quetiapine fumarate
Seroquel

Available forms
Available by prescription only
Tablets: 25 mg, 100 mg, 200 mg, 300 mg

Indications and dosages
 Management of signs and symptoms of psychotic disorders. Adults: Initially, 25 mg P.O. b.i.d., increased in increments of 25 to 50 mg b.i.d. or t.i.d. on days 2 and 3, as tolerated, to a target dosage range of 300 to 400 mg daily by day 4, divided into two or three doses. Further dosage adjustments, if indicated, should generally occur at intervals of at least 2 days. Dosages can be increased or decreased by 25 to 50 mg b.i.d. Antipsychotic efficacy usually occurs at 150 to 750 mg daily. Safety of doses above 800 mg daily hasn’t been evaluated.
≡ Dosage adjustment. For elderly or debilitated patients or those who have hepatic impairment or a predisposition to hypotensive reactions, consider lower doses, slower dosage adjustment, and careful monitoring during initial dosing period. No specific dosing recommendations are given.

Pharmacodynamics
Antipsychotic action: Exact mechanism of action is unknown. Quetiapine is a dibenzothiazepine derivative that is thought to exert antipsychotic activity through antagonism of dopamine type 2 (D₂) and serotonin type 2 (5-HT₂) receptors. Antagonism at serotonin 5-HT_1A, D₁, H₁, and alpha₁- and alpha₂-adrenergic receptors may explain other effects.

Pharmacokinetics
Absorption: Rapidly absorbed after oral administration. Absorption is affected by food, with maximum level increasing 25% and bioavailability increasing 15%.
Distribution: Apparent volume of distribution is 10±4 L/kg. Drug is 83% plasma protein-bound. Steady state levels are reached within 2 days.
Metabolism: Extensively metabolized by the liver via sulfoxidation and oxidation. Cytochrome P-450 3A4 is the major isoenzyme involved.
Excretion: Less than 1% of dose is excreted as unchanged drug. About 73% is recovered in urine and 20% in feces. Mean terminal half-life is about 6 hours.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug or its components.
  Use cautiously in patients with CV or cerebrovascular disease, conditions that predispose to hypotension, conditions that could contribute to increased core body temperature, conditions that could lower the seizure threshold, or a history of seizures. Also use cautiously in patients at risk for aspiration pneumonia from esophageal dysmotility and aspiration.

Interactions
Drug-drug. Anticholinergics: Potentiates anticholinergic effects. Use together cautiously.
Antihypertensives: May potentiate hypotensive effects. Monitor blood pressure.
Barbiturates, carbamazepine, glucocorticoids, rifampin: Increases metabolism of quetiapine. Adjust quetiapine dosage.
Cimetidine: Decreases oral clearance of quetiapine. No dosage adjustment needed.
CNS depressants: Increases CNS effects. Use cautiously together.
Dopamine agonists, levodopa: May antagonize effects of these drugs. Monitor patient closely.
Erythromycin, fluconazole, itraconazole, ketoconazole: Decreases quetiapine clearance. Use cautiously.
Lorazepam: Reduces lorazepam clearance. Monitor patient.
Phenytoin, thioridazine: Increases oral clearance of quetiapine. Quetiapine dosage may need adjustment.
Drug-lifestyle. Alcohol use: May potentiate cognitive and motor effects. Discourage alcohol use.

Adverse reactions
CNS: dizziness, headache, somnolence, hypertonia, asthenia, dysarthria, fever.
CV: orthostatic hypotension, tachycardia, palpitations, peripheral edema.
EENT: pharyngitis, rhinitis, ear pain.
GI: dry mouth, dyspepsia, abdominal pain, constipation, anorexia.
Hematologic: leukopenia.
Metabolic: weight gain.
Musculoskeletal: back pain.
Respiratory: increased cough, dyspnea.
Skin: rash, sweating.
Other: flulike syndrome.

Effects on lab test results
• May increase liver enzyme, cholesterol, and triglyceride levels. May decrease T₄ and thyroid-stimulating hormone levels.
• May decrease WBC count.

Overdose and treatment
Usually, overdose causes exaggeration of drug effects (drowsiness, sedation, tachycardia, hypotension). Hypokalemia and first-degree heart block also may occur.
 For acute overdose, treatment includes establishing and maintaining an airway to ensure adequate oxygenation and ventilation. Consider gastric lavage and administration of activated charcoal or a laxative. Begin CV monitoring, including ECG monitoring, immediately. Avoid use of disopyramide, procainamide, quinidine, and bretylium if antiarrhythmic therapy is indicated. Administer I.V. fluids or sympathomimetic drugs (not epinephrine or dopamine) to treat hypotension and circulatory collapse. For severe extrapyramidal symptoms, give anticholinergic agents.

Special considerations
• Total and free T₄ levels may decrease, although this change usually isn’t clinically significant. Although rare, some patients have increased thyroid-stimulating hormone levels and need thyroid replacement.
• Cholesterol and triglyceride levels sometimes increase.
• Asymptomatic, transient, reversible increases in serum transaminase (primarily ALT) levels have been reported. They usually occur during the first 3 weeks of therapy and promptly return to pretreatment levels with continued use.
• Neuroleptic malignant syndrome, a potentially fatal syndrome, has been reported with use of antipsychotics. Signs and symptoms include hyperpyrexia, muscle rigidity, altered mental status, and evidence of autonomic instability. Carefully monitor at-risk patients.
• Use smallest effective dose for shortest duration to minimize risk of tardive dyskinesia.
• To detect possible cataract formation, examine the patient’s ocular lenses before therapy starts or shortly thereafter and at 6-month intervals during treatment.
• Monitor schizophrenic patient closely during drug therapy because of the inherent risk of suicide.
 ALERT Don’t confuse Seroquel (quetiapine) with Serzone (nefazodone).
Breast-feeding patients
• Breast-feeding isn’t recommended during quetiapine therapy.
Pediatric patients
• Safety and efficacy in children haven’t been established.
Geriatric patients
• In general, elderly patients seem to tolerate quetiapine no differently than other adults. However, patients who have problems that could decrease drug clearance, increase response to the drug, decrease tolerance of the drug, or increase the risk of orthostasis may benefit from a reduced starting dosage, slower dosage adjustment, and careful monitoring during the initial treatment period.

Patient education
• Caution patient about the risk of orthostatic hypotension, especially during the first 3 to 5 days of treatment and any time the dosage is adjusted.
• Tell patient to avoid becoming overheated or dehydrated.
• When therapy starts or dosage increases, warn patient to avoid activities that require mental alertness until CNS effects of drug are known.
• Remind patient to have eyes examined at the start therapy and every 6 months during treatment to watch for cataract formation.
• Tell patient to call before taking other prescription or OTC drugs.
• Instruct women to report planned, suspected, or known pregnancy.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use