QuetiapinePA study guide

Why they happen and how to manage them

Sedation

Strong histamine H1 blockade. Management: Give larger doses at bedtime; caution with driving.

Orthostatic hypotension and falls

Alpha-1 adrenergic blockade dilates vessels. Management: Titrate slowly, check orthostatic vital signs, and teach slow position changes.

Weight gain, hyperglycemia, dyslipidemia

H1 and 5HT2C blockade increases appetite; insulin resistance develops. Management: Monitor weight, fasting glucose, and lipids at baseline and periodically.

Constipation, dry mouth, urinary retention

Muscarinic blockade by the metabolite norquetiapine. Management: Use caution with other anticholinergics, prostate enlargement, or constipation.

NMS and tardive dyskinesia

Dopamine D2 blockade in the hypothalamus and basal ganglia; quetiapine binds D2 loosely, so risk is lower than with older antipsychotics. Management: Stop for NMS and give supportive care; screen for abnormal movements.

Sources: [1][2][3][4][5][6]

Common and serious

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Narrow therapeutic index

The label does not describe a narrow therapeutic index or direct dosing by measured blood levels of the drug.

Sources: [1]

Blood glucose

Why

Hyperglycemia and diabetes

When

Fasting glucose at baseline and periodically with diabetes or risk factors; whenever hyperglycemia symptoms appear

Normal

Fasting 70 to 99 mg/dL.

Sources: [1][2]

Blood pressure

Why

Orthostatic hypotension; hypertension in children and teens

When

During titration; at baseline and periodically in children and adolescents

Normal

Below 120/80 mm Hg.

Sources: [1][2][3]

Body weight

Why

Weight gain

When

Regularly during treatment

Sources: [1]

LDL cholesterol

Why

Dyslipidemia

When

Fasting lipids at baseline and periodically

Normal

Below 100 mg/dL in adults 20 and older.

Sources: [1][2][3]

TSH (thyroid-stimulating hormone)

Why

Dose-related drop in thyroid hormone

When

If hypothyroidism is suspected

Normal

0.4 to 4.8 µU/mL.

Sources: [1][2]

White blood cell count

Why

Leukopenia, neutropenia, agranulocytosis

When

Frequently in the first few months for patients with prior low WBC or drug-induced neutropenia

Act on

Stop if neutrophils fall below 1000/mm³, or at the first WBC decline without another cause

Normal

4,500 to 11,000 per microliter.

Sources: [1][2]

Adult dose

Schizophrenia

Day 1: 25 mg twice daily; increase by 25 to 50 mg on days 2 and 3 to 300 to 400 mg by day 4. Usual 150 to 750 mg/day; maximum 750 mg/day.

Bipolar mania (alone or with lithium or divalproex)

Total daily dose of 100, 200, 300, then 400 mg on days 1 to 4, given twice daily; then up to 800 mg/day by day 6. Usual 400 to 800 mg/day; maximum 800 mg/day.

Bipolar depression

Once at bedtime: 50 mg day 1, 100 mg day 2, 200 mg day 3, 300 mg day 4. Target and maximum 300 mg/day.

Bipolar I maintenance (with lithium or divalproex)

400 to 800 mg/day in two doses, usually the dose that stabilized the patient.

Sources: [1]

Renal adjustment

No specific dose adjustment is given; clinical experience in renal impairment is limited.

Sources: [1]

Hepatic adjustment

Start at 25 mg/day and increase daily by 25 to 50 mg/day as tolerated. Levels are higher because quetiapine is mostly cleared by the liver.

Sources: [1][2]

Boxed warning

Older adults with dementia-related psychosis treated with antipsychotics have a higher risk of death; quetiapine is not approved for them. Antidepressants raised suicidal thoughts and behavior in children, teens, and young adults; monitor all patients for worsening or suicidality. Not approved under age 10.

Sources: [1]

Contraindications

• Hypersensitivity to quetiapine or any ingredient; anaphylaxis has been reported

Sources: [1]

Key interactions

Strong CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir, indinavir, nefazodone)

Raise quetiapine levels. Cut the quetiapine dose to one sixth; raise it 6-fold again when the inhibitor stops.

Strong CYP3A4 inducers (phenytoin, carbamazepine, rifampin, St. John's wort)

Lower quetiapine levels; up to 5-fold higher doses may be needed. Return to the original dose within 7 to 14 days after the inducer stops.

Other QT-prolonging drugs (class IA or III antiarrhythmics, other antipsychotics, some fluoroquinolones)

Avoid the combination.

Alcohol and other CNS depressants

Added cognitive and motor impairment; limit alcohol.

Antihypertensives

Additive hypotension.

Anticholinergic drugs

Higher risk of severe constipation and bowel hypomotility.

Levodopa and dopamine agonists

Quetiapine may block their effect.

Sources: [1][2][3][4][5]

Antidote or reversal

No specific antidote. Overdose causes drowsiness, sedation, tachycardia, hypotension, and anticholinergic toxicity, with QT prolongation reported. Secure the airway and breathing, start continuous ECG monitoring at once, and give supportive care.

Sources: [1]

Pregnancy

Available data have not shown a drug-related risk of major birth defects. Newborns exposed in the third trimester can have extrapyramidal or withdrawal symptoms such as agitation, tremor, sleepiness, breathing trouble, and feeding problems. Untreated maternal illness also carries risk. A pregnancy registry exists.

Sources: [1]

Lactation

Small amounts pass into breast milk, under 1% of the mother's weight-adjusted dose. No consistent infant adverse effects have been reported; weigh breastfeeding benefits against the mother's need for the drug.

Sources: [1]

Pediatric

Schizophrenia ages 13 to 17: start 25 mg twice daily and titrate to 400 mg/day by day 5; range 400 to 800 mg/day. Bipolar mania ages 10 to 17: same titration, range 400 to 600 mg/day. Not established for bipolar depression or maintenance in children. Monitor blood pressure, which rose in children and teens, and watch for suicidality.

Sources: [1][2][3][4]

Geriatric

Clearance is 30% to 50% lower in older adults. Start at 50 mg/day and increase by 50 mg/day as tolerated, with slower titration and close monitoring for orthostasis and falls. Not approved for dementia-related psychosis.

Sources: [1][2][3]