Schizophrenia
Seroquel 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 as well by extrapolation from three 6-week trials in adults with schizophrenia treated with SEROQUEL [see Clinical Studies (14.1)].
Bipolar Disorder
Seroquel XR is indicated for the acute treatment of manic or mixed episodes associated with bipolar I disorder, both as monotherapy and as an adjunct 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 as well by extrapolation from two 12-week monotherapy and one 3-week adjunctive trial in adults with manic episodes associated with bipolar I disorder treated with SEROQUEL [see Clinical Studies (14.2)].
Seroquel XR is indicated for the acute treatment of depressive episodes associated with bipolar disorder. The efficacy of Seroquel XR was established in one 8-week trial in adults with bipolar I or II disorder as well as extrapolation from two 8-week trials in adults with bipolar I or II disorder treated with SEROQUEL [see Clinical Studies (14.2)].
Seroquel XR is indicated for the maintenance treatment 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 disorder has not been systematically evaluated in controlled clinical trials [see Clinical Studies (14.2)].
Adjunctive Treatment of Major Depressive Disorder (MDD)
Seroquel 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-week trials in adults with MDD who had an inadequate response to antidepressant treatment [see Clinical Studies (14.3)].
Seroquel XR Dosage and Administration
Seroquel 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 Clinical Pharmacology (12.3)].
Schizophrenia
Dose Selection—Seroquel XR should be administered once daily, preferably in the evening. The recommended initial dose is 300 mg/day. Patients should be titrated within a dose range of 400 mg/day – 800 mg/day depending on the response and tolerance of the individual patient [see Clinical Studies (14.1)]. Dose increases can be made at intervals as short as 1 day and in increments of up to 300 mg/day. The safety of doses above 800 mg/day has not been evaluated in clinical trials.
Maintenance Treatment—A maintenance trial in adult patients with schizophrenia treated with Seroquel XR has shown this drug to be effective in delaying time to relapse in patients who were stabilized on Seroquel XR at doses of 400 mg/day to 800 mg/day for 16 weeks. Patients should be periodically reassessed to determine the need for maintenance treatment and the appropriate dose for such treatment [see Clinical Studies (14.1)].
Bipolar Disorder
Bipolar Mania
Usual Dose for Acute Monotherapy or Adjunct Therapy (with lithium or divalproex)
Dose Selection—When used as monotherapy or adjunct therapy (with lithium or divalproex), Seroquel XR should be administered once daily in the evening starting with 300 mg on Day 1 and 600 mg on Day 2. Seroquel XR can be adjusted between 400 mg and 800 mg beginning on Day 3 depending on the response and tolerance of the individual patient.
Recommended Dosing Schedule
Day
|
Day 1
|
Day 2
|
Day 3
|
Seroquel XR
|
300 mg
|
600 mg
|
400 mg to 800 mg
|
Depressive Episodes Associated with Bipolar Disorder
Usual Dose—Seroquel XR should be administered once daily in the evening to reach 300 mg/day by Day 4.
Recommended Dosing Schedule
Day
|
Day 1
|
Day 2
|
Day 3
|
Day 4
|
Seroquel XR
|
50 mg
|
100 mg
|
200 mg
|
300 mg
|
Maintenance Treatment for Bipolar I Disorder
Maintenance Treatment—Maintenance of efficacy in bipolar I disorder was demonstrated with SEROQUEL (administered twice daily totaling 400 mg/day to 800 mg/day) as adjunct therapy to lithium or divalproex. Generally, in the maintenance phase, patients continued on the same dose on which they were stabilized during the stabilization phase. Patients should be periodically reassessed to determine the need for maintenance treatment and the appropriate dose for such treatment [see Clinical Studies (14.2)].
