Quetiapine

Pharmacologic Category

Second Generation (Atypical) Antipsychotic

Dosing: Adult

Note: Available quetiapine preparations include oral IR (dosed 1 to 3 times daily) and 24-hour ER (dosed once daily) formulations; to convert between formulations, see "Dosing Conversion" below.

Agitation/aggression and psychosis associated with dementia, severe or refractory (alternative agent) (off-label use):

Note: For short-term adjunctive use while addressing underlying cause(s) of severe symptoms. In patients without a clinically significant response after an adequate trial (eg, up to 4 weeks), taper and withdraw therapy. Only continue in patients with demonstrated benefit; attempt to taper and withdraw at regular intervals (eg, within 4 months of initiation) (APA [Reus 2016]). In severe agitation associated with dementia with Lewy bodies, antipsychotics are generally avoided. If use is required, doses >12.5 mg/day are not recommended (Farlow 2019).

Immediate release: Oral: Initial: 25 mg at bedtime; may increase dose gradually (eg, weekly) based on response and tolerability up to 75 mg twice daily (Press 2019; Scharre 2002).

Agitation and/or delirium, ICU (alternative agent) (off-label use):

Note: Nonpharmacologic interventions and treatment of underlying conditions are initial steps to prevent and manage delirium. Antipsychotics may be used as short-term adjunctive treatment if distressing symptoms (eg, agitation, anxiety) are present (SCCM [Devlin 2018]).

Immediate release: Oral or via NG tube: Initial: 50 mg twice daily; may increase based on response and tolerability in 100 mg increments at intervals ≥1 day up to a maximum dose of 400 mg/day (Devlin 2010; SCCM [Devlin 2018]). In patients who may be more sensitive to adverse effects, some experts start at 12.5 mg twice daily or 25 to 50 mg at bedtime and increase dose more gradually (eg, in increments of 25 mg/day) based on response and tolerability (Tietze 2019).

Bipolar disorder:

Acute manic episodes (labeled use), mixed episodes (labeled use [extended release]; off-label use [immediate release]), and acute hypomania (off-label use) (monotherapy or adjunct to antimanic therapy):

Immediate release: Oral: Initial: 100 to 200 mg once daily at bedtime or in 2 divided doses on day 1, then increase by 100 mg/day (divided twice daily or as single dose at bedtime) until 400 mg/day is reached by day 4; thereafter, may further increase based on response and tolerability in increments of ≤200 mg/day (Pae 2005; Stovall 2018; manufacturer's labeling). Maximum dose: 800 mg/day (manufacturer's labeling); however, some patients may require doses up to 1.2 g/day for optimal response, according to some experts (Stovall 2018).

Extended release: Oral: Initial: 300 mg once daily on day 1; increase to 600 mg once daily on day 2, then adjust dose based on response and tolerability. Maximum dose: 800 mg once daily (manufacturer's labeling); however, some patients may require doses up to 1.2 g/day for optimal response, according to some experts (Stovall 2018).

Bipolar major depression (monotherapy [labeled use] or in combination with antimanic therapy [off-label use]): Immediate release, Extended release: Oral: Initial: 50 mg once daily at bedtime; increase to 100 mg once daily on day 2, further increase by 50 to 100 mg/day to reach a usual target dose of 300 mg once daily by day 4 to 7; maximum dose: 300 mg/day (Shelton 2019; manufacturer's labeling). Although increased efficacy with doses >300 mg/day has not been demonstrated in clinical trials, based upon clinical experience, individual patients may require doses up to 800 mg/day for optimal response (Shelton 2019).

Maintenance treatment (monotherapy [off-label use] or adjunct to antimanic therapy [labeled use]): Immediate release, Extended release: Oral: Continue dose and combination regimen that was used to achieve control of the acute episode (CANMAT [Yatham 2018]). Maximum dose: 800 mg/day; however, for patients who required doses up to 1.2 g/day to achieve remission, this dose is initially continued for maintenance treatment if it is tolerated (Stovall 2018).

Delusional infestation (delusional parasitosis) (off-label use):

Immediate release: Oral: Initial: 12.5 to 50 mg at bedtime; gradually increase dose based on response and tolerability every 3 to 7 days up to 200 to 300 mg at bedtime or in divided doses. Continue treatment for at least 3 months before attempting to decrease dose (Blasco-Fontecilla 2005; Freudenmann 2008; Heller 2013; Milia 2008; Suh 2018). Some experts suggest targeting a dose of 200 mg/day and would consider discontinuation as soon as 1 month after response (Suh 2018).

Generalized anxiety disorder (adjunct to antidepressants) (alternative agent) (off-label use):

Immediate release, Extended release: Oral: Initial: 25 mg once daily (immediate release only) to 50 mg once daily; may gradually increase dose based on response and tolerability every ≥7 days to a usual dosage range of 50 to 200 mg/day; maximum recommended dose: 300 mg/day (Altamura 2011; Craske 2018; Galynker 2005; Katzman 2011; Khan 2013). For the ER tablet, increasing the dose to 100 or 150 mg on day 3 or 4 of therapy may be appropriate for patients with severe symptoms (Khan 2013; Mezhebovsky 2013). Note: May also be used for monotherapy in patients who have not responded to or do not tolerate antidepressants and other first-line agents (Katzman 2014).

Major depressive disorder (unipolar):

Nonpsychotic depression as adjunct for insufficient response to antidepressants (labeled use [extended release]; off-label use [immediate release]) or psychotic depression in combination with an antidepressant (off-label use): Immediate release, Extended release: Oral: Initial: 50 mg/day on days 1 and 2; increase to 150 mg/day on day 3. Usual dosage range: 150 to 300 mg/day (Nelson 2018; manufacturer's labeling); however, doses up to 600 mg/day in psychotic depression may be needed and tolerated (Wijkstra 2010).

Nonpsychotic depression, monotherapy (alternative agent) (off-label use): Immediate release, Extended release: Oral: Initial: 50 mg once daily; may gradually increase up to 300 mg/day based on response and tolerability (Maneeton 2012; Thase 2013; Thase 2018).

Obsessive-compulsive disorder, treatment-resistant (augmentation to antidepressants) (off-label use):

Immediate release: Oral: Initial: 25 to 50 mg once daily; increase dose gradually based on response and tolerability in increments of 25 to 100 mg every 2 to 3 weeks up to 400 mg/day (Atmaca 2002; Denys 2004; Fineberg 2005).

Posttraumatic stress disorder (adjunct to antidepressants or monotherapy) (alternative agent) (off-label use):

Immediate release: Oral: Initial: 25 mg once daily at bedtime; increase dose in 25 mg increments every 1 to 2 days up to 100 mg at bedtime by the end of week 1; may further adjust dose based on response and tolerability in increments of 25 mg/day, up to 100 mg/week. Average dose in clinical trials: 100 to 336 mg/day (range: 25 to 800 mg/day) (Ahearn 2006; Hamner 2003; Kozaric-Kovacic 2007; Villarreal 2016). Some experts suggest gradually increasing dose based on response and tolerability in increments of 50 mg/week up to a total daily dose of 400 mg (Stein 2018).

Psychosis in Parkinson disease (off-label use):

Immediate release: Oral: Initial: 12.5 to 25 mg at bedtime; increase dose gradually based on response and tolerability in increments of 12.5 to 25 mg every 1 to 2 weeks; average dose in studies ranged from 40 to 185 mg/day (Fernandez 1999; Mancini 2004; Merims 2006). Some experts gradually increase dose based on response and tolerability up to 100 mg at bedtime and then add a morning dose if needed to control symptoms, up to a maximum of 200 mg/day as tolerated (Tarsy 2018).

Schizophrenia:

Immediate release: Oral: Initial: 25 mg twice daily; increase in increments of 25 to 50 mg/day in 2 or 3 divided doses on days 2 and 3 and increase further to a target dose of 300 to 400 mg/day by day 4. May further adjust dose based on response and tolerability in increments of 50 to 100 mg/day every ≥2 days. Acute therapy usual dosage range: 150 to 750 mg/day. Maintenance therapy usual dosage range: 400 to 800 mg/day; maximum dose: 800 mg/day.

Extended release: Oral: Initial: 300 mg once daily; may increase dose based on response and tolerability in increments of up to 300 mg/day every ≥1 day. Usual dosage range: 400 to 800 mg once daily; maximum dose: 800 mg/day.

Note: Doses up to 1.6 g/day have been evaluated in clinical studies; however, doses >800 mg/day were not found to offer greater efficacy, may result in greater adverse effects, and are generally not recommended (Honer 2012; Lindenmayer 2011; Nagy 2005; Stroup 2018).

Dosing conversion: To convert patients between immediate-release and ER tablets, administer the equivalent total daily dose. Administer immediate-release daily dose in 1 to 3 divided doses and extended release once daily; individual dosage adjustments may be necessary.

Reinitiation of treatment: Patients who have discontinued therapy for >1 week should generally be re-titrated using the initial dosing schedule; patients who have discontinued <1 week can generally be reinitiated on their previous maintenance dose.

Dosage adjustment for concomitant therapy:

Concomitant use with a strong CYP3A4 inhibitor (eg, voriconazole, itraconazole, ritonavir, nefazodone): Avoid combination if an appropriate noninteracting alternative is available; otherwise decrease quetiapine to one-sixth of the original dose; when strong CYP3A4 inhibitor is discontinued, increase quetiapine by 6-fold. Some combinations are considered contraindicated or not recommended.

Concomitant use with a strong CYP3A4 inducer (eg, phenytoin, carbamazepine, rifampin, St John's wort): Avoid combination if an appropriate noninteracting alternative is available; otherwise increase quetiapine up to 5-fold of the original dose when combined with chronic treatment (>7 to 14 days) of a strong CYP3A4 inducer; increase quetiapine dose based on response and tolerability; when the strong CYP3A4 inducer is discontinued, decrease quetiapine to the original dose within 7 to 14 days.

Discontinuation of therapy: Gradual dose reduction is advised to avoid withdrawal symptoms (ie, insomnia, headache, and GI symptoms) unless discontinuation is due to significant adverse effects. In general, when discontinuing antipsychotic therapy for chronic psychiatric disorders (eg, bipolar disorder, schizophrenia), decreasing the dose very gradually over weeks to months (eg, reducing the dose by 10% per month) with close monitoring is suggested to allow for detection of prodromal symptoms of disease recurrence (APA [Lehman 2004]; CPA 2005).

