Despite the plethora of CD/LD formulations available to address the increasing “off time” that accompanies progressive PD, what are the advantages and indications of the newly FDA-approved CD/LD scored, fractionable dosing formulation?
As we dive into talking about the newly approved fractional carbon Levodopa 2500 in the form of TV. I think it's important to acknowledge that there's a plethora of Parkinson's medication options. And as I said earlier, I think these options are a double edged sword in many ways. They both present us with an opportunity to fine tune medications for our patients, but also a challenge of how we select it and no one patient will respond to one medication or another. We may have to use a trial and error method to optimize it. And sometimes the beauty of managing Parkinson's is that you really use a combination therapy was I mentioned a poly pharmacy approach of different classes of medications and each class of medications is ads in its own component to it. And levodopa certainly being the dominant class in terms of giving you the most reduction in motor symptoms. What's called the gold standard class of medications. It's important to understand that we must be aware of all the different formulations of levodopa, from the fractional formulation to the immediate release to the extended release to the surgical option and the inhaled option because really this becomes the mainstay of Parkinson's management. Many times, individuals will ask, once I started one class of medications, how long will I be on this class? And I'll say, you know, we'll add a second class or third class when we start leva dopa many times, patients will ask that question and say how long before I change, add another medication? No, we don't add additional medications, we may add some. But this class of medications has a large pool in terms of the dozing from the smallest amount of dose to the highest dose. So really once you start levodopa, you have a lot of options. And now with a variety of different formulations, we have even more options. So having a fractional option is interesting because at first blush many of us might look and say, well why do we need a fractional option? Well, if you look at a 25 100 immediate really said that's a line through the center, which means patients, if they cut it diligently can cut in into a perfect half. Many times. I've seen individuals when they pull out their half a tablet. Usually it's more like a half plus or half less. So it's more like a 40% of a tablet or 65% of a tablet because they're not able to get an even scored cut in that sense. So there's a challenge right up there. Even with a score. Sometimes the cutting is a little bit more of a challenge. And many times patients will say that when they cut tablet, half the tablet retains and the other half powder rises and they can't take it. So having something that is scored and can be reliably cut into halves quarters or three quarters is an important unmet need for individuals with that said, we typically made dose. Individuals with the immediate release formulation at one tablet, 1.5, two or even 2.5 tablets for the most part. We're leaving gaps in between where they may need that fine tuning and sometimes we learn that patients don't always need the same dose of levodopa throughout the day. They may start with the higher dose in the morning and have a middle of the day dose. That's that's a lower dosage and they may take even a lower dose at nighttime because maybe taking a higher dose in the evening time may result in more vivid dreams or they may simply not need that and they may have more dyskinesia is towards the end of the day. So having that fractional precision may be helpful for individuals in taking the dose they want. Whether for individuals that may take one tablet might be a little too little but 1.5 might be too much. Well let's define too much. Too much. Might be something along the lines of I'm having dyskinesia at that point or I'm having more nausea at 1.5 or I'm having more lightheadedness at that point. And as earlier mentioned that we have a carbon Dopa formulation of 25 mg. We don't tend to use that as much because it's more user intense. Having to take a carbon dopa tablet, 30 minutes before you take the actual levodopa and all of that has to be taken apart from food, whereas having to take a lower dosage of it might be more helpful. So in that fractional population, obvious population that is at need for this as well. The individuals that find half a tablet cannot be reliably cut, That's an obvious one. The second are individuals that may need to start with a lower than half because of nausea even though they take half a tablet and sometimes I encourage them to even take it with a little bit of a snack to settle their stomach, nothing with protein, nothing with fat, so a little bit of fruit, a banana, a piece of bread or so or crackers to be able to settle their stomach. They still have that challenge of being able to manage the nausea. So starting with with something that gives me a reliable quarter 25 mg of levodopa. It may be helpful in that population. So individuals that are sensitive to the nausea, unable to cut in an exact half. Individuals that may be stuck in a dosage in between there where they may not quite need a half, but they may not need a full, they really need three quarters that's a population or somebody that needs one and a quarter, one and three quarters dozing. So those those fine tuning allows me to be able to give them this dosage with a fraction of a levodopa. And then there's of course the individuals that do not have a consistent need throughout the day. They may start their dosage off at 1.5, or 1 to 3 quarters have the middle of their day, uh and at one and a quarter and end their day off at three quarters. Well, there's no one formulation that's gonna work with them, but they can really adjust their dozing with fractional levodopa to exactly what they need throughout the day.
