Quetiapine Fumarate

Class: Atypical Antipsychotics
VA Class: CN709
Chemical Name: (E)-2-Butenedioate-2-[2-(4-dibenzo[b,f] [1,4]thiazepin-11-yl-1-piperazinyl)ethoxy]-ethanol (2:1) (salt)
Molecular Formula: (C₂₁H₂₅N₃O₂S)₂^•C₄H₄O₄
CAS Number: 111974-72-2
Brands: SEROquel

Warning(s)

Increased Mortality in Geriatric Patients
Substantially higher mortality rate (4.5%) in geriatric patients with dementia-related psychosis† receiving atypical antipsychotic agents (e.g., quetiapine, aripiprazole, olanzapine, risperidone) compared with those receiving placebo (2.6%).^a ⁹⁷ ⁹⁸
Most fatalities resulted from cardiac-related events (e.g., heart failure, sudden death) or infections (mostly pneumonia).^a ⁹⁷ ⁹⁸
Atypical antipsychotics are not approved for the treatment of dementia-related psychosis.^a ⁹⁷ ⁹⁸ (See Increased Mortality in Geriatric Patients with Dementia-related Psychosis under Cautions.)

Suicidality
Antidepressants increased risk of suicidal thinking and behavior (suicidality) compared with placebo in children, adolescents, and young adults (18–24 years of age) with major depressive disorder and other psychiatric disorders; balance this risk with clinical need.⁹⁹ ¹⁰⁰ ¹⁰³ (See Pediatric Use under Cautions.)
In pooled data analyses, risk of suicidality was not increased in adults >24 years of age and apparently was reduced in adults ≥65 years of age with antidepressant therapy compared with placebo.⁹⁹ ¹⁰⁰ ¹⁰³
Depression and certain other psychiatric disorders are themselves associated with an increased risk of suicide.⁹⁹ ¹⁰⁰ ¹⁰³
Appropriately monitor and closely observe all patients who are started on quetiapine therapy for clinical worsening, suicidality, or unusual changes in behavior; involve family members and/or caregivers in this process.⁹⁹ ¹⁰⁰ ¹⁰¹ ¹⁰³ (See Worsening of Depression and Suicidality Risk under Cautions.)

Introduction

Atypical or second-generation antipsychotic agent.¹ ² ³ ⁴ ⁵ ⁶ ⁷ ⁸ ⁹ ¹⁰ ¹¹ ¹² ¹³ ¹⁴ ¹⁵ ¹⁶ ¹⁷ ¹⁸ ²¹ ²² ²³ ²⁶ ²⁷ ²⁸

Uses for Quetiapine Fumarate

Schizophrenia

Symptomatic management of schizophrenia.¹ ² ³ ⁴ ⁵ ⁶ ¹⁸ ²² ²³ ²⁶

Bipolar Disorder

Management (alone or in combination with lithium or divalproex sodium) of acute manic episodes associated with bipolar I disorder.¹ ^a

Quetiapine Fumarate Dosage and Administration

General

Monitor for possible worsening of depression, suicidality, or unusual changes in behavior, especially at the beginning of therapy or during periods of dosage adjustments.⁹⁹ ¹⁰⁰ ¹⁰¹ ¹⁰³ (See Worsening of Depression and Suicidality Risk under Cautions.)

Administration

Oral Administration

Administer orally, generally 2–3 times daily without regard to meals.¹ ²⁵

When switching from other antipsychotic agents to quetiapine, abrupt discontinuance of previous agent may be acceptable for some patients with schizophrenia, but gradual discontinuance may be appropriate for others.¹ In all cases, minimize period of overlapping antipsychotic administration.¹

In patients being switched from long-acting (depot) parenteral antipsychotic therapy to oral quetiapine therapy, administer first oral dose in place of next scheduled depot injection of the long-acting preparation.¹

Periodically reevaluate need for continuing any existing drug therapy for symptomatic relief of adverse extrapyramidal effects.¹

Dosage

Available as quetiapine fumarate; dosage is expressed in terms of quetiapine.¹

Reinitiating therapy: In patients previously treated with quetiapine, dosage titration is not necessary if reinitiated after a drug-free period <1 week;¹ if reinitiated after a drug-free period >1 week, generally titrate dosage as with initial therapy.¹

Adults

Schizophrenia

Oral

Initially, 25 mg twice daily.¹ ²³

Increase dosage in increments of 25–50 mg 2 or 3 times daily on the second or third day, as tolerated, to a target dosage of 300–400 mg daily in 2 or 3 divided doses by the fourth day.¹ ²³

Make subsequent dosage adjustments at intervals of not less than 2 days, usually in increments or decrements of 25–50 mg twice daily.¹ ²⁰

Dosages ranging from 150–750 mg daily were effective in clinical trials.¹ ⁴ ⁵ ⁶ ⁷ ⁸ ¹¹ ¹⁸ ²² Dosages >300 mg daily usually do not result in greater efficacy, but dosages of 400–500 mg daily have been required in some patients.¹

Optimum duration of therapy currently not known, but efficacy of maintenance therapy with antipsychotics is well established.¹ ²² Continue therapy in responsive patients as long as clinically necessary and tolerated but at lowest possible effective dosage; reassess need for continued therapy and optimal dosage periodically (e.g., at least annually).¹ ²²

If discontinuance is considered, precautions include slow, gradual dose reduction over many months, more frequent clinician visits, and use of early intervention strategies.²²

Bipolar Disorder

Acute Mania

Oral

Initially, 100 mg daily in 2 divided doses.¹ Increase dosage (in increments of ≤100 mg daily in 2 divided doses) to 400 mg daily on the fourth day of therapy.¹ Make subsequent adjustments in increments of ≤200 mg daily to reach a dosage of up to 800 mg daily by the sixth day of therapy.¹

Majority of patients respond to 400–800 mg daily.¹

Optimum duration not established; efficacy has been demonstrated in two 12-week monotherapy trials and one 3-week adjunct therapy trial.^a If used for extended periods, periodically reevaluate long-term risks and benefits for the individual patient.¹ ^a

