Quetiapine is an atypical antipsychotic structurally similar to clozapine, a dibenzodiazepine antipsychotic. Atypical antipsychotics, also known as second generation antipsychotics (SGAs), are considered to be the standard of care for schizophrenia and related disorders, and may be considered as first-line treatment options for the management of psychosis (except for clozapine). Similar to other atypical antipsychotics, quetiapine carries a risk of metabolic changes including hyperglycemia, diabetes, dyslipidemia, and weight gain, and may increase the risk of cardiac events, such as QT prolongation. Quetiapine causes anticholinergic effects, sedation, and orthostatic hypotension. A meta-analysis comparing quetiapine to several other SGAs (e.g., olanzapine, risperidone, aripiprazole, and paliperidone) for the treatment of schizophrenia reported small differences in efficacy outcomes (as measured by the Positive and Negative Syndrome Scale, or PANSS), with some study results favoring other SGAs in efficacy outcomes, while others showed no differences between treatment options. These results were complicated by high drop out rates that occurred in most studies included in the meta-analysis. In terms of adverse effects, quetiapine induced less movement disorders, fewer parkinsonian symptoms, and had less effect on prolactin than the comparator drugs. In adults, quetiapine is approved for the treatment of schizophrenia, manic episodes associated with bipolar I disorder (as monotherapy or in combination with lithium or divalproex) and for maintenance treatment of bipolar I disorder, and for depressive episodes associated with bipolar I disorder. Quetiapine has also been found effective as an adjunct to antidepressant therapy in adults with treatment-resistant depression. In pediatric patients, quetiapine is approved for treatment of schizophrenia in adolescents 13 years and older and for the acute treatment of manic episodes associated with bipolar I disorder in children and adolescents 10 years and older. As with all antipsychotics, the product labels carry a boxed warning regarding the increased mortality risk in geriatric patients treated for dementia-related psychosis. Quetiapine initially received FDA approval in 1997.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
Oral Solid Formulations
Immediate-release tablets (e.g., Seroquel):
-May be administered without regard to meals.
Extended-release tablets (e.g., Seroquel XR):
-Administer once daily, preferably in the evening.
-May be administered without food or with a light meal (approximately 300 calories).
-Tablets should be swallowed whole. Do not split, chew, or crush.
During clinical trials in adult or pediatric patients, the following centrally-mediated effects occurred more frequently in patients receiving quetiapine than placebo: headache (17% to 21%), sinus headache (2%), migraine (2%), anxiety (2% to 4%), agitation (6% to 20%), drowsiness (18% to 57%), asthenia (2% to 10%), dysarthria (1% to 5%), hypersomnia (1% to 3%), paresthesias (2% to 3%), restless legs syndrome (RLS) (2%), balance disorder (2%), hypoesthesia (2%), orthostatic dizziness (1%), irritability (1% to 4%), abnormal dreams (2% to 3%), mental impairment (unspecified) (2%), confusion (1% to 2%), disorientation (2%), aggression (2%), disturbance in attention (2%), restlessness (1% to 2%), sluggishness (2%), and fatigue (3% to 14%). Effects that were reported infrequently (0.1% to 1%) during any phase of a trial included abnormal thinking, vertigo, catatonic reaction, confusion, amnesia, psychosis, hallucinations, incoordination, paranoia, abnormal gait, myoclonia, migraine, delusions, apathy, ataxia, depersonalization, stupor, teeth grinding (bruxism), and hemiplegia. Rare effects (less than 0.1%) included aphasia, buccoglossal syndrome, delirium, emotional lability, euphoria, neuralgia (neuropathic pain), stuttering (dysphemia), and subdural hematoma. Nightmares and somnambulism (and related events) were reported during clinical trials; however, the frequency is unknown. Retrograde amnesia and "confusional state" have been reported during postmarketing use.
During one trial for major depressive disorder and one trial for bipolar mania, depression (1 to 3%) occurred more frequently in patients receiving quetiapine than placebo. During short-term studies of extended-release quetiapine, the incidence of suicidal ideation was less in patients receiving active drug (0.6 to 1.3%) than placebo (0.9 to 3.8%). During premarketing evaluation of immediate-release quetiapine, suicide attempt and mania were reported in 0.1% to 1% of patients. Suicidal ideation and mania have been reported in clinical trials of traditional antidepressants (SSRIs and others). Monitor all antidepressant-treated patients for any indication for worsening of depression or the treated condition and the emergence of suicidal behaviors or suicidal ideation, especially during the initial few months of drug therapy and after dosage changes. In a pooled analysis of placebo-controlled trials of antidepressants (n = 4,500 pediatrics and 77,000 adults), there was an increased risk for suicidal thoughts and behaviors in patients 24 years of age and younger receiving an antidepressant versus placebo, with considerable variation in the risk of suicidality among drugs. The difference in the absolute risk of suicidal thoughts and behaviors across different indications was highest in those with major depression. No suicides occurred in any of the pediatric trials. Nevertheless, caregivers and/or patients should immediately notify the prescriber of changes in behavior or suicidal ideation.
The incidence of extrapyramidal symptoms during quetiapine administration is infrequent. During clinical trials in adult or pediatric patients, respectively, the following extrapyramidal effects were reported: dystonic reaction (e.g., nuchal rigidity, hypertonia, dystonia, muscle rigidity, oculogyric crisis) (0 to 5.6% vs. 0 to 7.8%), pseudoparkinsonism (e.g., cogwheel rigidity, drooling, hypokinesia, tremor) (0 to 5.5% vs. 0.7 to 7.8%), akathisia (0 to 5.4% vs. 0 to 7.8%), dyskinetic event (e.g., tardive dyskinesia, dyskinesia, choreoathetosis) (0 to 3.8% vs. 0 to 0.6%), and other extrapyramidal event (e.g., restlessness, movement disorder, extrapyramidal disorder) (0 to 5.9% vs. 0 to 7.8%). Extrapyramidal effects reported infrequently (0.1% to 1%) during any phase of a quetiapine trial included dyskinesia, involuntary movement, and hyperkinesis. Choreoathetosis was reported rarely (less than 0.1%). Dystonic reaction is a potential effect of all antipsychotics, and may occur in susceptible individuals during the first few days of treatment. This effect is observed more commonly in males, younger age groups, and with high potency antipsychotics. Dystonic reactions may manifest as torticollis with or without throat tightness, difficulty swallowing or breathing, oculogyric crisis, trismus, or protrusion of the tongue. Pseudoparkinsonism may occur 1 to 2 weeks after initiation of antipsychotic therapy and is more common in elderly patients. Akathisia may develop several days to weeks into therapy and may respond to dosage reduction or concomitant administration of a benzodiazepine (usually lorazepam) or a beta-blocker (e.g., propranolol, metoprolol). During initial placebo-controlled trials, there were no differences between quetiapine and placebo treatment groups in the incidence of extrapyramidal symptoms (e.g., akathisia, cogwheel rigidity, tremor, hypokinesia). This may be explained in part by the greater affinity of this drug for 5-HT2 receptors relative to D2 receptors, as well as the selectivity of quetiapine for dopamine receptors on mesolimbic rather than nigrostriatal neurons. The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study evaluated the effectiveness of selected atypical antipsychotics (olanzapine, quetiapine, risperidone, and ziprasidone) and perphenazine in schizophrenic patients. In the secondary evaluation of adverse events and reasons for drug discontinuation, the rate of occurrence of any serious adverse effect was similar among groups. However, the discontinuation of treatment due to extrapyramidal symptoms (EPS) was low in the quetiapine group (3%; 10/337) compared to the perphenazine group (8%; 22/261). Olanzapine, risperidone, and ziprasidone also had low incidences of EPS (2% to 4%).
Tardive dyskinesia was reported in 0.1 to 1% of patients receiving quetiapine during the pre-marketing evaluation of the drug. Tardive dyskinesia (TD), a potentially irreversible syndrome characterized by involuntary, dyskinetic movements, may develop in patients treated with antipsychotic drugs. Involuntary orofacial movements (tongue, mouth, jaw, eyelids, or face) or choreoathetoid movements in the extremities may occur. TD is observed more frequently in elderly women. It is believed that the likelihood of developing TD increases with prolonged treatment and cumulative doses; however, it can also develop, although less commonly, after short periods of time and with low dosages or after discontinuation of treatment. It is believed that this drug has a low propensity for producing TD because it does not appear to produce D2 supersensitivity in the striatal region of the brain. Nevertheless, in patients who require chronic treatment with quetiapine, the lowest possible dose and the shortest duration of treatment should be used. Patients should be monitored routinely (at 3 to 6 month intervals) for movement disorders. If signs and symptoms of TD appear in a patient on quetiapine, drug discontinuation should be considered. However, some patients may require treatment with quetiapine despite the presence of the syndrome.
Dysphagia occurred in 2% of patients receiving quetiapine at rates higher than with placebo during clinical trials. Aspiration and esophageal dysmotility resulting in dysphagia have been associated with antipsychotic drug use. Aspiration pneumonia is a common cause of morbidity and mortality in elderly patients.
During clinical trials with immediate-release quetiapine, seizures occurred in 0.5% of patients on active drug versus 0.2% on placebo. In clinical trials with extended-release quetiapine, seizures were reported in 0.05% of those on active drug versus 0.3% on placebo. As with other antipsychotic drugs, quetiapine should be used with caution in patients with a history of a seizure disorder or with conditions or drugs that may lower the seizure threshold.
Xerostomia is the most common gastrointestinal (GI) system effect of quetiapine, consistent with its anticholinergic activities. During clinical trials in adult or pediatric patients, xerostomia occurred in 7% to 44% of patients receiving quetiapine. During clinical trials in adult or pediatric patients, nausea (7 to 8%), vomiting (1 to 8%), and dyspepsia (2 to 7%) also occurred more frequently in patients receiving quetiapine than with placebo. Other reported GI effects occurring more frequently with quetiapine than placebo included gastroenteritis (2%), GI disorder (1%), gastroesophageal reflux disease (GERD, 2%), stomach discomfort (2%), and abdominal distension (0 to 1%). Gastritis was reported infrequently (0.1 to 1%) during pre-marketing evaluation and hematemesis was reported rarely (less than 0.1%). Constipation and decreased intestinal motility are also common side effects associated with the use of quetiapine and can be a risk factor for intestinal obstruction. During clinical trials of quetiapine in adult or pediatric patients, constipation occurred in 6% to 11% of patients receiving quetiapine. In the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) trial, quetiapine was associated with the highest rate (31%) of anticholinergic adverse effects (urinary hesitancy, dry mouth (xerostomia), constipation) compared to other atypical antipsychotics and perphenazine (range: 20% to 25%). GI effects that were reported infrequently (0.1% to 1%) with quetiapine during clinical trials included abdominal pain, flatulence, hemorrhoids, fecal incontinence, and rectal GI bleeding. Rare effects (less than 0.1%) included intestinal GI obstruction, enlarged abdomen, melena, and pancreatitis. Intestinal GI obstruction has been reported with quetiapine postmarketing, including fatal reports in patients who were receiving multiple current medications that decrease intestinal motility. Other GI-related effects reported during postmarketing use include ileus and bowel ischemia (colon). Gastric bezoar has been reported during quetiapine overdose postmarketing; appropriate diagnostic imaging is recommended to further guide patient management. Routine gastric lavage may not be effective in the removal of the bezoar due to gum-like sticky consistency of the mass. Endoscopic pharmacobezoar removal has been performed successfully.
Among the most frequent adverse events associated with the use of quetiapine is xerostomia (dry mouth). Other oral side effects included dry throat (1%), toothache (dental pain, 2% to 3%), dysgeusia (1%), and tooth abscess (1%). Effects that were reported infrequently (0.1% to 1%) during premarketing evaluation in any phase of a trial included increased salivation, dental caries, dysgeusia, gingivitis, gum hemorrhage, oral ulceration, stomatitis, and tongue edema. Rare effects (less than 0.1%) included glossitis.
Quetiapine can cause orthostatic hypotension associated with unsteadiness, tachycardia, and in rare cases, syncope. Orthostatic hypotension occurred in about 2% to 10% of patients during initial clinical trials, while syncope was reported in 2% of patients receiving immediate-release quetiapine and 0.3% of patients on extended-release quetiapine. Hypotension occurred in 1% to 3% of patients during clinical trials. Orthostatic hypotension is most likely to occur during the initial dosage titration period and is thought to be caused by alpha-1 adrenergic blockade, resulting in peripheral vasodilation. Conditions that may predispose patients to hypotension, such as hypovolemia and a dehydrated state, should be corrected before starting therapy when possible. The risk of orthostatic hypotension can be minimized by limiting the initial dose of quetiapine to 25 mg PO twice daily. Dizziness is among the most frequently reported adverse events associated with the use of quetiapine (at a rate of 10% to 12% in trials with both immediate- and extended-release formulations, respectively, and at a rate of 18%, versus 7% placebo, as a treatment-emergent adverse effect in trials designed to treat the depressive phase of bipolar disorder).
In clinical trials of immediate-release or extended-release quetiapine in pediatric or adult patients, the following cardiovascular effects were reported more frequently in those receiving quetiapine than placebo: sinus tachycardia (1 to 8%), increased heart rate (2 to 4%), palpitations (4%), and hemorrhage (1%). Other cardiac effects reported in 0.1 to 1% of patients during pre-marketing evaluation included vasodilation, bradycardia, cerebral ischemia, irregular pulse, T wave abnormality, bundle-branch block, stroke, deep thrombophlebitis, and T wave inversion. Rare effects (less than 0.1%) included angina, atrial fibrillation, first degree AV block, congestive heart failure, thrombophlebitis, T wave flattening, abnormal or elevated ST, and increased QRS duration. In a short-term, placebo-controlled study of pediatric patients 10 years and older receiving extended-release quetiapine, no patients in the active drug group had increases in heart rate above 110 beats/minute compared to 1.2% of patients in the placebo group. In the same study, the mean increase in heart rate was 3.4 beats/minute in the quetiapine group compared to 0.3 beats/minute in the placebo group.
A prolonged QT interval was observed in 0.1 to 1% of subjects receiving quetiapine during clinical trials. During post-marketing use, there have been cases of QT prolongation in patients with risk factors for developing QT prolongation such as overdose, concomitant illness, and in patients taking medications known to cause electrolyte imbalance or prolong the QT interval. Torsade de pointes (TdP) developed in one patient receiving low dose quetiapine (100 mg/day PO) following a generalized seizure; the patient was also receiving escitalopram 20 mg/day PO, and had accompanying risk factors for TdP including female gender, hypomagnesemia or other electrolyte imbalances, and QT prolongation. Quetiapine overdose associated with QT prolongation may involve concomitant use of other medications that have been implicated in QT prolongation, such as risperidone. The potential contribution of drugs that are likely to inhibit quetiapine metabolism has not been clearly established. The QTc reached 710 msec in one patient who reportedly ingested 9,600 mg of the drug while receiving therapeutic doses of fluvoxamine. One case suggested a possible association between the concurrent use of lovastatin and quetiapine with the development of a prolonged QT interval (569 msec). Conversely, results from a manufacturer-sponsored study obtained in 27 patients suggested that although mean quetiapine plasma concentrations increased from 1,280 ng/mL to 3,740 ng/mL after the addition of the potent CYP3A4 inhibitor ketoconazole, the mean QTc change was similar to that observed from baseline to steady-state on monotherapy (change of 5.7 msec). One case report found no evidence of QT prolongation after acute ingestion of 14,000 mg of the drug; the patient was also receiving therapeutic doses of divalproex, gabapentin, and sertraline.
Clinical trial data indicate that hypertension has occurred during quetiapine therapy in both adult and pediatric patients. In short term trials involving pediatric patients the incidence of systolic blood pressure elevations (20 mmHg or more) was reported as 15.2% during quetiapine use and 5.5% during placebo use, while the incidence of increased diastolic blood pressure (10 mmHg or more) was reported as 40.6% during quetiapine use and 24.5% during placebo use. In an open-label trial, one child with a history of hypertension experienced a hypertensive crisis. In adult patients, hypertension is reported to occur at similar incidences (1 to 2%) among those on quetiapine and those receiving placebo. Monitor blood pressure in children and adolescents at the beginning of and periodically during treatment, and in adults as clinically indicated.
Among the most frequent adverse events associated with the use of quetiapine is weight gain, which can contribute to metabolic adverse reactions associated with atypical antipsychotic therapy. Atypical antipsychotics have been associated with metabolic changes. These metabolic changes include blood glucose increases, dyslipidemia, and weight gain. In clinical trials of immediate-release quetiapine for all indications studied in adults, a weight gain of at least 7% of body weight occurred in 8% to 23% of quetiapine-treated patients. In clinical trials for extended-release quetiapine, weight gain of at least 7% of body weight occurred in 10% of those receiving active drug. In clinical trials of immediate-release quetiapine for schizophrenia or the manic phase of Bipolar disorder in children and adolescents, a weight gain of at least 7% of body weight occurred in 12% to 21% of quetiapine-treated patients. In a long-term extension trial in pediatrics, the mean increase in body weight was 4.4 kg, and 18.3% of patients gained at least 7% of their body weight when adjusted for normal growth. Other effects occurring more frequently with quetiapine than placebo included appetite stimulation (2% to 12%) and decreased appetite (2%). Anorexia was reported in at least 1% of patients during premarketing evaluation of quetiapine and weight loss occurred in 0.1% to 1% of patients.
Atypical antipsychotic use has been associated with changes in blood glucose. Hypoglycemia, hyperglycemia, diabetes mellitus, and excessive thirst were reported infrequently (0.1% to 1%) during premarketing evaluation of quetiapine. Glycosuria and polyuria were reported rarely (less than 0.1%). In some cases, hyperglycemia has been reported during quetiapine therapy even in patients with no prior history of glucose elevations. The possibility of impaired glucose tolerance should be considered in patients receiving quetiapine who develop symptoms of hyperglycemia or diabetes, such as polydipsia, polyuria, polyphagia, and weakness. In patients with severe treatment-emergent hyperglycemia, discontinuation of therapy should be considered. Continued antidiabetic treatment has been necessary despite discontinuation of the antipsychotic agent in some patients. Epidemiological studies suggest an increased risk of hyperglycemia-related adverse effects during atypical antipsychotic use; hyperglycemia, ketoacidosis, hyperosmolar coma, and death have occurred. One study noted that patients taking atypical agents (e.g., clozapine, olanzapine, quetiapine) were 9% more likely to have a new diagnosis of diabetes mellitus than patients taking older therapies. During short-term clinical trials in adults, 2.4% of patients receiving quetiapine had a change from normal to high fasting glucose (less than 100 mg/dL to at least 126 mg/dL) vs. 1.4% of those receiving placebo. In the same studies, 11.7% of quetiapine-treated patients experienced an increase from borderline to high fasting glucose (100 mg/dL to 125 mg/dL to at least 126 mg/dL) compared to 11.8% of placebo-treated patients. In a separate trial designed to evaluate glycemic parameters, 1.7% of patients had treatment-emergent glucose concentrations of at least 200 mg/dL after an oral glucose tolerance test, and 2.6% of patients had a fasting treatment-emergent blood glucose concentration of at least 126 mg/dL at week 24. The mean change in fasting glucose from baseline was 3.2 mg/dL, and the mean change in 2-hour glucose from baseline was -1.8 mg/dl. Long-term trials with quetiapine showed a mean change in glucose from baseline of 5 mg/dL for quetiapine-treated patients and -0.05 mg/dL for patients who received placebo. In a study of adolescents with schizophrenia, the mean change in fasting glucose was -0.75 mg/dL for quetiapine-treated patients vs. -1.70 for placebo-treated adolescents. During a study of children and adolescents (10 to 17 years of age) for manic phase of bipolar disorder, the mean change in fasting glucose was 3.62 mg/dL for quetiapine-treated patients vs. -1.17 mg/dL for pediatric patients on placebo. No patient in either pediatric study with a normal or borderline normal baseline fasting glucose (less than 126 mg/dL) had treatment-emergent blood glucose at or above 126 mg/dL. Atypical antipsychotics may have effects on glucose metabolism that are independent of their effect on weight gain. A well-supported case (temporal association, positive de-challenge) of Type 2 diabetes mellitus occurring in a patient shortly after initiation of quetiapine for bipolar disorder has been reported. Measured blood glucose reached a peak of 600 mg/dL. The patient had risk factors that predisposed her to development of diabetes (e.g., obesity, hyperlipidemia). The authors suspected that the diabetes onset was not due to antipsychotic-induced weight gain, as her weight was relatively stable during quetiapine treatment. Ziprasidone therapy was successfully instituted without return of diabetes.
Atypical antipsychotic use has been associated with dyslipidemia (hyperlipidemia), hypercholesterolemia and hypertriglyceridemia. During clinical trials of extended-release quetiapine for all indications studied, the percentage of adult patients with shifts in total cholesterol from baseline to clinically significant levels (240 mg/dL or more) was 7% to 16% of those receiving active drug and higher than with placebo. The incidence of clinically significant changes in triglycerides (200 mg/dL or more) was 8% to 18% of those adults receiving quetiapine and higher than with placebo. In adult patients receiving immediate-release quetiapine, significant changes in total cholesterol occurred in 9% to 18% and significant changes in triglycerides occurred in 14% to 22% of those receiving quetiapine at higher incidences than with those receiving placebo. Shifts in baseline LDL to an LDL of 160 mg/dL or higher occurred in 6% of quetiapine-treated patients. A decrease in HDL cholesterol to 40 mg/dL or less occurred equally among patients receiving quetiapine and placebo (14%). In clinical trials of children and adolescents receiving immediate-release quetiapine, the percentage of patients with shifts in total cholesterol from baseline to clinically significant levels (200 mg/dL or more) was 10% to 12% of those receiving quetiapine. A decrease in HDL cholesterol to 40 mg/dL or less occurred in 10% to 15% of pediatric patients receiving quetiapine. Clinically significant changes in triglycerides (150 mg/dL or higher) occurred in 17% to 22% of pediatric patients receiving active drug. Shifts from baseline LDL to an LDL of at least 130 mg/dL occurred in 4% to 8% of quetiapine-treated patients. In postmarketing clinical trials, elevations in total cholesterol and triglycerides have been observed. It is advisable to monitor cholesterol and triglyceride levels periodically in patients receiving antipsychotics, particularly those with pre-existing hypercholesterolemia or hypertriglyceridemia.
During clinical trials in adult or pediatric patients, the following dermatologic and/or allergic effects occurred more frequently in patients receiving quetiapine than placebo: rash (unspecified) (4%), hyperhidrosis (2%), and acne vulgaris (2%). Other dermatologic effects that were reported infrequently (0.1% to 1%) during premarketing evaluation included pruritus, atopic dermatitis, contact dermatitis, maculopapular rash, seborrhea, and skin ulcer. Rare effects (less than 0.1%) included exfoliative dermatitis, psoriasis, and skin discoloration. Postmarketing reports indicate that a temporal association exists between quetiapine use and the development of anaphylactoid reactions. Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), acute generalized exanthematous pustulosis (AGEP), and cutaneous vasculitis have been reported during postmarketing use of quetiapine.
