary.

Elderly:

SEROQUEL XR should be used with caution in the elderly, especially during the initial dosing period. The rate of dose titration of SEROQUEL XR 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 30-50% 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 tolerance of the individual patient.

In elderly patients with major depressive disorder initial dosing should begin at 50 mg on Days 1-3, the dose can be increased to 100 mg on Day 4, 150 mg on Day 8 and then up to 300 mg depending on clinical response and tolerability.

Children and adolescents:

The safety and efficacy of SEROQUEL XR have not been evaluated in children and adolescents.

Renal and hepatic impairment:

Renal impairment: Dosage adjustment is not necessary in patients with renal impairment.

Hepatic impairment: Quetiapine is extensively metabolised by the liver. Therefore, SEROQUEL XR 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.

SEROQUEL XR is contra-indicated in patients who are hypersensitive to any component of this product.

Hyperglycaemia and diabetes mellitus: Hyperglycaemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, has been reported in patients treated with atypical antipsychotics, including quetiapine. Patients with an established diagnosis of diabetes mellitus who are started on atypical antipsychotics should be monitored regularly for worsening of glucose control. Patients with risk factors for diabetes mellitus (e.g. obesity, family history of diabetes) who are starting treatment with atypical antipsychotics should be monitored for symptoms of hyperglycaemia including polydipsia, polyuria, polyphagia, and weakness. Patients who develop symptoms of hyperglycaemia during treatment with atypical antipsychotics should undergo fasting blood glucose testing. In some cases, hyperglycaemia has resolved when the atypical antipsychotic was discontinued; however, some patients required continuation of antidiabetic treatment despite discontinuation of the suspect medicine.

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. Other psychiatric conditions for which SEROQUEL XR 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.

Neutropenia: Severe neutropenia (< 0,5 X 10 9 /litre) has been uncommonly reported in SEROQUEL clinical trials. Most cases of severe neutropenia have occurred within the first 2 months of starting therapy with SEROQUEL XR. There was no apparent dose relationship. Possible risk factors for neutropenia include pre-existing low white cell count (WBC) and history of medicine induced neutropenia. SEROQUEL XR should be discontinued in patients with a neutrophil count < 1,0 X 10 9 /litre. These patients should be observed for signs and symptoms of infection and neutrophil counts followed (until they exceed 1,5 X 10 9 /litre).

Lipids: Increases in triglycerides and cholesterol, and decreases in HDL have been observed in clinical trials with SEROQUEL XR. Lipid changes should be managed as clinically appropriate.

Concomitant illness: SEROQUEL XR should be used with caution in patients with known cardiovascular disease, cerebrovascular disease, or other conditions predisposing to hypotension. SEROQUEL XR may induce orthostatic hypotension especially during the initial dose-titration period. Dysphagia (see u201c Side-effects u201d) and aspiration have been reported with SEROQUEL XR. Although a causal relationship with aspiration pneumonia has not been established, SEROQUEL XR should be used with caution in patients at risk for aspiration pneumonia. Seizures: Caution is recommended when treating patients with a history of seizures. Tardive dyskinesia and extrapyramidal symptoms: Tardive dyskinesia is a syndrome of potentially irreversible, involuntary, dyskinetic movements that may develop in patients treated with antipsychotic medicines including quetiapine. 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 u201c Side-effects u201d). Neuroleptic malignant syndrome: Neuroleptic malignant syndrome has been associated with SEROQUEL XR treatment. Clinical manifestations include hyperthermia, altered mental status, muscular rigidity, autonomic instability, and increased creatine phosphokinase. In such an event, SEROQUEL XR should be discontinued and appropriate medical treatment given. QT prolongation: In clinical trials quetiapine was not associated with a persistent increase in absolute QT intervals. However, in post marketing experience there were cases reported of QT prolongation with overdose. As with other antipsychotics, caution should be exercised when SEROQUEL XR is prescribed in patients with cardiovascular disease or family history of QT prolongation. Also caution should be exercised when SEROQUEL XR is prescribed either with medicines known to increase QT interval or with concomitant neuroleptics, especially for patients with increased risk of QT prolongation, i.e. the elderly, patients with congenital long QT syndrome, congestive heart failure, heart hypertrophy, hypokalemia, or hypomagnesaemia.