Prescribing Limits

Adults

Schizophrenia

Oral

Safety of dosages >800 mg daily not established.¹

Bipolar Disorder

Acute Mania

Oral

Safety of dosages >800 mg daily not established.¹

Special Populations

Hepatic Impairment

Initially, 25 mg daily; increase dosage by 25–50 mg daily according to clinical response and tolerability until an effective dosage is reached.¹

Renal Impairment

No dosage adjustment necessary.¹

Patients at Risk of Orthostatic Hypotension

Consider a slower rate of dosage titration and a lower target dosage in geriatric patients and in patients who are debilitated or have a predisposition to hypotensive reactions.¹ Adjust dosage with caution.¹

Initially, 25 mg twice daily to minimize risk of orthostatic hypotension and associated syncope.¹ If hypotension occurs during dosage titration, return to previous dosage in titration schedule.¹

Cautions for Quetiapine Fumarate

Contraindications

Known hypersensitivity to quetiapine or any ingredient in the formulation.¹

Warnings/Precautions

Warnings

Increased Mortality in Geriatric Patients with Dementia-related Psychosis

Possible increased risk of death with use of atypical antipsychotics in geriatric patients with dementia-related psychosis.^a ⁹⁷ ⁹⁸

Atypical antipsychotics are not approved for the treatment of dementia-related psychosis.^a ⁹⁷ ⁹⁸ (See Boxed Warning and see Geriatric Use under Cautions.)

Worsening of Depression and Suicidality Risk

Possible worsening of depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior in both adult and pediatric patients with major depressive disorder, whether or not they are taking antidepressants; may persist until clinically important remission occurs.⁹⁹ ¹⁰⁰ ¹⁰¹ ¹⁰² ¹⁰³ (See Boxed Warning and also see Pediatric Use under Cautions.) However, suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide.⁹⁹ ¹⁰⁰ ¹⁰¹ ¹⁰³

Appropriately monitor and closely observe patients receiving quetiapine for any reason, particularly during initiation of therapy (i.e., the first few months) and during periods of dosage adjustments.⁹⁹ ¹⁰⁰ ¹⁰¹ ¹⁰³

Anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, and/or mania may be precursors to emerging suicidality.¹⁰⁰ ¹⁰¹ ¹⁰³ Consider changing or discontinuing therapy in patients whose depression is persistently worse or in those with emerging suicidality or symptoms that might be precursors to worsening depression or suicidality, particularly if severe, abrupt in onset, or were not part of the patient’s presenting symptoms.¹⁰⁰ ¹⁰³

Prescribe in smallest quantity consistent with good patient management to reduce risk of overdosage.¹⁰⁰ ¹⁰³

Neuroleptic Malignant Syndrome

Neuroleptic malignant syndrome (NMS), a potentially fatal syndrome requiring immediate discontinuance of the drug and intensive symptomatic treatment, reported rarely.¹

Tardive Dyskinesia

Tardive dyskinesia, a syndrome of potentially irreversible, involuntary dyskinetic movements, reported infrequently.¹ Consider discontinuance of quetiapine.¹

Hyperglycemia and Diabetes Mellitus

Severe hyperglycemia, sometimes associated with ketoacidosis, hyperosmolar coma, or death, reported in patients receiving atypical antipsychotic agents, including quetiapine.¹ ³⁴ ³⁵ ³⁶ ³⁷ ³⁸ ³⁹ ⁴⁰ ⁴¹ ⁴² ⁴³ ⁴⁴ ⁴⁵ ⁴⁷ ⁶⁰ ⁶¹ ⁶² ⁶³ ⁶⁷ ⁸⁷ Closely monitor patients with preexisting diabetes mellitus for worsening of glucose control and perform fasting glucose tests at baseline and periodically for patients with risk factors for diabetes (e.g., obesity, family history of diabetes).¹ ³⁴ ³⁵ ³⁶ ³⁷ ³⁸ ³⁹ ⁴⁰ ⁴¹ ⁴² ⁴³ ⁴⁴ ⁴⁵ If manifestations of hyperglycemia occur in any patient, test for diabetes mellitus.¹ ³⁴ ³⁵ ³⁶ ³⁷ ³⁸ ³⁹ ⁴⁰ ⁴¹ ⁴² ⁴³ ⁴⁴ ⁴⁵

General Precautions

Orthostatic Hypotension

Orthostatic hypotension reported.¹ Use with caution in patients with known cardiovascular or cerebrovascular disease and/or conditions that would predispose patients to hypotension (e.g., dehydration, hypovolemia, concomitant antihypertensive therapy).¹ (See Patients at Risk of Orthostatic Hypotension under Dosage and Administration.)

Ocular Effects

Possible lenticular changes; ophthalmologic examination of the lens by methods adequate to detect cataract formation (e.g., slit lamp exam) recommended at initiation of therapy, or shortly thereafter, and at 6-month intervals during chronic therapy.¹

Nervous System Effects

Possible risk of seizures; use with caution in patients with a history of seizures or with conditions known to lower the seizure threshold (e.g., dementia of the Alzheimer’s type, geriatric patients).¹

Disruption of ability to reduce core body temperature possible; use with caution in patients exposed to conditions that may contribute to an elevation in core body temperature (e.g., dehydration, extreme heat, strenuous exercise, concomitant use of anticholinergic agents).¹

Somnolence reported.¹ Potential impairment of judgment, thinking, or motor skills.¹

Endocrine Effects

Hypothyroidism possible.¹

Elevated prolactin concentrations reported with some atypical antipsychotic agents; not observed in clinical trials with quetiapine but reported in animals.¹

Metabolic Effects

Weight gain possible.¹

Increases in cholesterol and triglyceride concentrations possible; weakly related to weight gain.¹