Switching antipsychotics: An optimal universal strategy for switching antipsychotic drugs has not been established. Strategies include: Cross-titration (gradually discontinuing the first antipsychotic while gradually increasing the new antipsychotic) and abrupt change (abruptly discontinuing the first antipsychotic and either increasing the new antipsychotic gradually or starting it at a treatment dose). In patients with schizophrenia at high risk of relapse, the current medication may be maintained at full dose as the new medication is increased (ie, overlap); once the new medication is at therapeutic dose, the first medication is gradually decreased and discontinued over 1 to 2 weeks (Cerovecki 2013; Remington 2005; Takeuchi 2017). Based upon clinical experience, some experts generally prefer cross-titration and overlap approaches rather than abrupt change (Post 2019; Stroup 2019).

* See Dosage and Administration in AHFS Essentials for additional information.

Dosing: Geriatric

Bipolar disorder or schizophrenia: Immediate release, Extended release: Oral: Initial: 50 mg/day; may increase in increments of 50 mg/day to an effective dose, based on individual clinical response and tolerability. Some experts recommend starting doses as low as 12.5 to 25 mg/day (Sajatovic 2018).

Major depressive disorder (unipolar): Adjunct to antidepressants or monotherapy (off-label): Extended release: Oral: Initial: 50 mg once daily; may increase by 50 mg/day to an effective dose, based on individual response and tolerability. Maximum dose (manufacturer's labeling): 300 mg/day

Refer to adult dosing for additional uses. Use caution; initiate at lower end of the dosing range, as elderly patients have an increased risk of adverse effects to antipsychotics.

Dosing conversion: Refer to adult dosing.

Reinitiation of treatment: Refer to adult dosing.

Dosage adjustment for concomitant therapy: Refer to adult dosing.

Discontinuation of therapy: Refer to adult dosing.

Switching antipsychotics: Refer to adult dosing.

Dosing: Renal Impairment: Adult

No dosage adjustment necessary.

Dosing: Hepatic Impairment: Adult

IR tablet: Initial: 25 mg once daily; increase dose by 25 to 50 mg/day to effective dose, based on individual clinical response and tolerability.

ER tablet: Initial: 50 mg once daily; increase dose by 50 mg once daily to effective dose, based on individual clinical response and tolerability.

Dosing: Pediatric

Bipolar disorder, mania or mixed episodes: Children and Adolescents ≥10 years: Oral:

Immediate-release tablet: Initial: 25 mg twice daily on day 1; increase to 50 mg twice daily on day 2, then 100 mg twice daily on day 3, then 150 mg twice daily on day 4, then continue at the target dose of 200 mg twice daily beginning on day 5. May increase further based on clinical response and tolerability at increments ≤100 mg/day up to 300 mg twice daily; however, no additional benefit was seen with 300 mg twice daily vs 200 mg twice daily. Usual dosage range: 200 to 300 mg twice daily; maximum daily dose: 600 mg/day. Total daily doses may also be divided into 3 doses per day. Continue therapy at lowest dose needed to maintain remission; periodically assess maintenance treatment needs.

Extended-release tablet: Initial: 50 mg once daily on day 1; increase to 100 mg once daily on day 2, then increase in 100 mg/day increments each day until a target dose of 400 mg once daily is reached on day 5. Usual dosage range: 400 to 600 mg once daily; maximum daily dose: 600 mg/day; continue therapy at lowest dose needed to maintain remission; periodically assess maintenance treatment needs.

Switching from immediate release to extended release: May convert patients from immediate-release to extended-release tablets at the equivalent total daily dose and administer once daily; individual dosage adjustments may be necessary.

Schizophrenia: Adolescents: Oral:

Immediate-release tablet: Initial: 25 mg twice daily on day 1; increase to 50 mg twice daily on day 2, 100 mg twice daily on day 3, then 150 mg twice daily on day 4, then continue at a target dose of 200 mg twice daily beginning on day 5. May increase further based on clinical response and tolerability at increments ≤100 mg/day up to 400 mg twice daily; however, no additional benefit was seen with 400 mg twice daily vs 200 mg twice daily. Usual dosage range: 200 to 400 mg twice daily; maximum daily dose: 800 mg/day. Total daily doses may also be divided into 3 doses per day. Periodically assess maintenance treatment needs.

Extended-release tablet: Initial: 50 mg once daily on day 1; increase to 100 mg once daily on day 2, then increase in 100 mg/day increments each day until a target dose of 400 mg once daily is reached on day 5. Usual dosage range: 400 to 800 mg once daily; maximum daily dose: 800 mg/day. Periodically assess maintenance treatment needs.

Switching from immediate release to extended release: May convert patients from immediate-release to extended-release tablets at the equivalent total daily dose and administer once daily; individual dosage adjustments may be necessary.

Dosing conversion: To convert patients between immediate-release and extended-release tablets, administer the equivalent total daily dose. Administer immediate release 1 to 3 times daily and extended release once daily; individual dosage adjustments may be necessary.

Reinitiation of treatment: Patients who have discontinued therapy for >1 week should generally be retitrated using the initial dosing schedule; patients who have discontinued <1 week can generally be reinitiated on their previous maintenance dose.

Dosage adjustment for concomitant therapy: Children ≥10 years and Adolescents:

Concomitant use with a strong CYP3A4 inhibitor (eg, ketoconazole, itraconazole, indinavir, ritonavir, nefazodone): Immediate release or extended release: Decrease quetiapine to one-sixth of the original dose; when strong CYP3A4 inhibitor is discontinued, increase quetiapine dose by sixfold.

Concomitant use with a strong CYP3A4 inducer (eg, phenytoin, carbamazepine, rifampin, St. John's wort): Immediate release or extended release: Increase quetiapine up to fivefold of the original dose when combined with chronic treatment (>7 to 14 days) of a strong CYP3A4 inducer; titrate based on clinical response and tolerance; when the strong CYP3A4 inducer is discontinued, decrease quetiapine to the original dose within 7 to 14 days.

Dosing: Renal Impairment: Pediatric

No adjustment required.

Dosing: Hepatic Impairment: Pediatric

Lower clearance in hepatic impairment (30% lower); higher plasma levels expected. Based on experience in adult patients, dosage adjustment suggested.

Use: Labeled Indications

Bipolar disorder: Acute treatment of manic (both immediate release and ER) or mixed (ER only) episodes and acute hypomanic episodes (off-label) associated with bipolar I disorder, both as monotherapy and as an adjunct to antimanic therapy; maintenance treatment of bipolar I disorder, as monotherapy (off-label) or as an adjunct to antimanic therapy; acute treatment of bipolar major depression, as monotherapy.

Major depressive disorder (unipolar) (ER only): Adjunctive therapy in patients with an inadequate response to antidepressants for the treatment of major depressive disorder.

Schizophrenia: Treatment of schizophrenia.

* See Uses in AHFS Essentials for additional information.

Use: Off-Label: Adult

Agitation/aggression and psychosis associated with dementia, severe or refractory (alternative agent)Level of Evidence [B, G]

Data from a randomized, double-blind, placebo-controlled study support the use of quetiapine in the treatment of psychosis/agitation in dementia ^Ref; data from a limited number of patients in open-label trials also suggest quetiapine may be beneficial in the treatment of psychosis/agitation in Alzheimer dementia ^Ref.

Based on the American Psychiatric Association (APA) practice guideline on the use of antipsychotics to treat agitation or psychosis in patients with dementia, antipsychotics such as quetiapine may be considered for the treatment of agitation and psychosis in certain patients; however, evidence for efficacy is modest and use should be limited to patients whose symptoms are dangerous, severe, or cause significant patient distress due to safety risks associated with antipsychotic use ^Ref. Based on the World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the treatment of Alzheimer disease and other dementias, drug treatment with quetiapine for behavioral and psychological aspects (including hyperactivity and psychosis) is recommended at low doses and for short durations, as a last option after addressing causative factors and using psychosocial interventions ^Ref.

Agitation and/or delirium, ICU (alternative agent)Level of Evidence [C, G]

Data from a limited number of patients in a prospective, randomized, double-blind, placebo-controlled study suggest that quetiapine may be beneficial in ICU delirium ^Ref.

Based on the Society of Critical Care Medicine guidelines for the prevention and management of pain, agitation/sedation, delirium, immobility, and sleep disruption in adult patients in the ICU, short-term use of antipsychotics like quetiapine may be useful for ICU patients who experience significantly distressing symptoms of delirium (eg, agitation, anxiety, delusions, fearfulness, hallucinations), or those who may be physically harmful to themselves or others. The guideline discourages routine use of antipsychotics for patients with delirium ^Ref.

Delusional infestation (delusional parasitosis)Level of Evidence [C]

Data from a limited number of patients studied in case reports suggest that quetiapine may be beneficial for the treatment of delusional infestation (also known as delusional parasitosis) ^Ref. Access Full Off-Label Monograph

Generalized anxiety disorder (alternative agent)Level of Evidence [B, G]

Data from double-blind, randomized, placebo-controlled trials and a meta-analysis support the use of quetiapine as monotherapy or as an adjunct to antidepressants in the treatment of generalized anxiety disorder (GAD) ^Ref.

Based on the WFSBP guidelines for the pharmacological treatment of anxiety, obsessive-compulsive, and posttraumatic stress disorders, quetiapine is effective and recommended in the management of GAD ^Ref. Based on the Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress, and obsessive-compulsive disorders, quetiapine monotherapy is recommended in patients who cannot take antidepressants, pregabalin, or benzodiazepines and as an adjunctive therapy in treatment-resistant GAD ^Ref.

Major depressive disorder (unipolar), monotherapy (alternative agent)Level of Evidence [B]

Data from a meta-analysis of 3 randomized, double-blind, placebo-controlled studies in adults and a randomized, double-blind, placebo-controlled study in elderly patients support the use of quetiapine monotherapy in the treatment of major depressive disorder ^Ref.

Obsessive-compulsive disorder, treatment-resistant (augmentation)Level of Evidence [C, G]

Data from a limited number of clinical trials suggest that quetiapine augmentation may be beneficial for the treatment of obsessive-compulsive disorder (OCD) ^Ref.

