Medical and Pharmacy Editor: Jay W. Marks, MD

GENERIC NAME: quetiapine

BRAND NAME: Seroquel

DRUG CLASS AND MECHANISM: Quetiapine is an oral antipsychotic drug used for treating schizophrenia and bipolar disorder. Although the mechanism of action of quetiapine is unknown, like other anti-psychotics, it inhibits communication between nerves of the brain. It does this by blocking receptors on the nerves for several neurotransmitters, the chemicals that nerves use to communicate with each other. It is thought that its beneficial effect is due to blocking of the dopamine type 2 (D2) and serotonin type 2 (5-HT2) receptors.

PRESCRIPTION: Yes

GENERIC AVAILABLE: No

PREPARATIONS: Tablets: 25, 50, 100, 200, 300, and 400 mg

STORAGE: Tablets should be stored at room temperature, 15-30°C (59-86°F).

PRESCRIBED FOR: Quetiapine is used alone or in combination with other drugs to treat schizophrenia and bipolar disorder .

DOSING: Quetiapine usually is taken two or three times daily. The dose usually is increased slowly over several days or weeks to achieve the desired effect. Quetiapine can be taken with or without food.

The initial dose for bipolar disorder is 50 mg twice daily (100 mg/d). The dose can be increased by 100 mg/d to a daily dose of 400 mg/d. Most patients respond to 400-800 mg/d. Doses greater than 800 mg/d have not been studied.

The initial dose for schizophrenia is 25 mg twice daily (50 mg/d). The dose can be increased by 25-50 mg two or three times daily. The target dose is 300-400 mg/d in two or three doses. Patients respond to 150-750 mg/d, and doses greater than 800 mg/d have not been evaluated.

DRUG INTERACTIONS: Phenytoin (Dilantin) and thioridazine (Mellaril) markedly decrease the amount of quetiapine that is absorbed from the intestine and thereby reduces its effectiveness. Therefore, patients taking phenytoin or thioridazine may require higher doses of quetiapine.

Quetiapine can cause hypotension (low blood pressure) and therefore increase the blood pressure lowering effects of antihypertensive drugs.

Quetiapine can increase the sedating effects of other drugs that sedate. Such drugs include narcotic pain relievers (e.g., Percocet), barbiturates, sedatives such as alprazolam (Xanax) and clonazepam (Klonopin), ethanol, and blood pressure drugs that can cause orthostatic hypotension, such as prazosin (Minipress) and terazosin (Hytrin).

Quetiapine is eliminated from the body by an enzyme in the liver called cytochrome P450 3A. There is a concern that drugs that strongly interfere with the enzyme, e.g., ketoconazole (Nizoral), itraconazole (Sporanox), fluconazole (Diflucan), and erythromycin, clarithromycin (Biaxin), nefazodone (Serzone), verapamil (Calan, Isoptin, Verelan), or diltiazem (Cardizem, Tiazac, Dilacor) may cause elevated and toxic levels of quetiapine.

PREGNANCY: There are no adequate studies of quetiapine in pregnant women . Studies in animals are inconsistent. Some studies suggest effects on the fetus and others show no effects. Quetiapine should only be used in pregnancy if the physician feels that it is absolutely necessary and that the potential benefits justify the unknown risks.

NURSING MOTHERS: Quetiapine is excreted in the milk of animals during lactation. Although it is not known if it is excreted in human milk, it is recommended that women taking quetiapine not breast feed.

SIDE EFFECTS: Frequent adverse effects include headache, agitation, dizziness, drowsiness, weight gain and stomach upset. Quetiapine can cause orthostatic hypotension (a drop in blood pressure upon standing that can lead to dizziness or fainting) especially during the first 3-5 day period of treatment, when it is restarted after temporary discontinuation, and after an increase in the dose. The risk of orthostatic hypotension is about 1 in 100 (one of every hundred patients who takes quetiapine). Quetiapine frequently causes tiredness (1 in 5 patients), especially during the first 3-5 days of treatment. Because of this tiredness, care should be exercised in any activity requiring mental alertness such as operating a motor vehicle or hazardous machinery. Less common side effects include seizures (1 in 125 patients) and hypothyroidism (1 in 250 patients).

As with other antipsychotics, long-term use of quetiapine may lead to irreversible tardive dyskinesia, a neurologic disease which consists of involuntary movements of the jaw, lips, and tongue.

A potentially fatal complex referred to as neuroleptic malignant syndrome (NMS) has been reported with antipsychotic drugs. Patients who develop NMS may have high fevers, muscle rigidity, altered mental status, irregular pulse or blood pressure, rapid heart rate, excessive sweating, and heart arrhythmias.

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