Converting Quetiapine XL 200mg to Immediate Release Formulation
When converting quetiapine extended-release 200mg to immediate-release formulation, the total daily dose should be divided into two doses with a 50% reduction in total daily dose, resulting in 50mg twice daily initially.
Conversion Principles
Quetiapine immediate-release (IR) and extended-release (XR/XL) formulations have significant differences in their pharmacokinetic profiles that must be considered when converting between them:
- Quetiapine XR has a lower peak plasma concentration (Cmax) and longer time to peak concentration (Tmax) compared to IR
- IR formulation reaches peak plasma levels faster and has higher sedation effects shortly after administration 1
- The bioavailability of XR is approximately 70% of the IR formulation 2
Conversion Algorithm
Calculate equivalent daily dose:
- Start with 50-60% of the XL dose when converting to IR
- For 200mg XL → approximately 100-120mg total daily IR dose
Divide for twice-daily dosing:
- IR formulation requires BID dosing due to shorter half-life (7 hours) 2
- 100-120mg total daily dose → 50-60mg BID
Titration schedule:
- Start with 50mg BID
- Assess response and tolerability
- May increase by 50mg increments every 2-3 days as needed
- Target effective dose typically between 150-750mg/day total 3
Important Clinical Considerations
Sedation Management
- IR formulation causes significantly greater sedation 1 hour after dosing compared to XR (VAS score 33.2 vs 11.3) 1
- Consider administering larger portion of daily dose at bedtime to manage sedation
- Morning sedation may be more pronounced with IR formulation
Monitoring Parameters
- Sedation and drowsiness (especially 1-2 hours post-dose)
- Orthostatic hypotension
- QTc prolongation
- Metabolic effects (weight, glucose, lipids)
- Therapeutic efficacy
Special Populations
- For elderly patients or those with hepatic impairment, consider starting with lower doses (25mg BID) 4
- Patients with difficulty swallowing tablets may benefit from compounded oral suspension (10mg/mL in Ora-Blend shows good stability for 60 days) 5
Practical Implementation
- Day 1: Discontinue 200mg XL and start 50mg IR twice daily
- Days 2-7: Monitor for efficacy and side effects
- After week 1: Adjust dose as needed in 50mg increments
- Dosing schedule: Consider uneven dosing (lower morning dose, higher evening dose) to minimize daytime sedation
Cautions
- Avoid abrupt discontinuation of XL formulation when switching
- Be prepared for potentially increased sedation with IR formulation, especially shortly after dosing
- Monitor more frequently during the transition period
- The conversion ratio is not exact and may need individualization based on clinical response
Remember that the IR formulation will produce more pronounced peak effects and may require dose adjustments to maintain efficacy while minimizing side effects.