What is the proper dosing and precautions for Quetiapine (Seroquel)?

Quetiapine (Seroquel) Dosing and Precautions

For schizophrenia in adults, start quetiapine at 25 mg twice daily on Day 1, increase to 300-400 mg/day by Day 4 in divided doses, with a recommended target of 300-450 mg/day and maximum of 750 mg/day. 1

Standard Dosing by Indication

Schizophrenia - Adults

• Day 1: 25 mg twice daily 1
• Days 2-3: Increase by 25-50 mg increments, divided 2-3 times daily 1
• Day 4: Target 300-400 mg/day 1
• Maintenance: 150-750 mg/day (optimal 300-450 mg/day) 1, 2
• Maximum: 750 mg/day 1
• Further adjustments in 25-50 mg increments, with at least 2 days between changes 1

Schizophrenia - Adolescents (13-17 years)

• Day 1: 25 mg twice daily 1
• Day 2: 100 mg total (divided) 1
• Day 3: 200 mg total 1
• Day 4: 300 mg total 1
• Day 5: 400 mg total 1
• Target: 400-800 mg/day 1
• Maximum: 800 mg/day 1

Bipolar Mania - Adults

• Day 1: 100 mg total (divided) 1
• Day 2: 200 mg total 1
• Day 3: 300 mg total 1
• Day 4: 400 mg total 1
• May increase to 800 mg/day by Day 6 in increments ≤200 mg/day 1
• Target: 400-800 mg/day 1

Bipolar Depression - Adults

• Administer once daily at bedtime 1
• Day 1: 50 mg 1
• Day 2: 100 mg 1
• Day 3: 200 mg 1
• Day 4 and maintenance: 300 mg/day 1
• Maximum: 300 mg/day 1

Special Population Dosing Adjustments

Elderly Patients

• Start at 50 mg/day 1
• Increase in 50 mg/day increments based on response 1
• Use slower titration and lower target doses due to predisposition to hypotensive reactions 1
• Consider starting at 25 mg/day in frail elderly 2

Hepatic Impairment

• Start at 25 mg/day 1
• Increase daily in 25-50 mg increments to effective dose 1
• Mean oral clearance reduced by approximately 25% in hepatic cirrhosis 2

Renal Impairment

• Use with caution 1
• Mean oral clearance reduced by approximately 25% in severe renal impairment 2

Critical Drug Interactions Requiring Dose Modification

With CYP3A4 Inhibitors (ketoconazole, itraconazole, ritonavir, nefazodone)

• Reduce quetiapine dose to one-sixth (1/6) of original dose 1
• When inhibitor discontinued, increase quetiapine by 6-fold 1

With CYP3A4 Inducers (phenytoin, carbamazepine, rifampin, St. John's wort)

• Increase quetiapine up to 5-fold of original dose for chronic treatment (>7-14 days) 1, 3
• Titrate based on clinical response 1
• When inducer discontinued, reduce to original level within 7-14 days 1

Key Precautions and Monitoring

Cardiovascular

• Monitor for orthostatic hypotension, especially during initial titration 4
• Common adverse events include dizziness (9.6% vs 4.4% placebo) and postural hypotension 2
• Tachycardia may occur 2

Metabolic

• Weight gain: Approximately 2.1 kg in short-term trials 2
• Monitor blood glucose and lipid parameters, as clinically relevant increases can occur 5
• Small dose-related decreases in total and free thyroxine (usually reversible) 2

Neurological

• Extrapyramidal symptoms occur at placebo-level incidence across entire dose range 6
• Sedation and somnolence common (17.5% vs 10.7% placebo) 2
• Does not elevate prolactin levels 2, 6

Hepatic

• Asymptomatic, transient elevations in hepatic transaminases (particularly ALT) may occur 2
• Monitor liver function periodically 2

Administration Considerations

• Administer on empty stomach to maximize effectiveness 4
• Can be given twice or three times daily depending on indication 1
• Twice daily administration as effective as three times daily for same total dose 2

Discontinuation and Reinitiation

Discontinuation

• Rapid dose decrease or abrupt discontinuation can produce withdrawal symptoms 4
• Taper gradually when discontinuing 4

Reinitiation

• Off >1 week: Follow initial dosing schedule 1
• Off <1 week: May reinitiate maintenance dose without gradual escalation 1

Common Pitfalls to Avoid

• Do not exceed 750 mg/day in adults with schizophrenia despite some literature suggesting higher doses—controlled data support standard range 1, 7
• Do not use during pregnancy or nursing 4
• Avoid concomitant CNS depressants and alcohol due to additive psychomotor effects 4
• Do not forget dose adjustments with CYP3A4 inhibitors/inducers—failure to adjust can lead to toxicity or treatment failure 1
• Monitor for signs of depression, compromised respiratory function, or hepatic/cardiac failure 4

Acute/Stat Dosing for Agitation

• For acute agitation or delirium: 25-50 mg stat with caution in elderly 4
• Maximum single dose for immediate administration: 750 mg/day (can be single or divided doses) 4
• Monitor closely for orthostatic hypotension and sedation 4