SEROQUEL (quetiapine) is indicated for the management of the manifestations of schizophrenia. The antipsychotic efficacy of SEROQUEL was established in short-term (6-week) controlled inpatient trials. The efficacy of SEROQUEL in long-term use, that is, for more than 6 weeks, has not been systematically evaluated in controlled trials of patients with manifestations of schizophrenia.

SEROQUEL is indicated as monotherapy for the acute management of manic episodes associated with bipolar disorder.

The efficacy of SEROQUEL in bipolar disorder-mania was established in two 12-week clinical trials of bipolar patients. The safety and effectiveness of SEROQUEL for long-term use, and for prophylactic use in bipolar disorder has not been evaluated.

SEROQUEL is not indicated in elderly patients with dementia. See Warnings and Precautions, Serious Warnings and Precautions Box and Special Populations.

The safety and efficacy of SEROQUEL in children under the age of 18 years have not been established.

SEROQUEL (quetiapine) is contraindicated in patients with a known hypersensitivity to this medication or any of its ingredients. For a complete listing, see Dosage Forms, Composition and Packaging.

Although not reported with SEROQUEL (quetiapine) disruption of the body's ability to reduce core body temperature has been attributed to antipsychotic agents. Appropriate care is advised when prescribing SEROQUEL for patients who will be experiencing conditions which may contribute to an elevation of core temperature, e.g., exercising strenuously, exposure to extreme heat, receiving concomitant medication with anticholinergic activity, or being subject to dehydration.

Acute withdrawal symptoms such as nausea, vomiting, and insomnia have very rarely been described after abrupt cessation of antipsychotic drugs including SEROQUEL. Gradual withdrawal is advisable.

As with other drugs that have high α1 adrenergic receptor blocking activity, SEROQUEL may induce orthostatic hypotension, dizziness, and sometimes syncope, especially during the initial dose titration period. Syncope was reported in 1% (23/2371) of patients treated with SEROQUEL, compared with 0% (0/404) on placebo, and 0.4% (2/527) on active control drugs. The risk of hypotension and syncope may be reduced by more gradual titration to the target dose (see Dosage and Administration). SEROQUEL should be used with caution in patients with known cardiovascular disease (e.g., history of myocardial infarction or ischemic heart disease, heart failure or conduction abnormalities), cerebrovascular disease, or other conditions predisposing to hypotension (e.g., dehydration, hypovolemia and treatment with antihypertensive medications) (see Overdosage).

In short-term placebo-controlled schizophrenia trials, SEROQUEL-treated patients showed mean increases from baseline in cholesterol and triglyceride of 11% and 17%, respectively, compared to mean decreases in the placebo-treated patients. LDL cholesterol was not measured in these trials.

Uncommon cases of small elevations in non-fasting serum triglyceride levels and total cholesterol (predominantly LDL cholesterol) have been observed during treatment with SEROQUEL in several clinical trials (see Adverse Reactions).

As with some other antipsychotics, exacerbation of pre-existing diabetes, hyperglycemia, diabetic ketoacidosis, and diabetic coma including some fatal cases have been reported very rarely (<0.01%) during the use of SEROQUEL, sometimes in patients with no reported history of hyperglycemia (see Adverse Reactions, Post-Market Adverse Drug Reactions).

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 events is not completely understood. However, epidemiological studies suggest an increased risk of treatment-emergent hyperglycemia-related adverse events in patients treated with the atypical antipsychotics. Precise risk estimates for hyperglycemia-related adverse events in patients treated with atypical antipsychotics are not available.

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. Patients with risk factors for diabetes mellitus (e.g., 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. Patients with an established diagnosis of diabetes mellitus who are started on atypical antipsychotics should be monitored regularly for worsening of glucose control.

Elevation of prolactin levels was not seen in clinical trials with SEROQUEL, increased prolactin levels were observed in rat studies with this compound. As is common with compounds which stimulate prolactin release, the administration of SEROQUEL resulted in an increase in the incidence of mammary neoplasms in rats. The physiological differences between rats and humans with regard to prolactin make the clinical significance of these findings unclear. To date, neither clinical nor epidemiological studies have shown an association between chronic administration of drugs that stimulate prolactin release, and mammary tumorigenesis. Tissue culture experiments, however, indicate that approximately one third of human breast cancers are prolactin dependent in vitro; a factor of potential importance if prescription of these drugs is contemplated in a patient with previously detected breast cancer.

Possible manifestations associated with elevated prolactin levels are amenorrhea, galactorrhea, and menorrhagia.

In the multiple fixed-dose schizophrenia clinical trial there were no differences in prolactin levels at study completion for SEROQUEL, across the recommended dose range, and placebo.

Clinical trials in schizophrenia demonstrated that SEROQUEL is associated with a dose-related decrease in total and free thyroxine (T₄). On average SEROQUEL was associated with about a 20% mean reduction in thyroxine levels (both total and free). Forty-two percent of SEROQUEL-treated patients showed at least a 30% reduction in total T₄ and 7% showed at least a 50% reduction. Maximum reduction of thyroxine levels generally occurred during the first two to four weeks of treatment with SEROQUEL. These reductions were maintained without adaptation or progression during longer term treatment. Decreases in T₄ were not associated with systematic changes in TSH or clinical signs or symptoms of hypothyroidism. Approximately 0.4% (12/2595) of patients treated with SEROQUEL (schizophrenia and bipolar studies combined) experienced persistent increases in TSH, and 0.25% of patients were treated with thyroid replacement.

In controlled schizophrenia clinical trials (up to 6 weeks), mean weight gain was approximately 2.3 kg compared to a mean weight gain of 0.1 kilograms in patients taking placebo (n=427). In open-label extension trials, after 9 to 13 weeks of quetiapine monotherapy, the mean weight increase was 1.58 kg (n=170). After 53 to 78 weeks of treatment, the mean weight increase was 1.98 kg (n=137). These data are obtained from uncontrolled, open-label trials; the relevance of these findings to clinical practice is unknown. Weight change over time appeared to be independent of quetiapine dose (see Adverse Reactions).

In the acute placebo-controlled bipolar mania clinical trials (up to 12 weeks) mean weight gain in patients taking SEROQUEL was 1.8 kg compared to a mean weight loss of 0.1 kg in patients taking placebo. In patients completing the entire 12 weeks of treatment mean weight gain in patients taking SEROQUEL was 2.8 kg.

Consistent with its dopamine antagonist effects, SEROQUEL may have an antiemetic effect. Such an effect may mask signs of toxicity due to overdosage of other drugs, or may mask symptoms of disease such as brain tumor or intestinal obstruction.

Decreased clearance of SEROQUEL was observed in patients with mild hepatic impairment (see Actions and Clinical Pharmacology, Special Populations and Conditions). Patients with mild hepatic impairment should be started on 25 mg/day. The dose should be increased daily in increments of 25 to 50 mg/day to an effective dose, depending on the clinical response and tolerability in the individual patient. No pharmacokinetic data are available for any dose of SEROQUEL in patients with moderate or severe hepatic impairment. However, should clinical judgement deem treatment with SEROQUEL necessary, the drug should be used with great caution in patients with moderate or severe hepatic impairment (see Actions and Clinical Pharmacology, Special Populations and Conditions and Dosage and Administration).

During premarketing clinical trials, therapy with SEROQUEL was associated with elevation of hepatic transaminases, primarily ALT. Within a clinical trial database of 1892 SEROQUEL-treated schizophrenia patients, with baseline ALT levels <60 IU/L, 5.3% (101/1892) had treatment-emergent ALT elevations to >120 IU/L, 1.5% (29/1892) had elevations to >200 IU/L, and 0.2% (3/1892) had elevations to >400 IU/L. No patients had values in excess of 800 IU/L. None of the SEROQUEL-treated patients who had elevated transaminase values manifested clinical symptomatology associated with liver impairment. The majority of transaminase elevations were seen during the first two months of treatment. Most elevations were transient (80%) while patients continued on SEROQUEL therapy. Of the 101 SEROQUEL-treated patients whose enzyme levels increased to >120 IU/L, 40 discontinued treatment while their ALT values were still raised. In 114 SEROQUEL-treated patients whose baseline ALT was >90 IU/L, only 1 experienced an elevation to >400 IU/L.

In the bipolar disorder-mania trials, the proportions of patients with transaminase elevations of >3 times the upper limits of the normal reference range, was approximately 1% for both SEROQUEL-treated and placebo-treated patients.

Precautions should be exercised when using SEROQUEL in patients with pre-existing hepatic disorders, in patients who are being treated with potentially hepatotoxic drugs, or if treatment-emergent signs or symptoms of hepatic impairment appear.

For patients who have known or suspected abnormal hepatic function prior to starting SEROQUEL, standard clinical assessment, including measurement of transaminase levels is recommended. Periodic clinical reassessment with transaminase levels is recommended for such patients, as well as for patients who develop any signs and symptoms suggestive of a new onset liver disorder during SEROQUEL therapy.

Neuroleptic Malignant Syndrome is a potentially fatal symptom complex that has been reported in association with antipsychotic drugs, including SEROQUEL.

The clinical manifestations of NMS are hyperthermia, 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.

In arriving at a diagnosis, it is important to identify cases where the clinical presentation includes both serious medical illness (e.g., pneumonia, systemic infection, etc.) and untreated or inadequately treated extrapyramidal signs and symptoms. Other important considerations in the differential diagnosis include central anticholinergic toxicity, heat stroke, drug fever and primary central nervous system pathology.

The management of NMS should include immediate discontinuation of antipsychotic drugs, including SEROQUEL, and other drugs not essential to concurrent therapy; intensive symptomatic treatment and medical monitoring; and treatment of any concomitant serious medical problems for which specific treatments are available. There is no general agreement about specific pharmacological treatment regimens for uncomplicated 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.

Tardive Dyskinesia is a syndrome of potentially irreversible, involuntary, dyskinetic movements that may develop in patients treated with antipsychotic drugs. Although the prevalence of the syndrome appears to be highest among the elderly, especially elderly women, it is impossible to rely upon estimates to predict which patients are likely to develop the syndrome.

It has been hypothesized that agents with a lower EPS liability may also have a lower liability to produce TD. In schizophrenia and bipolar mania placebo-controlled clinical trials with SEROQUEL, the incidence of EPS was not statistically significantly different than placebo across the recommended therapeutic dose range. This may predict that SEROQUEL has less potential than standard antipsychotic agents to induce TD in schizophrenia and bipolar mania patients (see Adverse Reactions).

The risk of developing TD 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.

There is no known treatment for established cases of TD, 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 should be prescribed in a manner that is most likely to minimize the occurrence of TD. Chronic antipsychotic treatment should generally be reserved for patients who appear to suffer from a chronic illness that is known to respond to antipsychotic drugs, and 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 TD appear in a patient on SEROQUEL, drug discontinuation should be considered. However, some patients may require treatment with SEROQUEL despite the presence of the syndrome.

In controlled schizophrenia clinical trials, there was no difference in the incidence of seizures in patients treated with SEROQUEL or placebo (incidence of 0.4% or 3 events per 100 patient years in patients given SEROQUEL, compared with 0.5% or 6.9 events per 100 patient years for placebo). Nevertheless, as with other antipsychotics, caution is recommended when treating patients with a history of seizures or with conditions associated with a lowered seizure threshold (see Adverse Reactions).

Somnolence was a commonly reported adverse event in patients treated with SEROQUEL, especially during the initial dose titration period. Since SEROQUEL may cause sedation and impair motor skill, patients should be cautioned about performing activities requiring mental alertness, such as operating a motor vehicle or hazardous machinery, until they are reasonably certain that SEROQUEL therapy does not affect them adversely.

The development of cataracts was observed in association with quetiapine treatment in chronic dog studies at 4 times the recommended human dose. Lens changes have also been observed in patients during long-term SEROQUEL treatment, but a causal relationship to SEROQUEL use has not been established. The possibility of lenticular changes during long-term use of SEROQUEL in man, thus can not be excluded at this time. Eye examinations (e.g., slit lamp exam) prior to or shortly after initiation of treatment with SEROQUEL and at 6 month intervals thereafter, are recommended. If clinically significant lens changes associated with SEROQUEL use are observed, discontinuation of SEROQUEL should be considered.

The possibility of suicide or attempted suicide is inherent in bipolar disorder and schizophrenia, and thus close supervision and appropriate clinical management of high-risk patients should accompany drug therapy.

There is little experience with SEROQUEL in patients with renal impairment, except in a low (subclinical) single dose study (see Actions and Clinical Pharmacology, Special Populations and Conditions). SEROQUEL should thus be used with caution in patients with known renal impairment, especially during the initial dosing period (see Dosage and Administration).

Patients should be advised to notify their physician if they become pregnant or intend to become pregnant during treatment with SEROQUEL. The safety and efficacy of SEROQUEL during human pregnancy have not been established. Therefore, SEROQUEL should only be used during pregnancy if the expected benefits justify the potential risks.

The degree to which quetiapine is excreted into human milk is unknown. Women who are breast-feeding should therefore be advised to avoid breast-feeding while taking SEROQUEL.

The safety and efficacy of SEROQUEL in children under the age of 18 years have not been established.

The number of patients 65 years of age or over, with schizophrenia or related disorders, exposed to SEROQUEL, during clinical trials was limited (n=38). When compared to younger patients the mean plasma clearance of quetiapine was reduced by 30% to 50% in elderly subjects. In addition, as this population has more frequent hepatic, renal, central nervous system, and cardiovascular dysfunctions, and more frequent use of concomitant medication, caution should be exercised with the use of SEROQUEL in the elderly patient (see Dosage and Administration).

Elderly patients with dementia treated with atypical antipsychotic drugs showed increased mortality compared to placebo in a meta-analysis of 13 controlled trials of various atypical antipsychotic drugs. In two placebo-controlled trials with oral SEROQUEL in this population, the incidence of mortality was 5.5% for SEROQUEL-treated patients compared to 3.2% for placebo-treated patients. SEROQUEL is not indicated in elderly patients with dementia.

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 and other antipsychotic drugs should be used cautiously in patients at risk for aspiration pneumonia.

The stated frequencies of adverse events represent the proportion of individuals who experienced, at least once, a treatment-emergent adverse event of the type listed. An event was considered treatment-emergent if it occurred for the first time or worsened while receiving therapy following baseline evaluation.

The prescriber should be aware that the figures in the tables and tabulations cannot be used to predict the incidence of side effects in the course of usual medical practice where patient characteristics and other factors differ from those that prevailed in the clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses, and investigators. The figures cited, however, do provide the prescribing physician with some basis for estimating the relative contribution of drug and nondrug factors to the side effect incidence in the populations studied.

Overall, 3.9% of SEROQUEL (quetiapine) treated patients (n=510) discontinued treatment due to adverse events compared with 2.9% of placebo-treated patients (n=206). Somnolence, the single most common adverse event leading to withdrawal from quetiapine treatment, led to the withdrawal of four quetiapine-treated patients and no placebo-treated patients. Postural hypotension, hypotension, and/or tachycardia led to withdrawal of 1.8% of quetiapine-treated subjects, compared to 0.5% of placebo-treated subjects.

Discontinuations due to adverse events were similar for SEROQUEL (5.7%) and placebo (5.1%).

In a premarketing controlled clinical trial database of 1710 SEROQUEL-treated patients, 5% discontinued due to an adverse event. Somnolence was the single most common adverse event leading to withdrawal of 24 patients from SEROQUEL, and was the only adverse event leading to withdrawal that occurred in more than 1% of patients. Cardiovascular adverse events (e.g., postural hypotension, hypotension, tachycardia, dizziness) accounted for 20% of all subject withdrawals from quetiapine treatment. Sixteen (0.9%) quetiapine-treated subjects were withdrawn due to elevated liver enzymes. Four quetiapine-treated subjects were withdrawn because of leukopenia. Two of these subjects had at least one clinically significant, non-baseline low neutrophil count. Two quetiapine-treated subjects were withdrawn from the trial because of suspected neuroleptic malignant syndrome (NMS).

The following treatment-emergent adverse events, derived from Table 1, commonly occurred during acute therapy with SEROQUEL (incidence of at least 5%, and an incidence at least 5% higher than that observed with placebo): somnolence, dizziness, dry mouth, postural hypotension, and elevated ALT levels.

In the bipolar mania studies, the following treatment-emergent adverse events, commonly occurred during acute therapy with SEROQUEL (incidence of at least 5%, and an incidence at least 5% higher than that observed with placebo): somnolence, dry mouth, and weight gain.

Certain portions of the discussion below relating to objective or numeric safety parameters are derived from studies in patients with schizophrenia and have not been duplicated for bipolar mania trials. However, this information is also generally applicable to bipolar mania. Table 1 enumerates the incidence, rounded to the nearest percent, of treatment-emergent adverse events that occurred during acute therapy (up to 6 weeks) of schizophrenia in 1% or more of patients treated with SEROQUEL (doses of 150 mg/day or more) where the incidence in patients treated with SEROQUEL was greater than the incidence in placebo-treated patients.

Table 1: SEROQUEL

Adverse Events Reported for at Least 1% of Quetiapine-treated Subjects (doses ≥150 mg/day) and for a Higher Percentage of Quetiapine-treated Subjects than Subjects who Received Placebo in Short-term, Placebo-controlled Schizophrenia Phase II-III Trials

^a. Subjects may have had more than one adverse event.

During acute therapy (up to 6 weeks) in placebo-controlled schizophrenia clinical trials, mean weight gain in patients taking SEROQUEL was 2.3 kilograms compared to a mean weight gain of 0.1 kilograms in patients taking placebo. In open-label extension trials with quetiapine monotherapy, mean weight gain after 9 to 13 weeks was 1.58 kg, after 14 to 26 weeks, 0.26 kg, after 27 to 39 weeks, 1.66 kg, after 40 to 52 weeks, −1.53 kg and after 53 to 78 weeks, 1.98 kg (see Warnings and Precautions, Endocrine and Metabolism). In the acute placebo-controlled bipolar mania clinical trials (up to 12 weeks) mean weight gain in patients taking SEROQUEL was 1.8 kg compared to a mean weight loss of 0.1 kg in patients taking placebo. In patients completing the entire 12 weeks of treatment mean weight gain in patients taking SEROQUEL was 2.8 kg.

There have been uncommon reports (≥0.1%-<1%) of seizures in patients administered SEROQUEL, although the frequency was no greater than that observed in patients administered placebo in controlled clinical trials (see Warnings and Precautions, Neurologic).

There have been rare reports (0.01%-<0.1%) of priapism in patients administered SEROQUEL.

Somnolence may occur, usually during the first two weeks of treatment, which generally resolves with the continued administration of SEROQUEL.

As with other antipsychotics, rare cases of neuroleptic malignant syndrome have been reported in patients treated with SEROQUEL (see Warnings and Precautions, Neurologic).

As with other antipsychotics with α1 adrenergic blocking activity, SEROQUEL may induce postural hypotension, associated with dizziness, tachycardia and, in some patients, syncope, especially during the initial dose titration period (see Warnings and Precautions, Cardiovascular). In placebo-controlled clinical trials in schizophrenia, postural hypotension was reported with an incidence of 8% in SEROQUEL-treated patients compared to 2% in placebo-treated patients. SEROQUEL was associated with a mean baseline to endpoint increase in heart rate of 3.9 beats per minute, compared to 1.6 beats per minute among placebo-treated patients.

As with other antipsychotic agents, common cases (≥1%-<10%) of peripheral edema have been reported in patients treated with SEROQUEL.

As with other antipsychotic agents, common cases of mild asthenia have been reported in patients treated with SEROQUEL.

Uncommon cases of hypersensitivity including angioedema have been reported.

Between group comparisons for pooled placebo-controlled trials revealed no statistically significant SEROQUEL/placebo differences in the proportions of patients experiencing potentially important changes in ECG parameters, including QT, QTc, and PR intervals. However, the proportions of patients meeting the criteria for tachycardia were compared in four 3- to 6-week-placebo-controlled clinical trials for the treatment of schizophrenia revealing a 1% (4/399) incidence for SEROQUEL compared to 0.6% (1/156) incidence for placebo. SEROQUEL use was associated with a mean increase in heart rate, assessed by ECG, of 7 beats per minute compared to a mean increase of 1 beat per minute among placebo patients. This slight tendency to tachycardia may be related to SEROQUEL's potential for inducing orthostatic changes (see Warnings and Precautions, Cardiovascular). In bipolar disorder-mania trials the proportion of patients meeting the criteria for tachycardia was 0.5% (1/192) for SEROQUEL compared to 0% (0/178) for placebo.

Table 2 enumerates the percentage of patients with treatment-emergent extrapyramidal symptoms in a short-term acute phase clinical trial in patients with schizophrenia comparing five fixed doses of SEROQUEL with placebo (n=~50 patients per group), as assessed by: 1) spontaneous complaints of parkinsonism (extrapyramidal syndrome, hypertonia, tremor and cogwheel rigidity), or akathisia; 2) Simpson-Angus scores (mean change from baseline); and 3) use of anticholinergic medication to treat emergent EPS.

Table 2: SEROQUEL

Treatment-emergent Extrapyramidal Symptoms, Assessed by Spontaneous Reports, Simpson Scale, and Incidence of Anticholinergic Use

	Placebo	SEROQUEL
		75 mg	150 mg	300 mg	600 mg	750 mg
Spontaneous Reports of Parkinsonian Symptomsa	10%	6%	4%	4%	8%	4%
Spontaneous Reports of Akathisia	8%	2%	2%	0%	0%	2%
Simpson Scale	−0.6	−1.0	−1.2	−1.6	−1.8	−1.8
Incidence of Anticholinergic Use	14%	11%	10%	8%	12%	11%

^a. Patients may have had more than 1 parkinsonism adverse event.

There were no differences between the SEROQUEL and placebo treatment groups in the incidence of EPS or concomitant use of anticholinergics and no evidence of dose-related increase in EPS or in the use of concomitant anticholinergics across the dose range of 75-750 mg/day.

In 2 bipolar disorder-mania placebo-controlled clinical trials using variable doses of SEROQUEL, there were no differences between the SEROQUEL and placebo treatment groups in the incidence of EPS, as assessed by Simpson-Angus total scores and Barnes Akathisia rating scale, spontaneous complaints of EPS and the use of concomitant anticholinergic medications to treat EPS.

As with other antipsychotics, common cases of leucopenia and/or very rare cases (<0.01%) of neutropenia have been observed in patients administered SEROQUEL. Uncommon cases of eosinophilia have been observed.

There were no cases of persistent severe neutropenia reported in controlled clinical trials with SEROQUEL.

In placebo-controlled monotherapy clinical trials (schizophrenia and bipolar mania), among patients with a baseline neutrophil count ≥1.5×10⁹ /L, the incidence of at least one occurrence of neutrophil count <1.5×10⁹ /L was 1.34% in patients treated with SEROQUEL, compared to 0.65% in placebo-treated patients.

Asymptomatic elevations in serum transaminases (AST, ALT) or gamma-GT levels have been observed in some patients administered SEROQUEL. These elevations were usually reversible on continued SEROQUEL treatment (see Warnings and Precautions, Hepatic/Biliary/Pancreatic).

SEROQUEL treatment was associated with small dose-related decreases in thyroid hormone levels, particularly total T₄ and free T₄. The reduction in total and free T₄ was maximal within the first 2 to 4 weeks of quetiapine treatment, with no further reduction during long-term treatment. There was no evidence of clinically significant changes in TSH concentration over time. 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 (see Warnings and Precautions, Endocrine and Metabolism). Smaller decreases in total T₃ and reverse T₃ were seen only at higher doses. Levels of TBG were unchanged and in general reciprocal increases in TSH were not observed, with no indication that SEROQUEL causes clinically relevant hypothyroidism.

Uncommon cases of small elevations in nonfasting serum triglyceride levels and total cholesterol (predominantly LDL cholesterol) have been observed during treatment with SEROQUEL in several clinical trials (see Warnings and Precautions, Cardiovascular).

In one 24-week clinical trial, where LDL cholesterol was directly measured as opposed to calculated, there was a slight mean increase in total cholesterol in patients administered SEROQUEL, which was driven by increases in LDL cholesterol. The mean LDL level increased at Week 24 by 10% in patients administered SEROQUEL, which was statistically significant. The total cholesterol/HDL ratio did not change significantly during therapy with SEROQUEL. Furthermore, neither did triglycerides increase significantly or HDL cholesterol decrease during therapy. (See Warnings and Precautions, Cardiovascular.)

During post-marketing experience, leukopenia and/or neutropenia have been reported during SEROQUEL treatment. Resolution of leukopenia and/or neutropenia has followed cessation of therapy with SEROQUEL. Possible risk factors for leukopenia and/or neutropenia include pre-existing low white cell count and history of drug induced leukopenia and/or neutropenia. As with some other antipsychotics, exacerbation of pre-existing diabetes, hyperglycaemia, diabetic ketoacidosis, and diabetic coma including some fatal cases have been reported very rarely (<0.01%) during the use of SEROQUEL, sometimes in patients with no reported history of hyperglycaemia. A causal relationship to SEROQUEL has not been established.