Based on the APA practice guideline for the treatment of patients with OCD and the WFSBP guidelines for the pharmacological treatment of anxiety, obsessive-compulsive, and posttraumatic stress disorders, antipsychotics given as augmentation are effective and recommended in the management of treatment-resistant OCD in patients who have a partial response to initial treatment; however, evidence supporting quetiapine is limited ^Ref.

Posttraumatic stress disorder, adjunct to antidepressants or monotherapy (alternative agent)Level of Evidence [C, G]

Data from a limited number of clinical trials suggest that monotherapy or adjunctive therapy with quetiapine may be beneficial for the treatment of posttraumatic stress disorder (PTSD) in patients who have had an inadequate response to antidepressants ^Ref.

Based on the APA practice guidelines for the treatment of patients with acute stress disorder and posttraumatic stress disorder and the WFSBP guidelines for the pharmacological treatment of anxiety, obsessive-compulsive, and posttraumatic stress disorders, therapy with antipsychotics like quetiapine is suggested as a treatment option when concomitant psychotic symptoms are present or when first-line approaches have been ineffective in controlling symptoms; however, evidence supporting use is greater for other antipsychotic agents including risperidone and olanzapine ^Ref. Based on the Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress, and obsessive-compulsive disorders, quetiapine is recommended as a third-line agent for monotherapy or as an adjunct to first-line agents in patients with refractory PTSD ^Ref. In contrast, the Veterans Affairs/Department of Defense clinical practice guideline for the management of posttraumatic stress disorder and acute stress disorder, suggests against the use of quetiapine for the treatment of PTSD due to the lack of strong evidence for efficacy and known adverse effects and associated risks.

Psychosis in Parkinson diseaseLevel of Evidence [C, G]

Data from a limited number of clinical trials suggest that quetiapine may be beneficial for the treatment of psychosis in patients with Parkinson disease ^Ref.

Based on joint guidelines on the management of Parkinson disease from the European Federation of Neurological Societies and the European section of the Movement Disorder Society, quetiapine is possibly useful when psychosis persists after managing triggering factors and reducing polypharmacy and antiparkinsonian drugs ^Ref.

Level of Evidence Definitions

Level of Evidence Scale

Clinical Practice Guidelines

Alzheimer Disease and other Dementias:

American Psychiatric Association, “Practice Guideline on the Use of Antipsychotics to Treat Agitation or Psychosis in Patients with Dementia,” May 2016

WFSBP, “Guidelines for the Biological Treatment of Alzheimer’s Disease and Other Dementias,” 2011

Anxiety Disorders:

Anxiety Disorders Association of Canada, "Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders," 2014

WFSBP, "Guidelines for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Post-Traumatic Stress Disorders, First Revision," 2008

Bipolar Disorder:

American Academy of Child and Adolescent Psychiatry. “Practice Parameter for the Assessment and Treatment of Children and Adolescents with Bipolar Disorder,” 2007

American Psychiatric Association. “Practice Guideline for the Treatment of Patients with Bipolar Disorder (Revision),” 2002

American Psychiatric Association, "Practice guideline for the treatment of patients with bipolar disorder, 2nd Edition, Guideline Watch," 2005

CANMAT/ISBD, "2018 Guidelines for the Management of Patients with Bipolar Disorder," March 2018

National Institute for Health and Clinical Excellence (NICE), National Collaborating Centre for Mental Health, “Bipolar Disorder: The Assessment and Management of Bipolar Disorder in Adults, Children and Young People in Primary and Secondary Care,” 2014

WFSBP, "Guidelines for the Biological Treatment of Bipolar Disorders: Acute and Long-Term Treatment of Mixed States in Bipolar Disorder," February 2018

WFSBP, “Guidelines for the Biological Treatment of Bipolar Disorders: Update 2009 on the Treatment of Acute Mania,” 2009

WFSBP, “Guidelines for the Biological Treatment of Bipolar Disorders: Update 2010 on the Treatment of Acute Bipolar Depression,” 2010

WFSBP, “Guidelines for the Biological Treatment of Bipolar Disorders: Update 2012 on the Long-term Treatment of Bipolar Disorder,” 2013

Delirium:

Society of Critical Care Medicine, "Guidelines for the prevention and management of pain, agitation/sedation, delirium, immobility, and sleep disruption in adult patients in the ICU," September 2018

Depression:

American Psychiatric Association, Practice Guideline for the Treatment of Patients with Major Depressive Disorder, Third Edition, May 2010

National Collaborating Centre for Mental Health (NCCMH), “Depression: The NICE Guideline on the Treatment and Management of Depression in Adults (Updated Edition).” 2010.

WFSBP, “Guidelines for Biological Treatment of Unipolar Depressive Disorders, Part 1: Update 2013 on the Acute and Continuation Treatment of Unipolar Depressive Disorders,” 2013

WFSBP, “Guidelines for Biological Treatment of Unipolar Depressive Disorders, Part 2: Maintenance Treatment of Major Depressive Disorder; Update 2015," 2015

Obsessive-Compulsive Disorder (OCD):

American Psychiatric Association, "Practice Guideline for the Treatment of Patients with Obsessive-Compulsive Disorder," 2007

WFSBP, "Guidelines for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Post-Traumatic Stress Disorders, First Revision," 2008

Posttraumatic Stress Disorder (PTSD):

American Psychiatric Association, “Practice Guideline for the Treatment of Patients with Acute Stress Disorder and Posttraumatic Stress Disorder,” 2004

American Psychiatric Association, “Practice Guideline for the Treatment of Patients with Acute Stress Disorder and Posttraumatic Stress Disorder: Guideline Watch,” March 2009

Anxiety Disorders Association of Canada, "Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders," 2014

US Department of Veterans Affairs/Department of Defense (VA/DoD), “Clinical Practice Guideline for the Management of Posttraumatic Stress Disorder and Acute Stress Disorder,” June 2017

WFSBP, "Guidelines for the Pharmacological Treatment of Anxiety, Obsessive-Compulsive and Post-Traumatic Stress Disorders, First Revision," 2008

Psychosis in Parkinson disease:

European Federation of Neurological Societies and the European section of the Movement Disorder Society, "Summary of the recommendations of the EFNS/MDS-ES review on therapeutic management of Parkinson’s disease," 2013

Schizophrenia:

American Psychiatric Association,” Practice Guideline for the Treatment of Patients with Schizophrenia, Second Edition,” 2004

American Psychiatric Association,” Guideline Watch: Practice Guideline for the Treatment of Patients with Schizophrenia, Second Edition.” September 2009

National Institute for Health and Clinical Excellence (NICE), National Collaborating Center for Mental Health, "Psychosis and Schizophrenia in Adults: Treatment and Management " March 2014

National Institute for Health and Clinical Excellence (NICE), National Collaborating Center for Mental Health, "Psychosis and Schizophrenia in Children and Young People: Recognition and Management" 2013

WFSBP, “Guidelines for the Biological Treatment of Schizophrenia, Part 1: Update 2012 on the Acute Treatment of Schizophrenia and the Management of Treatment Resistance,” 2012

WFSBP, “Guidelines for the Biological Treatment of Schizophrenia, Part 2: Update 2012 on the Long-Term Treatment of Schizophrenia and Management of Antipsychotic-Induced Side Effects,” 2013

Administration: Oral

Immediate-release tablet: Administer with or without food.

Extended-release tablet: Administer without food or with a light meal (≤300 calories), preferably in the evening. Swallow tablet whole; do not break, crush, or chew.

Administration: Other

Nasogastric/enteral tube (off-label route): Hold tube feeds for 30 minutes before administration; flush with 25 mL of sterile water. Crush dose using immediate-release formulation, mix in 10 mL water and administer via NG/enteral tube; follow with a 50 mL flush of sterile water (Devlin 2010).

Administration: Pediatric

Oral:

Immediate-release tablet: May be administered with or without food.

Extended-release tablet: Administer without food or with a light meal (≤300 calories), preferably in the evening. Swallow tablet whole; do not break, crush, or chew.

Nasogastric/enteral tube: Immediate-release tablet: Based on experience in adult patients: Hold tube feeds for 30 minutes before administration; flush with 25 mL of sterile water. Crush dose, mix in 10 mL water, and administer via NG/enteral tube; follow with a 50 mL flush of sterile water. Restart tube feedings after drug administration (Devlin 2010).

Dietary Considerations

Administer extended-release tablet without food or with a light meal (≤300 calories).

Storage/Stability

Store at 25°C (77°F); excursions permitted between 15°C and 30°C (59°F and 86°F).

Medication Patient Education with HCAHPS Considerations

What is this drug used for?

• It is used to treat bipolar problems.

• It is used to treat schizophrenia.

• It is used to treat low mood (depression).

• It may be given to you for other reasons. Talk with the doctor.

Frequently reported side effects of this drug

• Anxiety

• Dry mouth

• Fatigue

• Increased appetite

• Weight gain

• Nausea

• Vomiting

• Stuffy nose

• Back pain

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Low thyroid level like constipation; trouble handling heat or cold; memory problems; trouble with memory; or burning, numbness, or tingling feeling

• Depression like suicidal ideation, anxiety, emotional instability, agitation, irritability, panic attacks, mood changes, behavioral changes, or confusion

• Infection

• High blood sugar like confusion, feeling sleepy, more thirst, hunger, passing urine more often, flushing, fast breathing, or breath that smells like fruit.

• Severe dizziness

• Passing out

• Severe headache

• Abnormal heartbeat

• Fast heartbeat

• Chest pain

• Abnormal movements

• Twitching

• Change in balance

• Trouble swallowing

• Trouble speaking

• Tremors

• Trouble moving

• Rigidity

• Severe loss of strength and energy

• Drooling

• Seizures

• Severe abdominal pain

• Trouble urinating

• Flu-like symptoms

• Vision changes

• Enlarged breasts

• Nipple discharge

• Sexual dysfunction

• No menstrual periods

• Severe constipation

• Neuroleptic malignant syndrome like fever, muscle cramps or stiffness, dizziness, very bad headache, confusion, change in thinking, fast heartbeat, abnormal heartbeat, or sweating a lot

• Tardive dyskinesia like unable to control body movements; tongue, face, mouth, or jaw sticking out; mouth puckering; and puffing cheeks

• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Medication Safety Issues

Sound-alike/look-alike issues:

Geriatric Patients: High-Risk Medication:

Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:

Seroquel: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/020639s066lbl.pdf#page=49

Seroquel XR: https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/022047s040lbl.pdf#page=52

Contraindications

Hypersensitivity to quetiapine or any component of the formulation

Warnings/Precautions

Major psychiatric warnings:

• Suicidal thinking/behavior: [US Boxed Warning]: Antidepressants increase the risk of suicidal thinking and behavior in children, adolescents, and young adults (18 to 24 years of age) with major depressive disorder (MDD) and other psychiatric disorders; consider risk prior to prescribing. Short-term studies did not show an increased risk in patients >24 years of age and showed a decreased risk in patients ≥65 years of age. Closely monitor all patients for clinical worsening, suicidality, or unusual changes in behavior, particularly during the initial 1 to 2 months of therapy or during periods of dosage adjustments (increased or decreases); the patient's family or caregiver should be instructed to closely observe the patient and communicate condition with healthcare provider. A medication guide concerning the use of antidepressants should be dispensed with each prescription. Quetiapine is not approved in the US for use in children <10 years of age.

