Abstract
Levodopa inhalation powder (Inbrija®) is approved for the intermittent treatment of OFF episodes in patients with Parkinson’s disease (PD) treated with levodopa/dopa-decarboxylase inhibitor (LD-DCI) in the EU and specifically with carbidopa/levodopa in the USA. The approved dosage is 84 mg taken as needed up to five times a day. Administered via a breath-actuated inhaler, this formulation enables levodopa to bypass the gastrointestinal (GI) tract and, instead, rapidly enter the bloodstream through the pulmonary system. In the 12-week, double-blind, placebo-controlled, phase III SPAN-PD trial, as-needed levodopa inhalation powder 84 mg improved motor symptoms during OFF periods in PD patients (aged 30–86 years) treated with levodopa and carbidopa or benserazide. The likelihood of achieving an ON state 60 min postdose was significantly higher in the levodopa inhalation powder than the placebo group, with most patients in the levodopa inhalation powder group experiencing improvements in PD symptoms. Findings from longer-term, 52-week phase III studies were consistent with those from the SPAN-PD trial with regards to the treatment of OFF episodes. Levodopa inhalation powder was generally well tolerated and did not noticeably affect pulmonary function in PD patients. Providing a nonintrusive, convenient treatment method, levodopa inhalation powder is a promising option for the intermittent treatment of OFF episodes in patients with PD treated with a LD-DCI.
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References
Kalia LV, Lang AE. Parkinson's disease. Lancet. 2015;386(9996):896–912.
Cabreira V, Soares-da-Silva P, Massano J. Contemporary options for the management of motor complications in Parkinson's disease: updated clinical review. Drugs. 2019;79(6):593–608.
Ferreira JJ, Katzenschlager R, Bloem BR, et al. Summary of the recommendations of the EFNS/MDS-ES review on therapeutic management of Parkinson's disease. Eur J Neurol. 2013;20(1):5–15.
Aquino CC, Fox SH. Clinical spectrum of levodopa-induced complications. Mov Disord. 2015;30(1):80–9.
LeWitt PA. Levodopa therapy for Parkinson's disease: pharmacokinetics and pharmacodynamics. Mov Disord. 2015;30(1):64–72.
Patel AB, Jimenez-Shahed J. Profile of inhaled levodopa and its potential in the treatment of Parkinson's disease: evidence to date. Neuropsychiatric Dis Treatment. 2018;14:2955–64.
Poirier AA, Aube B, Cote M, et al. Gastrointestinal dysfunctions in Parkinson's disease: symptoms and treatments. Parkinsons Dis. 2016;2016:6762528.
Mukherjee A, Biswas A, Das SK. Gut dysfunction in Parkinson's disease. World J Gastroenterol. 2016;22(25):5742–52.
Cedarbaum JM. Clinical pharmacokinetics of anti-parkinsonian drugs. Clin Pharmacokinet. 1987;13(3):141–78.
Merck Sharp & Dohme. Sinemet® (carbidopa levodopa): US prescribing information. 2014. https://www.accessdata.fda.gov/. Accessed 4 Apr 2020.
Hauser RA. Levodopa: past, present, and future. Eur Neurol. 2009;62(1):1–8.
Deleu D, Northway MG, Hanssens Y. Clinical pharmacokinetic and pharmacodynamic properties of drugs used in the treatment of Parkinson's disease. Clin Pharmacokinet. 2002;41(4):261–309.
Acorda Therapeutics. Inbrija® (levodopa inhalation powder): US prescribing information. 2018. https://www.inbrija.com/. Accessed 4 Apr 2020.
Lipp MM, Batycky R, Moore J, et al. Preclinical and clinical assessment of inhaled levodopa for OFF episodes in Parkinson's disease. Sci Transl Med. 2016;8(360):360–6.
European Medicines Agency. Inbrija® (levodopa inhalation powder): EU summary of product characteristics. 2019. https://www.ema.europa.eu/. Accessed 4 Apr 2020.
Stocchi F, Vacca L, Stirpe P, et al. Pharmacokinetic drug evaluation of CVT-301 for the treatment of Parkinson's disease. Expert Opin Drug Metab Toxicol. 2018;14(12):1189–95.
LeWitt PA, Hauser RA, Pahwa R, et al. Safety and efficacy of CVT-301 (levodopa inhalation powder) on motor function during off periods in patients with Parkinson's disease: a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Neurol. 2019;18(2):145–54.
