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Quetiapine: Drug information

Quetiapine: Drug information
(For additional information see "Quetiapine: Patient drug information" and see "Quetiapine: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
ALERT: US Boxed Warning
Increased mortality in elderly patients with dementia-related psychosis:

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death. Quetiapine is not approved for the treatment of patients with dementia-related psychosis.

Suicidal thoughts and behavior:

Antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term studies. These studies did not show an increase in the risk of suicidal thoughts and behavior with antidepressant use in patients older than 24 years; there was a reduction in risk with antidepressant use in patients 65 years and older. In patients of all ages who are started on antidepressant therapy, monitor closely for clinical worsening and for emergence of suicidal thoughts and behaviors. Advise families and caregivers of the need for close observation and communication with the prescriber. Quetiapine is not approved for use in pediatric patients younger than 10 years.

Brand Names: US
  • SEROquel;
  • SEROquel XR
Brand Names: Canada
  • ACH-Quetiapine Fumarate XR;
  • ACT QUEtiapine;
  • AG-Quetiapine;
  • APO-QUEtiapine;
  • APO-Quetiapine Fumarate;
  • APO-QUEtiapine XR;
  • Auro-QUEtiapine;
  • BIO-QUEtiapine;
  • DOM-QUEtiapine;
  • JAMP-QUEtiapine;
  • JAMP-Quetiapine Fumarate;
  • Mar-QUEtiapine;
  • MINT-QUEtiapine;
  • NAT-QUEtiapine;
  • NRA-Quetiapine;
  • NRA-Quetiapine XR;
  • PMS-QUEtiapine;
  • Priva-QUEtiapine;
  • PRO-QUEtiapine;
  • RAN-QUEtiapine;
  • RIVA-QUEtiapine;
  • SANDOZ QUEtiapine XRT;
  • SANDOZ QUEtiapine [DSC];
  • SEROquel;
  • SEROquel XR;
  • TARO-Quetiapine;
  • TEVA-QUEtiapine XR;
  • TEVA-QUEtiapine [DSC];
  • VAN-QUEtiapine [DSC]
Pharmacologic Category
  • Antimanic Agent;
  • 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

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). Patients with dementia with Lewy bodies are at increased risk for severe adverse reactions; caution is required even with low doses (APA [Reus 2016]).

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 2022; Scharre 2002).

Agitation and/or delirium, ICU

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

Bipolar disorder:

Acute mania (labeled use), acute episodes with mixed features (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 (Bobo 2022; 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 (Bobo 2022).

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 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

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 2021; 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

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 2021).

Obsessive-compulsive disorder, treatment-resistant

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

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

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 (Chahine 2021).

Schizophrenia

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: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Discontinuation of therapy: In the treatment of chronic psychiatric disease switching therapy rather than discontinuation is generally advised if side effects are intolerable or treatment is not effective. If patient insists on stopping treatment, gradual dose reduction (ie, over several weeks to months) is advised to detect a re-emergence of symptoms and to avoid withdrawal reactions (eg, agitation, alternating feelings of warmth and chill, anxiety, diaphoresis, dyskinesias, GI symptoms, insomnia, irritability, myalgia, paresthesia, psychosis, restlessness, rhinorrhea, tremor, vertigo) unless discontinuation is due to significant adverse effects. Monitor closely to allow for detection of prodromal symptoms of disease recurrence (APA [Keepers 2020]; Lambert 2007; Moncrieff 2020; Post 2021).

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 (Stroup 2019).

Dosing: Kidney Impairment: Adult

The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.

No dosage adjustment necessary (Thyrum 2000; manufacturer's labeling). Removal by dialysis unlikely due to relatively high protein binding and large volume of distribution (expert opinion).

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

(For additional information see "Quetiapine: Pediatric drug information")

Bipolar disorder, mania or episodes with mixed features: 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: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

Altered kidney function: Children ≥10 years and Adolescents: Oral: No dosage adjustment necessary. Note: Removal by dialysis unlikely due to relatively high protein binding and large volume of distribution.

Dosing: Hepatic Impairment: Pediatric

Children ≥10 years and Adolescents:

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

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

Dosing: Older Adult

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. Dosages in the lower range of recommended adult dosing are generally sufficient with late-onset schizophrenia or psychosis. Titrate dosage slowly and monitor carefully (Howard 2000).

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.

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

Generic Equivalent Available: US

Yes

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

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/2022/020639s072lbl.pdf#page=49

Seroquel XR: https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/022047s046lbl.pdf#page=53

Administration: Adult

Oral:

IR tablet: Administer with or without food.

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

Bariatric surgery: Some institutions may have specific protocols that conflict with these recommendations; refer to institutional protocols as appropriate. IR tablet formulation is available. If safety and efficacy can be effectively monitored, no change in formulation or administration is required after bariatric surgery.

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).

Use: Labeled Indications

Bipolar disorder: Acute treatment of mania (both immediate release and extended release), episodes with mixed features (extended release only), and 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) (extended release only): Adjunctive therapy in patients with an inadequate response to antidepressants for the treatment of major depressive disorder.

Schizophrenia: Treatment of schizophrenia.

Use: Off-Label: Adult

Agitation/aggression and psychosis associated with dementia, severe or refractory (alternative agent); Agitation and/or delirium, ICU (alternative agent); Delusional infestation (delusional parasitosis); Generalized anxiety disorder (alternative agent); Major depressive disorder (unipolar), monotherapy (alternative agent); Obsessive-compulsive disorder, treatment-resistant (augmentation); Posttraumatic stress disorder, adjunct to antidepressants or monotherapy (alternative agent); Psychosis in Parkinson disease

Medication Safety Issues
Sound-alike/look-alike issues:

QUEtiapine may be confused with OLANZapine

SEROquel may be confused with Desyrel, SEROquel XR, Serzone, SINEquan

Geriatric Patients: High-Risk Medication:

Antipsychotics are identified in the Beers Criteria as potentially inappropriate medications to be avoided in patients 65 years and older due to an increased risk of cerebrovascular accidents (stroke) and a greater rate of cognitive decline and mortality in patients with dementia. Antipsychotics may be appropriate for schizophrenia, bipolar disorder, other mental health conditions or short-term use as antiemetic during chemotherapy but should be given in the lowest effective dose for the shortest duration possible. In addition, antipsychotics should be used with caution in older adults due to their potential to cause or exacerbate syndrome of inappropriate antidiuretic hormone secretion (SIADH) or hyponatremia; monitor sodium closely with initiation or dosage adjustments in older adults (Beers Criteria [AGS 2019]).

Adverse Reactions (Significant): Considerations
Anticholinergic effects

Anticholinergic activity of quetiapine at usual therapeutic doses is generally considered low relative to other second-generation antipsychotics (eg, clozapine) (Ref). However, dose-dependent increases in anticholinergic activity have been observed (Ref). Anticholinergic effects may include constipation, urinary retention (case report in a patient receiving a high dose), xerostomia, and blurred vision. In older adults, some scales have classified quetiapine as having a high anticholinergic burden which may lead to new-onset delirium, cognitive dysfunction, confusion, and falling. However, there is no standardized tool for measuring anticholinergic burden in older adults and some scales have also rated quetiapine as low or moderate (Ref).

Mechanism: Dose-related; believed to be mediated primarily through active metabolite, norquetiapine antagonism at muscarinic receptors. Variability in conversion to norquetiapine may be a factor involved in inconsistency in reports associated with quetiapine’s anticholinergic adverse reactions (Ref).

