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1、Adults - DOSAGE FORMS AND STRENGTHS Extended-Release Tablets: 50 mg, 150 mg, 200 mg, 300 mg, and 400 mg HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use SEROQUEL XR safely and effectively. See full prescribing information for SEROQUEL XR. SEROQU

2、EL XR®(quetiapine fumarate extended-release tablets, for oral useInitial U.S. Approval: 1997WARNING: INCREASED MORTALITY IN ELDERLY PATIENTSWITH DEMENTIA-RELATED PSYCHOSIS; and SUICIDALTHOUGHTS AND BEHAVIORS See full prescribing information for complete boxed warning. Psychosis Elderly patients

3、 with dementia-related psychosis treated with SEROQUEL XR is not approved for elderly patients with dementia-related psychosis. Increased risk of suicidal thoughts and behavior in children, adolescents and young adults taking antidepressants. Monitor for worsening and emergence of suicidal thoughts

4、and behaviors. -RECENT MAJOR CHANGES -­Warnings and Precautions, Cerebrovascular Adverse Reactions, Including Stroke, in Elderly Patients with Dementia-Related Psychosis (5.3 -4/2013 -INDICATIONS AND USAGE -­SEROQUEL XR is an atypical antipsychotic indicated for the treatment of: Schizophr

5、enia Bipolar I disorder, manic or mixed episodes (1.2 Bipolar disorder, depressive episodes Major depressive disorder, adjunctive therapy with antidepressants -DOSAGE AND ADMINISTRATION -­ Swallow tablets whole and do not split, chew or crush Take without food or with a light meal (approx. 300

6、calories (2.1 Administer once daily, preferably in the evening Geriatric Use: Consider a lower starting dose (50 mg/day, slowertitration, and careful monitoring during the initial dosing period in the elderly. (, Hepatic Impairment: Lower starting dose (50 mg/day and slower titration may be needed (

7、, , Dose Dose Schizophrenia-Adults (2.2 300 mg/day 400-800 mg/day 800 mg/day Schizophrenia-Adolescents (13 to 17 years50 mg/day 400-800 mg/day 800 mg/day manic or mixed-Acute monotherapy or adjunct to lithium or divalproex-Adults Bipolar I Disorder, manic Acute monotherapy ­Children and Adolesc

8、ents (10 to 17 years 50 mg/day 400-600 mg/day 600 mg/day DepressiveEpisodes-Adults Disorder, Adjunctive Therapy with Antidepressants­-CONTRAINDICATIONS -­Known hypersensitivity to SEROQUEL XR or any components in the formulation. -WARNINGS AND PRECAUTIONS -­ Cerebrovascular Adverse Re

9、actions: Increased incidence of cerebrovascular adverse events (e.g., stroke, transient ischemic attack has been seen in elderly patients with dementia-related psychoses treated with atypical antipsychotic drugs Neuroleptic Malignant Syndrome (NMS: Manage with immediate discontinuation and close mon

10、itoring Metabolic Changes: Atypical antipsychotics have been associated with metabolic changes. These metabolic changes include hyperglycemia, dyslipidemia, and weight gain (5.5 Hyperglycemia and Diabetes Mellitus: Monitor patients for symptoms of hyperglycemia including polydipsia, polyuria, polyph

11、agia, and weakness. Monitor glucose regularly in patients with diabetes or at risk for diabetes Dyslipidemia: Undesirable alterations have been observed in patients treated with atypical antipsychotics. Appropriate clinical monitoring is recommended, including fasting blood lipid testing at the begi

12、nning of, and periodically, during treatment Weight Gain: Gain in body weight has been observed; clinical monitoring of weight is recommended Tardive Dyskinesia: Discontinue if clinically appropriate (5.6 Hypotension: Use with caution in patients with known cardiovascular or cerebrovascular disease

13、Increased Blood Pressure in Children and Adolescents: Monitor blood pressure at the beginning of, and periodically during treatment in children and adolescents Leukopenia, Neutropenia and Agranulocytosis: Monitor complete blood count frequently during the first few months of treatment in patients wi

