What leads you to consider a non-oral form of levodopa for the treatment of Parkinson’s disease?

I agree with Dr. @Dr. First Last's excellent review.

Consider non-oral forms of medication when there are concerns about dysphagia. Additionally, if the dosing frequency becomes too high (e.g., five times a day of levodopa), and the patient finds it difficult to maintain this schedule, consider long-acting non-oral supplements such as rotigotine, etc. Try to simplify the regimen to improve the patient’s comfort by keeping a sustained regimen that reduces motor fluctuations.

Of course, DBS and Duopa are other considerations, but they are different topics entirely.

Great question.

At the moment, most levodopa formulations are oral medications. There are two non-oral forms of levodopa that are currently in clinical use; an inhalation powder and a continuous enteral solution.

The levodopa inhalation powder is a rescue, on-demand medication used as needed for OFF periods. Given that it is absorbed through the pulmonary system and bypasses the GI system, it works faster than oral levodopa and can be a good tool to help with OFF periods. I would consider it when patients with Parkinson's disease start having significant motor fluctuations with frequent and unpredictable OFF periods. The only problem is that it can be quite difficult for patients to use the inhaler, particularly when they are OFF.

The continuous enteral solution of levodopa is administered through a percutaneous endoscopic gastrostomy and jejunal tube (PEG-J). Given the invasive nature of the PEG-J placement, this form of levodopa is not commonly used. However, it can be an effective treatment modality for patients with severe and advanced Parkinson's disease who have significant motor fluctuations and frequent OFF periods.

Continuous subcutaneous levodopa is not yet available for clinical use. However, the recent results on its efficacy are certainly promising.