Risk factors:

Variable and dependent upon:

• Total anticholinergic burden (Ref)

• Baseline cognitive function (Ref)

• Comorbidities (Ref)

• Polypharmacy (Ref)

• Older adults (Ref)

• Interindividual variability of the pharmacokinetic and pharmacodynamic parameters (Ref)

Cataracts

There is insufficient evidence that quetiapine is associated with an increased risk of cataract development in humans, despite warnings in the manufacturer's labeling. There are some case reports of cataracts occurring in patients receiving quetiapine (Ref); however, a large population-based, nested case control study did not find an association between atypical antipsychotics and risk of cataract development in patients with schizophrenia (Ref). The concern stems from animal research observing cataracts in beagles receiving quetiapine at 4 times the recommended human dose (this was not observed in other animal studies) and cataracts occurring in patients receiving certain phenothiazine neuroleptic medications, such as chlorpromazine (Ref).

Dyslipidemia

Antipsychotics are associated with dyslipidemia in adult and pediatric patients, which is a component of the metabolic syndrome observed with this pharmacologic class. Dyslipidemia observed with quetiapine primarily manifests as hypertriglyceridemia (increased serum triglycerides), including cases of severe hypertriglyceridemia (>600 mg/dL) and acute pancreatitis (some cases were fatal). Hypercholesterolemia (increased LDL cholesterol, increased serum cholesterol, decreased HDL cholesterol) may also occur with use (Ref).

Mechanism: The mechanism is not entirely understood and is likely multifactorial (Ref).

Onset: Varied; metabolic alterations from antipsychotics can develop in as short as 3 months after initiation (Ref). In cases of hypertriglyceridemia-induced acute pancreatitis due to quetiapine, almost all occurred within the first 8 months of an established dose and most frequently at 3 months of treatment (Ref).

Risk factors:

• History of preexisting dyslipidemia or hypertriglyceridemia (Ref)

• Schizophrenia (regardless of medication use) is associated with a higher rate of morbidity/mortality compared to the general population primarily due to cardiovascular disease (Ref).

• Specific antipsychotic: Some authors consider quetiapine to have a high risk of hyperlipidemia, while others consider quetiapine’s risk to be intermediate (Ref). Overall, metabolic disturbances appear to be the greatest with clozapine and olanzapine and intermediate with quetiapine (Ref).

Extrapyramidal symptoms

Quetiapine may cause extrapyramidal symptoms (EPS), also known as drug-induced movement disorders. Antipsychotics can cause 4 main EPS: Acute dystonia, drug-induced parkinsonism, akathisia, and tardive dyskinesia (Ref). EPS presenting as dysphagia, esophageal dysmotility, or aspiration have also been reported with antipsychotics, which may not be recognized as EPS (Ref).

Mechanism: EPS: Dose-related; due to antagonism of dopaminergic D2 receptors in nigrostriatal pathways (Ref). Tardive dyskinesia: Time related (delayed); results from chronic exposure to dopamine 2 receptor antagonists leading to up-regulation of these receptors over time (Ref).

Onset:

Antipsychotics in general:

Acute dystonia: Rapid; in the majority of cases, dystonia usually occurs within the first 5 days after initiating antipsychotic therapy (and even with the first dose, particularly in patients receiving parenteral antipsychotics) or a dosage increase (Ref).

Drug-induced parkinsonism: Varied; onset may be delayed from days to weeks, with 50% to 75% of cases occurring within 1 month and 90% within 3 months of antipsychotic initiation, a dosage increase, or a change in the medication regimen (such as adding another antipsychotic agent or discontinuing an anticholinergic medication) (Ref).

Akathisia: Varied; may begin within several days after antipsychotic initiation but usually increases with treatment duration, occurring within 1 month in up to 50% of cases and within 3 months in 90% of cases (Ref).

Tardive dyskinesia: Delayed; symptoms usually appear after 1 to 2 years of continuous exposure to a dopamine 2 receptor antagonist, and almost never before 3 months, with an insidious onset, evolving into a full syndrome over days and weeks, followed by symptom stabilization and then a chronic waxing and waning of symptoms (Ref).

Esophageal dysfunction (associated with EPS): Varied; ranges from weeks to months following initiation (Ref).

Risk factors:

EPS (in general):

• Prior history of EPS (Ref)

• Higher doses (Ref)

• Younger age (in general, children and adolescents are usually at higher risk for EPS compared to adults) (Ref)

• Specific antipsychotic: Quetiapine is considered to have a low propensity to cause EPS (Ref)

Acute dystonia:

• Males (Ref)

• Young age (Ref)

Drug-induced parkinsonism:

• Females (Ref)

• Older patients (Ref)

Akathisia:

• Higher antipsychotic dosages (Ref)

• Polypharmacy (Ref)

• Mood disorders (Ref)

• Females (Ref)

• Older patients (Ref)

Tardive dyskinesia:

• Age >55 year (Ref)

• Cognitive impairment (Ref)

• Concomitant treatment with anticholinergic medications (Ref)

• Diabetes (Ref)

• Diagnosis of schizophrenia or affective disorders (Ref)

• Female sex (Ref)

• Greater total antipsychotic exposure (especially first-generation antipsychotics) (Ref)

• History of extrapyramidal symptoms (Ref)

• Substance misuse or dependence (Ref)

• Race (White or African descent). Note: Although early literature supported race as a potential risk factor for tardive dyskinesia (Morgenstern 1993), newer studies have challenged this assertion (Ref).

Esophageal dysfunction (associated with EPS):

• Certain comorbidities such as neurologic degenerative disease, dementia, stroke, Parkinson disease, or myasthenia gravis (Ref)

• Older adults >75 years of age (may be risk factor due to age related muscle atrophy, cognitive impairment, or reduced esophageal peristalsis) (Ref)

Hematologic abnormalities

Leukopenia, neutropenia, and thrombocytopenia have rarely been reported with quetiapine monotherapy (Ref). Agranulocytosis, including fatal agranulocytosis, has also been reported very rarely, including with monotherapy (Ref). The majority of reports involving quetiapine-associated leukopenia or neutropenia involve patients receiving concomitant valproate (Ref). In addition, there are case reports of thrombotic thrombocytopenic purpura (TTP) and autoimmune hemolytic anemia (AIHA) (pediatric patient) (Ref).

Mechanism: Unknown; hypothesized as the same direct toxicity or immune-mediated destruction as clozapine, due to chemical structure similarities (Ref). TTP and AIHA may occur due to a drug-induced immune response (Ref).

Onset: Varied; in general, drug-induced neutropenia usually manifests after 1 or 2 weeks of exposure and agranulocytosis usually appears 3 to 4 weeks following initiation of therapy; however, the onset may be insidious (Ref). For TTP, one case report described an onset within a few days after exposure with early thrombocytopenia, followed by delayed appearance (2 to 3 days) of microangiopathic hemolysis (Ref).

Risk factors:

• History of drug-induced leukopenia/neutropenia or low white blood cell count/absolute neutrophil count

• Older adults (Ref)

• Concomitant use of valproate (which is also associated with causing blood dyscrasias and may increase quetiapine concentrations by 77% via a drug-drug interaction) (Ref).