During clinical trials in adult or pediatric patients, the following respiratory or infectious effects occurred more frequently in patients receiving quetiapine than placebo: rhinitis (3% to 4%), pharyngitis (4% to 6%), sinusitis (2%), nasal congestion (3% to 5%), fever (1% to 2%), unspecified infection (2%), lymphadenopathy (1%), cough (3%), influenza (1% to 2%), upper respiratory tract infection (2% to 3%), and sinus congestion (2%). Increased cough and dyspnea occurred in 1% or more of quetiapine-treated patients during premarketing evaluation. Other effects that were reported infrequently (0.1% to 1%) included pneumonia, epistaxis, and asthma. Rare effects (less than 0.1%) included hiccups and hyperventilation. Sleep apnea has been reported during postmarketing use.
Patients should be monitored for signs and/or symptoms of hypothyroidism during treatment with quetiapine, since use of this drug has been associated with dose-dependent decreases in total and free thyroxine (T4). Although most of these changes were not clinically significant, 0.4% of patients receiving immediate-release quetiapine experienced clinically relevant increases in TSH. In clinical trials with extended-release quetiapine, decreases in T4 occurred in 0.5% of those on active drug versus none on placebo; 2.7% of those on extended-release quetiapine experienced increased TSH versus 1.2% on placebo. Hypothyroidism was reported in 2% of patients receiving quetiapine versus 1% of those receiving placebo during clinical trials with the immediate-release formulation. Effects that were reported infrequently (0.1 to 1%) during any phase of a trial included hypothyroidism and hyperthyroidism.
Anticholinergic effects may occur with quetiapine that may lead to urinary side effects. In the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) trial, quetiapine was associated with the highest rate of anticholinergic urinary adverse effects (e.g., urinary hesitancy) compared to other atypical antipsychotics and perphenazine. During clinical trials in adult or pediatric patients, the following urinary effects occurred more frequently in patients receiving quetiapine than placebo: urinary tract infection (2%), urinary tract disorder (unspecified) (1%), and pollakiuria (2%). The effects that were reported infrequently (0.1% to 1%) included urinary incontinence, cystitis, dysuria, increased urinary frequency, and urinary retention. Nocturia and acute renal failure (unspecified) were reported rarely (less than 0.1%). During clinical trials in adult or pediatric patients, the following genital and reproductive effects occurred more frequently in patients receiving quetiapine vs. placebo: female lactation (1%), impotence (erectile dysfunction) (1%), and libido decrease (up to 2%). Genital/reproductive effects that were reported infrequently (0.1% to 1%) included dysmenorrhea, vaginitis, metrorrhagia, impotence, vaginal candidiasis, abnormal ejaculation (ejaculation dysfunction), amenorrhea, breast discharge, leukorrhea, vaginal bleeding (hemorrhage), vulvovaginitis, libido increase, and orchitis. Libido decrease and gynecomastia were reported rarely (less than 0.1%). Galactorrhea and urinary retention have been reported during postmarketing use. Quetiapine may pose a reproductive risk by increasing serum prolactin concentrations. Hyperprolactinemia may suppress pituitary gonadotropin secretion and in turn inhibit reproductive function by impairing gonadal steroidogenesis in females and males; infertility if it occurs, is reversible. Across all clinical trials, prolactin concentrations shifted to a clinically significant value in 3.6% (158/4,416) of patients treated with quetiapine compared to 2.6% (51/1,968) of patients treated with placebo. Galactorrhea, amenorrhea, gynecomastia, and impotence (erectile dysfunction) have been observed in patients receiving prolactin-elevating drugs. One case of priapism has been reported in a patient treated with quetiapine. While a causal relationship has not been established, other drugs with alpha-adrenergic blocking effects have been reported to induce priapism and it is possible that quetiapine may also have this potential.
Clinical trial data and postmarketing reports indicate that leukopenia, neutropenia, and agranulocytosis have occurred during the use of antipsychotic agents. Agranulocytosis (severe neutropenia) has been reported with quetiapine, including fatal cases and cases in patients without pre-existing risk factors. Neutropenia should be considered in patients presenting with infection, particularly in the absence of apparent predisposing factor(s), or in patients with unexplainable fever, and such patients should be managed as clinically indicated. During premarketing evaluation, leukocytosis, ecchymosis, eosinophilia, hypochromic anemia, and cyanosis occurred in 0.1% to 1% of patients. Thrombocytopenia and hemolysis were reported rarely (less than 0.1%). During short-term placebo-controlled trials, decreases in hemoglobin to 13 grams/dL or less in males and 12 grams/dL or less in females on at least one occasion occurred in 8.3% of quetiapine-treated patients. In other clinical trial evaluations, similar decreases in hemoglobin occurred in 11% of quetiapine-treated patients on at least one occasion. Decreased platelet counts have been reported during postmarketing use of the drug. Carefully monitor patients with a history of drug-induced leukopenia or neutropenia or a history of clinically significant low white blood cell (WBC) count during quetiapine treatment, including regular laboratory monitoring of the complete blood count (CBC) during the first few months of therapy. Consider discontinuation of treatment if a clinically significant decline in WBC occurs in the absence of an identifiable cause. Quetiapine should be discontinued in patients who develop severe neutropenia (ANC less than 1,000/mm3).
Asymptomatic, transient, and reversible elevated hepatic enzymes (serum transaminases, primarily ALT) have been reported with quetiapine treatment. Hepatic enzyme elevations usually occur within the first 3 weeks of quetiapine treatment and usually promptly return to pre-study levels with ongoing treatment. Severe liver reactions, including hepatitis, hepatic necrosis and hepatic failure, have been reported during postmarketing use of quetiapine. In schizophrenia trials in adults, the proportion of patients with transaminase elevations of more than 3 times the upper limit of normal (ULN) was approximately 6% for quetiapine immediate-release vs. 1% for placebo. In acute bipolar mania trials, transaminase elevations of more than 3 times the ULN was approximately 1% for both olanzapine immediate-release and placebo. In bipolar depression trials, the proportions of patients with transaminase elevations of more than 3 times the ULN was 1% for quetiapine and 2% for placebo. The proportions of adults with transaminase elevations of more than 3 times the ULN ranged between 1% and 2% for quetiapine extended-release use compared to 2% for placebo.
Cardiomyopathy and myocarditis have been reported during postmarketing use of quetiapine, although a causal relationship to the drug has not been established.
During clinical trials in adult or pediatric patients, the following ophthalmic effects occurred more frequently in patients receiving quetiapine than placebo: blurred vision (1 to 4%) and amblyopia (2 to 3%). Ophthalmic effects that were reported infrequently (0.1 to 1%) during pre-marketing evaluation included conjunctivitis, abnormal vision, xerophthalmia, blepharitis, and ocular pain. Rare effects (less than 0.1%) included abnormal accommodation and ocular hypertension (glaucoma).
During clinical trials in adult or pediatric patients, the following otic effects occurred more frequently in patients receiving quetiapine than placebo: ear disorder (unspecified) (1%) and otalgia (otic pain, 1 to 2%). Tinnitus was reported infrequently (0.1 to 1%) during pre-marketing evaluation of quetiapine. Deafness (hearing loss) was reported rarely (less than 0.1%).
During clinical trials in adult or pediatric patients, the following musculoskeletal effects occurred more frequently in patients receiving quetiapine than placebo: twitching (4%), joint disorder (unspecified) (1%), arthralgia (1 to 4%), extremity pain (2%), back pain (2 to 5%), musculoskeletal pain/stiffness (2%), muscle spasms (1 to 3%), myalgia (2%), neck pain (2%), neck rigidity (1%), and pain (unspecified) (1 to 7%). Effects that were reported infrequently (0.1 to 1%) during any clinical trial included pathological bone fractures, myasthenia, twitching, arthralgia, arthritis, leg cramps, neck pain, pelvic pain, and bone pain.
During clinical trials in adult or pediatric patients, the following general effects occurred more frequently in patients receiving quetiapine than placebo: altered hormone levels (3%), heaviness (2%), peripheral edema (4%), unspecified injury (1%), seasonal allergy (2%), viral gastroenteritis (4%), chills (1%), and falls (0% to 2%). General effects that were reported infrequently (0.1% to 1%) during any phase of a trial included malaise, photosensitivity reaction, chills, and face edema. During clinical trials in adult or pediatric patients, the following general metabolic and nutritional effects were reported infrequently (0.1% to 1%) during any phase of a quetiapine trial: increased alkaline phosphatase, alcohol intolerance, dehydration, and increased serum creatinine. Gout, hand edema, and hypokalemia were reported rarely (less than 0.1%). Increased serum creatine phosphokinase (CPK) occurred during clinical trials; however, the frequency is unknown.
Thirst and polydipsia have occurred during treatment with antipsychotics. Polydipsia may be psychogenic in nature or a result of antipsychotic-induced metabolic complications such as diabetes; therefore, careful evaluation is recommended. Hyponatremia can develop from polydipsia which can progress to water intoxication, with symptoms such as confusion, lethargy, psychosis, and in severe cases, seizures or death. Some data suggest that antipsychotic-induced hyponatremia is most likely the result of syndrome of inappropriate antidiuretic hormone (SIADH). Water intoxication was reported in less than 0.1% of patients during clinical trial evaluation of quetiapine. Hyponatremia and SIADH have been reported during postmarketing use.
Antipsychotics have been reported to disrupt the body's ability to reduce core body temperature presumably through effects in the hypothalamus, and they predispose patients to hyperthermia. Patients receiving quetiapine should be advised of conditions that contribute to an elevation in core body temperature (e.g., strenuous exercise, ambient temperature increase, or dehydration). A less frequently described alteration in thermoregulatory processes reported with both conventional and atypical antipsychotics is hypothermia. Thermoregulation is multi-factorial; however, the dopaminergic system appears to have a primary role, and serotonin may also have modulatory activity (5-HT2a receptors). Most cases of hypothermia associated with antipsychotics have occurred in conjunction with other potential precipitating factors such as hypothyroidism, sepsis, organic brain injury, or environmental temperature. Hypothermia appears to occur more frequently during initiation of antipsychotic therapy or after dose increases. Hypothermia has been reported with quetiapine during postmarketing use.
A potentially fatal symptom complex referred to as neuroleptic malignant syndrome (NMS) has been associated with the administration of antipsychotics. Rare cases of NMS have been reported during use of quetiapine. NMS is characterized by hyperpyrexia, muscle rigidity, altered mental status, and autonomic instability (e.g., irregular pulse or blood pressure, tachycardia, diaphoresis, cardiac dysrhythmia). Increased serum creatine phosphokinase (CPK), rhabdomyolysis, and related acute renal failure also have occurred. The cause of NMS is not completely understood; however, dopamine receptor blockade is one of the mechanisms by which NMS is thought to occur. A primary risk factor for developing NMS appears to be the initiation or increase in dose of an antipsychotic. High potency and depot antipsychotics carry the greatest risk. Environmental risk factors include conditions that inhibit heat dissipation such as elevated ambient room temperature, prolonged heat exposure, the use of patient restraints, or dehydration. NMS occurs more frequently in young adults, which is most likely the result of the age of first exposure rather than an age-related risk. NMS occurs more frequently in men, which is thought to be related to the higher likelihood of male versus female exposure to the causative agent. Risk factors for recurrent NMS include a personal history of NMS, increasing age, and specific medical co-morbidities (e.g., electrolyte imbalances, dehydration). Quetiapine should be immediately discontinued and appropriate supportive therapy initiated as soon as symptoms of NMS are discovered. In an ISMP safety report, quetiapine was noted as 1 of the 19 overall drugs and one of the 3 antipsychotics having the strongest signals for serotonin syndrome with 31 cases reported over 1 year to the FDA Adverse Event Reporting System (FAERS). Serotonin syndrome, at its most severe, can resemble NMS. Serotonin syndrome rarely happens with single drug therapy, and more commonly is reported with interactions between multiple serotonergic drugs or accidental or intentional drug overdoses. The mechanism by which quetiapine might promote serotoninergic effects is not clear, given its combination of dopamine type 2 (D2) and serotonin type 2 (5-HT2) antagonism.
Abrupt discontinuation of atypical antipsychotics, including quetiapine, has been associated with a discontinuation syndrome with acute withdrawal symptoms including insomnia, nausea, and vomiting. During monotherapy clinical trials of extended-release quetiapine, discontinuation symptoms following abrupt discontinuation of treatment occurred in 12.1% of quetiapine-treated patients and 6.7% of placebo-treated patients. Adverse effects included insomnia, nausea, headache, diarrhea, vomiting, dizziness, and irritability. Resolution of symptoms usually occurs after 1 week of treatment discontinuation. When possible, gradual tapering of quetiapine is recommended.
Quetiapine use is contraindicated in anyone with a known hypersensitivity to quetiapine or to any excipients in the product formulations. The drug carries a risk of serious hypersensitivity or anaphylaxis. Anaphylactic reactions, serious skin rashes, and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) have been reported in patients treated with quetiapine.
Quetiapine can cause orthostatic hypotension associated with dizziness, tachycardia, and in rare cases, syncope. Orthostatic hypotension is most likely to occur during the initial dosage titration period and is thought to be caused by alpha-1 adrenergic blockade, resulting in peripheral vasodilation. Use quetiapine with caution in patients who have pre-existing hypotension or cerebrovascular disease. Orthostatic hypotension could lead to falls with the potential for fractures and other injuries. Complete a fall risk assessment upon antipsychotic initiation in patients with conditions, diseases, or taking concurrent medications that could exacerbate orthostasis and recurrently during long-term therapy in at-risk patients. Conditions that may predispose patients to hypotension, such as hypovolemia or a dehydrated state, should be corrected, if possible, before starting quetiapine therapy. Lower doses may be required in patients at increased risk for hypotension. Clinical trial data indicate that hypertension has occurred during quetiapine therapy in both adult and pediatric patients. Monitor blood pressure in pediatric patients at the beginning of and periodically during treatment, and in adults as clinically indicated. During postmarketing use of quetiapine, there have been cases of QT prolongation in patients who had predisposing risk factors such as overdose, concomitant illness, and receiving medications known to prolong the QT interval or cause electrolyte imbalance. Avoid the use of quetiapine with other medications known to prolong QT interval and in patients with a history of cardiac arrhythmias (e.g., bradycardia), with uncorrected hypokalemia or hypomagnesemia, or with congenital long QT syndrome. Use quetiapine with caution in patients with conditions that may increase the risk of QT prolongation including cardiovascular disease, family history of QT prolongation, heart hypertrophy, AV block, heart failure, stress-related cardiomyopathy, myocardial infarction, cerebrovascular disease, hypocalcemia, or in patients receiving medications known to cause electrolyte imbalances. Females, people 65 years and older, patients with sleep deprivation, pheochromocytoma, sickle cell disease, decreased thyroid function, hyperparathyroidism, hypothermia, systemic inflammation (e.g., human immunodeficiency virus (HIV) infection, fever, and some autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus (SLE), and celiac disease) and patients undergoing apheresis procedures (e.g., plasmapheresis [plasma exchange], cytapheresis) may also be at increased risk for QT prolongation. Some medications that prolong the QT interval have been associated with the development of torsade de pointes (TdP), a life-threatening arrhythmia. Existent QT prolongation increases the risk of TdP. Although TdP occurred in one patient receiving low-dose quetiapine, the exact contribution of the drug cannot be determined due to the presence of multiple medical conditions and risk factors.
Quetiapine should be used with caution in patients with hematological disease. Hematologic effects including leukopenia, neutropenia, and agranulocytosis have been associated with antipsychotic use. Agranulocytosis (severe neutropenia) has been reported with quetiapine, including fatal cases and cases in patients without pre-existing risk factors. Neutropenia should be considered in patients presenting with infection, particularly in the absence of obvious predisposing factor(s) or in patients with unexplainable fever, and such patients should be managed as clinically indicated. A history of drug-induced leukopenia or neutropenia or pre-existing low white blood cell (WBC) count may increase the likelihood of developing hematologic effects during treatment with an antipsychotic. Patients with a history of clinically significant low WBC count or drug-induced leukopenia/neutropenia should have frequent complete blood count (CBC) assessments during the first few months of treatment. Discontinuation of quetiapine should be considered if a clinically significant decline in WBC occurs in the absence of an identifiable cause. Patients with clinically significant neutropenia should be closely monitored for fever and infection and appropriate medical intervention should be instituted if necessary. Quetiapine should be discontinued in patients with severe neutropenia (ANC less than 1,000/mm3); ongoing medical care is recommended until the symptoms resolve.
Quetiapine was associated with the development of cataracts in animal studies. Lens changes have also been observed with long-term therapy in humans, however, a causal relationship has not been established. Nevertheless, examination of the lens by methods adequate to detect cataract formation is recommended upon initiation of quetiapine or shortly thereafter, and at six-month intervals during chronic treatment.
Quetiapine has been associated with dose-dependent decreases in total and free thyroxine (T4), or increase in thyroid stimulating hormone (TSH). Maximal effects are usually apparent in the first 2 to 4 weeks of treatment. In clinical trials with extended-release quetiapine, decreases in T4 occurred in 0.5% of those on active drug versus none on placebo; 2.7% of those on extended-release quetiapine experienced increased TSH versus 1.2% on placebo. No cases of hypothyroidism were reported in these studies. In clinical trials with immediate-release quetiapine, decreases in T4 of about 20% occurred at the higher end of the dose range. Although most of these changes were not clinically significant, a few cases of clinically relevant hypothyroidism were reported. Patients should be monitored for signs and/or symptoms of hypothyroidism during treatment with quetiapine. Reversal of effects generally occurs after discontinuation of the drug. Of note, hypothyroidism may increase the risk of prolonging the QT interval when using quetiapine.
Tardive dyskinesia is a syndrome of potentially irreversible, involuntary, dyskinetic movements that may develop in patients treated with antipsychotics. Regular evaluation for movement disorders is recommended (e.g., AIMS, DISCUS). Factors associated with a greater susceptibility to tardive dyskinesia include an age above 55 years, female gender, white or African ethnicity, presence of a mood disorder, intellectual disability, CNS injury, prior or current akathisia, significant parkinsonism, or acute dystonic reaction. The rate of tardive dyskinesia in adults treated with a first generation antipsychotic appears to be at least 3 times that observed with second generation antipsychotics. The risk of developing tardive dyskinesia and the likelihood that it will become irreversible are believed to increase as the duration of treatment and the total cumulative dose of antipsychotics administered to the patient increase. However, the syndrome can develop, although much less commonly, after relatively brief periods at low doses or may arise after drug discontinuation. Antipsychotics may suppress the signs and symptoms of tardive dyskinesia and thereby mask the underlying process; however, the syndrome may also remit partially or completely if the antipsychotic is withdrawn. The effect that symptomatic suppression has upon the long-term course of the syndrome is unknown. If signs and symptoms of tardive dyskinesia appear, quetiapine discontinuation should be considered. However, some patients may require treatment despite the presence of the syndrome.
Patients with dysphagia or who are at risk for aspiration pneumonia should be closely monitored while receiving quetiapine. Antipsychotic drug use has been associated with esophageal dysmotility and aspiration of gastric contents, which may increase the incidence of aspiration pneumonia in certain patient populations, such as patients with advanced Alzheimer's disease.
Antipsychotics can cause motor and sensory instability, which may lead to falls with the potential for fractures and other injuries. A fall risk assessment should be completed when initiating an antipsychotic in patients with diseases (e.g., neurological disease), conditions, or concurrent medication use that could exacerbate motor and sensory instability. A fall risk assessment should be completed recurrently in at-risk patients on long-term antipsychotic therapy. Antipsychotics (including quetiapine) should be used with caution in patients with Parkinson's disease, as dopamine-receptor blockade from antipsychotic treatment may lead to worsening of Parkinson's-related motor symptoms and an increased risk of extrapyramidal symptoms.
In clinical trials with extended-release quetiapine, seizures were reported in 0.1% of those on active drug versus 0.9% on placebo. In clinical trials with immediate-release quetiapine, seizures occurred in 0.6% of patients on active drug versus 0.2% on placebo. Quetiapine should be used with caution in patients with a seizure disorder or with conditions that may lower the seizure threshold (e.g. brain tumor, cerebrovascular disease).
Somnolence is a commonly reported adverse effect of quetiapine, and may result in impairment of cognitive and motor skills. The sedative effects of quetiapine may be most evident in the initial days of treatment; patients should be advised to use caution when driving or operating machinery, or performing other tasks that require mental alertness, until they know how quetiapine affects them. Somnolence could lead to falls with the potential for fractures and other injuries. A fall risk assessment should be completed when initiating an antipsychotic in patients with conditions, diseases, or concurrent medication use that could exacerbate somnolence. A fall risk assessment should be completed recurrently in at-risk patients on long-term antipsychotic therapy. Given the primary CNS effects of quetiapine, caution should be used during coadministration with other CNS depressants and alcohol. Ethanol ingestion may further impair cognitive and motor skills and patients should be advised to avoid use of alcoholic beverages.
Since quetiapine is extensively metabolized by the liver, higher plasma levels are expected in patients with hepatic impairment. In those with hepatic disease, a lower starting dose and slower titration are recommended. Additionally, elevations in transaminases have occurred with quetiapine use; these are typically asymptomatic, transient, and reversible. Most elevations occur within the first 3 weeks of treatment and return to baseline levels with ongoing treatment.
Atypical antipsychotics have been associated with metabolic changes that include hyperglycemia, diabetes mellitus, dyslipidemia (hypercholesterolemia and hypertriglyceridemia), body weight gain, and obesity risk. In some patients, a worsening of more than one of the metabolic parameters of weight, blood glucose, and lipids was observed in clinical studies. Changes in these metabolic profiles should be managed as clinically appropriate. Adults receiving quetiapine should receive regular monitoring of weight; monitor weight and growth in pediatric patients treated with quetiapine. Hyperglycemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, has been reported in patients treated with atypical antipsychotics, including quetiapine. Patients with an established diagnosis of diabetes mellitus who are started on atypical antipsychotics should be monitored regularly for worsening of glucose control. Patients with risk factors for diabetes mellitus (e.g., obesity, family history of diabetes) who are starting treatment with atypical antipsychotics should undergo fasting blood glucose testing at the beginning of treatment and periodically during treatment. Any patient treated with atypical antipsychotics should be monitored for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness. Patients who develop symptoms of hyperglycemia during treatment with atypical antipsychotics should undergo fasting blood glucose testing. In some cases, hyperglycemia has resolved when the atypical antipsychotic was discontinued; however, some patients required continuation of anti-diabetic treatment despite antipsychotic discontinuation.
Significant increases in serum prolactin concentrations occurred during clinical trials with quetiapine across all indications. Increased prolactin concentrations were observed in rat studies and were associated with an increase in mammary gland neoplasia. There is insufficient evidence linking chronic administration of antipsychotics with tumorigenesis in humans. However, because up to one-third of human breast cancer cases may be prolactin dependent (based on in vitro studies), quetiapine should be used with caution in women with breast cancer.
Quetiapine may increase serum prolactin concentrations. Prolactin elevation may persist during chronic administration of quetiapine. Hyperprolactinemia, regardless of etiology, may suppress hypothalamic GnRH, resulting in reduced pituitary gonadotrophin secretion. Hyperprolactinemia may inhibit reproductive function by impairing gonadal steroidogenesis in both female and male patients. Galactorrhea, amenorrhea, gynecomastia, and impotence have been reported in patients receiving prolactin-elevating compounds. Long-standing hyperprolactinemia when associated with hypogonadism may lead to decreased bone density in both female and male subjects. Based on the pharmacologic action of quetiapine (D2 antagonism) and elevated prolactin levels, treatment with quetiapine may lead to a reversible reduction in fertility (reversible infertility) in females of reproductive potential; practitioners should be aware of this potential reproductive risk.
