Quetiapine

& ADMINISTRATION · Quetiapine tablets, USP can be taken with or without food ( 2.1 ) Indication Initial Dose Recommended Dose Maximum Dose Schizophrenia-Adults (2.2) 25 mg twice daily 150 to 750 mg/day 750 mg/day Schizophrenia-Adolescents (13 to 17 years) (2.2) 25 mg twice daily 400 to 800 mg/day 800 mg/day Bipolar Mania- Adults Monotherapy or as an adjunct to lithium or divalproex (2.2) 50 mg twice daily 400 to 800 mg/day 800 mg/day Bipolar Mania- Children and Adolescents (10 to 17 years), Monotherapy (2.2) 25 mg twice daily 400 to 600 mg/day 600 mg/day Bipolar Depression-Adults (2.2) 50 mg once daily at bedtime 300 mg/day 300 mg/day Geriatric Use: Consider a lower starting dose (50 mg/day), slower titration and careful monitoring during the initial dosing period in the elderly ( 2.3 , 8.5 ) Hepatic Impairment: Lower starting dose (25 mg/day) and slower titration may be needed ( 2.4 , 8.7 , 12.3 ) 2.1 Important Administration Instructions Quetiapine tablets, USP can be taken with or without food. 2.2 Recommended Dosing The recommended initial dose, titration, dose range and maximum quetiapine dose for each approved indication is displayed in Table 1. After initial dosing, adjustments can be made upwards or downwards, if necessary, depending upon the clinical response and tolerability of the patient [ see Clinical Studies ( 14.1 and 14.2 ) ]. Table 1: Recommended Dosing for quetiapine Indication Initial Dose and Titration Recommended Dose Maximum Dose Schizophrenia-Adults Day 1: 25 mg twice daily. Increase in increments of 25 mg-50 mg divided two or three times on Days 2 and 3 to range of 300 to 400 mg by Day 4. Further adjustments can be made in increments of 25 to 50 mg twice a day, in intervals of not less than 2 days. 150 to 750 mg/day 750 mg/day Schizophrenia- Adolescents (13 to 17 years) Day 1: 25 mg twice daily. Day 2: Twice daily dosing totaling 100 mg. Day 3: Twice daily dosing totaling 200 mg. Day 4: Twice daily dosing totaling 300 mg. Day 5: Twice daily dosing totaling 400 mg. Further adjustments should be in increments no greater than 100 mg/day within the recommended dose range of 400-800 mg/day. Based on response and tolerability, may be administered three times daily. 400 to 800 mg/day 800 mg/day Schizophrenia-Maintenance Not applicable. 400 to 800 mg/day 800 mg/day Bipolar Mania- Adults Monotherapy or as an adjunct to lithium or divalproex Day 1: Twice daily dosing totaling 100 mg. Day 2: Twice daily dosing totaling 200 mg. Day 3: Twice daily dosing totaling 300 mg. Day 4: Twice daily dosing totaling 400 mg. Further dosage adjustments up to 800 mg/day by Day 6 should be in increments of no greater than 200 mg/day. 400 to 800 mg/day 800 mg/day Bipolar Mania- Children and Adolescents (10 to 17 years), Monotherapy Day 1: 25 mg twice daily. Day 2: Twice daily dosing totaling 100 mg. Day 3: Twice daily dosing totaling 200 mg. Day 4: Twice daily dosing totaling 300 mg. Day 5: Twice daily dosing totaling 400 mg. Further adjustments should be in increments no greater than 100 mg/day within the recommended dose range of 400-600 mg/day. Based on response and tolerability, may be administered three times daily. 400 to 600 mg/day 600 mg/day Bipolar Depression- Adults Administer once daily at bedtime. Day 1: 50 mg Day 2: 100 mg Day 3: 200 mg Day 4: 300 mg 300 mg/day 300 mg/day Bipolar I Disorder Maintenance Therapy- Adults Administer twice daily totaling 400-800 mg/day as adjunct to lithium or divalproex. Generally, in the maintenance phase, patients continued on the same dose on which they were stabilized. 400 to 800 mg/day 800 mg/day Maintenance Treatment for Schizophrenia and Bipolar I Disorder Maintenance Treatment– Patients should be periodically reassessed to determine the need for maintenance treatment and the appropriate dose for such treatment [see Clinical Studies (14.2) ] . 2.3 Dose Modifications in Elderly Patients Consideration should be given to a slower rate of dose titration and a lower target dose in the elderly and in patients who are debilitated or who have a predisposition to hypotensive reactions [see Clinical Pharmacology (12.3) ] . When indicated, dose escalation should be performed with caution in these patients. Elderly patients should be started on quetiapine 50 mg/day and the dose can be increased in increments of 50 mg/day depending on the clinical response and tolerability of the individual patient. 2.4 Dose Modifications in Hepatically Impaired Patients Patients with hepatic impairment should be started on 25 mg/day. The dose should be increased daily in increments of 25 mg/day - 50 mg/day to an effective dose, depending on the clinical response and tolerability of the patient. 