Hyperglycemia

Antipsychotics are associated with hyperglycemia, to varying degrees, which is a component of the metabolic syndrome observed with this pharmacologic class. Glycemic abnormalities range from mild insulin resistance or hyperglycemia to new-onset diabetes mellitus and diabetic ketoacidosis, including fatal cases (Ref)

Mechanism: The mechanism is not entirely understood and is likely multifactorial (Ref).

Onset: Varied; new-onset diabetes has been observed within first 3 months to a median onset of 3.9 years (Ref)

Risk factors:

Antipsychotics in general:

• African American race (Ref)

• Males (Ref)

• Age <35 years (Ref)

• Preexisting obesity, poor exercise habits, or other risk factors for diabetes, including family history of diabetes (Ref)

• Exposure to other agents that also increase the risk of hyperglycemia (Ref)

• Type 2 diabetes mellitus: Extended exposure (mean: 17.2 months) in pediatric patients 10 to 18 years (Ref)

• Specific antipsychotic: Quetiapine is associated with a moderate risk of hyperglycemia (Ref)

Hypothyroidism

Hypothyroidism, likely dose-related, has been observed rarely with quetiapine use, including cases requiring discontinuation or initiation of thyroid replacement therapy, and one case with spontaneous resolution without quetiapine discontinuation (Ref). However, some studies have observed changes in total thyroxine (T4) levels only, without a significant increase in thyroid stimulating hormone (TSH) levels (Ref).

Mechanism: The mechanism of action by which quetiapine causes hypothyroidism is unknown (Ref). It has been presumed to result from thyroid gland dysfunction (primary hypothyroidism); although, due to the presence of a low T4 without TSH changes, in many cases, a central [secondary] hypothyroidism rather than a primary hypothyroidism may also be a potential mechanism (Ref).

Risk factors:

• Higher quetiapine doses (Ref)

In general (regardless of quetiapine use):

• Bipolar disorder (overt or subclinical hypothyroidism [more common]) (Ref)

• Schizophrenia (thyroid dysfunction) (Ref)

• Concomitant lithium treatment (may induce or exacerbate preexisting hypothyroidism) (Ref)

Mortality in older adults

Older adults with dementia-related psychosis treated with antipsychotics are at an increased risk of death compared to placebo. Although the causes of death were varied, most of the deaths appeared to be either cardiovascular (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature. Of note, quetiapine is not approved for the treatment of dementia-related psychosis (Ref).

Mechanism: Unknown; possible mechanisms include arrhythmia, cardiac arrest, and extrapyramidal effects that may increase the risk of falls, aspirations, and pneumonia (Ref).

Risk factors:

Antipsychotics in general:

• Higher antipsychotic dosage (Ref)

• Dementia-related psychosis (eg, Lewy body dementia, Parkinson disease dementia)

• Older adults

Neuroleptic malignant syndrome

All antipsychotics have been associated with neuroleptic malignant syndrome (NMS) in all ages, although the incidence is less with second-generation (atypical) antipsychotics compared to first-generation (typical) antipsychotics. There are case reports of NMS with quetiapine monotherapy, although most involve concomitant administration of another neuroleptic or other confounding conditions (Ref).

Mechanism: Non-dose-related; idiosyncratic. Believed to be due to a reduction in CNS dopaminergic tone, along with the dysregulation of autonomic nervous system activity (Ref).

Onset: Varied; in general, most patients develop NMS within 2 weeks of initiating an antipsychotic, and in some patients, prodromal symptoms emerge within hours of initiation; once the syndrome starts, the full syndrome usually develops in 3 to 5 days (Ref). In a review of the few cases reported with quetiapine, the mean time of onset was 21 days (median: 9 days) (Ref). However, there are many cases of NMS occurring months after stable antipsychotic therapy (Ref).

Risk factors:

Antipsychotics in general:

• Males (twice as likely to develop NMS compared to females) (Ref)

• Dehydration (Ref)

• High-dose antipsychotic treatment (Ref)

• Concomitant lithium or benzodiazepine (potential risk factors) (Ref)

• Catatonia (Ref)

• Disorganized speech or behavior (Ref)

• Polypharmacy (Ref)

• Pharmacokinetic interactions (Ref)

• Intramuscular administration (Ref)

• Rapid dosage escalation (Ref)

• Psychomotor agitation (Ref)

Orthostatic hypotension

Quetiapine may cause orthostatic hypotension and accompanying tachycardia and syncope in adults, particularly with rapid titration (Ref). Orthostatic hypotension may result in subsequent falling and fracture, particularly in older adults (Ref).

Mechanism: Orthostatic hypotension is attributed to alpha-1 adrenergic receptor antagonism (Ref).

Onset: Rapid; per the manufacturer's labeling, orthostatic hypotension is most common in the first few days of initiation or following a dosage increase; may also occur after only 1 dose (Ref).

Risk factors:

• Known cardiovascular disease (history of myocardial infarction or ischemic heart disease, heart failure, or conduction abnormalities) or cerebrovascular disease

• Known predisposing conditions (eg, hypovolemia/dehydration)

• Concomitant medications that also cause or exacerbate orthostatic hypotension (eg, tricyclic antidepressants, antihypertensive medications)

• Older adults (Ref)

• Rapid dose titration (Ref)

QT prolongation

Quetiapine has been associated with prolonged QT interval on ECG, including rare reports of torsades de pointes (TdP), predominately in the setting of overdose or in patients with multiple risk factors (Ref). Compared to other antipsychotics, quetiapine is generally associated with a low risk for QTc (Ref). In a study of healthy adult volunteers designed to evaluate the QTc prolongation potential of a single dose of quetiapine immediate release (100 mg), the mean change in QTc was 13.7 ms (Ref). In another study in 27 healthy psychiatric patients reaching steady state on quetiapine 750 mg/day, the mean change in QTc was 5.7 ms (Ref).

Mechanism: Likely dose-related (Ref).

Risk factors:

Drug-induced QTc prolongation (in general):

• Females (Ref)

• Age >65 years (Ref)

• Structural heart disease (eg, history of myocardial infarction or heart failure with a reduced ejection fraction) (Ref)

• History of drug-induced TdP (Ref)

• Genetic defects of cardiac ion channels (Ref)

• Congenital long QT syndrome (Ref)

• Baseline QTc interval prolongation (eg, >500 msec) or lengthening of the QTc by ≥60 msec (Ref)

• Electrolyte disturbances (eg, hypokalemia, hypocalcemia, hypomagnesemia) (Ref)

• Bradycardia (Ref)

• Hepatic impairment (Ref)

• Kidney impairment (Ref)

• Coadministration of multiple medications (≥2) that prolong the QT interval or increase drug interactions that increase serum drug concentrations of QTc prolonging medications (Ref)

• Substance use (Ref)

Sedation

Sedated state (drowsiness) is common with use; may cause nonadherence and impair physical and/or mental abilities resulting in subsequent falling and fracture, particularly in older adults (Ref).

Mechanism: Dose-related; sedation is believed to be due to H1 antagonism leading to potential CNS depressant effects (Ref)

Onset: Rapid; per the manufacturer’s labeling, sedation is most common in the first few days of initiation or following a dosage increase.

Sexual dysfunction

Antipsychotics have been associated with sexual disorder in both males and females. Antipsychotic treatment has been associated with effects on all phases of sexual activity (libido, arousal, orgasm); however, many patients with schizophrenia experience more frequent sexual dysfunction, with or without antipsychotic treatment (Ref). Decreased libido, erectile dysfunction, and orgasm disturbance have been reported with quetiapine (Ref).

