A-Z Drug Facts > Quetiapine Fumarate

Quetiapine Fumarate

Pronunciation: (kwe-TYE-a-peen FUE-ma-rate)
Class: Antipsychotic, Dibenzapine derivative

Trade Names:
Seroquel
- Tablets 25 mg
- Tablets 50 mg
- Tablets 100 mg
- Tablets 200 mg
- Tablets 300 mg
- Tablets 400 mg

Trade Names:
Seroquel XR
- Tablets, ER 50 mg
- Tablets, ER 150 mg
- Tablets, ER 200 mg
- Tablets, ER 300 mg
- Tablets, ER 400 mg

Pharmacology

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Has antipsychotic effects, apparently caused by dopamine- and serotonin-receptor blockade in the CNS.

Pharmacokinetics

Absorption

Rapid absorption. T _max is 1.5 h. Bioavailability is 100%. Food increases C _max by 25% and AUC by 15%.

ER tablets

C _max is approximately 6 h. High-fat meal increases C _max and AUC by as much as 52% and 22%, respectively; however, a light meal has no effect.

Distribution

Widely distributed throughout. Vd is about 10 L/kg. It is 83% bound to plasma proteins.

Metabolism

Highly metabolized by the liver via CYP3A4 isoenzyme. Major metabolic pathways are sulfoxidation to the sulfoxide metabolite and oxidation to parent acid metabolite; both metabolites are inactive. Active metabolite is N-desalkyl quetiapine.

Elimination

Mainly via hepatic metabolism; less than 1% excreted as unchanged drug. About 73% of dose recovered in urine and 20% in feces. The mean terminal half-life for immediate-release is 6 h, for ER is 7 h, and for N-desalkyl quetiapine is 9 to 12 h.

Special Populations

Renal Function Impairment

CrCl 10 to 30 mL/min had 25% lower Cl; dosage adjustment not needed.

Hepatic Function Impairment

30% lower Cl; AUC and C _max 3-fold higher. Dosage adjustment may be needed.

Elderly

Oral Cl reduced 40%. Dosage adjustments may be needed.

Gender, race, smoking

No effect on the pharmacokinetics.

Indications and Usage

Treatment of schizophrenia ( Seroquel or Seroquel XR ); treatment of acute manic episodes associated with bipolar I disorder, as either monotherapy or adjunct therapy to lithium or divalproex ( Seroquel ); treatment of depressive episodes associated with bipolar I disorder ( Seroquel ); maintenance treatment of bipolar I disorder as adjunct therapy to lithium or divalproex ( Seroquel or Seroquel XR ); treatment of depression ( Seroquel ); treatment of acute depressive episodes associated with bipolar disorder ( Seroquel XR ); acute manic or mixed episodes associated with bipolar disorder as monotherapy and as an adjunct to lithium or divalproex therapy ( Seroquel XR ).

Unlabeled Uses

Alcohol dependence; Tourette syndrome in children and adolescents.

Contraindications

Standard considerations.

Dosage and Administration

Acute Bipolar Mania
Adults

PO ( Seroquel ) 100 mg/day in 2 divided doses on day 1; increase to 400 mg/day on day 4 in increments of up to 100 mg/day in 2 divided doses. Further dosage adjustments of up to 800 mg/day by day 6 should be in increments of no more than 200 mg/day. ( Seroquel XR ) Start with 300 mg on day one in the evening, then increase dose to 600 mg on day 2. Adjust dose between 400 and 800 mg beginning on day 3, depending on the response and tolerability.

Maintenance in Bipolar I Disorder
Adults

PO ( Seroquel ) Generally, in the maintenance phase, patients are continued on the same dose on which they were stabilized during dose stabilization.

Depression
Adults

PO ( Seroquel ) Start with 50 mg once daily at bedtime. Increase to 100 mg on day 2, 200 mg on day 3, and 300 mg on day 4. If indicated, the dose may be increased to 400 mg on day 5 and 600 mg on day 8.