Hepatic Effects

Asymptomatic, transient, and reversible increases in serum transaminases (principally ALT) reported; usually occurred within first 3 weeks and resolved despite continued quetiapine therapy.¹

Sexual Dysfunction

Priapism possible.¹

GI Effects

Esophageal dysmotility and aspiration possible; use with caution in patients at risk for aspiration pneumonia (e.g., geriatric patients, those with advanced Alzheimer’s dementia).¹

Possible Prescribing and Dispensing Precautions

Ensure accuracy of prescription; similarity in spelling of Seroquel (quetiapine) and Serzone (former trade name for nefazodone hydrochloride, an antidepressant agent) may result in errors associated with adverse CNS (e.g., mental status deterioration, hallucination, paranoia, muscle weakness, lethargy, dizziness) and GI (e.g., nausea, vomiting, diarrhea) effects.²⁹ ³⁰ ³¹

Specific Populations

Pregnancy

Category C.¹

Risk for extrapyramidal and/or withdrawal symptoms (e.g., agitation, hypertonia, hypotonia, tardive dyskinetic-like symptoms, tremor, somnolence, respiratory distress, feeding disorder) in neonates exposed to antipsychotic agents during the third trimester; monitor neonates exhibiting such symptoms.¹⁰³ ¹⁰⁷ ¹⁰⁸ ¹⁰⁹ Symptoms were self-limiting in some neonates but varied in severity; some infants required intensive support and prolonged hospitalization.¹⁰³ ¹⁰⁷ ¹⁰⁸ ¹⁰⁹

Lactation

Distributes into human milk in relatively small amounts.¹⁰³ ¹¹⁰ ¹¹¹ ¹¹² Women receiving quetiapine should not breast-feed.¹⁰³

Pediatric Use

Safety and efficacy not established in children <18 years of age.¹

FDA warns that a greater risk of suicidal thinking or behavior (suicidality) occurred during the first few months of antidepressant treatment compared with placebo in children and adolescents with major depressive disorder, obsessive-compulsive disorder (OCD), or other psychiatric disorders based on pooled analyses of 24 short-term, placebo-controlled trials of 9 antidepressant drugs (SSRIs and other antidepressants).¹⁰⁰ ¹⁰² ¹⁰³ However, a later meta-analysis of 27 placebo-controlled trials of 9 antidepressants (SSRIs and others) in patients <19 years of age with major depressive disorder, OCD, or non-OCD anxiety disorders suggests that the benefits of antidepressant therapy in treating these conditions may outweigh the risks of suicidal behavior or ideation.¹⁰² No suicides occurred in these pediatric trials.¹⁰⁰ ¹⁰² ¹⁰³

Carefully consider these findings when assessing potential benefits and risks of quetiapine in a child or adolescent for any clinical use.¹⁰⁰ ¹⁰¹ ¹⁰² ¹⁰³ (See Boxed Warning and also see Worsening of Depression and Suicidality Risk under Cautions.)

Geriatric Use

No substantial differences in safety relative to younger adults, but factors that decrease pharmacokinetic clearance, increase the pharmacodynamic response, or cause poorer tolerance or orthostasis may be present.¹ (See Patients at Risk of Orthostatic Hypotension under Dosage and Administration.)

Possible increased risk of death in geriatric patients with dementia-related psychosis.^a ⁹⁷ ⁹⁸ Substantial (1.6- to 1.7-fold) increase in mortality rate reported in geriatric patients with dementia who received atypical antipsychotic agents (e.g., aripiprazole, olanzapine, quetiapine, risperidone) for treatment of behavioral disorders; most fatalities resulted from cardiac-related events (e.g., heart failure, sudden death) or infections (mostly pneumonia).^a ⁹⁷ ⁹⁸

Atypical antipsychotics are not approved for the treatment of dementia-related psychosis.^a ⁹⁷ ⁹⁸ (See Boxed Warning and see Increased Mortality in Geriatric Patients with Dementia-related Psychosis under Cautions.)

In pooled data analyses, a reduced risk of suicidality was observed in adults ≥65 years of age with antidepressant therapy compared with placebo.⁹⁹ ¹⁰⁰ ¹⁰³ (See Boxed Warning and also see Worsening of Depression and Suicidality Risk under Cautions.)

Hepatic Impairment

Increased plasma concentrations expected in patients with hepatic impairment; dosage adjustment may be necessary.¹

Renal Impairment

Clearance may be decreased in severe renal impairment, but dosage adjustment not necessary.¹

Common Adverse Effects

Somnolence, dizziness, dry mouth, constipation, increased ALT, weight gain, dyspepsia.^a

Interactions for Quetiapine Fumarate

Metabolized principally by CYP3A4.¹ ^b Does not appear to inhibit CYP1A2, CYP2C9, CYP2C19, CYP2D6, or CYP3A4 in vitro; pharmacokinetic interaction with substrates of these isoenzymes unlikely.¹ ^b

Drugs Affecting Hepatic Microsomal Enzymes

Inhibitors or inducers of CYP3A4; potential pharmacokinetic interaction (altered quetiapine metabolism).¹ ^b

