quetiapine (Rx)

>10%

Dizziness (1-18%)

Fatigue (3-14%)

Extrapyramidal symptoms (1-13%)

Increased diastolic blood pressure (41%)

Increased triglycerides (8-22%)

Increased total cholesterol (7-18%)

Increased appetite (2-12%)

Constipation (6-11%)

Dry mouth (9-44%)

Headache (7-21)

Somnolence (18-57%)

1-10%

Abdominal pain (4-7%; dose related)

Dyspepsia (2-7%; dose related

Tremor (2-8%)

Back pain (3-5%)

Postural hypotension (2-7%)

Tachycardia (1-6%)

Pharyngitis (4-6%)

Rhinitis (3-4%)

Rash (4%)

Blurred vision (1-4%)

Arthralgia (1-4%)

Myalgia (2%)

Neck pain (2%)

Dyskinesia (4%)

Neutropenia (2%)

Hemorrhage (1%)

< 1%

Priapism

Cardiomyopathy, myocarditis

QTc prolongation

Night mares

Pancreatitis

Rhabdomyolysis

Palpitation

Leukocytosis

Epistaxis

Exfoliative dermatitis

Postmarketing Reports

Drug reaction with eosinophilia and systemic symptoms (DRESS)

Falls

Contraindications

Documented hypersensitivity

Cautions

Use with caution in cardiovascular and cerebrovascular disease

May worsen hypotensive conditions

Use with caution in breast cancer and history of seizure

Increased risk of hyperglycemia and diabetes; in some cases, hyperglycemia concomitant with use of atypical antipsychotics has been associated with ketoacidosis, hyperosmolar coma, or death; monitor blood glucose of high-risk patients for symptoms of hyperglycemia including polydipsia, polyuria, polyphagia, and weakness; monitor glucose regularly in patients with diabetes or at risk for diabetes

Increased incidence of cerebrovascular adverse effects, including stroke and TIAs, in elderly with dementia (not approved for the treatment of patients with dementia-related psychosis); see Black Box Warnings

Neuroleptic malignant syndrome (NMS) reported with use

Tardive dyskinesia possible after discontinuance

Clinical worsening of depression and suicide ideation may occur despite treatment

Hyperlipidemia may occur; appropriate clinical monitoring is recommended, including fasting blood lipid testing at the beginning of, and periodically, during treatment

Weight gain may occur; monitoring of weight recommended

Cataract may occur; monitor

Increased blood pressure in children and adolescents reported; monitor blood pressure at the beginning of, and periodically during treatment

Leukopenia, neutropenia, and agranulocytosis may occur; perform a complete blood count (CBC) during first few months of therapy; in such patients, consider discontinuation of therapy at first sign of clinically significant decline in WBC in absence of other causative factors

Can elevate prolactin levels, and elevation can persist during chronic administration; hyperprolactinemia may suppress hypothalamic GnRH, resulting in reduced pituitary gonadotropin secretion; this, in turn, may inhibit reproductive function by impairing gonadal steroidogenesis in both female and male patients

Orthostatic vital signs should be monitored in patients who are vulnerable to hypotension (elderly patients, patients with dehydration, hypovolemia, concomitant treatment with antihypertensive medications

May cause somnolence, postural hypotension, motor and sensory instability, which may lead to falls and, consequently, fractures or other injuries; perform complete fall risk assessments when initiating antipsychotic treatment and recurrently for patients on long-term antipsychotic therapy

Potential for withdrawal symptoms after abrupt discontinuance

False-positive urine drug screens reported when immunoassays for methadone or tricyclic antidepressants used

FDA warning regarding off-label use for dementia in elderly (see Black Box Warnings)

QT interval prolongation

• Not associated with persistent increase in QT interval in trials, but QT effect was not systematically evaluated in thorough study
• QT prolongation reported with acute overdose during postmarketing experience
• Avoid using in combination with other drugs known to prolong QTc or in patients with increased risk of QT prolongation

Pregnancy

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to atypical antipsychotics, including quetiapine, during pregnancy; healthcare providers are encouraged to register patients by contacting the National Pregnancy Registry for Atypical Antipsychotics at 1-866-961-2388 or online at http://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry

Neonates exposed during third trimester are at risk for extrapyramidal and/or withdrawal symptoms following delivery; overall available data from published epidemiologic studies of pregnant women exposed to drug have not established a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes; there are risks to the mother associated with untreated schizophrenia, bipolar I, or major depressive disorder, and with exposure to drug during pregnancy

There is a risk to the mother from untreated schizophrenia, or bipolar I disorder, including increased risk of relapse, hospitalization, and suicide; schizophrenia and bipolar I disorder are associated with increased adverse perinatal outcomes, including preterm birth; it is not known if this is a direct result of the illness or other comorbid factors

Extrapyramidal and/or withdrawal symptoms, including agitation, hypertonia, hypotonia, tremor, somnolence, respiratory distress, and feeding disorder reported in neonates exposed to drug, during third trimester of pregnancy; symptoms varied in severity; monitor neonates for extrapyramidal and/or withdrawal symptoms and manage symptoms appropriately; some neonates recovered within hours or days without specific treatment; others required prolonged hospitalization

Based on pharmacologic action of drug, treatment may result in an increase in serum prolactin levels, which may lead to a reversible reduction in fertility in females of reproductive potential

Animal data

• In animal studies, embryo-fetal toxicity occurred including delays in skeletal ossification at approximately 1 and 2 times maximum recommended human dose (MRHD) of 800 mg/day in both rats and rabbits, and an increased incidence of carpal/tarsal flexure (minor soft tissue anomaly) in rabbit fetuses at approximately 2 times the MRHD; in addition, fetal weights were decreased in both species; maternal toxicity (observed as decreased body weights and/or death) occurred at 2 times the MRHD in rats and approximately 1-2 times the MRHD in rabbits

Lactation

Limited data from published literature report the presence of drug in human breast milk at relative infant dose of <1% of maternal weight-adjusted dosage; there are no consistent adverse events reported in infants exposed to quetiapine through breast milk; there is no information on effects of quetiapine on milk production; developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed child from drug or from mother’s underlying condition

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Atypical antipsychotic related to clozapine; reduces positive and negative symptoms of psychotic disorders via antagonism of multiple neurotransmitter receptors in brain, including dopamine D1 and D2, histamine H1, alpha1- and alpha2-adrenergic, and serotonin types 1 and 2 (5-HT1A, 5-HT2); has no affinity for benzodiazepine and cholinergic muscarinic receptors

Absorption

Bioavailability: 100% (oral solution)

Peak plasma time: Immediate release, 1.5 hr; extended release, 6 hr

Distribution

Protein bound: 83%

Vd: 6-14 L/kg

Metabolism

Metabolized in liver by CYP3A4

Elimination

Half-life: Immediate release, 6 hr; extended release, 7 hr

Excretion: Urine (73%), feces (20%)