Mechanism: Antipsychotic-induced sexual dysfunction has been attributed to many potential mechanisms, including dopamine receptor antagonism, dopamine D2 receptor antagonism in the infundibular dopaminergic pathway causing hyperprolactinemia, histamine receptor antagonism, cholinergic receptor antagonism, and alpha-adrenergic receptor antagonism. Quetiapine is associated with a minimal risk of causing hyperprolactinemia in adults (Ref); however, clinically significant prolactin levels have been observed in pediatric patients (ages 10 to 17 years).

Risk factors:

• Hyperprolactinemia (although a correlation with sexual dysfunction has been observed, a relationship has not been confirmed) (Ref)

• Schizophrenia (the prevalence antipsychotic-induced sexual dysfunction in patients with schizophrenia is high [~50% to 60% compared with 31% of males in the general population]) (Ref).

• Specific antipsychotic: Quetiapine is usually associated with relatively lower rates of sexual dysfunction compared to other antipsychotics, such as risperidone and haloperidol) (Ref).

Temperature dysregulation

Antipsychotics may impair the body’s ability to regulate core body temperature, which may cause a potentially life-threatening heat stroke during predisposing conditions such as a heat wave or strenuous exercise. There are also several case reports of potentially life-threatening hypothermia associated with quetiapine use (Ref).

Mechanism: Non-dose-related; idiosyncratic. Exact mechanism is unknown; however, body temperature is regulated by the hypothalamus with involvement of the dopamine, serotonin, and norepinephrine neurotransmitters. D2 antagonism may cause an increase in body temperature, while 5-HT2A (serotonin) receptor antagonism may cause a decrease in body temperature. In addition, antagonism of peripheral alpha-adrenergic receptors has also been suggested as a factor in the hypothermic effect, by inhibiting peripheral responses to cooling (vasoconstriction and shivering) (Ref).

Onset: Hypothermia: Varied; antipsychotic-induced hypothermia cases indicate a typical onset in the period shortly after initiation of therapy or a dosage increase (first 7 to 10 days) (Ref)

Risk factors:

Heat stroke:

• Psychiatric illness (regardless of medication use) (Ref)

• Dehydration (Ref)

• Strenuous exercise (Ref)

• Heat exposure (Ref)

• Concomitant medications possessing anticholinergic effects (Ref)

Hypothermia:

• In general, predisposing risk factors include: Older adults, cerebrovascular accident, preexisting brain damage, hypothyroidism, malnutrition, shock, sepsis, adrenal insufficiency, diabetes, disability, burns, exfoliative dermatitis, benzodiazepine use, alcohol intoxication, kidney or liver failure (Ref)

• Schizophrenia (regardless of antipsychotic use) (Ref)

Weight gain

Quetiapine is associated with significant weight gain (increase of ≥7% from baseline) in adult and pediatric patients, which is a component of the metabolic syndrome observed with this pharmacologic class (Ref).

Mechanism: Multiple proposed mechanisms, including actions at serotonin, dopamine, histamine, and muscarinic receptors, with differing effects explained by differing affinity of antipsychotics at these receptors (Ref).

Onset: Varied; antipsychotic-induced weight gain usually occurs rapidly in the initial period following initiation, then gradually decreases and plateaus over several months with patients continuing to gain weight in the long term (Ref).

Risk factors:

• Family history of obesity (Ref)

• Parental BMI (Ref)

• Children and adolescents (Ref)

• Rapid weight gain in the initial period: Younger patients, lower baseline BMI, more robust response to antipsychotic, and increase in appetite; rapid weight gain of >5% in the first month has been observed as the best predictor for significant long-term weight gain (Ref)

• Duration of therapy (although weight gain plateaus, patients continue to gain weight over time) (Ref)

• Schizophrenia (regardless of medication) is associated with a higher prevalence of obesity compared to the general population due to components of the illness such as negative symptoms, sedentary lifestyles, and unhealthy diets (Ref).

• Specific antipsychotic: Quetiapine is considered to display moderate propensity for weight gain (Ref)

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. 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%), orthostatic hypotension (children and adolescents: <1%; adults: 2% to 7%; older adults: literature suggests the incidence may be as high as 18%) (Sajatovic 2008) (table 1), tachycardia (≤11%) (table 2)

Quetiapine: Adverse Reaction: Orthostatic Hypotension

Drug (Quetiapine)

Placebo

Population

Dosage Form

Dose

Indication

Number of Patients (Quetiapine)

Number of Patients (Placebo)

Source

4%

3%

Adults

IR tablets

300 to 600 mg/day

Bipolar depression

698

347

Prescribing information

2%

1%

Adults

XR tablets

300 mg/day

Bipolar depression

137

140

Prescribing information

3%

0%

Adults

XR tablets

400 to 800 mg/day

Bipolar mania

151

160

Prescribing information

7%

5%

Adults

XR tablets

300 to 800 mg/day

Schizophrenia

951

319

Prescribing information

4%

1%

Adults

IR tablets

75 to 800 mg/day

Schizophrenia and bipolar mania

719

404

Prescribing information

18%

3%

Older adults

IR tablets

400 to 800 mg/day

Bipolar mania

28

31

Sajatovic 2008

Quetiapine: Adverse Reaction: Tachycardia

Drug (Quetiapine)

Placebo

Population

Dosage Form

Dose

Indication

Number of Patients (Quetiapine)

Number of Patients (Placebo)

9%

0%

Children & adolescents

IR tablets

600 mg

Bipolar mania

98

90

6%

0%

Children & adolescents

IR tablets

400 mg

Bipolar mania

95

90

11%

0%

Adolescents

IR tablets

800 mg

Schizophrenia

74

75

6%

0%

Adolescents

IR tablets

400 mg

Schizophrenia

73

75

0.5%

0%

Adults

IR tablets

N/A

Acute bipolar mania

192

178

2%

1%

Adults

XR tablets

400 to 800 mg/day

Bipolar mania

151

160

3%

1%

Adults

XR tablets

300 to 800 mg/day

Schizophrenia

951

319

6%

4%

Adults

IR tablets

75 to 800 mg/day

Schizophrenia and bipolar mania

719

404

2%

0.5%

Adults

XR tablets

N/A

N/A

N/A

N/A

Endocrine & metabolic: Decreased HDL cholesterol (≤40 mg/dL: 9% to 20%) (table 3), increased serum cholesterol (7% to 18%) (table 4), increased serum triglycerides (8% to 28%) (table 5), weight gain (dose related; 4% to 23%) (table 6)

Quetiapine: Adverse Reaction: Decreased HDL Cholesterol

Drug (Quetiapine)

Placebo

Population

Dosage Form

Indication

Number of Patients (Quetiapine)

Number of Patients (Placebo)

20%

15%

Children & adolescents

XR tablets

Bipolar depression

65

74

10%

7%

Children & adolescents

IR tablets

Bipolar mania

154

61

15%

19%

Children & adolescents

IR tablets

Schizophrenia

104

54

14%

14%

Adults

IR tablets

Bipolar depression

393

214

9%

7%

Adults

XR tablets

Bipolar depression

78

83

19%

13%

Adults

XR tablets

Bipolar mania

100

115

15%

12%

Adults

XR tablets

Schizophrenia

600

195

Quetiapine: Adverse Reaction: Increased Serum Cholesterol

Drug (Quetiapine)

Placebo

Population

Dosage Form

Dose

Indication

Number of Patients (Quetiapine)