There are no adequate and well-controlled studies of quetiapine in pregnant women; therefore, quetiapine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. In animal studies during the period of organogenesis, evidence of embryo/fetal toxicity was observed, including delays in skeletal ossification, minor soft tissue anomalies, and reduced body weight. In addition, maternal toxicity (decreases in body weight gain and/or death) was observed in these studies. Neonates exposed to antipsychotics during the third trimester of pregnancy are at risk for extrapyramidal and/or withdrawal symptoms following delivery. There have been reports of agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress and feeding disorder in these neonates. These complications have varied in severity and have ranged from self-limited to those requiring intensive care unit support and prolonged hospitalization. Neonates exhibiting signs or symptoms of extrapyramidal effects or withdrawal should be carefully monitored. The knowledge about long-term neurobehavioral effects in offspring is limited for all antipsychotic agents and requires further investigation. It is not known if antipsychotics, through their effect on prolactin, would affect labor or obstetric delivery. According to the American Psychiatric Association treatment guidelines for schizophrenia, consider pregnancy testing in women of childbearing potential prior to initiation of an antipsychotic. There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to quetiapine; information about the registry can be obtained at womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry or by calling 1-866-961-2388.
According to the manufacturer, quetiapine is excreted into human breast milk and a decision should be made to discontinue breast-feeding or the drug, taking into account the importance of the drug to the mother's health. Case reports have indicated that the level of quetiapine in breast milk ranges from undetectable to 170 mcg/L; the estimated infant dose ranged from 0.09% to 0.43% of the weight-adjusted maternal dose. Limited data of mother/infant pairs (n = 8) have indicated that the calculated infant daily doses range from less than 0.01 mg/kg for a maternal dose up to 100 mg/day to 0.1 mg/kg for a maternal dose of 400 mg/day. Due to individual variability in response to antipsychotics, it may be prudent to continue the existing quetiapine regimen if ongoing treatment is deemed necessary during breast-feeding. However, olanzapine may be considered as an alternate atypical agent. Data related to the safety of antipsychotics during breast-feeding are limited and chronic administration of any antipsychotic during breast-feeding should be avoided if possible. Regardless of the antipsychotic used, the nursing infant should be closely monitored for excessive drowsiness, lethargy, and developmental delays. Combination treatment with antipsychotics may increase the risk of these adverse events. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.
Quetiapine is indicated for the treatment of bipolar I disorder, including mania and bipolar depression, in children and adolescents 10 years and older and for the treatment of schizophrenia in adolescents. Quetiapine is not approved for the treatment of major depressive disorder (MDD) in pediatric patients less than 18 years of age. In a pooled analysis of placebo-controlled trials of antidepressants (n = 4,500 pediatrics and 77,000 adults), there was an increased risk for suicidal thoughts and behaviors in patients 24 years of age and younger receiving an antidepressant versus placebo, with considerable variation in the risk of suicidality among drugs. The difference in absolute risk of suicidal thoughts and behaviors across different indications was highest in those with major depression. The need for an antidepressant in children, adolescents, or young adults for any use must be weighed against the risk of suicidality; it is unknown if this risk extends to long-term use. All patients should be monitored for symptom worsening or suicidality, especially at treatment initiation or after dose changes. Caregivers and/or patients should immediately notify the prescriber of changes in behavior or suicidal ideation. A change to the treatment regimen or discontinuation of quetiapine may be necessary in patients with emerging suicidality or worsening depression.
Antipsychotics have been reported to disrupt the body's ability to reduce core body temperature presumably through effects in the hypothalamus, and they predispose patients to hyperthermia. Patients receiving quetiapine should be advised of conditions that contribute to an elevation in core body temperature (e.g., strenuous exercise, ambient temperature increase, or dehydration).
Quetiapine should be used cautiously in patients with a current diagnosis or prior history of urinary retention, clinically significant prostatic hypertrophy, constipation, or increased intraocular pressure. Norquetiapine, the active metabolite of quetiapine, is thought to be associated with the anticholinergic effects observed during clinical use of quetiapine, during concurrent use of quetiapine and anticholinergic medications, and following overdose of quetiapine. Intestinal obstruction has been reported with quetiapine, including fatal reports in patients who were also receiving multiple medications that decrease intestinal motility.
Clinical trials with quetiapine did not indicate differences in responses between geriatric and younger adults. Older adults may be more sensitive to the sedative, anticholinergic, and orthostatic effects of quetiapine; consider a slower rate of dose titration and lower target dose. Antipsychotics are not approved for the treatment of dementia-related psychosis in geriatric adults; avoid use of quetiapine if possible due to an increase in morbidity and mortality in geriatric patients with dementia receiving antipsychotics. Deaths have typically resulted from heart failure, sudden death, or infections (primarily pneumonia). An increased incidence of cerebrovascular adverse events (e.g., stroke, transient ischemic attack), including fatal events, has also been reported. Lower initial dosages of risperidone are generally recommended for the geriatric adult, with careful titration, to minimize risks for orthostasis and hypotension. Monitor blood pressure and renal function. The Beers Criteria consider antipsychotics to be potentially inappropriate medications (PIMs) in geriatric adults and use should be avoided except for treating schizophrenia, bipolar disorder, or as part of antiemetic regimens during chemotherapy. In general, avoid use in those with delirium or dementia. Non-pharmacological strategies are first-line options for treating delirium- or dementia-related behavioral problems unless they have failed or are not possible and the patient is a substantial threat to self or others. If antipsychotic use is necessary in those with a history of falls or fractures, consider reducing the use of other CNS depressants and implement other fall risk reduction strategies. Due to the potential for antipsychotic-induced hyponatremia and SIADH, sodium levels should be closely monitored at initiation and after dose changes. The U.S. Omnibus Budget Reconciliation Act (OBRA) regulates antipsychotic use in residents of long-term care facilities (LTCFs) and use must be supported by an appropriate clinical indication that is thoroughly documented within the medical record. When used to manage behavior, stabilize mood, or treat a psychiatric disorder, the facility should attempt to taper the antipsychotic as outlined in the OBRA guidelines, unless a taper is clinically contraindicated. Indications, dosages, and the duration of antipsychotic treatment in the geriatric adult should be in accordance with prescribing labels, published literature recommendations, and expert guidelines. "As needed" (PRN) use for acute behavioral/medical situations in the LTCF must be limited to 14 days, and any use beyond this duration requires that the attending physician/prescribing practitioner evaluate the patient prior to continued use.
In general, short-term antipsychotic therapy is not associated with symptoms related to abrupt discontinuation; however, some patients on maintenance treatment experience transient dyskinetic movements following abrupt withdrawal. In some cases, these movements are not distinguishable from tardive dyskinesia except for duration. Other discontinuation symptoms of antipsychotics (including quetiapine) include nausea, vomiting, anorexia, diaphoresis, headache, insomnia, restlessness, anxiety, and agitation. In clinical studies of quetiapine, the incidence of withdrawal symptoms usually resolved after 1 week post discontinuation. When clinical feasible, a gradual withdrawal taper is advised. Carefully observe patients for symptom exacerbation and dyskinetic movements after drug discontinuation.
There are literature reports indicating that quetiapine use has been associated with laboratory test interference. Patients taking quetiapine have had false positive urine drug screens for methadone and tricyclic antidepressants. Caution should be exercised when interpreting positive urine drug screens for these medications, and confirmation by alternate analytical techniques (e.g., chromatographic methods) should be considered.
For the treatment of major depression:
-for the adjunctive treatment of major depression in patients who have had an inadequate response to antidepressants alone:
Oral dosage (extended-release tablets):
Adults: 50 mg PO once daily in the evening on Day 1 and Day 2. On Day 3, increase to 150 mg PO once daily in the evening. Effectiveness has been demonstrated at a range of 150 mg/day to 300 mg/day PO. Doses above 300 mg/day have not been studied. Consider a slower rate of dose titration and a lower target dose in debilitated patients or patients at risk for hypotension. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. During clinical trials, a dose-dependent increase in adverse reactions was observed in the recommended dose range. Because of the frequency and severity of adverse effects with antipsychotics, it is advisable to reserve the use of quetiapine for patients refractory to traditional therapies for depression and whose severity of illness outweighs the long-term risks of treatment with an antipsychotic. RE-INITIATION OF TREATMENT: If therapy is discontinued for less than 1 week and subsequently re-initiated, the same dose/schedule may be used without titration. If therapy has been discontinued for more than 1 week, follow the initial titration schedule.
Geriatric adults: 50 mg PO once daily in the evening initially on Day 1 and Day 2. The dose may be increased in increments of 50 mg/day depending on individual response and tolerability within the adult dose range. Effectiveness has been demonstrated at a range of 150 mg/day to 300 mg/day PO. Doses above 300 mg/day have not been studied. Consider a slow rate of dose titration and a lower target dose in debilitated patients or patients at risk for hypotension. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Because of the frequency and severity of adverse effects with antipsychotics, it is advisable to reserve the use of quetiapine for patients refractory to traditional therapies for depression and whose severity of illness outweighs the long-term risks of treatment with an antipsychotic. RE-INITIATION OF TREATMENT: If therapy is discontinued for less than 1 week and subsequently re-initiated, the same dose/schedule may be used without titration. If therapy has been discontinued for more than 1 week, follow the initial titration schedule.
-for the treatment of major depressive disorder as monotherapy*:
Oral dosage (extended-release formulation e.g., Seroquel XR):
Adults: 50 mg/day PO initially, and titrate according to response and tolerability. Consider a slow rate of dose titration and a lower target dose in debilitated patients or patients at risk for hypotension, such as the elderly. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In large randomized clinical trials, quetiapine XR 50 mg/day PO up to 300 mg/day PO has been effective as monotherapy treatment and improvement may occur as early as Day 4 of treatment. Doses above 300 mg/day have not been studied. In one large comparison trial (n = 612) for patients with major depressive disorder (MDD), quetiapine XR 150 mg/day PO, quetiapine XR 300 mg/day PO, and duloxetine 60 mg/day PO showed significant improvement in the primary outcome, change in Montgomery-Asberg Depression Rating Scale (MADRS), compared to placebo; however, only the quetiapine XR 300 mg/day group and the duloxetine group were superior to placebo in MADRS remission rates (absolute score 8 or less). In a fixed-dose comparison of quetiapine XR 50 mg/day PO, 150 mg/day PO, 300 mg/day PO, and placebo in patients with MDD, all three active treatments significantly improved MADRS scores compared to placebo beginning on day 4 and throughout the study (6 weeks); however, only the 50 mg/day and 300 mg/day groups separated from placebo in remission rates. Overall, the 150 mg/day dose was associated with more positive secondary efficacy results than 50 mg/day and 300 mg/day versus placebo. The most common side effects were dry mouth, sedation, somnolence, headache, and dizziness. Further study is needed to determine the long-term risks and benefits of quetiapine in the monotherapy treatment of major depression. RE-INITIATION OF TREATMENT: If therapy is discontinued for less than 1 week and subsequently re-initiated, the same dose/schedule may be used without titration. If therapy has been discontinued for more than 1 week, follow the initial titration schedule.
For the treatment of bipolar disorder, including mania and bipolar depression:
-for the treatment of mania associated with bipolar I disorder:
Oral dosage (immediate-release):
Adults : 50 mg PO twice daily, initially. Increase the dose by 100 mg/day every day up to 400 mg/day. May further increase dose by 200 mg/day every day based on clinical response and tolerability. Usual dose: 400 to 800 mg/day. Max: 800 mg/day in 2 divided doses. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
Older Adults: 25 mg PO twice daily, initially. Increase the dose by 50 mg/day based on clinical response and tolerability. Usual dose: 400 to 800 mg/day. Max: 800 mg/day in 2 divided doses. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
Children and Adolescents 10 to 17 years: 25 mg PO twice daily for 1 day, then 50 mg PO twice daily, initially. Increase the dose by 100 mg/day every day up to 400 mg/day. May further increase dose by 100 mg/day or less every day based on clinical response and tolerability. Usual dose: 400 to 600 mg/day. Max: 600 mg/day in 2 or 3 divided doses. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
Oral dosage (extended-release):
Adults : 300 mg PO once daily for 1 day, then 600 mg PO once daily for 1 day, then 400 to 800 mg PO once daily. Adjust dose based on clinical response and tolerability. Usual dose: 400 to 800 mg/day. Max: 800 mg/day. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
Older Adults: 50mg PO once daily, initially. Increase the dose by 50 mg/day based on clinical response and tolerability. Usual dose: 400 to 800 mg/day. Max: 800 mg/day. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
Children and Adolescents 10 years to 17 years: 50 mg PO once daily for 1 day, then 100 mg PO once daily, initially. Increase the dose by 100 mg/day every day up to 400 mg/day. Adjust dose based on clinical response and tolerability. Usual dose: 400 to 600 mg/day. Max: 600 mg/day. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
-for the treatment of bipolar disorder depressive episodes:
Oral dosage:
Adults: 50 mg PO once daily for 1 day, then 100 mg PO once daily, initially. Increase the dose by 100 mg/day every day up to 300 mg/day. Usual dose: 300 mg/day. Max: 300 mg/day. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
Older Adults: 50 mg PO once daily, initially. Increase the dose by 50 mg/day based on clinical response and tolerability. Usual dose: 300 mg/day. Max: 300 mg/day. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
For the treatment of schizophrenia:
Oral dosage (immediate-release tablets):
Adults: 25 mg PO twice daily on Day 1. Increase by 25 mg to 50 mg, on Day 2 and Day 3 to a target range of 300 mg/day to 400 mg/day PO, in divided doses two or three times per day, by Day 4. Further dosage adjustments can be made in increments/decrements of 25 mg to 50 mg twice a day, at intervals of at least 2 days, within the initial recommended dose range of 150 mg/day to 750 mg/day. The recommended maintenance dose range is 400 mg/day to 800 mg/day. Maximum: 800 mg/day PO. Consider a slower rate of dose titration and a lower target dose in debilitated patients or patients at risk for hypotension. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Efficacy in adults was established in three short-term (6-week) controlled trials in inpatients. In short-term clinical trials evaluating 5 doses (i.e., daily doses of 75 mg, 150 mg, 300 mg, 600 mg, or 750 mg), the maximum benefit as measured by the BPRS total score, the BPRS psychosis cluster, and the CGI severity score, occurred at a dose of 300 mg/day. The 75 mg dose was not superior to placebo. In other short-term clinical trial evaluation, high dose treatment (450 mg/day to 750 mg/day) was superior to low dose treatment (250 mg/day or less). Long-term use in schizophrenia has not been systematically evaluated. Periodically re-assess to determine the need for continued therapy. RE-INITIATION OF TREATMENT: If therapy is discontinued for less than 1 week and subsequently re-initiated, the same dose/schedule may be used without titration. If therapy has been discontinued for more than 1 week, follow the initial titration schedule.
Geriatric adults: Initially, 25 mg PO twice daily and increase based upon individual response and tolerability. Compared to the adult dosing schedule, a slower rate of titration and a lower target dose should be considered for geriatric or debilitated patients, and patients predisposed to hypotension. The younger adult target range is 300 mg/day to 400 mg/day PO, in divided doses two or three times per day. Adjust in increments/decrements of 25 mg to 50 mg twice a day, at intervals of at least 2 days, within range of 150 mg/day to 750 mg/day. Usual younger adult maintenance dose range: 400 mg/day to 800 mg/day. Maximum: 800 mg/day PO. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. RE-INITIATION OF TREATMENT: If therapy is discontinued for less than 1 week and subsequently re-initiated, the same dose/schedule may be used without titration. If therapy has been discontinued for more than 1 week, follow the initial titration schedule.
Adolescents: 25 mg PO twice daily on Day 1, then 50 mg PO twice daily on Day 2, 100 mg PO twice daily on Day 3, 150 mg PO twice daily on Day 4, and 200 mg PO twice daily beginning on Day 5. Thereafter, dosage adjustments may be made within the dose range of 400 mg/day to 800 mg/day, given in two or three divided doses based upon response and tolerability. Make dose adjustments in increments of 100 mg/day or less. Based on clinical trials, there appears to be no additional benefit at doses greater than 400 mg/day. Individualize. Long-term use in schizophrenia has not been systematically evaluated. Use lowest effective dose. Periodically re-assess the need for continued treatment. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. RE-INITIATION OF TREATMENT: If therapy is discontinued for less than 1 week and subsequently re-initiated, the same dose/schedule may be used without titration. If therapy has been discontinued for more than 1 week, follow the initial titration schedule.
Children: Safety and efficacy have not been established.
Oral dosage (extended-release tablets i.e., Seroquel XR):
Adults: Initially, 300 mg PO once daily, preferably in the evening. Titrate to a range of 400 mg to 800 mg PO once daily, based on response and tolerability. The dose may be increased in increments up to 300 mg/day and at intervals of at least 1 day each. Maximum: 800 mg/day PO. Consider a slower rate of dose titration and a lower target dose in debilitated patients or patients at risk for hypotension. Patients currently receiving the immediate-release formulation may be switched to the extended-release formulation at the equivalent total daily dose taken once daily. Individualize dosage. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. RE-INITIATION OF TREATMENT: If therapy is discontinued for less than 1 week and subsequently re-initiated, the same dose/schedule may be used without titration. If therapy has been discontinued for more than 1 week, follow the initial titration schedule.
Geriatric adults: An initial dose of 50 mg/day PO is recommended for geriatric patients. The dosage may be titrated in increments of 50 mg/day depending upon individual response and tolerability. Younger adult dose range: 400 mg to 800 mg PO once daily, based on response and tolerability. Maximum: 800 mg/day PO. Consider a slower rate of dose titration and a lower target dose in debilitated patients or patients at risk for hypotension. Patients currently receiving the immediate-release formulation may be switched to the extended-release formulation at the equivalent total daily dose taken once daily. Individualize dosage. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. RE-INITIATION OF TREATMENT: If therapy is discontinued for less than 1 week and subsequently re-initiated, the same dose/schedule may be used without titration. If therapy has been discontinued for more than 1 week, follow the initial titration schedule.
Adolescents: Initially, 50 mg PO on Day 1. Thereafter, use the following titration schedule: 100 mg/day on Day 2, 200 mg/day on Day 3, 300 mg/day on Day 4, and 400 mg PO once daily beginning on Day 5. Adjust based upon response and tolerability within the recommended dose range of 400 mg/day to 800 mg/day. Maximum: 800 mg/day PO. Periodically re-assess the need for continued treatment. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. RE-INITIATION OF TREATMENT: If therapy is discontinued for less than 1 week and subsequently re-initiated, the same dose/schedule may be used without titration. If therapy has been discontinued for more than 1 week, follow the initial titration schedule.
For the adjunct treatment of refractory obsessive-compulsive disorder (OCD)*:
Oral dosage (immediate-release tablets):
Adults: Dosage not established. Quetiapine use cannot be routinely recommended; although, quetiapine has been studied as an adjunct to either an SSRI or clomipramine, which have been previously titrated to optimal doses for OCD. Randomized controlled trials have shown mixed results for the adjunct treatment of OCD. Several of these trials have not proven a benefit for add-on therapy with quetiapine vs. placebo. Initial doses: 25 mg or 50 mg PO once daily; dose may be administered at bedtime. The dose is typically titrated at weekly intervals, as tolerated and clinically indicated. In a well-controlled clinical trial, the target dose of quetiapine after titration was 200 mg/day PO. Trials have allowed doses up to 300 mg/day to 600 mg/day PO, in divided doses. Somnolence is the major side effect. Use with caution in patients at risk for hypotension. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Larger controlled clinical trials are needed to validate any long-term efficacy, as well as effectiveness when co-morbid disease states exist.
For the treatment of neurocognitive symptoms (e.g., impulsivity, executive functioning) associated with borderline personality disorder*:
Oral dosage (extended-release tablets):
Adults: Further study is needed to establish the effective dose range. Benefit-to-risk should be thoroughly evaluated prior to initiating treatment. Data suggest that 150 mg PO once daily dosing provides the best benefit-to-risk ratio, after titration. In one placebo-controlled, randomized study, use of 150 mg/day (low-dose) resulted in statistically significant improvement on the primary endpoint (Zanarini scale total score), but 300 mg/day (moderate-dose) did not separate from placebo. The initial dose: 50 mg PO once daily for 1 week, followed by titration to 150 mg PO once daily, with subsequent titration of the higher dose group to 300 mg/day PO after 4 weeks. Among those completing the study, 82% in the low-dose quetiapine group were responders vs. 74% in the moderate-dose group and vs. 48% in the placebo group (responder defined as a reduction of 50% or more on the Zanarini scale total score). Baseline symptom severity was greatest in the 300 mg/day group and least for the placebo group (p = 0.029), which may have confounded the results. The time to response was significantly shorter for both the low-dose and moderate-dose quetiapine groups vs. placebo. There were significant improvements in both quetiapine groups on some secondary measures, such as self-rated Zanarini subscales for affective disturbance, cognitive disturbance, and disturbed relationships and the clinician-rated aggression scale score. Unlike other studies, impulsivity was not significantly improved. Common side effects included sedation, change in appetite, and dry mouth. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Periodically re-assess the need for continued therapy.
Oral dosage (immediate-release tablets):
Adults: Evaluate benefit-to-risk prior to treatment. Initially, use low doses of 25 mg to 50 mg PO twice daily to minimize side effects (e.g., orthostatic hypotension), followed by titration as clinically indicated and tolerated. Studies indicate an average effective dose range of 250 mg/day to 550 mg/day PO, given in divided doses (range: 100 mg/day to 800 mg/day PO). Maximum: 800 mg/day PO. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Quetiapine may improve impulsivity, hostility, and affective symptoms, and results of one study suggests improvement of executive functioning. Common side effects include somnolence, dizziness, increased appetite, and dry mouth. Somnolence is the primary side effect associated with discontinuation. Periodically re-assess the need for continued therapy. Most studies are limited by open-label design, lack of controls, high dropout rates, and small sample sizes.
For the treatment of severe behavioral or psychological symptoms of dementia* (BPSD)*:
Oral dosage (immediate-release tablets):
Adults: 25 mg PO once or twice daily, initially. Dosage adjustments of 25 to 50 mg twice per day, if indicated, should occur at intervals of not less than 2 to 7 days. Use the lowest effective dosage. Doses greater than 150 mg/day are not usually needed. Quetiapine has not been found to be more efficacious than placebo for symptoms of BPSD in studies, so its use is not usually recommended. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.
Maximum Dosage Limits:
-Adults
800 mg/day PO.
-Geriatric
800 mg/day PO.
-Adolescents
800 mg/day PO.
-Children
10 to 12 years: 600 mg/day PO.
Less than 10 years: Safety and effectiveness have not been established.
-Infants
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Patients with hepatic impairment have a 30% lower mean clearance of quetiapine than normal subjects; therefore, initial dosage adjustment is necessary.
Immediate-release formulation: Initiate with 25 mg/day PO. The dose should be increased daily in increments of 25 to 50 mg/day to an effective dose and given in divided doses twice daily, depending on the clinical response and tolerability of the patient.
Extended-release formulation: Initially, give 50 mg PO once daily, preferably in the evening. The dose can be increased daily in increments of 50 mg/day to an effective dose, depending on the clinical response and tolerability of the patient.