Specific Drugs

Drug	Interaction	Comments
Alcohol	Potentiation of cognitive and motor effects of alcohol¹	Avoid alcohol during therapy with quetiapine¹
Antifungals, azole (e.g., fluconazole, itraconazole, ketoconazole)	Substantial decrease in quetiapine clearance with concomitant use of ketoconazole, resulting in increased peak plasma quetiapine concentrations¹	Use concomitantly with caution; dosage adjustment of quetiapine may be necessary¹
Barbiturates	Possible increased quetiapine clearance¹	Increased quetiapine dosage may be required¹
Carbamazepine	Possible increased quetiapine clearance¹	Increased quetiapine dosage may be required¹
Cimetidine	Decreased quetiapine mean clearance¹	No dosage adjustment of quetiapine required¹
CNS agents	Possible additive CNS effects¹	Use with caution¹
Divalproex sodium	Increased peak plasma quetiapine concentrations, with no effect on extent of absorption or mean quetiapine clearance; decreased peak plasma valproic acid concentrations and extent of absorption, but not significant¹
Dopamine agonists	Antagonistic effects¹
Erythromycin	Decreased quetiapine clearance¹	Use concomitantly with caution¹
Fluoxetine	No effect on quetiapine pharmacokinetics¹
Glucocorticoids	Possible increased quetiapine clearance¹	Increased quetiapine dosage may be required¹
Haloperidol	No effect on quetiapine pharmacokinetics¹
Hypotensive agents	Additive hypotensive effects¹
Imipramine	No effect on quetiapine pharmacokinetics¹
Levodopa	Antagonistic effects¹
Lithium	No effect on lithium pharmacokinetics¹
Lorazepam	Decreased lorazepam clearance¹
Phenytoin	Substantially increased quetiapine clearance¹	Increased quetiapine dosage may be required;¹ ²³ caution advised if phenytoin is withdrawn and replaced with a non-inducer (e.g., valproate)¹
Rifampin	Possible increased quetiapine clearance¹	Increased quetiapine dosage may be required¹
Risperidone	No effect on quetiapine pharmacokinetics¹
Thioridazine	Substantially increased quetiapine clearance¹

Quetiapine Fumarate Pharmacokinetics

Absorption

Bioavailability

Rapidly absorbed after oral administration, with peak plasma concentrations attained within 1.5 hours.¹ ^b Bioavailability of tablet formulation is 100% relative to an oral solution (not commercially available in US).¹ ^b

Food

Bioavailability is marginally affected by food.¹ ^b

Distribution

Extent

Widely distributed throughout the body.¹

Distributed into milk in relatively small amounts.¹⁰³ ¹¹⁰ ¹¹¹ ¹¹²

Plasma Protein Binding

83%.¹ ^b

Elimination

Metabolism

Extensively metabolized to inactive metabolites, principally via CYP3A4.¹ ^b

Elimination Route

Excreted in urine (73%) and feces (20%), with <1% of the drug excreted unchanged.¹ ^b

Half-life

Approximately 6 hours.¹ ^b

Special Populations

In patients with hepatic impairment, clearance is 30% lower and AUC and peak plasma concentrations are 3 times higher than those of healthy individuals.¹

In patients with severe renal impairment (Cl_cr 10–30 mL/minute), clearance may be reduced by 25% compared with healthy individuals; however, plasma concentrations in patients with renal impairment were within the range of those seen in healthy patients.¹

In geriatric patients, clearance is decreased by about 40% compared with younger patients.¹

Stability

Storage

Oral

Tablets

25°C (may be exposed to 15–30°C).¹

Actions

Exact mechanism of antipsychotic action is not known; may involve antagonism at serotonin type 1 (5-hydroxytryptamine [5-HT_1A]),¹ ⁶ ⁷ ¹⁵ ¹⁷ type 2 (5-HT_2A, 5-HT_2C),¹ ² ³ ⁴ ⁵ ⁶ ⁷ ⁸ ⁹ ¹⁰ ¹¹ ¹² ¹⁴ ¹⁵ ¹⁶ ¹⁷ ²³ and type 6 (5-HT₆) receptors,¹⁷ and at dopamine receptors.¹ ² ³ ⁴ ⁵ ⁶ ⁷ ⁸ ⁹ ¹⁰ ¹¹ ¹² ¹⁴ ¹⁵ ¹⁶ ¹⁷ ²⁶ ²⁸
Antagonism at other receptors (e.g., α₁-adrenergic receptors, histamine H₁ receptors) may contribute to other therapeutic and adverse effects (e.g., orthostatic hypotension, somnolence).¹

Advice to Patients

Importance of providing written patient information (medication guide) each time quetiapine is dispensed.⁹⁹ ¹⁰⁰ ¹⁰¹ ¹⁰³
Importance of advising patients and caregivers that geriatric patients with dementia-related psychosis treated with antipsychotic agents are at an increased risk of death.⁹⁷ ¹⁰³ Inform patients and caregivers that quetiapine is not approved for treating geriatric patients with dementia-related psychosis.⁹⁷ ¹⁰³
Risk of suicidality; importance of patients, family, and caregivers being alert to and immediately reporting emergence of suicidality, worsening depression, or unusual changes in behavior, especially during the first few months of therapy or during periods of dosage adjustment.⁹⁹ ¹⁰⁰ ¹⁰¹ ¹⁰³
Risk of orthostatic hypotension, especially during initial dosage titration and at times of re-initiation of therapy or increases in dosage.¹
Risk of somnolence and impairment of judgment, thinking, or motor skills; avoid driving, operating machinery, or performing hazardous tasks until effects on the individual are known.¹
Importance of avoiding alcohol during quetiapine therapy.¹
Importance of avoiding overheating or dehydration.¹
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses (e.g., diabetes mellitus, seizures, dementia).¹
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹⁰³ ¹⁰⁹ Importance of clinicians informing patients about the benefits and risks of taking antipsychotics during pregnancy (see Pregnancy under Cautions).¹⁰³ ¹⁰⁹ Importance of advising patients not to stop taking quetiapine if they become pregnant without consulting their clinician; abruptly discontinuing antipsychotic agents may cause complications.¹⁰⁹ Importance of advising patients not to breast-feed during therapy.¹⁰³
Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

QUEtiapine Fumarate
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets, film-coated	25 mg (of quetiapine)	SEROquel (with povidone)	AstraZeneca
		50 mg (of quetiapine)	SEROquel (with povidone)	AstraZeneca
		100 mg (of quetiapine)	SEROquel (with povidone)	AstraZeneca
		200 mg (of quetiapine)	SEROquel (with povidone)	AstraZeneca
		300 mg (of quetiapine)	SEROquel (with povidone)	AstraZeneca
		400 mg (of quetiapine)	SEROquel (with povidone)	AstraZeneca

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. AstraZeneca Pharmaceuticals. Seroquel (quetiapine fumarate) tablets prescribing information. Wilmington, DE; 2004 Jul.