14、th a pre-existing low white cell count or a history of leukopenia/neutropenia and discontinue SEROQUEL XR at the first sign of a decline in WBC in absence of other causative factors Cataracts: Lens changes have been observed in patients during long-term quetiapine treatment. Lens examination is reco

15、mmended when starting treatment and at 6-month intervals during chronic treatment - ADVERSE REACTIONS Most common adverse reactio ns (incidence 5% and twice placebo: Adults: somnolence, dry mouth, constipation, dizziness, increased appetite, dyspepsia, weight gain, fatigue, dysarthria, and nasal con

16、gestion (6.1 Children and Adolescents: somnolence, dizziness, fatigue, i ncreased appetite, nausea, vomiting, dry mouth, tachycardia, weight increased (6.1to one sixth when coadministered with strong CYP3A4 inhibitors (e.g., ketoconazole, ritonavir (2.5, 7.1, 12.3 Concomitant use of strong CYP3A4 in

17、ducers: Increase quetiapine doseup to 5 fold when used in combination with a chronic treatment (more than 7-14 days of potent CYP3A4 inducers (e.g., phenytoin, rifampin, St. Johns wort (, , Discontinuation of strong CYP3A4 inducers: Reduce quetiapine doseby 5 fold within 7-14 days of discontinuation

18、 of CYP3A4 inducers (, , - USE IN SPECIFIC POPULATIONS Pregnancy: Limited human data. Based on animal data, may cause fetal harm. Quetiapine should be used only if the potential benefit justifies the potential r isk Nursing Mothers: Discontinue drug or nursing, taking intoconsideration importance of

19、 drug to mothers health See 17 for PATIENT COUNSELING INFORMATION and Medication Guide Revised: October 2013FULL PRESCRIBING INFORMATION: CONTENTSWARNING: INCREASED MORTALITY IN ELDERLY PATIENTS WITH DEMENTIA-RELATED PSYCHOSIS; AND SUICIDAL THOUGHTS AND BEHAVIORSRECENT MAJOR CHANGES1 INDICATIONS AND

20、 USAGE1.1 Schizophrenia1.2 Bipolar Disorder1.3 Adjunctive Treatment of Major Depressive Disorder (MDD1.4 Special Considerations in Treating Pediatric Schizophrenia and Bipolar I Disorder2 DOSAGE AND ADMINISTRATION2.1 Important Administration Instructions2.2 Recommended Dosing2.3 Dose Modifications i

21、n Elderly Patients2.4 Dose Modifications in Hepatically Impaired Patients2.5 Dose Modifications when used with CYP3A4 Inhibitors2.6 Dose Modifications when used with CYP3A4 Inducers2.7 Reinitiation of Treatment in Patients Previously Discontinued2.8 Switching Patients from SEROQUEL Tablets to SEROQU

22、EL XR Tablets2.9 Switching from Antipsychotics3 DOSAGE FORMS AND STRENGTHS4 CONTRAINDICATIONS5 WARNINGS AND PRECAUTIONS5.1 Increased Mortality in Elderly Patients with Dementia-RelatedPsychosis5.2 Suicidal Thoughts and Behaviors in Adolescents and Young Adults 5.3 Cerebrovascular Adverse Reactions,

23、Including Stroke, in Elderly Patients with Dementia-Related Psychosis5.4 Neuroleptic Malignant Syndrome (NMS5.5 Metabolic Changes5.6 Tardive Dyskinesia5.7 Hypotension5.8 Increases in Blood Pressure (Children and Adolescents5.9 Leukopenia, Neutropenia and Agranulocytosis5.10 Cataracts5.11 QT Prolonga

24、tion5.12 Seizures5.13 Hypothyroidism5.14 HyperprolactinemiaFULL PRESCRIBING INFORMATION5.15 Potential for Cognitive and Motor Impairment5.16 Body Temperature Regulation5.17 Dysphagia5.18 Discontinuation Syndrome6 ADVERSE REACTIONS6.1 Clinical Studies Experience6.2 Post-Marketing Experience7 DRUG INT