Patients with Renal Impairment Dosing
CrCl 10 mL/minute and above: No dosage adjustment is needed. Although patients with severe renal impairment (10 to 30 mL/minute) have a 25% lower mean clearance than normal subjects (CrCl more than 80 mL/minute), plasma quetiapine concentrations are still within the range of concentrations seen in normal subjects receiving the same dose.
CrCl less than 10 mL/minute: There are no dosing guidelines available.
Intermittent hemodialysis:
There are no dosing guidelines available for patients with CrCl less than 10 mL/minute or those receiving dialysis.
*non-FDA-approved indication
Acarbose: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Monitor for unusual drowsiness and sedation, urinary retention, and reduced gastric motility during coadministration of diphenhydramine and quetiapine. Concomitant use may result in additive CNS depression or anticholinergic effects.
Acetaminophen; Caffeine; Dihydrocodeine: (Major) Concomitant use of opioid agonists with quetiapine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with quetiapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. Avoid prescribing opioid cough medication in patients taking quetiapine.
Acetaminophen; Chlorpheniramine: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
Acetaminophen; Codeine: (Major) Concomitant use of opioid agonists with quetiapine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with quetiapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. Avoid prescribing opioid cough medication in patients taking quetiapine.
Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Monitor for unusual drowsiness and sedation, urinary retention, and reduced gastric motility during coadministration of doxylamine and quetiapine. Concomitant use may result in additive CNS depression or anticholinergic effects.
Acetaminophen; Diphenhydramine: (Moderate) Monitor for unusual drowsiness and sedation, urinary retention, and reduced gastric motility during coadministration of diphenhydramine and quetiapine. Concomitant use may result in additive CNS depression or anticholinergic effects.
Acetaminophen; Hydrocodone: (Major) Concomitant use of opioid agonists with quetiapine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with quetiapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. Avoid prescribing opioid cough medication in patients taking quetiapine.
Acetaminophen; Oxycodone: (Major) Concomitant use of opioid agonists with quetiapine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with quetiapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Acetazolamide: (Moderate) Caution is advisable during concurrent use of quetiapine and acetazolamide as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with quetiapine.
Adagrasib: (Major) Avoid concomitant use of adagrasib and quetiapine due to the potential for increased quetiapine exposure and additive risk for QT/QTc prolongation and torsade de pointes (TdP). If use is necessary, reduce quetiapine dose to one sixth and consider taking additional steps to minimize the risk for QT prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring. Quetiapine is a CYP3A substrate, adagrasib is a strong CYP3A inhibitor, and both medications have been associated with QT interval prolongation. Coadministration with another strong CYP3A inhibitor increased the exposure of quetiapine by approximately 6-fold.
Alfentanil: (Major) Concomitant use of opioid agonists with quetiapine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with quetiapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Alfuzosin: (Major) Concomitant use of quetiapine and alfuzosin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Alogliptin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Alogliptin; Metformin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and metformin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Alogliptin; Pioglitazone: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Alpha-glucosidase Inhibitors: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Alprazolam: (Moderate) Monitor for excessive sedation and somnolence during coadministration of alprazolam and quetiapine. Concurrent use may result in additive CNS depression.
Amifampridine: (Major) Carefully consider the need for concomitant treatment with atypical antipsychotics and amifampridine, as coadministration may increase the risk of seizures. If coadministration occurs, closely monitor patients for seizure activity. Seizures have been observed in patients without a history of seizures taking amifampridine at recommended doses. Atypical antipsychotics may increase the risk of seizures.
Amiodarone: (Major) Concomitant use of amiodarone and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after drug discontinuation.
Amisulpride: (Major) Concomitant use of quetiapine and amisulpride increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Amobarbital: (Major) Coadministration of barbiturates, potent CYP3A4 inducers, with quetiapine, a CYP3A4 substrate, may result in decreased exposure to quetiapine. The dose of quetiapine should be increased by up to 5-fold when combined with chronic administration (7 to 14 days) of a potent CYP3A4 inducer. Adjust the dose based on patient response and tolerability. When the potent CYP3A4 inducer is discontinued, the quetiapine dose should be reduced to the original dose within 1 to 2 weeks. Also, somnolence is a commonly reported adverse effect of quetiapine; coadministration of quetiapine with barbiturates may result in additive sedative effects.
Amoxapine: (Moderate) Use caution during co-administration of amoxapine and quetiapine. Amoxapine exhibits some antipsychotic activity and may increase the risk of tardive dyskinesia or neuroleptic malignant syndrome (NMS) when antipsychotics are given concurrently. CNS effects, orthostatic hypotension, anticholinergic effects, and lowering of seizure threshold are potential problems with the combined use of amoxapine and antipsychotics.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Avoid concurrent use of quetiapine and clarithromycin due to the potential for additive effects on the QT interval and torsade de pointes (TdP) and the potential for greatly increased quetiapine exposure. Clarithromycin is a potent inhibitor of CYP3A4 that is expected to signficantly reduce metabolism of quetiapine. If administration of clarithromycin is required in a patient taking quetiapine, reduce the quetiapine dose to one sixth of the current dose. Monitor for quetiapine-related side effects. If clarithromycin is discontinued, increase the quetiapine dose by 6-fold. Clarithromycin has an established causal association with QT prolongation and TdP (torsade de pointes). Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances.
Anagrelide: (Major) Concomitant use of quetiapine and anagrelide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Apalutamide: (Major) Increase the dose of quetiapine by up to 5-fold if coadministration with apalutamide is necessary. If apalutamide is discontinued, reduce the quetiapine dose to the original level in 7 to 14 days. Quetiapine is a sensitive CYP3A4 substrate and apalutamide is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer increased the mean oral clearance of quetiapine by 5-fold.
Apomorphine: (Major) Avoid use of quetiapine and apomorphine if possible due to an increased risk for QT prolongation and sedation. Also, quetiapine and apomorphine may reduce the effectiveness of each other through opposing effects on dopamine. Additive CNS effects are also possible. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. In general, atypical antipsychotics are less likely to interfere with Parkinson's disease treatments than traditional antipsychotics. Monitor for movement disorders, unusual changes in moods or behavior, sedation, fast, irregular heartbeat, and diminished effectiveness of either agent if coadministration cannot be avoided.
Aprepitant, Fosaprepitant: (Major) Use caution if quetiapine and aprepitant, fosaprepitant are used concurrently and monitor for an increase in quetiapine-related adverse effects, including QT prolongation and torsade de pointes (TdP), for several days after administration of a multi-day aprepitant regimen. Quetiapine is a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and may increase plasma concentrations of quetiapine. For example, a 5-day oral aprepitant regimen increased the AUC of another CYP3A4 substrate, midazolam (single dose), by 2.3-fold on day 1 and by 3.3-fold on day 5. After a 3-day oral aprepitant regimen, the AUC of midazolam (given on days 1, 4, 8, and 15) increased by 25% on day 4, and then decreased by 19% and 4% on days 8 and 15, respectively. As a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.5-fold and 1.2-fold, respectively. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction. Fosaprepitant 150 mg IV as a single dose increased the AUC of midazolam (given on days 1 and 4) by approximately 1.8-fold on day 1; there was no effect on day 4. Less than a 2-fold increase in the midazolam AUC is not considered clinically important.
Aripiprazole: (Major) Concomitant use of aripiprazole and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP) and additive CNS depression. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Monitor for unusual drowsiness and sedation during coadministration.
Arsenic Trioxide: (Major) Concomitant use of quetiapine and arsenic trioxide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Artemether; Lumefantrine: (Major) Concomitant use of quetiapine and lumefantrine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Asenapine: (Major) Concomitant use of quetiapine and asenapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Aspirin, ASA; Butalbital; Caffeine: (Major) Coadministration of barbiturates, potent CYP3A4 inducers, with quetiapine, a CYP3A4 substrate, may result in decreased exposure to quetiapine. The dose of quetiapine should be increased by up to 5-fold when combined with chronic administration (7 to 14 days) of a potent CYP3A4 inducer. Adjust the dose based on patient response and tolerability. When the potent CYP3A4 inducer is discontinued, the quetiapine dose should be reduced to the original dose within 1 to 2 weeks. Also, somnolence is a commonly reported adverse effect of quetiapine; coadministration of quetiapine with barbiturates may result in additive sedative effects.
Aspirin, ASA; Carisoprodol; Codeine: (Major) Concomitant use of opioid agonists with quetiapine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with quetiapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. Avoid prescribing opioid cough medication in patients taking quetiapine.
Aspirin, ASA; Oxycodone: (Major) Concomitant use of opioid agonists with quetiapine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with quetiapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Atazanavir: (Major) Avoid concurrent use of quetiapine and anti-retroviral protease inhibitors, such as atazanavir. Atazanavir may inhibit the CYP3A4 metabolism of quetiapine, resulting in elevated quetiapine plasma concentrations. If administration of atazanavir is required in a patient taking quetiapine, reduce the quetiapine dose to one sixth of the current dose and monitor for quetiapine-related adverse events. If atazanavir is discontinued, increase the quetiapine dose by 6-fold.
Atazanavir; Cobicistat: (Major) Avoid concurrent use of quetiapine and anti-retroviral protease inhibitors, such as atazanavir. Atazanavir may inhibit the CYP3A4 metabolism of quetiapine, resulting in elevated quetiapine plasma concentrations. If administration of atazanavir is required in a patient taking quetiapine, reduce the quetiapine dose to one sixth of the current dose and monitor for quetiapine-related adverse events. If atazanavir is discontinued, increase the quetiapine dose by 6-fold. (Major) The plasma concentrations of quetiapine may be elevated when administered concurrently with cobicistat. The manufacturer of quetiapine recommends a quetiapine dose reduction to one-sixth the original dose during concurrent administration of CYP3A4 inhibitors, such as cobicistat. When cobicistat is discontinued, the dose should be increased by 6-fold.
Atomoxetine: (Major) Concomitant use of atomoxetine and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Atropine: (Moderate) Monitor for unusual drowsiness or excess sedation and for signs or symptoms of anticholinergic toxicity during concomitant quetiapine and atropine use. Concomitant use may result in additive CNS depression or anticholinergic adverse effects.
Atropine; Difenoxin: (Moderate) Monitor for unusual drowsiness or excess sedation and for signs or symptoms of anticholinergic toxicity during concomitant quetiapine and atropine use. Concomitant use may result in additive CNS depression or anticholinergic adverse effects.
Azithromycin: (Major) Concomitant use of azithromycin and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Barbiturates: (Major) Coadministration of barbiturates, potent CYP3A4 inducers, with quetiapine, a CYP3A4 substrate, may result in decreased exposure to quetiapine. The dose of quetiapine should be increased by up to 5-fold when combined with chronic administration (7 to 14 days) of a potent CYP3A4 inducer. Adjust the dose based on patient response and tolerability. When the potent CYP3A4 inducer is discontinued, the quetiapine dose should be reduced to the original dose within 1 to 2 weeks. Also, somnolence is a commonly reported adverse effect of quetiapine; coadministration of quetiapine with barbiturates may result in additive sedative effects.
Bedaquiline: (Major) Concomitant use of quetiapine and bedaquiline increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Belladonna; Opium: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant quetiapine and belladonna use. Concomitant use may result in additive anticholinergic adverse effects.
Benzhydrocodone; Acetaminophen: (Major) Concomitant use of opioid agonists with quetiapine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with quetiapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. If benzhydrocodone is initiated in a patient taking quetiapine, reduce initial dosage and titrate to clinical response. If quetiapine is initiated a patient taking an opioid agonist, use a lower initial dose of quetiapine and titrate to clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant quetiapine and hyoscyamine use. Concomitant use may result in additive anticholinergic adverse effects.
Benztropine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant quetiapine and benztropine use. Concomitant use may result in additive anticholinergic adverse effects.
Bexagliflozin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and SGLT2 inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Major) Concomitant use of metronidazole and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Major) Concomitant use of metronidazole and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Brexpiprazole: (Major) Caution is advisable during concurrent use of brexpiprazole with other antipsychotics such as quetiapine. The risk of drowsiness, dizziness, hypotension, extrapyramidal symptoms, anticholinergic effects, neuroleptic malignant syndrome, or seizures may be increased during combined use; therefore, it may be advisable to initiate treatment with lower dosages if combination therapy is deemed necessary.
Bromocriptine: (Moderate) The effectiveness of bromocriptine may be reduced by most of the atypical antipsychotics, via their action as dopamine antagonists. Monitor the patient for reduced response to bromocriptine. The atypical antipsychotics elevate prolactin to various degrees. Atypical antipsychotics may also aggravate diabetes mellitus and cause metabolic changes including hyperglycemia; use caution if bromocriptine is taken for diabetes. If bromocriptine is taken for diabetes, monitor for worsening glycemic control.
Brompheniramine: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
Brompheniramine; Phenylephrine: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
Brompheniramine; Pseudoephedrine: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
Budesonide; Glycopyrrolate; Formoterol: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant quetiapine and glycopyrrolate use. Concomitant use may result in additive anticholinergic adverse effects.
Buprenorphine: (Major) Due to the potential for QT prolongation and additive CNS depressant effects, cautious use and close monitoring are advisable if concurrent use of quetiapine and buprenorphine is necessary. Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). Quetiapine has a possible risk for QT prolongation and TdP. FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval. If concurrent use of quetiapine and buprenorphine is necessary, consider a dose reduction of one or both drugs. Hypotension, profound sedation, coma, respiratory depression, or death may occur during co-administration of buprenorphine and other CNS depressants. Prior to concurrent use of buprenorphine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Evaluate the patient's use of alcohol or illicit drugs. It is recommended that the injectable buprenorphine dose be halved for patients who receive other drugs with CNS depressant effects; for the buprenorphine transdermal patch, start with the 5 mcg/hour patch. Monitor patients for sedation or respiratory depression.
Buprenorphine; Naloxone: (Major) Due to the potential for QT prolongation and additive CNS depressant effects, cautious use and close monitoring are advisable if concurrent use of quetiapine and buprenorphine is necessary. Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). Quetiapine has a possible risk for QT prolongation and TdP. FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval. If concurrent use of quetiapine and buprenorphine is necessary, consider a dose reduction of one or both drugs. Hypotension, profound sedation, coma, respiratory depression, or death may occur during co-administration of buprenorphine and other CNS depressants. Prior to concurrent use of buprenorphine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Evaluate the patient's use of alcohol or illicit drugs. It is recommended that the injectable buprenorphine dose be halved for patients who receive other drugs with CNS depressant effects; for the buprenorphine transdermal patch, start with the 5 mcg/hour patch. Monitor patients for sedation or respiratory depression.
Buspirone: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant atypical antipsychotic and buspirone use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Butalbital; Acetaminophen: (Major) Coadministration of barbiturates, potent CYP3A4 inducers, with quetiapine, a CYP3A4 substrate, may result in decreased exposure to quetiapine. The dose of quetiapine should be increased by up to 5-fold when combined with chronic administration (7 to 14 days) of a potent CYP3A4 inducer. Adjust the dose based on patient response and tolerability. When the potent CYP3A4 inducer is discontinued, the quetiapine dose should be reduced to the original dose within 1 to 2 weeks. Also, somnolence is a commonly reported adverse effect of quetiapine; coadministration of quetiapine with barbiturates may result in additive sedative effects.
Butalbital; Acetaminophen; Caffeine: (Major) Coadministration of barbiturates, potent CYP3A4 inducers, with quetiapine, a CYP3A4 substrate, may result in decreased exposure to quetiapine. The dose of quetiapine should be increased by up to 5-fold when combined with chronic administration (7 to 14 days) of a potent CYP3A4 inducer. Adjust the dose based on patient response and tolerability. When the potent CYP3A4 inducer is discontinued, the quetiapine dose should be reduced to the original dose within 1 to 2 weeks. Also, somnolence is a commonly reported adverse effect of quetiapine; coadministration of quetiapine with barbiturates may result in additive sedative effects.
Butalbital; Acetaminophen; Caffeine; Codeine: (Major) Coadministration of barbiturates, potent CYP3A4 inducers, with quetiapine, a CYP3A4 substrate, may result in decreased exposure to quetiapine. The dose of quetiapine should be increased by up to 5-fold when combined with chronic administration (7 to 14 days) of a potent CYP3A4 inducer. Adjust the dose based on patient response and tolerability. When the potent CYP3A4 inducer is discontinued, the quetiapine dose should be reduced to the original dose within 1 to 2 weeks. Also, somnolence is a commonly reported adverse effect of quetiapine; coadministration of quetiapine with barbiturates may result in additive sedative effects. (Major) Concomitant use of opioid agonists with quetiapine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with quetiapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. Avoid prescribing opioid cough medication in patients taking quetiapine.
Butalbital; Aspirin; Caffeine; Codeine: (Major) Coadministration of barbiturates, potent CYP3A4 inducers, with quetiapine, a CYP3A4 substrate, may result in decreased exposure to quetiapine. The dose of quetiapine should be increased by up to 5-fold when combined with chronic administration (7 to 14 days) of a potent CYP3A4 inducer. Adjust the dose based on patient response and tolerability. When the potent CYP3A4 inducer is discontinued, the quetiapine dose should be reduced to the original dose within 1 to 2 weeks. Also, somnolence is a commonly reported adverse effect of quetiapine; coadministration of quetiapine with barbiturates may result in additive sedative effects. (Major) Concomitant use of opioid agonists with quetiapine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with quetiapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. Avoid prescribing opioid cough medication in patients taking quetiapine.
Butorphanol: (Moderate) Concomitant use of butorphanol with quetiapine can potentiate the effects of butorphanol on CNS and/or respiratory depression. Use together with caution. If a centrally acting medication needs to be used with butorphanol, use the smallest effective dose and the longest dosing frequency of butorphanol.
Cabergoline: (Moderate) Cabergoline should not be coadministered with quetiapine due to mutually antagonistic effects on dopaminergic function. The dopamine antagonist action of quetiapine may diminish the prolactin-lowering ability of cabergoline while the dopamine agonist effects of cabergoline may exacerbate a psychotic disorder, reducing the effectiveness of antipsychotics such as quetiapine.
Cabotegravir; Rilpivirine: (Major) Concomitant use of rilpivirine and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. The degree of QT prolongation associated with rilpivirine is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Canagliflozin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and SGLT2 inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Canagliflozin; Metformin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and metformin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and SGLT2 inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Cannabidiol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and quetiapine. Concurrent use may result in additive CNS depression.
Carbamazepine: (Major) Increase the dose of quetiapine by up to 5-fold if coadministered with carbamazepine. Coadministration may significantly decrease quetiapine exposure leading to reduced efficacy as well as increase concentrations of the carbamazepine active metabolite, carbamazepine-10,11 epoxide. If carbamazepine is discontinued, reduce the quetiapine dose to the original level in 7 to 14 days. Quetiapine is a sensitive CYP3A4 substrate and carbamazepine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer increased the mean oral clearance of quetiapine by 5-fold. Quetiapine also inhibits epoxide hydrolase.
Carbidopa; Levodopa: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or levodopa during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and levodopa may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with levodopa and other antiparkinson's treatments than traditional antipsychotics.
Carbidopa; Levodopa; Entacapone: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or COMT inhibitor during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and COMT inhibitors may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with COMT inhibitors and other Parkinson's treatments than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease. (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or levodopa during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and levodopa may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with levodopa and other antiparkinson's treatments than traditional antipsychotics.
Carbinoxamine: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
Cariprazine: (Moderate) The risk of adverse effects may be increased during concurrent use of cariprazine with other antipsychotics, such as quetiapine. Similar to other antipsychotics, cariprazine administration has been associated with drowsiness, dizziness, orthostatic hypotension, extrapyramidal symptoms, neuroleptic malignant syndrome, and seizures. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. The incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, but the risk appears to be increased.
Celecoxib; Tramadol: (Moderate) If concomitant use of tramadol and quetiapine is warranted, monitor patients for seizures, excessive sedation and/or somnolence, and the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. Concomitant use of tramadol and quetiapine may increase seizure risk and cause additive CNS depression. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Cenobamate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cenobamate and quetiapine. Concurrent use may result in additive CNS depression.
Ceritinib: (Major) Avoid coadministration of ceritinib with quetiapine due to an increased risk for QT prolongation. Systemic exposure of quetiapine may also be increased resulting in increase in treatment-related adverse reactions. Ceritinib is a strong CYP3A4 inhibitor that has been shown to prolong the QT interval in a concentration-dependent manner. Limited data, including some case reports, suggest that quetiapine, a sensitive CYP3A4 substrate, may also be associated with a significant prolongation of the QTc interval in rare instances. Coadministration with another strong CYP3A4 inhibitor significantly increased quetiapine exposure; the manufacturer recommends a large dose reduction when coadministered with strong CYP3A4 inhibitors that do not cause QT prolongation.
Cetirizine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of atypical antipsychotics and cetirizine due to the risk for additive CNS depression.
Cetirizine; Pseudoephedrine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of atypical antipsychotics and cetirizine due to the risk for additive CNS depression.
Cetrorelix: (Moderate) Antipsychotic-induced hyperprolactinemia results in down-regulation of the number of pituitary GnRH receptors and may interfere with the response to any of the gonadotropin-releasing hormone (GnRH) analogs including cetrorelix.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
Chloramphenicol: (Major) Coadministration of chloramphenicol, a potent CYP3A4 inhibitor, with quetiapine, a CYP3A4 substrate, may result in increased exposure to quetiapine. If administration of chloramphenicol is required in a patient taking quetiapine, reduce the quetiapine dose to one sixth of the current dose and monitor for quetiapine-related adverse events. If chloramphenicol is discontinued, increase the quetiapine dose by 6-fold.
Chlorcyclizine: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
Chlordiazepoxide: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine; coadministration of quetiapine with anxiolytics, sedatives, and hypnotics, or other CNS depressants may result in additive sedative effects.
Chlordiazepoxide; Amitriptyline: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine; coadministration of quetiapine with anxiolytics, sedatives, and hypnotics, or other CNS depressants may result in additive sedative effects.
Chlordiazepoxide; Clidinium: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine; coadministration of quetiapine with anxiolytics, sedatives, and hypnotics, or other CNS depressants may result in additive sedative effects.
Chloroquine: (Major) Concomitant use of quetiapine and chloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Chlorpheniramine: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
Chlorpheniramine; Codeine: (Major) Concomitant use of opioid agonists with quetiapine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with quetiapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. Avoid prescribing opioid cough medication in patients taking quetiapine. (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
Chlorpheniramine; Dextromethorphan: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
Chlorpheniramine; Hydrocodone: (Major) Concomitant use of opioid agonists with quetiapine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with quetiapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. Avoid prescribing opioid cough medication in patients taking quetiapine. (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
Chlorpheniramine; Phenylephrine: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
Chlorpheniramine; Pseudoephedrine: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
Chlorpromazine: (Major) Concurrent use of quetiapine and chlorpromazine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Chlorpromazine, a phenothiazine, is associated with an established risk of QT prolongation and TdP. Limited data, including some case reports, suggest that quetiapine may also be associated with a significant prolongation of the QTc interval in rare instances. In addition, co-administration of quetiapine with phenothiazines may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The likelihood of pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Chlorzoxazone: (Moderate) Additive CNS depression is possible if chlorzoxazone is used concomitantly with other CNS depressants including quetiapine. Additive effects of sedation and dizziness can occur, which can impair the ability to undertake tasks requiring mental alertness. Dosage adjustments of one or both medications may be necessary.
Cimetidine: (Minor) Cimetidine may cause a decrease in quetiapine clearance. Although it is not usually necessary to adjust the dose of quetiapine when cimetidine is coadministered, patients should be monitored for a potential increase in the pharmacologic effects of quetiapine.
