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QUEtiapine

Medically reviewed on Nov 15, 2018

Pronunciation

See also: Ingrezza

(kwe TYE a peen)

Index Terms

  • Quetiapine Fumarate

Dosage Forms

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

Brand Names: U.S.

  • SEROquel
  • SEROquel XR

Pharmacologic Category

  • Second Generation (Atypical) Antipsychotic

Pharmacology

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.

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 (10-17 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

Metabolism

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

Excretion

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

Time to Peak

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

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

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

Protein Binding

Plasma: 83%

Special Populations: 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.

Special Populations: Hepatic Function Impairment

30% lower clearance; AUC and Cmax is 3-fold higher.

Special Populations: Elderly

Clearance reduced 40%.

Use: Labeled Indications

Bipolar disorder: Acute treatment of manic (both immediate release and ER) or mixed (ER only) episodes associated with bipolar I disorder, both as monotherapy and as an adjunct to lithium or divalproex; maintenance treatment of bipolar I disorder, as an adjunct to lithium or divalproex; acute treatment of depressive episodes associated with bipolar disorder, as monotherapy

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

Schizophrenia: Treatment of schizophrenia.

Off Label Uses

Delirium, ICU

Data from a limited number of patients in a prospective, randomized, double-blind, placebo-controlled study suggest that quetiapine may be beneficial in ICU delirium [Devlin 2010].

Based on the Society of Critical Care Medicine guidelines for the prevention and management of pain, agitation/sedation, delirium, immobility, and sleep disruption of adult patients in the ICU, short-term use of antipsychotics like quetiapine may be useful for ICU patients who experience significantly distressing symptoms of delirium, including agitation, anxiety, delusions, fearfulness, or hallucinations, or those who may be physically harmful to themselves or others. The guideline discourages against the routine use of antipsychotics for patients with delirium [SCCM [Devlin 2018]].

Delusional infestation (also called delusional parasitosis)

Data from a limited number of patients studied in case reports suggest that quetiapine may be beneficial for the treatment of delusional infestation (also called delusional parasitosis) [Freudenmann 2008], [Milia 2008].

Generalized anxiety disorder

Data from double-blind, randomized, placebo-controlled trials and a meta-analysis support the use of quetiapine as monotherapy or as an adjunct to antidepressants in the treatment of generalized anxiety disorder (GAD) [Altamura 2011], [Khan 2013], [Maneeton 2016].

Based on the World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the treatment of anxiety, obsessive-compulsive, and posttraumatic stress disorders, quetiapine is effective and recommended in the management of GAD [WFSBP [Bandelow 2008]]. Based on the Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress, and obsessive-compulsive disorders, quetiapine monotherapy is recommended in patients who cannot take antidepressants, pregabalin, or benzodiazepines and as an adjunct therapy in treatment-resistant GAD [Katzman 2014].

Major depressive disorder (unipolar), monotherapy

Data from a meta-analysis of 3 randomized, double-blind, placebo-controlled studies in adults and a randomized, double-blind, placebo-controlled study in elderly patients support the use of quetiapine monotherapy in the treatment of major depressive disorder [Katila 2013], [Maneeton 2012].

Obsessive compulsive disorder, treatment-resistant (augmentation)

Data from a limited number of clinical trials suggest that quetiapine augmentation may be beneficial for the treatment of obsessive compulsive disorder [Dold 2013], [Skapinakis 2007].

Based on the American Psychiatric Association (APA) practice guideline for the treatment of patients with obsessive-compulsive disorder and the WFSBP guidelines for the pharmacological treatment of obsessive-compulsive disorder, antipsychotics given as augmentation in treatment-resistant obsessive compulsive disorder are effective and recommended in the management of this condition in patients who have a partial response to initial treatment; however, evidence supporting quetiapine is limited [APA [Koran 2007]], [WFSBP [Bandelow 2008]].

Posttraumatic stress disorder, adjunct to antidepressants or monotherapy

Data in a limited number of clinical trials suggest that mono- or adjunctive therapy with quetiapine may be beneficial for the treatment of posttraumatic stress disorder in patients who have had an inadequate response with antidepressants [Ahearn 2006], [Hamner 2003], [Kozaric-Kovacic 2007], [Villarreal 2016].

