Recommended Topic Related To:

Seroquel XR

"What are anxiety medications and how do they work?

Anxiety is both a normal and useful response to potentially stressful or dangerous situations. It helps by increasing our awareness of what's going on around us and in other ways. For"...

Seroquel XR

Seroquel XR

WARNINGS

Included as part of the PRECAUTIONS section.

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 Quetiapine 572 67 (11.7%)
<126 mg/dL to ≥ 126 mg/dL) 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 Schizophreniaa SEROQUEL XR 718 67 (9%)
Placebo 232 21 (9%)
Bipolar Depressionb SEROQUEL XR 85 6 (7%)
Placebo 106 3 (3%)
Bipolar Maniac SEROQUEL XR 128 9 (7%)
Placebo 134 5 (4%)
Major Depressive Disorder (Adjunct Therapy)d SEROQUEL XR 420 67 (16%)
Placebo 213 15 (7%)
Triglycerides ≥ 200mg/dL Schizophreniaa SEROQUEL XR 659 118 (18%)
Placebo 214 11 (5%)
Bipolar Depressionb SEROQUEL XR 84 7 (8%)
Placebo 93 7 (8%)
Bipolar Maniac SEROQUEL XR 102 15 (15%)
Placebo 125 8 (6%)
Major Depressive Disorder (Adjunct Therapy)d SEROQUEL XR 458 75 (16%)
Placebo 223 18 (8%)
LDL-Cholesterol ≥ 160 mg/dL Schizophreniaa SEROQUEL XR 691 47 (7%)
Placebo 227 17 (8%)
Bipolar Depressionb SEROQUEL XR 86 3 (4%)
Placebo 104 2 (2%)
Bipolar Maniac SEROQUEL XR 125 5 (4%)
Placebo 135 2 (2%)
Major Depressive Disorder (Adjunct Therapy)d SEROQUEL XR 457 51 (11%)
Placebo 219 21 (10%)
HDL-Cholesterol ≥ 40 mg/dL Schizophreniaa SEROQUEL XR 600 87 (15%)
Placebo 195 23 (12%)
Bipolar Depressionb SEROQUEL XR 78 7 (9%)
Placebo 83 6 (7%)
Bipolar Maniac SEROQUEL XR 100 19 (19%)
Placebo 115 15 (13%)
Major Depressive Disorder (Adjunct Therapy)d SEROQUEL XR 470 34 (7%)
Placebo 230 19 (8%)
a: 6 weeks duration
b: 8 weeks duration
c: 3 weeks duration
d: 6 weeks duration

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 Arma 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%)
a: 6 weeks duration

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 Schizophreniaa SEROQUEL 107 13 (12%)
Placebo 56 1 (2%)
Bipolar Maniab SEROQUEL 159 16 (10%)
Placebo 66 2 (3%)
Triglycerides ≥ 150 mg/dL Schizophreniaa SEROQUEL 103 17 (17%)
Placebo 51 4 (8%)
Bipolar Maniab SEROQUEL 149 32 (22%)
Placebo 60 8 (13%)
LDL-Cholesterol ≥ 30 mg/dL Schizophreniaa SEROQUEL 112 4 (4%)
Placebo 60 1 (2%)
Bipolar Maniab SEROQUEL 169 13 (8%)
Placebo 74 4 (5%)
HDL-Cholesterol ≤ 40 mg/dL Schizophreniaa SEROQUEL 104 16 (15%)
Placebo 54 10 (19%)
Bipolar Maniab SEROQUEL 154 16 (10%)
Placebo 61 4 (7%)
a: 13- 17 years, 6 weeks duration b: 10-17 years, 3 weeks duration

Weight Gain

Increases in weight have been observed in clinical trials. Patients receiving quetiapine should receive regular monitoring of weight [see PATIENT INFORMATION].