Ciprofloxacin: (Major) Concomitant use of ciprofloxacin and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Cisapride: (Contraindicated) Avoid concomitant use of quetiapine and cisapride due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Citalopram: (Major) Concurrent use of quetiapine and citalopram should be avoided if possible. Citalopram causes dose-dependent QT interval prolongation and quetiapine is associated with a risk for QT prolongation and torsade de pointes (TdP). According to the manufacturer of citalopram, concurrent use of citalopram with other drugs that prolong the QT interval is not recommended. However, if concurrent therapy is considered essential, ECG monitoring is recommended.
Clarithromycin: (Major) Avoid concurrent use of quetiapine and clarithromycin due to the potential for additive effects on the QT interval and torsade de pointes (TdP) and the potential for greatly increased quetiapine exposure. Clarithromycin is a potent inhibitor of CYP3A4 that is expected to signficantly reduce metabolism of quetiapine. If administration of clarithromycin is required in a patient taking quetiapine, reduce the quetiapine dose to one sixth of the current dose. Monitor for quetiapine-related side effects. If clarithromycin is discontinued, increase the quetiapine dose by 6-fold. Clarithromycin has an established causal association with QT prolongation and TdP (torsade de pointes). Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances.
Clemastine: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
Clobazam: (Moderate) Clobazam, a benzodiazepine, should be combined cautiously with atypical antipsychotics because of the potential for additive CNS depressant effects. Antipsychotics may also lower the seizure threshold, which might effect the efficacy of clobazam to treat seizures. Clobazam is a weak inducer of CYP3A4 and may reduce the efficacy of atypical antipsychotics that are significantly metabolized by CYP3A4; consult the atypical antipsychotic product labeling for clinical relevance.
Clofazimine: (Major) Concomitant use of clofazimine and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Clonazepam: (Moderate) Monitor for excessive sedation and somnolence during coadministration of clonazepam and quetiapine. Concurrent use may result in additive CNS depression.
Clonidine: (Moderate) Monitor blood pressure and for unusual drowsiness and sedation during coadministration of clonidine and quetiapine. Coadministration may induce or exacerbate orthostatic regulation disturbances, such as orthostatic hypotension, dizziness, or fatigue, as well as produce additive CNS depression.
Clozapine: (Major) Concurrent use of quetiapine and clozapine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Treatment with clozapine has been associated with QT prolongation, TdP, cardiac arrest, and sudden death. Limited data, including some case reports, suggest that quetiapine may also be associated with a significant prolongation of the QTc interval in rare instances. In addition, co-administration of quetiapine with clozapine may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The likelihood of pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Cobicistat: (Major) The plasma concentrations of quetiapine may be elevated when administered concurrently with cobicistat. The manufacturer of quetiapine recommends a quetiapine dose reduction to one-sixth the original dose during concurrent administration of CYP3A4 inhibitors, such as cobicistat. When cobicistat is discontinued, the dose should be increased by 6-fold.
Codeine: (Major) Concomitant use of opioid agonists with quetiapine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with quetiapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. Avoid prescribing opioid cough medication in patients taking quetiapine.
Codeine; Guaifenesin: (Major) Concomitant use of opioid agonists with quetiapine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with quetiapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. Avoid prescribing opioid cough medication in patients taking quetiapine.
Codeine; Guaifenesin; Pseudoephedrine: (Major) Concomitant use of opioid agonists with quetiapine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with quetiapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. Avoid prescribing opioid cough medication in patients taking quetiapine.
Codeine; Phenylephrine; Promethazine: (Major) Concomitant use of opioid agonists with quetiapine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with quetiapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. Avoid prescribing opioid cough medication in patients taking quetiapine. (Major) Concomitant use of quetiapine and promethazine increases the risk of QT/QTc prolongation and torsade de pointes (TdP) and additive anticholinergic effects, CNS depression, and serotonin syndrome. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Monitor for gastrointestinal adverse reactions related to hypomotility, unusual drowsiness and sedation, and signs and symptoms of serotonin syndrome during concomitant use, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of therapy.
Codeine; Promethazine: (Major) Concomitant use of opioid agonists with quetiapine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with quetiapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. Avoid prescribing opioid cough medication in patients taking quetiapine. (Major) Concomitant use of quetiapine and promethazine increases the risk of QT/QTc prolongation and torsade de pointes (TdP) and additive anticholinergic effects, CNS depression, and serotonin syndrome. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Monitor for gastrointestinal adverse reactions related to hypomotility, unusual drowsiness and sedation, and signs and symptoms of serotonin syndrome during concomitant use, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of therapy.
COMT inhibitors: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or COMT inhibitor during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and COMT inhibitors may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with COMT inhibitors and other Parkinson's treatments than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Crizotinib: (Major) Concomitant use of quetiapine and crizotinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Cyproheptadine: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
Dabrafenib: (Major) The concomitant use of dabrafenib and quetiapine may lead to decreased quetiapine concentrations and loss of efficacy. Use of an alternative agent is recommended. If concomitant use of these agents together is unavoidable, monitor patients for loss of quetiapine efficacy. Dabrafenib is a moderate CYP3A4 inducer and quetiapine is a sensitive CYP3A4 substrate. Concomitant use of dabrafenib with a single dose of another sensitive CYP3A4 substrate decreased the AUC value of the sensitive CYP3A4 substrate by 65%.
Dantrolene: (Moderate) Simultaneous use of dantrolene and other CNS depressants such as antipsychotics can increase CNS depression (e.g., drowsiness).
Dapagliflozin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and SGLT2 inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Dapagliflozin; Metformin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and metformin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and SGLT2 inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Dapagliflozin; Saxagliptin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and SGLT2 inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Darifenacin: (Moderate) When coadministering quetiapine and darifenacin, monitor for additive anticholinergic effects such as constipation, blurred vision, urinary retention, xerostomia, and tachycardia. Constipation is a commonly reported adverse effect of quetiapine and anticholinergic agents such as darifenacin. Constipation may lead to ileus. Intestinal obstruction has been reported with quetiapine, including fatal cases in patients who were receiving multiple concomitant medications that decrease intestinal motility. Anticholinergic effects observed during therapeutic use of quetiapine are thought to be associated with norquetiapine, the active metabolite of quetiapine which has demonstrated a moderate to strong in vitro binding affinity for several muscarinic receptor subtypes.
Darunavir: (Major) Avoid concurrent use of quetiapine and darunavir. Darunavir may inhibit the CYP3A4 metabolism of quetiapine, resulting in elevated quetiapine plasma concentrations. If coadministration is required, reduce the quetiapine dose to one-sixth of the current dose and monitor for quetiapine-related adverse events. If darunavir is discontinued, increase the quetiapine dose by 6-fold.
Darunavir; Cobicistat: (Major) Avoid concurrent use of quetiapine and darunavir. Darunavir may inhibit the CYP3A4 metabolism of quetiapine, resulting in elevated quetiapine plasma concentrations. If coadministration is required, reduce the quetiapine dose to one-sixth of the current dose and monitor for quetiapine-related adverse events. If darunavir is discontinued, increase the quetiapine dose by 6-fold. (Major) The plasma concentrations of quetiapine may be elevated when administered concurrently with cobicistat. The manufacturer of quetiapine recommends a quetiapine dose reduction to one-sixth the original dose during concurrent administration of CYP3A4 inhibitors, such as cobicistat. When cobicistat is discontinued, the dose should be increased by 6-fold.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Avoid concurrent use of quetiapine and darunavir. Darunavir may inhibit the CYP3A4 metabolism of quetiapine, resulting in elevated quetiapine plasma concentrations. If coadministration is required, reduce the quetiapine dose to one-sixth of the current dose and monitor for quetiapine-related adverse events. If darunavir is discontinued, increase the quetiapine dose by 6-fold. (Major) The plasma concentrations of quetiapine may be elevated when administered concurrently with cobicistat. The manufacturer of quetiapine recommends a quetiapine dose reduction to one-sixth the original dose during concurrent administration of CYP3A4 inhibitors, such as cobicistat. When cobicistat is discontinued, the dose should be increased by 6-fold.
Dasatinib: (Major) Concomitant use of quetiapine and dasatinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Degarelix: (Major) Concomitant use of quetiapine and degarelix increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Delavirdine: (Major) If coadministration is required, reduce the quetiapine dose to one sixth of the current dose and monitor for adverse events. Delavirdine is expected to significantly increase exposure to quetiapine. Delavirdine is a potent CYP3A4 inhibitor and quetiapine is a CYP3A4 substrate. If delavirdine is discontinued, increase the quetiapine dose by 6-fold.
Desflurane: (Major) Concomitant use of quetiapine and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Deutetrabenazine: (Major) Avoid use of quetiapine in combination with deutetrabenazine due to the potential for additive QT prolongation. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. Deutetrabenazine may prolong the QT interval, but the degree of QT prolongation is not clinically significant when deutetrabenazine is administered within the recommended dosage range. Also, deutetrabenazine is a reversible, dopamine depleting drug and quetiapine is a dopamine antagonist. The risk for parkinsonism, neuroleptic malignant syndrome (NMS), and akathisia may be increased with concomitant administration. Concurrent use of deutetrabenazine and drugs that cause CNS depression, such as quetiapine, may have additive effects and worsen drowsiness or sedation.
Dexchlorpheniramine: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
Dexmedetomidine: (Major) Concomitant use of dexmedetomidine and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Monitor for unusual drowsiness and sedation, urinary retention, and reduced gastric motility during coadministration of diphenhydramine and quetiapine. Concomitant use may result in additive CNS depression or anticholinergic effects.
Dextromethorphan; Quinidine: (Major) Concomitant use of quinidine and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Diazepam: (Moderate) Monitor for excessive sedation and somnolence during coadministration of diazepam and quetiapine. Concurrent use may result in additive CNS depression.
Dicyclomine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant quetiapine and dicyclomine use. Concomitant use may result in additive anticholinergic adverse effects.
Difelikefalin: (Moderate) Monitor for dizziness, somnolence, mental status changes, and gait disturbances if concomitant use of difelikefalin with CNS depressants is necessary. Concomitant use may increase the risk for these adverse reactions.
Dimenhydrinate: (Moderate) Monitor for unusual drowsiness and sedation, urinary retention, and reduced gastric motility during coadministration of dimenhydrinate and quetiapine. Concomitant use may result in additive CNS depression or anticholinergic effects.
Dipeptidyl Peptidase-4 Inhibitors: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Diphenhydramine: (Moderate) Monitor for unusual drowsiness and sedation, urinary retention, and reduced gastric motility during coadministration of diphenhydramine and quetiapine. Concomitant use may result in additive CNS depression or anticholinergic effects.
Diphenhydramine; Ibuprofen: (Moderate) Monitor for unusual drowsiness and sedation, urinary retention, and reduced gastric motility during coadministration of diphenhydramine and quetiapine. Concomitant use may result in additive CNS depression or anticholinergic effects.
Diphenhydramine; Naproxen: (Moderate) Monitor for unusual drowsiness and sedation, urinary retention, and reduced gastric motility during coadministration of diphenhydramine and quetiapine. Concomitant use may result in additive CNS depression or anticholinergic effects.
Diphenhydramine; Phenylephrine: (Moderate) Monitor for unusual drowsiness and sedation, urinary retention, and reduced gastric motility during coadministration of diphenhydramine and quetiapine. Concomitant use may result in additive CNS depression or anticholinergic effects.
Diphenoxylate; Atropine: (Moderate) Monitor for unusual drowsiness or excess sedation and for signs or symptoms of anticholinergic toxicity during concomitant quetiapine and atropine use. Concomitant use may result in additive CNS depression or anticholinergic adverse effects.
Disopyramide: (Major) Quetiapine should be used cautiously and with close monitoring with disopyramide. Disopyramide is associated with QT prolongation and torsades de pointes (TdP). Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval. Additive anticholinergic effects are also possible with disopyramide, as both quetiapine and disopyramide exhibit significant anticholinergic activity.
Dofetilide: (Major) Concomitant use of quetiapine and dofetilide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Dolasetron: (Major) Concomitant use of quetiapine and dolasetron increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Dolutegravir; Rilpivirine: (Major) Concomitant use of rilpivirine and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. The degree of QT prolongation associated with rilpivirine is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Donepezil: (Major) Concomitant use of quetiapine and donepezil increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Donepezil; Memantine: (Major) Concomitant use of quetiapine and donepezil increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Dopamine: (Major) Antipsychotic agents may inhibit the clinical antiparkinsonian response to therapy by blocking dopamine receptors in the brain. Quetiapine may also cause additive sedation with drugs like dopamine. In general, however, atypical antipsychotics like quetiapine are less likely to interfere with these therapies than traditional antipsychotic agents.
Doxylamine: (Moderate) Monitor for unusual drowsiness and sedation, urinary retention, and reduced gastric motility during coadministration of doxylamine and quetiapine. Concomitant use may result in additive CNS depression or anticholinergic effects.
Doxylamine; Pyridoxine: (Moderate) Monitor for unusual drowsiness and sedation, urinary retention, and reduced gastric motility during coadministration of doxylamine and quetiapine. Concomitant use may result in additive CNS depression or anticholinergic effects.
Dronabinol: (Moderate) Drugs that can cause CNS depression such as dronabinol, if used concomitantly with atypical antipsychotics, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness.
Dronedarone: (Contraindicated) Concomitant use of dronedarone and quetiapine is contraindicated. Dronedarone is an inhibitor of CYP3A. Quetiapine is a substrate for CYP3A4. Coadministration of dronedarone and quetiapine may result in elevated plasma concentrations of quetiapine. In addition, quetiapine has been established to have a possible risk for QT prolongation and Torsade de Pointes (TdP). Dronedarone administration is associated with a dose-related increase in the QTc interval. The increase in QTc is approximately 10 milliseconds at doses of 400 mg twice daily (the FDA-approved dose) and up to 25 milliseconds at doses of 1600 mg twice daily. Although there are no studies examining the effects of dronedarone in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation.
Droperidol: (Major) Concomitant use of quetiapine and droperidol increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Dulaglutide: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and incretin mimetic use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Duloxetine: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant duloxetine and quetiapine use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Duvelisib: (Moderate) Monitor for increased toxicity of quetiapine if coadministered with duvelisib. Coadministration may increase the exposure of quetiapine. Quetiapine is a sensitive CYP3A substrate; duvelisib is a moderate CYP3A inhibitor.
Efavirenz: (Major) Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval, such as efavirenz. In addition, efavirenz may induce the CYP3A4 metabolism of quetiapine, and thus, decrease the serum concentration of quetiapine.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval, such as efavirenz. In addition, efavirenz may induce the CYP3A4 metabolism of quetiapine, and thus, decrease the serum concentration of quetiapine.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval, such as efavirenz. In addition, efavirenz may induce the CYP3A4 metabolism of quetiapine, and thus, decrease the serum concentration of quetiapine.
Elbasvir; Grazoprevir: (Moderate) Administering quetiapine with elbasvir; grazoprevir may result in elevated quetiapine plasma concentrations. Quetiapine is a substrate of CYP3A; grazoprevir is a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of adverse events.
Elexacaftor; tezacaftor; ivacaftor: (Moderate) Use caution when administering ivacaftor and quetiapine concurrently. Ivacaftor is an inhibitor of CYP3A. Co-administration of ivacaftor with CYP3A substrates, such as quetiapine, can increase quetiapine exposure leading to increased or prolonged therapeutic effects and adverse events.
Eliglustat: (Major) Concomitant use of quetiapine and eliglustat increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) The plasma concentrations of quetiapine may be elevated when administered concurrently with cobicistat. The manufacturer of quetiapine recommends a quetiapine dose reduction to one-sixth the original dose during concurrent administration of CYP3A4 inhibitors, such as cobicistat. When cobicistat is discontinued, the dose should be increased by 6-fold.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) The plasma concentrations of quetiapine may be elevated when administered concurrently with cobicistat. The manufacturer of quetiapine recommends a quetiapine dose reduction to one-sixth the original dose during concurrent administration of CYP3A4 inhibitors, such as cobicistat. When cobicistat is discontinued, the dose should be increased by 6-fold.
Empagliflozin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and SGLT2 inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Empagliflozin; Linagliptin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and SGLT2 inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Empagliflozin; Linagliptin; Metformin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and metformin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and SGLT2 inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Empagliflozin; Metformin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and metformin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and SGLT2 inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Major) Concomitant use of rilpivirine and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. The degree of QT prolongation associated with rilpivirine is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Major) Concomitant use of rilpivirine and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. The degree of QT prolongation associated with rilpivirine is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Encorafenib: (Major) Avoid concurrent use of encorafenib with quetiapine due to the risk for decreased quetiapine exposure and efficacy and additive risk for QT/QTc prolongation and torsade de pointes (TdP). If concomitant use is necessary, increase the dose of quetiapine by up to 5-fold. If encorafenib is discontinued, reduce the quetiapine dose to the original level in 7 to 14 days. Additionally, consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring. Quetiapine is a CYP3A substrate, encorafenib is a strong CYP3A inducer, and both medications have been associated with QT/QTc prolongation. Coadministration with another strong CYP3A inducer increased the mean oral clearance of quetiapine by 5-fold.
Entacapone: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or COMT inhibitor during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and COMT inhibitors may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with COMT inhibitors and other Parkinson's treatments than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Entrectinib: (Major) Concomitant use of quetiapine and entrectinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Enzalutamide: (Major) Increase the dose of quetiapine by up to 5-fold if coadministration with enzalutamide is necessary. If enzalutamide is discontinued, reduce the quetiapine dose to the original level in 7 to 14 days. Quetiapine is a sensitive CYP3A4 substrate and enzalutamide is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer increased the mean oral clearance of quetiapine by 5-fold.
Eribulin: (Major) Concomitant use of quetiapine and eribulin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ertugliflozin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and SGLT2 inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Ertugliflozin; Metformin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and metformin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and SGLT2 inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Ertugliflozin; Sitagliptin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and SGLT2 inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Erythromycin: (Major) Concomitant use of quetiapine and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Concomitant use may also increase quetiapine concentrations. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Quetiapine is a CYP3A4 substrate and erythromycin is a moderate CYP3A4 inhibitor. Coadministration of with erythromycin resulted in decreased quetiapine clearance, increased quetiapine plasma concentrations, and prolonged quetiapine half-life. Nineteen patients received quetiapine (200 mg PO twice a day) for roughly 7 days, then erythromycin (500 mg PO 3 times a day) was added for 5 days. Mean quetiapine AUC increased 129% (range 15 to 300%) and the half-life was elevated from 7 to 16 hours.
Escitalopram: (Major) Concomitant use of escitalopram and quietiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Monitor patients for signs and symptoms of serotonin syndrome during concomitant use, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of therapy. The concomitant use of serotonergic drugs increases the risk of serotonin syndrome.
Esketamine: (Major) Closely monitor patients receiving esketamine and quetiapine for sedation and other CNS depressant effects. Instruct patients who receive a dose of esketamine not to drive or engage in other activities requiring alertness until the next day after a restful sleep.
Eslicarbazepine: (Moderate) In vivo studies suggest eslicarbazepine is an inducer of CYP3A4 thereby having the potential to lower the plasma levels of medications metabolized through these pathways. The effectiveness of CNS medications such as quetiapine could theoretically be decreased.
Estazolam: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine; coadministration of quetiapine with anxiolytics, sedatives, and hypnotics, or other CNS depressants may result in additive sedative effects.
Eszopiclone: (Moderate) A reduction in the dose of eszopiclone should be considered during co-administration of other CNS depressants, such as antipsychotics, to minimize additive sedative effects. In addition, the risk of next-day psychomotor impairment is increased during co-administration of eszopiclone and other CNS depressants, which may decrease the ability to perform tasks requiring full mental alertness such as driving. Antipsychotics with a higher incidence of sedation, such as olanzapine, clozapine, quetiapine, lurasidone, chlorpromazine, and thioridazine, are more likely to interact with eszopiclone. In one evaluation, concurrent use of eszopiclone and olanzapine reduced psychomotor function as measured by the Digit Symbol Substitution Test (DSST).
Ethanol: (Major) Advise patients to avoid alcohol consumption while taking CNS depressants. Alcohol consumption may result in additive CNS depression.
Ethiodized Oil: (Major) Quetiapine lowers the seizure threshold and should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Etrasimod: (Major) Concomitant use of etrasimod and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Etrasimod has a limited effect on the QT/QTc interval at therapeutic doses but may cause bradycardia and atrioventricular conduction delays which may increase the risk for TdP in patients with a prolonged QT/QTc interval.
Exenatide: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and incretin mimetic use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Fenfluramine: (Moderate) Use fenfluramine and quetiapine with caution due to an increased risk of serotonin syndrome and additive CNS depression. Monitor for excessive sedation, somnolence, and serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Fentanyl: (Major) Concomitant use of opioid agonists with quetiapine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with quetiapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Fesoterodine: (Moderate) When coadministering quetiapine and fesoterodine, monitor for additive anticholinergic effects such as constipation, blurred vision, urinary retention, xerostomia, and tachycardia. Constipation is a commonly reported adverse effect of quetiapine and anticholinergic agents such as fesoterodine. Constipation may lead to ileus. Intestinal obstruction has been reported with quetiapine, including fatal cases in patients who were receiving multiple concomitant medications that decrease intestinal motility. Anticholinergic effects observed during therapeutic use of quetiapine are thought to be associated with norquetiapine, an active metabolite of quetiapine which has demonstrated a moderate to strong in vitro binding affinity for several muscarinic receptor subtypes.
Fexinidazole: (Major) Concomitant use of fexinidazole and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Fingolimod: (Major) Concomitant use of quetiapine and fingolimod increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Flavoxate: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant quetiapine and flavoxate use. Concomitant use may result in additive anticholinergic adverse effects.
Flecainide: (Major) Concomitant use of flecainide and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Fluconazole: (Contraindicated) Concurrent use of fluconazole and quetiapine is contraindicated due to the risk of life threatening arrhythmias such as torsade de pointes (TdP). Fluconazole is an inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of quetiapine. These drugs used in combination may result in elevated quetiapine plasma concentrations, causing an increased risk for quetiapine-related adverse events, such as QT prolongation. Additionally, fluconazole has been associated with prolongation of the QT interval; do not use with other drugs that may prolong the QT interval and are metabolized through CYP3A4, such as quetiapine.
Fluoxetine: (Major) Avoid use together if possible. Coadministration may increase the risk for QT prolongation and torsade de pointes. Caution is also advised since both drugs act on the CNS. If use together is necessary, consider using lower initial doses of the concomitantly administered drugs, using conservative titration schedules, and monitoring of clinical status. According to the manufacturer of quetiapine, other drugs having an association with QT prolongation should not be used with quetiapine. QT prolongation and torsade de pointes (TdP) have been reported during postmarketing use of fluoxetine. The manufacturer of fluoxetine recommends caution with combined use. The effects of fluoxetine on interacting drugs may persist for several weeks after discontinuation of fluoxetine because of its long elimination half-life. In a study conducted by the manufacturer, concurrent use of 60 mg/day of fluoxetine and 300 mg twice daily of quetiapine did not alter the pharmacokinetics of quetiapine.