- The possibility of a suicide attempt is inherent in major depression and may persist until remission occurs. Worsening depression and severe abrupt suicidality that are not part of the presenting symptoms may require discontinuation or modification of drug therapy. Use caution in high-risk patients during initiation of therapy.

- Prescriptions should be written for the smallest quantity consistent with good patient care. The patient's family or caregiver should be alerted to monitor patients for the emergence of suicidality and associated behaviors such as anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia, hypomania, and mania; patients should be instructed to notify their healthcare provider if any of these symptoms or worsening depression or psychosis occur.

Concerns related to adverse effects:

• Anticholinergic effects: May cause anticholinergic effects (confusion, agitation, constipation, xerostomia, blurred vision, urinary retention); use with caution in patients with decreased gastrointestinal motility, urinary retention, BPH, or increased intraocular pressure. Relative to other antipsychotics, quetiapine has a low potency of cholinergic blockade (Richelson 1999).

• Blood dyscrasias: Leukopenia, neutropenia, and agranulocytosis (sometimes fatal) have been reported with quetiapine use, including cases in patients without risk factors. Consider neutropenia in patients with infection or unexplained fever. Presence of risk factors (eg, preexisting low WBC or history of drug-induced leuko-/neutropenia) should prompt periodic blood count assessment; discontinue therapy with WBC decline without other causative factors. Carefully monitor patients with neutropenia for fever and signs/symptoms of infection and discontinue therapy if absolute neutrophil count <1,000/mm³.

• Cataracts: Use has been noted to cause cataracts in animals; lens changes have been observed in humans during long-term treatment. Lens examination, such as a slit-lamp exam, on initiation of therapy and every 6 months is recommended by manufacturer.

• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving).

• Esophageal dysmotility/Aspiration: Antipsychotic use has been associated with esophageal dysmotility and aspiration; risk increases with age. Use with caution in patients at risk for aspiration pneumonia (ie, Alzheimer disease), particularly in patients >75 years of age (Herzig 2017; Maddalena 2004).

• Extrapyramidal symptoms: May cause extrapyramidal symptoms (EPS), including pseudoparkinsonism, acute dystonic reactions, akathisia, and tardive dyskinesia (risk of these reactions is generally much lower relative to typical/conventional antipsychotics; frequencies reported are similar to placebo). Risk of dystonia (and probably other EPS) may be greater with increased doses, use of conventional antipsychotics, males, and younger patients. Factors associated with greater vulnerability to tardive dyskinesia include older in age, female gender combined with postmenopausal status, Parkinson disease, pseudoparkinsonism symptoms, affective disorders (particularly major depressive disorder), concurrent medical diseases such as diabetes, previous brain damage, alcoholism, poor treatment response, and use of high doses of antipsychotics (APA [Lehman 2004]; Soares-Weiser 2007). Consider therapy discontinuation with signs/symptoms of tardive dyskinesia.

• Falls: May increase the risk for falls due to somnolence, orthostatic hypotension, and motor or sensory instability. Complete fall risk assessments at baseline and periodically during treatment in patients with diseases or on medications that may also increase fall risk.

• Hyperglycemia: Atypical antipsychotics have been associated with development of hyperglycemia; in some cases, may be extreme and associated with ketoacidosis, hyperosmolar coma, or death. All patients should be monitored for symptoms of hyperglycemia (eg, polydipsia, polyuria, polyphagia, weakness) and undergo a fasting blood glucose test if symptoms develop during treatment. Patients with risk factors for diabetes (eg, obesity or family history) should have a baseline fasting blood sugar (FBS) and periodically during treatment. Compared to other antipsychotics, the risk of metabolic adverse reactions including hyperglycemia with quetiapine is moderate (Solmi 2017).

• Hyperlipidemia: Increases in cholesterol and triglycerides have been noted. Use with caution in patients with pre-existing abnormal lipid profile. Compared to other antipsychotics, the risk of metabolic adverse reactions including hyperlipidemia with quetiapine is moderate (Solmi 2017).

• Hyperprolactinemia: May increase prolactin levels; clinical significance of hyperprolactinemia in patients with breast cancer or other prolactin-dependent tumors is unknown.

• Hypersensitivity: Anaphylactic reactions have been reported.

• Hypothyroidism: May cause dose-related decreases in thyroid levels, including cases requiring thyroid replacement therapy. Reversal of thyroid effects occurred in almost all cases following discontinuation. Measure both TSH and free T₄, along with clinical assessment, at baseline and follow-up to determine thyroid status; measurement of TSH alone may not be accurate (exact mechanism of quetiapine's effect on the thyroid axis is unknown).

• Neuroleptic malignant syndrome (NMS): Use may be associated with neuroleptic malignant syndrome (NMS); monitor for mental status changes, fever, muscle rigidity and/or autonomic instability. Rare cases have been reported with quetiapine.

• Orthostatic hypotension: May cause orthostatic hypotension; use with caution in patients at risk of this effect or in those who would not tolerate transient hypotensive episodes (cerebrovascular disease, cardiovascular disease, dehydration, hypovolemia, or concurrent medication use which may predispose to hypotension/bradycardia). Risk may be minimized by using a low initial dose (eg, immediate release 25 mg twice daily); if hypotension occurs during titration to the target dose, a return to the previous dose in the titration schedule is appropriate.

• QT prolongation: Use has been associated with QT prolongation; postmarketing reports have occurred in patients with concomitant illness, quetiapine overdose, or who were receiving concomitant therapy known to increase QT interval or cause electrolyte imbalance. Avoid use in patients at increased risk of torsade de pointes/sudden death (eg, hypokalemia, hypomagnesemia, history of cardiac arrhythmias, congenital prolongation of QT interval, concomitant medications with QTc interval-prolonging properties). Use with caution in patients at increased risk of QT prolongation (eg, cardiovascular disease, heart failure, cardiac hypertrophy, elderly, family history of QT prolongation).

• Temperature regulation: Impaired core body temperature regulation may occur; caution with strenuous exercise, heat exposure, dehydration, and concomitant medication possessing anticholinergic effects.

• Weight gain: Significant weight gain has been observed with antipsychotic therapy; incidence varies with product. Monitor waist circumference and BMI. Compared to other antipsychotics, the risk of weight gain with quetiapine is moderate (Solmi 2017).

Disease-related concerns:

• Dementia: [US Boxed Warning]: Elderly patients with dementia-related psychosis treated with antipsychotics are at an increased risk of death compared to placebo. Most deaths appeared to be either cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature. Use with caution in patients with Lewy body dementia or Parkinson disease dementia due to greater risk of adverse effects, increased sensitivity to extrapyramidal effects, and association with irreversible cognitive decompensation or death (APA [Reus 2016]). Quetiapine is not approved for the treatment of dementia-related psychosis.

• Hepatic impairment: Use with caution in patients with hepatic disease or impairment; may increase transaminases (primarily ALT; transient, reversible). Dose adjustment recommended.

• Renal impairment: Use with caution in patients with renal disease; experience is limited.

• Seizures: Use with caution in patients at risk of seizures, including those with a history of seizures, head trauma, brain damage, alcoholism, or concurrent therapy with medications which may lower seizure threshold. Elderly patients may be at increased risk of seizures due to an increased prevalence of predisposing factors.

Special populations:

• Pediatric: Pharmacologic treatment for pediatric bipolar I disorder or schizophrenia should be initiated only after thorough diagnostic evaluation and a careful consideration of potential risks vs benefits. If a pharmacologic agent is initiated, it should be a component of a total treatment program including psychological, educational and social interventions. Increased blood pressure (including hypertensive crisis) has been reported in children and adolescents; monitor blood pressure at baseline and periodically during use.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Other warnings/precautions:

• Discontinuation of therapy: When discontinuing antipsychotic therapy, gradual dose reduction is advised to avoid withdrawal symptoms (ie, insomnia, headache, and GI symptoms) unless discontinuation is due to significant adverse effects. The risk of withdrawal symptoms is highest following abrupt discontinuation of highly anti-cholinergic or dopaminergic antipsychotics (Cerovecki 2013). Additional factors such as duration of antipsychotic exposure, the indication for use, medication half-life, and risk for relapse should be considered. In schizophrenia, there is no reliable indicator to differentiate the minority who will not from the majority who will relapse with drug discontinuation. However, studies in which the medication of well-stabilized patients were discontinued indicate that 75% of patients relapse within 6 to 24 months. Indefinite maintenance antipsychotic medication is generally recommended, and especially for patients who have had multiple prior episodes or 2 episodes within 5 years (APA [Lehman 2004]).

* See Cautions in AHFS Essentials for additional information.

Geriatric Considerations

Elderly patients have an increased risk of adverse effects to antipsychotics. In light of this risk, and relative to their small beneficial effect size in the treatment of dementia-related psychosis and behavioral disorders, patients should be evaluated for possible reversible causes before being started on an antipsychotic. Nonpharmacologic interventions should be tried before initiating an antipsychotic.