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 Schizophreniaa SEROQUEL XR 907 90 (10%)
Placebo 299 16 (5%)
Bipolar Maniab SEROQUEL XR 138 7 (5%)
Placebo 150 0 (0%)
Bipolar Depressionc SEROQUEL XR 110 9 (8%)
Placebo 125 1 (1%)
Major Depressive Disorder (Adjunctive Therapy)d SEROQUEL XR 616 32 (5%)
Placebo 302 5 (2%)
a: 6 weeks duration
b: 3 weeks duration
c: 8 weeks duration
d: 6 weeks duration

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 Schizophreniaa SEROQUEL 111 23 (21%)
Placebo 44 3 (7%)
Bipolar Maniab SEROQUEL 157 18 (12%)
Placebo 68 0 (0%)
a: 6 weeks duration
b: 3 weeks duration

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 quetiapine. Although the prevalence of the syndrome appears to be highest among the elderly, especially elderly women, it is impossible to rely upon prevalence estimates to predict, at the inception of antipsychotic treatment, which patients are likely to develop the syndrome. Whether antipsychotic drug products differ in their potential to cause tardive dyskinesia is unknown.

The risk of developing tardive dyskinesia and the likelihood that it will become irreversible are believed to increase as the duration of treatment and the total cumulative dose of antipsychotic drugs administered to the patient increase. However, the syndrome can develop, although much less commonly, after relatively brief treatment periods at low doses or may even arise after discontinuation of treatment.

There is no known treatment for established cases of tardive dyskinesia, although the syndrome may remit, partially or completely, if antipsychotic treatment is withdrawn. Antipsychotic treatment, itself, however, may suppress (or partially suppress) the signs and symptoms of the syndrome and thereby may possibly mask the underlying process. The effect that symptomatic suppression has upon the long-term course of the syndrome is unknown.

Given these considerations, SEROQUEL XR should be prescribed in a manner that is most likely to minimize the occurrence of tardive dyskinesia. Chronic antipsychotic treatment should generally be reserved for patients who appear to suffer from a chronic illness that (1) is known to respond to antipsychotic drugs, and (2) for whom alternative, equally effective, but potentially less harmful treatments are not available or appropriate. In patients who do require chronic treatment, the smallest dose and the shortest duration of treatment producing a satisfactory clinical response should be sought. The need for continued treatment should be reassessed periodically.

If signs and symptoms of tardive dyskinesia appear in a patient on SEROQUEL XR, drug discontinuation should be considered. However, some patients may require treatment with quetiapine despite the presence of the syndrome.

Orthostatic Hypotension

Quetiapine may induce orthostatic hypotension associated with dizziness, tachycardia and, in some patients, syncope, especially during the initial dose-titration period, probably reflecting its α1-adrenergic antagonist properties. Syncope was reported in 0.3% (5/1866) of the patients treated with SEROQUEL XR across all indications, compared with 0.2% (2/928) on placebo. Syncope was reported in 1% (28/3265) of the patients treated with SEROQUEL, compared with 0.2% (2/954) on placebo. Orthostatic hypotension, dizziness, and syncope may lead to falls.

Quetiapine should be used with particular caution in patients with known cardiovascular disease (history of myocardial infarction or ischemic heart disease, heart failure or conduction abnormalities), cerebrovascular disease or conditions which would predispose patients to hypotension (dehydration, hypovolemia and treatment with antihypertensive medications) [see ADVERSE REACTIONS]. If hypotension occurs during titration to the target dose, a return to the previous dose in the titration schedule is appropriate.

Increases in Blood Pressure (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 placebo-controlled trials in children and adolescents with schizophrenia (6-week duration) or bipolar mania (3week duration), the incidence of increases at any time in systolic blood pressure ( ≥ 20 mmHg) was 15.2% (51/335) for SEROQUEL and 5.5% (9/163) for placebo; the incidence of increases at any time in diastolic blood pressure ( ≥ 10 mmHg) was 40.6% (136/335) for SEROQUEL and 24.5% (40/163) for placebo. In the 26-week open-label clinical trial, one child with a reported history of hypertension experienced a hypertensive crisis. Blood pressure in children and adolescents should be measured at the beginning of, and periodically during treatment.

Leukopenia, Neutropenia and Agranulocytosis

In clinical trials and postmarketing experience, events of leukopenia/neutropenia have been reported temporally related to atypical antipsychotic agents, including quetiapine fumarate. Agranulocytosis (including fatal cases) has also been reported.

Possible risk factors for leukopenia/neutropenia include pre-existing low white cell count (WBC) and history of drug induced leukopenia/neutropenia. Patients with a pre-existing low WBC or a history of drug induced leukopenia/neutropenia should have their complete blood count (CBC) monitored frequently during the first few months of therapy and should discontinue SEROQUEL XR at the first sign of a decline in WBC in absence of other causative factors.