Given the primary central nervous system effects of quetiapine, SEROQUEL XR should be used with caution in combination with other centrally acting medicines and alcohol. Caution should be exercised when SEROQUEL XR is used concomitantly with medicines known to cause electrolyte imbalance or to increase QT interval (see u201c Side-effects and Special precautions u201d). The pharmacokinetics of lithium were not altered when co-administered with quetiapine. The pharmacokinetics of sodium valproate and quetiapine were not altered to a clinically relevant extent when co-administered. The pharmacokinetics of quetiapine were not significantly altered following co-administration with the antipsychotics risperidone or haloperidol. However, co-administration of quetiapine and thioridazine caused increases in clearance of quetiapine. Quetiapine did not induce the hepatic enzyme systems involved in the metabolism of antipyrine. However, in a multiple dose trial in patients to assess the pharmacokinetics of quetiapine given before and during treatment with carbamazepine (a known hepatic enzyme inducer), co-administration of carbamazepine significantly increased the clearance of quetiapine. This increase in clearance reduced systemic quetiapine exposure (as measured by AUC) to an average of 13% of the exposure during administration of quetiapine alone; although a greater effect was seen in some patients. As a consequence of this interaction, lower plasma concentrations can occur, and hence, in each patient, consideration for a higher dose of SEROQUEL XR, depending on clinical response, should be considered. The safety of doses above 800 mg/day has not been established in the clinical trials. Continued treatment at higher doses should only be considered as a result of careful consideration of the benefit risk assessment for an individual patient. Co-administration of quetiapine with another microsomal enzyme inducer, phenytoin, also caused increases in the clearance of quetiapine. Increased doses of SEROQUEL XR may be required to maintain control of psychotic symptoms in patients co-administered SEROQUEL XR and phenytoin, and other hepatic enzyme inducers (e.g. barbiturates, rifampicin etc). The dose of SEROQUEL XR may need to be reduced if phenytoin or carbamazepine or other hepatic enzyme inducers are withdrawn and replaced with a non-inducer (e.g. sodium valproate). CYP3A4 is the primary enzyme responsible for cytochrome P450 mediated metabolism of quetiapine. The pharmacokinetics of quetiapine were not altered following co-administration with cimetidine, a known P450 enzyme inhibitor. The pharmacokinetics of quetiapine were not significantly altered following co-administration with the antidepressants imipramine (a known CYP2D6 inhibitor) or fluoxetine (a known CYP3A4 and CYP2D6 inhibitor). In a multiple-dose trial in healthy volunteers to assess the pharmacokinetics of SEROQUEL XR given before and during treatment with ketoconazole, co-administration of ketoconazole resulted in an increase in mean C max and AUC of SEROQUEL XR of 235% and 522%, respectively, with a corresponding decrease in mean oral clearance of 84%. The mean half-life of SEROQUEL XR increased from 2,6-6,8 hours, but the mean T max was unchanged. Due to the potential for an interaction of similar magnitude in a clinical setting, the dosage of quetiapine should be reduced during concomitant use of SEROQUEL XR and potent CYP3A4 inhibitors (such as azole antifungals, macrolide antibiotics and protease inhibitors).

SEROQUEL XR is contra-indicated during pregnancy and lactation, as safety has not been demonstrated. The degree to which quetiapine is excreted into human milk is unknown. Women who are breast-feeding should therefore be advised to avoid breast-feeding while taking SEROQUEL XR.

SEROQUEL XR may cause somnolence, which may interfere with activities requiring mental alertness. Therefore, patients should be advised not to drive or operate machinery, until individual susceptibility is known.