2. Small JG, Hirsch SR, Arvanitis LA et al and the Seroquel Study Group. Quetiapine in patients with schizophrenia: a high- and low-dose double-blind comparison with placebo. Arch Gen Psychiatry. 1997; 54:549-557. [PubMed 9193196]

3. Borison RL, Arvanitis LA, Miller BG and the U.S. SEROQUEL Study Group. ICI 204,636, an atypical antipsychotic: efficacy and safety in a multicenter, placebo-controlled trial in patients with schizophrenia. J Clin Psychopharmacol. 1996; 16:158-169. [PubMed 8690831]

4. Arvanitis LA, Miller BG and the Seroquel Trial 13 Study Group. Multiple fixed doses of “Seroquel” (quetiapine) in patients with acute exacerbation of schizophrenia: a comparison with haloperidol and placebo. Biol Psychiatry. 1997; 42:233-246. [PubMed 9270900]

5. Anon. Academic highlights: Seroquel: a putative atypical antipsychotic drug with serotonin- and dopamine-receptor antagonist properties: preclinical and early clinical trials in schizophrenia. J Clin Psychiatry. 1995; 56:438-445. [PubMed 7665549]

6. Casey DE. ’seroquel’ (quetiapine): preclinical and clinical findings of a new atypical antipsychotic. Exp Opin Invest Drugs. 1996; 5:939-957.

7. Robinson CP, Robinson KA, Castaner J. Quetiapine fumarate. Drugs Future. 1996; 21:483-489.

8. Fleischhacker WW, Hummer M. Drug treatment of schizophrenia in the 1990s: achievements and future possibilities in optimising outcomes. Drugs. 1997; 53:915-929. [PubMed 9179524]

9. Richelson E. Preclinical pharmacology of neuroleptics: focus on new generation compounds. J Clin Psychiatry. 1996; 57(Suppl 11):4-11. [PubMed 8941166]

10. Fabre LF, Arvanitis L, Pultz J et al. ICI 204,636, a novel, atypical antipsychotic: early indication of safety and efficacy in patients with chronic and subchronic schizophrenia. Clin Ther. 1995; 17:366-378. [PubMed 7585841]

11. Buckley PF. New dimensions in the pharmacologic treatment of schizophrenia and related psychoses. J Clin Pharmacol. 1997; 37:363-378. [PubMed 9156369]

12. Kuperberg GR. Advances in the treatment of schizophrenia. Br J Clin Pract. 1996; 50:315-323. [PubMed 8983320]

13. Citrome L. New antipsychotic medications: what advantages do they offer? Postgrad Med. 1997; 101:207-210,213,214. (IDIS 380687)

14. Lieberman JA. Atypical antipsychotic drugs as a first-line treatment of schizophrenia: a rationale and hypothesis. J Clin Psychiatry. 1996; 57(Suppl 11):68-71. [PubMed 8941173]

15. Hirsch SR, Link CGG, Goldstein JM et al. ICI 204,636: a new atypical antipsychotic drug. Br J Psychiatry. 1996; 168(Suppl 29):45-56.

16. Meltzer HY. Pre-clinical pharmacology of atypical antipsychotic drugs: a selective review. Br J Psychiatry. 1996; 168(Suppl 29):23-31.

17. Goldstein JM. Preclinical profile of Seroquel (quetiapine): an atypical antipsychotic with clozapine-like pharmacology. In: Holliday SG, Ancill RJ, MacEwan GW eds. Schizophrenia: Breaking Down the Barriers. New York: John Wiley & Sons Ltd; 1996:177-208.

18. Arvanitis LA. Clinical profile of Seroquel™ (quetiapine): an overview of recent clinical studies. In: Holliday SG, Ancill RJ, MacEwan GW eds. Schizophrenia: Breaking Down the Barriers. New York: John Wiley & Sons Ltd; 1996:209-236.

19. Lahti AC, Tamminga CA. Recent developments in the neuropharmacology of schizophrenia. Am J Health-Syst Pharm. 1995; 52(Suppl 1):S5-8. [PubMed 7749964]

20. Casey DE. Will the new antipsychotics bring hope of reducing the risk of developing extrapyramidal syndromes and tardive dyskinesia? Int Clin Psychopharmacol. 1997; 12(Suppl 1):S19-27.

21. Link C, Smith A, Miller B et al and the European Seroquel Study Group. A multicentre, double-blind, controlled comparison of Seroquel and chlorpromazine in the treatment of hospitalised patients with acute exacerbation of subchronic and chronic schizophrenia. Eur Neuropsychopharmacol. 1994; 4:385.

22. American Psychiatric Association. Practice guideline for the treatment of patients with schizophrenia. Am J Psychiatry. 2004; 161(Suppl):1-56.

23. Anon. Quetiapine for schizophrenia. Med Lett Drugs Ther. 1997; 39:117-8. [PubMed 9422044]

24. American Psychiatric Association. DSM-IV: diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Association; 1994:273-86.

25. Zeneca, Wilmington, DE: Personal communication.

26. Meats P. Quetiapine (’seroquel’); an effective and well-tolerated atypical antipsychotic. Int J Psychiatry Clin Pract. 1997; 1:231-9. [PubMed 24946189]

27. Borison RL, Arvanitis LA, Miller BG. A comparison of five fixed doses of ’seroquel’ (ICI 204,636) with haloperidol and placebo in patients with schizophrenia. Schizophr Res. 1996; 18:132A.

28. Fleischhacker WW, Linkz CGG, Hurst BC. ICI 204636 (’seroquel’)—a putative new atypical antipsychotic: results from phase III trials. Schizophr Res. 1996; 18:132A.

29. Block G. Dear healthcare professional letter: dispensing errors alert. Wilmington, DE: AstraZeneca LP; 2002 May 20.

30. Kim H, Phillips J. Medication errors associated with Serzone and Seroquel. Drug Topics. 2002;1:38. From the Drug Topics website.

