Dhivy Carbidopa/Levodopa Fractional Tablet Now Commercially Available

The fractional tablet aims to allow for more precise medication dosing for patients with Parkinson disease who often require several doses daily.

The first carbidopa/levodopa (CD/LD) fractional tablet (Dhivy; Avion Pharmaceuticals) designed to be divided, has been commercially launched for the treatment of Parkinson disease (PD), the company recently announced. The announcement follows FDA approval of the formulationin November 2021, which facilitates more precise medication dosing in patients with PD.1

The smallest precise dose of CD/LD available, 6.25/25 mg, is contained in each tablet’s 4 segments, totaling 25/100 mg per tablet. As patients treated with CD/LD report difficulty managing individual off-time and adverse effects related to precise dosing of medication, the fractional tablet is designed with deep scores and in order to allow patients to divide it and precisely match their recommended dose of medication.

"Fine tuning each individual's optimal CD/LD dose in increments of less than 50 mg of levodopa is extremely unreliable. The option to accurately and reliably fractionate the CD/LD dose in 6.25/25 mg increments provides physicians and patients with the long-overdue possibility to better personalize PD management," Leo Verhagen Metman, MD, PhD, associate professor, Department of Neurological Sciences, Rush Medical College, and medical director, Neurosurgery Program for Movement Disorders, Rush University Medical Group, said in a statement.1 "This can be helpful not only for brittle patients who aim to navigate the rocky road of motor fluctuations and dyskinesia, but also for those with milder disease who want to take no more CD/LD than strictly needed."

If too much CD/LD is taken, patients can develop complications such as dyskinesia. Additionally, imprecise dosing can trigger off-episodes that result in temporary paralysis.

"While no 2 patients with Parkinson's Disease are the same, the burden all patients face is significant. Avion is pleased to bring Dhivyto the market to help these patients and their providers better manage CD/LD dosing needs with a more individualized experience," Harold Deas, CEO, Alora Pharmaceuticals, added in a statement.1 "The innovative tablet design provides a new way to individualize every dose and mitigate some of the challenges patients currently face when it comes to their medication management."

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In a new clinical practice guideline for treatment of early PD motor symptoms published by the American Academy of Neurology in November 2021, a panel of authors concluded that immediate release (IR) levodopa was not more or less effective than levodopa with entacapone or long-acting forms of the drug. Recommendations included prescribing IR levodopa initially, prescribing the lowest effective dose to minimize risk of dyskinesia and other adverse events, and continually counseling patients on potential treatment effects and risks, and monitoring for treatment response—all Level B recommendations, meaning it encompasses what clinicians “should” do, and was presented as the preferential treatment for patients choosing initial pharmacologic treatment for motor symptoms.2,3

Levodopa was found to provide superior benefit to dopamine agonists and MAO-B inhibitors in improving motor symptoms (Level B), but it was more likely than dopamine agonists to cause dyskinesia for up to 5 years of follow-up, leading panel authors to recommend prescribing DAs as the initial therapy for patients with early PD who are less than 60 years and at a higher risk for dyskinesia (Level C recommendation, meaning practices clinicians “may” want to consider).3

“We carefully reviewed the available research on the effectiveness and possible risks of medications to treat motor symptoms in people with early Parkinson disease and found that levodopa is usually the best first treatment for these symptoms,” lead guideline author Tamara Pringsheim, MD, MSc, professor of neurology, department of clinical neurosciences, psychiatry, pediatrics and community health science, the University of Calgary in Alberta, Canada; and a Fellow of the AAN, said in a statement.2 “Still, there are side effects with levodopa as well as other drugs, so it is important that a person newly diagnosed with Parkinson's disease discusses all options with their neurologist before deciding on the best treatment plan for them.”

REFERENCES
1. Avion Pharmaceuticals, LLC, an ALora Pharmaceuticals company, announces the FDA approval and availability of DHIVY for the treatment of Parkinson’s disease. News release. Avion Pharmaceuticals. February 14, 2022. Accessed February 15, 2022. https://www.biospace.com/article/releases/avion-pharmaceuticals-llc-an-alora-pharmaceuticals-company-announces-the-fda-approval-and-availability-of-dhivytm-for-the-treatment-of-parkinson-s-disease/
2. AAN issues guideline for treatment of early Parkinson’s disease. News release. American Academy of Neurology. November 15, 2021. Accessed February 15, 2022. https://www.prnewswire.com/news-releases/aan-issues-guideline-for-treatment-of-early-parkinsons-disease-301424702.html
3. Pringsheim T, Day GS, Smith DB, et al. Dopaminergic therapy for motor symptoms in early Parkinson disease practice guideline summary: A report of the AAN Guideline Subcommittee. Neurology. 2021;97:942-957. doi:10.1212/WNL.0000000000012868