25、ERACTIONS7.1 Effect of Other Drugs on Quetiapine7.2 Effect of Quetiapine on Other Drugs8 USE IN SPECIFIC POPULATIONS8.1 Pregnancy8.2 Labor and Delivery8.3 Nursing Mothers8.4 Pediatric Use8.5 Geriatric Use8.6 Renal Impairment8.7 Hepatic Impairment9 DRUG ABUSE AND DEPENDENCE9.1 Controlled Substance9.2

26、 Abuse10 OVERDOSAGE10.1 Human Experience10.2 Management of Overdosage11 DESCRIPTION12 CLINICAL PHARMACOLOGY12.1 Mechanism of Action12.2 Pharmacodynamics12.3 Pharmacokinetics13 NONCLINICAL TOXICOLOGY13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility13.2 Animal Toxicology and/or Pharmacology14

27、CLINICAL STUDIES14.1 Schizophrenia14.2 Bipolar Disorder14.3 Major Depressive Disorder, Adjunctive Therapy to Antidepressants 16 HOW SUPPLIED/STORAGE AND HANDLING17 PATIENT COUNSELING INFORMATION17.1 Information for PatientsSections or subsections omitted from the full prescribing information are not

28、 listed. 1 INDICATIONS AND USAGE1.1 SchizophreniaSEROQUEL XR is indicated for the treatment of schizophrenia. The efficacy of SEROQUEL XR in schizophrenia was established in one 6-week and one maintenance trial in adults with schizophrenia. Efficacy was supported by three 6­week trials in adult

29、s with schizophrenia and one 6-week trial in adolescents with schizophrenia (13-17 years treated with SEROQUEL see Clinical Studies .1.2 Bipolar DisorderSEROQUEL XR is indicated for the acute treatment of manic or mixed episodes associated with bipolar I disorder, both as monotherapy and as an adjun

30、ct to lithium or divalproex. The efficacy of SEROQUEL XR in manic or mixed episodes of bipolar I disorder was established in one 3-week trial in adults with manic or mixed episodes associated with bipolar I disorder. Efficacy was supported by two 12-week monotherapy trials and one 3-week adjunctive

31、trial in adults with manic episodes associated with bipolar I disorder as well as one 3-week monotherapy trial in children and adolescents (10 17 years with manic episodes associated with bipolar I disorder treated with SEROQUEL see . SEROQUEL XR is indicated for the acute treatment of depressive ep

32、isodes associated with bipolar disorder. The efficacy of SEROQUEL XR was established in one 8-week trial in adults with bipolar I or II disorder and supported by two 8­week trials in adults with bipolar I or II disorder treated with SEROQUEL see .SEROQUEL XR is indicated for the maintenance tre

33、atment of bipolar I disorder, as an adjunct to lithium or divalproex. Efficacy was extrapolated from two maintenance trials in adults with bipolar I disorder treated with SEROQUEL. The effectiveness of monotherapy for the maintenance treatment of bipolar I disorder has not been systematically evalua

34、ted in controlled clinical trials see .1.3 Adjunctive Treatment of Major Depressive Disorder (MDDSEROQUEL XR is indicated for use as adjunctive therapy to antidepressants for the treatment of MDD. The efficacy of SEROQUEL XR as adjunctive therapy to antidepressants in MDD was established in two 6-we

35、ek trials in adults with MDD who had an inadequate response to antidepressant treatment see .1.4 Special Considerations in Treating Pediatric Schizophrenia and Bipolar I DisorderPediatric schizophrenia and bipolar I disorder are serious mental disorders, however, diagnosis can be challenging. For pe

36、diatric schizophrenia, symptom profiles can be variable, and for bipolar I disorder, patients may have variable patterns of periodicity of manic or mixed symptoms. It is recommended that medication therapy for pediatric schizophrenia and bipolar I disorder be initiated only after a thorough diagnost