Warnings: Additional Pediatric Considerations

Significant weight gain has been observed with antipsychotic therapy; incidence varies with specific drug. Monitor growth (including weight, height, BMI, and waist circumference) in pediatric patients receiving quetiapine; compare weight gain to standard growth curves. The SATIETY (Second-Generation Antipsychotic Treatment Indications, Effectiveness and Tolerability in Youth) study showed children and adolescents aged 4 to 19 years taking second-generation antipsychotics for the first time experienced significant weight gain, increase in BMI from baseline, and an increase in waist circumference with aripiprazole, olanzapine, quetiapine, and risperidone compared to untreated patients. Average weight gain after a median of 10.8 weeks was 8.5 kg with olanzapine, 6.1 kg with quetiapine, 5.3 kg with risperidone, and 4.4 kg with aripiprazole compared to 0.2 kg in untreated group. A significant increase in total cholesterol, triglycerides, and nonhigh density lipoprotein was seen with quetiapine and olanzapine. Biannual monitoring of cardiometabolic indices after the first 3 months of therapy is suggested (Correll 2009). Increases in cholesterol and triglycerides have been noted; in pediatric trials (ages: 10 to 17 years), total cholesterol increased to a clinically significant level (≥200 mg/dL) in 10% to 12% of patients, and triglycerides (≥150 mg/dL) in 17% to 22% of patients. Use with caution in patients with preexisting abnormal lipid profile; monitor lipid profile.

Hyperglycemia has been reported with atypical antipsychotics, which may be severe and include potentially fatal ketoacidosis or hyperosmolar coma. In pediatric (ages 10 to 17 years) clinical trials of quetiapine (exposure duration: 3 to 8 weeks), slight increases in fasting glucose levels were reported (mean change: -0.75 to 3.62 mg/dL vs. -1.7 to 1.6 mg/dL for placebo); however, no pediatric patients with baseline fasting glucose <126 mg/dL developed treatment-emergent hyperglycemia (≥126 mg/dL). However, with longer exposure (mean: 17.2 months), an increased risk for the development of type 2 diabetes mellitus (DM) was observed in pediatric patients 10 to 18 years receiving second-generation antipsychotics (SGA); for patients initiated on SGA: 0.4% incidence with mean exposure at time type 2 DM diagnosed: 13.5 months; for SGA noniniators (patients receiving another agent prior to SGA initiation): 0.2% incidence with mean exposure at time of type 2 DM diagnosed: 14.6 months. Amongst specific SGAs, the risk was highest for aripiprazole (p=0.001) followed by ziprasidone (p=0.06) compared to risperidone as the reference group but not quetiapine or olanzapine (Rubin 2015).

Quetiapine increases prolactin concentrations; in pediatric clinical trials (ages: 10 to 17 years), development of clinically significant prolactin levels occurred in 13.4% of male patients and 8.7% of females; high concentrations of prolactin may reduce pituitary gonadotropin secretion; galactorrhea, amenorrhea, gynecomastia, impotence, decreased bone density may occur. Use with caution in children and adolescents; adverse effects due to increased prolactin concentrations have been observed; long-term effects on growth or sexual maturation have not been evaluated.

In children and adolescents, increases in blood pressure (including hypertensive crisis) have been reported. In pediatric clinical trials (ages: 10 to 17 years), an increase in SBP (≥20 mm Hg) and DBP (≥10 mm Hg) was observed more frequently with quetiapine than placebo (SBP: 15.2% vs 5.5%; DBP: 40.6% vs 24.5%). Monitor blood pressure at baseline and periodically during therapy with quetiapine.

Pediatric psychiatric disorders are frequently serious mental disorders which present with variable symptoms that do not always match adult diagnostic criteria. Conduct a thorough diagnostic evaluation and carefully consider risks of psychotropic medication before initiation in pediatric patients. Medication therapy for pediatric patients with bipolar disorder and schizophrenia is indicated as part of a total treatment program that frequently includes educational, psychological, and social interventions.

Similar to adult experience, the American Academy of Child and Adolescent Psychiatry (AACAP) guidelines recommend gradually tapering antipsychotics to avoid withdrawal symptoms and minimize the risk of relapse (AACAP [McClellan 2007]). Although some atypical antipsychotics (eg, aripiprazole, risperidone) are used for management of autism spectrum disorders, efficacy of quetiapine is much less impressive (Martin 1999; Masi 2015).

Pregnancy Considerations

Quetiapine crosses the placenta and can be detected in cord blood (Newport 2007). Congenital malformations have not been observed in humans (based on available data). Antipsychotic use during the third trimester of pregnancy has a risk for abnormal muscle movements (extrapyramidal symptoms) and/or withdrawal symptoms in newborns following delivery. Symptoms in the newborn may include agitation, feeding disorder, hypertonia, hypotonia, respiratory distress, somnolence, and tremor; these effects may be self-limiting or require hospitalization.

Treatment algorithms have been developed by the American College of Obstetricians and Gynecologists (ACOG) and the American Psychiatric Association (APA) for the management of depression in women prior to conception and during pregnancy (Yonkers 2009). The ACOG recommends that therapy during pregnancy be individualized; treatment with psychiatric medications during pregnancy should incorporate the clinical expertise of the mental health clinician, obstetrician, primary health care provider, and pediatrician. Safety data related to atypical antipsychotics during pregnancy are limited; as such, routine use is not recommended. However, if a woman is inadvertently exposed to an atypical antipsychotic while pregnant, continuing therapy may be preferable to switching to an agent that the fetus has not yet been exposed to; consider risk:benefit (ACOG 2008). If treatment is needed in a woman planning a pregnancy or if treatment is initiated during pregnancy, use of quetiapine may be considered (Larsen 2015).

Quetiapine may cause hyperprolactinemia, which may decrease reproductive function in both males and females.

Health care providers are encouraged to enroll women 18 to 45 years of age exposed to quetiapine during pregnancy in the Atypical Antipsychotics Pregnancy Registry (1-866-961-2388 or http://www.womensmentalhealth.org/pregnancyregistry).

Breast-Feeding Considerations

Quetiapine is present in breast milk.

The relative infant dose (RID) of quetiapine is 0.43% when calculated using the highest breast milk concentration located and compared to a weight-adjusted maternal dose of 200 mg/day.

In general, breastfeeding is considered acceptable when the RID of a medication is <10% (Anderson 2016; Ito 2000).

The RID of quetiapine was calculated using a milk concentration of 62 mcg/L, providing an estimated daily infant dose via breast milk of 9.3 mcg/kg/day. This milk concentration was obtained following maternal administration of quetiapine 200 mg daily throughout pregnancy and after delivery; sampling occurred 3 weeks postpartum. The RID was calculated using the actual maternal weight. The maximum concentration of quetiapine in breast milk occurred 1 hour after the maternal dose (Lee 2004). In one case report, quetiapine was measured in the serum of a breastfed infant; the concentration was 6% of the maternal level obtained at the same time (Rampono 2007). Adverse events have not been reported in breastfeeding infants (Larsen 2015; Pacchiarotti 2016; Uguz 2016).

According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother. In general, infants exposed to second-generation antipsychotics via breast milk should be monitored weekly for the first month of exposure for symptoms such as appetite changes, insomnia, irritability, or lethargy (Uguz 2016). When an antipsychotic medication is needed in a breastfeeding woman, quetiapine may be used (Larsen 2015; Pacchiarotti 2016; Uguz 2016).

Briggs' Drugs in Pregnancy & Lactation

• Quetiapine

Adverse Reactions

Actual frequency may be dependent upon dose and/or indication. Unless otherwise noted, frequency of adverse effects is reported for adult patients; spectrum and incidence of adverse effects similar in children (with significant exceptions noted).

>10%:

Cardiovascular: Increased diastolic blood pressure (≥10 mm Hg; children and adolescents: 41% to 47%), increased systolic blood pressure (≥20 mm Hg; children and adolescents: 7% to 15%), tachycardia (1% to 11%)

Central nervous system: Drowsiness (16% to 57%), headache (17% to 21%), agitation (6% to 20%), dizziness (7% to 19%), fatigue (3% to 14%), extrapyramidal reaction (1% to 13%)

Endocrine & metabolic: Weight gain (dose related; 3% to 28%), increased serum triglycerides (≥200 mg/dL, 14% to 22%), decreased HDL cholesterol (≤40 mg/dL, 9% to 20%), total cholesterol increased (≥240 mg/dL, 7% to 18%), increased LDL cholesterol (≥160 mg/dL, 4% to 12%), hyperglycemia (≥200 mg/dL post glucose challenge or fasting glucose ≥126 mg/dL, 2% to 3%)

Gastrointestinal: Xerostomia (adults: 9% to 44%; children and adolescents: 4% to 10%), increased appetite (2% to 12%), constipation (2% to 11%)

1% to 10%:

Cardiovascular: Orthostatic hypotension (2% to 7%; children and adolescents <1%), palpitations (4%), peripheral edema (4%), increased heart rate (2% to 4%), hypotension (3%), hypertension (adults 2%), hypertension (1% to 2%), syncope (1% to 2%)

Central nervous system: Pain (7%), drug-induced Parkinson disease (2% to ≤6%), irritability (3% to 5%), lethargy (2% to 5%), dysarthria (2% to 5%), akathisia (1% to 5%), hypertonia (4%), twitching (4%), anxiety (2% to 4%), abnormal dreams (2% to 3%), depression (2% to 3%), hypersomnia (2% to 3%), paresthesia (2% to 3%), aggressive behavior (children and adolescents: 1% to 3%), dystonic reaction (1% to 3%), abnormality in thinking (2%), ataxia (2%), confusion (2%), decreased mental acuity (2%), disorientation (2%), disturbance in attention (2%), falling (2%), hypoesthesia (2%), lack of concentration (2%), migraine (2%), restless leg syndrome (2%), restlessness (2%), vertigo (2%)

Dermatologic: Skin rash (4%), acne vulgaris (children and adolescents: 2% to 3%), diaphoresis (2%), hyperhidrosis (2%), pallor (children and adolescents: 1% to 2%)

Endocrine & metabolic: Hyperprolactinemia (4%), increased thirst (children and adolescents: 2%), decreased libido (≤2%), hypothyroidism (≤2%)

Gastrointestinal: Nausea (5% to 10%), vomiting (3% to 8%), dyspepsia (2% to 7%), abdominal pain (1% to 7%), diarrhea (children and adolescents: 5%), viral gastroenteritis (4%), toothache (2% to 3%), anorexia (1% to 3%), periodontal abscess (adolescents: 1% to 3%), decreased appetite (2%), dysphagia (2%), gastroenteritis (2%), gastroesophageal reflux disease (2%)

Genitourinary: Pollakiuria (2%), urinary tract infection (2%)

Hematologic & oncologic: Neutropenia (≤2%), leukopenia (≥1%)