The most commonly reported adverse drug reactions (ADRs) with SEROQUEL XR are somnolence, dizziness, dry mouth, asthenia, constipation, tachycardia, orthostatic hypotension, and dyspepsia. Weight gain, syncope, neuroleptic malignant syndrome, leucopenia, neutropenia and peripheral oedema; have been associated with SEROQUEL XR.

System Organ Class Frequency Event

Gastrointestinal disorders Very common ( uf0b3 10%) Dry mouth

Common ( uf0b3 1% - < 10%) Constipation; Dyspepsia

Uncommon ( uf0b3 0,1% - < 1%) Dysphagia

Nervous system disorders Very common ( uf0b3 10%) Dizziness; Somnolence

Common ( uf0b3 1% - < 10%) Syncope; Extrapyramidal symptoms; Dysarthria

Uncommon ( uf0b3 0,1% - < 1%) Seizure; Restless legs syndrome; Tardive dyskinesia

Blood and lymphatic system disorders Common ( uf0b3 1% - < 10%) Leukopenia

Uncommon ( uf0b3 0,1% - < 1%) Eosinophilia

Cardiac disorders Common ( uf0b3 1% - < 10%) Tachycardia

Eye disorders Common ( uf0b3 1% - < 10%) Blurred vision

Metabolism and nutrition disorders Common ( uf0b3 1% - < 10%) Increased appetite

Psychiatric disorders Common ( uf0b3 1% - < 10%) Abnormal dreams and nightmares

Respiratory, thoracic, and mediastinal disorders Common ( uf0b3 1% - < 10%) Rhinitis

Vascular disorders Common ( uf0b3 1% - < 10%) Orthostatic hypotension

Renal and urinary disorders Common ( uf0b3 1% - < 10%) Urinary tract infection

Immune system disorders Uncommon ( uf0b3 0,1% - < 1%) Hypersensitivity

Rare ( uf0b3 0,01% - < 0,1%) Anaphylactic reaction

Reproductive system and breast disorders Rare ( uf0b3 0,01% - < 0,1%) Priapism; Galactorrhoea

General disorders and administration site conditions Very common ( uf0b3 10%) Headache; Withdrawal (discontinuation) symptoms

Common ( uf0b3 1% - < 10%) Asthenia; Peripheral oedema; Irritability

Rare ( uf0b3 0,01% - < 0,1%) Neuroleptic malignant syndrome

Investigations Very common ( uf0b3 10%) Elevations in serum triglyceride levels; Elevations in total cholesterol (predominantly LDL cholesterol); Decreases in HDL Cholesterol; Weight gain

Common ( uf0b3 1% - < 10%) Elevations in serum transaminases (ALT, AST); Decreased neutrophil count; Increased blood glucose to hyperglycaemic level; Elevations in serum prolactin

Uncommon ( uf0b3 0,1% - < 1%) Elevations in gamma-GT levels; Platelet count decreased

Rare ( uf0b3 0,01% - < 0,1%) Elevations in blood creatine phosphokinase

In clinical trials, survival has been reported in acute overdoses of up to 30 grams of quetiapine. Most patients who overdosed reported no adverse events or recovered fully from the reported events. Death has been reported in a clinical trial following an overdose of 13,6 grams of quetiapine alone. In post marketing experience, there have been very rare reports of overdose of SEROQUEL XR alone resulting in death or coma. In post marketing experience, there were cases reported of QT prolongation with overdose (see u201c Side-effects and Special precautions u201d). Patients with pre-existing severe cardiovascular disease may be at an increased risk of the effects of overdose. (See u201c Side-effects and Special precautions: Concomitant illness u201d). In general, reported signs and symptoms were those resulting from an exaggeration of the medicineu2019s known pharmacological effects, i.e. drowsiness, sedation, tachycardia and hypotension. There is no specific antidote to quetiapine. In cases of severe intoxication, the possibility of multiple drug involvement should be considered, and intensive care procedures are recommended, including establishing and maintaining a patent airway, ensuring adequate oxygenation and ventilation, and monitoring and support of the cardiovascular system. Close medical supervision and monitoring should be continued until the patient recovers.