Major Depressive Disorder, Adjunctive Therapy with Antidepressants
Dose Selection—Seroquel XR in a dose range of 150 mg/day to 300 mg/day was demonstrated to be effective as adjunctive therapy to antidepressants. Begin with 50 mg once daily in the evening. On Day 3, the dose can be increased to 150 mg once daily in the evening. There were dose-dependent increases in adverse reactions in the recommended dose range of 150 mg/day to 300 mg/day. Doses above 300 mg/day were not studied [see Clinical Studies (14.3)].
Dosing in Special Populations
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 Use in Specific Populations (8.5, 8.7) and Clinical Pharmacology (12)]. 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 response and tolerance of the individual patient.
Patients 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 tolerance of the patient.
The elimination of quetiapine was enhanced in the presence of phenytoin. Higher maintenance doses of quetiapine may be required when it is coadministered with phenytoin and other enzyme inducers such as carbamazepine and phenobarbital [see Drug Interactions (7.1)].
Re-initiation of Treatment in Patients Previously Discontinued
Although there are no data to specifically address reinitiation of treatment, it is recommended that when restarting therapy of patients who have been off Seroquel XR for 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.
Switching Patients from SEROQUEL Tablets to Seroquel XR Tablets
Patients 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.
Switching from Antipsychotics
There are no systematically collected data to 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 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 extrapyramidal syndrome medication should be re-evaluated periodically.
Dosage Forms and Strengths
50 mg extended-release tablets
150 mg extended-release tablets
200 mg extended-release tablets
300 mg extended-release tablets
400 mg extended-release tablets
Contraindications
None
Warnings and Precautions
Increased Mortality in Elderly Patients with Dementia-Related Psychosis
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death compared to placebo. Seroquel XR (quetiapine fumarate) is not approved for the treatment of patients with dementia-related psychosis [see Boxed Warning].
Clinical Worsening and Suicide Risk
Patients with 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 themselves are the strongest predictors of suicide. There has been a long-standing concern, however, that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment. Pooled analyses of short-term placebo-controlled trials of antidepressant drugs (SSRIs and others) showed that these drugs increase the risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (ages 18-24) with major depressive disorder (MDD) and other psychiatric disorders. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction with antidepressants compared to placebo in adults aged 65 and older.
The pooled analyses of placebo-controlled trials in children and adolescents with MDD, obsessive compulsive disorder (OCD), or other psychiatric disorders included a total of 24 short-term trials of 9 antidepressant drugs in over 4400 patients. The pooled analyses of placebo-controlled trials in adults with MDD or other psychiatric disorders included a total of 295 short-term trials (median duration of 2 months) of 11 antidepressant drugs in over 77,000 patients. There was considerable variation in risk of suicidality among drugs, but a tendency toward an increase in the younger patients for almost all drugs studied. There were differences in absolute risk of suicidality across the different indications, with the highest incidence in MDD. The risk differences (drug vs. placebo), however, were relatively stable within age strata and across indications. These risk differences (drug-placebo difference in the number of cases of suicidality per 1000 patients treated) are provided in Table 1.
Table 1:
| Age Range |
Drug-Placebo Difference in Number of Cases of Suicidality per 1000 Patients Treated |
|---|
|
Increases Compared to Placebo
|
<18
|
14 additional cases
|
18–24
|
5 additional cases
|
|
Decreases Compared to Placebo
|
25–64
|
1 fewer case
|
≥65
|
6 fewer cases
|
No suicides occurred in any of the pediatric trials. There were suicides in the adult trials, but the number was not sufficient to reach any conclusion about drug effect on suicide.
It is unknown whether the suicidality risk extends to longer-term use, i.e., beyond several months. However, there is substantial evidence from placebo-controlled maintenance trials in adults with depression that the use of antidepressants can delay the recurrence of depression.
All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases.
The following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have been reported in adult and pediatric patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and nonpsychiatric. Although a causal link between the emergence of such symptoms and either the worsening of depression and/or the emergence of suicidal impulses has not been established, there is concern that such symptoms may represent precursors to emerging suicidality.
Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse, or who are experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality, especially if these symptoms are severe, abrupt in onset, or were not part of the patient's presenting symptoms.
Families and caregivers of patients being treated with antidepressants for major depressive disorder or other indications, both psychiatric and nonpsychiatric, should be alerted about the need to monitor patients for the emergence of agitation, irritability, unusual changes in behavior, and the other symptoms described above, as well as the emergence of suicidality, and to report such symptoms immediately to healthcare providers. Such monitoring should include daily observation by families and caregivers. Prescriptions for Seroquel XR should be written for the smallest quantity of tablets consistent with good patient management, in order to reduce the risk of overdose.
Screening Patients for Bipolar Disorder: A major depressive episode may be the initial presentation of bipolar disorder. It is generally believed (though not established in controlled trials) that treating such an episode with an antidepressant alone may increase the likelihood of precipitation of a mixed/manic episode in patients at risk for bipolar disorder. Whether any of the symptoms described above represent such a conversion is unknown. However, prior to initiating treatment with an antidepressant, patients with depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression.
Neuroleptic Malignant Syndrome (NMS)
A potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) has been reported in association with administration of antipsychotic drugs, including quetiapine. Rare cases of NMS have been reported with quetiapine. Clinical manifestations of NMS are hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis, and cardiac dysrhythmia). Additional signs may include elevated creatine phosphokinase, myoglobinuria (rhabdomyolysis) and acute renal failure.
The diagnostic evaluation of patients with this syndrome is complicated. In arriving at a diagnosis, it is important to exclude cases where the clinical presentation includes both serious medical illness (eg, pneumonia, systemic infection, etc.) and untreated or inadequately treated extrapyramidal signs and symptoms (EPS). Other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, drug fever and primary central nervous system (CNS) pathology.
The management of NMS should include: 1) immediate discontinuation of antipsychotic drugs and other drugs not essential to concurrent therapy; 2) intensive symptomatic treatment and medical monitoring; and 3) treatment of any concomitant serious medical problems for which specific treatments are available. There is no general agreement about specific pharmacological treatment regimens for NMS.
If a patient requires antipsychotic drug treatment after recovery from NMS, the potential reintroduction of drug therapy should be carefully considered. The patient should be carefully monitored since recurrences of NMS have been reported.
Hyperglycemia and Diabetes Mellitus
Hyperglycemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, has been reported in patients treated with atypical antipsychotics, including quetiapine. Assessment of the relationship between atypical antipsychotic use and glucose abnormalities is complicated by the possibility of an increased background risk of diabetes mellitus in patients with schizophrenia and the increasing incidence of diabetes mellitus in the general population. Given these confounders, the relationship between atypical antipsychotic use and hyperglycemia-related adverse reactions is not completely understood. However, epidemiological studies suggest an increased risk of treatment-emergent hyperglycemia-related adverse reactions in patients treated with the atypical antipsychotics. Precise risk estimates for hyperglycemia-related adverse reactions in patients treated with atypical antipsychotics are not available.
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 (eg, obesity, family history of diabetes) who are starting treatment with atypical antipsychotics should undergo fasting blood glucose testing at the beginning of treatment and periodically during treatment. Any patient treated with atypical antipsychotics should be monitored for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness. Patients who develop symptoms of hyperglycemia during treatment with atypical antipsychotics should undergo fasting blood glucose testing. In some cases, hyperglycemia has resolved when the atypical antipsychotic was discontinued; however, some patients required continuation of anti-diabetic treatment despite discontinuation of the suspect drug.
In some patients, a worsening of more than one of the metabolic parameters of weight, blood glucose and lipids was observed in clinical studies. Changes in these parameters should be managed as clinically appropriate.
