Switching from Immediate-Release to Extended-Release Carbidopa-Levodopa
When converting from immediate-release (IR) to extended-release (ER) carbidopa-levodopa, start by approximately doubling the total daily levodopa dose and reducing dosing frequency, then titrate based on individual motor response over several weeks.
Initial Conversion Strategy
The fundamental principle is that ER formulations require higher total daily doses than IR due to different pharmacokinetics. 1, 2
Starting Dose Calculation
- Begin with approximately 2:1 conversion ratio (ER:IR total daily levodopa dose) 2, 3
- Calculate the patient's current total daily IR levodopa dose
- Multiply by 2 to estimate initial ER daily dose 2
- Note: Individual ratios can range from 1.0 to 3.5:1, with a mean of 2.0±0.6:1 3
Important caveat: Patients taking fewer IR doses per day may require higher conversion ratios (closer to 3:1), while those on more frequent dosing may need ratios closer to 2:1 3
Dosing Frequency Adjustment
Reduce the number of daily doses compared to IR regimen 1, 4
- IR patients typically dose 5 times daily 1, 4
- ER formulations (IPX066/Rytary) typically require 3-4 doses daily 1, 4
- IPX203 typically requires 3 doses daily 4
Tailor initial frequency to the patient's specific motor complications: 2
- For wearing-off: Use relatively high individual doses at lower frequency
- For dyskinesia: Use relatively lower individual doses, potentially maintaining similar frequency to IR
Titration Period
Expect a 4-7 week conversion and optimization period 1, 4
- Week 1-3: Open-label IR dose optimization if needed 1, 4
- Week 4-7: ER conversion and titration phase 1, 4
- Continue adjustments based on motor response, off-time, and dyskinesia 2
Monitor closely during conversion: 1
- 5% of patients may withdraw due to adverse events during conversion
- 3% may withdraw due to lack of efficacy
- Most common early adverse events include insomnia (3%), nausea (3%), and falls (3%)
Expected Outcomes
ER formulations provide superior motor control compared to IR: 1, 4
- Reduction in off-time by approximately 1.17 hours per day compared to IR 1
- Increase in good on-time (without troublesome dyskinesia) by 0.53 hours per day 4
- Good on-time per dose increases by 1.55 hours with ER versus IR 4
- Fewer daily doses required (3 vs 5 times daily) 1, 4
Clinical Pearls and Pitfalls
Set appropriate patient expectations before conversion: 2
- The primary goal is steadier levodopa response, not necessarily reduced dosing frequency
- Some patients may maintain similar frequency but with improved motor control
- Higher total daily levodopa doses are expected and appropriate
Common conversion errors to avoid:
- Using 1:1 conversion ratio will result in underdosing 2, 3
- Attempting to maintain the same dosing frequency as IR may not optimize ER benefits 1, 4
- Abandoning conversion too early—allow adequate titration time (4-7 weeks) 1, 4
Predictors of higher conversion ratios: 3
- Patients on fewer baseline IR doses per day require higher ER:IR ratios
- Presence of dyskinesia does NOT predict conversion ratio
Tolerability considerations: 4
- Nausea occurs in 4.3% with ER vs 0.8% with IR during maintenance
- Anxiety occurs in 2.7% with ER vs 0% with IR
- Most adverse events are mild and manageable