Optimal Management of OFF Episodes in Parkinson's Disease - Episode 3

Apomorphine Subcutaneous Injection: Efficacy and Administration for Off-Episodes in Parkinson Disease

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Rajeev Kumar, MD: It should be noted that when you first begin Apokyn [apomorphine hydrochloride], most patients will need to premedicate with trimethobenzamide, or Tigan. After a few weeks to a few months, most patients can titrate off the antiemetic.

Daniel E. Kremens, MD, JD: Rajeev, for the folks who aren’t as familiar with Apokyn or apomorphine, in general, it’s a pretty potent emetic for some people.

Rajeev Kumar, MD: ln fact, that’s how it was first approved in the United States. To induce emesis, right?

Daniel E. Kremens, MD, JD: Right.

Rajeev Kumar, MD: When people would take something that they shouldn’t have taken—for example, in the 1950s—apomorphine could be administered and they would vomit. If you have ever been exposed to it, it can make you puke pretty nicely.

Daniel E. Kremens, MD, JD: Right. As you pointed out, for most people, when we’re using apomorphine, we have them premedicate for 3 days before starting with Tigan [trimethobenzamide]. Then the majority of the patients after they’ve been exposed to Apokyn [apomorphine hydrochloride], even for a brief period—eg, a couple of weeks—are able to titrate off the Tigan [trimethobenzamide]. The studies went out to about 2 months, but in the real world, I often have patients on it for 2 weeks. Then, if they’re using their Apokyn [apomorphine hydrochloride] regularly by that point, they no longer need their Tigan [trimethobenzamide].

Rajeev Kumar, MD: Yeah, that’s very true. As we’ll discuss with apomorphine infusion, usually before beginning apomorphine subcutaneous infusion in Europe, and also investigational use in the United States, we began with the orally administered antiemetic. In the United States, we use Tigan, or trimethobenzamide. In Europe and in Canada, we use domperidone. After a few weeks, even with continuous infusion and a higher total dose being administered throughout the day, the vast majority of patients come off the antiemetic within a few weeks.

Daniel E. Kremens, MD, JD: We’re going to get to that in a minute. For the audience, there is under development in the United States an infusion of apomorphine, which we’ll talk about in a second. It’s already approved in Europe, and that’s the drug Rajeev is referring to. There are also data for morning off-episodes, as you pointed out, with Apokyn [apomorphine hydrochloride]. They have the AM IMPAKT study. In that study, there were over 80 patients, and 96% of them had improvement in their morning off-periods using Apokyn [apomorphine hydrochloride] injections. It was a pretty robust response, and the time was reduced. Before these people were taking Apokyn [apomorphine hydrochloride], sometimes it would take them over an hour to turn on in the morning.

Could you imagine trying to get up if you were working, functioning in situations where you can’t get dressed and can’t bathe because you’re waiting for your oral medication to kick in? With Apokyn [apomorphine hydrochloride] injection in these people, the average time was reduced to 23 minutes until they were on. It’s a robust response. Also, in clinical data, 95% of off-periods were aborted in some pivotal studies submitted to the FDA for drug approval in the United States, with a levodopa-like response in the Unified Parkinson’s Disease Rating Scale [UPDRS], a 23- or 24-point improvement. The only other drug that gives that kind of improvement is levodopa. 

Rajeev Kumar, MD: Absolutely. The effect is very hard to replicate with any other drug. We’re talking about a motor improvement of about 23 or 24 points. We’re not talking about the other parts of the UPDRS. It’s quite tremendous. The patients who were in most of these studies had fairly advanced disease and often had a motor UPDRS score. This is using the older UPDRS and not the MDS-UPDRS [Movement Disorder Society–Sponsored Revision of the UPDRS]. The total score is less. The maximum motor score is 108, as opposed to the MDS-UPDRS, which has quite a few more points. A 25-point improvement is a big improvement. These people typically had a UPDRS score off-episode of around 40 points, so they were very severely affected in the off-episode state. These are patients who typically, without Apokyn [apomorphine hydrochloride], would need surgery.