Patients with neutropenia should be carefully monitored for fever or other symptoms or signs of infection and treated promptly if such symptoms or signs occur. Patients with severe neutropenia (absolute neutrophil count < 1000/mm³) should discontinue SEROQUEL XR and have their WBC followed until recovery [see ADVERSE REACTIONS].

Cataracts

The development of cataracts was observed in association with quetiapine treatment in chronic dog studies [see Animal Toxicology]. Lens changes have also been observed in adults, children, and adolescents during long-term quetiapine treatment, but a causal relationship to quetiapine use has not been established. Nevertheless, the possibility of lenticular changes cannot be excluded at this time. Therefore, examination of the lens by methods adequate to detect cataract formation, such as slit lamp exam or other appropriately sensitive methods, is recommended at initiation of treatment or shortly thereafter, and at 6-month intervals during chronic treatment.

Seizures

During short-term clinical trials with SEROQUEL XR, seizures occurred in 0.05% (1/1866) of patients treated with SEROQUEL XR across all indications compared to 0.3% (3/928) on placebo. During clinical trials with SEROQUEL, seizures occurred in 0.5% (20/3490) of patients treated with SEROQUEL compared to 0.2% (2/954) on placebo. As with other antipsychotics, quetiapine fumarate should be used cautiously in patients with a history of seizures or with conditions that potentially lower the seizure threshold, e.g., Alzheimer's dementia. Conditions that lower the seizure threshold may be more prevalent in a population of 65 years or older.

Hypothyroidism

Adults: Clinical trials with quetiapine demonstrated dose-related decreases in thyroid hormone levels. The reduction in total and free thyroxine (T4) of approximately 20% at the higher end of the therapeutic dose range was maximal in the first six weeks of treatment and maintained without adaptation or progression during more chronic therapy. In nearly all cases, cessation of quetiapine treatment was associated with a reversal of the effects on total and free T4, irrespective of the duration of treatment. In SEROQUEL XR clinical trials across all indications 1.8% (24/1336) of patients on SEROQUEL XR vs. 0.6% (3/530) on placebo experienced decreased free thyroxine and 1.6% (21/1346) on SEROQUEL XR vs. 3.4% (18/534) on placebo experienced increased thyroid stimulating hormone (TSH); however, no patients experienced a combination of clinically significant decreased free thyroxine and increased TSH. About 0.7% (26/3489) of SEROQUEL patients did experience TSH increases in monotherapy studies. Some patients with TSH increases needed replacement thyroid treatment.

In all quetiapine trials, the incidence of potentially clinically significant shifts in thyroid hormones and TSH were*: decrease in free T4, 2.0% (357/17513); decrease in total T4, 4.0% (75/1861); decrease in free T3, 0.4% (53/13766); decrease in total T3, 2.0% (26/1312), and increase in TSH, 4.9% (956/19412). In eight patients, where TBG was measured, levels of TBG were unchanged.

Table 10 shows the incidence of these shifts in short-term placebo-controlled clinical trials.

Table 10: Incidence of potentially clinically significant shifts in thyroid hormone levels and TSH in short term placebo-controlled clinical trials*

Total T4 Free T4 Total T3 Free T3 TSH
Quetiapine Placebo Quetiapine Placebo Quetiapine Placebo Quetiapine Placebo Quetiapine Placebo
3.4 % 0.6% 0.7% 0.1% 0.5% 0.0% 0.2% 0.0% 3.2% 2.7%
(37/1097) (4/651) (52/7218) (4/3668) (2/369) (0/113) (11/5673) (1/2679) (240/7587) (105/3912)
* Based on shifts from normal baseline to potentially clinically important value at anytime post-baseline. Shifts in total T4, free T4, total T3 and free T3 are defined as < 0.8 x LLN (pmol/L) and shift in TSH is > 5 mIU/L at any time.

In short-term placebo-controlled monotherapy trials, the incidence of reciprocal, potentially clinically significant shifts in T3 and TSH was 0.0 % for both quetiapine (1/4800) and placebo (0/2190) and for T4 and TSH the shifts were 0.1% (7/6154) for quetiapine versus 0.0 % (1/3007) for placebo.

Generally, these changes in thyroid hormone levels were of no clinical significance.

