The Many Lives of Levodopa

jbeck.jpgThe start of 2015 has been noteworthy for those with Parkinson’s disease (PD) as two new therapies  – Rytary™ and Duopa™ – were approved by the FDA at the start of January. Both therapies are updates to the gold-standard treatment of carbidopa/levodopa for those with PD. Manufacturers of both therapies hope to have the medications available on pharmacy shelves in the next few months.

Yes, carbidopa/levodopa first came into use around 1970. However, these new therapies address a real need that current carbidopa/levodopa or Sinemet cannot meet … and that is good news. PDF has covered what Rytary and Duopa are (check out my videos too on both here and here), but let’s discuss them in detail and find out what makes them different.

MedicineRtyary: Briefly, Rytary is an extended release, pill form of carbidopa/levodopa that helps maintain more stable blood levels of levodopa in order to minimize the “off” times or drop in symptom relief that some people with moderate to advanced PD can experience between regular doses of their Parkinson’s medication. One of the nice benefits of Rytary is that people may be able to modestly reduce the number of pills they take as they switch from Sinemet to Rytary. That switch is not a straightforward pill swap. That is, it is unlikely that the same pill strength and timing of Sinemet will match what one would need to take for Rytary, and each person will need careful adjustment from his or her neurologist.

Duopa: The other new therapy, Duopa, is a combination of medication and medical device. The medication part of Duopa is carbidopa/levodopa in a gel form, which is packaged in a cassette and then slowly infused into the small intestine. The medical device part of Duopa is a pump. In the end, the two work together so that one gets their own fill-er-up tube just for the PD medication. Here’s how: the pump is connected to a port that is surgically implanted in the abdomen, which in turn, connects to a tube that snakes from the stomach into the small intestine. The surgical procedure to install the port and tube, called percutaneous endoscopic gastrostomy or PEG, is one of the most common endoscopic procedures in the US and takes about 15-30 minutes. With the port in place and the pump operational, Duopa can provide a continuous infusion of carbidopa/levodopa gel for up to 16 hours.

This infusion has been shown to produce near constant levels of levodopa in the bloodstream and, in trials sponsored by the manufacturer, an increase in “on” time of nearly five hours with a similar reduction in “off” time. For people with advanced PD and severe motor complications, Duopa may be a good therapy. However, it is important to remember that it involves surgery and thus presents possible complications. It isn’t for everyone, but for those hesitant or unable to undergo deep brain stimulation (DBS), it may be an option.

How do these new drugs fit in with existing PD therapies?

Immediate release carbidopa/levodopa, or Sinemet®, remains the mainstay of PD symptom treatment. Evidence strongly suggests that early use of levodopa versus other medications may not only be beneficial but it is also unlikely to influence when many people will experience motor complications (e.g., “off” times and dyskinesias) that can be side-effects of levodopa therapy.

Nevertheless, as PD progresses, the efficacy of Sinemet changes too, particularly the wearing off of its benefits between doses. This is where Rytary may be a useful tool for neurologists to use in order to help maintain maximum symptom relief. As PD progresses further and motor complications become more pronounced, Duopa or DBS may be the next stage of treatments that neurologists discuss next. It is even possible that a person could use both Duopa and DBS to help control motor symptoms.

But wait, there is more.

These two products are not the end of new uses of carbidopa/levodopa. Scientists are still thinking of creative and effective ways in which to deliver this drug in order to help better manage PD symptoms.

  • For example, Acorda is working on an inhaled form of levodopa to rescue people who suddenly experience an “off” episode, much like asthmatics use inhalers when their asthma flares up. And like asthma inhalers, this inhaled levodopa is not intended to replace regular carbidopa/levodopa therapy. If successful in clinical trials, it will join Apokyn, the injectable apomorphine drug, as one of two medications available for rescue from “off” episodes.
  • Also, scientists are trying to streamline the Duopa approach by envisioning a levodopa infusion that does not require surgery or a bulky pump. Two companies, SynAgile and Neuroderm, are working on infusible forms of levodopa that can be administered with a small needle under the skin with a small pump much like how insulin is administered for many people with diabetes. Like Duopa, the goal of both companies is to provide nearly constant levels of levodopa in the blood to increase “on” times with less fuss than Duopa.

So while carbidopa/levodopa may be from the 1970s, there is clearly still a lot of life left in this drug combination and new ways it can be administered to help better manage Parkinson’s disease symptoms. Until Parkinson’s disease can be stopped, these drugs will make living with it a bit easier.

13 thoughts on “The Many Lives of Levodopa

  1. Karla Golden

    After readng this and with the intresting effects that I have experienced with carbidopa/levodopa I believe I would have better results.

    Reply
    1. James Beck, Ph.D., Vice President, Scientific Affairs Post author

      Worth talking with your movement disorder neurologist to find out.

      Reply
  2. Michael Shepheard

    Thank you Dr. Beck for your work. I currently take Carb/Levo 25/100 tabs, 6ea. per day, entacapone 200 mg 3ea. per day and ropinerole, 12ea .25mg (4 .25 at ea. dose) 3 times per day. I am doing well with few side effects including no dyskinesia symptoms so far. Does the new drug Rtyary, reduce the amount of the drugs I take now, can I get a smaller pillbox? Also, are the positive effects equal to, and are side effects different than what I currently take? What kind of cost is involved as entacapone is very expensive but it works. Thanks in advance for you comments. Look forward to hearing from you.
    Mike Shepheard

    Reply
    1. James Beck, Ph.D., Vice President, Scientific Affairs Post author

      Those are great questions. It is likely you could downsize your pill box. A recent study demonstrated that Rytary was better at providing symptom relief than Stalevo, which is similar to the levodopa/carbidopa/entacapone combination you are currently taking. My guess (and it is only that) is that you may be able to cut the number of pills nearly in half, e.g., from 9 pills to maybe 5. I do not know about your ropinerole. Keep in mind, it will take careful consultation with your neurologist not only to dial in the right dosing of Rytary, assuming it is right for you, but also to determine your final drug regime. I have not heard any more about what pricing will be (respond below if you know!), but it is estimated that it will be $12 per day.

      Reply
  3. Mary Reardon

    I seem to have a very aggressive form of PD. I am 85 years old and had no symptoms two years ago. I take six levodopa/carbidopa 25/250 per day. I am now totally dependent on a walker and often must use a wheelchair. I have no tremors.

    Reply
  4. Bill Millholen

    I wonder if Rtyary is compatible with DBS. DBS has been very good for me and the idea is intriguing. I will be speaking to my doctor. 11 yrs in now.

    Reply
    1. James Beck, Ph.D., Vice President, Scientific Affairs Post author

      On its face, there is no reason Rytary would not be compatible with DBS – it is essentially an extended release version of Sinemet (levodopa/carbidopa), but determining if it is the right therapy for you is really the issue. Checking with your neurologist is the next step to finding out for sure.

      Reply
  5. HARESH

    I anxiously awaiting RYTARY . I hope it is available all over the world so that I can have in INDIA.
    I have late stage Parkinson with too many pills to take. This should reduce my no. of pills and shorten my off periods.

    Reply
    1. James Beck, Ph.D., Vice President, Scientific Affairs Post author

      Unfortunately, Rytary is only currently approved in the U.S. I do not know the company’s plan to seek approval elsewhere in the world.

      Reply
  6. Miguel Ruiz

    Thank you all for your dedication in developing new medicine for this sickness. My Mother is 76 and has had this desease for 25 years now. Its been real hard for me to see her like this and for her self. Recently we had her do the DBS surgery which help her out a bit but not what was expected. We are still trying to find a good tuning for her. GOD BLESS

    Reply

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