Based on the APA practice guidelines for the treatment of patients with posttraumatic stress disorder and the WFSBP guidelines for the pharmacological treatment of anxiety, obsessive-compulsive, and posttraumatic stress disorders, therapy with antipsychotics like quetiapine is suggested as a treatment option for patients when concomitant psychotic symptoms are present or when first-line approaches have been ineffective in controlling symptoms; however, evidence supporting use is greater for other antipsychotic agents including risperidone and olanzapine [APA [Ursano 2004]], [WFSBP [Bandelow 2008]]. Based on the Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress, and obsessive-compulsive disorders, quetiapine is recommended as a third line-agent for monotherapy or as an adjunct for first-line agents in patients with refractory posttraumatic stress disorder [Katzman 2014].

Psychosis/agitation associated with dementia

Data from a randomized, double-blind, placebo-controlled study support the use of quetiapine in the treatment of psychosis/agitation in dementia [Zhong 2007]; data from a limited number of patients in open-label trials also suggest quetiapine may be beneficial in the treatment of psychosis/agitation in Alzheimer dementia [Fujikawa 2004], [McManus 1999], [Scharre 2002].

Based on the APA practice guideline on the use of antipsychotics to treat agitation or psychosis in patients with dementia, antipsychotics, such as quetiapine, may be considered for the treatment of agitation and psychosis in certain patients; however, evidence for efficacy is modest and use should be limited to patients whose symptoms are dangerous, severe, or cause significant patient distress due to safety risks associated with antipsychotic use [APA [Reus 2016]]. Based on the WFSBP guidelines for the biological treatment of Alzheimer disease and other dementias, drug treatment with quetiapine for behavioral and psychological aspects (including hyperactivity and psychosis) is recommended at low doses and for short durations, as a last option after addressing causative factors and using psychosocial interventions [WFSBP [Ihl 2011]].

Psychosis in Parkinson disease

Data in a limited number of clinical trials suggest that quetiapine may be beneficial for the treatment of psychosis in patients with Parkinson disease [Fernandez 1999], [Fernandez 2009], [Juncos 2004], [Mancini 2004], [Merims 2006], [Morgante 2002], [Morgante 2004].

Based on joint guidelines on the management of Parkinson disease from the European Federation of Neurological Societies and the European section of the Movement Disorder Society, quetiapine is possibly useful when psychosis persists after managing triggering factors and reducing polypharmacy and antiparkinsonian drugs [Ferreira 2013].

Contraindications

Hypersensitivity to quetiapine or any component of the formulation

Dosing: Adult

Note: Quetiapine is available as immediate-release and 24-hour ER tablets; to convert between formulations, see Dosing Conversion below.

Bipolar disorder: Oral:

Acute manic or mixed episodes (monotherapy or as an adjunct to lithium or valproic acid):

Immediate release: Initial: 50 mg twice daily on day 1, further increase by 100 mg/day (divided twice daily) until 200 mg twice daily is reached by day 4; may further increase to 800 mg/day by day 6 in increments of ≤200 mg/day. Usual dosage range: 400 to 800 mg/day; maximum dose: 800 mg/day. Some experts recommend doses as high as 1,200 mg/day for treatment refractory patients (Stovall 2018a).

ER: Initial: 300 mg once daily on day 1; increase to 600 mg once daily on day 2 then adjust dose to between 400 to 800 mg once daily on day 3; usual dosage range: 400 to 800 mg once daily; maximum dose: 800 mg once daily. Some experts recommend doses as high as 1,200 mg/day for treatment refractory patients (Stovall 2018a).

Depressive episodes: Immediate release and ER: 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 dose of 300 mg once daily by day 4; maximum dose (manufacturer labeling): 300 mg/day. Doses up to 600 mg/day have been used in practice (Stovall 2018b); however, for doses >300 mg/day, clinical trials did not find additional benefit and adverse effects were greater (Chiesa 2012; Porcelli 2014).

Maintenance therapy (adjunct to lithium or divalproex): Immediate release and ER: Usual dosage range: 400 to 800 mg/day; maximum dose: 800 mg/day. Note: In the maintenance phase, patients generally continue on the same dose on which they were stabilized. During maintenance treatment, periodically reassess need for continued therapy and the appropriate dose.

