Treating Morning OFF Episodes in Parkinson’s Disease - Episode 5
Peter A. LeWitt, MD, discusses the use of sublingual apomorphine hydrochloride compared with its subcutaneous formulation in Parkinson disease.
Peter A. LeWitt, MD: Apomorphine is a dopaminergic agonist that, in addition to being given subcutaneously, can also be given sublingually in a strip that is rapidly absorbed through the mucosa of the mouth and going into the circulation to treat Parkinsonian symptoms. Like the injected form, apomorphine has an optimal dose for many patients, and several different dose strips are available so that a patient can determine for themselves whether adverse effects would occur or whether they get optimal effect. Patients typically are asked to start with the lowest dose and build up gradually in repeated trials as to whether a particular dose is giving them the effect they want without adverse effects.
Apomorphine is not absorbed orally, so patients have to maintain these strips for at least 2 minutes under their tongue lest they swallow it and lose the opportunity for getting that full dose absorbed. Sometimes there is some irritation from these strips. Apomorphine is potentially irritating to mucosa or can cause allergic reactions, so patients have to become acquainted with a drug from initial trials that might require them to limit their intake to a particular dose. Some patients will find the irritation of the mouth something that has to be balanced against the benefits and the convenience of use. The package is easy to open. Patients can learn easily how to put the strip under their tongue and keep it there in order to have the drug absorbed. Its onset of effect is designed to be more rapid than levodopa taken in tablet form.
Patients with Parkinson disease can have excessive salivation or swallowing difficulties. Fortunately, those situations with Parkinson don’t impact on the use of sublingual apomorphine strips. Patients can place these strips under their tongue. They’re asked not to swallow the drug; it isn’t absorbed through the stomach and needs to be absorbed through the mucosa of the mouth. The instructions are to maintain that strip, which is dissolved spontaneously. It needs to be left there for about 2 minutes, so that the full effect of the drug can be absorbed in that time.
Apomorphine is available in 2 different delivery options for the on-demand use by the patient with Parkinson disease. The injectable form that is given subcutaneously, typically in the abdomen or one of the limbs, is given in a manner that goes to work more rapidly than apomorphine given as a sublingual strip. Blood level data have been published that show a much more rapid rise of the injected form, as one might expect, getting right into the bloodstream by injection under the skin, than crossing through the oral mucosa. The study data indicate that the onset of clinical effect may be more rapid with injection, but then the patient must use an injection. And there are certainly those patients who would opt for the ease of just opening a simple package and putting a strip under their tongue, which dissolves and after 2 minutes is fully in their system in a manner that also can help to deal with OFF time.
Now, which therapy is more effective? It’s the same drug, a more rapid onset of effect with injected, perhaps a more sustained effect with the sublingual form. It’s also a question as to how rapidly apomorphine has to go to work for a particular patient in a certain situation. If the primary end point of the sublingual apomorphine study was 30 minutes, and that goal was met in the pivotal clinical trials, for some patients that will be sufficient speed of onset of action. On the other hand, if you look at the published study data, you can see that injected apomorphine does go to work more rapidly for the typical patient compared to sublingual apomorphine.
Transcript edited for clarity.