Adults:
Table 2: Fasting Glucose—Proportion of Patients Shifting to ≥ 126 mg/dL in short-term (≤ 12 weeks) Placebo-Controlled Studies
| Laboratory Analyte |
Category Change (At Least Once) from Baseline |
Treatment Arm |
N |
Patients
n (%) |
|---|
Fasting Glucose
|
Normal to High
(<100 mg/dL to ≥ 126 mg/dL)
|
Quetiapine
|
2907
|
71 (2.4%)
|
Placebo
|
1346
|
19 (1.4%)
|
|
|
Borderline to High
(≥ 100 mg/dL and <126 mg/dL to ≥ 126 mg/dL)
|
Quetiapine
|
572
|
67 (11.7%)
|
|
Placebo
|
279
|
33 (11.8%)
|
|
|
In a 24-week trial (active-controlled, 115 patients treated with SEROQUEL) designed to evaluate glycemic status with oral glucose tolerance testing of all patients, at week 24 the incidence of a treatment-emergent post-glucose challenge glucose level ≥ 200 mg/dL was 1.7% and the incidence of a fasting treatment-emergent blood glucose level ≥ 126 mg/dL was 2.6%. The mean change in fasting glucose from baseline was 3.2 mg/dL and mean change in 2 hour glucose from baseline was -1.8 mg/dL for quetiapine.
In 2 long-term placebo-controlled randomized withdrawal clinical trials for bipolar maintenance, mean exposure of 213 days for SEROQUEL (646 patients) and 152 days for placebo (680 patients), the mean change in glucose from baseline was +5.0 mg/dL for quetiapine and –0.05 mg/dL for placebo. The exposure-adjusted rate of any increased blood glucose level (≥ 126 mg/dL) for patients more than 8 hours since a meal (however, some patients may not have been precluded from calorie intake from fluids during fasting period) was 18.0 per 100 patient years for SEROQUEL (10.7% of patients; n=556) and 9.5 for placebo per 100 patient years (4.6% of patients; n=581).
Table 3 shows the percentage of patients with shifts in blood glucose to ≥ 126 mg/dL from normal baseline in MDD adjunct therapy trials by dose.
Table 3: Percentage of Patients with Shifts from Normal Baseline in Blood Glucose to ≥ 126 mg/dL (assumed fasting) in MDD Adjunct Therapy Trials by Dose
| Laboratory Analyte |
Treatment Arm |
N |
Patients n (%) |
|---|
Blood Glucose ≥ 126 mg/dL
|
Placebo
|
277
|
17 (6%)
|
Seroquel XR 150 mg
|
280
|
19 (7%)
|
|
Seroquel XR 300 mg
|
269
|
32 (12%)
|
|
Children and Adolescents: Safety and effectiveness of Seroquel XR have not been established in pediatric patients and Seroquel XR is not approved for patients under the age of 18 years. In a placebo-controlled SEROQUEL monotherapy study of adolescent patients (13– 17 years of age) with schizophrenia (6 weeks duration), the mean change in fasting glucose levels for SEROQUEL (n=138) compared to placebo (n=67) was –0.75 mg/dL versus –1.70 mg/dL. In a placebo-controlled SEROQUEL monotherapy study of children and adolescent patients (10–17 years of age) with bipolar mania (3 weeks duration), the mean change in fasting glucose level for SEROQUEL (n=170) compared to placebo (n=81) was 3.62 mg/dL versus –1.17 mg/dL. No patient in either study with a baseline normal fasting glucose level (<100 mg/dL) or a baseline borderline fasting glucose level (≥100 mg/dL and <126 mg/dL) had a treatment-emergent blood glucose level of ≥126 mg/dL.
Hyperlipidemia
Undesirable alterations in lipids have been observed with quetiapine use. Clinical monitoring, including baseline and periodic follow-up lipid evaluations in patients using quetiapine is recommended.
In some patients, a worsening of more than one of the metabolic parameters of weight, blood glucose and lipids was observed in clinical studies. Changes in these parameters should be managed as clinically appropriate.
Adults:
Table 4 shows the percentage of patients with changes in cholesterol and triglycerides from baseline by indication in clinical trials with Seroquel XR.