Delirium, ICU (alternative agent) (off-label use): Limited data available: Oral: Immediate release: Initial: 50 mg twice daily; may increase daily as necessary in 100 mg/day increments to a maximum dose of 400 mg/day (Devlin 2010).

Delusional infestation (also called delusional parasitosis) (off-label use): Limited data available: Oral: Initial: Immediate release:12.5 to 50 mg at bedtime; gradually increase every 3 to 7 days based on response and tolerability up to 200 to 300 mg at bedtime or in divided doses; maximum dose: 800 mg/day. Continue treatment for at least 3 months before attempting to taper (Blasco-Fontecilla 2005; Freudenmann 2008; Heller 2013; Milia 2008; Suh 2018).

Generalized anxiety disorder (alternative agent) (off-label): Oral: Immediate release and ER: Initial: 25 mg/day (immediate release only) to 50 mg/day; gradually increase dose every 2 to 7 days based on response and tolerability to a target dose of 150 to 300 mg/day (Altamura 2011; Galynker 2005; Katzman 2011; Khan 2013). Note: May be used for monotherapy in patients who cannot take antidepressants, pregabalin or benzodiazepines and as an adjunct therapy in treatment-resistant generalized anxiety disorder (Katzman 2014).

Major depressive disorder (unipolar): Adjunct to antidepressants: Oral: ER: Initial: 50 mg once daily on days 1 and 2; increase to 150 mg once daily on day 3. Usual dosage range: 150 to 300 mg/day; maximum dose: 300 mg/day (manufacturer's labeling); however, doses up to 600 mg/day in psychotic depression may be considered (Wijkstra 2010). Note: The use of immediate release formulation (off-label) may also be considered (Chaput 2008; McIntyre 2007). Quetiapine has also been used as an alternative agent as monotherapy (off-label) for major depressive disorder (Maneeton 2012; Vieta 2013).

Obsessive-compulsive disorder, treatment-resistant (augmentation; off-label use): Oral: Immediate release: Initial: 25 to 50 mg once daily; increase gradually based on response and tolerability up to 400 mg/day. Increases of 25 to 100 mg increments every 2 to 3 weeks were used in clinical trials (Atmaca 2002; Denys 2004; Fineberg 2005).

Posttraumatic stress disorder, adjunct to antidepressants or monotherapy (alternative agent) (off-label use): Oral: Immediate release: Initial: 25 mg 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 or up to 100 mg/week. Average dose in clinical trials: 100 to 336 mg/day (range: 25 to 800 mg/day); maximum dose: 800 mg/day administered in 1 or 2 divided doses (Ahearn 2006; Hamner 2003; Kozaric-Kovacic 2007; Villarreal 2016). Note: For use in refractory patients or those with concomitant psychosis (APA [Benedek 2009]).

Psychosis in Parkinson disease (off-label use): Oral: Immediate release: Initial: 12.5 to 25 mg at bedtime; gradually increase based on response and tolerability in 12.5 to 25 mg increments every 1 to 2 weeks; average dose in studies ranged from 40 to 185 mg/day (Fernandez 1999; Mancini 2004; Merims 2006).

Schizophrenia: Oral:

Immediate release: Initial: 25 mg twice daily; increase in increments of 25 to 50 mg divided 2 to 3 times on days 2 and 3 and increase further to a target dose of 300 to 400 mg/day by day 4. Further adjustments as needed at intervals of at least 2 days in increments of 25 to 50 mg twice daily. Acute therapy usual dosage range: 150 to 750 mg/day; maximum dose: 750 mg/day. Maintenance therapy usual dosage range: 400 to 800 mg/day; maximum dose: 800 mg/day.

ER: Initial: 300 mg once daily; increase in increments of up to 300 mg once daily (in intervals of ≥1 day). Usual dosage range: 400 to 800 mg once daily; maximum dose: 800 mg/day.

Note: Doses up to 1,600 mg/day have been evaluated in clinical studies; however, doses >800 mg/day were not found to offer greater efficacy and may result in greater adverse effects (Honer 2012; Lindenmayer 2011; Nagy 2005).

