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Management of Sialorrhea in Parkinson Disease - Episode 10

Dose Escalation of Botulinum Toxin Injectables

Stuart Isaacson, MD: Since these studies have been conducted, I’ve changed my practice of how I inject. I tend to use ultrasound when they don’t have a good response initially. But also I tend to use higher doses first, based on the studies showing that it was safe to inject 2500 units as the first injection into the parotid gland and the submandibular, 250 units of Myobloc in the submandibular, and 1000 units into each parotid.

Richard M. Trosch, MD: Do you use submandibulars and parotids in everyone?

Stuart Isaacson, MD: I’ve changed with these studies showing that it was safe because I was concerned about the safety of injecting submandibular and usually would reserve that based on their response and increase the parotids. And then the third time maybe add the submandibular. But seeing that even with anatomical localization, it was safe in these studies—not just safe in the pivotal blinded randomized part of the trial but also on subsequent injections that patients had over a year period—I began to inject the parotid and submandibular every time.

Richard M. Trosch, MD: What’s your starting dose that you’re using?

Stuart Isaacson, MD: I use 1000 units and 250, but if somebody had a lot of dry mouth, if they had some swallowing problems that weren’t so clinically evident, but we knew they were there, then I might start with 750 and 250 units, or 750 and avoid the submandibular the first time. I’d still adjust it to the patient, but in general, unless there’s a reason not to, I’ll give 1000 and 250 units on each side as a first injection with anatomical localization. Though sometimes I use ultrasound for the first time as well.

Richard M. Trosch, MD: And how high of a dose will you go with Myobloc?

Stuart Isaacson, MD: I’ll move to 2500 units, giving 1500 units into each parotid and 250 still into the submandibular, for a total of 3500 units.

Richard M. Trosch, MD: You’re keeping your submandibular dose constant, and you’re just raising the parotid.

Stuart Isaacson, MD: Yeah. And it’s not based on the science of what we need to block the release of acetylcholine. It’s based on the safety that was found using that paradigm in the trial.

Richard M. Trosch, MD: Do you find your dose escalating drifting up over time? Some patients who do well on the lower dose suddenly aren’t doing as well, and you have to give a little more. I’ve certainly had that experience. I don’t know if you’ve shared that.

Stuart Isaacson, MD: I tend to repeat the 3500 units with ultrasound before I go above it to make sure that I’m at the right location and depth, and then if they’re still having a problem and they don’t have adverse effects, I’ll go up a little more. I tend not to increase the submandibular because I don’t know the safety of increasing it. I tend to increase the parotids more, maybe up to 1750 or even 2000 units in each parotid.

Richard M. Trosch, MD: I’ve gotten very high. We’ve had this conversation.

Stuart Isaacson, MD: Yes.

Richard M. Trosch, MD: I think the highest dose I did was 14,000 units, and a lot of my patients settle around 5000 units of Myobloc.

Stuart Isaacson, MD: What do you tell patients when you inject them? Do you tell them this is going to get better today? Next week? How long will it last? When should you be reinjected? What types of things should people know if they’re going to start to inject these patients?

Richard M. Trosch, MD: I tell the patient that they’ll probably see a benefit beginning in a week. The full effect may be several weeks out, maybe 2 to 4 weeks. For most patients it lasts about 3 months. I have some patients who last up to 6 months, and I have quite a few who wear off a few weeks before that 13-week visit. In Michigan, I’m limited to injecting every 91 days. I can’t inject before 91 days, and for immunologic reasons, you probably don’t want to anyway.

Stuart Isaacson, MD: Yeah, I agree.

Richard M. Trosch, MD: We really respect that boundary of 91 days. Some patients find that it’s still working. If it is, we’ll push back the repeat injections, but a lot will tell me it’s starting to wear off and that the drooling is returning but maybe not returning to baseline. They tend to come back.

Stuart Isaacson, MD: Patients have had drooling for a long time, yet in the studies, 1 week after injection there was significant improvement. So it could be the therapy that can be pretty reliable in its effect. How do you gauge response? Do you have patients come back in a

week or a month, or do you have them call or keep notes? How do you tend to figure out if it was the right dose for knowing how much drooling there was?

Richard M. Trosch, MD: A lot of my patients travel a long distance, and it’s not practical for them to come back. So I ask them to keep notes. I say, when you come back, I’m going to ask you the follow things, so maybe you write it down on your calendar. I’m going to ask you when it started working. I’m going to ask if there were any adverse effects. When did the adverse effects start and how long did they last? When it was working, what degree of benefit did you have, did the drooling stop, or is it just reduced? Was the coughing better at night, or is that reduced? I’m going to ask them to gauge both the severity and duration of adverse effects as well as the degree of benefit. Then I’m going to want them to tell me when it wore off. I tell them these are the things I’m going to want you to do. I’m speaking to the caregiver at this point. I say, “Try to mark it down on your calendar, so when you come back we can have a discussion.” It helps me know how to modify the injection, dosing, and the sites for the next visit.