Sublingual Apomorphine for Parkinson’s Disease


Key opinion leaders explain the use of sublingual apomorphine and trimethobenzamide for Parkinson’s disease.

Stuart Isaacson, MD: Laxman, you’ve had a lot of patients you’ve treated recently where Tigan has not been available. What’s your experience?

Laxman Bahroo, DO: There are variations of what Khas has done. The first thing I’ll do is look at my patients and say, “Are they a moderate dose of levodopa, plus a dopamine agonist?” If they are, I’m going to start them at 0.2 mL. If they get nausea at that point, I’d titrate and I’d start them at 0.2 mL and see how they do. Maybe I’d keep them at 0.2 mL a little longer, so we don’t advance and optimize in this quickly. That’s group 1.

If they’re on lower dose of levodopa instead of a dopamine agonist, I’d say, “Let’s start at 0.1 mL. Once you’ve tolerated this to 0.1 mL, we’ll migrate it over to 0.2 mL gradually and still be optimized.”

I’ll stratify my patients and start some at 0.2 mL. If they get nauseated, they come back down to 0.1 mL. If they don’t, they stay there and then optimize. Others will start at 0.1 mL tolerate and then go up there, and that’s a good way to do it. Part of my experience with this has been anecdotal with patients coming into the clinic. We gave them a Tigan prescription based on the dogma of the time. They forgot to fill it, or they filled it but the medication was on back order, and they’re showing up to my clinic with everything ready. Many times they’ll say, “I didn’t take it.” I say, “That boat has sailed. Let’s start.” We discovered that they weren’t having nausea, and that’s when Tigan was available.

The lack of Tigan availability in some ways hasn’t been as much of a hindrance as we were led to believe initially.

Stuart Isaacson, MD: I wonder if some of the barriers we spoke about with this remarkably rapid, reliable, and robust therapy relates to the need to pretreat in the label—at least it’s recommended. With Tigan, I’ve begun to see that. Now that we no longer rely on Tigan, patients seem more readily to want to adopt this therapy. What’s your experience over the past 4 to 8 months when Tigan has become unavailable? Do we know now that many patients, if not most patients, are beginning apomorphine injections without Tigan? What’s your experience like?

Daniel E. Kremens, MD, JD: The experience at my center is similar to what the others have suggested. If you start low and go slow, doing the 0.5 mL, then do the 0.1 mL for a few days, make sure the patient is doing OK, then go up to 0.2 mL slowly. Patients who’ve been exposed to dopamine agonists already have a low likelihood of experiencing nausea.

One of the nice things that we also have available with the subcutaneous form of apomorphine is a program called the “Circle of Care,” a company-sponsored program that provides nurses and nurse educators to help with that titration process, even in the days with COVID, so that they can go out to the patient’s home and do the titration if you don’t want the patient coming into the office for some reason. Some physicians prefer to do the titrations in the office. Other people don’t have as much office space for the patient to do it at home. Some patients with COVID-19 don’t want to travel. Having a Circle of Care program is an advantage in terms of initiating a drug.

Stuart Isaacson, MD: It’s important to recognize that this has been a well-established therapy for a long time. Apomorphine is a molecule that’s been used in Parkinson disease in Europe and Asia for decades and in this country for 15 years.

There’s been concern that some patients don’t want to use a needle; there’s needle phobia. Now that we have a new formulation available sublingually for morphine formulation, how is it used? What’s its dosing? What was seen in the pivotal trials in terms of efficacy, safety, and tolerability?

William G. Ondo, MD: Apomorphine is the most important thing. I always mention to my patients that this isn’t a morphine preparation. I’m not putting them on an opioid medication. It has that name from a chemical relation to morphine, but it’s not a physiological relation at all.

One of the problems apomorphine historically has is that it’s somewhat acidic. It has a pH of about 5.7. There have been previous attempts at sublingual preparations that the acidity of the drug seems to have gotten in the way with a significant amount of gingival irritation and things like this.

This is a new strip of apomorphine that has been buffered to minimize the effect of the acidity. It comes in a Listerine-type strip of apomorphine in doses from 10, 15, 20, 25, and 30 mg. Typically, you put it under your tongue. On average, it will take about 2 minutes to dissolve. Then there’s a very quick onset to action.

There are 2 parts of the studies. There was the inpatient part, where people are looking at the drug vs placebo and how fast it turns on. There was a robust and rapid onset to ON time, which seems to be similar to the ON time patients had with levodopa. There was a series of extensive open-label components where patients took it home. Officially, they could use it up to 5 times a day. I didn’t have anyone that used it over 3 times a day, or at OFF times.

In these open-label trials, they continue to show efficacy. There are 2 adverse-event profiles. The first is the known April morphine adverse event: nausea, hypotension being the most common 1, and sedation. These typically resolve in most patients with subsequent use.

There are some long-term issues, where you still can get irritation in the gums. They buffer the acidity, but with chronic use in some of our patients that were taking this for 4 or 5 years, they did have some irritation, sometimes even some teeth irritation, enamel breakdown because of the acidity.

It’s something that you have to keep in mind. Sometimes we did take some little breaks for this to improve, and then patients would start up again. The bottom line is that it’s meant for as-needed therapy and on-demand therapy with patients wearing off. It’s very consistent and robustly effective with a fairly established adverse-effect profile that most people tolerate reasonably well.

Stuart Isaacson, MD: Does anybody have any thoughts on how they might deal with the oral erythema issues that can that emerge?

William G. Ondo, MD: One thing we often recommend doing with chronic therapy is to use an alkaline toothpaste. The toothpaste would have a baking soda in them. There’s never been a study to show whether that’s helpful, but it’s something that we often recommend to our patients.

Stuart Isaacson, MD: Thank you all for joining me and for watching this Neurology Live® Peer Exchange. I hope you enjoyed the content. Please subscribe to our e-newsletters to receive upcoming Peer Exchanges and other great content right in your inbox.

Transcript edited for clarity.

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