31. Jody D. Dear healthcare provider letter: dispensing error alert involving Serzone (nefazodone) and Seroquel (quetiapine) tablets. Princeton, NJ: Bristol Myer Squibb; 2002 Dec 9. From the FDA website

32. Cheer SM, Wagstaff AJ. Quetiapine. A review of its use in the management of schizophrenia. CNS Drugs. 2004; 18:173-99. [PubMed 14871161]

33. American Psychiatric Association. Practice guideline for the treatment of patients with bipolar disorder (revision). Am J Psychiatry. 2002; 159(4 Suppl):1-50.

34. Otsuka America Pharmaceutical, Inc. Abilify (aripiprazole) tablets prescribing information. Rockville, MD; 2004 Sep.

35. Novartis Pharmaceuticals. Clozaril (clozapine) prescribing information. East Hanover, NJ; 2003 Dec.

36. Eli Lilly and Company. Zyprexa (olanzapine) tablets and Zyprexa Zydis (olanzapine) orally disintegrating tablets prescribing information. Indianapolis, IN; 2004 Sep 22.

37. Janssen Pharmaceutica. Risperdal (risperidone) tablets and oral solution prescribing information. Titusville, NJ; 2003 Oct.

38. Pfizer Inc. Geodon (ziprasidone) prescribing information. New York, NY; 2004 Aug.

39. Lewis-Hall F. Dear health care professional letter regarding class labeling for atypical antipsychotics and risk of hyperglycemia and diabetes. Princeton, NJ: Briston-Myers Squibb Company; 2004 Mar 25. From FDA website.

40. Bess AL, Cunningham SR. Dear health care professional letter regarding class labeling for atypical antipsychotics and risk of hyperglycemia and diabetes. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2004 Apr 1. From the FDA website.

41. Eli Lilly and Company. Lilly announces FDA notification of class labeling for atypical antipsychotics regarding hyperglycemia and diabetes. Indianapolis, IN; 2003 Sep 17. Press release.

42. Eisenberg P. Dear health care professional letter regarding safety data on Zyprexa (olanzapine) – hyperglycemia and diabetes. Indianapolis, IN: Eli Lilly and Company; 2004 Mar 1. From the FDA website.

43. Macfadden W. Dear health care professional letter regarding class labeling for atypical antipsychotics and risk of hyperglycemia and diabetes. Wilmington, DE: AstraZeneca Pharmaceuticals; 2004 Apr 22. From the FDA website.

44. Mahmoud RA. Dear health care professional letter regarding class labeling for atypical antipsychotics and risk of hyperglycemia and diabetes. Titusville, NJ: Janssen Pharmaceutica, Inc; 2004. From the FDA website.

45. Clary CM. Dear health care practitioner letter regarding class labeling for atypical antipsychotics and risk of hyperglycemia and diabetes. New York NY: Pfizer Global Pharmaceuticals; 2004 Aug. From the FDA website.

46. Cunningham F, Lambert B, Miller DR et al. Antipsychotic induced diabetes in veteran schizophrenic patients. In: Abstracts of the 1st International Conference on Therapeutic Risk Management and 19th International Conference on Pharmacoepidemiology, Philadelphia, PA, 2003 Aug 21-24. Pharmacoepidemiol Drug Saf. 2003; 12(suppl 1): S154-5.

47. American Diabetes Association; American Psychiatric Association; American Association of Clinical Endocrinologists; North American Association for the Study of Obesity. Consensus development conference on antipsychotic drugs and obesity and diabetes. Diabetes Care. 2004; 27:596-601. [PubMed 14747245]

48. Melkersson K, Dahl ML. Adverse metabolic effects associated with atypical antipsychotics. Drugs. 2004; 64:701-23. [PubMed 15025545]

49. Citrome LL, Jaffe AB. Relationship of atypical antipsychotics with development of diabetes mellitus. Ann Pharmacother. 2003; 37:1849-57. [PubMed 14632602]

50. Sumiyoshi T, Roy A, Anil AE et al. A comparison of incidence of diabetes mellitus between atypical antipsychotic drugs. J Clin Psychopharmacol. 2004; 24:345-8. [PubMed 15118492]

51. Expert Group. ’Schizophrenia and Diabetes 2003’ expert consensus meeting, Dublin, 3–4 October 2003: consensus summary. Br J Psychiatry. 2004; 47(Suppl):S112-4.

52. Marder SR, Essock SM, Miller AL et al. Physical health monitoring of patients with schizophrenia. Am J Psychiatry. 2004; 161:1334-49. [PubMed 15285957]

53. Holt RI. Consensus development conference on antipsychotic drugs and obesity and diabetes: response to consensus statement. Diabetes Care. 2004; 27:2086-7. [PubMed 15277449]

54. Citrome L, Volavka J. Consensus development conference on antipsychotic drugs and obesity and diabetes: response to consensus statement. Diabetes Care. 2004; 27:2087-8. [PubMed 15277450]

55. Isaac MT, Isaac MB. Consensus development conference on antipsychotic drugs and obesity and diabetes: response to consensus statement. Diabetes Care. 2004; 27:2088. [PubMed 15277451]

56. Boehm G, Racoosin JA, Laughren TP et al. Consensus development conference on antipsychotic drugs and obesity and diabetes: response to consensus statement. Diabetes Care. 2004; 27:2088-9. [PubMed 15277452]

57. Barrett EJ. Consensus development conference on antipsychotic drugs and obesity and diabetes: response to Holt, Citrome and Volevka, Isaac and Isaac, and Boehm et al. Diabetes Care. 2004; 27:2089-90.

58. Fuller MA, Shermock KM, Secic M et al. Comparative study of the development of diabetes mellitus in patients taking risperidone and olanzapine. Pharmacotherapy. 2002; 23:1037-43.

