No

Antipsychotic Agent, Dibenzothiazepine

Treatment of manifestations of psychotic disorders

C

Hypersensitivity to quetiapine or any component; severe CNS depression, bone marrow suppression, blood dyscrasias, severe hepatic disease, coma

Has been noted to cause cataracts in animals, although QTP-associated cataracts have not been observed in humans; lens examination on initiation of therapy and every 6 months is recommended. May be sedating, use with caution in disorders where CNS depression is a feature. Use with caution in Parkinson's disease. Caution in patients with hemodynamic instability; prior myocardial infarction or ischemic heart disease; hypercholesterolemia; thyroid disease; predisposition to seizures; subcortical brain damage; hepatic impairment; severe cardiac, renal, or respiratory disease. May alter temperature regulation or mask toxicity of other drugs due to antiemetic effects. May alter cardiac conduction - life-threatening arrhythmias have occurred with therapeutic doses of antipsychotics. May cause orthostatic hypotension - use with caution in patients at risk of this effect or those who would tolerate transient hypotensive episodes (cerebrovascular disease, cardiovascular disease, or other medications which may predispose). Esophageal dysmotility and aspiration have been associated with antipsychotic use - use with caution in patients at risk of pneumonia (ie, Alzheimer's disease).

>10%:

Central nervous system: Headache, somnolence

Gastrointestinal: Weight gain

1% to 10%:

Cardiovascular: Postural hypotension, tachycardia, palpitations

Central nervous system: Dizziness, hypotension

Dermatologic: Rash

Gastrointestinal: Abdominal pain, constipation, xerostomia, dyspepsia, anorexia

Hematologic: Leukopenia

Neuromuscular & skeletal: Dysarthria, back pain, weakness

Respiratory: Rhinitis, pharyngitis, cough, dyspnea

Miscellaneous: Diaphoresis

<1%: QT prolongation, bradycardia, abnormal dreams, tardive dyskinesia, vertigo, involuntary movements, increased salivation, increased appetite, elevated GGT, rash, leukocytosis, anemia, hypothyroidism, diabetes, epistaxis, hyperlipidemia, elevated alkaline phosphatase

CYP3A4 enzyme substrate; CYP2D6 substrate (minor); CYP2C9 substrate (minor)

May enhance effects of antihypertensive agents; may antagonize levodopa, dopamine agonists

Increased clearance when given with phenytoin (5-fold) or thioridazine (65%), caution with other liver enzyme inducers (carbamazepine, barbiturates, rifampin, glucocorticoids)

Although data is not yet available, caution is advised with inhibitors of CYP3A4 (eg, ketoconazole, erythromycin)

Cimetidine in combination with quetiapine decreased quetiapine's clearance by 20%

Lorazepam's clearance is reduced 20% in the presence of quetiapine

Mechanism of action of quetiapine, as with other antipsychotic drugs, is unknown. However, it has been proposed that this drug's antipsychotic activity is mediated through a combination of dopamine type 2 (D₂) and serotonin type 2 (5HT₂) antagonism. However, it is an antagonist at multiple neurotransmitter receptors in the brain: serotonin 5HT_1A and 5HT₂, dopamine D₁ and D₂, histamine H₁, and adrenergic alpha₁- and alpha₂-receptors; but appears to have no appreciable affinity at cholinergic muscarinic and benzodiazepine receptors.

Absorption: Accumulation is predictable upon multiple dosing

Distribution: Steady-state concentrations are expected to be achieved within 2 days of dosing; unlikely to interfere with the metabolism of drugs metabolized by cytochrome P-450 enzymes

Metabolism: Both metabolites are pharmacologically inactive

Half-life, mean terminal: ~6 hours

Time to peak plasma concentrations: 1.5 hours

Elimination: Mainly via hepatic metabolism

Adults: Oral: 25-100 mg 2-3 times/day; usual starting dose: 25 mg twice daily and then increased in increments of 25-50 mg 2-3 times/day on the second or third day; by day 4, the dose should be in the range of 300-400 mg/day in 2-3 divided doses. Make further adjustments as needed at intervals of at least 2 days in adjustments of 25-50 mg twice daily. Usual maintenance range: 150-750 mg/day

Dosing comments in hepatic insufficiency: 30% lower mean oral clearance of quetiapine than normal subjects; higher plasma levels expected in hepatically impaired subjects; dosage adjustment may be needed

In healthy volunteers, administration of quetiapine with food resulted in an increase in the peak serum concentration and AUC (each by ~15%) compared to the fasting state; can be taken with or without food

Patients should have eyes checked every 6 months for cataracts while on this medication

No information available to require special precautions

No effects or complications reported

Use exactly as directed (do not increase dose or frequency); may cause physical and/or psychological dependence. It may take 2-3 weeks to achieve desired results; do not discontinue without consulting prescriber. Avoid excess alcohol or caffeine and other prescription or OTC medications not approved by prescriber. Maintain adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid intake). You may experience excess drowsiness, restlessness, dizziness, or blurred vision (use caution driving or when engaging in tasks requiring alertness until response to drug is known); mouth sores or GI upset (small frequent meals, frequent mouth care, chewing gum, or sucking lozenges may help); constipation (increased exercise, fluids, or dietary fruit and fiber may help); or postural hypotension (use caution climbing stairs or when changing position from lying or sitting to standing). Report persistent CNS effects (eg, somnolence, agitation, insomnia); severe dizziness; vision changes; difficulty breathing; or worsening of condition. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be pregnant. Breast-feeding is not recommended.

Seroquel® has a very low incidence of extrapyramidal symptoms such as restlessness and abnormal movement; is at least as effective as conventional antipsychotics (ie, Haldol®)

Tablet: 25 mg, 100 mg, 200 mg

Goldberg RJ, "Managing Psychosis-Related Behavioral Problems in the Elderly," Consult Pharm, 1997, 12(Suppl C):4-10.