Splitting Levodopa/Carbidopa CR 100/25 mg Tablets
Do not split levodopa/carbidopa controlled-release (CR) 100/25 mg tablets, as this destroys the controlled-release mechanism and converts the medication into an immediate-release formulation with altered pharmacokinetics.
Why CR Tablets Should Not Be Split
The controlled-release formulation is specifically designed to provide sustained levodopa delivery over an extended period. When you split these tablets:
- The controlled-release matrix is disrupted, causing immediate release of the medication rather than the intended gradual release 1
- Bioavailability changes significantly - CR formulations have approximately 70-75% bioavailability compared to immediate-release products, and splitting alters this unpredictably 1
- Plasma level fluctuations increase, potentially worsening motor fluctuations rather than improving them 2
Alternative Approaches for Dose Adjustment
If you need smaller or more frequent doses for this patient:
Switch to Immediate-Release Formulation
- Use immediate-release (IR) levodopa/carbidopa tablets instead, which can be safely split if needed 2
- A new functionally scored IR formulation of carbidopa/levodopa 25/100 mg is specifically designed for precise splitting and demonstrated 44% reduction in plasma levodopa peaks when half-tablets were given every 2 hours versus whole tablets every 4 hours 2
- This approach provides more constant levodopa levels and reduces peak-to-trough fluctuations by 51% 2
Adjust CR Dosing Strategy
- Increase dosing frequency with whole CR tablets rather than splitting them 3
- CR 25/100 has a plasma half-life of approximately 1.7 hours and does not accumulate with twice-daily dosing 3
- Consider switching between available CR strengths (25/100,50/200) to achieve desired total daily dose 1
Important Clinical Considerations
- Timing with meals matters: Administer levodopa at least 30 minutes before meals to avoid protein interference with absorption 4, 5, 6
- Monitor for motor fluctuations when making any formulation changes, as the pharmacokinetic profiles differ substantially between CR and IR products 1
- Orally disintegrating tablets (ODTs) are another alternative for patients with swallowing difficulties, though these are IR formulations 7