How to manage motor fluctuations in a patient with Parkinson's disease on carbidopa (Carbidopa)/levodopa (Levodopa), 25/100 milligrams, two tabs four times a day (QID) plus 50/200 milligrams, one tab at bedtime (QHS), and Rasagiline (Rasagilene) 0.5 milligrams daily?

Management of Motor Fluctuations in Parkinson's Disease

For a patient with Parkinson's disease experiencing motor fluctuations on carbidopa/levodopa therapy, I recommend optimizing the current regimen by implementing a protein redistribution diet and increasing the rasagiline dose to 1 mg daily.

Current Clinical Situation

• 77-year-old male with Parkinson's disease
• Current medication: carbidopa/levodopa 25/100 mg, two tabs QID plus 50/200 mg one tab QHS
• Recently started rasagiline 0.5 mg daily
• Experiencing motor fluctuations: wearing off 30-60 minutes before next dose
• Symptoms during "off" periods: worsening tremor, shorter steps, freezing of gait
• MRI brain normal, DAT scan shows decreased uptake in bilateral putamen consistent with PD

Management Strategy

Step 1: Optimize Rasagiline Dosing

• Increase rasagiline from 0.5 mg to 1 mg daily 1
  • Clinical trials show rasagiline 1 mg/day is more effective than 0.5 mg/day in reducing "off" time
  • In advanced PD with motor fluctuations, rasagiline 1 mg reduced "off" time by 1.9 hours compared to 1.4 hours with 0.5 mg 1

Step 2: Implement Dietary Modifications

• Advise protein redistribution diet 2
  • Low protein breakfast and lunch with normal protein intake at dinner
  • This approach improves motor function, reduces disability, and increases "ON" state duration 2
  • Take levodopa at least 30 minutes before meals to maximize absorption 2
  • Consider using specialized low-protein foods designed for renal patients to help achieve protein redistribution 2

Step 3: Adjust Carbidopa/Levodopa Regimen

• Consider one of these modifications to the levodopa regimen:
  • Option 1: Increase frequency of dosing to reduce "off" time (e.g., five times daily instead of four) 3
  • Option 2: Switch to controlled-release formulation for nighttime dose to improve morning function 4
  • Option 3: Add an extra dose between current doses when "wearing off" occurs 3

Step 4: Monitor for Side Effects and Complications

• Watch for dyskinesias - may require reduction in levodopa dose if they develop or worsen 2
• Monitor nutritional status - protein redistribution diets require monitoring for weight loss and micronutrient deficiencies 2
• Check homocysteine levels and vitamin B status - levodopa therapy can cause hyperhomocysteinemia 2
• Monitor blood pressure - rasagiline may cause hypertension, especially when combined with levodopa 1

Additional Considerations

Potential Future Interventions if Above Strategy Fails

• Consider adding entacapone to extend levodopa half-life 3
• Evaluate for duodenal levodopa infusion for severe fluctuations 5
• Consider inhaled levodopa for rapid relief of "off" episodes 6
• Assess candidacy for deep brain stimulation if fluctuations become severe despite medication optimization 3

Important Precautions

• Do not exceed rasagiline 1 mg daily due to risk of hypertension 1
• Avoid certain medications with rasagiline including meperidine, tramadol, methadone, propoxyphene, St. John's wort, cyclobenzaprine, and dextromethorphan due to risk of serotonin syndrome 1
• Monitor for potential side effects of rasagiline including nausea, dizziness, insomnia, and dyskinesia 1

By implementing this comprehensive approach focusing on optimizing medication timing, dosing, and dietary modifications, most patients with motor fluctuations can achieve significant improvement in symptom control and quality of life 2.