Schizophrenia
Adults

PO ( Seroquel ) 25 mg twice daily initially; may increase in increments of 25 to 50 mg twice daily to 3 times daily on days 2 and 3 to target range of 300 to 400 mg/day by day 4. Increase dosage every 2 days by 25 to 50 mg twice daily as indicated. Therapeutic dosage range is 150 to 750 mg/day.

Adults

PO ( Seroquel XR ) Start with 300 mg once daily, preferably in the evening. Dosage increases can be made at daily intervals in increments of up to 300 mg/day. Dosages above 800 mg/day have not been evaluated.

Maintenance in Schizophrenia
Adults

PO ( Seroquel XR ) Studies have shown drug to be effective in delaying time to relapse in patients stabilized on Seroquel XR 400 to 800 mg/day for 16 wk.

Switching from Seroquel to Seroquel XR
Adults

PO Patients may be switched from the immediate-release formulation to the ER formulation at the equivalent total daily dose taken once daily. Individual dosage adjustments may be necessary.

Elderly/Hepatic Function Impairment
Adults Seroquel

PO Start with 25 mg/day; increase in daily increments of 25 to 50 mg/day to an effective dose.

Seroquel XR

PO Start with 50 mg/day and increase the dose in increments of 50 mg/day depending on the response and tolerability.

General Advice

• Safety of dosages higher than 800 mg/day has not been evaluated.
• Take immediate-release without regard to meals. Take with food if stomach upset occurs.
• Seroquel XR should be taken without food or with a light meal (about 300 calories).
• Long-term use (more than 6 wk) not evaluated. Periodically reevaluate usefulness.
• When restarting patients who have had an interval of less than 1 wk off quetiapine, resume maintenance dose. If the interval is more than 1 wk, follow initial titration period.
• Seroquel XR tablets should be swallowed whole and not split, chewed, or crushed.
• Use immediate-release tablet for schizophrenic patients requiring less than 200 mg per dose of Seroquel XR during the initial titration.
• Start schizophrenic elderly patients and/or patients with hepatic function impairment on the immediate-release formulation. Dose can be incrementally increased daily. When an effective dose has been reached, the patient may switch to an equivalent total daily dose of the ER formulation.
• Schizophrenic patients currently treated with divided doses of the immediate-release formulation may be switched to equivalent total daily doses of the ER formulation taken once daily.
• Consider a slower rate of dose titration and a lower target dose in elderly patients and in patients who are debilitated or who are predisposed to hypotension.

Storage/Stability

Store at 59° to 86°F.

Drug Interactions

Alcohol, CNS-acting drugs

Possible additive CNS depressant effects; use with caution. Avoid alcohol.

Antihypertensive agents

Hypotensive effects may be enhanced.

Cimetidine

Quetiapine concentrations may be increased slightly; dosage adjustment does not appear to be needed.

Dopamine agonists (eg, pramipexole, ropinirole), levodopa

Quetiapine may antagonize therapeutic effects of dopamine agonists and levodopa.

Fluvoxamine

Risk of NMS may be increased.

Hepatic enzyme inducers (eg, barbiturates, carbamazepine, glucocorticoids, phenytoin, rifampin)

May decrease the effects of quetiapine; increased doses of quetiapine may be necessary to maintain control of psychotic symptoms.

Inhibitors of CYP3A (eg, divalproex, erythromycin, fluconazole, itraconazole, ketoconazole, protease inhibitors, voriconazole)

May increase the effects of quetiapine; use with caution.

Lorazepam

Quetiapine increases the effects of lorazepam.

Thioridazine

May decrease the effects of quetiapine.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Seroquel

Postural hypotension (7%); tachycardia (6%); palpitation (at least 1%); cardiomyopathy, myocarditis (postmarketing).

Seroquel XR

Orthostatic hypotension (7%); hypotension, increased heart rate, syncope (less than 5%); tachycardia (4%).

CNS

Seroquel

Somnolence (57%); headache (21%); agitation (20%); dizziness (18%); extrapyramidal symptoms (13%); asthenia, fatigue (10%); lethargy (5%); anxiety (4%); akathisia, dyskinesia, dystonia, involuntary muscle contractions, psychomotor hyperactivity, restlessness (4% or less); dysarthria, hypertonia (at least 1%).

