What is a typical dosing regimen for Immediate Release (IR) and Extended Release (ER) levodopa?

Typical Levodopa Dosing Regimens

For immediate-release (IR) carbidopa-levodopa, start with 25/100 mg three times daily, titrating upward based on response; for extended-release (ER) formulations like IPX203, start with conversion from IR at approximately a 2.8-3:1 ratio and dose 3 times daily. 1, 2, 3

Immediate-Release (IR) Carbidopa-Levodopa Dosing

Initial Dosing

• Start with 25/100 mg (carbidopa/levodopa) three times daily 1
• Administer at least 30 minutes before meals to optimize absorption and avoid competition with dietary proteins 4
• Do not attempt to titrate to complete "normality" as this leads to toxicity 1

Typical Maintenance Dosing

• Standard regimen: 25/100 mg dosed 4-5 times daily for patients with motor fluctuations 3
• Total daily levodopa dose typically ranges from 400 mg or more in patients experiencing motor fluctuations 3
• Dosing frequency of every 4 hours is common, though every 2-hour dosing with half-tablets (50 mg levodopa) reduces plasma fluctuations by 44% 5

Higher Dose Formulations

• Levodopa/carbidopa/entacapone 200/50/200 mg is available for patients requiring higher individual doses, providing improved symptomatic control with reduced pill burden 6

Extended-Release (ER) Carbidopa-Levodopa Dosing

IPX203 (CREXONT®) - Novel ER Formulation

Conversion from IR to ER:

• Use a conversion ratio of approximately 2.8-2.9:1 (ER dose to IR dose) based on the patient's most frequent single IR dose 2, 3
• For example, if a patient takes 100 mg levodopa IR per dose, convert to approximately 280-290 mg levodopa ER per dose 2

Initial ER Dosing:

• Start with 3 times daily dosing for most patients after conversion 2, 3
• 84% of patients remain on 3 times daily dosing after titration 2
• Dosing range: 2-4 times daily based on clinical response 2

Clinical Advantage:

• IPX203 dosed 3 times daily provides equivalent or superior on-time compared to IR dosed 5 times daily 3
• Provides 1.55 additional hours of good on-time per dose compared to IR 3

Critical Dosing Considerations

Timing and Absorption

• Avoid high-protein meals when dosing, as dietary amino acids compete with levodopa absorption 4
• Consider protein redistribution diet: low-protein breakfast and lunch, normal protein at dinner to maximize daytime medication efficacy 4

Titration Strategy

• Titrate based on clinical response, not to achieve complete symptom resolution 1
• Monitor for dyskinesias, which may require dose reduction 4
• Adjust timing if sleep disturbances occur (take 1-2 hours before bedtime for insomnia) 7

Common Pitfalls

• Avoid taking with protein-rich meals - this is the most common cause of reduced efficacy 4
• Do not use controlled-release formulations interchangeably with IR without proper conversion ratios 3
• Watch for nausea (4.3% with ER formulations) - most common adverse effect 3