Farbman ES, Lew M, Waters CH, et al. Efficacy results of a 12-month, dose-level blinded study of CVT-301 (levodopa inhalation powder) in patients with Parkinson's disease [abstract no. 52]. Mov Disord. 2019;34(Suppl 1):S17.
Grosset DG, Dhall R, Gurevich T, et al. Inhaled levodopa in Parkinson's disease patients with OFF periods: a randomized 12-month pulmonary safety study. Parkinsonism Relat Disord. 2020;71:4–10.
LeWitt PA, Hauser RA, Grosset DG, et al. A randomized trial of inhaled levodopa (CVT-301) for motor fluctuations in Parkinson's disease. Mov Disord. 2016;31(9):1356–65.
Hauser RA, Isaacson SH, Ellenbogen A, et al. Orally inhaled levodopa (CVT-301) for early morning OFF periods in Parkinson's disease. Parkinsonism Relat Disord. 2019;64:175–80.
European Medicines Agency. Inbrija® (levodopa inhalation powder): EU public assessment report. 2019. https://www.ema.europa.eu/. Accessed 4 Apr 2020.
Hauser RA, Waters CH, Lew M, et al. Safety results of a 12-month, dose-level blinded study of CVT-301 (levodopa inhalation powder) in patients with Parkinson's disease [abstract no. 3]. Mov Disord. 2019;34(Suppl 1):S3.
Fox SH, Katzenschlager R, Lim SY, et al. International Parkinson and Movement Disorder Society evidence-based medicine review: update on treatments for the motor symptoms of Parkinson's disease. Mov Disord. 2018;33(8):1248–66.
Odin P, Ray Chaudhuri K, Slevin JT, et al. Collective physician perspectives on non-oral medication approaches for the management of clinically relevant unresolved issues in Parkinson's disease: consensus from an international survey and discussion program. Parkinsonism Relat Disord. 2015;21(10):1133–44.
National Institute for Health and Care Excellence. Parkinson's disease in adults. 2017. https://www.nice.org.uk/. Accessed 4 Apr 2020.
Poewe W, Antonini A, Zijlmans JC, et al. Levodopa in the treatment of Parkinson's disease: an old drug still going strong. Clin Interv Aging. 2010;5:229–38.
Luinstra M, Rutgers AW, Dijkstra H, et al. Can patients with Parkinson's disease use dry powder inhalers during OFF periods? PLoS ONE. 2015;10(7):e0132714.
Britannia Pharmaceuticals. Apokyn® (apomorphine hydrochloride injection): US prescribing information. 2014. https://www.accessdata.fda.gov/. Accessed 4 Apr 2020.
Electronic Medicines Compendium. APO-go PFS 5 mg/mL solution for infusion in pre-filled syringe: summary of product characteristics. 2018. https://www.medicines.org.uk/. Accessed 4 Apr 2020.
Electronic Medicines Compendium. Madopar 50 mg/12.5 mg dispersible tablets: summary of product characteristics. 2016. https://www.medicines.org.uk/. Accessed 4 Apr 2020.
Vijayakumar D, Jankovic J. Drug-induced dyskinesia, part 1: treatment of levodopa-induced dyskinesia. Drugs. 2016;76(7):759–77.
Kaakkola S. Clinical pharmacology, therapeutic use and potential of COMT inhibitors in Parkinson's disease. Drugs. 2000;59(6):1233–50.
US National Institutes of Health. ClinicalTrials.gov identifier NCT02240030. 2019. https://www.clinicaltrials.gov/. Accessed 4 Apr 2020.
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During the peer review process, the manufacturer of levodopa inhalation powder was also offered an opportunity to review this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.
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The preparation of this review was not supported by any external funding.
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Julia Paik is a salaried employee of Adis International Ltd/Springer Nature, is responsible for the article content and declares no relevant conflicts of interest.
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Enhanced material for this Adis Drug Evaluation can be found at https://doi.org/10.6084/m9.figshare.12073881.
The manuscript was reviewed by:F. Stocchi, Institute of Neurology, IRCCS San Raffaele Pisana, Rome, Italy; J. Jimenez-Shahed, Department of Neurology, Baylor College of Medicine Houston, TX, USA; T. Müller, Department of Neurology, St. Joseph Hospital, Gartenstr 1, 13088 Berlin, Berlin, Germany.
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Paik, J. Levodopa Inhalation Powder: A Review in Parkinson’s Disease. Drugs 80, 821–828 (2020). https://doi.org/10.1007/s40265-020-01307-x
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DOI: https://doi.org/10.1007/s40265-020-01307-x