37、ic evaluation has been performed and careful consideration given to the risks associated with medication treatment. Medication treatment for both pediatric schizophrenia and bipolar I disorder is indicated as part of a total treatment program that often includes psychological, educational and social

38、 interventions.2 DOSAGE AND ADMINISTRATION2.1 Important Administration InstructionsSEROQUEL XR tablets should be swallowed whole and not split, chewed or crushed.It is recommended that SEROQUEL XR be taken without food or with a light meal (approximately 300 calories see .SEROQUEL XR should be admin

39、istered once daily, preferably in the evening.2.2 Recommended DosingThe recommended initial dose, titration, dose range and maximum SEROQUEL XR dose for each approved indication is displayed in Table 1 below. After initial dosing, adjustments can be made upwards or downwards, if necessary, depending

40、 upon the clinical response and tolerability of the patient see Clinical Studies (, and .Table 1 Recommended Dosing for SEROQUEL XRIndication Initial Dose and Titration Recommended Dose Maximum Dose Schizophrenia-Adults Day 1: 300 mg/dayDose increases can be madeat intervals as short as 1 dayand in

41、increments of up to300 mg/day400-800 mg/day 800 mg/daySchizophrenia-Adolescents (13 to 17 years Day 1: 50 mg/dayDay 2: 100 mg/dayDay 3: 200 mg/dayDay 4: 300 mg/dayDay 5: 400 mg/day400-800 mg/day 800 mg/daySchizophrenia Maintenance­Monotherapy-Adultsn/a 400-800 mg/day 800 mg/dayBipolar I Disorde

42、r manic or mixed-Acute monotherapy or adjunct to lithium or divalproex-Adults Day 1: 300 mg/dayDay 2: 600 mg/dayDay 3: between 400 and 800mg/day400-800 mg/day 800 mg/dayBipolar I Disorder, manic ­Acute monotherapy ­Children and Adolescents (10 to 17 years Day 1: 50 mg/dayDay 2: 100 mg/dayD

43、ay 3: 200 mg/dayDay 4: 300 mg/dayDay 5: 400 mg/day400-600 mg/day 600 mg/dayDepressive Episodes-Adults Day 2: 100 mg/dayDay 3: 200 mg/dayDay 4: 300 mg/dayBipolar I DisorderMaintenance-Adjunct tolithium or divalproex-Adultsn/a 400-800 mg/day 800 mg/dayMajor Depressive Disorder-Adjunctive Therapy with

44、Antidepressants-Adults Day 1: 50 mg/dayDay 2: 50 mg/dayDay 3: 150 mg/day150-300 mg/day 300 mg/dayn/a-not applicableMaintenance Treatment for Schizophrenia and Bipolar I DisorderMaintenance TreatmentPatients should be periodically reassessed to determine the need for maintenance treatment and the app

45、ropriate dose for such treatment see Clinical Studies (, .2.3 Dose Modifications in Elderly PatientsConsideration 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 Us

46、e in Specific Populations (, and . When indicated, dose escalation should be performed with caution in these patients. Elderly patients should be started on SEROQUEL XR 50 mg/day and the dose can be increased in increments of 50 mg/day depending on the clinical response and tolerability of the indiv

47、idual patient.2.4 Dose Modifications in Hepatically Impaired PatientsPatients with hepatic impairment should be started on SEROQUEL XR 50 mg/day. The dose can be increased daily in increments of 50 mg/day to an effective dose, depending on the clinical response and tolerability of the patient.2.5 Do

48、se Modifications when used with CYP3A4 InhibitorsSEROQUEL XR 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 SEROQUEL

49、 XR should be increased by 6 fold see Clinical Pharmacology and Drug Interactions . 2.6 Dose Modifications when used with CYP3A4 InducersSEROQUEL XR dose should be increased up to 5 fold of the original dose when used in combination with a chronic treatment (e.g., greater than 7-14 days of a potent

