Optimal Management of OFF Episodes in Parkinson's Disease - Episode 8
Daniel E. Kremens, MD, JD: There are other on-demand therapies aside from apomorphine. Recently in the United States, we had levodopa inhaled powder [Inbrija] approved for the treatment of OFF episodes. What do you perceive are the advantages and potential disadvantages of this drug?
Rajeev Kumar, MD: Inbrija is an interesting medication in that it’s levodopa without carbidopa. It’s a relatively small dose, about 84 mg of levodopa, and results in 50 mg of absorbable levodopa. It’s about the equivalent of taking half of an immediate release Sinemet [carbidopa/levodopa] 25/100 mg tablet in terms of the amount of levodopa administered.
Although that sounds like a relatively small amount, you’re absorbing it from the large pulmonary tree relatively quickly, it would seem. If one looks at the PK [pharmacokinetic] data, the time to increase levodopa concentration by 300 to 400 ng/mL is quite fast—less than 10 minutes or so. You can take a patient who has some levodopa in their system from feeling OFF or partially OFF to back ON and over 1000 [ng/mL] again. The majority of patients, upon taking the inhalation, which consists of 2 standard-dosed capsules, can get back ON in about 20 to 30 minutes in most situations.
It’s a small amount of levodopa, and it’s a standard dose. It does not require titration, and that’s an advantage compared to Apokyn [intermittent subcutaneous injection apomorphine hydrochloride]. However, the small amount is a disadvantage. It can’t take someone from fully OFF to fully ON. The absence of carbidopa is also a disadvantage. If the patient has not taken their last dose of oral levodopa/carbidopa for many hours, such as overnight, it’s unlikely to make much of an impact in getting the patient back ON because the levodopa that is absorbed is going to get metabolized fairly quickly by DOPA [dihydroxyphenylalanine] decarboxylase. One should be aware of that.
It might be helpful to simultaneously inhale it while taking the oral levodopa/carbidopa in the morning. It might slightly reduce the time to ON. There are some data that suggest that, but it’s a small study that wasn’t powered adequately to truly assess the efficacy of that strategy. Regardless, I think it would be a small benefit.
On the other hand, if somebody took controlled-release Sinemet CR 4 hours earlier, let’s say at 4 AM and then again at 8 AM, and were OFF at that time, it would be very reasonable for them to inhale Inbrija, as well as take their oral drug to decrease their time to ON. That might have a very substantial effect because they would still have a fair bit of carbidopa in their system at that time. That’s a nice advantage of the drug.
Daniel E. Kremens, MD, JD: One of the keys to using Inbrija successfully, this is what I instruct my patients to do, is as soon as patients start to feel that they’re turning OFF, that’s when to use Inbrija. At that moment is when it will work best to help bridge to your next dose, as opposed to waiting till you get to that deep OFF state. In a situation like that [deep OFF state], you may need something more like apomorphine, either subcutaneously or sublingually, to get you back to that full ON state. When you look at the UPDRS [Unified Parkinson’s Disease Rating Scale] motor scores between the apomorphine products versus inhaled levodopa, the apomorphine products tend to be more robust. I do think in the appropriate patient, if the patient can inhale at the start of recognized turning OFF, it can be a nice option.
The other thing is for a lot of people the inhalation formulation is more socially acceptable and relatively easy to use. In the study, 99.8% of patients who were in an OFF episode were able to do their inhalation successfully. Some people have a little bit of a challenge when they first do inhalation. You must teach them how to inhale appropriately; some people had cough in the study. In the real world, I’m finding for some people cough is a challenge. However, they can learn not to suck it in all at once. Take a gentle inhalation and breathe in slowly. Sometimes taking a little water with it can help with coughing issues.
Rajeev Kumar, MD: Yes, that’s very well put, Dan. That’s the most common adverse effect that’s specific to the therapy. The particles, which are an interesting new formulation designed by Arcus Technology, [Inc], can be irritating, especially to the upper airway, and can induce cough. Being in the right position and slow inhalation are helpful. Because it can be irritating, the most important contraindication for the use of Inbrija is patients who have asthma or COPD [chronic obstructive pulmonary disease]. Patients with reactive airway disease, or any kind of chronic pulmonary disease, should be considered for other therapies rather than Inbrija.
It is a helpful drug. I have 1 or 2 patients who have used both Apokyn and Inbrija, and they recognize, “In the morning, I take my Apokyn, and if I’m starting to wear off between doses, I take my Inbrija. If a have a really bad OFF, I take out my Apokyn.” Therefore, it’s nice to have options.
Daniel E. Kremens, MD, JD: Again, I like having options for patients. I also have patients who have tried both and like one or the other for particular situations.