Quetiapine Extended Release

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 quetiapine extended-release tablets therapy in place of the next scheduled injection. The need for continuing existing extrapyramidal syndrome medication should be re-evaluated periodically.

9% (6/309) on placebo. Somnolence was the only adverse reaction leading to discontinuation that occurred at an incidence of ≥ 2% in quetiapine extended-release tablets in MDD trials.

Commonly Observed Adverse Reactions in Short-Term, Placebo-Controlled Trials:

In short-term placebo-controlled studies for schizophrenia the most commonly observed adverse reactions associated with the use of quetiapine extended-release tablets (incidence of 5% or greater) and observed at a rate on quetiapine extended-release tablets at least twice that of placebo were somnolence (25%), dry mouth (12%), dizziness (10%), and dyspepsia (5%).

Adverse Reactions occurring at an Incidence of 2% or More Among quetiapine extended-release tablets Treated Patients in Short-Term, Placebo-Controlled Trials. Table 12 enumerates the incidence, rounded to the nearest percent, of adverse reactions that occurred during acute therapy of schizophrenia (up to 6 weeks) in 2% or more in patients treated with quetiapine extended-release tablets (doses ranging from 300 to 800 mg/day) where the incidence in patients treated with quetiapine extended-release tablets was greater than the incidence in placebo-treated patients.

Table 12:

Adverse Reactions in 6-Week Placebo-Controlled Clinical Trials for the Treatment of Schizophrenia Preferred Term Quetiapine extended-release tablets (N=951) Placebo (N=319) Somnolence 1 25% 10% Dry Mouth 12% 1% Dizziness 10% 4% Extrapyramidal Symptoms 2 8% 5% Orthostatic Hypotension 7% 5% Constipation 6% 5% Dyspepsia 5% 2% Heart Rate Increased 4% 1% Tachycardia 3% 1% Fatigue 3% 2% Hypotension 3% 1% Vision Blurred 2% 1% Toothache 2% 0% Increased Appetite 2% 0% Muscle Spasms 2% 1% Tremor 2% 1% Akathisia 2% 1% Anxiety 2% 1% Schizophrenia 2% 1% Restlessness 2% 1% 1.

Somnolence combines adverse reaction terms somnolence and sedation. 2. Extrapyramidal symptoms include the terms: cogwheel rigidity, drooling, dyskinesia dystonia, extrapyramidal disorder, hypertonia, movement disorder, muscle rigidity, parkinsonism, parkinsonian gait, and tardive dyskinesia.

In a 3-week, placebo-controlled study in bipolar mania the most commonly observed adverse reactions associated with the use of quetiapine extended-release tablets (incidence of 5% or greater) and observed at a rate on quetiapine extended-release tablets at least twice that of placebo were somnolence (50%), dry mouth (34%), dizziness (10%), constipation (10%), weight gain (7%), dysarthria (5%), and nasal congestion (5%).

Table 13 enumerates the incidence, rounded to the nearest percent, of adverse reactions that occurred during acute therapy of bipolar mania (up to 3 weeks) in 2% or more of patients treated with quetiapine extended-release tablets (doses ranging from 400 to 800 mg/day) where the incidence in patients treated with quetiapine extended-release tablets was greater than the incidence in placebo-treated patients.

Table 13:

Adverse Reactions in a 3-Week Placebo-Controlled Clinical Trial for the Treatment of Bipolar Mania Preferred Term Quetiapine extended-release tablets (N=151) Placebo (N=160) Somnolence 1 50% 12% Dry Mouth 34% 7% Dizziness 10% 4% Constipation 10% 3% Dyspepsia 7% 4% Fatigue 7% 4% Weight Gain 7% 1% Extrapyramidal Symptoms 2 7% 4% Nasal Congestion 5% 1% Dysarthria 5% 0% Increased Appetite 4% 2% Back Pain 3% 2% Toothache 3% 1% Heart Rate Increased 3% 0% Abnormal Dreams 3% 0% Orthostatic Hypotension 3% 0% Tachycardia 2% 1% Vision Blurred 2% 1% Sluggishness 2% 1% Lethargy 2% 1% 1.

Somnolence combines adverse reaction terms somnolence and sedation. 2. Extrapyramidal symptoms include the terms: muscle spasms, akathisia, cogwheel rigidity, dystonia, extrapyramidal disorder, restlessness and tremor. In the 8-week placebo-controlled bipolar depression study in adults, the most commonly observed adverse reactions associated with the use of quetiapine extended-release tablets (incidence of 5% or greater) and observed at a rate on quetiapine extended-release tablets at least twice that of placebo were somnolence (52%), dry mouth (37%), increased appetite (12%), weight gain (7%), dyspepsia (7%), and fatigue (6%).

Table 14 enumerates the incidence, rounded to the nearest percent, of adverse reactions that occurred during acute therapy of bipolar depression (up to 8 weeks) in 2% or more of adult patients treated with quetiapine extended-release tablets 300 mg/day where the incidence in patients treated with quetiapine extended-release tablets was greater than the incidence in placebo-treated patients.

Table 14:

Adverse Reactions in an 8-Week Placebo-Controlled Clinical Trial for the Treatment of Bipolar Depression Preferred Term Quetiapine extended-release tablets (N=137) Placebo (N=140) Somnolence 1 52% 13% Dry Mouth 37% 7% Dizziness 13% 11% Increased Appetite 12% 6% Constipation 8% 6% Dyspepsia 7% 1% Weight Gain 7% 1% Fatigue 6% 2% Irritability 4% 3% Viral Gastroenteritis 4% 1% Arthralgia 4% 1% Extrapyramidal Symptoms 2 4% 1% Paresthesia 3% 2% Back Pain 3% 1% Muscle Spasms 3% 1% Toothache 3% 0% Abnormal Dreams 3% 0% Ear Pain 2% 1% Seasonal Allergy 2% 1% Sinusitis 2% 1% Decreased Appetite 2% 1% Myalgia 2% 1% Disturbance in Attention 2% 1% Migraine 2% 1% Restless Legs Syndrome 2% 1% Anxiety 2% 1% Sinus Headache 2% 1% Libido Decreased 2% 1% Pollakiuria 2% 1% Sinus Congestion 2% 1% Hyperhidrosis 2% 1% Orthostatic Hypotension 2% 1% Urinary Tract Infection 2% 0% Heart Rate Increased 2% 0% Neck Pain 2% 0% Dysarthria 2% 0% Akathisia 2% 0% Hypersomnia 2% 0% Mental Impairment 2% 0% Confusional State 2% 0% Disorientation 2% 0% 1.

Somnolence combines adverse reaction terms somnolence and sedation. 2. Extrapyramidal symptoms include the terms: dystonia, extrapyramidal disorder, hypertonia, and tremor. In the 6-week placebo-controlled fixed dose adjunctive therapy clinical trials, for MDD, the most commonly observed adverse reactions associated with the use of quetiapine extended-release tablets (incidence of 5% or greater and observed at a rate on quetiapine extended-release tablets and at least twice that of placebo) were somnolence (150 mg: 37%; 300 mg: 43%), dry mouth (150 mg: 27%; 300 mg: 40%), fatigue (150 mg: 14%; 300 mg: 11%), constipation (300 mg only: 11%) and weight increased (300 mg only: 5%).

Table 15 enumerates the incidence, rounded to the nearest percent, of adverse reactions that occurred during short-term adjunctive therapy of MDD (up to 6 weeks) in 2% or more of patients treated with quetiapine extended-release tablets (at doses of either 150 mg or 300 mg/day) where the incidence in patients treated with quetiapine extended-release tablets was greater than the incidence in placebo-treated patients.

Table 15:

Adverse Reactions in Placebo-Controlled Adjunctive Therapy Clinical Trials for the Treatment of MDD by Fixed Dose Preferred Term Quetiapine extended-release tablets 150 mg (N=315) Quetiapine extended-release tablets 300 mg (N=312) Placebo (N=309) Somnolence 1 37% 43% 9% Dry Mouth 27% 40% 8% Fatigue 14% 11% 4% Dizziness 11% 12% 7% Nausea 7% 8% 7% Constipation 6% 11% 4% Irritability 4% 2% 3% Extrapyramidal Symptoms 2 4% 6% 4% Vomiting 3% 1% 1% Upper Respiratory Tract Infection 3% 2% 2% Weight Increased 3% 5% 0% Increased Appetite 3% 5% 3% Back pain 3% 3% 1% Vertigo 2% 2% 1% Vision Blurred 2% 1% 1% Dyspepsia 2% 3% 2% Influenza 2% 1% 0% Fall 2% 0% 1% Muscle Spasms 2% 1% 1% Lethargy 2% 1% 1% Akathisia 2% 2% 1% Abnormal Dreams 2% 2% 1% Anxiety 2% 2% 1% Depression 2% 1% 1% 1.

Somnolence combines the adverse reaction terms somnolence and sedation. 2. Extrapyramidal symptoms include the terms: cogwheel rigidity, drooling, dyskinesia, extrapyramidal disorder, hypertonia, hypokinesia, psychomotor hyperactivity, restlessness, and tremor.

Adverse Reactions in clinical trials with quetiapine and not listed elsewhere in the label: Pyrexia, nightmares, peripheral edema, dyspnea, palpitations, rhinitis, eosinophilia, hypersensitivity, elevations in gamma-GT levels, and elevations in serum creatine phosphokinase (not associated with NMS), somnambulism (and other related events), hypothermia, decreased platelets, galactorrhea, bradycardia (which may occur at or near initiation of treatment and be associated with hypotension and/ or syncope), and priapism.

Extrapyramidal Symptoms (EPS):

Dystonia Class Effect : Symptoms of dystonia, prolonged abnormal contractions of muscle groups, may occur in susceptible individuals during the first few days of treatment. Dystonic symptoms include: spasm of the neck muscles, sometimes progressing to tightness of the throat, swallowing difficulty, difficulty breathing, and/or protrusion of the tongue.

While these symptoms can occur at low doses, they occur more frequently and with greater severity with high potency and at higher doses of first generation antipsychotic drugs. An elevated risk of acute dystonia is observed in males and younger age groups.

Four methods were used to measure EPS: (1) Simpson-Angus total score (mean change from baseline) which evaluates Parkinsonism and akathisia, (2) Barnes Akathisia Rating Scale (BARS) Global Assessment Score, (3) incidence of spontaneous complaints of EPS (akathisia, akinesia, cogwheel rigidity, extrapyramidal syndrome, hypertonia, hypokinesia, neck rigidity, and tremor), and (4) use of anticholinergic medications to treat EPS.

Adults :

In placebo-controlled clinical trials with quetiapine, utilizing doses up to 800 mg per day, the incidence of any adverse reactions related to EPS ranged from 8% to 11% for quetiapine and 4% to 11% for placebo. In three-arm placebo-controlled clinical trials for the treatment of schizophrenia, utilizing doses between 300 mg and 800 mg of quetiapine extended-release tablets, the incidence of any adverse reactions related to EPS was 8% for quetiapine extended-release tablets and 8% for SEROQUEL (without evidence of being dose related), and 5% in the placebo group.

In these studies, the incidence of the individual adverse reactions (akathisia, extrapyramidal disorder, tremor, dyskinesia, dystonia, restlessness, and muscle rigidity) was generally low and did not exceed 3% for any treatment group.

At the end of treatment, the mean change from baseline in SAS total score and BARS Global Assessment score was similar across the treatment groups. The use of concomitant anticholinergic medications was infrequent and similar across the treatment groups.

The incidence of extrapyramidal symptoms was consistent with that seen with the profile of SEROQUEL in schizophrenia patients. In Tables 16 to 19, dystonic event included nuchal rigidity, hypertonia, dystonia, muscle rigidity, oculogyration; parkinsonism included cogwheel rigidity, tremor, drooling, hypokinesia; akathisia included akathisia, psychomotor agitation; dyskinetic event included tardive dyskinesia, dyskinesia, choreoathetosis; and other extrapyramidal event included restlessness, extrapyramidal disorder, movement disorder.

8% in the placebo group. 0% for any adverse reaction. 3 1. There were no adverse reactions with the preferred term of dyskinetic event. 7% in the placebo group. 5% for any individual adverse reaction. 0 1. There were no adverse reactions with the preferred term of dyskinetic event.

2% for the placebo group. 6 Children and Adolescents The information below is derived from a clinical trial database for SEROQUEL consisting of over 1,000 pediatric patients. This database includes 677 adolescents (13 to 17 years old) exposed to SEROQUEL for the treatment of schizophrenia and 393 children and adolescents (10 to 17 years old) exposed to SEROQUEL for the treatment of acute bipolar mania.

7%, respectively. 7% and 0% for placebo). 4%, respectively. 1% vs. 1% vs. 0%).

Commonly Observed Adverse Reactions in Short-Term, Placebo-Controlled Trials:

In an acute (8-week) quetiapine extended-release tablets trial in children and adolescents (10 to 17 years of age) with bipolar depression, in which efficacy was not established, the most commonly observed adverse reactions associated with the use of quetiapine extended-release tablets (incidence of 5% or greater and at least twice that for placebo) were: dizziness (7%), diarrhea (5%), fatigue (5%) and nausea (5%).

In therapy for schizophrenia (up to 6 weeks), the most commonly observed adverse reactions associated with the use of quetiapine in adolescents (incidence of 5% or greater and quetiapine incidence at least twice that for placebo) were somnolence (34%), dizziness (12%), dry mouth (7%), tachycardia (7%).

In bipolar mania therapy (up to 3 weeks) the most commonly observed adverse reactions associated with the use of quetiapine in children and adolescents (incidence of 5% or greater and quetiapine incidence at least twice that for placebo) were somnolence (53%), dizziness (18%), fatigue (11%), increased appetite (9%), nausea (8%), vomiting (8%), tachycardia (7%), dry mouth (7%), and weight increased (6%).

Adverse Reactions Occurring at an Incidence of ≥ 2% among SEROQUEL Treated Patients in Short-Term, Placebo-Controlled Trials Schizophrenia (Adolescents, 13 to 17 years old) The following findings were based on a 6-week placebo-controlled trial in which quetiapine was administered in either doses of 400 or 800 mg/day.

Table 20 enumerates the incidence, rounded to the nearest percent, of adverse reactions that occurred during therapy (up to 6 weeks) of schizophrenia in 2% or more of patients treated with SEROQUEL (doses of 400 or 800 mg/day) where the incidence in patients treated with SEROQUEL was greater than the incidence in placebo-treated patients.

Adverse reactions that were potentially dose-related with higher frequency in the 800 mg group compared to the 400 mg group included dizziness (8% vs. 15%), dry mouth (4% vs. 10%), and tachycardia (6% vs. 11%).

Table 20:

Adverse Reactions in a 6-Week Placebo-Controlled Clinical Trial for the Treatment of Schizophrenia in Adolescent Patients Preferred Term SEROQUEL 400 mg (N=73) SEROQUEL 800 mg (N=74) Placebo (N=75) Somnolence 1 33% 35% 11% Dizziness 8% 15% 5% Dry Mouth 4% 10% 1% Tachycardia 2 6% 11% 0% Irritability 3% 5% 0% Arthralgia 1% 3% 0% Asthenia 1% 3% 1% Back Pain 1% 3% 0% Dyspnea 0% 3% 0% Abdominal Pain 3% 1% 0% Anorexia 3% 1% 0% Tooth Abscess 3% 1% 0% Dyskinesia 3% 0% 0% Epistaxis 3% 0% 1% Muscle Rigidity 3% 0% 0% 1.

Somnolence combines adverse reaction terms somnolence and sedation. 2. Tachycardia combines adverse reaction terms tachycardia and sinus tachycardia. Bipolar I Mania (Children and Adolescents 10 to 17 years old) The following findings were based on a 3-week placebo-controlled trial in which quetiapine was administered in either doses of 400 or 600 mg/day.

Table 21 enumerates the incidence, rounded to the nearest percent, of adverse reactions that occurred during therapy (up to 3 weeks) of bipolar mania in 2% or more of patients treated with SEROQUEL (doses of 400 or 600 mg/day) where the incidence in patients treated with SEROQUEL was greater than the incidence in placebo-treated patients.

Adverse reactions that were potentially dose-related with higher frequency in the 600 mg group compared to the 400 mg group included somnolence (50% vs. 57%), nausea (6% vs. 10%) and tachycardia (6% vs. 9%).

Table 21:

Adverse Reactions in a 3-Week Placebo-Controlled Clinical Trial for the Treatment of Bipolar Mania in Children and Adolescent Patients Preferred Term SEROQUEL 400 mg (N=95) SEROQUEL 600 mg (N=98) Placebo (N=90) Somnolence 1 50% 57% 14% Dizziness 19% 17% 2% Nausea 6% 10% 4% Fatigue 14% 9% 4% Increased Appetite 10% 9% 1% Tachycardia 2 6% 9% 0% Dry Mouth 7% 7% 0% Vomiting 8% 7% 3% Nasal Congestion 3% 6% 2% Weight Increased 6% 6% 0% Irritability 3% 5% 1% Pyrexia 1% 4% 1% Aggression 1% 3% 0% Musculoskeletal Stiffness 1% 3% 1% Accidental Overdose 0% 2% 0% Acne 3% 2% 0% Arthralgia 4% 2% 1% Lethargy 2% 2% 0% Pallor 1% 2% 0% Stomach Discomfort 4% 2% 1% Syncope 2% 2% 0% Vision Blurred 3% 2% 0% Constipation 4% 2% 0% Ear Pain 2% 0% 0% Paresthesia 2% 0% 0% Sinus Congestion 3% 0% 0% Thirst 2% 0% 0% 1.

Somnolence combines adverse reaction terms somnolence and sedation. 2. Tachycardia combines adverse reaction terms tachycardia and sinus tachycardia. 2 )]. 1% (1/92) for quetiapine extended-release tablets and 0% (0/100) for placebo. 1% in any treatment group.

1% (1/90) for placebo. In Tables 22 and 23, dystonic events included nuchal rigidity, hypertonia, dystonia, and muscle rigidity; parkinsonism included cogwheel rigidity and tremor; akathisia included akathisia only; dyskinetic event included tardive dyskinesia, dyskinesia and choreoathetosis; and other extrapyramidal event included restlessness and extrapyramidal disorder.

Table 22 below presents a listing of patients with adverse reactions associated with EPS in the short-term placebo-controlled SEROQUEL monotherapy trial in adolescent patients with schizophrenia (6-week duration). 0 Table 23 below presents a listing of patients with adverse reactions associated with EPS in a short-term placebo-controlled monotherapy trial in children and adolescent patients with bipolar mania (3-week duration).

0 1. There were no adverse reactions with the preferred term of dystonic or dyskinetic events. 8% in placebo-treated patients. 10) ].

Transaminase Elevations Adults:

Asymptomatic, transient and reversible elevations in serum transaminases (primarily ALT) have been reported. The proportions of adult 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 quetiapine extended-release tablets 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. 2% (219/3536) of patients treated with placebo. In a database of controlled and uncontrolled clinical trials, decreases in hemoglobin to ≤ 13 g/dL males, ≤ 12 g/dL females on at least one occasion occurred in 11% (2277/20729) of quetiapine-treated patients.

Interference with Urine Drug Screens There have been literature reports suggesting false positive results in urine enzyme immunoassays for methadone and tricyclic antidepressants in patients who have taken quetiapine. , chromatographic methods) should be considered.

3% of placebo patients, had tachycardia (>120 bpm) at any time during the trials. 4 beats per minute for placebo. This is consistent with the rates for SEROQUEL. 5% 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.

7 )]. 2 )]. 2% of patients receiving placebo. 7 )]. 5% of patients receiving SEROQUEL 800 mg compared to 0% of patients receiving placebo. 7) ]. 7% of patients receiving SEROQUEL 600 mg compared to 0% of patients receiving placebo. 7) ]. 2 Postmarketing Experience The following adverse reactions were identified during post approval use of SEROQUEL.

Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Adverse reactions reported since market introduction which were temporally related to quetiapine therapy include anaphylactic reaction, cardiomyopathy, drug reaction with eosinophilia and systemic symptoms (DRESS), hyponatremia, myocarditis, nocturnal enuresis, pancreatitis, retrograde amnesia, rhabdomyolysis, syndrome of inappropriate antidiuretic hormone secretion (SIADH), Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), decreased platelet count, serious liver reactions (including hepatitis, liver necrosis, and hepatic failure), agranulocytosis, intestinal obstruction, ileus, colon ischemia, sleep apnea, urinary retention, and acute generalized exanthematous pustulosis (AGEP), confusional state and cutaneous vasculitis, and fecal incontinence.

Bezoar observed in overdosage [See Overdosage (10) ] .

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 to 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 4,400 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 1,000 patients treated) are provided in Table 2.

Table 2:

Drug-Placebo Difference in Number of Cases of Suicidality per 1,000 Patients Treated Age Range Drug-Placebo Difference in Number of Cases of Suicidality per 1,000 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. , 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 non-psychiatric, 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 quetiapine extended-release tablets 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, including quetiapine extended-release tablets, 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.

3 Cerebrovascular Adverse Reactions, Including Stroke, in Elderly Patients with Dementia-Related Psychosis In placebo-controlled trials with risperidone, aripiprazole, and olanzapine in elderly subjects with dementia, there was a higher incidence of cerebrovascular adverse reactions (cerebrovascular accidents and transient ischemic attacks), including fatalities, compared to placebo-treated subjects.

1) ]. 4 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. ) 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. 5 Metabolic Changes Atypical antipsychotic drugs have been associated with metabolic changes that include hyperglycemia/diabetes mellitus, dyslipidemia, and body weight gain.

While all of the drugs in the class have been shown to produce some metabolic changes, each drug has its own specific risk profile. 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 metabolic profiles should be managed as clinically appropriate. 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 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.

, 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.

8%) 1. Includes SEROQUEL and quetiapine extended-release tablets data. 6%. 8 mg/dL for quetiapine. 05 mg/dL for placebo. 6% of patients; n=581). Table 4 shows the percentage of patients with shifts in blood glucose to ≥ 126 mg/dL from normal baseline in MDD adjunct therapy trials by dose.

2) ] . 6 mg/dL. In this study, there were no patients in the quetiapine extended-release tablets or placebo-treated groups with a baseline normal fasting glucose level (< 100 mg/dL) that had an increase in blood glucose level ≥ 126 mg/dL.

There was one patient in the quetiapine extended-release tablets group with a baseline borderline fasting glucose level (≥ 100 mg/dL) and < 126 mg/dL) who had an increase in blood glucose level of > 126 mg/dL compared to zero patients in the placebo group.

70 mg/dL. 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 blood glucose level of ≥ 126 mg/dL.

Dyslipidemia Adults:

Table 5 shows the percentage of patients with changes in cholesterol and triglycerides from baseline by indication in clinical trials with quetiapine extended-release tablets.

Table 5:

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 1 Quetiapine extended-release tablets 718 67 (9%) Placebo 232 21 (9%) Bipolar Depression 2 Quetiapine extended-release tablets 85 6 (7%) Placebo 106 3 (3%) Bipolar Mania 3 Quetiapine extended-release tablets 128 9 (7%) Placebo 134 5 (4%) Major Depressive Disorder (Adjunct Therapy) 1 Quetiapine extended-release tablets 420 67 (16%) Placebo 213 15 (7%) Triglycerides ≥ 200 mg/dL Schizophrenia 1 Quetiapine extended-release tablets 659 118 (18%) Placebo 214 11 (5%) Bipolar Depression 2 Quetiapine extended-release tablets 84 7 (8%) Placebo 93 7 (8%) Bipolar Mania 3 Quetiapine extended-release tablets 102 15 (15%) Placebo 125 8 (6%) Major Depressive Disorder (Adjunct Therapy) 1 Quetiapine extended-release tablets 458 75 (16%) Placebo 223 18 (8%) LDL-Cholesterol ≥ 160 mg/dL Schizophrenia 1 Quetiapine extended-release tablets 691 47 (7%) Placebo 227 17 (8%) Bipolar Depression 2 Quetiapine extended-release tablets 86 3 (4%) Placebo 104 2 (2%) Bipolar Mania 3 Quetiapine extended-release tablets 125 5 (4%) Placebo 135 2 (2%) Major Depressive Disorder (Adjunct Therapy) 1 Quetiapine extended-release tablets 457 51 (11%) Placebo 219 21 (10%) HDL-Cholesterol ≤ 40 mg/dL Schizophrenia 1 Quetiapine extended-release tablets 600 87 (15%) Placebo 195 23 (12%) Bipolar Depression 2 Quetiapine extended-release tablets 78 7 (9%) Placebo 83 6 (7%) Bipolar Mania 3 Quetiapine extended-release tablets 100 19 (19%) Placebo 115 15 (13%) Major Depressive Disorder (Adjunct Therapy) 1 Quetiapine extended-release tablets 470 34 (7%) Placebo 230 19 (8%) 1.

6 weeks duration 2. 8 weeks duration 3. 3 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 6 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 6:

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 1 N Patients n (%) Cholesterol ≥ 240 mg/dL Quetiapine extended-release tablets 150 mg 223 41 (18%) Quetiapine extended-release tablets 300 mg 197 26 (13%) Placebo 213 15 (7%) Triglycerides ≥ 200 mg/dL Quetiapine extended-release tablets 150 mg 232 36 (16%) Quetiapine extended-release tablets 300 mg 226 39 (17%) Placebo 223 18 (8%) LDL-Cholesterol ≥ 160 mg/dL Quetiapine extended-release tablets 150 mg 242 29 (12%) Quetiapine extended-release tablets 300 mg 215 22 (10%) Placebo 219 21 (10%) HDL-Cholesterol ≤ 40 mg/dL Quetiapine extended-release tablets 150 mg 238 14 (6%) Quetiapine extended-release tablets 300 mg 232 20 (9%) Placebo 230 19 (8%) 1.

2 )]. In a placebo-controlled quetiapine extended-release tablets monotherapy study (8 weeks duration) of children and adolescent patients (10 to 17 years of age) with bipolar depression, in which efficacy was not established, the percentage of children and adolescents with shifts in total cholesterol (≥200 mg/dL), triglycerides (≥150 mg/dL), LDL-cholesterol (≥ 130 mg/dL) and HDL-cholesterol (≤40 mg/dL) from baseline to clinically significant levels were: total cholesterol 8% (7/83) for quetiapine extended-release tablets vs.

6% (5/84) for placebo; triglycerides 28% (22/80) for quetiapine extended-release tablets vs. 9% (7/82) for placebo; LDL-cholesterol 2% (2/86) for quetiapine extended-release tablets vs. 4% (3/85) for placebo and HDL-cholesterol 20% (13/65) for quetiapine extended-release tablets vs 15% (11/74) for placebo.