50、CYP3A4 inducer (e.g., phenytoin, carbamazepine, rifampin, avasimibe, St. Johns wort etc. The dose should be titrated based on the clinical response and tolerance of the individual patient. When the CYP3A4 inducer is discontinued, the dose of SEROQUEL XR should be reduced to the original level within

51、 7­14 days see Clinical Pharmacology and Drug Interactions .2.7 Reinitiation of Treatment in Patients Previously DiscontinuedAlthough there are no data to specifically address re-initiation of treatment, it is recommended that when restarting therapy of patients who have been off SEROQUEL XR fo

52、r more than one week, the initial dosing schedule should be followed. When restarting patients who have been off SEROQUEL XR for less than one week, gradual dose escalation may not be required and the maintenance dose may be reinitiated.2.8 Switching Patients from SEROQUEL Tablets to SEROQUEL XR Tab

53、letsPatients who are currently being treated with SEROQUEL (immediate release formulation may be switched to SEROQUEL XR at the equivalent total daily dose taken once daily. Individual dosage adjustments may be necessary. 2.9 Switching from AntipsychoticsThere are no systematically collected data to

54、 specifically address switching patients from other antipsychotics to SEROQUEL XR, or concerning concomitant administration with other antipsychotics. While immediate discontinuation of the previous antipsychotic treatment may be acceptable for some patients, more gradual discontinuation may be most

55、 appropriate for others. In all cases, the period of overlapping antipsychotic administration should be minimized. When switching patients from depot antipsychotics, if medically appropriate, initiate SEROQUEL XR therapy in place of the next scheduled injection. The need for continuing existing extr

56、apyramidal syndrome medication should be re-evaluated periodically.3 DOSAGE FORMS AND STRENGTHS 50 mg extended-release tablets are peach, film coated, capsule-shaped, biconvex, intagliated tablet with “XR 50” on one side and plain on the other side 150 mg extended-release tablets are white, film-coa

57、ted, capsule-shaped, biconvex, intagliated tablet with “XR 150” on one side and plain on the other side 200 mg extended-release tablets are yellow, film-coated, capsule-shaped, biconvex, intagliated tablet with “XR 200” on one side and plain on the other side 300 mg extended-release tablets are pale

58、 yellow, film-coated, capsule-shaped, biconvex, intagliated tablet with “XR 300” on one side and plain on the other side 400 mg extended-release tablets are white, film-coated, capsule-shaped, biconvex, intagliated tablet with “XR 400” on one side and plain on the other side4 CONTRAINDICATIONSHypers

59、ensitivity to quetiapine or to any excipients in the SEROQUEL XR formulation. Anaphylactic reactions have been reported in patients treated with SEROQUEL XR.5 WARNINGS AND PRECAUTIONS5.1 Increased Mortality in Elderly Patients with Dementia-Related PsychosisElderly patients with dementia-related psy

60、chosis treated with antipsychotic drugs are at an increased risk of death. Analysis of 17 placebo-controlled trials (modal duration of 10 weeks, largely in patients taking atypical antipsychotic drugs, revealed a risk of death in drug-treated patients of between 1.6 to 1.7 times the risk of death in

61、 placebo-treated patients. Over the course of a typical 10-week controlled trial, the rate of death in drug-treated patients was about 4.5%, compared to a rate of about 2.6% in the placebo group. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (e.g.,

62、 heart failure, sudden death or infectious (e.g., pneumonia in nature. Observational studies suggest that, similar to atypical antipsychotic drugs, treatment with conventional antipsychotic drugs may increase mortality. The extent to which the findings of increased mortality in observational studies

63、 may be attributed to the antipsychotic drug as opposed to some characteristic(s of the patients is not clear. SEROQUEL XR is not approved for the treatment of patients with dementia-related psychosis see Boxed Warning.5.2 Suicidal Thoughts and Behaviors in Adolescents and Young AdultsPatients with

64、major depressive disorder (MDD, both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality or unusual changes in behavior, whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders th