Converting Quetiapine Fumarate Extended-Release to Immediate-Release
When converting from quetiapine XR 200 mg to immediate-release formulation, use a 1:1 total daily dose ratio, but divide the immediate-release dose into twice daily administration.
Conversion Principles
The conversion between quetiapine extended-release (XR) and immediate-release (IR) formulations should be based on maintaining equivalent therapeutic effects while accounting for the different pharmacokinetic profiles of each formulation.
- Total daily dose remains the same (1:1 ratio)
- Change in administration frequency is required
- Pharmacokinetic differences must be considered
Specific Conversion Instructions
From XR 200 mg to IR:
- Maintain the same total daily dose of 200 mg
- Divide into twice daily dosing:
- 100 mg in the morning
- 100 mg in the evening
Key Pharmacokinetic Considerations:
- Quetiapine IR reaches peak plasma concentration in 1-2 hours 1
- Quetiapine XR has a more gradual absorption profile with peak at approximately 5 hours 2
- Both formulations have similar overall drug exposure (AUC) at equivalent daily doses 3, 2
- The AUC ratio of quetiapine XR to IR is 1.04 (90% CI: 0.92-1.19), confirming bioequivalence 2
Clinical Implications of the Switch
Benefits of IR Formulation:
- More flexibility in dosing
- May be useful for patients who need more rapid onset of action
- Can be divided into unequal doses if needed (e.g., higher evening dose for sedation)
Potential Challenges:
- Twice-daily dosing may reduce adherence
- More pronounced peak effects may increase sedation shortly after dosing
- More variable plasma concentrations throughout the day 3
Monitoring After Conversion
After switching from XR to IR formulation:
- Monitor for increased sedation or somnolence within the first few hours after each dose
- Assess for any changes in efficacy due to different pharmacokinetic profile
- Consider temporarily holding quetiapine during acute illness with significant fluid losses 4
Special Considerations
- For elderly patients or those with hepatic impairment, consider starting with lower divided doses (e.g., 50 mg twice daily) 4
- If daytime sedation becomes problematic, the dosing can be adjusted to an unequal split (e.g., 75 mg morning/125 mg evening)
- If adherence is a concern with twice-daily dosing, reconsider whether the switch from XR to IR is appropriate
The pharmacokinetic studies confirm that while the overall drug exposure remains equivalent between formulations, the administration pattern must be adjusted to maintain therapeutic efficacy and minimize adverse effects.