Table 4: Percentage of Adult Patients with Shifts in Total Cholesterol, Triglycerides, LDL-Cholesterol and HDL-Cholesterol from Baseline to Clinically Significant Levels by Indication
| Laboratory Analyte |
Indication |
Treatment Arm |
N |
Patients
n (%) |
|---|
|
Total Cholesterol ≥240 mg/dL
|
Schizophrenia
|
Seroquel XR
|
718
|
67 (9%)
|
Placebo
|
232
|
21 (9%)
|
|
|
Bipolar Depression
|
Seroquel XR
|
85
|
6 (7%)
|
|
Placebo
|
106
|
3 (3%)
|
|
|
Bipolar Mania
|
Seroquel XR
|
128
|
9 (7%)
|
|
Placebo
|
134
|
5 (4%)
|
|
|
Major Depressive Disorder (Adjunct Therapy)
|
Seroquel XR
|
420
|
67 (16%)
|
|
Placebo
|
213
|
15 (7%)
|
|
|
Triglycerides ≥200 mg/dL
|
Schizophrenia*
|
Seroquel XR
|
659
|
118 (18%)
|
Placebo
|
214
|
11 (5%)
|
|
|
Bipolar Depression†
|
Seroquel XR
|
84
|
7 (8%)
|
|
Placebo
|
93
|
7 (8%)
|
|
|
Bipolar Mania‡
|
Seroquel XR
|
102
|
15 (15%)
|
|
Placebo
|
125
|
8 (6%)
|
|
|
Major Depressive Disorder (Adjunct Therapy)§
|
Seroquel XR
|
458
|
75 (16%)
|
|
Placebo
|
223
|
18 (8%)
|
|
|
LDL-Cholesterol ≥ 160 mg/dL
|
Schizophrenia*
|
Seroquel XR
|
691
|
47 (7%)
|
Placebo
|
227
|
17 (8%)
|
|
|
Bipolar Depression†
|
Seroquel XR
|
86
|
3 (4%)
|
|
Placebo
|
104
|
2 (2%)
|
|
|
Bipolar Mania‡
|
Seroquel XR
|
125
|
5 (4%)
|
|
Placebo
|
135
|
2 (2%)
|
|
|
Major Depressive Disorder (Adjunct Therapy)§
|
Seroquel XR
|
457
|
51 (11%)
|
|
Placebo
|
219
|
21 (10%)
|
|
|
HDL-Cholesterol ≤ 40 mg/dL
|
Schizophrenia*
|
Seroquel XR
|
600
|
87 (15%)
|
Placebo
|
195
|
23 (12%)
|
|
|
Bipolar Depression†
|
Seroquel XR
|
78
|
7 (9%)
|
|
Placebo
|
83
|
6 (7%)
|
|
|
Bipolar Mania‡
|
Seroquel XR
|
100
|
19 (19%)
|
|
Placebo
|
115
|
15 (13%)
|
|
|
Major Depressive Disorder (Adjunct Therapy)§
|
Seroquel XR
|
470
|
34 (7%)
|
|
Placebo
|
230
|
19 (8%)
|
|
|
In SEROQUEL clinical trials for schizophrenia, the percentage of patients with shifts in cholesterol and triglycerides from baseline to clinically significant levels were 18% (placebo: 7%) and 22% (placebo: 16%). HDL-cholesterol and LDL-cholesterol parameters were not measured in these studies. In SEROQUEL clinical trials for bipolar depression, the following percentage of patients had shifts from baseline to clinically significant levels for the four lipid parameters measured: total cholesterol 9% (placebo: 6%); triglycerides 14% (placebo: 9%); LDL-cholesterol 6% (placebo: 5%) and HDL-cholesterol 14% (placebo: 14%). Lipid parameters were not measured in the bipolar mania studies.
Table 5 shows the percentage of patients in MDD adjunctive therapy trials with clinically significant shifts in total-cholesterol, triglycerides, LDL-cholesterol and HDL-cholesterol from baseline by dose.