Hepatic: Increased serum transaminases (1% to 6%)

Hypersensitivity: Seasonal allergy (2%)

Neuromuscular & skeletal: Asthenia (1% to 10%), tremor (2% to 8%), back pain (1% to 5%), dyskinesia (3% to 4%), arthralgia (1% to 4%), muscle rigidity (3%), stiffness (children and adolescents: 3%), muscle spasm (2% to 3%), limb pain (2%), myalgia (2%), neck pain (2%)

Ophthalmic: Blurred vision (2% to 4%), amblyopia (2% to 3%)

Otic: Otalgia (2%)

Respiratory: Pharyngitis (4% to 6%), nasal congestion (3% to 6%), rhinitis (3% to 4%), epistaxis (adolescents: 3%), upper respiratory tract infection (3%), paranasal sinus congestion (2% to 3%), cough (≥1% to 3%), dyspnea (≥1% to 3%), sinus headache (2%), sinusitis (2%), influenza (1% to 2%)

Miscellaneous: Fever (2% to 4%)

<1%, postmarketing, and/or case reports: Abnormal gait, abnormality of accommodation, abnormal T waves on ECG, acute renal failure, agranulocytosis, alcohol intolerance, amenorrhea, amnesia, anaphylaxis, anemia, angina pectoris, apathy, aphasia, arthritis, asthma, atrial arrhythmia, atrial fibrillation, atrioventricular block, blepharitis, bradycardia, bruxism, buccoglossal syndrome, bundle branch block, candidiasis, cardiomyopathy, cataract, catatonia, cerebral ischemia, cerebrovascular accident, chills, choreoathetosis, colonic ischemia, conjunctivitis, contact dermatitis, cyanosis, cystitis, deafness, deep vein thrombophlebitis, dehydration, delirium, delusions, dental caries, depersonalization, dermal ulcer, diabetes mellitus, DRESS syndrome, dysmenorrhea, dysuria, ecchymosis, eczema, ejaculatory disorder, emotional lability, enlargement of abdomen, eosinophilia, euphoria, exfoliative dermatitis, eye pain, facial edema, fecal incontinence, first degree atrioventricular block, flattened T wave on ECG, flatulence, flu-like symptoms, galactorrhea not associated with childbirth, gastritis, gingival hemorrhage, gingivitis, glaucoma, glossitis, glycosuria, gout, gynecomastia, hallucination, hand edema, hematemesis, hemiplegia, hemolysis, hemorrhoids, hepatic failure, hepatic necrosis, hepatitis, hiccups, hyperglycemic hyperosmolar syndrome, hyperkinesia, hyperlipemia, hypersensitivity reaction, hyperthyroidism, hyperventilation, hypochromic anemia, hypoglycemia, hypokalemia, hyponatremia, hypothermia, impotence, increased creatine phosphokinase, increased gamma-glutamyl transferase, increased libido, increased salivation, increased serum alkaline phosphatase, increased serum creatinine, increased ST segment on ECG, insomnia, intestinal obstruction, inversion T wave on ECG, involuntary body movements, irregular pulse, ketoacidosis, lactation (females), leukocytosis, leukorrhea, lower limb cramp, lymphadenopathy, maculopapular rash, malaise, manic reaction, melena, myasthenia, myocarditis, myoclonus, neuralgia, neuroleptic malignant syndrome, nightmares, nocturia, obstructive sleep apnea syndrome (Health Canada 2016; Shirani 2011), oral mucosal ulcer, orchitis, ostealgia, pancreatitis, paranoia, pathological fracture, pelvic pain, pneumonia, polyuria, priapism, prolonged Q-T interval on ECG, pruritus, psoriasis, psychosis, rectal hemorrhage, retrograde amnesia, rhabdomyolysis, seborrhea, seizure, skin discoloration, skin photosensitivity, SIADH, sleep apnea, somnambulism, Stevens-Johnson syndrome, stomatitis, ST segment changes on ECG, stupor, stuttering, subdural hematoma, suicidal ideation, suicidal tendencies, tardive dyskinesia, taste perversion, thrombocytopenia, thrombophlebitis, tinnitus, tongue edema, toxic epidermal necrolysis, urinary frequency, urinary incontinence, urinary retention, uterine hemorrhage, vaginal hemorrhage, vaginitis, vasodilation, visual disturbance, vulvovaginal candidiasis, vulvovaginitis, water intoxication, weight loss, widened QRS complex on ECG, xerophthalmia

* See Cautions in AHFS Essentials for additional information.

Allergy and Idiosyncratic Reactions

• QUEtiapine Allergy

Toxicology

• Antipsychotic Agents, Atypical

Metabolism/Transport Effects

Substrate of CYP2D6 (minor), CYP3A4 (major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential

Drug Interactions Open Interactions

Acetylcholinesterase Inhibitors: May diminish the therapeutic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Risk C: Monitor therapy

Acetylcholinesterase Inhibitors (Central): May enhance the neurotoxic (central) effect of Antipsychotic Agents. Severe extrapyramidal symptoms have occurred in some patients. Risk C: Monitor therapy

Aclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination

Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy

Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Amifampridine: Agents With Seizure Threshold Lowering Potential may enhance the neuroexcitatory and/or seizure-potentiating effect of Amifampridine. Risk C: Monitor therapy

Amisulpride: Antipsychotic Agents may enhance the adverse/toxic effect of Amisulpride. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Risk X: Avoid combination

Amisulpride: May enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk). Risk X: Avoid combination

Amphetamines: Antipsychotic Agents may diminish the stimulatory effect of Amphetamines. Risk C: Monitor therapy

Anticholinergic Agents: May enhance the adverse/toxic effect of other Anticholinergic Agents. Risk C: Monitor therapy

Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy

Anti-Parkinson Agents (Dopamine Agonist): Antipsychotic Agents (Second Generation [Atypical]) may diminish the therapeutic effect of Anti-Parkinson Agents (Dopamine Agonist). Management: Consider using an alternative antipsychotic agent when possible in patients with Parkinson disease. If an atypical antipsychotic is necessary, consider using clozapine or quetiapine, which may convey the lowest interaction risk. Risk D: Consider therapy modification

Aprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Risk X: Avoid combination

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Risk D: Consider therapy modification

Blood Pressure Lowering Agents: May enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor therapy

Bosentan: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Botulinum Toxin-Containing Products: May enhance the anticholinergic effect of Anticholinergic Agents. Risk C: Monitor therapy

Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Risk C: Monitor therapy

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Bromopride: May enhance the adverse/toxic effect of Antipsychotic Agents. Risk X: Avoid combination

Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Risk D: Consider therapy modification

BuPROPion: May enhance the neuroexcitatory and/or seizure-potentiating effect of Agents With Seizure Threshold Lowering Potential. Risk C: Monitor therapy

Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Cannabis: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

CarBAMazepine: QUEtiapine may increase serum concentrations of the active metabolite(s) of CarBAMazepine. CarBAMazepine may decrease the serum concentration of QUEtiapine. Management: Quetiapine dose increases to as much as 5 times the regular dose may be required to maintain therapeutic benefit. Reduce the quetiapine dose back to the previous/regular dose within 7 to 14 days of discontinuing carbamazepine. Risk D: Consider therapy modification

Chloral Betaine: May enhance the adverse/toxic effect of Anticholinergic Agents. Risk C: Monitor therapy

Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider therapy modification

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy

Cimetropium: Anticholinergic Agents may enhance the anticholinergic effect of Cimetropium. Risk X: Avoid combination

Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

CloZAPine: Anticholinergic Agents may enhance the constipating effect of CloZAPine. Management: Consider alternatives to this combination whenever possible. If combined, monitor closely for signs and symptoms of gastrointestinal hypomotility and consider prophylactic laxative treatment. Risk D: Consider therapy modification

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy

Conivaptan: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

CYP3A4 Inducers (Moderate): May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

CYP3A4 Inducers (Strong): May decrease the serum concentration of QUEtiapine. Management: An increase in quetiapine dose (as much as 5 times the regular dose) may be required to maintain therapeutic benefit. Reduce the quetiapine dose back to the previous/regular dose within 7-14 days of discontinuing the inducer. Risk D: Consider therapy modification

CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

CYP3A4 Inhibitors (Strong): May increase the serum concentration of QUEtiapine. Management: In quetiapine treated patients, reduce quetiapine to one-sixth of regular dose after starting strong CYP3A4 inhibitor. In those on strong CYP3A4 inhibitors, start quetiapine at lowest dose and up-titrate as needed. Exceptions discussed separately. Exceptions: Ceritinib; Clarithromycin; Saquinavir; Voriconazole. Risk D: Consider therapy modification

Dabrafenib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Seek alternatives to the CYP3A4 substrate when possible. If concomitant therapy cannot be avoided, monitor clinical effects of the substrate closely (particularly therapeutic effects). Risk D: Consider therapy modification

Deferasirox: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Deutetrabenazine: May enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, the risk for akathisia, parkinsonism, or neuroleptic malignant syndrome may be increased. Risk C: Monitor therapy

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Domperidone: QT-prolonging Agents (Moderate Risk) may enhance the QTc-prolonging effect of Domperidone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification

Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Risk C: Monitor therapy

Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Droperidol: QT-prolonging Antipsychotics (Moderate Risk) may enhance the QTc-prolonging effect of Droperidol. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

Duvelisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Eluxadoline: Anticholinergic Agents may enhance the constipating effect of Eluxadoline. Risk X: Avoid combination

Enzalutamide: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Concurrent use of enzalutamide with CYP3A4 substrates that have a narrow therapeutic index should be avoided. Use of enzalutamide and any other CYP3A4 substrate should be performed with caution and close monitoring. Risk D: Consider therapy modification

Erdafitinib: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Erdafitinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Esketamine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Fexinidazole [INT]: May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk X: Avoid combination

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Risk D: Consider therapy modification

Flupentixol: QT-prolonging Antipsychotics (Moderate Risk) may enhance the QTc-prolonging effect of Flupentixol. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

Fosaprepitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Fosnetupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Gastrointestinal Agents (Prokinetic): Anticholinergic Agents may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Risk C: Monitor therapy

Glucagon: Anticholinergic Agents may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Risk C: Monitor therapy

Glycopyrrolate (Oral Inhalation): Anticholinergic Agents may enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation). Risk X: Avoid combination

Glycopyrronium (Topical): May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination

Guanethidine: Antipsychotic Agents may diminish the therapeutic effect of Guanethidine. Risk C: Monitor therapy

Haloperidol: QT-prolonging Antipsychotics (Moderate Risk) may enhance the QTc-prolonging effect of Haloperidol. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Idelalisib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination

Iohexol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iohexol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iohexol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants. Risk D: Consider therapy modification

Iomeprol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iomeprol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iomeprol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants. Risk D: Consider therapy modification

Iopamidol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iopamidol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iopamidol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants. Risk D: Consider therapy modification

Ipratropium (Oral Inhalation): May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination

Itopride: Anticholinergic Agents may diminish the therapeutic effect of Itopride. Risk C: Monitor therapy

Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy

Larotrectinib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Lefamulin: May enhance the QTc-prolonging effect of QT-prolonging CYP3A4 Substrates. Management: Do not use lefamulin tablets with QT-prolonging CYP3A4 substrates. Lefamulin prescribing information lists this combination as contraindicated. Risk X: Avoid combination

Lemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider therapy modification

Levosulpiride: Anticholinergic Agents may diminish the therapeutic effect of Levosulpiride. Risk X: Avoid combination

Lithium: May enhance the neurotoxic effect of Antipsychotic Agents. Lithium may decrease the serum concentration of Antipsychotic Agents. Specifically noted with chlorpromazine. Risk C: Monitor therapy

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Mequitazine: Antipsychotic Agents may enhance the arrhythmogenic effect of Mequitazine. Management: Consider alternatives to one of these agents when possible. While this combination is not specifically contraindicated, mequitazine labeling describes this combination as discouraged. Risk D: Consider therapy modification

Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Risk D: Consider therapy modification

Methylphenidate: Antipsychotic Agents may enhance the adverse/toxic effect of Methylphenidate. Methylphenidate may enhance the adverse/toxic effect of Antipsychotic Agents. Risk C: Monitor therapy

Metoclopramide: May enhance the adverse/toxic effect of Antipsychotic Agents. Risk X: Avoid combination

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy

MetyroSINE: May enhance the adverse/toxic effect of Antipsychotic Agents. Risk C: Monitor therapy

Mianserin: May enhance the anticholinergic effect of Anticholinergic Agents. Risk C: Monitor therapy

MiFEPRIStone: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Minimize doses of CYP3A4 substrates, and monitor for increased concentrations/toxicity, during and 2 weeks following treatment with mifepristone. Avoid cyclosporine, dihydroergotamine, ergotamine, fentanyl, pimozide, quinidine, sirolimus, and tacrolimus. Risk D: Consider therapy modification

Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Mirabegron: Anticholinergic Agents may enhance the adverse/toxic effect of Mirabegron. Risk C: Monitor therapy

Mitotane: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Doses of CYP3A4 substrates may need to be adjusted substantially when used in patients being treated with mitotane. Risk D: Consider therapy modification

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Netupitant: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Nitroglycerin: Anticholinergic Agents may decrease the absorption of Nitroglycerin. Specifically, anticholinergic agents may decrease the dissolution of sublingual nitroglycerin tablets, possibly impairing or slowing nitroglycerin absorption. Risk C: Monitor therapy

OLANZapine: QT-prolonging Antipsychotics (Moderate Risk) may enhance the QTc-prolonging effect of OLANZapine. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

Ondansetron: May enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

Opioid Agonists: CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination

Oxatomide: May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination

OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification

Palbociclib: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination

Pentamidine (Systemic): May enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Risk D: Consider therapy modification

Pimozide: May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk X: Avoid combination

Piribedil: Antipsychotic Agents may diminish the therapeutic effect of Piribedil. Piribedil may diminish the therapeutic effect of Antipsychotic Agents. Management: Use of piribedil with antiemetic neuroleptics is contraindicated, and use with antipsychotic neuroleptics, except for clozapine, is not recommended. Risk X: Avoid combination

Posaconazole: May increase the serum concentration of QT-prolonging CYP3A4 Substrates. Such increases may lead to a greater risk for proarrhythmic effects and other similar toxicities. Risk X: Avoid combination

Potassium Chloride: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Chloride. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium chloride. Risk X: Avoid combination

Potassium Citrate: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Citrate. Risk X: Avoid combination

Pramlintide: May enhance the anticholinergic effect of Anticholinergic Agents. These effects are specific to the GI tract. Risk D: Consider therapy modification

QT-prolonging Agents (Highest Risk): May enhance the QTc-prolonging effect of QUEtiapine. Risk X: Avoid combination

QT-prolonging Antidepressants (Moderate Risk): QT-prolonging Antipsychotics (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Antidepressants (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

QT-prolonging Antipsychotics (Moderate Risk): May enhance the QTc-prolonging effect of QUEtiapine. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Exceptions: Amisulpride; CloZAPine; Droperidol; Flupentixol; OLANZapine; Pimozide; QUEtiapine. Risk C: Monitor therapy

QT-prolonging Class IC Antiarrhythmics (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

QT-prolonging Kinase Inhibitors (Moderate Risk): QT-prolonging Antipsychotics (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Kinase Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

QT-prolonging Miscellaneous Agents (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Exceptions: Domperidone. Risk C: Monitor therapy

QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk): May enhance the QTc-prolonging effect of QUEtiapine. QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of QUEtiapine. Management: Monitor for increased quetiapine toxicities including QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

QT-prolonging Quinolone Antibiotics (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Antipsychotics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy

QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk): QUEtiapine may enhance the QTc-prolonging effect of QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of QUEtiapine. Management: Reduce the quetiapine dose to one-sixth of the regular dose when combined with strong CYP3A4 inhibitors. Monitor patients for quetiapine toxicities, including QTc prolongation and torsades de pointes. Risk D: Consider therapy modification

Quinagolide: Antipsychotic Agents may diminish the therapeutic effect of Quinagolide. Risk C: Monitor therapy

Ramosetron: Anticholinergic Agents may enhance the constipating effect of Ramosetron. Risk C: Monitor therapy

Revefenacin: Anticholinergic Agents may enhance the anticholinergic effect of Revefenacin. Risk X: Avoid combination

Ritonavir: May increase the serum concentration of QUEtiapine. Management: The ritonavir Canadian labeling states this combination should not be used. U.S. labeling recommends using an alternative when possible; if the combination must be used, quetiapine dose reductions are needed. Risk D: Consider therapy modification

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Secretin: Anticholinergic Agents may diminish the therapeutic effect of Secretin. Management: Avoid concomitant use of anticholinergic agents and secretin. Discontinue anticholinergic agents at least 5 half-lives prior to administration of secretin. Risk D: Consider therapy modification

Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Risk C: Monitor therapy

Serotonergic Agents (High Risk): May enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, serotonergic agents may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Risk C: Monitor therapy

Siltuximab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Simeprevir: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy

Sodium Oxybate: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. Risk D: Consider therapy modification

St John's Wort: QUEtiapine may enhance the serotonergic effect of St John's Wort. This could result in serotonin syndrome. St John's Wort may decrease the serum concentration of QUEtiapine. Management: Quetiapine dose increases to as much as 5 times the regular dose may be required to maintain therapeutic benefit. Reduce the quetiapine dose back to the previous/regular dose within 7-14 days of discontinuing the inducer. Monitor closely. Risk D: Consider therapy modification

Stiripentol: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Use of stiripentol with CYP3A4 substrates that are considered to have a narrow therapeutic index should be avoided due to the increased risk for adverse effects and toxicity. Any CYP3A4 substrate used with stiripentol requires closer monitoring. Risk D: Consider therapy modification

Sulpiride: Antipsychotic Agents may enhance the adverse/toxic effect of Sulpiride. Risk X: Avoid combination

Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification

Tetrabenazine: May enhance the adverse/toxic effect of Antipsychotic Agents. Risk C: Monitor therapy

Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Tetrahydrocannabinol and Cannabidiol: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination

Thiazide and Thiazide-Like Diuretics: Anticholinergic Agents may increase the serum concentration of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy

Tiotropium: Anticholinergic Agents may enhance the anticholinergic effect of Tiotropium. Risk X: Avoid combination

Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Risk C: Monitor therapy

Topiramate: Anticholinergic Agents may enhance the adverse/toxic effect of Topiramate. Risk C: Monitor therapy

Umeclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Risk X: Avoid combination

Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider therapy modification

Food Interactions

In healthy volunteers, administration of quetiapine (immediate release) with food resulted in an increase in the peak serum concentration and AUC by 25% and 15%, respectively, compared to the fasting state. Administration of the extended-release formulation with a high-fat meal (~800-1000 calories) resulted in an increase in peak serum concentration by 44% to 52% and AUC by 20% to 22% for the 50 mg and 300 mg tablets; administration with a light meal (≤300 calories) had no significant effect on the C_max or AUC. Management: Administer without food or with a light meal (≤300 calories).

Test Interactions

May interfere with urine detection of methadone (false-positives); may cause false-positive serum TCA screen

Genes of Interest

• Alpha-1A Receptor
• Brain-Derived Neurotropic Factor
• Cytochrome P450 3A4
• Dopamine Receptor D₂
• Potassium Voltage-Gated Channel, Isk-Related Family, Member 1
• Voltage-Gated Sodium Channel 5A

Monitoring Parameters

Mental status; vital signs (as clinically indicated); blood pressure (baseline; repeat 3 months after antipsychotic initiation, then yearly, particularly in children and adolescents); weight, height, BMI, waist circumference (baseline; repeat at 4, 8, and 12 weeks after initiating or changing therapy, then quarterly; consider switching to a different antipsychotic for a weight gain ≥5% of initial weight); CBC (as clinically indicated; monitor frequently during the first few months of therapy in patients with pre-existing low WBC or history of drug-induced leukopenia/neutropenia); electrolytes and liver function (annually and as clinically indicated); TSH, free T₄, and thyroid clinical assessment (baseline and follow-up); fasting plasma glucose level/HbA_1c (baseline; repeat 3 months after starting antipsychotic, then yearly); fasting lipid panel (baseline; repeat 3 months after initiation of antipsychotic; if LDL level is normal, repeat at 2-5 year intervals or more frequently if clinically indicated); changes in menstruation, libido, development of galactorrhea, erectile and ejaculatory function (at each visit for the first 12 weeks after the antipsychotic is initiated or until the dose is stable, then yearly); abnormal involuntary movements or parkinsonian signs (baseline; repeat weekly until dose stabilized for at least 2 weeks after introduction and for 2 weeks after any significant dose increase); tardive dyskinesia (every 12 months; high-risk patients every 6 months); lens examination, such as a slit-lamp exam, on initiation of therapy and every 6 months is recommended by manufacturer; alternatively, experts suggest it may be reasonable to inquire yearly about visual changes and perform ocular examinations yearly in patients >40 years or every 2 years in younger patients (ADA 2004; Lehman 2004; Marder 2004).