Table 7 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 in adolescents (13 to 17 years) with schizophrenia and in children and adolescents (10 to 17 years) with bipolar mania.

Table 7:

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 1 SEROQUEL 107 13 (12%) Placebo 56 1 (2%) Bipolar Mania 2 SEROQUEL 159 16 (10%) Placebo 66 2 (3%) Triglycerides ≥ 150 mg/dL Schizophrenia 1 SEROQUEL 103 17 (17%) Placebo 51 4 (8%) Bipolar Mania 2 SEROQUEL 149 32 (22%) Placebo 60 8 (13%) LDL-Cholesterol ≥ 130 mg/dL Schizophrenia 1 SEROQUEL 112 4 (4%) Placebo 60 1 (2%) Bipolar Mania 2 SEROQUEL 169 13 (8%) Placebo 74 4 (5%) HDL-Cholesterol ≤ 40 mg/dL Schizophrenia 1 SEROQUEL 104 16 (15%) Placebo 54 10 (19%) Bipolar Mania 2 SEROQUEL 154 16 (10%) Placebo 61 4 (7%) 1.

13 to 17 years, 6 weeks duration 2. 10 to 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.

Adults:

Table 8 shows the percentage of adult patients with weight gain of ≥7% of body weight by indication.

Table 8:

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 1 Quetiapine extended-release tablets 907 90 (10%) Placebo 299 16 (5%) Bipolar Mania 2 Quetiapine extended-release tablets 138 7 (5%) Placebo 150 0 (0%) Bipolar Depression 3 Quetiapine extended-release tablets 110 9 (8%) Placebo 125 1 (1%) Major Depressive Disorder (Adjunctive Therapy) 1 Quetiapine extended-release tablets 616 32 (5%) Placebo 302 5 (2%) 1.

6 weeks duration 2. 3 weeks duration 3. 8 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 9 shows the percentage of adult patients with weight gain of ≥7% of body weight for MDD by dose. 2 )]. In a clinical trial for quetiapine extended-release tablets in children and adolescents (10 to 17 years of age) with bipolar depression, in which efficacy was not established, the percentage of patients with weight gain ≥7% of body weight at any time was 15% (14/92) for quetiapine extended-release tablets vs.

10% (10/100) for placebo. 4 kg in the quetiapine extended-release tablets group vs. 6 kg in the placebo group. Weight gain was greater in patients 10 to 12 years of age compared to patients 13 to 17 years of age. The percentage of patients 10 to 12 years of age with weight gain ≥7% at any time was 28% (7/25) for quetiapine extended-release tablets vs.

0% (0/28) for placebo. 4% (7/67) for quetiapine extended-release tablets vs. 9% (10/72) for placebo. Table 10 shows the percentage of children and adolescents with weight gain ≥7% of body weight in clinical trials with SEROQUEL in adolescents (13 to 17 years) with schizophrenia and in children and adolescents (10 to 17 years) with bipolar mania.

Table 10:

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 1 SEROQUEL 111 23 (21%) Placebo 44 3 (7%) Bipolar Mania 2 SEROQUEL 157 18 (12%) Placebo 68 0 (0%) 1.

6 weeks duration 2. 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. 4 kg. Forty-five percent of the patients gained ≥ 7% of their body weight, not adjusted for normal growth.

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. 6 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.

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.

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. Tardive dyskinesia 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, quetiapine extended-release tablets 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 quetiapine extended-release tablets, drug discontinuation should be considered.

However, some patients may require treatment with quetiapine despite the presence of the syndrome. 7 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 ά1-adrenergic antagonist properties.

2% (2/928) on placebo. 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).

If hypotension occurs during titration to the target dose, a return to the previous dose in the titration schedule is appropriate. 8 Falls Atypical antipsychotic drugs, including quetiapine extended-release tablets, may cause somnolence, postural hypotension, motor and sensory instability, which may lead to falls and, consequently, fractures or other injuries.

For patients with diseases, conditions, or medications that could exacerbate these effects, complete fall risk assessments when initiating antipsychotic treatment and recurrently for patients on long-term antipsychotic therapy. 2 )].

0% (36/100) for placebo. 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.

10 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. Agranulocytosis has also been reported.

Agranulocytosis has been reported with quetiapine, including fatal cases and cases in patients without pre-existing risk factors. Neutropenia should be considered in patients presenting with infection, particularly in the absence of obvious predisposing factor(s), or in patients with unexplained fever, and should be managed as clinically appropriate.