Table 5: Percentage of Patients with Shifts in Total Cholesterol, Triglycerides, LDL-Cholesterol and HDL-Cholesterol from Baseline to Clinically Significant Levels in MDD Adjunctive Therapy Trials by Dose
| Laboratory Analyte |
Treatment Arm |
N |
Patients
n (%) |
|---|
|
Cholesterol ≥ 240 mg/dL
|
Placebo
|
213
|
15 (7%)
|
Seroquel XR 150 mg
|
223
|
41 (18%)
|
|
Seroquel XR 300 mg
|
197
|
26 (13%)
|
|
Triglycerides ≥ 200 mg/dL
|
Placebo
|
223
|
18 (8%)
|
Seroquel XR 150 mg
|
232
|
36 (16%)
|
|
Seroquel XR 300 mg
|
226
|
39 (17%)
|
|
LDL-Cholesterol ≥ 160 mg/dL
|
Placebo
|
219
|
21 (10%)
|
Seroquel XR 150 mg
|
242
|
29 (12%)
|
|
Seroquel XR 300 mg
|
215
|
22 (10%)
|
|
HDL-Cholesterol ≤ 40 mg/dL
|
Placebo
|
230
|
19 (8%)
|
Seroquel XR 150 mg
|
238
|
14 (6%)
|
|
Seroquel XR 300 mg
|
232
|
20 (9%)
|
|
Children and Adolescents:
Safety and effectiveness of Seroquel XR have not been established in pediatric patients, and Seroquel XR is not approved for patients under the age of 18 years.
Table 6 shows the percentage of children and adolescents with shifts in total cholesterol, triglycerides, LDL-cholesterol and HDL-cholesterol from baseline to clinically significant levels by indication in clinical trials with SEROQUEL.
Table 6: Percentage of Children and Adolescents with Shifts in Total Cholesterol, Triglycerides LDL-Cholesterol and HDL-Cholesterol from Baseline to Clinically Significant Levels by Indication
| Laboratory Analyte |
Indication |
Treatment Arm |
N |
Patients
n (%) |
|---|
|
Total Cholesterol ≥ 200 mg/dL
|
Schizophrenia
|
SEROQUEL
|
107
|
13 (12%)
|
Placebo
|
56
|
1 (2%)
|
|
|
Bipolar Mania
|
SEROQUEL
|
159
|
16 (10%)
|
|
Placebo
|
66
|
2 (3%)
|
|
|
Triglycerides ≥150 mg/dL
|
Schizophrenia*
|
SEROQUEL
|
103
|
17 (17%)
|
Placebo
|
51
|
4 (8%)
|
|
|
Bipolar Mania†
|
SEROQUEL
|
149
|
32 (22%)
|
|
Placebo
|
60
|
8 (13%)
|
|
|
LDL-Cholesterol ≥ 130 mg/dL
|
Schizophrenia*
|
SEROQUEL
|
112
|
4 (4%)
|
Placebo
|
60
|
1 (2%)
|
|
|
Bipolar Mania†
|
SEROQUEL
|
169
|
13 (8%)
|
|
Placebo
|
74
|
4 (5%)
|
|
|
HDL-Cholesterol ≤ 40 mg/dL
|
Schizophrenia*
|
SEROQUEL
|
104
|
16 (15%)
|
Placebo
|
54
|
10 (19%)
|
|
|
Bipolar Mania†
|
SEROQUEL
|
154
|
16 (10%)
|
|
Placebo
|
61
|
4 (7%)
|
|
|
Weight Gain
Increases in weight have been observed in clinical trials. Patients receiving quetiapine should receive regular monitoring of weight [see Patient Counseling Information (17)].
In some patients, a worsening of more than one of the metabolic parameters of weight, blood glucose and lipids was observed in clinical studies. Changes in these parameters should be managed as clinically appropriate.