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 acute placebo-controlled trials in children and adolescent patients with schizophrenia (6-week duration) or bipolar mania (3-week duration), the incidence of shifts to potentially clinically important thyroid function values at any time for SEROQUEL treated patients and placebo-treated patients for elevated TSH was 2.9% (8/280) vs. 0.7% (1/138), respectively and for decreased total thyroxine was 2.8% (8/289) vs. 0% (0/145), respectively. Of the SEROQUEL treated patients with elevated TSH levels, 1 had simultaneous low free T4 level at end of treatment.

Hyperprolactinemia

Adults: During clinical trials with quetiapine across all indications, the incidence of shifts in prolactin levels to a clinically significant value occurred in 3.6% (158/4416) of patients treated with quetiapine compared to 2.6% (51/1968) on placebo.

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 acute placebo-controlled trials in children and adolescent patients with bipolar mania (3-week duration) or schizophrenia (6-week duration), the incidence of shifts in prolactin levels to a clinically significant value ( > 20 μg/L males; > 26 μg/L females at any time) was 13.4% (18/134) for SEROQUEL compared to 4% (3/75) for placebo in males and 8.7% (9/104) for SEROQUEL compared to 0% (0/39) for placebo in females.

Like other drugs that antagonize dopamine D2 receptors, SEROQUEL XR elevates prolactin levels in some patients and the elevation may persist during chronic administration. Hyperprolactinemia, regardless of etiology, may suppress hypothalamic GnRH, resulting in reduced pituitary gonadotrophin secretion. This, in turn, may inhibit reproductive function by impairing gonadal steroidogenesis in both female and male patients. Galactorrhea, amenorrhea, gynecomastia, and impotence have been reported in patients receiving prolactin-elevating compounds. Long-standing hyperprolactinemia when associated with hypogonadism may lead to decreased bone density in both female and male subjects.

Tissue culture experiments indicate that approximately one-third of human breast cancers are prolactin dependent in vitro , a factor of potential importance if the prescription of these drugs is considered in a patient with previously detected breast cancer. As is common with compounds which increase prolactin release, mammary gland, and pancreatic islet cell neoplasia (mammary adenocarcinomas, pituitary and pancreatic adenomas) was observed in carcinogenicity studies conducted in mice and rats. Neither clinical studies nor epidemiologic studies conducted to date have shown an association between chronic administration of this class of drugs and tumorigenesis in humans, but the available evidence is too limited to be conclusive [see Carcinogenesis, Mutagenesis, Impairment of Fertility].

Transaminase Elevations

Asymptomatic, transient and reversible elevations in serum transaminases (primarily ALT) have been reported. The proportions of patients with transaminase elevations of > 3 times the upper limits of the normal reference range in a pool of placebo-controlled trials ranged between 1% and 2% for SEROQUEL XR compared to 2% for placebo. In schizophrenia trials in adults, the proportions of patients with transaminase elevations of > 3 times the upper limits of the normal reference range in a pool of 3- to 6-week placebo-controlled trials were approximately 6% (29/483) for SEROQUEL compared to 1% (3/194) for placebo. These hepatic enzyme elevations usually occurred within the first 3 weeks of drug treatment and promptly returned to pre-study levels with ongoing treatment with quetiapine.

Potential for Cognitive and Motor Impairment

Somnolence was a commonly reported adverse event reported in patients treated with quetiapine especially during the 3-day period of initial dose titration. In schizophrenia trials, somnolence was reported in 24.7% (235/951) of patients on SEROQUEL XR compared to 10.3% (33/319) of placebo patients. In a bipolar depression clinical trial, somnolence was reported in 51.8% (71/137) of patients on SEROQUEL XR compared to 12.9% (18/140) of placebo patients. In a clinical trial for bipolar mania, somnolence was reported in 50.3% (76/151) of patients on SEROQUEL XR compared to 11.9% (19/160) of placebo patients. Since quetiapine has the potential to impair judgment, thinking, or motor skills, patients should be cautioned about performing activities requiring mental alertness, such as operating a motor vehicle (including automobiles) or operating hazardous machinery until they are reasonably certain that quetiapine therapy does not affect them adversely. Somnolence may lead to falls.

In short-term adjunctive therapy trials for MDD, somnolence was reported in 40% (252/627) of patients on SEROQUEL XR respectively compared to 9% (27/309) of placebo patients. Somnolence was dose-related in these trials (37% (117/315) and 43% (135/312) for the 150 mg and 300 mg groups, respectively).

Priapism

One case of priapism in a patient receiving quetiapine was reported prior to market introduction. While a causal relationship to use of quetiapine has not been established, other drugs with α-adrenergic blocking effects have been reported to induce priapism, and it is possible that quetiapine may share this capacity. Severe priapism may require surgical intervention.

Body Temperature Regulation

Disruption of the body's ability to reduce core body temperature has been attributed to antipsychotic agents. Appropriate care is advised when prescribing SEROQUEL XR for patients who will be experiencing conditions which may contribute to an elevation in core body temperature, eg, exercising strenuously, exposure to extreme heat, receiving concomitant medication with anticholinergic activity, or being subject to dehydration.

Dysphagia

Esophageal dysmotility and aspiration have been associated with antipsychotic drug use. Aspiration pneumonia is a common cause of morbidity and mortality in elderly patients, in particular those with advanced Alzheimer's dementia. SEROQUEL XR and other antipsychotic drugs should be used cautiously in patients at risk for aspiration pneumonia.

Suicide

The possibility of a suicide attempt is inherent in schizophrenia, bipolar disorder and depression; close supervision of high risk patients should accompany drug therapy. 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.

In three, 6-week clinical studies in patients with schizophrenia (N=951) the incidence of treatment emergent suicidal ideation or suicide attempt was 0.6% (n=6) in SEROQUEL XR treated patients and 0.9% (n=3) in placebo-treated patients.

In an 8-week clinical study in patients with bipolar depression (N=137 for SEROQUEL XR and 140 for placebo) the incidence of treatment emergent suicidal ideation or suicide attempt was 0.7% (n=1) for SEROQUEL XR treated patients and 1.4% (n=2) for placebo.

In a 3-week clinical study in patients with bipolar mania (N=311, 151 for SEROQUEL XR and 160 for placebo) the incidence of treatment emergent suicidal ideation or suicide attempt was 1.3% (n=2) for SEROQUEL XR compared to 3.8% (n=6) for placebo.

In two, 6-week MDD adjunctive therapy trials (n=936, 627 on SEROQUEL XR and 309 on placebo) the incidence of treatment emergent suicidal ideation or suicide attempt was 0.5% (n=3) in SEROQUEL XR treated patients and 0.6% (n=2) in placebo.

Use in Patients with Concomitant Illness

Clinical experience with SEROQUEL XR in patients with certain concomitant systemic illnesses [see Pharmacokinetics] is limited.

SEROQUEL XR has not been evaluated or used to any appreciable extent in patients with a recent history of myocardial infarction or unstable heart disease. Patients with these diagnoses were excluded from premarketing clinical studies. Because of the risk of orthostatic hypotension with SEROQUEL XR, caution should be observed in cardiac patients [see WARNINGS AND PRECAUTIONS].

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 in patients who overdosed on quetiapine [see OVERDOSAGE], in patients with concomitant illness, and in patients taking medicines known to cause electrolyte imbalance or increase QT interval [see DRUG INTERACTIONS]. Caution should be exercised when quetiapine is prescribed in patients with cardiovascular disease or family history of QT prolongation. Also caution should be exercised when quetiapine is prescribed with medicines known to cause electrolyte imbalance or 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 hypomagnesemia.

Withdrawal

Acute withdrawal symptoms, such as insomnia, nausea and vomiting have been described after abrupt cessation of atypical antipsychotic drugs, including quetiapine fumarate. In short-term placebo-controlled, monotherapy clinical trials with SEROQUEL XR that included a discontinuation phase which evaluated discontinuation symptoms, the aggregated incidence of patients experiencing one or more discontinuation symptoms after abrupt cessation was 12.1% (241/1993) for SEROQUEL XR and 6.7% (71/1065) for placebo. The incidence of the individual adverse events (i.e., insomnia, nausea, headache, diarrhea, vomiting, dizziness and irritability) did not exceed 5.3% in any treatment group and usually resolved after 1 week post-discontinuation. Gradual withdrawal is advised.