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

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

Dosage adjustment for concomitant therapy:

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

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

Discontinuation of therapy: The manufacturer and American Psychiatric Association (APA), Canadian Psychiatric Association (CPA), and World Federation of Societies of Biological Psychiatry (WFSBP) guidelines recommend gradually tapering antipsychotics to avoid withdrawal symptoms and minimize the risk of relapse (APA [Lehman 2004]; Cerovecki 2013; CPA 2005; WFSBP [Hasan 2012]); risk for withdrawal symptoms may be highest with highly anti-cholinergic or dopaminergic antipsychotics (Cerovecki 2013). When stopping antipsychotic therapy in patients with schizophrenia, the CPA guidelines recommend a gradual taper over 6 to 24 months, and the APA guidelines recommend reducing the dose by 10% each month (APA [Lehman 2004]; CPA 2005). Continuing anti-parkinsonism agents for a brief period after discontinuation may prevent withdrawal symptoms (Cerovecki 2013).

Switching antipsychotics: Two strategies have primarily been suggested: 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). Evidence supporting ideal switch strategies and taper rates is limited, and results are conflicting (Cerovecki 2013; Remington 2005; Takeuchi 2017).

Dosing: Geriatric

Bipolar disorder or schizophrenia: Oral: Immediate release and ER: 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): Oral: ER: 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

Psychosis/agitation associated with dementia (off-label use): Oral: Immediate release: Initial: 12.5 to 25 mg at bedtime; if necessary, gradually increase based on response and tolerability up to 200 to 300 mg/day (APA [Rabins 2007]; Fujikawa 2004; Scharre 2002). In patients without a clinically significant response after 4 weeks, taper and withdraw therapy. In patients with an adequate response, attempt to taper and withdraw therapy within 4 months, unless symptoms recurred with a previous taper attempt. Assess symptoms at least monthly during taper and for at least 4 months after withdrawal of therapy (APA [Reus 2016]).

Dosing conversion: Refer to adult dosing.

Reinitiation of treatment: Refer to adult dosing.

Dosage adjustment for concomitant therapy: Refer to adult dosing.

Discontinuation of therapy: Refer to adult dosing.

Switching antipsychotics: Refer to adult dosing.

Dosing: Pediatric

Bipolar disorder: Children ≥10 years and Adolescents ≤17 years: Oral: Mania (monotherapy):

Immediate release: Initial: 25 mg twice daily on day 1; increase to 50 mg twice daily on day 2, then increase by 100 mg (administered twice daily) each day until 200 mg twice day is reached on day 5. May further increase up to 600 mg/day in increments of ≤100 mg daily. Usual dosage range: 400 to 600 mg/day; maximum: 600 mg/day. Note: Total daily doses may also be divided into 3 doses per day, based on response and tolerability.

ER: Initial: 50 mg once daily on day 1; increase to 100 mg once daily on day 2, further increase by 100 mg once daily until 400 mg once daily is reached on day 5. Usual dosage range: 400 to 600 mg once daily; maximum dose: 600 mg once daily.

Schizophrenia: Adolescents 13 to ≤17 years: Oral:

Immediate release: Initial: 25 mg twice daily on day 1; increase to 50 mg twice daily on day 2, further increase by 100 mg each day (divided twice daily) until 400 mg twice daily is reached on day 5. May further increase up to 800 mg/day in increments of ≤100 mg/day. Usual dosage range: 400 to 800 mg/day; maximum dose: 800 mg daily. Note: Total daily doses may also be divided into 3 doses per day, based on response and tolerability.

ER: Initial: 50 mg once daily on day 1; increase to 100 mg once daily on day 2, further increase by 100 mg once daily until 400 mg once daily is reached on day 5. Usual dosage range: 400 to 800 mg once daily; maximum dose: 800 mg once daily.

Dosing conversion: Refer to adult dosing.

Reinitiation of treatment: Refer to adult dosing.

Dosage adjustment for concomitant therapy: Refer to adult dosing.

Discontinuation of therapy: Refer to adult dosing.

Switching antipsychotics: Refer to adult dosing.

Dosing: Renal Impairment

No dosage adjustment necessary.

Dosing: Hepatic Impairment

Immediate release tablet: Initial: 25 mg daily, increase dose by 25 to 50 mg daily to effective dose, based on individual clinical response and tolerability

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

Administration

Oral:

Immediate release tablet: Administer with or without food.