Number of Patients (Placebo)

8%

6%

Children & adolescents

XR tablets

N/A

Bipolar depression

83

84

10%

3%

Children & adolescents

IR tablets

N/A

Bipolar mania

159

66

12%

2%

Children & adolescents

IR tablets

N/A

Schizophrenia

107

56

9%

6%

Adults

IR tablets

N/A

Bipolar depression

463

250

7%

3%

Adults

XR tablets

N/A

Bipolar depression

85

106

7%

4%

Adults

XR tablets

N/A

Bipolar mania

128

134

18%

7%

Adults

IR tablets

N/A

Schizophrenia

137

92

9%

9%

Adults

XR tablets

N/A

Schizophrenia

718

232

Quetiapine: Adverse Reaction: Increased Serum Triglycerides

Drug (Quetiapine)

Placebo

Population

Dosage Form

Dose

Indication

Number of Patients (Quetiapine)

Number of Patients (Placebo)

28%

9%

Children & adolescents

XR tablets

N/A

Bipolar depression

80

82

22%

13%

Children & adolescents

IR tablets

N/A

Bipolar mania

149

60

17%

8%

Children & adolescents

IR tablets

N/A

Schizophrenia

103

51

14%

9%

Adults

IR tablets

N/A

Bipolar depression

436

232

8%

8%

Adults

XR tablets

N/A

Bipolar depression

84

93

15%

6%

Adults

XR tablets

N/A

Bipolar mania

102

125

22%

16%

Adults

IR tablets

N/A

Schizophrenia

120

70

18%

5%

Adults

XR tablets

N/A

Schizophrenia

659

214

Quetiapine: Adverse Reaction: Weight Gain

Drug (Quetiapine)

Placebo

Population

Dosage Form

Dose

Indication

Number of Patients (Quetiapine)

Number of Patients (Placebo)

Comments

21%

7%

Adolescents

IR tablets

N/A

Schizophrenia

111

44

≥7% of Body Weight

15%

10%

Children & adolescents

XR tablets

N/A

Bipolar depression

92

100

≥7% of Body Weight

12%

0%

Children & adolescents

IR tablets

N/A

Bipolar mania

157

68

≥7% of Body Weight

6%

0%

Children & adolescents

IR tablets

400 to 600 mg/day

Bipolar mania

193

90

N/A

8%

2%

Adults

IR tablets

N/A

Bipolar depression

554

295

≥7% of Body Weight

8%

1%

Adults

XR tablets

N/A

Bipolar depression

110

125

≥7% of Body Weight

7%

1%

Adults

XR tablets

300 mg/day

Bipolar depression

137

140

N/A

4%

1%

Adults

IR tablets

300 to 600 mg/day

Bipolar depression

698

347

N/A

21%

7%

Adults

IR tablets

N/A

Bipolar mania

209

198

≥7% of Body Weight

7%

1%

Adults

XR tablets

400 to 800 mg/day

Bipolar mania

151

160

N/A

5%

0%

Adults

XR tablets

N/A

Bipolar mania

138

150

≥7% of Body Weight

23%

6%

Adults

IR tablets

N/A

Schizophrenia

391

206

≥7% of Body Weight

10%

5%

Adults

XR tablets

N/A

Schizophrenia

907

299

≥7% of Body Weight

5%

1%

Adults

IR tablets

75 to 800 mg/day

Schizophrenia and bipolar mania

719

404

N/A

Gastrointestinal: Increased appetite (2% to 12%), xerostomia (children and adolescents: 4% to 10%; adults: 9% to 44%) (table 7)

Quetiapine: Adverse Reaction: Xerostomia

Drug (Quetiapine)

Placebo

Population

Dosage Form

Dose

Indication

Number of Patients (Quetiapine)

Number of Patients (Placebo)

7%

0%

Children & adolescents

IR tablets

400 to 600 mg/day

Bipolar mania

193

90

10%

1%

Adolescents

IR tablets

800 mg/day

Schizophrenia

74

75

4%

1%

Adolescents

IR tablets

400 mg/day

Schizophrenia

73

75

44%

13%

Adults

IR tablets

300 and 600 mg/day

Bipolar depression

698

347

37%

7%

Adults

XR tablets

300 mg/day

Bipolar depression

137

140

34%

7%

Adults

XR tablets

400 to 800 mg/day

Bipolar mania

151

160

12%

1%

Adults

XR tablets

300 to 800 mg/day

Schizophrenia

951

319

9%

3%

Adults

IR tablets

75 to 800 mg/day

Schizophrenia and bipolar mania

719

404

Hematologic & oncologic: Decreased hemoglobin (8% to 11%)

Nervous system: Agitation (20%), dizziness (7% to 19%), drowsiness (18% to 57%) (table 8), extrapyramidal reaction (1% to 13%), fatigue (3% to 14%), headache (21%), withdrawal syndrome (12%)

Quetiapine: Adverse Reaction: Drowsiness

Drug (Quetiapine)

Placebo

Population

Dosage Form

Dose

Indication

Number of Patients (Quetiapine)

Number of Patients (Placebo)

57%

14%

Children & adolescents

IR tablets

600 mg/day

Bipolar mania

98

90

50%

14%

Children & adolescents

IR tablets

400 mg/day

Bipolar mania

95

90

35%

11%

Adolescents

IR tablets

800 mg/day

Schizophrenia

74

75

33%

11%

Adolescents

IR tablets

400 mg/day

Schizophrenia

73

75

57%

15%

Adults

IR tablets

300 to 600 mg/day

Bipolar depression

698

347

52%

13%

Adults

XR tablets

300 mg/day

Bipolar depression

137

140

50%

12%

Adults

XR tablets

400 to 800 mg/day

Bipolar mania

151

160

25%

10%

Adults

XR tablets

300 to 800 mg/day

Schizophrenia

951

319

18%

8%

Adults

IR tablets

75 to 800 mg/day

Schizophrenia and bipolar mania

719

404

1% to 10%:

Cardiovascular: Hypotension (3%), palpitations (4%), syncope (1% to 2%) (table 9)

Quetiapine: Adverse Reaction: Syncope

Drug (Quetiapine)

Placebo

Population

Dosage Form

Dose

Indication

Number of Patients (Quetiapine)

Number of Patients (Placebo)

2%

0%

Children & adolescents

IR tablets

400 to 600 mg/day

Bipolar mania

193

90

1%

0.2%

N/A

IR tablets

N/A

N/A

3,265

954

Dermatologic: Acne vulgaris (children and adolescents: 2% to 3%), hyperhidrosis (2%), pallor (children and adolescents: 1% to 2%), skin rash (4%)

Endocrine & metabolic: Decreased free T4 (3%), decreased libido (2%) (table 10), decreased total T4 (≤3%), hyperglycemia (fasting glucose <100 mg/dL to ≥126 mg/dL: 2%) (table 11), hyperprolactinemia (4%), increased LDL cholesterol (2% to 8%) (table 12), increased thirst (children and adolescents: 2%), increased thyroid stimulation hormone level (≤3%)

Quetiapine: Adverse Reaction: Decreased Libido

Drug (Quetiapine)

Placebo

Population

Dosage Form

Dose

Indication

Number of Patients (Quetiapine)

Number of Patients (Placebo)

2%

1%

Adults

XR tablets

300 mg/day

Bipolar depression

137

140

Quetiapine: Adverse Reaction: Hyperglycemia

Drug (Quetiapine)