Patient Counseling Information

Information for Patients

[see Medication Guide]

Prescribers or other health professionals should inform patients, their families, and their caregivers about the benefits and risks associated with treatment with SEROQUEL XR and should counsel them in its appropriate use. A patient Medication Guide about “Antidepressant Medicines, Depression and other Serious Mental Illness, and Suicidal Thoughts or Actions” is available for SEROQUEL XR. The prescriber or health professional should instruct patients, their families, and their caregivers to read the Medication Guide and should assist them in understanding its contents. Patients should be given the opportunity to discuss the contents of the Medication Guide and to obtain answers to any questions they may have. The complete text of the Medication Guide is reprinted at the end of this document.

Patients should be advised of the following issues and asked to alert their prescriber if these occur while taking SEROQUEL XR.

Increased Mortality in Elderly Patients with Dementia-Related Psychosis

Patients and caregivers should be advised that elderly patients with dementia-related psychoses treated with atypical antipsychotic drugs are at increased risk of death compared with placebo. Quetiapine is not approved for elderly patients with dementia-related psychosis [see WARNINGS AND PRECAUTIONS].

Clinical Worsening and Suicide Risk

Patients, their families, and their caregivers should be encouraged to be alert to the emergence of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, mania, other unusual changes in behavior, worsening of depression, and suicidal ideation, especially early during antidepressant treatment and when the dose is adjusted up or down. Families and caregivers of patients should be advised to look for the emergence of such symptoms on a day-to-day basis, since changes may be abrupt. Such symptoms should be reported to the patient's prescriber or health professional, especially if they are severe, abrupt in onset, or were not part of the patient's presenting symptoms. Symptoms such as these may be associated with an increased risk for suicidal thinking and behavior and indicate a need for very close monitoring and possibly changes in the medication [see WARNINGS AND PRECAUTIONS].

Neuroleptic Malignant Syndrome (NMS)

Patients should be advised to report to their physician any signs or symptoms that may be related to NMS. These may include muscle stiffness and high fever [see WARNINGS AND PRECAUTIONS].

Hyperglycemia and Diabetes Mellitus

Patients should be aware of the symptoms of hyperglycemia (high blood sugar) and diabetes mellitus. Patients who are diagnosed with diabetes, those with risk factors for diabetes, or those that develop these symptoms during treatment should have their blood glucose monitored at the beginning of and periodically during treatment [see WARNINGS AND PRECAUTIONS].

Hyperlipidemia

Patients should be advised that elevations in total cholesterol, LDL-cholesterol and triglycerides and decreases in HDL-cholesterol may occur. Patients should have their lipid profile monitored at the beginning of and periodically during treatment [see WARNINGS AND PRECAUTIONS].

Weight Gain

Patients should be advised that they may experience weight gain. Patients should have their weight monitored regularly [see WARNINGS AND PRECAUTIONS].

Orthostatic Hypotension

Patients should be advised of the risk of orthostatic hypotension (symptoms include feeling dizzy or lightheaded upon standing, which may lead to falls) especially during the period of initial dose titration, and also at times of re-initiating treatment or increases in dose [see WARNINGS AND PRECAUTIONS].

Increased Blood Pressure in Children and Adolescents

Blood pressure should be measured at the beginning of, and periodically during, treatment [see WARNINGS AND PRECAUTIONS].

Leukopenia/Neutropenia

Patients with a pre-existing low WBC or a history of drug induced leukopenia/neutropenia should be advised that they should have their CBC monitored while taking SEROQUEL XR [see WARNINGS AND PRECAUTIONS].

Interference with Cognitive and Motor Performance

Patients should be advised of the risk of somnolence or sedation (which may lead to falls), especially during the period of initial dose titration. Patients should be cautioned about performing any activity requiring mental alertness, such as operating a motor vehicle (including automobiles) or operating machinery, until they are reasonably certain quetiapine therapy does not affect them adversely. Patients should limit consumption of alcohol during treatment with quetiapine [see WARNINGS AND PRECAUTIONS].

Heat Exposure and Dehydration

Patients should be advised regarding appropriate care in avoiding overheating and dehydration [see WARNINGS AND PRECAUTIONS].

Concomitant Medication

As with other medications, patients should be advised to notify their physicians if they are taking, or plan to take, any prescription or overthe-counter drugs [see WARNINGS AND PRECAUTIONS].

Pregnancy and Nursing

Patients should be advised to notify their physician if they become pregnant or intend to become pregnant during therapy. Patients should be advised not to breast feed if they are taking quetiapine [see Use In Specific Populations].