59. Koller EA, Cross JT, Doraiswamy PM et al. Risperidone-associated diabetes mellitus: a pharmacovigilance study. Pharmacotherapy. 2003; 23:735-44. [PubMed 12820816]

60. Koller EA, Weber J, Doraiswamy PM et al. A survey of reports of quetiapine-associated hyperglycemia and diabetes mellitus. J Clin Psychiatry. 2004; 65:857-63. [PubMed 15291665]

61. Ananth J, Johnson KM, Levander EM et al. Diabetic ketoacidosis, neuroleptic malignant syndrome, and myocardial infarction in a patient taking risperidone and lithium carbonate. J Clin Psychiatry. 2004; 65:724. [PubMed 15163265]

62. Torrey EF, Swalwell CI. Fatal olanzapine-induced ketoacidosis. Am J Psychiatry. 2003; 160:2241. [PubMed 14638601]

63. Wehring HJ, Kelly DL, Love RC et al. Deaths from diabetic ketoacidosis after long-term clozapine treatment. Am J Psychiatry. 2003; 160:2241-2. [PubMed 14638600]

64. Koro CE, Fedder DO, L’Italien GJ et al. Assessment of independent effect of olanzapine and risperidone on risk of diabetes among patients with schizophrenia: population based nested case-control study. BMJ. 2002; 325:243. [PubMed 12153919]

65. Citrome LL. Efficacy should drive atypical antipsychotic treatment. BMJ. 2003; 326:283. [PubMed 12561827]

66. Anon. Which atypical antipsychotic for schizophrenia?. Drug Ther Bull. 2004; 42:57-60. [PubMed 15310154]

67. Anon. Atypical antipsychotics and hyperglycaemia. Aust Adv Drug React Bull. 2004; 23:11-2.

68. Sussman N. The implications of weight changes with antipsychotic treatment. J Clin Psychopharmacol. 2003; 23 (Suppl 1):S21-6.

69. Gianfrancesco F, Grogg A, Mahmoud R et al. Differential effects of antipsychotic agents on the risk of development of type 2 diabetes mellitus in patients with mood disorders. Clin Ther. 2003; 25:1150-71. [PubMed 12809963]

70. Bushe C, Leonard B. Association between atypical antipsychotic agents and type 2 diabetes: review of prospective clinical data. Br J Psychiatry Suppl. 2004; 47:S87-93. [PubMed 15056600]

71. Cavazzoni P, Mukhopadhyay N, Carlson C et al. Retrospective analysis of risk factors in patients with treatment-emergent diabetes during clinical trials of antipsychotic medications. Br J Psychiatry Suppl. 2004; 47:s94-101. [PubMed 15056601]

72. Gianfrancesco FD, Grogg AL, Mahmoud RA et al. Differential effects of risperidone, olanzapine, clozapine, and conventional antipsychotics on type 2 diabetes: findings from a large health plan database. J Clin Psychiatry. 2002; 63:920-30. [PubMed 12416602]

73. Etminan M, Streiner DL, Rochon PA. Exploring the association between atypical neuroleptic agents and diabetes mellitus in older adults. Pharmacotherapy. 2003; 23:1411-15. [PubMed 14620387]

74. Leslie DL, Rosenheck RA. Incidence of newly diagnosed diabetes attributable to atypical antipsychotic medications. Am J Psychiatry. 2004; 161:1709-11. [PubMed 15337666]

75. Sernyak MJ, Leslie DL, Alarcon RD et al. Association of diabetes mellitus with use of atypical neuroleptics in the treatment of schizophrenia. Am J Psychiatry. 2002; 159:561-6. [PubMed 11925293]

76. Geller WK, MacFadden W. Diabetes and atypical neuroleptics. Am J Psychiatry. 2003; 160:388. [PubMed 12562601]

77. Gianfrancesco FD. Diabetes and atypical neuroleptics. Am J Psychiatry. 2003; 160:388-9; author reply 389. [PubMed 12562599]

78. Lamberti JS, Crilly JF, Maharaj K. Prevalence of diabetes mellitus among outpatients with severe mental disorders receiving atypical antipsychotic drugs. J Clin Psychiatry. 2004; 65:702-6. [PubMed 15163259]

79. Lee DW, Fowler RB. Olanzapine/risperidone and diabetes risk. J Clin Psychiatry. 2003; 64:847-8; author reply 848. [PubMed 12934988]

80. Reviewers’ comments (personal observations).

81. Bristol-Myers Squibb, Princeton, NJ: Personal communication.

82. AstraZeneca, Wayne, PA: Personal communication.

83. Eli Lilly and Company, Indianapolis, IN: Personal communication.

84. Novartis Pharmaceuticals Corporation, East Hanover, NJ: Personal communication.

85. Janssen Pharmaceuticals, Titusville, NJ: Personal communication.

86. Citrome LL. The increase in risk of diabetes mellitus from exposure to second generation antipsychotic agents. Drugs Today (Barc). 2004; 40: 445-64. [PubMed 15319799]

87. Citrome L, Jaffe A, Levine J et al. Relationship between antipsychotic medication treatment and new cases of diabetes among psychiatric inpatients. Psychiatr Serv. 2004; 55:1006-13 [PubMed 15345760]

88. Sachs G, Chengappa KN, Suppes T et al. Quetiapine with lithium or divalproex for the treatment of bipolar mania: a randomized, double-blind, placebo-controlled study. Bipolar Disord. 2004;6:213-23.