Fluphenazine: (Moderate) Concurrent use of quetiapine and fluphenazine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Fluphenazine, a phenothiazine, is associated with a possible risk for QT prolongation. Limited data, including some case reports, suggest that quetiapine may also be associated with a significant prolongation of the QTc interval in rare instances. In addition, co-administration of quetiapine with phenothiazines may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The likelihood of pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Flurazepam: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine; coadministration of quetiapine with anxiolytics, sedatives, and hypnotics, or other CNS depressants may result in additive sedative effects.
Fluvoxamine: (Major) There may be an increased risk for QT prolongation, torsade de pointes (TdP), and elevated quetiapine concentrations during concurrent use of fluvoxamine and quetiapine. Cases of QT prolongation and TdP have been reported during postmarketing use of fluvoxamine. The manufacturer of quetiapine recommends avoiding combined use of quetiapine with drugs known to increase the QT interval. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. In addition, fluvoxamine is a moderate CYP3A4 inhibitor and may decrease the clearance of CYP3A4 substrates such as quetiapine. Decreased metabolism of quetiapine may lead to adverse effects such as orthostatic hypotension, sedation, QT prolongation, or extrapyramidal symptoms.
Food: (Major) Advise patients to avoid cannabis use while taking CNS depressants due to the risk for additive CNS depression and potential for other cognitive adverse reactions.
Fosamprenavir: (Major) Avoid concurrent use of quetiapine, a CYP3A4 substrate, and fosamprenavir, a potent CYP3A4 inhibitor, due to the potential for increased exposure to quetiapine. If administration of fosamprenavir is required in a patient taking quetiapine, reduce the quetiapine dose to one sixth of the current dose. If fosamprenavir is discontinued, increase the quetiapine dose by 6-fold.
Foscarnet: (Major) Concomitant use of quetiapine and foscarnet increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Fosphenytoin: (Major) Increase the dose of quetiapine by up to 5-fold if coadministered with fosphenytoin. Coadministration may significantly decrease quetiapine exposure leading to reduced efficacy. If fosphenytoin is discontinued, reduce the quetiapine dose to the original level in 7 to 14 days. Quetiapine is a sensitive CYP3A4 substrate and fosphenytoin is a strong CYP3A4 inducer. Coadministration with phenytoin increased the mean oral clearance of quetiapine by 5-fold.
Fostemsavir: (Major) Concomitant use of quetiapine and fostemsavir increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. The degree of QT prolongation associated with fostemsavir is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 2 times the maximum recommended dose.
Gabapentin: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and quetiapine. Concomitant use of gabapentin with quetiapine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
Ganirelix: (Moderate) Antipsychotic-induced hyperprolactinemia results in down-regulation of the number of pituitary GnRH receptors and may interfere with the response to ganirelix, a gonadotropin-releasing hormone (GnRH) analog.
Gemifloxacin: (Major) Concomitant use of quetiapine and gemifloxacin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Gemtuzumab Ozogamicin: (Major) Concomitant use of quetiapine and gemtuzumab ozogamicin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Gilteritinib: (Major) Concomitant use of quetiapine and gilteritinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Glasdegib: (Major) Concomitant use of quetiapine and glasdegib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Glimepiride: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and sulfonylurea use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Glipizide: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and sulfonylurea use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Glipizide; Metformin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and metformin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and sulfonylurea use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Glyburide: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and sulfonylurea use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Glyburide; Metformin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and metformin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and sulfonylurea use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Glycopyrrolate: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant quetiapine and glycopyrrolate use. Concomitant use may result in additive anticholinergic adverse effects.
Glycopyrrolate; Formoterol: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant quetiapine and glycopyrrolate use. Concomitant use may result in additive anticholinergic adverse effects.
Goserelin: (Major) Concomitant use of quetiapine and goserelin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Granisetron: (Major) Concomitant use of quetiapine and granisetron increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Halogenated Anesthetics: (Major) Concomitant use of quetiapine and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Haloperidol: (Major) Quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs that have established causal association with QT prolongation and TdP (torsade de pointes), like haloperidol. Coadministration may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Histrelin: (Major) Concomitant use of quetiapine and histrelin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Homatropine; Hydrocodone: (Major) Concomitant use of opioid agonists with quetiapine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with quetiapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. Avoid prescribing opioid cough medication in patients taking quetiapine. (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant quetiapine and homatropine use. Concomitant use may result in additive anticholinergic adverse effects.
Hydrocodone: (Major) Concomitant use of opioid agonists with quetiapine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with quetiapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. Avoid prescribing opioid cough medication in patients taking quetiapine.
Hydrocodone; Ibuprofen: (Major) Concomitant use of opioid agonists with quetiapine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with quetiapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. Avoid prescribing opioid cough medication in patients taking quetiapine.
Hydromorphone: (Major) Concomitant use of opioid agonists with quetiapine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with quetiapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Hydroxychloroquine: (Major) Concomitant use of hydroxychloroquine and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Hydroxyzine: (Major) Concomitant use of hydroxyzine and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). In addition, because hydroxyzine causes pronounced sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including quetiapine. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Hyoscyamine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant quetiapine and hyoscyamine use. Concomitant use may result in additive anticholinergic adverse effects.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant quetiapine and hyoscyamine use. Concomitant use may result in additive anticholinergic adverse effects.
Ibuprofen; Oxycodone: (Major) Concomitant use of opioid agonists with quetiapine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with quetiapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Ibutilide: (Major) Concomitant use of quetiapine and ibutilide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Idelalisib: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with quetiapine, a CYP3A substrate, as quetiapine toxicities may be significantly increased. If coadministration cannot be avoided, the manufacturer of quetiapine recommends reducing the dose of quetiapine to one sixth of the current dose in combination with a potent CYP3A4 inhibitor. When the CYP3A4 inhibitor is discontinued, the dose of quetiapine should be increased by 6-fold. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Iloperidone: (Major) Iloperidone has been associated with QT prolongation; however, torsade de pointes (TdP) has not been reported. According to the manufacturer, since iloperidone may prolong the QT interval, it should be avoided in combination with other agents also known to have this effect, such as quetiapine. Quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. In addition, coadministration may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Imatinib: (Moderate) The cytochrome P450 3A4 isoenzyme is involved in the metabolism of quetiapine. Imatinib, STI-571 may increase plasma concentrations of quetiapine through CYP3A4 inhibition. The manufacturer of quetiapine recommends a reduced dosage during concurrent administration of CYP3A4 inhibitors.
Incretin Mimetics: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and incretin mimetic use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Indacaterol; Glycopyrrolate: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant quetiapine and glycopyrrolate use. Concomitant use may result in additive anticholinergic adverse effects.
Indinavir: (Major) Avoid concurrent use of quetiapine and anti-retroviral protease inhibitors, such as indinavir. Indinavir may inhibit the CYP3A4 metabolism of quetiapine, resulting in elevated quetiapine plasma concentrations. If administration of indinavir is required in a patient taking quetiapine, reduce the quetiapine dose to one sixth of the current dose and monitor for quetiapine-related adverse events. If indinavir is discontinued, increase the quetiapine dose by 6-fold.
Inotuzumab Ozogamicin: (Major) Concomitant use of quetiapine and inotuzumab increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Insulin Aspart: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and insulin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Insulin Aspart; Insulin Aspart Protamine: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and insulin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Insulin Degludec: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and insulin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Insulin Degludec; Liraglutide: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and incretin mimetic use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and insulin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Insulin Detemir: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and insulin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Insulin Glargine: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and insulin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Insulin Glargine; Lixisenatide: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and incretin mimetic use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and insulin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Insulin Glulisine: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and insulin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Insulin Lispro: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and insulin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Insulin Lispro; Insulin Lispro Protamine: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and insulin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Insulin, Inhaled: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and insulin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Insulins: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and insulin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Iodixanol: (Major) Quetiapine lowers the seizure threshold and should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Iohexol: (Major) Quetiapine lowers the seizure threshold and should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Iomeprol: (Major) Quetiapine lowers the seizure threshold and should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Iopamidol: (Major) Quetiapine lowers the seizure threshold and should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Iopromide: (Major) Quetiapine lowers the seizure threshold and should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Ioversol: (Major) Quetiapine lowers the seizure threshold and should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Isavuconazonium: (Moderate) Concomitant use of isavuconazonium with quetiapine may result in increased serum concentrations of quetiapine. Quetiapine is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Isocarboxazid: (Major) Avoid concomitant use, or use in rapid succession, of monoamine oxidase inhibitors (MAOIs) and quetiapine. If concomitant use is necessary, monitor for signs and symptoms of serotonin syndrome, blood pressure, and for unusual drowsiness and sedation. Concomitant use increases the risk for serotonin syndrome and additive hypotension and CNS depression. If serotonin syndrome occurs, discontinue therapy.
Isoflurane: (Major) Concomitant use of quetiapine and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Coadministration of rifampin, a potent CYP3A4 inducer, with quetiapine, a CYP3A4 substrate, may result in decreased exposure to quetiapine. The dose of quetiapine should be increased by up to 5-fold when combined with chronic administration (7 to 14 days) of a potent CYP3A4 inducer. Adjust the dose based on patient response and tolerability. When the potent CYP3A4 inducer is discontinued, the quetiapine dose should be reduced to the original dose within 1 to 2 weeks.
Isoniazid, INH; Rifampin: (Major) Coadministration of rifampin, a potent CYP3A4 inducer, with quetiapine, a CYP3A4 substrate, may result in decreased exposure to quetiapine. The dose of quetiapine should be increased by up to 5-fold when combined with chronic administration (7 to 14 days) of a potent CYP3A4 inducer. Adjust the dose based on patient response and tolerability. When the potent CYP3A4 inducer is discontinued, the quetiapine dose should be reduced to the original dose within 1 to 2 weeks.
Isophane Insulin (NPH): (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and insulin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Isosulfan Blue: (Major) Quetiapine lowers the seizure threshold and should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Itraconazole: (Major) Avoid coadministration of itraconazole with quetiapine due to the potential for additive effects on the QT interval; increased exposure to quetiapine may also occur. Both quetiapine and itraconazole are associated with QT prolongation; coadministration may increase this risk. In addition, coadministration of itraconazole (a potent CYP3A4 inhibitor) with quetiapine (a CYP3A4 substrate) may result in elevated quetiapine plasma concentrations and could increase the risk for adverse events, including QT prolongation. The manufacturer recommends a quetiapine dose reduction to one-sixth the original dose during concurrent administration of CYP3A4 inhibitors, such as itraconazole. When itraconazole is discontinued, the dose should be increased by 6-fold. Of note, once itraconazole is discontinued, plasma concentrations decrease to almost undetectable concentrations within 7 to 14 days. The decline in plasma concentrations may be even more gradual in patients with hepatic cirrhosis or who are receiving concurrent CYP3A4 inhibitors.
Ivacaftor: (Moderate) Use caution when administering ivacaftor and quetiapine concurrently. Ivacaftor is an inhibitor of CYP3A. Co-administration of ivacaftor with CYP3A substrates, such as quetiapine, can increase quetiapine exposure leading to increased or prolonged therapeutic effects and adverse events.
Ivosidenib: (Major) Avoid coadministration of ivosidenib with quetiapine due to an increased risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QTc prolongation and monitor electrolytes; correct any electrolyte abnormalities as clinically appropriate. An interruption of therapy and dose reduction of ivosidenib may be necessary if QT prolongation occurs. Additionally, monitor for loss of efficacy of quetiapine during coadministration of ivosidenib; a quetiapine dose adjustment may be necessary. Quetiapine is a sensitive substrate of CYP3A4; ivosidenib induces CYP3A4 and may lead to decreased quetiapine concentrations. Prolongation of the QTc interval and ventricular arrhythmias have been reported in patients treated with ivosidenib. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances.
Ketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and quetiapine due to an increased risk for QT prolongation and a risk for torsade de pointes (TdP). Concomitant use may also increase the exposure of quetiapine, further increasing the risk for adverse effects. If concomitant use is necessary, reduce the dose of quetiapine to one-sixth the original dose; consider monitoring ECG and serum electrolytes. Quetiapine is a CYP3A substrate and ketoconazole is a strong CYP3A inhibitor. Coadministration with ketoconazole increased the exposure of quetiapine by approximately 6-fold.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Avoid concurrent use of quetiapine and clarithromycin due to the potential for additive effects on the QT interval and torsade de pointes (TdP) and the potential for greatly increased quetiapine exposure. Clarithromycin is a potent inhibitor of CYP3A4 that is expected to signficantly reduce metabolism of quetiapine. If administration of clarithromycin is required in a patient taking quetiapine, reduce the quetiapine dose to one sixth of the current dose. Monitor for quetiapine-related side effects. If clarithromycin is discontinued, increase the quetiapine dose by 6-fold. Clarithromycin has an established causal association with QT prolongation and TdP (torsade de pointes). Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances.
Lapatinib: (Major) Concomitant use of quetiapine and lapatinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Lasmiditan: (Moderate) Monitor for excessive sedation, somnolence, and serotonin syndrome during coadministration of lasmiditan and quetiapine. Inform patients taking this combination of the risks and symptoms of excessive CNS depression and serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Lefamulin: (Major) Coadministration of lefamulin tablets is contraindicated with quetiapine due to increased quetiapine exposure which may result in QT prolongation and torsade de pointes (TdP). Avoid use of lefamulin injection with quetiapine. If coadministration of lefamulin injection cannot be avoided, ECG monitoring is recommended during treatment. Quetiapine is a sensitive CYP3A4 substrate that may be associated with a significant prolongation of the QTc interval in rare instances. Lefamulin is a CYP3A4 inhibitor that has a concentration dependent QTc prolongation effect. The pharmacodynamic interaction potential to prolong the QT interval of the electrocardiogram between lefamulin and other drugs that effect cardiac conduction is unknown.
Lemborexant: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and atypical antipsyhotics. Dosage adjustments of lemborexant and the atypical antipsychotic may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Lenvatinib: (Major) Concomitant use of quetiapine and lenvatinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Letermovir: (Moderate) Caution is advised when administering quetiapine with letermovir, as taking these drugs together may increase quetiapine concentration and risk for adverse events. Reduce the quetiapine dose to 1/6 the original dose in patients also receiving cyclosporine, because the magnitude of this interaction may be increased. If letermovir or cyclosporine are discontinued, the quetiapine dose should be increased by 6-fold. Quetiapine is a substrate of CYP3A4. Letermovir is a moderate CYP3A4 inhibitor; however, when given with cyclosporine, the combined effect on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor. Concurrent administration with another strong CYP3A4 inhibitors decreased quetiapine clearance by 84%, thereby resulting in a 6.2-fold increase in quetiapine exposure (AUC).
Leuprolide: (Major) Concomitant use of quetiapine and leuprolide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Leuprolide; Norethindrone: (Major) Concomitant use of quetiapine and leuprolide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Levocetirizine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of atypical antipsychotics and cetirizine due to the risk for additive CNS depression.
Levodopa: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or levodopa during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and levodopa may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with levodopa and other antiparkinson's treatments than traditional antipsychotics.
Levofloxacin: (Major) Concomitant use of levofloxacin and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Levoketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and quetiapine due to an increased risk for QT prolongation and a risk for torsade de pointes (TdP). Concomitant use may also increase the exposure of quetiapine, further increasing the risk for adverse effects. If concomitant use is necessary, reduce the dose of quetiapine to one-sixth the original dose; consider monitoring ECG and serum electrolytes. Quetiapine is a CYP3A substrate and ketoconazole is a strong CYP3A inhibitor. Coadministration with ketoconazole increased the exposure of quetiapine by approximately 6-fold.
Levorphanol: (Major) Concomitant use of opioid agonists with quetiapine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with quetiapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Reduce the initial dose of levorphanol by approximately 50% or more. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Linagliptin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Linagliptin; Metformin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and metformin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Liraglutide: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and incretin mimetic use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Lithium: (Major) Concomitant use of lithium and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP) as well as an encephalopathic syndrome that may be similar to or the same as neuroleptic malignant syndrome. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Monitor for early evidence of neurologic toxicity and discontinue treatment promptly if such signs appear. An encephalopathic syndrome has occurred in a few patients treated with lithium plus a neuroleptic. In some instances, the syndrome was followed by irreversible brain damage.
Lixisenatide: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and incretin mimetic use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Lofexidine: (Major) Avoid coadministration of lofexidine and quetiapine due to the potential for additive QT prolongation. Monitor ECG if coadministration cannot be avoided. Additionally, monitor for excessive hypotension and sedation during coadministration as lofexidine can potentiate the effects of CNS depressants. Lofexidine prolongs the QT interval. In addition, there are postmarketing reports of torsade de pointes. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances.
Lonafarnib: (Major) Reduce quetiapine dose to one sixth when coadministered with lonafarnib. Coadministration may significantly increase quetiapine exposure and related side effects. If lonafarnib is discontinued, increase the quetiapine dose by 6-fold. Quetiapine is a sensitive CYP3A4 substrate and lonafarnib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the exposure of quetiapine by approximately 6-fold.
Loperamide: (Major) Concomitant use of loperamide and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Loperamide; Simethicone: (Major) Concomitant use of loperamide and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Lopinavir; Ritonavir: (Major) Concomitant use of quetiapine and lopinavir increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. (Major) The manufacturer of quetiapine recommends a quetiapine dose reduction to one-sixth the original dose during concurrent administration of strong CYP3A4 inhibitors, such as ritonavir. When ritonavir is discontinued, the dose should be increased by 6-fold. The plasma concentrations of quetiapine may be elevated when administered concurrently with ritonavir.
Lorazepam: (Moderate) Monitor for excessive sedation and somnolence during coadministration of alprazolam and quetiapine. Concurrent use may result in additive CNS depression. Quetiapine decreases lorazepam clearance by about 20%.
Lovastatin: (Moderate) In a published case, it has been hypothesized that the combination of lovastatin and quetiapine resulted in prolongation of the QTc interval. The suggested mechanism is competitive inhibition of the CYP3A4 isoenzyme leading to elevated quetiapine plasma concentrations. Both lovastatin and quetiapine are CYP3A4 substrates. The QTc interval returned to baseline when the lovastatin dose was reduced. The clinical significance and reproducibility of this interaction is unknown.
Loxapine: (Major) Caution is advisable during concurrent use of loxapine and other antipsychotics. Loxapine use has been associated with adverse events such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, and seizures. These effects may be potentiated during concurrent use of loxapine and other antipsychotics. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Lumacaftor; Ivacaftor: (Major) Lumacaftor; ivacaftor may reduce the efficacy of quetiapine by decreasing its systemic exposure. When used in combination with chronic lumacaftor; ivacaftor treatment (i.e., more than 7 to 14 days), titrate the quetiapine dosage based on clinical response and tolerability. Patients taking strong CYP3A4 inducers may require up to 5-fold of the original quetiapine dose to achieve therapeutic efficacy. If lumacaftor; ivacaftor is subsequently discontinued, reduce the quetiapine to its original dose within 7 to 14 days of discontinuation. Quetiapine is a CYP3A substrate, and lumacaftor is a strong CYP3A inducer. (Moderate) Use caution when administering ivacaftor and quetiapine concurrently. Ivacaftor is an inhibitor of CYP3A. Co-administration of ivacaftor with CYP3A substrates, such as quetiapine, can increase quetiapine exposure leading to increased or prolonged therapeutic effects and adverse events.
Lumacaftor; Ivacaftor: (Major) Lumacaftor; ivacaftor may reduce the efficacy of quetiapine by decreasing its systemic exposure. When used in combination with chronic lumacaftor; ivacaftor treatment (i.e., more than 7 to 14 days), titrate the quetiapine dosage based on clinical response and tolerability. Patients taking strong CYP3A4 inducers may require up to 5-fold of the original quetiapine dose to achieve therapeutic efficacy. If lumacaftor; ivacaftor is subsequently discontinued, reduce the quetiapine to its original dose within 7 to 14 days of discontinuation. Quetiapine is a CYP3A substrate, and lumacaftor is a strong CYP3A inducer.
Lumateperone: (Moderate) Coadministration of antipsychotics, such as lumateperone and quetiapine, may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. Although the incidence of tardive dyskinesia from antipsychotic combinations has not been established and data are very limited, the risk may be increased during combined use versus use of an antipsychotic alone.
Lurasidone: (Major) Similar to other antipsychotics, lurasidone administration has been associated with drowsiness, dizziness, orthostatic hypotension, extrapyramidal symptoms, neuroleptic malignant syndrome, and seizures. The risk of these adverse effects may be increased during concurrent use of lurasidone with other antipsychotics. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Macimorelin: (Major) Concomitant use of quetiapine and macimorelin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Maprotiline: (Major) Concomitant use of quetiapine and maprotiline increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Meclizine: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine. Co-administration of quetiapine with sedating H1-blockers may result in additive effects. Additive drowsiness or other CNS effects may occur.
Mefloquine: (Major) Concomitant use of quetiapine and mefloquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Meglitinides: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Meperidine: (Major) Concomitant use of opioid agonists with quetiapine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with quetiapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Meprobamate: (Moderate) The CNS-depressant effects of meprobamate can be potentiated with concomitant administration of other drugs known to cause CNS depression including antipsychotics.
Metformin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and metformin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Metformin; Repaglinide: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and metformin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Metformin; Saxagliptin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and metformin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Metformin; Sitagliptin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and metformin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Methadone: (Major) Concurrent use of quetiapine and methadone should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). The need to coadminister these drugs should be done with extreme caution and a careful assessment of treatment risks versus benefits. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. Methadone is also considered to be associated with an increased risk for QT prolongation and TdP, especially at higher doses averaging approximately 400 mg/day in adult patients. In addition, concomitant use of methadone with another CNS depressant, such as quetiapine, can lead to additive respiratory depression, hypotension, profound sedation, or coma. Prior to concurrent use of methadone in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Consider the patient's use of alcohol or illicit drugs. Methadone should be used with caution and in reduced dosages if used concurrently with a CNS depressant; also consider a using a lower dose of the CNS depressant. Monitor patients for sedation and respiratory depression.
Methazolamide: (Moderate) Caution is advisable during concurrent use of quetiapine and methazolamide as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with quetiapine.
Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant quetiapine and hyoscyamine use. Concomitant use may result in additive anticholinergic adverse effects.
Methohexital: (Major) Coadministration of barbiturates, potent CYP3A4 inducers, with quetiapine, a CYP3A4 substrate, may result in decreased exposure to quetiapine. The dose of quetiapine should be increased by up to 5-fold when combined with chronic administration (7 to 14 days) of a potent CYP3A4 inducer. Adjust the dose based on patient response and tolerability. When the potent CYP3A4 inducer is discontinued, the quetiapine dose should be reduced to the original dose within 1 to 2 weeks. Also, somnolence is a commonly reported adverse effect of quetiapine; coadministration of quetiapine with barbiturates may result in additive sedative effects.
Methscopolamine: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant quetiapine and methscopolamine use. Concomitant use may result in additive anticholinergic adverse effects.
Metoclopramide: (Contraindicated) Avoid metoclopramide in patients receiving atypical antipsychotics. There is a potential for additive effects, including increased frequency and severity of tardive dyskinesia (TD), other extrapyramidal symptoms (EPS), and neuroleptic malignant syndrome (NMS). Some manufacturer labels for metoclopramide contraindicate the use of these drugs together, while others state avoidance is necessary. If these agents must be used together, monitor closely for movement disorders and additive CNS effects. There also may be additive sedation. Discontinue these medications at the first signs of dyskinesia.