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

Carcinogenicity studies were conducted in C57BL mice and Wistar rats. Quetiapine was administered in the diet to mice at doses of 20, 75, 250, and 750 mg/kg and to rats by gavage at doses of 25, 75, and 250 mg/kg for two years. These doses are equivalent to 0.1, 0.5, 1.5, and 4.5 times the maximum human dose for schizophrenia and bipolar mania (800 mg/day) on a mg/m² basis (mice) or 0.3, 0.9, and 3.0 times the maximum human dose on a mg/m² basis (rats). There were statistically significant increases in thyroid gland follicular adenomas in male mice at doses of 250 and 750 mg/kg or 1.5 and 4.5 times the maximum human dose on a mg/m² basis and in male rats at a dose of 250 mg/kg or 3.0 times the maximum human dose on a mg/m² basis. Mammary gland adenocarcinomas were statistically significantly increased in female rats at all doses tested (25, 75, and 250 mg/kg or 0.3, 0.9, and 3.0 times the maximum recommended human dose on a mg/m² basis).

Thyroid follicular cell adenomas may have resulted from chronic stimulation of the thyroid gland by thyroid stimulating hormone (TSH) resulting from enhanced metabolism and clearance of thyroxine by rodent liver. Changes in TSH, thyroxine, and thyroxine clearance consistent with this mechanism were observed in subchronic toxicity studies in rat and mouse and in a 1-year toxicity study in rat; however, the results of these studies were not definitive. The relevance of the increases in thyroid follicular cell adenomas to human risk, through whatever mechanism, is unknown.

Antipsychotic drugs have been shown to chronically elevate prolactin levels in rodents. Serum measurements in a 1-year toxicity study showed that quetiapine increased median serum prolactin levels a maximum of 32- and 13-fold in male and female rats, respectively. Increases in mammary neoplasms have been found in rodents after chronic administration of other antipsychotic drugs and are considered to be prolactin-mediated. The relevance of this increased incidence of prolactin-mediated mammary gland tumors in rats to human risk is unknown [see WARNINGS AND PRECAUTIONS].

Mutagenesis

The mutagenic potential of quetiapine was tested in six in vitro bacterial gene mutation assays and in an in vitro mammalian gene mutation assay in Chinese Hamster Ovary cells. However, sufficiently high concentrations of quetiapine may not have been used for all tester strains. Quetiapine did produce a reproducible increase in mutations in one Salmonella typhimurium tester strain in the presence of metabolic activation. No evidence of clastogenic potential was obtained in an in vitro chromosomal aberration assay in cultured human lymphocytes or in the in vivo micronucleus assay in rats.

Impairment of Fertility

Quetiapine decreased mating and fertility in male Sprague-Dawley rats at oral doses of 50 and 150 mg/kg or 0.6 and 1.8 times the maximum human dose on a mg/m² basis. Drug-related effects included increases in interval to mate and in the number of matings required for successful impregnation. These effects continued to be observed at 150 mg/kg even after a two-week period without treatment. The no-effect dose for impaired mating and fertility in male rats was 25 mg/kg, or 0.3 times the maximum human dose on a mg/m² basis. Quetiapine adversely affected mating and fertility in female Sprague-Dawley rats at an oral dose of 50 mg/kg, or 0.6 times the maximum human dose on a mg/m² basis. Drug-related effects included decreases in matings and in matings resulting in pregnancy, and an increase in the interval to mate. An increase in irregular estrus cycles was observed at doses of 10 and 50 mg/kg, or 0.1 and 0.6 times the maximum human dose on a mg/m² basis. The no-effect dose in female rats was 1 mg/kg, or 0.01 times the maximum human dose on a mg/m² basis.

Use In Specific Populations

Pregnancy

Pregnancy Category C

There are no adequate and well-controlled studies of SEROQUEL XR use in pregnant women. In limited published literature, there were no major malformations associated with quetiapine exposure during pregnancy. In animal studies, embryo-fetal toxicity occurred. Quetiapine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

There are limited published data on the use of quetiapine for treatment of schizophrenia and other psychiatric disorders during pregnancy. In a prospective observational study, 21 women exposed to quetiapine and other psychoactive medications during pregnancy delivered infants with no major malformations. Among 42 other infants born to pregnant women who used quetiapine during pregnancy, there were no major malformations reported (one study of 36 women, 6 case reports). Due to the limited number of exposed pregnancies, these postmarketing data do not reliably estimate the frequency or absence of adverse outcomes.