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

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).

Dietary Considerations

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

Storage

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

Drug Interactions

AbobotulinumtoxinA: Anticholinergic Agents may enhance the anticholinergic effect of AbobotulinumtoxinA. Monitor therapy

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

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

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

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

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

Amifampridine: May diminish the anticholinergic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Amifampridine. Monitor therapy

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

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

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

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

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

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

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

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

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

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

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

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

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

Bromperidol: May enhance the CNS depressant effect of CNS Depressants. 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 patches (Butrans brand) at 5 mcg/hr in adults when used with other CNS depressants. Consider therapy modification

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

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

Cannabis: May enhance the CNS depressant effect of CNS Depressants. 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. Consider therapy modification

Chloral Betaine: May enhance the adverse/toxic effect of Anticholinergic Agents. 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. Consider therapy modification

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

FLUoxetine: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Highest Risk). Monitor therapy

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. Monitor therapy

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

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

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

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

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

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

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

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

HYDROcodone: CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Avoid concomitant use of hydrocodone 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. Consider therapy modification

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

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

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

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

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

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

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

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

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

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

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. 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. Consider therapy modification

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

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

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

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

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

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

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

Minocycline: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

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

Mirtazapine: CNS Depressants may enhance the CNS depressant effect of Mirtazapine. Monitor therapy

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

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

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

OnabotulinumtoxinA: Anticholinergic Agents may enhance the anticholinergic effect of OnabotulinumtoxinA. Monitor therapy

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

Opioid Analgesics: CNS Depressants may enhance the CNS depressant effect of Opioid Analgesics. Management: Avoid concomitant use of opioid analgesics 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. Consider therapy modification

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

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

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

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

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

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. 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. Monitor therapy

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

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

Pitolisant: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). Management: Combined use of pitolisant with a CYP3A4 substrate that has a narrow therapeutic index should be avoided. Other CYP3A4 substrates should be monitored more closely when used with pitolisant. Consider therapy modification

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. Avoid combination

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

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

QT-prolonging Agents (Highest Risk): May enhance the QTc-prolonging effect of QUEtiapine. 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. Monitor therapy

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

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

QT-prolonging Moderate CYP3A4 Inhibitors (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. 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. Monitor therapy

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

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

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

RimabotulinumtoxinB: Anticholinergic Agents may enhance the anticholinergic effect of RimabotulinumtoxinB. Monitor therapy

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

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

Sarilumab: May decrease the serum concentration of CYP3A4 Substrates (High risk with Inducers). 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. Consider therapy modification

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

Serotonin Modulators: May enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Exceptions: Nicergoline. Monitor therapy

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

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

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

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

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

Sulpiride: Antipsychotic Agents may enhance the adverse/toxic effect of Sulpiride. 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. Consider therapy modification

Tapentadol: May enhance the CNS depressant effect of CNS Depressants. Management: Avoid concomitant use of tapentadol 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. Consider therapy modification

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

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

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

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

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

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

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

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

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

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

Test Interactions

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

Adverse Reactions

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

>10%:

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

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

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

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

1% to 10%:

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

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

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

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

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

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

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

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

Hypersensitivity: Seasonal allergy (2%)

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

Ophthalmic: Blurred vision (1% to 4%), amblyopia (2% to 3%)

Otic: Otalgia (2%)

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

Miscellaneous: Fever (2% to 4%)