Placebo

Population

Dosage Form

Dose

Indication

Number of Patients (Quetiapine)

Number of Patients (Placebo)

Comments

2%

1%

Adults

IR and XR tablets

N/A

N/A

2,907

1,346

Normal to high (<100 mg/dL to ≥126 mg/dL)

Quetiapine: Adverse Reaction: Increased LDL Cholesterol

Drug (Quetiapine)

Placebo

Population

Dosage Form

Dose

Indication

Number of Patients (Quetiapine)

Number of Patients (Placebo)

2%

4%

Children & adolescents

XR tablets

N/A

Bipolar depression

86

85

8%

5%

Children & adolescents

IR tablets

N/A

Bipolar mania

169

74

4%

2%

Children & adolescents

IR tablets

N/A

Schizophrenia

112

60

6%

5%

Adults

IR tablets

N/A

Bipolar depression

465

256

4%

2%

Adults

XR tablets

N/A

Bipolar depression

86

104

4%

2%

Adults

XR tablets

N/A

Bipolar mania

125

135

7%

8%

Adults

XR tablets

N/A

Schizophrenia

691

227

Gastrointestinal: Abdominal pain (1% to 4%), anorexia (1% to 3%), constipation (2% to 10%) (table 13), decreased appetite (2%), diarrhea (children and adolescents: 5%), dyspepsia (5% to 7%), dysphagia (2%) (table 14), gastroenteritis (2%), nausea (5% to 10%), periodontal abscess (adolescents: 1% to 3%), toothache (2% to 3%), vomiting (5% to 8%)

Quetiapine: Adverse Reaction: Constipation

Drug (Quetiapine)

Placebo

Population

Dosage Form

Dose

Indication

Number of Patients (Quetiapine)

Number of Patients (Placebo)

4%

0%

Children & adolescents

IR tablets

400 mg/day

Bipolar mania

95

90

2%

0%

Children & adolescents

IR tablets

600 mg/day

Bipolar mania

98

90

10%

4%

Adults

IR tablets

300 to 600 mg/day

Bipolar depression

698

347

8%

6%

Adults

XR tablets

300 mg/day

Bipolar depression

137

140

10%

3%

Adults

XR tablets

400 to 800 mg/day

Bipolar mania

151

160

6%

5%

Adults

XR tablets

300 to 800 mg/day

Schizophrenia

951

319

8%

3%

Adults

IR tablets

75 to 800 mg/day

Schizophrenia and bipolar mania

719

404

Quetiapine: Adverse Reaction: Dysphagia

Drug (Quetiapine)

Placebo

Population

Dosage Form

Dose

Indication

Number of Patients (Quetiapine)

Number of Patients (Placebo)

2%

0%

Adults

IR tablets

300 to 600 mg/day

Bipolar depression

698

347

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

Hematologic & oncologic: Neutropenia (≤2%) (table 15)

Quetiapine: Adverse Reaction: Neutropenia

Drug (Quetiapine)

Placebo

Population

Dosage Form

Dose

Indication

Number of Patients (Quetiapine)

Number of Patients (Placebo)

Comments

2%

0.8%

N/A

IR tablets

N/A

N/A

N/A

N/A

Neutrophil count <1.5 x 109/L

2%

0.8%

N/A

XR tablets

N/A

N/A

N/A

N/A

Neutrophil count <1.5 x 109/L

0.3%

0.1%

Adults

N/A

N/A

N/A

3368

1515

Neutrophil count <1.0 x 109/L

Hepatic: Increased serum alanine aminotransferase (5%), increased serum aspartate aminotransferase (3%), increased serum transaminases (1% to 6%)

Nervous system: Abnormal dreams (2% to 3%), aggressive behavior (children and adolescents: 1% to 3%), akathisia (≤5%) (table 16), anxiety (2% to 4%), ataxia (2%), confusion (2%) (table 17), decreased mental acuity (2%), disorientation (2%), disturbance in attention (2%), dysarthria (2% to 5%), dystonic reaction (≤6%) (table 18), hypersomnia (2% to 3%), hypoesthesia (2%), irritability (3% to 5%), lethargy (2% to 5%), migraine (2%), pain (7%), paresthesia (2% to 3%), parkinsonism (≤6%) (table 19), restless leg syndrome (2%), restlessness (2%)

Quetiapine: Adverse Reaction: Akathisia

Drug (Quetiapine)

Placebo

Population

Dosage Form

Dose

Indication

Number of Patients (Quetiapine)

Number of Patients (Placebo)

1%

0%

Children & adolescents

IR tablets

400 to 600 mg/day

Bipolar mania

193

90

5%

4%

Adolescents

IR tablets

800 mg/day

Schizophrenia

74

75

4%

4%

Adolescents

IR tablets

400 mg/day

Schizophrenia

73

75

4%

1%

Adults

IR tablets

300 to 600 mg/day

Bipolar depression

698

347

2%

0%

Adults

XR tablets

300 mg/day

Bipolar depression

137

140

1%

0.6%

Adults

XR tablets

400 to 800 mg/day

Bipolar mania

151

160

2%

8%

Adults

IR tablets

75 mg/day

Schizophrenia

53

51

2%

8%

Adults

IR tablets

150 mg/day

Schizophrenia

48

51

2%

8%

Adults

IR tablets

750 mg/day

Schizophrenia

54

51

0% to 2%

1%

Adults

XR tablets

300 to 800 mg/day

Schizophrenia

951

319

0%

8%

Adults

IR tablets

300 mg/day

Schizophrenia

52

51

0%

8%

Adults

IR tablets

600 mg/day

Schizophrenia

51

51

Quetiapine: Adverse Reaction: Confusion

Drug (Quetiapine)

Placebo

Population

Dosage Form

Dose

Indication

Number of Patients (Quetiapine)

Number of Patients (Placebo)

2%

0%

Adults

XR tablets

300 mg/day

Bipolar depression

137

140

Quetiapine: Adverse Reaction: Dystonic Reaction

Drug (Quetiapine)

Placebo

Population

Dosage Form

Dose

Indication

Number of Patients (Quetiapine)

Number of Patients (Placebo)

3%

0%

Adolescents

IR tablets

400 mg

Schizophrenia

73

75

0%

0%

Adolescents

IR tablets

800 mg

Schizophrenia

74

75

2%

0%

Adults

XR tablets

300 mg/day

Bipolar depression

137

140

0.7%

0%

Adults

XR tablets

400 to 800 mg/day

Bipolar mania

151

160

6%

8%

Adults

IR tablets

750 mg/day

Schizophrenia

54

51

4%

8%

Adults

IR tablets

75 mg/day

Schizophrenia

53

51

4%

8%

Adults

IR tablets

150 mg/day

Schizophrenia

48

51

4%

8%

Adults

IR tablets

600 mg/day

Schizophrenia

51

51

0% to 3%

0%

Adults

XR tablets

300 to 800 mg/day

Schizophrenia

951

319

0%

8%

Adults

IR tablets

300 mg/day

Schizophrenia

52

51

Quetiapine: Adverse Reaction: Parkinsonism

Drug (Quetiapine)

Placebo

Population

Dosage Form

Dose

Indication

Number of Patients (Quetiapine)

Number of Patients (Placebo)