When pregnant rats and rabbits were exposed to quetiapine during organogenesis, there was no increase in the incidence of major malformations in fetuses at doses up to 2.4 times the maximum recommended human dose for schizophrenia (MRHD, 800 mg/day on a mg/m² basis); however, there was evidence of embryo-fetal toxicity. In rats, delays in skeletal ossification occurred at 0.6 and 2.4 times the MRHD and in rabbits at 1.2 and 2.4 times the MRHD. At 2.4 times the MRHD, there was an increased incidence of carpal/tarsal flexure (minor soft tissue anomaly) in rabbit fetuses and decreased fetal weights in both species. Maternal toxicity (decreased body weights and/or death) occurred at 2.4 times the MRHD in rats and at 0.6-2.4 times the MRHD (all doses) in rabbits.

In a peri/postnatal reproductive study in rats, no drug-related effects were observed when pregnant dams were treated with quetiapine at doses 0.01, 0.12, and 0.24 times the MRHD. However, in a preliminary peri/postnatal study, there were increases in fetal and pup death, and decreases in mean litter weight at 3.0 times the MRHD.

Non-Teratogenic Effects

Neonates exposed to antipsychotic drugs (including SEROQUEL XR), during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress and feeding disorder in these neonates. These complications have varied in severity; while in some cases symptoms have been self-limited, in other cases neonates have required intensive care unit support and prolonged hospitalization.

SEROQUEL XR should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Labor and Delivery

The effect of SEROQUEL XR on labor and delivery in humans is unknown.

Nursing Mothers

SEROQUEL XR was excreted into human milk. Caution should be exercised when SEROQUEL XR is administered to a nursing woman.

In published case reports, the level of quetiapine in breast milk ranged from undetectable to 170 μg/L. The estimated infant dose ranged from 0.09% to 0.43% of the weight-adjusted maternal dose. Based on a limited number (N=8) of mother/infant pairs, calculated infant daily doses range from less than 0.01 mg/kg (at a maternal daily dose up to 100 mg quetiapine) to 0.1 mg/kg (at a maternal daily dose of 400 mg).

Pediatric Use

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 [see WARNINGS AND PRECAUTIONS and ADVERSE REACTIONS].

In general, the adverse reactions observed in children and adolescents during the clinical trials with SEROQUEL 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%).

Geriatric Use

Sixty-eight patients in clinical studies with SEROQUEL XR were 65 years of age or over. In general, there was no indication of any different tolerability of SEROQUEL XR in the elderly compared to younger adults. Nevertheless, the presence of factors that might decrease pharmacokinetic clearance, increase the pharmacodynamic response to SEROQUEL XR, or cause poorer tolerance or orthostasis, should lead to consideration of a lower starting dose, slower titration, and careful monitoring during the initial dosing period in the elderly. The mean plasma clearance of quetiapine was reduced by 30% to 50% in elderly patients when compared to younger patients [see DOSAGE AND ADMINISTRATION and Pharmacokinetics].

Renal Impairment

Clinical experience with SEROQUEL XR in patients with renal impairment [see CLINICAL PHARMACOLOGY] is limited.

Hepatic Impairment

Since quetiapine is extensively metabolized by the liver, higher plasma levels are expected in the hepatically impaired population, and dosage adjustment may be needed [see DOSAGE AND ADMINISTRATION and CLINICAL PHARMACOLOGY].

Last reviewed on RxList: 6/24/2011
This monograph has been modified to include the generic and brand name in many instances.

A A A

Seroquel XR - User Reviews

Seroquel XR User Reviews

Now you can gain knowledge and insight about a drug treatment with Patient Discussions.

Here is a collection of user reviews for the medication Seroquel XR sorted by most helpful. Patient Discussions FAQs

Report Problems to the Food and Drug Administration

 

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.


Emotional Wellness

Get tips on therapy and treatment.

Related Supplements
advertisement
advertisement
Use Pill Finder Find it Now See Interactions

Pill Identifier on RxList

  • quick, easy,
    pill identification

Find a Local Pharmacy

  • including 24 hour, pharmacies

Interaction Checker

  • Check potential drug interactions
Search the Medical Dictionary for Health Definitions & Medical Abbreviations