Advanced Practitioners Physical Assessment/Monitoring

Assess mental status for depression and suicidal ideation. Assess other medicines patient may be taking; alternate therapy or dosage adjustments may be needed. Obtain vital signs (as clinically indicated); blood pressure (baseline; repeat 3 months after antipsychotic initiation, then yearly, particularly in children and adolescents); weight, height, BMI, waist circumference (baseline; repeat at 4, 8, and 12 weeks after initiating or changing therapy, then quarterly consider switching to a different antipsychotic for a weight gain ≥5% of initial weight). Obtain CBC, electrolytes, liver function tests, thyroid function tests, glucose, and fasting lipids. Assess for changes in menstruation, libido, development of galactorrhea, erectile dysfunction, tardive dyskinesia, involuntary movements, or parkinsonian signs. Obtain lens exam at start of therapy and then every 6 months.

Nursing Physical Assessment/Monitoring

Check ordered labs and report abnormalities. Check vitals, height, and weight as ordered. Monitor for depression or suicidal ideation. Educate patient to report signs of depression, changes in movement, vision changes, changes in menstruation, or changes in sexual function.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

SEROquel: 25 mg, 50 mg, 100 mg, 200 mg, 300 mg, 400 mg

Generic: 25 mg, 50 mg, 100 mg, 200 mg, 300 mg, 400 mg

Tablet Extended Release 24 Hour, Oral:

SEROquel XR: 50 mg, 150 mg, 200 mg, 300 mg, 400 mg

Generic: 50 mg, 150 mg, 200 mg, 300 mg, 400 mg

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

SEROquel: 25 mg, 100 mg, 200 mg, 300 mg

Generic: 25 mg, 50 mg, 100 mg, 150 mg, 200 mg, 300 mg

Tablet Extended Release 24 Hour, Oral:

SEROquel XR: 50 mg, 150 mg, 200 mg, 300 mg, 400 mg

Generic: 50 mg, 150 mg, 200 mg, 300 mg, 400 mg

Anatomic Therapeutic Chemical (ATC) Classification

• N05AH04

Generic Available (US)

Yes

Pricing: US

Tablet, 24-hour (QUEtiapine Fumarate ER Oral)

50 mg (per each): $0.85 - $15.00

150 mg (per each): $0.94 - $15.93

200 mg (per each): $1.06 - $17.53

300 mg (per each): $1.22 - $22.98

400 mg (per each): $1.38 - $27.01

Tablet, 24-hour (SEROquel XR Oral)

50 mg (per each): $9.85

150 mg (per each): $17.70

200 mg (per each): $19.48

300 mg (per each): $25.54

400 mg (per each): $30.01

Tablets (QUEtiapine Fumarate Oral)

25 mg (per each): $0.35 - $4.00

50 mg (per each): $0.56 - $6.80

100 mg (per each): $0.56 - $6.86

200 mg (per each): $1.14 - $12.95

300 mg (per each): $0.54 - $16.96

400 mg (per each): $1.68 - $19.93

Tablets (SEROquel Oral)

25 mg (per each): $4.66

50 mg (per each): $7.66

100 mg (per each): $8.00

200 mg (per each): $15.09

300 mg (per each): $19.79

400 mg (per each): $23.26

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Mechanism of Action

Quetiapine is a dibenzothiazepine atypical antipsychotic. It has been proposed that this drug's antipsychotic activity is mediated through a combination of dopamine type 2 (D₂) and serotonin type 2 (5-HT₂) antagonism. It is an antagonist at multiple neurotransmitter receptors in the brain: Serotonin 5-HT_1A and 5-HT₂, dopamine D₁ and D₂, histamine H₁, and adrenergic alpha₁- and alpha₂-receptors; but appears to have no appreciable affinity at cholinergic muscarinic and benzodiazepine receptors. Norquetiapine, an active metabolite, differs from its parent molecule by exhibiting high affinity for muscarinic M1 receptors.

Antagonism at receptors other than dopamine and 5-HT₂ with similar receptor affinities may explain some of the other effects of quetiapine. The drug's antagonism of histamine H₁-receptors may explain the somnolence observed. The drug's antagonism of adrenergic alpha₁-receptors may explain the orthostatic hypotension observed.

Pharmacodynamics/Kinetics

Absorption: Rapidly absorbed following oral administration; high-fat meals (800 to 1000 calories) increase C_max 8% and AUC 2% of quetiapine XR; light meals (300 calories) had no effect; parent compound AUC and C_max were 41% and 39% lower, respectively, in pediatric patients (10 to 17 years) compared to adults when adjusted for weight, but pharmacokinetics of active metabolite were similar to adult values after adjusting for weight.

Distribution: V_d: 10 ± 4 L/kg

Protein binding, plasma: 83%

Metabolism: Primarily hepatic; via CYP3A4; forms the metabolite N-desalkyl quetiapine (active) and two inactive metabolites [sulfoxide metabolite (major metabolite) and parent acid metabolite]

Bioavailability: 100% (relative to oral solution)

Half-life elimination:

Children and Adolescents 12 to 17 years: Quetiapine: 5.3 hours (McConville 2000)

Adults: Mean: Terminal: Quetiapine: ~6 hours; Extended release: ~7 hours

Metabolite: N-desalkyl quetiapine: 12 hours

Time to peak, plasma:

Children and Adolescents 12 to 17 years: Immediate release: 0.5 to 3 hours (McConville 2000)

Adults: Immediate release: 1.5 hours; Extended release: 6 hours

Excretion: Urine (73% as metabolites, <1% of total dose as unchanged drug); feces (20%)

Pharmacodynamics/Kinetics: Additional Considerations

Renal function impairment: CrCl 10 to 30 mL/minute had 25% lower clearance; plasma concentrations were within the range of concentrations seen in normal subjects.

Hepatic function impairment: 30% lower clearance; AUC and C_max is 3-fold higher.

Geriatric: Clearance reduced 40%.

Local Anesthetic/Vasoconstrictor Precautions

Quetiapine is one of the drugs confirmed to prolong the QT interval and is accepted as having a risk of causing torsade de pointes. The risk of drug-induced torsade de pointes is extremely low when a single QT interval prolonging drug is prescribed. In terms of epinephrine, it is not known what effect vasoconstrictors in the local anesthetic regimen will have in patients with a known history of congenital prolonged QT interval or in patients taking any medication that prolongs the QT interval. Until more information is obtained, it is suggested that the clinician consult with the physician prior to the use of a vasoconstrictor in suspected patients, and that the vasoconstrictor (epinephrine, mepivacaine and levonordefrin [Carbocaine 2% with Neo-Cobefrin]) be used with caution.

Dental Health Professional Considerations

See Local Anesthetic/Vasoconstrictor Precautions

Effects on Dental Treatment

Key adverse event(s) related to dental treatment: Xerostomia (normal salivary flow resumes upon discontinuation).

Effects on Bleeding

No information available to require special precautions

Related Information

• Agents Approved for Bipolar Disorder
• Antipsychotic Receptor Profile
• Beers Criteria 2019: Potentially Inappropriate Medication Use in Older Adults ≥65 Years of Age
• Comparison of Antipsychotic Adverse Effects
• Oral Medications That Should Not Be Crushed or Altered
• Relative Infant Dose

Index Terms

Quetiapine Fumarate

FDA Approval Date

September 26, 1997

References

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Brand Names: International

Alvoquel (SG); Aretaeus (MX); Biatrix (AR); Bipresso (JP); Biquelle XL (GB); Cacepin (KR); Calm-EZ (TW); Catepsin (PY); Delucon (AU); Ebesque XL (GB); Edagan (PE, UY); Geroquel (IE); Gofyl (CL); Hedonin (LV); Hiloca (TW); Keepquet (EG); Kesaquil (HK); Ketilept (LV, PH, UA); Ketipinor (MY, SG); Kitapen (BR); Kventiax (LV); Limus (TW); Mintreleq XL (GB); Neutapin (TH, TW); Ovex (LK); Psyquel (EG); Q-Win (PH); Qmax (BD); Qtipine (PH); Quantia (HK, PH, TW); Quentiax (IE); Querok (BR); Quetapel (NZ); Quetapin (KR); Quetiap RD (PH); Quetiazic (EC); Quetidin (CO, EC, PY); Quetinil (BD); Quetiron (UA); Quety (KR); Quiet (BD); Quitcool (EG); Qurax (CL); Qutero (MY); Qutiapine (KR); Qutipin (KR); Rezal XR (AE, LB); Sequase (CH); Serogen (HK); Seroquel (AE, AR, AT, BB, BE, BG, BH, BM, BO, BR, BS, BZ, CH, CL, CN, CO, CR, CU, CY, CZ, DE, DK, DO, EC, EE, EG, ES, FI, GB, GR, GT, GY, HK, HN, HR, IE, IL, IS, IT, JM, JO, KR, KW, LB, LK, LT, LU, MX, MY, NI, NL, NO, NZ, PA, PE, PH, PK, PL, PR, PT, PY, QA, RO, RU, SA, SE, SG, SI, SR, SV, TH, TR, TT, TW, UA, UY, VE, VN); Seroquel IR (HK); Seroquel Prolong (IS); Seroquel SR (SI); Seroquel XR (AU, BB, BE, BH, CH, CN, CU, CY, EG, GB, HK, HR, ID, IL, KW, LB, LK, LT, LU, LV, MT, MY, PH, QA, RO, SG, SK, TH, VN, ZW); Seroquet (BD); Serotia (PH); Serroquel XR (AE); Setinin (HK, MT); Smoodipin (KR); Socalm (IN); Sondate XL (GB); Squro (TH); Tevaquel (IE); Tiamax (CO); Toliken (BD); Torquite SR (TZ, ZW); Utapine (TW); Vesparax (AR); Victus (PH); Zaluron XL (GB)

Last Updated 2/25/20