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 quetiapine extended-release tablets 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 <1,000/mm 3 ) should discontinue quetiapine extended-release tablets and have their WBC followed until recovery.

2) ]. 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.

12 QT Prolongation In clinical trials quetiapine was not associated with a persistent increase in QT intervals. However, the QT effect was not systematically evaluated in a thorough QT study. 1) ] , in patients with concomitant illness, and in patients taking medicines known to cause electrolyte imbalance or increase QT interval.

, pentamidine, levomethadyl acetate, methadone). Quetiapine should also be avoided in circumstances that may increase the risk of occurrence of torsade de pointes and/or sudden death including (1) a history of cardiac arrhythmias such as bradycardia; (2) hypokalemia or hypomagnesemia; (3) concomitant use of other drugs that prolong the QTc interval; and (4) presence of congenital prolongation of the QT interval.

, cardiovascular disease, family history of QT prolongation, the elderly, congestive heart failure and heart hypertrophy). 3% (3/928) on placebo. 2% (2/954) on placebo. , Alzheimer’s dementia. Conditions that lower the seizure threshold may be more prevalent in a population of 65 years or older.

14 Hypothyroidism Adults: Clinical trials with quetiapine demonstrated dose-related decreases in thyroid hormone levels. The reduction in total and free thyroxine (T 4 ) 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 T 4 , irrespective of the duration of treatment. The mechanism by which quetiapine effects the thyroid axis is unclear.

If there is an effect on the hypothalamic-pituitary axis, measurement of TSH alone may not accurately reflect a patient’s thyroid status. Therefore, both TSH and free T 4 , in addition to clinical assessment, should be measured at baseline and at follow-up.

4% (18/534) on placebo experienced increased thyroid stimulating hormone (TSH). 7% (26/3489) of SEROQUEL patients did experience TSH increases in monotherapy studies. Some patients with TSH increases needed replacement thyroid treatment.

9% (956/19412). In eight patients, where TBG was measured, levels of TBG were unchanged. Table 11 shows the incidence of these shifts in short term placebo-controlled clinical trials. 7% (105/3912) 1. Based on shifts from normal baseline to potentially clinically important value at any time post-baseline.

8 x LLN (pmol/L) and shift in TSH is > 5 mIU/L at any time. 2. Includes SEROQUEL and quetiapine extended-release tablets data. 0 % (1/3007) for placebo. 2) ]. 9% (8/280) vs. 8% (8/289) vs. 0% (0/145), respectively. Of the SEROQUEL treated patients with elevated TSH levels, 1 had simultaneous low free T 4 level at end of treatment.

6% (51/1968) on placebo. 2 )]. 7% (9/104) for SEROQUEL compared to 0% (0/39) for placebo in females. Like other drugs that antagonize dopamine D 2 receptors, quetiapine extended-release tablets 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.

1) ] . Published epidemiologic studies have shown inconsistent results when exploring the potential association between hyperprolactinemia and breast cancer. 16 Potential for Cognitive and Motor Impairment Somnolence was a commonly reported adverse reaction reported in patients treated with quetiapine especially during the 3-day period of initial dose titration.

3% (33/319) of placebo patients. 9% (18/140) of placebo patients. 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 quetiapine extended-release tablets 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).

17 Body Temperature Regulation Disruption of the body's ability to reduce core body temperature has been attributed to antipsychotic agents. , exercising strenuously, exposure to extreme heat, receiving concomitant medication with anticholinergic activity, or being subject to dehydration.

18 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.

Quetiapine extended-release tablets and other antipsychotic drugs should be used cautiously in patients at risk for aspiration pneumonia. 19 Discontinuation Syndrome Acute withdrawal symptoms, such as insomnia, nausea and vomiting have been described after abrupt cessation of atypical antipsychotic drugs, including quetiapine.

7% (71/1065) for placebo. 3% in any treatment group and usually resolved after 1-week post-discontinuation. 1) ]. 20 Anticholinergic (antimuscarinic) Effects Norquetiapine, an active metabolite of quetiapine, has moderate to strong affinity for several muscarinic receptor subtypes.

This contributes to anticholinergic adverse reactions when quetiapine extended-release tablets are used at therapeutic doses, taken concomitantly with other anticholinergic medications, or taken in overdose. 1) ] . Constipation was a commonly reported adverse event in patients treated with quetiapine and represents a risk factor for intestinal obstruction.

Intestinal obstruction has been reported with quetiapine, including fatal reports in patients who were receiving multiple concomitant medications that decrease intestinal motility.