Metronidazole: (Major) Concomitant use of metronidazole and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Midazolam: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine; coadministration of quetiapine with anxiolytics, sedatives, and hypnotics, or other CNS depressants may result in additive sedative effects.
Midostaurin: (Major) Concomitant use of quetiapine and midostaurin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Mifepristone: (Major) Concomitant use of quetiapine and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Concomitant use may also increase the exposure of quetiapine, further increasing the risk for adverse effects. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. If concomitant use is necessary, reduce the dose of quetiapine to one-sixth the original dose and consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring. Quetiapine is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor.
Miglitol: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Mirtazapine: (Major) Concomitant use of quetiapine and mirtazapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Also monitor for unusual drowsiness, sedation, and serotonin syndrome during coadministration due to the risk for additive CNS depression and serotonin syndrome.
Mitotane: (Major) Use caution if mitotane and quetiapine are used concomitantly. If quetiapine is used with chronic (> 7 to 10 days) mitotane treatment, increase the dose of quetiapine by up to 5-fold, based on clinical response and tolerability. When mitotane is discontinued, reduce the dose of quetiapine to the original level within 7 to 14 days. Mitotane is a strong CYP3A4 inducer and quetiapine is a CYP3A4 substrate; coadministration may result in decreased plasma concentrations of quetiapine. Additionally, mitotane can cause sedation, lethargy, vertigo, and other CNS adverse reactions; additive CNS effects may occur initially when mitotane is given concurrently with quetiapine.
Mobocertinib: (Major) Concomitant use of mobocertinib and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Molindone: (Major) Close monitoring is advisable during concurrent use of molindone with other antipsychotics. Because molindone shares certain pharmacological properties with other antipsychotics, additive cardiac effects (e.g., hypotension), CNS effects (e.g., drowsiness), anticholinergic effects (e.g., constipation, xerostomia), extrapyramidal effects, neuroleptic malignant syndrome, or seizures may occur. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Monoamine oxidase inhibitors: (Major) Avoid concomitant use, or use in rapid succession, of monoamine oxidase inhibitors (MAOIs) and quetiapine. If concomitant use is necessary, monitor for signs and symptoms of serotonin syndrome, blood pressure, and for unusual drowsiness and sedation. Concomitant use increases the risk for serotonin syndrome and additive hypotension and CNS depression. If serotonin syndrome occurs, discontinue therapy.
Morphine: (Major) Concomitant use of opioid agonists with quetiapine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with quetiapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at one-third to one-half the recommended starting dosage. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Morphine; Naltrexone: (Major) Concomitant use of opioid agonists with quetiapine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with quetiapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at one-third to one-half the recommended starting dosage. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Moxifloxacin: (Major) Concomitant use of quetiapine and moxifloxacin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Nabilone: (Moderate) Drugs that can cause CNS depression, if used concomitantly with atypical antipsychotics, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness.
Nafarelin: (Moderate) Antipsychotics may cause hyperprolactinemia and should not be administered concomitantly with nafarelin since hyperprolactinemia down-regulates the number of pituitary GnRH receptors.
Nalbuphine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lumateperone and nalbuphine. Concurrent use may result in additive CNS depression.
Nateglinide: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Nefazodone: (Major) Nefazodone may inhibit the CYP3A4 metabolism of quetiapine, resulting in elevated quetiapine plasma concentrations. If administration of nefazodone is required in a patient taking quetiapine, reduce the quetiapine dose to one sixth of the current dose and monitor for quetiapine-related adverse events. If nefazodone is discontinued, increase the quetiapine dose by 6-fold.
Nelfinavir: (Major) Avoid concurrent use of quetiapine and nelfinavir. Nelfinavir may inhibit the CYP3A4 metabolism of quetiapine, resulting in elevated quetiapine plasma concentrations. If administration of nelfinavir is required in a patient taking quetiapine, reduce the quetiapine dose to one sixth of the current dose. If nelfinavir is discontinued, increase the quetiapine dose by 6-fold.
Neostigmine; Glycopyrrolate: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant quetiapine and glycopyrrolate use. Concomitant use may result in additive anticholinergic adverse effects.
Nilotinib: (Major) Avoid the concomitant use of nilotinib with other agents that prolong the QT interval, such as quetiapine. Additionally, nilotinib is a moderate inhibitor of CYP3A4 and quetiapine is a substrate of CYP3A4; administering these drugs together may result in increased quetiapine levels. If the use of quetiapine is necessary, hold nilotinib therapy. If these drugs are used together, consider a quetiapine dose reduction and monitor patients for toxicity (e.g., QT interval prolongation).
Nirmatrelvir; Ritonavir: (Major) The manufacturer of quetiapine recommends a quetiapine dose reduction to one-sixth the original dose during concurrent administration of strong CYP3A4 inhibitors, such as ritonavir. When ritonavir is discontinued, the dose should be increased by 6-fold. The plasma concentrations of quetiapine may be elevated when administered concurrently with ritonavir.
Non-Ionic Contrast Media: (Major) Quetiapine lowers the seizure threshold and should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Ofloxacin: (Major) Concomitant use of ofloxacin and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Olanzapine: (Major) Concurrent use of quetiapine and olanzapine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Limited data, including some case reports, suggest that both olanzapine and quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. In addition, co-administration of quetiapine with olanzapine may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The likelihood of pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Olanzapine; Fluoxetine: (Major) Avoid use together if possible. Coadministration may increase the risk for QT prolongation and torsade de pointes. Caution is also advised since both drugs act on the CNS. If use together is necessary, consider using lower initial doses of the concomitantly administered drugs, using conservative titration schedules, and monitoring of clinical status. According to the manufacturer of quetiapine, other drugs having an association with QT prolongation should not be used with quetiapine. QT prolongation and torsade de pointes (TdP) have been reported during postmarketing use of fluoxetine. The manufacturer of fluoxetine recommends caution with combined use. The effects of fluoxetine on interacting drugs may persist for several weeks after discontinuation of fluoxetine because of its long elimination half-life. In a study conducted by the manufacturer, concurrent use of 60 mg/day of fluoxetine and 300 mg twice daily of quetiapine did not alter the pharmacokinetics of quetiapine. (Major) Concurrent use of quetiapine and olanzapine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Limited data, including some case reports, suggest that both olanzapine and quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. In addition, co-administration of quetiapine with olanzapine may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The likelihood of pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Olanzapine; Samidorphan: (Major) Concurrent use of quetiapine and olanzapine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Limited data, including some case reports, suggest that both olanzapine and quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. In addition, co-administration of quetiapine with olanzapine may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The likelihood of pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Oliceridine: (Major) Concomitant use of oliceridine with quetiapine may cause excessive sedation and somnolence. Limit the use of oliceridine with quetiapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Omeprazole; Amoxicillin; Rifabutin: (Moderate) Increased doses of quetiapine may be required to maintain symptom control if rifabutin is used concomitantly. Rifabutin is a less potent inducer of CYP3A4 than rifampin, a potent inducer. However, increased doses of quetiapine up to 5 fold may be required to maintain control of symptoms in patients receiving quetiapine and known potent CYP3A4 inducers. There are no specific recommendations for moderate inducers. When rifabutin is discontinued, the dose of quetiapine should be reduced to the original level within 7 to 14 days.
Ondansetron: (Major) Avoid coadministration of ondansetron and quetiapine due to the risk of QT prolongation. Monitor ECG for evidence of QT prolongation if concurrent use cannot be avoided. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. Ondansetron has been associated with a dose-related increase in the QT interval and postmarketing reports of torsade de pointes (TdP).
Opicapone: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or COMT inhibitor during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and COMT inhibitors may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with COMT inhibitors and other Parkinson's treatments than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Oritavancin: (Moderate) Quetiapine is metabolized by CYP3A4; oritavancin is a weak CYP3A4 inducer. Plasma concentrations and efficacy of quetiapine may be reduced if these drugs are administered concurrently.
Osilodrostat: (Major) Concomitant use of quetiapine and osilodrostat increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Osimertinib: (Major) Concomitant use of quetiapine and osimertinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Oxaliplatin: (Major) Concomitant use of quetiapine and oxaliplatin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Oxazepam: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine; coadministration of quetiapine with anxiolytics, sedatives, and hypnotics, or other CNS depressants may result in additive sedative effects.
Oxybutynin: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant quetiapine and oxybutynin use. Concomitant use may result in additive anticholinergic adverse effects.
Oxycodone: (Major) Concomitant use of opioid agonists with quetiapine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with quetiapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Oxymorphone: (Major) Concomitant use of opioid agonists with quetiapine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with quetiapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Reduce the initial oxymorphone dosage by one-third to one-half. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Ozanimod: (Major) In general, do not initiate ozanimod in patients taking quetiapine due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). Additionally, there is a potential for hypertensive crisis. If treatment initiation is considered, seek advice from a cardiologist and monitor for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Ozanimod may also result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Quetiapine is a serotonergic drug that has been associated with a significant prolongation of the QTc interval in rare instances.
Pacritinib: (Major) Concomitant use of pacritinib and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Paliperidone: (Major) Paliperidone has been associated with QT prolongation; torsade de pointes (TdP) and ventricular fibrillation have been reported in the setting of overdose. According to the manufacturer, since paliperidone may prolong the QT interval, it should be avoided in combination with other agents also known to have this effect, such as quetiapine. In addition, coadministration may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, tardive dyskinesia, or seizures. If coadministration is considered necessary and the patient has known risk factors for cardiac disease or arrhythmias, close monitoring is essential.
Panobinostat: (Major) Concomitant use of quetiapine and panobinostat increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Paroxetine: (Moderate) Monitor patients for signs and symptoms of serotonin syndrome during concomitant use of paroxetine and quetiapine, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of therapy. The concomitant use of serotonergic drugs increases the risk of serotonin syndrome.
Pasireotide: (Major) Concomitant use of quetiapine and pasireotide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Pazopanib: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval is not advised; pazopanib has been reported to prolong the QT interval. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. If pazopanib and quetiapine must be continued, closely monitor the patient for QT interval prolongation. In addition, pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and quetiapine, a CYP3A4 substrate, may cause an increase in systemic concentrations of quetiapine. Use caution when concurrent administration is necessary.
Pentamidine: (Major) Concomitant use of quetiapine and pentamidine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Pentazocine; Naloxone: (Moderate) Coadministration of pentazocine with atypical antipsychotics may result in additive respiratory and CNS depression and anticholinergic effects, such as urinary retention and constipation. Use pentazocine with caution in any patient receiving medication with CNS depressant and/or anticholinergic activity.
Pentobarbital: (Major) Coadministration of barbiturates, potent CYP3A4 inducers, with quetiapine, a CYP3A4 substrate, may result in decreased exposure to quetiapine. The dose of quetiapine should be increased by up to 5-fold when combined with chronic administration (7 to 14 days) of a potent CYP3A4 inducer. Adjust the dose based on patient response and tolerability. When the potent CYP3A4 inducer is discontinued, the quetiapine dose should be reduced to the original dose within 1 to 2 weeks. Also, somnolence is a commonly reported adverse effect of quetiapine; coadministration of quetiapine with barbiturates may result in additive sedative effects.
Perampanel: (Moderate) Co-administration of perampanel with CNS depressants, including ethanol, may increase CNS depression. The combination of perampanel (particularly at high doses) with ethanol has led to decreased mental alertness and ability to perform complex tasks (such as driving), as well as increased levels of anger, confusion, and depression; similar reactions should be expected with concomitant use of other CNS depressants, such as quetiapine.
Perphenazine: (Moderate) Avoid coadministration of perphenazine and quetiapine due to the potential for additive effects on the QT interval. Both quetiapine and perphenazine may be associated with QT prolongation. Concurrent use may increase this risk. Coadministration of perphenazine with atypical agents (e.g., quetiapine) may also increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Perphenazine; Amitriptyline: (Moderate) Avoid coadministration of perphenazine and quetiapine due to the potential for additive effects on the QT interval. Both quetiapine and perphenazine may be associated with QT prolongation. Concurrent use may increase this risk. Coadministration of perphenazine with atypical agents (e.g., quetiapine) may also increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Phenelzine: (Major) Avoid concomitant use, or use in rapid succession, of monoamine oxidase inhibitors (MAOIs) and quetiapine. If concomitant use is necessary, monitor for signs and symptoms of serotonin syndrome, blood pressure, and for unusual drowsiness and sedation. Concomitant use increases the risk for serotonin syndrome and additive hypotension and CNS depression. If serotonin syndrome occurs, discontinue therapy.
Phenobarbital: (Major) Coadministration of barbiturates, potent CYP3A4 inducers, with quetiapine, a CYP3A4 substrate, may result in decreased exposure to quetiapine. The dose of quetiapine should be increased by up to 5-fold when combined with chronic administration (7 to 14 days) of a potent CYP3A4 inducer. Adjust the dose based on patient response and tolerability. When the potent CYP3A4 inducer is discontinued, the quetiapine dose should be reduced to the original dose within 1 to 2 weeks. Also, somnolence is a commonly reported adverse effect of quetiapine; coadministration of quetiapine with barbiturates may result in additive sedative effects.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Coadministration of barbiturates, potent CYP3A4 inducers, with quetiapine, a CYP3A4 substrate, may result in decreased exposure to quetiapine. The dose of quetiapine should be increased by up to 5-fold when combined with chronic administration (7 to 14 days) of a potent CYP3A4 inducer. Adjust the dose based on patient response and tolerability. When the potent CYP3A4 inducer is discontinued, the quetiapine dose should be reduced to the original dose within 1 to 2 weeks. Also, somnolence is a commonly reported adverse effect of quetiapine; coadministration of quetiapine with barbiturates may result in additive sedative effects. (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant quetiapine and hyoscyamine use. Concomitant use may result in additive anticholinergic adverse effects. (Moderate) Monitor for unusual drowsiness or excess sedation and for signs or symptoms of anticholinergic toxicity during concomitant quetiapine and atropine use. Concomitant use may result in additive CNS depression or anticholinergic adverse effects. (Moderate) Monitor for unusual drowsiness or excess sedation and for signs or symptoms of anticholinergic toxicity during concomitant quetiapine and scopolamine use. Concomitant use may result in additive CNS depression or anticholinergic adverse effects.
Phenytoin: (Major) Increase the dose of quetiapine by up to 5-fold if coadministered with phenytoin. Coadministration may significantly decrease quetiapine exposure leading to reduced efficacy. If phenytoin is discontinued, reduce the quetiapine dose to the original level in 7 to 14 days. Quetiapine is a sensitive CYP3A4 substrate and phenytoin is a strong CYP3A4 inducer. Coadministration with phenytoin increased the mean oral clearance of quetiapine by 5-fold.
Pimavanserin: (Major) Concomitant use of quetiapine and pimavanserin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Pimozide: (Contraindicated) Quetiapine has a risk of QT prolongation and is contraindicated with pimozide. Concurrent use of pimozide with atypical agents may increase the risk of adverse effects such as drowsiness, sedation, dizziness, orthostatic hypotension, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Pioglitazone: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Pioglitazone; Glimepiride: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and sulfonylurea use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Pioglitazone; Metformin: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition. (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and metformin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Pitolisant: (Major) Concomitant use of quetiapine and pitolisant increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ponesimod: (Major) In general, do not initiate ponesimod in patients taking quetiapine due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ponesimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ponesimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Quetiapine has been associated with a significant prolongation of the QTc interval in rare instances.
Posaconazole: (Contraindicated) Concurrent use of posaconazole and quetiapine is contraindicated due to the risk of life threatening arrhythmias such as torsade de pointes (TdP). Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of quetiapine. These drugs used in combination may result in elevated quetiapine plasma concentrations, causing an increased risk for quetiapine-related adverse events, such as QT prolongation. Additionally, posaconazole has been associated with prolongation of the QT interval as well as rare cases of TdP; avoid use with other drugs that may prolong the QT interval and are metabolized through CYP3A4, such as quetiapine.
Pramipexole: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or pramipexole during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and pramipexole may interfere with the effectiveness of each other. Additive CNS depressant effects are also possible. In general, atypical antipsychotics are less likely to interfere with pramipexole than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Pramlintide: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Pregabalin: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and quetiapine. Concomitant use of pregabalin with quetiapine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
Primaquine: (Major) Concomitant use of quetiapine and primaquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Primidone: (Major) Coadministration of barbiturates, potent CYP3A4 inducers, with quetiapine, a CYP3A4 substrate, may result in decreased exposure to quetiapine. The dose of quetiapine should be increased by up to 5-fold when combined with chronic administration (7 to 14 days) of a potent CYP3A4 inducer. Adjust the dose based on patient response and tolerability. When the potent CYP3A4 inducer is discontinued, the quetiapine dose should be reduced to the original dose within 1 to 2 weeks. Also, somnolence is a commonly reported adverse effect of quetiapine; coadministration of quetiapine with barbiturates may result in additive sedative effects.
Procainamide: (Major) Concomitant use of quetiapine and procainamide increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Prochlorperazine: (Moderate) Prochlorperazine, a phenothiazine, is associated with a possible risk for QT prolongation. According to the manufacturer, quetiapine should be avoided in combination with other drugs having an association with QT prolongation. In addition, co-administration of prochlorperazine with atypical agents (e.g., aripiprazole, lurasidone and others) may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent (see separate drug monographs). Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Promethazine: (Major) Concomitant use of quetiapine and promethazine increases the risk of QT/QTc prolongation and torsade de pointes (TdP) and additive anticholinergic effects, CNS depression, and serotonin syndrome. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Monitor for gastrointestinal adverse reactions related to hypomotility, unusual drowsiness and sedation, and signs and symptoms of serotonin syndrome during concomitant use, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of therapy.
Promethazine; Dextromethorphan: (Major) Concomitant use of quetiapine and promethazine increases the risk of QT/QTc prolongation and torsade de pointes (TdP) and additive anticholinergic effects, CNS depression, and serotonin syndrome. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Monitor for gastrointestinal adverse reactions related to hypomotility, unusual drowsiness and sedation, and signs and symptoms of serotonin syndrome during concomitant use, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of therapy.
Promethazine; Phenylephrine: (Major) Concomitant use of quetiapine and promethazine increases the risk of QT/QTc prolongation and torsade de pointes (TdP) and additive anticholinergic effects, CNS depression, and serotonin syndrome. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Monitor for gastrointestinal adverse reactions related to hypomotility, unusual drowsiness and sedation, and signs and symptoms of serotonin syndrome during concomitant use, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of therapy.
Propafenone: (Major) Concomitant use of propafenone and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Propantheline: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant quetiapine and propantheline use. Concomitant use may result in additive anticholinergic adverse effects.
Pseudoephedrine; Triprolidine: (Moderate) Co-administration of quetiapine with sedating H1-blockers such as triprolidine may result in additive CNS effects including somnolence and drowsiness.
Quazepam: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine; coadministration of quetiapine with anxiolytics, sedatives, and hypnotics, or other CNS depressants may result in additive sedative effects.
Quinidine: (Major) Concomitant use of quinidine and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Quinine: (Major) Concurrent use of quinine and quetiapine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Limited data, including some case reports, suggest that quetiapine may also be associated with a significant prolongation of the QTc interval in rare instances. In addition, concentrations of quetiapine may be increased with concomitant use of quinine. Quetiapine is a CYP3A4 substrate and quinine is a CYP3A4 inhibitor.
Quizartinib: (Major) Concomitant use of quizartinib and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ranolazine: (Major) Ranolazine may increase plasma concentrations of quetiapine through CYP3A4 inhibition. Avoid co-use if possible, as both drugs have been noted to cause QTc interval prolongation. If co-use is necessary, use the combination with caution. The manufacturer of quetiapine recommends a reduced dosage of quetiapine during concurrent administration of CYP3A4 inhibitors.
Rasagiline: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or rasagiline during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and rasagiline may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with rasagiline than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Regular Insulin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and insulin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Regular Insulin; Isophane Insulin (NPH): (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and insulin use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Relugolix: (Major) Concomitant use of relugolix and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Relugolix; Estradiol; Norethindrone acetate: (Major) Concomitant use of relugolix and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Remifentanil: (Major) Concomitant use of opioid agonists with quetiapine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with quetiapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Repaglinide: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. The atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Ribociclib: (Major) Avoid coadministration of ribociclib with quetiapine due to an increased risk for QT prolongation. Systemic exposure of quetiapine may also be increased resulting in increase in treatment-related adverse reactions. Ribociclib is a strong CYP3A4 inhibitor that has been shown to prolong the QT interval in a concentration-dependent manner. Limited data, including some case reports, suggest that quetiapine, a sensitive CYP3A4 substrate, may also be associated with a significant prolongation of the QTc interval in rare instances. Concomitant use may increase the risk for QT prolongation.
Ribociclib; Letrozole: (Major) Avoid coadministration of ribociclib with quetiapine due to an increased risk for QT prolongation. Systemic exposure of quetiapine may also be increased resulting in increase in treatment-related adverse reactions. Ribociclib is a strong CYP3A4 inhibitor that has been shown to prolong the QT interval in a concentration-dependent manner. Limited data, including some case reports, suggest that quetiapine, a sensitive CYP3A4 substrate, may also be associated with a significant prolongation of the QTc interval in rare instances. Concomitant use may increase the risk for QT prolongation.
Rifabutin: (Moderate) Increased doses of quetiapine may be required to maintain symptom control if rifabutin is used concomitantly. Rifabutin is a less potent inducer of CYP3A4 than rifampin, a potent inducer. However, increased doses of quetiapine up to 5 fold may be required to maintain control of symptoms in patients receiving quetiapine and known potent CYP3A4 inducers. There are no specific recommendations for moderate inducers. When rifabutin is discontinued, the dose of quetiapine should be reduced to the original level within 7 to 14 days.
Rifampin: (Major) Coadministration of rifampin, a potent CYP3A4 inducer, with quetiapine, a CYP3A4 substrate, may result in decreased exposure to quetiapine. The dose of quetiapine should be increased by up to 5-fold when combined with chronic administration (7 to 14 days) of a potent CYP3A4 inducer. Adjust the dose based on patient response and tolerability. When the potent CYP3A4 inducer is discontinued, the quetiapine dose should be reduced to the original dose within 1 to 2 weeks.
Rifapentine: (Major) Increase the dose of quetiapine by up to 5-fold if coadministered with rifapentine. Coadministration may significantly decrease quetiapine exposure leading to reduced efficacy. If rifapentine is discontinued, reduce the quetiapine dose to the original level in 7 to 14 days. Quetiapine is a sensitive CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer increased the mean oral clearance of quetiapine by 5-fold.
Rilpivirine: (Major) Concomitant use of rilpivirine and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. The degree of QT prolongation associated with rilpivirine is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Risperidone: (Major) Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes; however, data are currently lacking to establish causality in association with torsades de pointes (TdP). Reports of QT prolongation and torsades de pointes during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. Since risperidone may prolong the QT interval, it should be used cautiously with other agents also known to have this effect, taking into account the patient's underlying disease state(s) and additional potential risk factors. If coadministration is chosen, and the patient has known risk factors for cardiac disease or arrhythmia, then the patient should be closely monitored clinically. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with risperidone include quetiapine. Quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. Additionally, according to the manufacturer, no significant kinetic drug interactions were identified when quetiapine was coadministered with haloperidol or risperidone.
Ritonavir: (Major) The manufacturer of quetiapine recommends a quetiapine dose reduction to one-sixth the original dose during concurrent administration of strong CYP3A4 inhibitors, such as ritonavir. When ritonavir is discontinued, the dose should be increased by 6-fold. The plasma concentrations of quetiapine may be elevated when administered concurrently with ritonavir.