2%

1%

Children & adolescents

IR tablets

400 mg

Bipolar mania

95

90

1%

1%

Children & adolescents

IR tablets

600 mg

Bipolar mania

98

90

6%

3%

Adolescents

IR tablets

400 mg

Schizophrenia

73

75

5%

3%

Adolescents

IR tablets

800 mg

Schizophrenia

74

75

0.7%

0.7%

Adults

XR tablets

300 mg/day

Bipolar depression

137

140

3%

2%

Adults

XR tablets

400 to 800 mg/day

Bipolar mania

151

160

4%

8%

Adults

IR tablets

75 mg/day

Schizophrenia

53

51

1% to 4%

1%

Adults

XR tablets

300 to 800 mg/day

Schizophrenia

951

319

2%

8%

Adults

IR tablets

300 mg/day

Schizophrenia

52

51

2%

8%

Adults

IR tablets

600 mg/day

Schizophrenia

51

51

2%

8%

Adults

IR tablets

750 mg/day

Schizophrenia

54

51

0%

8%

Adults

IR tablets

150 mg/day

Schizophrenia

48

51

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

Ophthalmic: Amblyopia (2%), blurred vision (2% to 4%) (table 20)

Quetiapine: Adverse Reaction: Blurred Vision

Drug (Quetiapine)

Placebo

Population

Dosage Form

Dose

Indication

Number of Patients (Quetiapine)

Number of Patients (Placebo)

3%

0%

Children & adolescents

IR tablets

400 mg/day

Bipolar mania

95

90

2%

0%

Children & adolescents

IR tablets

600 mg/day

Bipolar mania

98

90

4%

2%

Adults

IR tablets

300 to 600 mg/day

Bipolar depression

698

347

2%

1%

Adults

XR tablets

400 to 800 mg/day

Bipolar mania

151

160

2%

1%

Adults

XR tablets

300 to 800 mg/day

Schizophrenia

951

319

Otic: Otalgia (2%)

Respiratory: Cough (1% to 3%), dyspnea (1% to 3%), epistaxis (adolescents: 3%), nasal congestion (3% to 6%), paranasal sinus congestion (2% to 3%), pharyngitis (4%), rhinitis (3%), sinus headache (2%), sinusitis (2%)

Miscellaneous: Fever (2% to 4%)

<1%: Endocrine & metabolic: Decreased T3 blood level

Frequency not defined:

Cardiovascular: Hypertensive crisis (one case in a child with a history of hypertension)

Nervous system: Falling, suicidal tendencies

Postmarketing:

Cardiovascular: Atrial fibrillation (Chou 2017), atrial flutter (Chou 2017), cardiomyopathy (rare: <1%) (Coffey 2011), colonic ischemia, myocarditis (rare: <1%) (Bhogal 2018), prolonged QT interval on ECG (Kim 2016), torsades de pointes (rare: <1%) (Vieweg 2005)

Dermatologic: Acute generalized exanthematous pustulosis, Stevens-Johnson syndrome, toxic epidermal necrolysis

Endocrine & metabolic: Diabetes mellitus (new onset; less frequent: ≥1% to <4%) (Nanasawa 2017; Nielson 2010), diabetic ketoacidosis (rare: <1%) (Ely 2013), hyponatremia, hypothyroidism (Feret 2000), SIADH

Gastrointestinal: Intestinal obstruction, pancreatitis (rare: <1%) (Alastal 2016)

Genitourinary: Erectile dysfunction (common: ≥10%) (Nagaraj 2009), nocturia, orgasm disturbance (common: ≥10%) (Nagaraj 2009), urinary retention (high-dose therapy; rare: <1%) (Sokolski 2004)

Hematologic & oncologic: Agranulocytosis (rare: <1%) (Glocker 2017), autoimmune hemolytic anemia (rare: <1%) (Huynh 2005), eosinophilia (rare: <1%) (Chen 2015), leukopenia (Fan 2015), thrombocytopenia (rare: <1%) (Arslan 2016), thrombotic thrombocytopenic purpura (rare: <1%) (Husnain 2017)

Hepatic: Hepatic failure, hepatic necrosis, hepatitis

Hypersensitivity: Anaphylaxis

Immunologic: Drug reaction with eosinophilia and systemic symptoms

Nervous system: Choreoathetosis (rare: <1%) (Netherlands Pharmacovigilance Centre Lareb 2006), cognitive dysfunction (El-Saifi 2016), delirium (rare: <1%) (Almeida 2019), diabetes mellitus with hyperosmolar coma, neuroleptic malignant syndrome (rare: <1%) (Schattner 2016), retrograde amnesia, sleep apnea, suicidal ideation (rare: <1%) (Katila 2013), tardive dyskinesia (rare: <1%) (Hou 2014)

Neuromuscular & skeletal: Hypokinesia (rare: <1%) (Netherlands Pharmacovigilance Centre Lareb 2006), rhabdomyolysis

Ophthalmic: Cataract (rare: <1%) (Fraunfelder 2004), intraoperative floppy iris syndrome (Chatziralli 2016)

Respiratory: Obstructive sleep apnea syndrome (Health Canada 2016; Shirani 2011)

Contraindications

Hypersensitivity to quetiapine or any component of the formulation

Warnings/Precautions

Disease-related concerns:

• Cancer (eg, breast cancer): The clinical significance of hyperprolactinemia in patients with breast cancer or other prolactin-dependent tumors is unknown.

• GI motility: Use with caution in patients with decreased GI motility as anticholinergic effects may exacerbate underlying condition.

• Hepatic impairment: Use with caution in patients with hepatic disease or impairment; dosage adjustment may be required.

• 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.

• Urinary retention (eg, benign prostatic hyperplasia): Use with caution in patients with urinary retention as anticholinergic effects may exacerbate underlying condition.

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.

Other warnings/precautions:

• Discontinuation of therapy: When discontinuing antipsychotic therapy, gradually taper antipsychotics to avoid physical withdrawal symptoms and rebound symptoms (APA [Keepers 2020]; WFSBP [Hasan 2012]). Withdrawal symptoms may include agitation, alternating feelings of warmth and cold, anxiety, diaphoresis, dyskinesia, GI symptoms, insomnia, irritability, myalgia, paresthesia, psychosis, restlessness, rhinorrhea, tremor, and vertigo (Lambert 2007; Moncrieff 2020). The risk of withdrawal symptoms is highest following abrupt discontinuation of highly anticholinergic or dopaminergic antipsychotics (Cerovecki 2013). Patients with chronic symptoms, repeated relapses, and clear diagnostic features of schizophrenia are at risk for poor outcomes if medications are discontinued (APA [Keepers 2020]).

Warnings: Additional Pediatric Considerations

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).

