Parkinson’s Disease On-Demand Morning Therapy - Episode 12

Side Effects of Apomorphine Usage in Parkinson’s Disease

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A panel of experts debate the disadvantages and side effects of apomorphine therapies for Parkinson’s disease.

Stuart Isaacson, MD: Like any therapy, there are advantages and disadvantages. We know [the rate of] orthostatic hypotension is about 11%, and nausea and vomiting. Bill, you’ve looked specifically at the use of the apomorphine injection subcutaneously in terms of nausea and the use of Tigan that’s recommended on the label. What are your feelings on this because we’ve have some difficulty in the United States of having availability of Tigan now?

William G. Ondo, MD: Nausea is one of the main potential adverse effects of any apomorphine preparation. In the studies, Tigan has been used, which is kind of a dirty drug but largely an antihistamine-type medication. The first person who did one of the studies in the United States in the early ’90s used Tigan, and it became dogma that you use Tigan for this.

We looked at a real-world open-label series in patients who took Tigan versus patients who did not, and we really didn’t see any increase in nausea in patients who were not taking Tigan. In fact, there was a trend toward increased nausea in patients who took Tigan. That was not a controlled trial in any way, shape, or form. I can’t speak for other antinausea medications, most of which you can’t use in Parkinson disease because they block dopamine receptors, which makes them contraindicated. But there isn’t compelling information that these medicines reduce the rates of nausea with apomorphine.

Stuart Isaacson, MD: Khash, how about you? What’s your experience using the injection of apomorphine in terms of both nausea and is Tigan necessary in your experience, as well as other injection-site reactions?

Khashayar Dashtipor, MD: If the site reaction is basically more potent than some other on-demand therapies, then we can expect that you develop more adverse effects as well. One of them is sleepiness. This is the way that I measure if a medication kicks in because as soon as a patient’s medication kicks in they start to yawn. Sometimes they can handle it because they get this really good feeling of the medication kicking in so fast, and they [perceive it] as even stronger than levodopa. They perceive it that way because it kicks in so fast that they love it at the beginning.

However, because of that, we have to then deal with some adverse effects, like sleepiness and orthostasis. That’s why we keep them and check their blood pressure in the clinic.

With the Tigan, I used to use it when it was available. Now, since it’s not available, the way that I do it, I change my titration a little. I minimize the titration now to 0.1 mL instead of 0.2 mL, and ask the nurse specifically to not escalate it. Even if the patient tolerates it, let’s keep them at 0.1 mL for a while and then go back after a week or so to 0.2 mL.

I’m being more cautious because I’ve seen patients when they have nasty nausea and vomiting, they don’t want to touch it again, and I don’t blame them. Therefore, I try to avoid it as much as possible with these strategies. I use in some of my patients a very small dose of….. We have some data to support that with the apomorphine compounds, that when our patients are exposed to the…agonist oral before, they have less nausea.

I give them a very small dose without getting to the point that they have an adverse effect, for example, 0.25 mg, and then start apomorphine. These are the strategies that I use because it’s an excellent medication, and we have to be able to use it. It’s in the category of most potent medication. I use this for my patients who inject and walk, which gives them that understanding that this medication really can be injected when walking.

Stuart Isaacson, MD: We studied this in a placebo-controlled randomized large trial a few years back, and this was published. The primary end point was to see if, on the initiation day when patients came in and got 2 mg, and if they didn’t turn fully ON, 2 hours later they got 4 mg; almost no one went to 6 mg, but it was that one day. Some patients got Tigan, free treatment, beginning 3 days before, and some didn’t and just got placebo. There was no significant difference in nausea or vomiting or discontinuations in that initiation day. As a secondary end point, there was less nausea and vomiting over the next 8 weeks, but not at that initiation day. The evidence is lacking in that regard.

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Transcript edited for clarity.