By William Elliott, MD, FACP, and James Chan, PharmD, PhD
The U.S. Food and Drug Administration has approved apomorphine as a constant subcutaneous infusion for the treatment of advanced Parkinson’s disease with persistent motor fluctuations. It is the second subcutaneous infusion for this indication following foscarbidopa/foslevodopa (as Vyalev). Apomorphine is delivered with a small, lightweight wearable device. Apomorphine (as Apokyn) initially was approved in 2004 for acute, intermittent treatment of hypomobility, “off” episodes (end-of-dose wearing off and unpredictable “‘on/off” episodes) associated with advanced Parkinson’s disease. Apomorphine subcutaneous infusion is distributed by Supernus Pharmaceutical Inc. as Onapgo.
Indications
Apomorphine subcutaneous infusion is indicated for the treatment of motor fluctuations in adults with advanced Parkinson’s disease.1
Dosage
The recommended initial dose is a continuous 1 mg/hour (maximum 6 mg/hour) for up to 16 hours per day given by subcutaneous infusion using with the Onapgo pump.1 The maximum recommended total daily dose (including continuous dosage and any extra dose) is 98 mg over the waking day (i.e., 16 hours). The extra dose may be titrated in increments of 0.5 mg or 1 mg based on clinical response and tolerability. For patients with mild or moderate renal impairment, the recommended extra dose is 0.5 mg to 1 mg and should not exceed 1 mg. Treatment with trimethobenzamide is recommended starting three days prior to the first dose and continued as long as necessary to control nausea and vomiting — but generally no longer than two months.1 Apomorphine is available as 98 mg/20 mL single-dose cartridges.
Potential Advantages
Apomorphine provides another option for patients whose motor fluctuations are uncontrolled despite optimized oral or transdermal therapy. In patients inadequately controlled by medical treatment, apomorphine infusion produced a mean of 1.65 hour per day difference from placebo in “off” time.1
Potential Disadvantages
The use of apomorphine is contraindicated with 5HT3 antagonists (e.g., ondansetron, granisetron). The most frequent (> 10%) reported adverse reactions (vs. placebo) are infusion site nodule (44% vs. 0%), nausea (22% vs. 9%), somnolence (22% vs. 4%), infusion site erythema (17% vs. 4%), dyskinesia (15% vs. 0%), headache (13% vs. 4%), and insomnia (11% vs. 2%).1
Apomorphine may cause hypotension/orthostatic hypotension, hallucinations and psychotic-like behavior, dyskinesia or exacerbate preexisting dyskinesia, hemolytic anemia, cardiac events, and may prolong QTc and increase risk of torsades de pointes or sudden death.1
Comments
Apomorphine, unrelated to morphine, is a potent broad spectrum dopamine receptor agonist that has overlapping efficacy to levodopa.2 The efficacy and safety of apomorphine infusion was demonstrated in a study of Parkinson’s patients with motor fluctuation while receiving carbidopa/levodopa and other concomitant Parkinson’s disease medications. The study design was a parallel-group, double-blind, randomized, placebo-controlled trial.1,3 At baseline, participants had been diagnosed with Parkinson’s disease for more than three years and had motor fluctuations not adequately controlled by medical treatment. Participants had a mean age of 63.4 years, 62% were male, and 100% were white.
The mean daily “off” time was 6.7 hours. All participants were taking at least one concomitant Parkinson’s disease medication (dopamine agonist 87%, catechol-O-methyltransferase-inhibitor 58%). They were randomly assigned to apomorphine (n = 53) or placebo saline infusion (n = 53) during waking hours (16 hours per day) for 12 weeks.
The primary endpoint was the absolute change in daily “off” time based on participant’s diaries. A key secondary endpoint was the change in daily “on” time without troublesome dyskinesia from baseline. The analytical dataset included all participants who received at least one dose of study drug and had efficacy data available at any time-point post-baseline.
Patient-reported outcomes using the Patient Global Impression of Change (PGIC) also was assessed. This evaluates the change in Parkinson’s disease symptoms as perceived by the patient on a seven-point single-item scale ranging from “very much worse” to “very much improved.” There was a significant reduction in the mean daily “off” time with a placebo subtracted -1.65 hours (95% confidence interval [CI], -2.91 to -0.38). There also was a significant increase in mean “on” time without troublesome dyskinesia of 1.64 hours (95% CI, 0.28 to 3.00) from a mean baseline of approximately 8.6 hours. In terms of PGIC, 34.9% reported very much or much improved compared to 5.9% on placebo. Apomorphine appears to provide similar placebo adjusted efficacy to that reported for foscarbidopa/foslevodopa injection.4
Clinical Implications
Parkinson’s disease is a neurodegenerative disease where oral levodopa remains the standard of treatment. As the disease progresses, most patients experience motor fluctuation (on/off phenomenon) that may require shortening the interval between levodopa doses or increasing the dosage, adding drugs to prolong levodopa effectiveness (e.g., adding selective monoamine oxidase type B inhibitors), or using catechol-O-methyltransferase inhibitors.3,5 Other options include amantadine, and infusions of levodopa or apomorphine.
Many patients with Parkinson’s disease also face gastrointestinal issues, such as delayed gastric emptying or constipation, which may affect absorption of oral medications.6 Apomorphine infusion, along with subcutaneous carbidopa/levodopa provides similarly effective therapy options for patients who are no longer controlled with existing oral treatment options. Cost was not available at the time of this review.
References
- Supernus Pharmaceuticals Inc. Onapgo prescribing information. Revised February 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/214056s000lbl.pdf
- Carbone F, Djamshidian A, Seppi K, Poewe W. Apomorphine for Parkinson’s disease: Efficacy and safety of current and new formulations. CNS Drugs. 2019;33(9):905-918.
- Katzenschlager R, Poewe W, Rascol O, et al. Apomorphine subcutaneous infusion in patients with Parkinson’s disease with persistent motor fluctuations (TOLEDO): A multicentre, double-blind, randomised, placebo-controlled trial. Lancet Neurol. 2018;17(9):749-759.
- AbbVie Inc. Vyalev prescribing information. Revised October 2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/216962s000lbl.pdf
- Pirker W, Katzenschlager R, Hallett M, Poewe W. Pharmacological treatment of tremor in Parkinson’s disease revisited. J Parkinsons Dis. 2023;13(2):127-144.
- Tan AH, Chuah KH, Beh YY, et al. Gastrointestinal dysfunction in Parkinson’s disease: Neuro-gastroenterology perspectives on a multifaceted problem. J Mov Disord. 2023;16(2):138-151.
The U.S. Food and Drug Administration has approved apomorphine as a constant subcutaneous infusion for the treatment of advanced Parkinson’s disease with persistent motor fluctuations. It is the second subcutaneous infusion for this indication following foscarbidopa/foslevodopa (as Vyalev).
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