Seroquel XR

Somnolence (52%); dizziness (13%); extrapyramidal symptoms (11%); insomnia (9%); fatigue, headache (7%); dysarthria (5%); extrapyramidal disorder, hypertonia (4%); akathisia, dystonia, tardive dyskinesia, tremor (less than 5%); cogwheel rigidity (2% or less).

Dermatologic

Seroquel

Rash (4%); sweating (at least 1%); Stevens-Johnson syndrome (postmarketing).

Seroquel XR

Rash (less than 5%).

EENT

Seroquel

Pharyngitis (6%); nasal congestion (5%); rhinitis (3%); amblyopia (2%).

Seroquel XR

Nasal congestion (5%).

GI

Seroquel

Dry mouth (44%); constipation (10%); abdominal pain, dyspepsia (7%); vomiting (6%); abdominal pain (4%); gastroenteritis (2%); anorexia (at least 1%).

Seroquel XR

Dry mouth (37%); constipation (10%); dyspepsia (7%); dysphagia (less than 5%).

Genitourinary

Seroquel XR

Galactorrhea (postmarketing).

Hematologic

Seroquel

Leukopenia (at least 1%); agranulocytosis, decreased platelets (postmarketing).

Seroquel XR

Leukopenia (less than 5%); neutropenia (2%).

Hepatic

Seroquel

Increased ALT (5%); increased AST (3%).

Hypersensitivity

Seroquel

Anaphylactic reaction (postmarketing).

Lab Tests

Seroquel

Increased gamma-glutamyltransferase (1%).

Metabolic-Nutritional

Seroquel

Weight gain (6%); hyponatremia, SIADH (postmarketing).

Seroquel XR

Weight increased (10%).

Musculoskeletal

Seroquel

Back pain (5%); muscle rigidity (4% or less); rhabdomyolysis (postmarketing).

Respiratory

Seroquel

Dyspnea, increased cough (at least 1%).

Miscellaneous

Seroquel

Increased appetite (8%); pain (7%); fever (2%); flu-like syndrome (at least 1%).

Seroquel XR

Increased appetite (12%).

Precautions

Warnings Increased mortality Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death compared with taking placebo. Over the course of a 10-wk controlled trial, the rate of death in drug-treated patients was about 4.5% compared with 2.6% in the placebo group. Although the causes of death were varied, most of the deaths appeared to be either CV (eg, heart failure, sudden death) or infectious (eg, pneumonia) in nature. Suicidality Compared with placebo, antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults taking antidepressants for major depressive disorders and other psychiatric disorders. Appropriately monitor patients of all ages who are started on antidepressant therapy and observe closely for clinical worsening, suicidality, or unusual changes in behavior. Advise families and caregivers of the need for close observation and communication with the prescriber.

Monitor Monitor patients for symptoms of hyperglycemia. Perform fasting glucose testing in patients who develop hyperglycemia during treatment. Ensure that patients with risk factors for diabetes undergo fasting blood glucose testing at the start of therapy and periodically thereafter. Monitor patients with established diagnosis of diabetes mellitus regularly for worsening of glucose control. Perform eye exam at initiation of therapy to detect cataract formation and at 6mo intervals during chronic treatment. Monitor patients for any unusual changes in behavior (eg, agitation, irritability). Monitor patients requiring reintroduction of antipsychotic drug treatment after recovery from NMS for recurrence of NMS. Monitor WBC frequently during the first few months of therapy in patients with a preexisting low WBC or history of drug-induced leukopenia/neutropenia. Periodically reassess patients to determine the need for maintenance treatment and the appropriate dose for such treatment.

Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Elderly

May be more susceptible to effects. Consider lower starting dose, slower titration, and careful monitoring. May be at increased risk of tardive dyskinesia, especially elderly women.

Hepatic Function

Dosage adjustment may be needed.

Body temperature regulation

Antipsychotics can disrupt the body's ability to reduce core temperature.

