A discussion on the use of apomorphine subcutaneous injections in managing Parkinson’s disease.
Stuart Isaacson, MD: Let’s turn now to another recently available on-demand therapy, the apomorphine subcutaneous injection. It’s been available for about 15 years in the country, but it’s not used as often perhaps, and there could be a lot of different reasons why, a number of different barriers. Laxman, what can you tell us about this injection of apomorphine subcutaneously; how is it used, what is its efficacy, safety, and tolerability?
Laxman Bahroo, DO: You are absolutely right. As long as it’s been available, its uptake has been slower. The main reason is because it’s injectable, which is off-putting to a lot of folks up front. My patients are always looking for, “What’s the easiest thing I can administer?” But sometimes the most appropriate thing for you to administer isn’t always the easiest thing to administer. But from a dosing point of view when we look at apomorphine subcutaneous doses, you are looking at 0.2 to 0.6 mL dosing for the most part. The titration of dosing is incredibly important. We want you to titrate to a dose where you feel there’s a levodopa-like ON, you get a full ON. People must titrate to a point where they feel a full ON.
What’s interesting is the most commonly utilized dosing is 0.4 mL. That alone tells you that not everybody stays at 0.2 mL. If individuals stay at a lower dosage, they will discontinue therapy because A) they are injecting themselves, and B) they’re not achieving the desired results. That’s important from a dosing point of view.
From an efficacy point of view, optimally titrated patients will notice a full reduction of their OFF symptoms within about 10 minutes, maybe 12 minutes, and there are reports in the literature that it works as quickly as 7 minutes.
This can work as a bridge and a rescue. Bridge is taking you before you hit an OFF, from one ON to another ON, bridging over that valley of OFF. Rescue is when you’re already in the valley. You wake up in an OFF state, and we want to get you to a full ON, or close to a full ON as quickly as possible. From an efficacy point of view, it gives you the most robust efficacy with a reduction in the UPDRS [Unified Parkinson Disease Rating Scale] score that we see.
Safety-wise, we see typical dopaminergic adverse effects. We’re typically seeing issues with nausea, depending on the person. We might see orthostasis with this as it is a dopamine agonist, and it’s coming in more powerfully than other medications.
Some people may complain about skin reactions, though that didn’t show up in the study as much, but then there are other things that we don’t typically see as much, such as swelling of the legs. Orthostasis and nausea tend to be the bigger adverse effects that we want to caution our patients about. Just as we caution about a cough with the inhaled powder, we want to caution about nausea and orthostasis in this setting.
Stuart Isaacson, MD: This is a medication that has been studied for OFF episodes, and we also looked at it specifically for morning OFF. How do you use it, and what kind of an evidence base is there to use this specifically for morning OFF?
William G. Ondo, MD: This has been specifically looked at in the scenario of patients with OFF time. The study enrolled about 90 patients who tried the medication. These were patients who had some complaints that it took a little while to get going in the morning.
Otherwise, it was a standard group of patients with Parkinson disease. It didn’t have all of the inclusion/exclusion criteria that rarify a population when you’re looking to try to make a drug look good. They were given injections of apomorphine upon awakening. They could take the regular levodopa as well, and it was an open-label study. They were comparing diary data of how long it took to kick in with the regular levodopa, what they were doing, versus after they started and titrated subcutaneous apomorphine. The dose range was 2 to 6 mg.
The subcutaneous apomorphine was very effective at getting patients ON quicker. It went from about 61 minutes to about 24 minutes on average. And many of the patients who were enrolled in this study did have dose failures. Sometimes the levodopa just never kicks in, and it’s considered a dose failure. In the diary data, at least 46% of patients over a course of a week reported at least 1 dose failure on levodopa. When they started the subcutaneous apomorphine, it went down to 7%. That consistency of turning ON is arguably the most impressive finding in this study of subcutaneous apomorphine. It’s a very nice niche for apomorphine preparations as a first dose in the morning to get people up and ON faster.
Stuart Isaacson, MD: We were surprised by those dose failures, at least I would define it not turning ON within an hour. We didn’t expect that. These were patients who at a clinic visit said the first dose might not work quickly enough, and we sent them home to do 5-minute diaries till they turned ON, and we were surprised at how long some patients would wait. One of my patients I remember came in and said, “Geez doctor, I had no idea that I waited an hour for this medicine to work.”
It really speaks to this idea of reliability. In all the studies, the subcutaneous apomorphine injection has turned people from OFF to ON in 95% to 97% of uses of injections. That’s pretty reliable, and the speed of onset is certainly very quick.
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Transcript edited for clarity.