Too Many Pills: Improving Delivery Systems for Parkinson’s Disease Drugs

You can find out more about NPF's National Medical Director, Dr. Michael S. Okun, by also visiting the NPF Center of Excellence, University of Florida Center for Movement Disorders & Neurorestoration.

If you ask a Parkinson’s disease (PD) patient to place a single day’s pills into the palm of one hand, you will find in most cases that it a harder task than expected. Though some early stage (PD) patients require only two or three doses of a dopaminergic drug each day, as the disease progresses most patients will need many more pills. Therefore, any new therapies with the potential to lessen the “pill burden” would be a welcome addition to the PD medication arsenal. In this month’s What’s Hot column we will discuss patches applied to the skin (transdermal), and intestinal gel formulations. Both of these therapies have the potential to lessen the medication burden placed on the PD patient.

Transdermal dopaminergic patches have important advantages over pill formulations and injectable medications. A patch formulation provides a more constant drug delivery, offers better compliance, avoids drug-food interactions, and offers the possibility of a once a day alternative. Additionally, pills may lose some clinical effectiveness when they are processed in the liver. The idea of a patch for a disease such as PD, where there are multiple drugs and multiple doses, is therefore very attractive to patients and to caregivers.

The transdermal patch Neupro® is a dopamine agonist that was recently removed from pharmacies by the FDA because of a manufacturing and quality control issue (crystallization of the drug on the patch). Recently, in 2012, following improvements and a study of the new formulation, it was reintroduced to the U.S. market.

Multiple pharmaceutical trials over many years have demonstrated that the effectiveness of the patch is similar to oral preparations of other dopamine agonists (e.g. pramipexole and roperinerole), and that the patch only needs to be applied once a day. Sleep disturbances and early morning functioning may be added advantages for some patch users, probably due to the continuous and slow delivery of the drug. The side effects of the patch were roughly identical to the other dopamine agonists, and all of the issues that occurred with the other dopamine agonists, were also observed with Rotigotine (e.g. leg swelling, nausea, sleepiness, impulse control, behavioral issues, hallucinations, etc.). Additionally, the patch formulations have been associated with local skin reactions in some patients. Recently, extended release preparations of the pill form of dopamine agonists have become available, and can be an option for patients with a reaction to the patch or a preference for a pill.

Another new therapy fresh out of clinical trials in the United States is Duodopa®. Duodopa was approved for use in Europe in 2004. Though we await the official published study results, late breaking data presented at the American Academy of Neurology conference in New Orleans (April 2012) suggested that there were significant benefits in improving “on” time and in reducing on-off fluctuations and dyskinesia. This therapy is pump-based and requires the patient to wear an external large “box” in the belt region which is used to administer the intestinal gel preparation through a surgically placed intestinal tube. One advantage of this type of therapy is that it does not require brain surgery (i.e. like DBS), however, Duodopa does require a very attentive caregiver who will need to attend to device management, skin management (for the tube), and also attend to medication refills. Early studies of Duodopa have revealed high rates of device-related problems with the intestinal tube (e.g. clogging, kinking, moving out of the correct location). Despite these tube related issues, Duodopa will likely be a great choice for many patients with on-off fluctuations, and will in most cases allow discontinuation of oral PD drugs.

In summary, all new PD therapies that can address the “pill burden” will be a welcome addition to the PD treatment options. Patients interested in the patch should be aware that the side effects are almost identical to oral dopamine agonists, and therefore great caution should be used in elderly patients and in those with histories of hallucinations, impulse control, and other behavioral or thinking disorders. The patch will not serve as a replacement for levodopa therapy in most PD cases, but it can augment levodopa in carefully selected patients. For those interested in the Duodopa pump they should keep in mind that is not yet available in the U.S. The pump could be an option for patients with severe on-off fluctuations and dyskinesia who cannot be easily managed with available oral/patch therapies and also may be an option for those who do not wish to undergo brain surgery.

Selected References:

Sprenger FS, Seppi K, Poewe W. Drug safety evaluation of rotigotine. Expert Opin Drug Saf. 2012 May;11(3):503-12. Epub 2012 Apr 3. PubMed PMID: 22468676.

Elmer LW, Surmann E, Boroojerdi B, Jankovic J. Long-term safety and tolerability of rotigotine transdermal system in patients with early-stage idiopathic Parkinson's disease: A prospective, open-label extension study. Parkinsonism Relat Disord. 2012 Feb 9. [Epub ahead of print] PubMed PMID: 22326237.

Elshoff JP, Braun M, Andreas JO, Middle M, Cawello W. Steady-state plasma concentration profile of transdermal rotigotine: an integrated analysis of three, open-label, randomized, phase I multiple dose studies. Clin Ther. 2012 Apr;34(4):966-78. Epub 2012 Mar 7. PubMed PMID: 22401642.

Perez-Lloret S, Rey MV, Ratti PL, Rascol O. Rotigotine transdermal patch for the treatment of Parkinson's Disease. Fundam Clin Pharmacol. 2012 Feb 9. doi: 10.1111/j.1472-8206.2012.01028.x. [Epub ahead of print] PubMed PMID: 22320451.

Nyholm D, Klangemo K, Johansson A. Levodopa/carbidopa intestinal gel infusion long-term therapy in advanced Parkinson's disease. Eur J Neurol. 2012 Feb 23. doi: 10.1111/j.1468-1331.2012.03679.x. [Epub ahead of print] PubMed PMID: 22360705.

Krones E, Zollner G, Petritsch W. Knotting of percutaneous endoscopic jejunostomy feeding tubes in two patients with Parkinson's disease and continuous Duodopa® treatment. Z Gastroenterol. 2012 Feb;50(2):213-6. Epub 2012 Feb 1. PubMed PMID: 22298101.

Posted: 5/2/2012 11:25:22 AM by Cathy Whitlock

Browse current and archived What's Hot in PD? articles, the National Parkinson Foundation's monthly blog for people with Parkinson's written by our National Medical Director, Dr. Michael S. Okun. 

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Each month, we will feature a new column by NPF's National Medical Director, Dr. Michael Okun, on the latest developments in Parkinson's disease research. Read the latest "What's Hot in PD?" below.

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