Treating Morning OFF Episodes in Parkinson’s Disease - Episode 4
Expert insight on the mechanism of action and use of subcutaneous apomorphine hydrochloride in patients with Parkinson disease.
Peter A. LeWitt, MD: Another option for treating, on demand, the need for getting dopaminergic effect for rescuing a patient from an OFF state is injected apomorphine or apomorphine hydrochloride, which is available in liquid form and an injector that the patient can choose to give up to several times per day. Patients who are started on this therapy are titrated to an effective dose and to get to know it, both from the point of view of its benefits and adverse effects. This medication has been available for many years. It’s the first on-demand therapy and can augment the effect of levodopa or other dopaminergic drugs because apomorphine, although it’s a synthetic compound as far as the brain is concerned, is a very effective dopaminergic drug. And patients who are injecting this drug get a blood level rapidly, and usually within 10 to 15 minutes can experience a recovery from an OFF state to an ON state.
The nice thing about this drug is it can be used at any time of day or night. It has a predictable effect, and patients with the injector that’s available have the option of taking a little more or a little less than their usual dose in accordance with possible adverse effects or what their needs are. For example, a higher dose might cause some dyskinesias but might be more rapid and more effective, whereas a lower dose might not cause dyskinesias and yet be an acceptable choice for that patient. There’s a certain amount of control possible.
Patients who become used to giving themselves injections don’t find the notion of an injection as bothersome as perhaps the patient in the first few times where the idea of sticking oneself with a needle, much as people who are insulin-dependent diabetics have to get used to that. Many patients find that this is a reliable therapy. It does have a need to sort of set up the needle and sterilize the skin with alcohol wipes and to prepare for it with the possibility of adverse effects such as yawning, or feeling sedated, or a bit of nausea. It’s not a drug without the potential for adverse effects, but it’s extremely reliable in terms of achieving an ON state for those who’ve found it to be a useful therapy for themselves.
Apomorphine given in the morning hours to improve control of Parkinsonism and to go from OFF to ON is a rather established treatment worldwide, including in the United States. The use of subcutaneous apomorphine as the first dose of the day can be much speedier than oral levodopa or other medications taken to treat Parkinsonian symptoms. Its reliability is there. Patients can often get going and get those activities of their morning much more quickly and much more reliably undertaken than waiting for a levodopa dose to absorb, sometimes a 30-, or 45-, or even a 60 minute wait, depending on how advanced their Parkinson disease is and what factors affect the absorption of oral levodopa, even its immediate release form.
Patients in the United States who are starting on injected apomorphine given subcutaneously must learn how to assemble the device, they must learn what their optimal dose is. In their first few trials of this, they may experience adverse effects, such as a drop in blood pressure, or nausea, or vomiting. So the startup of medication needs some guidance. The sponsor of marketing apomorphine injection, the product is called Apokyn®, has a benefit of an in-home program called Circle of Care, where an experienced nurse who can train the patient in the use of the therapy and work with the patient the first few times of injection provides a benefit for a patient to have confidence and knowledge as to how to use injected apomorphine. This therapy is usually started in the home setting when a patient in the morning has not taken any levodopa or other Parkinson medications so that the effect of apomorphine can be tested in just that setting where it is very likely to be used, the first dose of the day. And in that situation, a gradual increase of dose, a titration to typically effective intake is tried out in a structured way by the Circle of Care nurse in the home to get that patient ready to use it on their own.
Transcript edited for clarity.