<1%, postmarketing, and/or case reports: Abnormal gait, abnormality of accommodation, abnormal T waves on ECG, abnormal vision, acute renal failure, agranulocytosis, alcohol intolerance, amenorrhea, amnesia, anaphylaxis, anemia, angina pectoris, apathy, aphasia, arthritis, asthma, atrial arrhythmia, atrial fibrillation, atrioventricular block, blepharitis, bone pain, bradycardia, bruxism, buccoglossal syndrome, bundle branch block, candidiasis, cardiomyopathy, cataract, catatonic reaction, cerebral ischemia, cerebrovascular accident, chills, choreoathetosis, conjunctivitis, contact dermatitis, cyanosis, cystitis, deafness, deep vein thrombophlebitis, dehydration, delirium, delusions, dental caries, depersonalization, DRESS syndrome, dysmenorrhea, diabetes mellitus, dysuria, ecchymosis, eczema, ejaculatory disorder, emotional lability, enlargement of abdomen, eosinophilia, euphoria, exfoliative dermatitis, eye pain, facial edema, fecal incontinence, first degree atrioventricular block, flattened T wave on ECG, flatulence, flu-like symptoms, galactorrhea, gastritis, gingival hemorrhage, gingivitis, glaucoma, glossitis, glycosuria, gout, gynecomastia, hallucination, hand edema, hematemesis, hemiplegia, hemolysis, hemorrhoids, hiccups, hyperkinesia, hyperlipemia, hypersensitivity reaction, hyperthyroidism, hyperventilation, hypochromic anemia, hypoglycemia, hypokalemia, hyponatremia, hypothermia, impotence, increased creatine phosphokinase, increased gamma-glutamyl transferase, increased libido, increased serum alkaline phosphatase, increased serum creatinine, increased ST segment on ECG, increased salivation, increased ST segment on ECG, insomnia, intestinal obstruction, inversion T wave on ECG, involuntary body movements, irregular pulse, lactation (females), leg cramps, leukocytosis, leukorrhea, lymphadenopathy, maculopapular rash, malaise, manic reaction, melena, mouth ulceration, myasthenia, myocarditis, myoclonus, neuralgia, neuroleptic malignant syndrome, nightmares, nocturia, orchitis, pancreatitis, paranoid reaction, pathological fracture, pelvic pain, pneumonia, polyuria, priapism, prolonged Q-T interval on ECG, pruritus, psoriasis, psychosis, psychosis, rectal hemorrhage, retrograde amnesia, rhabdomyolysis, seborrhea, seizure, skin discoloration, skin photosensitivity, skin ulcer, SIADH, sleep apnea syndrome (obstructive) (Health Canada 2016, Shirani 2011), somnambulism, Stevens-Johnson syndrome, stomatitis, ST segment changes on ECG, stupor, stuttering, subdural hematoma, suicidal ideation, suicidal tendencies, tardive dyskinesia, taste perversion, thrombocytopenia, thrombophlebitis, tinnitus, tongue edema, toxic epidermal necrolysis, urinary frequency, urinary Incontinence, urinary retention, uterine hemorrhage, vaginal hemorrhage, vaginitis, vasodilatation, vulvovaginal moniliasis, vulvovaginitis, water intoxication, weight loss, widened QRS complex on ECG, xerophthalmia

ALERT: U.S. 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.

Warnings/Precautions

Major psychiatric warnings:

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

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

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

Concerns related to adverse effects:

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

• Blood dyscrasias: Leukopenia, neutropenia, and agranulocytosis (sometimes fatal) have been reported with antipsychotic use; presence of risk factors (eg, preexisting low WBC or history of drug-induced leuko-/neutropenia) should prompt periodic blood count assessment. Discontinue therapy at first signs of blood dyscrasias or if absolute neutrophil count <1,000/mm3.

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

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

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

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

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

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

• Hyperlipidemia: Increases in cholesterol and triglycerides have been noted. Use with caution in patients with pre-existing abnormal lipid profile.

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

• Hypersensitivity: Anaphylactic reactions have been reported.

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

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

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

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

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

• Weight gain: Significant weight gain has been observed with antipsychotic therapy; incidence varies with product. Monitor waist circumference and BMI.

Disease-related concerns:

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

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

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

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

Special populations:

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

Concurrent drug therapy issues:

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

Other warnings/precautions:

• Discontinuation of therapy: When discontinuing antipsychotic therapy, the manufacturer and American Psychiatric Association (APA), Canadian Psychiatric Association (CPA), and World Federation of Societies of Biological Psychiatry (WFSBP) guidelines recommend gradually tapering antipsychotics to avoid physical withdrawal symptoms, including anorexia, anxiety, diaphoresis, diarrhea, dizziness, dyskinesia, headache, myalgia, nausea, paresthesia, restlessness, tremulousness, and vomiting (APA [Lehman 2004]; CPA [Addington 2005]; Lambert 2007; WFSBP [Hasan 2012]). The risk of withdrawal symptoms is highest following abrupt discontinuation of highly anti-cholinergic or dopaminergic antipsychotics (Cerovecki 2013). Additional factors such as duration of antipsychotic exposure, the indication for use, medication half-life, and risk for relapse should be considered. In schizophrenia, there is no reliable indicator to differentiate the minority who will not from the majority who will relapse with drug discontinuation. However, studies in which the medication of well-stabilized patients were discontinued indicate that 75% of patients relapse within 6 to 24 months. Indefinite maintenance antipsychotic medication is generally recommended, and especially for patients who have had multiple prior episodes or 2 episodes within 5 years (APA [Lehman 2004]).