Romidepsin: (Major) Concomitant use of romidepsin and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ropinirole: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or ropinirole during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and ropinirole may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with ropinirole than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Rosiglitazone: (Moderate) Atypical antipsychotic therapy may aggravate diabetes mellitus and cause metabolic changes such as hyperglycemia. Monitor patients on antidiabetic agents for worsening glycemic control. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Aggravation of diabetes mellitus has been reported. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Rotigotine: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, excess sedation, and diminished effectiveness of the atypical antipsychotic or rotigotine during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and rotigotine may interfere with the effectiveness of each other. Additive CNS depressant effects are also possible. In general, atypical antipsychotics are less likely to interfere with rotigotine than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Safinamide: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or safinamide during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and safinamide may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with safinamide than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Saquinavir: (Major) Avoid concurrent use of quetiapine and saquinavir due to the potential for additive effects on the QT interval and torsade de pointes. If no acceptable alternative therapy is available, perform a baseline ECG prior to initiation of concomitant therapy and carefully follow monitoring recommendations. Saquinavir may be associated with QT prolongation. Limited data, including some case reports, suggest that quetiapine may also be associated with a significant prolongation of the QTc interval in rare instances. Saquinavir may also inhibit the CYP3A4 metabolism of quetiapine, resulting in elevated quetiapine plasma concentrations. If administration of saquinavir is required in a patient taking quetiapine, reduce the quetiapine dose to one sixth of the current dose. If saquinavir is discontinued, increase the quetiapine dose by 6-fold.
Saxagliptin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Scopolamine: (Moderate) Monitor for unusual drowsiness or excess sedation and for signs or symptoms of anticholinergic toxicity during concomitant quetiapine and scopolamine use. Concomitant use may result in additive CNS depression or anticholinergic adverse effects.
Secobarbital: (Major) Coadministration of barbiturates, potent CYP3A4 inducers, with quetiapine, a CYP3A4 substrate, may result in decreased exposure to quetiapine. The dose of quetiapine should be increased by up to 5-fold when combined with chronic administration (7 to 14 days) of a potent CYP3A4 inducer. Adjust the dose based on patient response and tolerability. When the potent CYP3A4 inducer is discontinued, the quetiapine dose should be reduced to the original dose within 1 to 2 weeks. Also, somnolence is a commonly reported adverse effect of quetiapine; coadministration of quetiapine with barbiturates may result in additive sedative effects.
Selegiline: (Moderate) Monitor for loss of selegiline efficacy, signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, and unusual drowsiness and sedation during concomitant atypical antipsychotic and selegiline use. Dopamine antagonists, such as atypical antipsychotics, may diminish the effectiveness of selegiline. Concomitant use may increase the risk for serotonin syndrome or additive CNS depression. If serotonin syndrome occurs, discontinue therapy.
Selpercatinib: (Major) Concomitant use of selpercatinib and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Semaglutide: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and incretin mimetic use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Sertraline: (Major) Avoid coadministration of quetiapine with sertraline due to the potential for additive QT prolongation. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. QTc prolongation and torsade de pointes (TdP) have been reported during postmarketing use of sertraline; most cases had confounding risk factors. The risk of sertraline-induced QT prolongation is generally considered to be low in clinical practice. Its effect on QTc interval is minimal (typically less than 5 msec), and the drug has been used safely in patients with cardiac disease (e.g., recent myocardial infarction, unstable angina, chronic heart failure).
Sevoflurane: (Major) Concomitant use of quetiapine and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
SGLT2 Inhibitors: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and SGLT2 inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Siponimod: (Major) Concomitant use of siponimod and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Sitagliptin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and dipeptidyl peptidase-4 (DPP-4) inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Sodium Stibogluconate: (Major) Concomitant use of sodium stibogluconate and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Solifenacin: (Major) Concurrent use of quetiapine and solifenacin should be avoided if possible due to an increased risk for QT prolongation and torsade de pointes (TdP) and an increased risk of anticholinergic side effects. Solifenacin has been associated with dose-dependent prolongation of the QT interval; TdP has been reported during post-marketing use, although causality was not determined. Limited data, including some case reports, suggest that quetiapine may also be associated with a significant prolongation of the QTc interval in rare instances. If concurrent use is required, also monitor for additive anticholinergic effects such as constipation, blurred vision, urinary retention, xerostomia, and tachycardia. Constipation is a commonly reported adverse effect of quetiapine and anticholinergic agents, such as solifenacin. Constipation may lead to ileus. Intestinal obstruction has been reported with quetiapine, including fatal cases in patients who were receiving multiple concomitant medications that decrease intestinal motility. Anticholinergic effects observed during therapeutic use of quetiapine are thought to be associated with norquetiapine, the active metabolite of quetiapine which has demonstrated a moderate to strong in vitro affinity for several muscarinic receptor subtypes.
Sorafenib: (Major) Concomitant use of sorafenib and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Sotagliflozin: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and SGLT2 inhibitor use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Sotalol: (Major) Concomitant use of sotalol and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
St. John's Wort, Hypericum perforatum: (Major) If possible, avoid use of St. John's wort with quetiapine due to a potential for decreased quetiapine efficacy. Coadministration may significantly decrease quetiapine exposure. If St. John's wort must be used, the quetiapine dose may need to be increased based on clinical response. Quetiapine is a sensitive CYP3A4 substrate and St. John's wort is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer increased the mean oral clearance of quetiapine by 5-fold.
Stiripentol: (Moderate) Consider a dose adjustment of quetiapine when coadministered with stiripentol. Coadministration may alter plasma concentrations of quetiapine resulting in an increased risk of adverse reactions and/or decreased efficacy. Additive somnolence and sedation may occur. Quetiapine is a sensitive CYP3A4 substrate. In vitro data predicts inhibition or induction of CYP3A4 by stiripentol potentially resulting in clinically significant interactions.
Sufentanil: (Major) Concomitant use of opioid agonists with quetiapine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with quetiapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Sulfonylureas: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and sulfonylurea use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Sunitinib: (Major) Concomitant use of sunitinib and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Suvorexant: (Moderate) Monitor for excessive sedation and somnolence during coadministration of suvorexant and atypical antipsyhotics. Dosage adjustments of suvorexant and the atypical antipsychotic may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if suvorexant is taken with other CNS depressants.
Tacrolimus: (Major) Concurrent use of quetiapine and tacrolimus should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. Tacrolimus also causes QT prolongation. Additionally, both tacrolimus and quetiapine are substrates for CYP3A4. When coadministrating tacrolimus with other substrates of CYP3A4, it is recommended to reduce the tacrolimus dose and closely monitor tacrolimus whole blood concentrations.
Tamoxifen: (Major) Concomitant use of tamoxifen and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Tapentadol: (Major) Concomitant use of opioid agonists with quetiapine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with quetiapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Telavancin: (Major) Concomitant use of telavancin and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Temazepam: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine; coadministration of quetiapine with anxiolytics, sedatives, and hypnotics, or other CNS depressants may result in additive sedative effects.
Tetrabenazine: (Major) Concomitant use of tetrabenazine and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Tezacaftor; Ivacaftor: (Moderate) Use caution when administering ivacaftor and quetiapine concurrently. Ivacaftor is an inhibitor of CYP3A. Co-administration of ivacaftor with CYP3A substrates, such as quetiapine, can increase quetiapine exposure leading to increased or prolonged therapeutic effects and adverse events.
Thioridazine: (Contraindicated) Thioridazine, a phenothiazine, is associated with an established risk of QT prolongation and torsade de pointes (TdP) and is contraindicated for use with other drugs that are known to prolong the QT interval, such as quetiapine. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. In addition, co-administration of quetiapine with a phenothiazine may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The likelihood of pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone. Further, thioridazine increases the oral clearance of quetiapine by about 65%.
Thiothixene: (Major) Caution is advisable during concurrent use of thiothixene and other antipsychotics. Thiothixene use may be associated with adverse events such as drowsiness, dizziness, hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, and seizures. These effects may be potentiated during concurrent use of thiothixene and other antipsychotics. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Tipranavir: (Major) Avoid concurrent use of quetiapine and tipranavir. Tipranavir boosted with ritonavir may inhibit the CYP3A4 metabolism of quetiapine, resulting in elevated quetiapine plasma concentrations. If administration of tipranavir is required in a patient taking quetiapine, reduce the quetiapine dose to one sixth of the current dose and monitor for quetiapine-related adverse events. If tipranavir is discontinued, increase the quetiapine dose by 6-fold.
Tirzepatide: (Moderate) Monitor blood glucose during concomitant atypical antipsychotic and incretin mimetic use. Atypical antipsychotic therapy may aggravate diabetes mellitus. Atypical antipsychotics have been associated with metabolic changes, including hyperglycemia, diabetic ketoacidosis, hyperosmolar, hyperglycemic states, and diabetic coma. Possible mechanisms include atypical antipsychotic-induced insulin resistance or direct beta-cell inhibition.
Tolcapone: (Moderate) Monitor for movement disorders, unusual changes in moods or behavior, and diminished effectiveness of the atypical antipsychotic or COMT inhibitor during coadministration. Due to mutually opposing effects on dopamine, atypical antipsychotics and COMT inhibitors may interfere with the effectiveness of each other. In general, atypical antipsychotics are less likely to interfere with COMT inhibitors and other Parkinson's treatments than traditional antipsychotics. The Beers Criteria recognize quetiapine and clozapine as exceptions to the general recommendation to avoid all antipsychotics in older adults with Parkinson's disease.
Tolterodine: (Major) Concurrent use of quetiapine and tolterodine should be avoided if possible due to an increased risk for QT prolongation, torsade de pointes (TdP), and anticholinergic effects. Tolterodine has been associated with dose-dependent prolongation of the QT interval, especially in poor CYP2D6 metabolizers. Limited data, including some case reports, suggest that quetiapine may also be associated with a significant prolongation of the QTc interval in rare instances. If concurrent use is required, also monitor for additive anticholinergic effects such as constipation, blurred vision, urinary retention, xerostomia, and tachycardia. Constipation is a commonly reported adverse effect of quetiapine and anticholinergic agents, such as tolterodine. Constipation in some cases may lead to ileus. Intestinal obstruction has been reported with quetiapine, including fatal cases in patients who were receiving multiple concomitant medications that decrease intestinal motility. Anticholinergic effects observed during therapeutic use of quetiapine are thought to be associated with norquetiapine, the active metabolite of quetiapine which has demonstrated a moderate to strong in vitro binding affinity for several muscarinic receptor subtypes.
Toremifene: (Major) Concomitant use of toremifene and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Tramadol: (Moderate) If concomitant use of tramadol and quetiapine is warranted, monitor patients for seizures, excessive sedation and/or somnolence, and the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. Concomitant use of tramadol and quetiapine may increase seizure risk and cause additive CNS depression. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Tramadol; Acetaminophen: (Moderate) If concomitant use of tramadol and quetiapine is warranted, monitor patients for seizures, excessive sedation and/or somnolence, and the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. Concomitant use of tramadol and quetiapine may increase seizure risk and cause additive CNS depression. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Trandolapril; Verapamil: (Minor) Verapamil may inhibit the CYP3A4-mediated metabolism of quetiapine, leading to increased serum concentrations of quetiapine. The manufacturer of quetiapine recommends a reduced dosage during concurrent administration of CYP3A4 inhibitors.
Tranylcypromine: (Major) Avoid concomitant use, or use in rapid succession, of monoamine oxidase inhibitors (MAOIs) and quetiapine. If concomitant use is necessary, monitor for signs and symptoms of serotonin syndrome, blood pressure, and for unusual drowsiness and sedation. Concomitant use increases the risk for serotonin syndrome and additive hypotension and CNS depression. If serotonin syndrome occurs, discontinue therapy.
Trazodone: (Major) Avoid coadministration of trazodone and quetiapine. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval. Trazodone can prolong the QT/QTc interval at therapeutic doses. In addition, there are postmarketing reports of TdP. Therefore, the manufacturer recommends avoiding trazodone in patients receiving other drugs that increase the QT interval.
Triazolam: (Moderate) Somnolence is a commonly reported adverse effect of quetiapine; coadministration of quetiapine with anxiolytics, sedatives, and hypnotics, or other CNS depressants may result in additive sedative effects.
Triclabendazole: (Major) Concomitant use of triclabendazole and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Trifluoperazine: (Moderate) Trifluoperazine, a phenothiazine, is associated with a possible risk for QT prolongation. According to the manufacturer, quetiapine should not be used with other drugs having an association with QT prolongation. Co-administration of trifluoperazine with atypical agents (e.g., lurasidone and others) may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures. The likelihood of these pharmacodynamic interactions varies based upon the individual properties of the co-administered antipsychotic agent. Although the incidence of tardive dyskinesia from combination antipsychotic therapy has not been established and data are very limited, the risk appears to be increased during use of a conventional and atypical antipsychotic versus use of a conventional antipsychotic alone.
Trihexyphenidyl: (Moderate) Monitor for signs or symptoms of anticholinergic toxicity during concomitant quetiapine and trihexyphenidyl use. Concomitant use may result in additive anticholinergic adverse effects.
Triprolidine: (Moderate) Co-administration of quetiapine with sedating H1-blockers such as triprolidine may result in additive CNS effects including somnolence and drowsiness.
Triptorelin: (Major) Concomitant use of triptorelin and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Trospium: (Moderate) When coadministering quetiapine and trospium, monitor for additive anticholinergic effects such as constipation, blurred vision, urinary retention, xerostomia, and tachycardia. Constipation is a commonly reported adverse effect of quetiapine and anticholinergic agents such as trospium. Constipation may lead to ileus. Intestinal obstruction has been reported with quetiapine, including fatal cases in patients who were receiving multiple concomitant medications that decrease intestinal motility. Anticholinergic effects observed during therapeutic use of quetiapine are thought to be associated with norquetiapine, an active metabolite of quetiapine which has demonstrated a moderate to strong in vitro binding affinity for several muscarinic receptor subtypes.
Tucatinib: (Major) Decrease the quetiapine dose to one sixth of the original dose if coadministered with tucatinib. Concurrent use may increase quetiapine exposure and adverse effects. When tucatinib is discontinued, increase the quetiapine dose by 6-fold. Quetiapine is a CYP3A4 substrate and tucatinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased quetiapine exposure by approximately 6-fold.
Valproic Acid, Divalproex Sodium: (Minor) The combined use of valproic acid, divalproex sodium and quetiapine could lead to increased sedation.
Vandetanib: (Major) Concomitant use of vandetanib and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Vardenafil: (Major) Concomitant use of vardenafil and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Vemurafenib: (Major) Concomitant use of vemurafenib and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Venlafaxine: (Major) Avoid coadministration of venlafaxine and quetiapine due to the potential for QT prolongation. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. Venlafaxine administration is associated with a possible risk of QT prolongation; torsade de pointes (TdP) has reported with postmarketing use.
Verapamil: (Minor) Verapamil may inhibit the CYP3A4-mediated metabolism of quetiapine, leading to increased serum concentrations of quetiapine. The manufacturer of quetiapine recommends a reduced dosage during concurrent administration of CYP3A4 inhibitors.
Voclosporin: (Major) Concomitant use of voclosporin and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. The degree of QT prolongation associated with voclosporin is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 3 times the maximum recommended dose.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Avoid concurrent use of quetiapine and clarithromycin due to the potential for additive effects on the QT interval and torsade de pointes (TdP) and the potential for greatly increased quetiapine exposure. Clarithromycin is a potent inhibitor of CYP3A4 that is expected to signficantly reduce metabolism of quetiapine. If administration of clarithromycin is required in a patient taking quetiapine, reduce the quetiapine dose to one sixth of the current dose. Monitor for quetiapine-related side effects. If clarithromycin is discontinued, increase the quetiapine dose by 6-fold. Clarithromycin has an established causal association with QT prolongation and TdP (torsade de pointes). Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances.
Voriconazole: (Major) Avoid coadministration of voriconazole with quetiapine due to the potential for additive effects on the QT interval; increased exposure to quetiapine may also occur. Both drugs are associated with QT prolongation; coadministration may increase this risk. Voriconazole has also been associated with rare cases of torsades de pointes, cardiac arrest, and sudden death. In addition, coadministration of voriconazole (a strong CYP3A4 inhibitor) with quetiapine (a CYP3A4 substrate) may result in elevated quetiapine plasma concentrations and could increase the risk for adverse events, including QT prolongation. The manufacturer recommends a quetiapine dose reduction to one-sixth the original dose during concurrent administration of CYP3A4 inhibitors, such as voriconazole. When voriconazole is discontinued, the dose should be increased by 6-fold. If these drugs are given together, closely monitor for prolongation of the QT interval. Rigorous attempts to correct any electrolyte abnormalities (i.e., potassium, magnesium, calcium) should be made before initiating concurrent therapy.
Vorinostat: (Major) Concomitant use of vorinostat and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Zafirlukast: (Moderate) Zafirlukast may inhibit the CYP3A4-mediated metabolism of quetiapine, leading to increased serum concentrations of quetiapine. The manufacturer of quetiapine recommends a reduced dosage during concurrent administration of CYP3A4 inhibitors.
Zaleplon: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of atypical antipsychotics and zaleplon due to the risk for additive CNS depression and next-day psychomotor impairment; dose adjustments may be necessary.
Ziconotide: (Moderate) Quetiapine is a CNS depressant medication that may increase drowsiness, dizziness, and confusion that are associated with ziconotide. Due to potentially additive effects, dosage adjustments may be necessary if ziconotide is used with a drug that has CNS depressant effects.
Ziprasidone: (Major) Concomitant use of ziprasidone and quetiapine should be avoided due to the potential for additive QT prolongation. Clinical trial data indicate that ziprasidone causes QT prolongation; there are postmarketing reports of torsade de pointes (TdP) in patients with multiple confounding factors. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to the manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval. In addition, coadministration of atypical antipsychotics may increase the risk of adverse effects such as drowsiness, dizziness, orthostatic hypotension, anticholinergic effects, extrapyramidal symptoms, neuroleptic malignant syndrome, or seizures.
Zolpidem: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of atypical antipsychotics and zolpidem due to the risk for additive CNS depression and next-day psychomotor impairment; dose adjustments may be necessary. Limit the dose of Intermezzo sublingual tablets to 1.75 mg/day.
Zonisamide: (Moderate) Zonisamide may cause decreased sweating (oligohidrosis), elevated body temperature (hyperthermia), heat intolerance, or heat stroke. The manufacturer recommends caution in using concurrent drug therapies that may predispose patients to heat-related disorders such as antipsychotics. Monitor patients for heat intolerance, decreased sweating, or increased body temperature if zonisamide is used with any of these agents.
Zuranolone: (Major) Avoid the use of multiple sedating agents due to the risk for additive CNS depression. If use is necessary, consider a downward dosage adjustment of either or both medications, especially in patients with additional risk factors for sedation-related harm.
The exact mechanism of action of quetiapine in treating schizophrenia has not been determined. However, it is thought that atypical antipsychotics such as quetiapine reduce the positive and negative symptoms of schizophrenia through modulation of central dopaminergic and serotonergic activity. Available data suggest that the efficacy of quetiapine in treating schizophrenia is primarily attributable to a combination of dopamine D2 and serotonin 5-HT2A antagonism. Similar to clozapine, quetiapine has a rapid dissociation rate from the D2 receptor, allowing for antipsychotic effects but a lower incidence of extrapyramidal symptoms and hyperprolactinemia with quetiapine compared to many other antipsychotics. Quetiapine and norquetiapine, the active metabolite of quetiapine, also have activity at serotonin 5-HT1A and 5-HT2A, histamine H-1, and adrenergic alpha-1 and alpha-2 receptor sites. The orthostatic hypotension commonly observed with quetiapine is likely the result of alpha-1 antagonism while somnolence correlates with H-1 antagonism. Norquetiapine exhibits moderate to high in vitro muscarinic antagonism at several muscarinic receptor subtypes, unlike quetiapine which has no appreciable activity at the muscarinic receptor site. Muscarinic antagonism of norquetiapine contributes to the anticholinergic effects observed when quetiapine is used clinically, during concurrent use of quetiapine with other anticholinergic medications, or following quetiapine overdose. The mechanism of action of quetiapine in the treatment of bipolar depression and major depressive disorder is also unclear, but may be related to downregulation of 5-HT2A receptors in the brain, decreased activation of dopamine receptors, and the high affinity and blockade of norquetiapine at the norepinephrine transporter.
Quetiapine is administered orally as immediate-release or extended-release tablets. It is widely distributed throughout the body with a volume of distribution of about 10 L/kg. About 83% of the drug is bound to plasma proteins. Quetiapine is extensively metabolized in the liver. The inactive parent acid metabolite is produced by oxidation, and the major inactive sulfoxide metabolite is produced through CYP3A4. In vitro studies indicate that CYP3A4 is involved in the metabolism of the active metabolite norquetiapine. The elimination half-lives of quetiapine and norquetiapine are 6 to 7 hours and 12 hours, respectively. Excretion is 20% fecal and 73% renal. Less than 1% of the dose is excreted as unchanged drug.
Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: CYP3A4
Quetiapine is a major substrate of CYP3A4. During concomitant use of strong CYP3A4 inhibitors (e.g., ketoconazole, ritonavir), reduce the quetiapine dose to one-sixth of the previous dose. During concomitant use of strong CYP3A4 inducers, increase the quetiapine dose up to 5-fold when used in combination with chronic treatment (more than 7 to 14 days) of potent CYP3A4 inducers (e.g., phenytoin, rifampin, St. John's wort). Quetiapine and its metabolites are not inhibitors of CYP1A2, CYP2C9, CYP2C19, CYP2D6, or CYP3A.
-Route-Specific Pharmacokinetics
Oral Route
The bioavailability of the formulations is comparable. After oral administration, peak plasma concentrations of the immediate-release and extended-release formulations are achieved in about 1.5 hours and 6 hours, respectively. Food increases Cmax and AUC of immediate-release quetiapine marginally by 25% and 15%, respectively; therefore, the drug can be administered without regard to meals. Statistically significant increases in Cmax and AUC occur with extended-release quetiapine during administration with a high-fat meal (800 to 1,000 calories) whereas no significant effects have been seen with a light meal of about 300 calories. Therefore, extended-release quetiapine should be administered without food or with a light meal only. Steady-state concentrations are expected to occur within 2 days of dosing.
-Special Populations
Hepatic Impairment
In one small study (n = 8), hepatically impaired patients had a 30% lower mean oral clearance of quetiapine than healthy subjects. In 2 of the 8 hepatically impaired patients, AUC and Cmax were 3 times higher than those typically observed in healthy subjects.
Renal Impairment
In one study, patients with severe renal impairment (CrCl 10 to 30 mL/minute) had a 25% lower mean oral clearance than healthy subjects, although plasma quetiapine concentrations in the subjects with renal insufficiency were within the range of concentrations seen in healthy subjects receiving the same dose. Therefore, dosage adjustments are not needed in patients with renal impairment.
Geriatric
Oral clearance of quetiapine is reduced by about 40% in geriatric patients compared with younger adult patients.
Gender Differences
There are no differences in the pharmacokinetics of quetiapine based upon gender.
Ethnic Differences
There are no differences in the pharmacokinetics of quetiapine based upon race.
Other
Smoking
Tobacco smoking has no effect on the clearance of quetiapine.