IPX066 (now called Rytary) and What Patients Really Want in New Carbidopa/Levodopa (Sinemet) Formulations
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.
We frequently hear from Parkinson’s disease patients that their current carbidopa/levodopa medication preparations fail to adequately address their disease-related symptoms. The frequently cited medication related problems include:
- Medication dosages taking too long to “kick in” and start working
- Medication wearing off before the next scheduled medication dose
- Severe on-off medication fluctuation periods (e.g. rapid cycling during the day ranging from feeling completely on medication to completely off medication)
- Dyskinesia (too much movement, usually resulting from too high of a blood level of dopamine)
- Too many pills
- Too many medication dosage intervals (e.g. taking medications every 1-2 hours throughout the waking day).
Patients also have other issues that levodopa does not address, including walking, balance, talking, and thinking issues, but these will likely require a totally different approach than simple levodopa replacement. Dr. Robert Hauser at the National Parkinson Foundation Center of Excellence at the University of South Florida, along with colleagues from 68 North American and European study sites, recently published a paper on a new extended release formulation of carbidopa/levodopa (IPX066 -- called Rytary as of January 2015). In this month’s What’s Hot in PD? Column, I will review the results of the Hauser et. al. study, and also discuss the pressing need for better medication formulations to address the symptoms Parkinson’s disease.
The new formulation that was studied, carbidopa/levodopa extended release (IPX066/Rytary), is different than its predecessors. It contains special beads designed to dissolve at different rates within the stomach and the intestines. The medication capsule was in general designed to provide longer lasting benefit for patients with Parkinson’s disease. This current randomized study included 393 Parkinson’s disease patients who all reported at least of 2.5 hours of “off time,” defined as periods when they felt the medication was not working. The authors aimed to improve the number of hours of “off time” each day for patients randomized to the new extended release formulation (IPX066/Rytary) as compared to the older and standard regular release carbidopa/levodopa. The results revealed that the group on extended release formulations took less overall medication dosages (3.6 vs. 5 doses per day); however they also took more total pills. The daily “off-time” improved by over an hour each day in the extended release formulation. Both medications in this trial were safe and well tolerated.
If we return to the six areas where Parkinson’s disease patients have been seeking improved medication formulations, IPX066 (Rytary) was observed to improve issues in two categories: wearing off between dosages, and improvement by increasing the time interval between dosages. The results of the current study cannot be widely applied to patients with severe dyskinesia, severe on-off fluctuations, and later stage disease. The new extended release formulation also increased the total blood-stream levodopa exposure by 30-40% as compared to conventional immediate release levodopa. Increasing levodopa in the bloodstream is thought to decrease the threshold for dyskinesia, as has been observed with other Parkinson’s drugs such as Entacapone and Stalevo. Although dosed less frequently, the extended release formulation actually required more total pills per day. The authors felt that a newer formulation of the same drug, which they anticipate will be used in clinical practice, would allow for a decrease in pill number.
Patients and families should be excited by the news that a new formulation of carbidopa/levodopa will be released in the next several months. However, patients and clinicians should be aware that there are limitations in the use of IPX066 (Rytary), and that caution should be exercised, especially in potentially lowering the dyskinesia threshold. Dosages and dosage intervals of any formulation of carbidopa/levodopa, including IPX066 (Rytary), should be carefully adjusted at each clinic visit to address changes in Parkinson’s symptoms. The success or failure of dopamine replacement therapy is more dependent on the expert adjusting the therapy than the formulation. It is good news that drug manufacturers are now listening to Parkinson’s disease patients, and are trying to address their six major concerns, though it would seem obvious there is a lot of room for improvement.
Posted: 4/2/2013 10:49:17 AM by
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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Finally a DBS Expert Consensus Statement Aimed at Their True Customers: The Patients
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