Adults: Table 7 shows the percentage of adult patients with weight gain of ≥ 7% of body weight by indication.
Table 7: Percentage of Patients with Weight Gain ≥ 7% of Body Weight (Adults) by Indication
| Vital sign |
Indication |
Treatment Arm |
N |
Patients
n (%) |
|---|
|
Weight Gain ≥ 7% of Body Weight
|
Schizophrenia
|
Seroquel XR
|
907
|
90 (10%)
|
Placebo
|
299
|
16 (5%)
|
|
|
Bipolar Mania
|
Seroquel XR
|
138
|
7 (5%)
|
|
Placebo
|
150
|
0 (0%)
|
|
|
Bipolar Depression
|
Seroquel XR
|
110
|
9 (8%)
|
|
Placebo
|
125
|
1 (1%)
|
|
|
Major Depressive Disorder (Adjunctive Therapy)
|
Seroquel XR
|
616
|
32 (5%)
|
|
Placebo
|
302
|
5 (2%)
|
|
|
In schizophrenia trials, the proportions of patients meeting a weight gain criterion of ≥ 7% of body weight were compared in a pool of four 3- to 6-week placebo-controlled clinical trials, revealing a statistically significant greater incidence of weight gain for SEROQUEL (23%) compared to placebo (6%).
Table 8 shows the percentage of adult patients with weight gain of ≥ 7% of body weight for MDD by dose.
Table 8: Percentage of Patients with Weight Gain ≥ 7% of Body Weight in MDD Adjunctive Therapy Trials by Dose (Adults)
| Vital sign |
Treatment Arm |
N |
Patients
n (%) |
|---|
Weight Gain ≥7% of Body weight in MDD Adjunctive Therapy
|
Placebo
|
302
|
5 (2%)
|
Seroquel XR 150 mg
|
309
|
10 (3%)
|
|
Seroquel XR 300 mg
|
307
|
22 (7%)
|
|
Children and Adolescents: Safety and effectiveness of Seroquel XR have not been established in pediatric patients and Seroquel XR is not approved for patients under the age of 18 years. In two clinical trials with SEROQUEL, one in bipolar mania and one in schizophrenia, reported increases in weight are included in table 9 below.
Table 9 shows the percentage of patients with weight gain ≥ 7% of body weight in clinical trials with SEROQUEL.
Table 9: Percentage of Patients with Weight Gain ≥ 7% of Body Weight (Children and Adolescents)
| Vital Sign |
Indication |
Treatment Arm |
N |
Patients
n (%) |
|---|
|
Weight gain ≥ 7% of Body Weight
|
Schizophrenia
|
SEROQUEL
|
111
|
23 (21%)
|
Placebo
|
44
|
3 (7%)
|
|
|
Bipolar Mania
|
SEROQUEL
|
157
|
18 (12%)
|
|
Placebo
|
68
|
0 (0%)
|
|
|
The mean change in body weight in the schizophrenia trial was 2.0 kg in the SEROQUEL group and -0.4 kg in the placebo group and in the bipolar mania trial it was 1.7 kg in the SEROQUEL group and 0.4 kg in the placebo group.
In an open-label study that enrolled patients from the above two pediatric trials, 63% of patients (241/380) completed 26 weeks of therapy with SEROQUEL. After 26 weeks of treatment, the mean increase in body weight was 4.4 kg. Forty-five percent of the patients gained ≥ 7% of their body weight, not adjusted for normal growth. In order to adjust for normal growth over 26 weeks, an increase of at least 0.5 standard deviation from baseline in BMI was used as a measure of a clinically significant change; 18.3% of patients on SEROQUEL met this criterion after 26 weeks of treatment.
When treating pediatric patients with SEROQUEL for any indication, weight gain should be assessed against that expected for normal growth.
Tardive Dyskinesia
A syndrome of potentially irreversible, involuntary, dyskinetic movements may develop in patients treated with antipsychotic drugs including
