Subcutaneous infusions treat “off” periods in Parkinson disease

Abstract

• A newly approved pump, Onapgo, provides constant infusion of apomorphine to reduce the “off” periods in Parkinson disease.
• Another recently approved pump, Vyalev, provides constant subcutaneous infusion of carbidopa/levodopa.

According to the Michael J. Fox Foundation for Parkinson's Research, nearly 1 million people in the United States have Parkinson disease, a chronic, progressive, neurologic movement disorder in which less dopamine is produced, leading to resting tremor, slowness (bradykinesia), muscle stiffness, and walking and balance difficulties. Other non–movement-related symptoms of Parkinson disease, such as constipation, depression, anxiety, fatigue, and memory problems, are also related to dopamine deficiency.

Dopamine is a neurotransmitter made in brain cells that works primarily in the central nervous system to coordinate and create smooth movement. In the brain, it also provides pleasurable reward and motivation and feelings of happiness, alertness, and focus. Acetylcholine promotes muscle contraction throughout the body, including the heart and motor fibers (when it stimulates the peripheral nervous system) and aids memory and cognition (when it stimulates the central nervous system). Acetylcholine is an excitatory neurotransmitter, while dopamine can be either an excitatory or inhibitory neurotransmitter. Dopamine and acetylcholine are normally in balance in order to appropriately stimulate the nervous system.

Treatment of Parkinson disease focuses on decreasing the effects of acetylcholine or increasing the amount of dopamine to rebalance the two neurotransmitters. One problem with drug therapy, however, is that patients can experience “off” times, when the therapy does not control the symptoms of Parkinson disease or there are motor fluctuations (changes in the ability to move). Both motor and nonmotor symptoms of Parkinson disease can be affected during “off” times, which often happens when circulating drug levels are low, such as just before a dose of medication is due.

The Food and Drug Administration (FDA) has now approved a pump to provide continuous subcutaneous infusions of the previously approved drug apomorphine hydrochloride (Apokyn). Apomorphine is a dopaminergic agonist approved in 2004 for intermittent subcutaneous dosing. The trade name for the continuous infusion is Onapgo. The drug is not related to morphine and is not a controlled substance. Approval was based on results of a randomized, double-blind, placebo-controlled clinical trial. Those who received the drug had nearly two hours less of “off” time than those who received placebo.

The most common adverse effects of Onapgo include infusion site nodules, nausea, somnolence, infusion site erythema, dyskinesia, headache, and insomnia.

Nurses should be aware that premedicating can minimize the risk of nausea and vomiting from Onapgo, which can be severe. The labeling states that generic oral trimethobenzamide can be given three days prior to the initial dose of Onapgo. Trimethobenzamide should only be used while symptoms last and should not exceed two months' duration. Trimethobenzamide increases the risk of somnolence, dizziness, and falls. Alternatively, Onapgo therapy can be started without antiemetics, at a low infusion rate and titrated upward as tolerated. Nurses should avoid administering serotonin antagonist antiemetics, such as ondansetron, as they may induce drug reactions to Onapgo, including profound hypotension and loss of consciousness.

Nurses and NPs should study the Onapgo infusion set and pump kit directions (see www.onapgo.com/onapgo_IFU.pdf). Patients should be provided with instructions on how to insert the cannula and connect the infusion set. Patients must insert the cannula into the subcutaneous space, never into a vein, as this route can cause thrombus formation or pulmonary embolism. The infusion site should be changed daily, and a new infusion set should be used to prevent infections.

For complete prescribing information for Onapgo, see www.accessdata.fda.gov/drugsatfda_docs/label/2025/214056s000lbl.pdf.

The FDA also approved Vyalev, a drug and pump to treat motor fluctuations from Parkinson disease that delivers a continuous infusion of levodopa and carbidopa. Levodopa converts to dopamine in the brain. Carbidopa prevents levodopa from being broken down in the peripheries and reaching the brain. The combination of levodopa and carbidopa has been used to treat Parkinson disease since 1975. A clinical trial of Vyalev found that patients with advanced Parkinson disease treated with subcutaneous infusions had about three more hours daily of “on” time compared with patients taking the medication orally.

For complete prescribing information for Vyalev, see www.accessdata.fda.gov/drugsatfda_docs/label/2024/216962s000lbl.pdf.