Current FDA-Approved Slow Release Levodopa Preparations
Licensed Formulations
The FDA has licensed two slow-release levodopa preparations: Sinemet CR (carbidopa 50 mg/levodopa 200 mg controlled-release tablets) and Rytary/IPX066 (carbidopa/levodopa extended-release capsules with multiple dosage strengths). 1, 2
Sinemet CR (Controlled-Release)
- Formulation design: Monolithic matrix tablet using an erodible polymer matrix that releases both carbidopa and levodopa through surface dissolution and erosion at a first-order release rate 3
- Standard strength: 50 mg carbidopa/200 mg levodopa 1
- Pharmacokinetics: Time to peak levodopa concentration is approximately 2.3 hours (versus 1.1 hours for immediate-release), with onset of maximal clinical improvement at 2.2 hours 1
- Duration of effect: Nearly double that of conventional Sinemet 25/100, providing more sustained levodopa delivery over 3-4 hours 4
- Clinical use: Reduces peak-dose and "wearing-off" responses, though requires higher total daily levodopa dosage (mean 1,781 mg/day versus 1,340 mg/day for IR) while reducing dosing frequency (mean 5.4 versus 10.2 doses daily) 1
Rytary (Numient in EU) - Extended-Release Capsules
- Formulation design: Contains beads of carbidopa and levodopa designed to release at different rates in the gastrointestinal tract 2
- Pharmacokinetics: Provides initial rapid absorption comparable to immediate-release formulation (peak at approximately 1 hour), followed by sustained therapeutic levodopa concentrations maintained for 4-5 hours 2, 5
- Clinical efficacy: Significantly reduces daily "off-time" compared to immediate-release carbidopa/levodopa or carbidopa/levodopa plus entacapone in advanced Parkinson's disease, without increasing troublesome dyskinesia 2
- Advantages: Reduces peak-to-trough plasma concentration excursions to minimize motor fluctuations associated with pulsatile dopamine receptor stimulation 5
Clinical Context
Important Caveats
- Slower onset with Sinemet CR: The delayed onset of clinical response (2.2 hours versus 1.1 hours) means some patients may benefit from combination therapy using immediate-release Sinemet 25/100 as a "booster dose" with Sinemet CR for sustained effect 4
- Bioavailability considerations: Controlled-release formulations with slower in vitro release rates produce lower plasma levels, which influenced the selection of the current Sinemet CR formulation 3
- Not for restless legs syndrome: Current guidelines suggest against standard use of levodopa for RLS due to augmentation risk with long-term use, though it may be considered for short-term symptom reduction in select patients 6