89. Geddes J, Freemantle N, Harrison P et al. Atypical antipsychotics in the treatment of schizophrenia: systematic overview and meta-regression analysis. BMJ. 2000; 321: 1371-6. [PubMed 11099280]

90. Tandon R. Improvement without impairment: a review of clinical data for quetiapine in the treatment of schizophrenia. J Clin Psychopharmacol. 2003; 23: S15-20. [PubMed 12832945]

91. Schulz SC, Thomson R, Brecher M. The efficacy of quetiapine vs haloperidol and placebo: a meta-analytic study of efficacy. Schizophr Res. 2003; 62:1-12. [PubMed 12765737]

92. Srisurapanont M, Maneeton B, Maneeton N. Quetiapine for schizophrenia. Cochrane Database Syst Rev. 2004; 2: CD00967.

93. Emsley RA, Raniwalla J, Bailey PJ et al. A comparison of the effects of quetiapine (‘Seroquel’) and haloperidol in schizophrenic patients with a history of and a demonstrated, partial response to conventional antipsychotic treatment. Int Clin Psychopharmacol. 2000; 15:121-31. [PubMed 10870870]

94. Leucht S, Wahlbeck K, Hamann J et al. New generation antipsychotics versus low-potency conventional antipsychotics: a systematic review and meta-analysis. Lancet. 2003; 361: 1581-89. [PubMed 12747876]

95. Peuskens J, Link CGG. A comparison of quetiapine and chlorpromazine in the treatment of schizophrenia. Acta Psychiatr Scand. 1997; 96: 265-73.

96. Copolov DL, Link CGG, Kowalcyk B. A multicenter, double-blind, randomized comparison of quetiapine (ICI 204, 636, ‘Seroquel’) and haloperidol in schizophrenia. Psychol Med. 2000; 30:95-105. [PubMed 10722180]

97. Food and Drug Administration. Public health advisory: deaths with antipsychotics in elderly patients with behavioral disturbances. Rockville, MD; 2005 Apr 11. From the FDA website.

98. Dear healthcare professional letter regarding adding important safety information regarding the use of atypical antipsychotics in elderly patients with dementia-related psychosis to the prescribing information for Seroquel (quetiapine fumarate). Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2005 Jul.

99. Food and Drug Administration. FDA news: FDA proposes new warnings about suicidal thinking, behavior in young adults who take antidepressant medications. Rockville, MD; 2007 May 2. From the FDA web site.

100. Food and Drug Administration. Antidepressant use in children, adolescents, and adults: class revisions to product labeling. Rockville, MD; 2007 May 2. From the FDA web site.

101. Food and Drug Administration. Revisions to medication guide: antidepressant medicines, depression and other serious mental illnesses and suicidal thoughts or actions. Rockville, MD; 2007 May 2. From the FDA web site.

102. Bridge JA, Iyengar S, Salary CB. Clinical response and risk for reported suicidal ideation and suicide attempts in pediatric antidepressant treatment: a meta-analysis of randomized controlled trials. JAMA. 2007; 297:1683-96. [PubMed 17440145]

103. AstraZeneca Pharmaceuticals LP. Seroquel (quetiapine fumarate) tablets prescribing information. Wilmington, DE; 2011 Jul.

107. Sexson WR, Barak Y. Withdrawal emergent syndrome in an infant associated with maternal haloperidol therapy. J Perinatol. 1989; 9:170-2. [PubMed 2738729]

108. Coppola D, Russo LJ, Kwarta RF Jr. et al. Evaluating the postmarketing experience of risperidone use during pregnancy: pregnancy and neonatal outcomes. Drug Saf. 2007; 30:247-64. [PubMed 17343431]

109. US Food and Drug Administration. FDA drug safety communication: Antipsychotic drug labels updated in use during pregnancy and risk of abnormal muscle movements and withdrawal symptoms in newborns. Rockville, MD; 2011 Feb 22. From the FDA website: .

110. Lee A, Giesbrecht E, Dunn E et al. Excretion of quetiapine in breast milk. Am J Psychiatry. 2004; 161:1715-6. [PubMed 15337669]

111. Rampono J, Kristensen JH, Ilett KF et al. Quetiapine and breast feeding. Ann Pharmacother. 2007; 41:711-4. [PubMed 17374621]

112. Misri S, Corral M, Wardrop AA et al. Quetiapine augmentation in lactation: a series of case reports. J Clin Psychopharmacol. 2006; 26:508-11. [PubMed 16974194]

a. AstraZeneca Pharmaceuticals. Seroquel (quetiapine fumarate) tablets prescribing information. Wilmington, DE; 2005 Dec.

b. DeVane CL, Nemeroff CB. Clinical pharmacokinetics of quetiapine. An atypical antipsychotic. Clin Pharmacokinet. 2001; 40:509-22. [PubMed 11510628]

Quetiapine Fumarate

Warning(s)

Introduction

Uses for Quetiapine Fumarate

Schizophrenia

Bipolar Disorder

Quetiapine Fumarate Dosage and Administration

General

Administration

Oral Administration

Dosage

Adults

Schizophrenia

Oral

Bipolar Disorder

Acute Mania

Prescribing Limits

Adults

Schizophrenia

Oral

Bipolar Disorder

Acute Mania

Special Populations

Hepatic Impairment

Renal Impairment

Patients at Risk of Orthostatic Hypotension

Cautions for Quetiapine Fumarate

Contraindications

Warnings/Precautions

Warnings

Increased Mortality in Geriatric Patients with Dementia-related Psychosis

Worsening of Depression and Suicidality Risk

Neuroleptic Malignant Syndrome

Tardive Dyskinesia

Hyperglycemia and Diabetes Mellitus

General Precautions

Orthostatic Hypotension

Ocular Effects

Nervous System Effects

Endocrine Effects

Metabolic Effects

Hepatic Effects

Sexual Dysfunction

GI Effects

Possible Prescribing and Dispensing Precautions

Specific Populations

Pregnancy

Lactation

Pediatric Use

Geriatric Use

Hepatic Impairment

Renal Impairment

Common Adverse Effects

Interactions for Quetiapine Fumarate

Drugs Affecting Hepatic Microsomal Enzymes

Specific Drugs

Quetiapine Fumarate Pharmacokinetics

Absorption

Bioavailability

Food

Distribution

Extent

Plasma Protein Binding

Elimination

Metabolism

Elimination Route

Half-life

Special Populations

Stability

Storage

Oral

Tablets

Actions

Advice to Patients

Preparations

References

More about quetiapine

Consumer resources

Professional resources

Related treatment guides