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

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 (Oral): May enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, the risk of neuroleptic malignant syndrome may be increased. 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 avoiding atypical antipsychotic use in patients with Parkinson disease. If an atypical antipsychotic is necessary, consider using clozapine, quetiapine, or ziprasidone at lower initial doses, or a non-dopamine antagonist (eg, pimavanserin). Risk D: Consider therapy modification

Armodafinil: May decrease the serum concentration of QUEtiapine. Risk C: Monitor therapy

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

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with 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

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

Cabergoline: May diminish the therapeutic effect of Antipsychotic Agents. Risk X: Avoid combination

Cannabinoid-Containing Products: Anticholinergic Agents may enhance the tachycardic effect of Cannabinoid-Containing Products. Risk C: Monitor therapy

Cannabinoid-Containing Products: CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products. 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

CYP3A4 Inducers (Moderate): May decrease the serum concentration of QUEtiapine. 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 to 14 days of discontinuing the inducer. Risk D: Consider therapy modification

CYP3A4 Inhibitors (Moderate): May increase the serum concentration of QUEtiapine. 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 original dose after starting a strong CYP3A4 inhibitor. In those on strong CYP3A4 inhibitors, start quetiapine at lowest dose and up-titrate as needed. Risk D: Consider therapy modification

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

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

Dexmethylphenidate-Methylphenidate: Antipsychotic Agents may enhance the adverse/toxic effect of Dexmethylphenidate-Methylphenidate. Dexmethylphenidate-Methylphenidate may enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, the risk of extrapyramidal symptoms may be increased when these agents are combined. Risk C: Monitor therapy

Difelikefalin: May enhance the CNS depressant effect of CNS Depressants. 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

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

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

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: QT-prolonging Antipsychotics (Moderate Risk) may enhance the QTc-prolonging effect of Fexinidazole. 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

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. 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

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

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 antiseizure drugs. 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 antiseizure drugs. 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 antiseizure drugs. 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 CNS depressant effect of CNS Depressants. Risk C: Monitor therapy

Kratom: May enhance the CNS depressant effect of QUEtiapine. Kratom may increase the serum concentration of QUEtiapine. Risk X: Avoid combination

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

Levoketoconazole: QT-prolonging CYP3A4 Substrates may enhance the QTc-prolonging effect of Levoketoconazole. Levoketoconazole may increase the serum concentration of QT-prolonging CYP3A4 Substrates. Risk X: Avoid combination

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 the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider therapy modification

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

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

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

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

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

Oxybate Salt Products: CNS Depressants may enhance the CNS depressant effect of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interrupt oxybate salt treatment during short-term opioid use Risk D: Consider therapy modification

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

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. Risk C: Monitor therapy

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 X: Avoid combination

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. 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. 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 initiating these strong CYP3A4 inhibitors. In patients already receiving these strong CYP3A4 inhibitors, initiate quetiapine at the lowest dose and titrate cautiously as needed. 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

Ropeginterferon Alfa-2b: CNS Depressants may enhance the adverse/toxic effect of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). 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

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

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

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 to 14 days of discontinuing St John's wort. Monitor closely. 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

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

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

Trimeprazine: QUEtiapine may enhance the CNS depressant effect of Trimeprazine. Trimeprazine may increase the serum concentration of QUEtiapine. Risk C: Monitor therapy

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

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

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 Cmax or AUC. Management: Administer without food or with a light meal (≤300 calories).

Reproductive Considerations

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

If treatment with atypical antipsychotic is needed in a woman planning a pregnancy, use of quetiapine may be considered (Larsen 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 initiated during pregnancy, use of quetiapine may be considered (Larsen 2015).

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).

Breastfeeding 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).

Dietary Considerations

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

Monitoring Parameters

Frequency of Antipsychotic Monitoringa,b

Monitoring parameter

Frequency of monitoring

Comments

a For all monitoring parameters, it is appropriate for check at baseline and when clinically relevant (based on symptoms or suspected adverse reactions) in addition to the timeline.

b ADA 2004; APA [Keepers 2020]; De Hert 2011; Gugger 2011; manufacturer's labeling.

c Risk factors for extrapyramidal symptoms (EPS) include prior history of EPS, high doses of antipsychotics, young age (children and adolescents at higher risk than adults), and dopaminergic affinity of individual antipsychotic.

d Risk factors for tardive dyskinesia include age >55 years; females; White or African ethnicity; presence of a mood disorder, intellectual disability, or CNS injury; past or current EPS.

Adherence

Every visit

Blood chemistries (electrolytes, renal function, liver function, TSH)

Annually

CBC

As clinically indicated

Check frequently during the first few months of therapy in patients with preexisting low WBC or history of drug-induced leukopenia/neutropenia

Extrapyramidal symptoms

Every visit; 4 weeks after initiation and dose change; annually. Use a formalized rating scale at least annually or every 6 months if high risk.c

Fall risk

Every visit

Fasting plasma glucose/HbA1c

12 weeks after initiation and dose change; annually

Check more frequently than annually if abnormal. Follow diabetes guidelines.

Lipid panel

12 weeks after initiation and dose change; annually

Check more frequently than annually if abnormal. Follow lipid guidelines.

Mental status

Every visit

Metabolic syndrome history

Annually

Evaluate for personal and family history of obesity, diabetes, dyslipidemia, hypertension, or cardiovascular disease

Prolactin

Ask about symptoms at every visit until dose is stable. Check prolactin level if symptoms are reported.

Hyperprolactinemia symptoms: Changes in menstruation, libido, gynecomastia, development of galactorrhea, and erectile and ejaculatory function

Tardive dyskinesia

Every visit; annually. Use a formalized rating scale at least annually or every 6 months if high risk.d

Vital signs (BP, orthostatics, temperature, pulse, signs of infection)

Every visit (at least weekly during first 3 to 4 weeks of treatment); 4 weeks after dose change.

Weight/Height/BMI

8 and 12 weeks after initiation and dose change; quarterly

Consider monitoring waist circumference at baseline and annually, especially in patients with or at risk for metabolic syndrome.

Consider changing antipsychotic if BMI increases by ≥1 unit.

Some experts recommend checking weight and height at every visit.

Reference Range

Timing of serum samples: Draw trough just before next dose (Hiemke 2018).

Therapeutic reference range: 100 to 500 ng/mL (SI: 261 to 1305 nmol/L) (Hiemke 2018). Note: Dosing should be based on therapeutic response as opposed to serum concentrations; however, therapeutic drug monitoring can be used to confirm adherence (APA [Keepers 2020]).

Laboratory alert level: 1,000 ng/mL (SI: 2,610 nmol/L) (Hiemke 2018).

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-HT1A 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.

Pharmacokinetics

Onset of action:

Bipolar disorder, acute mania: Initial effects may be observed within days of treatment with continued improvements over 1 to 2 weeks (Goikolea 2013; Tohen 2000; Welten 2016).

Bipolar disorder, depressive episode: Initial effects may be observed within 1 week of treatment with continued improvements through 6 weeks (Cruz 2010).

Generalized anxiety disorder: Extended release: Initial effects may be observed within 4 to 7 days with continued improvements over 8 weeks (Bandelow 2010; Khan 2011; Merideth 2012).

Major depressive disorder, unipolar: Initial effects may be observed within 1 week with continued improvements over 6 to 12 weeks (Wen 2014).

Schizophrenia: Oral: Initial effects may be observed within 1 to 2 weeks of treatment with continued improvements through 4 to 6 weeks (Agid 2003; Levine 2010).

Absorption: Rapidly absorbed following oral administration; high-fat meals (800 to 1000 calories) increase Cmax 8% and AUC 2% of quetiapine XR; light meals (300 calories) had no effect; parent compound AUC and Cmax 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: Vd: 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%)

Pharmacokinetics: 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 Cmax is 3-fold higher.

Geriatric: Clearance reduced 40%.

Pricing: US

Tablet, 24-hour (QUEtiapine Fumarate ER Oral)

50 mg (per each): $8.87 - $15.00

150 mg (per each): $1.25 - $15.93

200 mg (per each): $1.50 - $17.53

300 mg (per each): $1.75 - $22.98

400 mg (per each): $2.29 - $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.

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)


For country abbreviations used in Lexicomp (show table)

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