2.5 Dose Modifications when used with CYP3A4 Inhibitors Quetiapine dose should be reduced to one sixth of original dose when co-medicated with a potent CYP3A4 inhibitor (e.g., ketoconazole, itraconazole, indinavir, ritonavir, nefazodone, etc.). When the CYP3A4 inhibitor is discontinued, the dose of quetiapine should be increased by 6-fold [see Clinical Pharmacology (12.3) and Drug Interactions (7.1) ] . 2.6 Dose Modifications when used with CYP3A4 Inducers Quetiapine dose should be increased up to 5-fold of the original dose when used in combination with a chronic treatment (e.g., greater than 7 to 14 days) of a potent CYP3A4 inducer (e.g., phenytoin, carbamazepine, rifampin, avasimibe, St. John’s wort etc.). The dose should be titrated based on the clinical response and tolerability of the individual patient. When the CYP3A4 inducer is discontinued, the dose of quetiapine should be reduced to the original level within 7-14 days [see Clinical Pharmacology (12.3) and Drug Interactions (7.1) ] . 2.7 Re-initiation of Treatment in Patients Previously Discontinued Although there are no data to specifically address re-initiation of treatment, it is recommended that when restarting therapy of patients who have been off quetiapine for more than one- week, the initial dosing schedule should be followed. When restarting patients who have been off quetiapine for less than one-week, gradual dose escalation may not be required and the maintenance dose may be re-initiated. 2.8 Switching from Antipsychotics There are no systematically collected data to specifically address switching patients with schizophrenia from antipsychotics to quetiapine, or concerning concomitant administration with antipsychotics. While immediate discontinuation of the previous antipsychotic treatment may be acceptable for some patients with schizophrenia, more gradual discontinuation may be most appropriate for others. In all cases, the period of overlapping antipsychotic administration should be minimized. When switching patients with schizophrenia from depot antipsychotics, if medically appropriate, initiate quetiapine therapy in place of the next scheduled injection. The need for continuing existing EPS medication should be re-evaluated periodically.

8.4 Pediatric Use In general, the adverse reactions observed in children and adolescents during the clinical trials were similar to those in the adult population with few exceptions. Increases in systolic and diastolic blood pressure occurred in children and adolescents and did not occur in adults. Orthostatic hypotension occurred more frequently in adults (4-7%) compared to children and adolescents (< 1%) [see Warnings and Precautions ( 5.7 ) and Adverse Reactions ( 6.1 )]. Schizophrenia The efficacy and safety of quetiapine in the treatment of schizophrenia in adolescents aged 13 to 17 years were demonstrated in one 6-week, double-blind, placebo-controlled trial [see Indications and Usage ( 1.1 ), Dosage and Administration ( 2.2 ), Adverse Reactions ( 6.1 ), and Clinical Studies ( 14.1 )]. Safety and effectiveness of quetiapine in pediatric patients less than 13 years of age with schizophrenia have not been established. Maintenance The safety and effectiveness of quetiapine in the maintenance treatment of bipolar disorder has not been established in pediatric patients less than 18 years of age. The safety and effectiveness of quetiapine in the maintenance treatment of schizophrenia has not been established in any patient population, including pediatric patients. Bipolar Mania The efficacy and safety of quetiapine in the treatment of mania in children and adolescents ages 10 to 17 years with bipolar I disorder was demonstrated in a 3-week, double-blind, placebo-controlled, multicenter trial [see Indications and Usage ( 1.2 ), Dosage and Administration ( 2.3 ), Adverse Reactions ( 6.1 ), and Clinical Studies ( 14.2 )] . Safety and effectiveness of quetiapine in pediatric patients less than 10 years of age with bipolar mania have not been established. Bipolar Depression Safety and effectiveness of Quetiapine in pediatric patients less than 18 years of age with bipolar depression have not been established. A clinical trial with SEROQUEL XR was conducted in children and adolescents (10 to 17 years of age) with bipolar depression, efficacy was not established. Some differences in the pharmacokinetics of quetiapine were noted between children/adolescents (10 to 17 years of age) and adults. When adjusted for weight, the AUC and Cmax of quetiapine were 41% and 39% lower, respectively, in children and adolescents compared to adults. The pharmacokinetics of the active metabolite, norquetiapine, were similar between children/adolescents and adults after adjusting for weight [see Clinical Pharmacology ( 12.3 )] .