Cardiac patients

Use with caution because of the risk of hypotension.

Cataracts

Lens changes have been observed in patients during long-term treatment.

Cognitive and motor performance

Mental and/or physical abilities may be impaired, especially during the first few days of therapy.

Debilitated patients

Consider lower starting dose, slower titration, and careful monitoring.

Dysphagia

Antipsychotics have been associated with esophageal dysmotility and aspiration. Use with caution in patients at risk for aspiration pneumonia.

Hematologic effects

Agranulocytosis, leukopenia, and neutropenia have been reported during postmarketing experience.

Hyperglycemia and diabetes mellitus

Hyperglycemia, in some cases extreme and associated with ketoacidosis or hyperosmolar coma or death, may occur.

Hyperlipidemia

Increased cholesterol and/or triglycerides may occur.

Hyperprolactinemia

Patients treated with antipsychotic agents often have elevation in prolactin levels.

Hypothyroidism

May occur.

NMS

Has occurred with antipsychotics and is potentially fatal.

Orthostatic hypotension

May occur, especially during the initial dose-titration period. Use with caution in patients with known CV disease, cerebrovascular disease, or conditions that predispose to hypotension (eg, dehydration).

Priapism

Has been reported.

Seizures

Use with caution in patients with a history of seizures or with conditions that potentially lower the seizure threshold (eg, Alzheimer dementia).

Suicide

Closely supervise high-risk patients; prescribe small quantities.

Tardive dyskinesia

A potentially irreversible syndrome of involuntary body and facial movements may occur.

Transaminase elevations

Asymptomatic, transient, and reversible elevations in serum transaminases (mainly ALT) may occur.

Weight gain

Has been reported in patients receiving quetiapine.

Withdrawal

Acute withdrawal symptoms, including nausea, vomiting, and insomnia, have been reported rarely after abrupt cessation of therapy.

Overdosage

Symptoms

Coma, death, drowsiness, first-degree heart block, hypokalemia, hypotension, QTc prolongation, sedation, tachycardia.

Patient Information

• Explain risk of developing tardive dyskinesia and NMS to patient.
• Advise patient to read Medication Guide before starting therapy and with each refill.
• Instruct patient to take Seroquel dose 2 or 3 times daily as prescribed, without regard to meals. Advise patient to take Seroquel XR once daily in the evening. Advise patient to take with food if stomach upset occurs.
• Advise patient that dose will be started low and then increased until max benefit is obtained.
• Instruct patient not to stop taking quetiapine when feeling better.
• Caution patient that if medication is stopped for more than 1 wk and then restarted, to follow the initial dose and titration schedule.
• Instruct patients with diabetes to monitor blood glucose more frequently when drug is started or dose is changed, and to inform health care provider of significant changes in readings.
• Tell patient to immediately report altered mental status, high fever, irregular or fast pulse, muscle rigidity, rash, seizures, or sweating to health care provider.
• Advise patient to notify health care provider of the following: excessive drowsiness, excessive urination and thirst, involuntary body or facial movements, weight gain.
• Advise patient to take frequent sips of water, suck on ice chips or sugarless hard candy, or chew sugarless gum if dry mouth occurs.
• Advise patient to avoid strenuous activity during periods of high temperature or humidity.
• Advise patients and family to be alert for the emergence of agitation, irritability, and unusual changes in behavior, as well as the emergence of suicidality, and to report such symptoms immediately to the health care provider.
• Instruct patient to avoid alcoholic beverages and sedatives (eg, diazepam) while taking quetiapine.
• Instruct patient to rise slowly from lying or sitting position and to avoid sudden position changes to prevent postural hypotension. Advise patient to report dizziness with position changes to health care provider. Caution patient that hot tubs and hot showers or baths may make dizziness worse.
• Advise patient taking antihypertensives to monitor BP at regular intervals.
• Advise patient that drug may impair judgment, thinking, or motor skills, or cause drowsiness, and to use caution while driving or performing other tasks requiring mental alertness until tolerance is determined.

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