PD OFF Episodes: Optimizing Use of On-Demand Therapy

Peter A. LeWitt, MD: In addition to apomorphine, which this patient is using as a subcutaneous injection, there's another available therapy for on-demand use with levodopa itself. It's an inhaled form of levodopa, a micropowder that is absorbed into the lungs. The pace of onset of apomorphine injection effect is within 10 to 15 minutes, and this inhaled form of levodopa goes to work within the same timeframe.

Studies comparing these 2 drugs show a rather comparable mode of action, a dopaminergic effect lasting for about an hour, usually not exacerbating dyskinesias. In many instances, patients find these to be very reliable in terms of going into effect when used. There is no need to use them frequently for most patients, but the option of using them multiply during the day—perhaps anticipating going OFF—represents a therapeutic option.

Which one to use? It's hard to know. Most patients haven't switched from one to the other. There haven't been head-to-head comparisons. The mode of delivery is different. One is an injection, the other is inhaled. There are possible adverse effects to each formulation in terms of how they're administered. Patients, fortunately, have the option of trying both of them and could perhaps make the right decision as to which one they stick with or how effective it might be.

I've mentioned apomorphine hydrochloride injections given subcutaneously for managing OFF episodes. Let me give some more details as to how this therapy can be used effectively, how it can be tested, and whether the choice to use this is a good idea for all patients. For the typical patient who has unpredictable OFF time, we've talked about the different patterns of OFF episodes.

If there's marked delay in onset of effect, particularly with their first dose of the day, that patient might be a candidate for use of apomorphine injections to get going in the morning quickly and reliably, especially if eating food is necessary. Some patients, for example, take insulin and have diabetes. They cannot afford the time to wait for the levodopa to kick in, given the fact that their blood sugar has to be controlled.

Other examples include a patient who wakes up in the middle of the night and hasn't had levodopa for many hours because they were asleep. This might be a scenario where getting rapid and reliable dopaminergic effect might be helpful. But keep in mind that apomorphine injections can be used at any time of day. They can be used sequentially because each dose lasts for about an hour. If circumstances led to the first oral levodopa dose not getting absorbed effectively, it may last for more than an hour to 2 hours.

It might be necessary, since the apomorphine can wear off after about an hour, to use a second dose in sequence. What is apomorphine doing as a drug? It's a fast acting and very potent dopaminergic agent. It has morphine in its title, but it is not a narcotic. It's not habit-forming. It's not something that patients develop a tolerance to either. In animal studies, apomorphine is one of the most potent dopaminergic drugs. One of the nice things I find about using a subcutaneous injection is that the dose the patient receives is adjustable.

When it's first started, it's titrated to effect, starting with a suboptimal dose to make sure that a patient will not experience some of the common adverse effects, such as hypotension, nausea, yawning, or some of the other things that can occur with dopaminergic drugs. The careful adjustment of dose upward leads to a regimen somewhere between 3 mg to 6 mg per day for the typical patient using it for dealing with OFF states. But a patient may have the option of taking a little bit more or a little bit less depending on how they're doing during the day.

For example, a patient who has dyskinesias as a possible adverse effect might be in a social situation. They want to get back ON. They certainly don't want to have involuntary movements that make them look odd in the social setting. That patient whose typical dose might be 4.5 mg might choose to dial down to 3.5 mg. The syringe that is used to inject is very adjustable. The patient may have a lot of familiarity with what a little bit extra or a little bit less will accomplish.

This drug is adjustable in a way that pills are not. You either take a pill or you don't, but you can't dial down 20% or up 20% in oral administration. Apomorphine is a drug that can also bring out dyskinesias or dystonic spasms for those who are sensitive to too much dopaminergic effect, so it's an adjustable therapy. But usually, patients experience a fairly reliable absorption and a typical pattern of clinical responses once they get to know how it works. A patient who might only be using it once a week can count on the same experience as the last time, unlike the way oral levodopa behaves.