From the Guidelines
For BC's delayed morning "on" times, I strongly recommend taking an immediate-release Sinemet (before getting out of bed in the morning) to quickly achieve therapeutic levels and improve morning mobility. This approach is supported by the fact that controlled-release formulations like Sinemet CR can take 1-2 hours to reach therapeutic levels, which may contribute to delayed "on" times 1. To further enhance absorption, it is advised to take levodopa-containing medications at least 30 minutes before meals, as dietary protein can compete with levodopa for intestinal absorption and transport across the blood-brain barrier 1. Some key points to consider in managing BC's condition include:
- Taking immediate-release Sinemet upon awakening to address morning akinesia
- Continuing rasagiline to help maintain dopamine levels
- Considering the tapering and potential discontinuation of benztropine if possible, due to its potential to contribute to cognitive issues and worsen motor symptoms in advanced Parkinson's disease
- Exploring additional options such as adding entacapone to extend levodopa's effect or using a bedtime dose of controlled-release levodopa to maintain therapeutic levels until morning if morning akinesia persists. It's also worth noting that a protein-redistribution dietary regimen, which involves consuming a low-protein breakfast and lunch and a higher protein dinner, may help maximize levodopa absorption and efficacy, as suggested by the ESPEN guideline on clinical nutrition in neurology 1.
From the FDA Drug Label
DOSAGE AND ADMINISTRATION Instructions for Use/Handling Carbidopa and Levodopa Orally Disintegrating Tablets, USP Just prior to administration, GENTLY remove the tablet from the bottle with dry hands. IMMEDIATELY place the carbidopa and levodopa orally disintegrating tablet on top of the tongue where it will dissolve in seconds, then swallow with saliva.
The recommended therapeutic plan for BC, who is experiencing delayed 'on' times in the morning, is to take an immediate release Sinemet (before getting out of bed in the morning). This approach can help alleviate the delayed 'on' times by providing a quicker release of levodopa, which can help BC get out of bed more easily in the morning. Another option is to take Amantadine extended-release (Gocovri) at bedtime. Option C is the recommended plan. 2
From the Research
Therapeutic Plans for Delayed 'On' Times in Parkinson's Disease
To address BC's issue of delayed 'on' times in the morning while taking Sinemet CR tid with rasagiline and benztropine, several therapeutic plans can be considered:
- Taking an immediate-release Sinemet before getting out of bed in the morning: This approach can help alleviate morning 'off' symptoms by providing a quicker onset of action compared to controlled-release formulations 3, 4.
- Using Amantadine extended-release (Gocovri) at bedtime: Amantadine can help reduce 'off' time and improve motor function in patients with Parkinson's disease, and its extended-release formulation allows for once-daily dosing at bedtime, which may help with morning 'on' times 5.
- Considering the use of Ongentys or Nourianz around lunchtime: Although not directly related to morning 'on' times, these medications can help reduce 'off' time and improve motor function in patients with Parkinson's disease, and their use around lunchtime may help with overall motor control throughout the day 6.
- Supplementing with an extra dose of Sinemet CR in the morning and/or taking rasagiline at bedtime: Adjusting the dosing schedule of current medications can help optimize their effectiveness, but this should be done under the guidance of a healthcare professional to avoid potential interactions or side effects 7, 5.
Key Considerations
When evaluating these therapeutic plans, it's essential to consider the individual patient's response to different medications and dosing regimens, as well as potential side effects and interactions. The goal is to find a balance between minimizing 'off' time and maximizing 'on' time without causing undue side effects or complications.
Relevant Studies
Studies have shown that delayed 'on' times are a common issue in patients with Parkinson's disease, affecting up to 56% of patients experiencing motor fluctuations 6. The use of controlled-release levodopa/carbidopa formulations, such as Sinemet CR, can help reduce motor fluctuations, but may not entirely eliminate delayed 'on' times 3, 4. Other medications, such as dopamine agonists and MAO-B inhibitors, can also be used to manage motor fluctuations and improve 'on' time 7, 5.