Monitoring Parameters

Mental status; vital signs (as clinically indicated); blood pressure (baseline; repeat 3 months after antipsychotic initiation, then yearly, particularly in children and adolescents); weight, height, BMI, waist circumference (baseline; repeat at 4, 8, and 12 weeks after initiating or changing therapy, then quarterly; consider switching to a different antipsychotic for a weight gain ≥5% of initial weight); CBC (as clinically indicated; monitor frequently during the first few months of therapy in patients with pre-existing low WBC or history of drug-induced leukopenia/neutropenia); electrolytes and liver function (annually and as clinically indicated); TSH, free T4, and thyroid clinical assessment (baseline and follow-up); fasting plasma glucose level/HbA1c (baseline; repeat 3 months after starting antipsychotic, then yearly); fasting lipid panel (baseline; repeat 3 months after initiation of antipsychotic; if LDL level is normal, repeat at 2-5 year intervals or more frequently if clinically indicated); changes in menstruation, libido, development of galactorrhea, erectile and ejaculatory function (at each visit for the first 12 weeks after the antipsychotic is initiated or until the dose is stable, then yearly); abnormal involuntary movements or parkinsonian signs (baseline; repeat weekly until dose stabilized for at least 2 weeks after introduction and for 2 weeks after any significant dose increase); tardive dyskinesia (every 12 months; high-risk patients every 6 months); lens examination, such as a slit-lamp exam, on initiation of therapy and every 6 months is recommended by manufacturer; alternatively, experts suggest it may be reasonable to inquire yearly about visual changes and perform ocular examinations yearly in patients >40 years or every 2 years in younger patients (ADA 2004; Lehman 2004; Marder 2004).

Pregnancy Risk Factor

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Pregnancy Considerations

Adverse events were observed in animal reproduction studies. Quetiapine crosses the placenta and can be detected in cord blood (Newport 2007). Congenital malformations have not been observed in humans (based on limited data). Antipsychotic use during the third trimester of pregnancy has a risk for abnormal muscle movements (extrapyramidal symptoms [EPS]) 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 ACOG and the 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 is limited, as such, routine use is not recommended. However, if a woman is inadvertently exposed to an atypical antipsychotic while pregnant, continuing therapy may be preferable to switching to an agent that the fetus has not yet been exposed to; consider risk:benefit (ACOG 2008). If treatment is needed in a woman planning a pregnancy or if treatment is initiated during pregnancy, use of quetiapine may be considered (Larsen 2015)

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

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

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience anxiety, constipation, dry mouth, fatigue, weight gain, nausea, vomiting, or abdominal pain. Have patient report immediately to prescriber signs of depression (suicidal ideation, anxiety, emotional instability, illogical thinking), signs of infection, signs of high blood sugar (confusion, feeling sleepy, more thirst, hunger, passing urine more often, flushing, fast breathing, or breath that smells like fruit), severe dizziness, passing out, severe headache, tachycardia, arrhythmia, angina, abnormal movements, twitching, change in balance, dysphagia, difficulty speaking, tremors, difficulty moving, rigidity, loss of strength and energy, bruising, bleeding, vision changes, burning or numbness feeling, enlarged breasts, nipple discharge, sexual dysfunction, amenorrhea, signs of neuroleptic malignant syndrome (fever, muscle cramps or stiffness, dizziness, very bad headache, confusion, change in thinking, fast heartbeat, abnormal heartbeat, or sweating a lot), signs of tardive dyskinesia (unable to control body movements; tongue, face, mouth, or jaw sticking out; mouth puckering; and puffing cheeks), or priapism (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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