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NOURIANZ^® (istradefylline) safety profile^1,2

Clinical trial details

Study design: Studies were 12-week trials of 734 patients (NOURIANZ 20 mg [n=356], NOURIANZ 40 mg [n=378])¹
Methodology:
- Study 1: Patients taking a stable dose of levodopa/carbidopa with or without other medications for PD^1,2
- Study 2: Patients taking a stable dose of levodopa medications for PD^1,2
- Study 3-4: Patients taking a stable dose of levodopa/carbidopa or levodopa/benserazide with or without other medications for PD^1,2
Select patient baseline characteristics: Mean age: 65 years (range: 33 to 84 years); 53% were aged 65 years or older, 13% were aged 75 years or older, 67% were Asian, 32% were White¹

Over 100,000 patients have been prescribed NOURIANZ in the US and Japan²

NOURIANZ: Safety data¹

Incidence of adverse reactions ≥2% with either dose of NOURIANZ and greater than placebo^1*

Table shows NOURIANZ® (istradefylline) adverse effects

^*Four 12-week studies included 734 patients (NOURIANZ 20 mg [n=356] and NOURIANZ 40 mg [n=378]).
^aIncludes hallucinations (visual, olfactory, somatic, and auditory).

ADDITIONAL INFORMATION ON DYSKINESIA

Treatment-emergent adverse reactions of special interest^2,3

Table shows NOURIANZ® (istradefylline) treatment-emergent adverse effects of special interest

aIncludes falls fracture terms and injury terms. bIncludes hallucinations; visual, olfactory, somatic, auditory, tactile, and mixed hallucinations; and illusions. cIncludes sleep disorder, irregular sleep phase, poor quality sleep, rapid eye movements, and sleep abnormal. dIncludes agranulocytosis, granulocytopenia, leukopenia, neutropenia, neutrophil count decreased, neutrophil percentage decreased, pancytopenia, and white blood cell count decreased.

NOURIANZ: Low rates of discontinuation due to adverse events compared with placebo^1†

Discontinuation rates due to adverse reactions¹

5% discontinuation rate with placebo
5% discontinuation rate with NOURIANZ 20 mg
6% discontinuation rate with NOURIANZ 40 mg

Discontinuation due to dyskinesia & hallucinations¹

1% of patients treated with either NOURIANZ 20 mg or 40 mg discontinued treatment because of dyskinesia compared with 0% on placebo
1% of patients treated with NOURIANZ 40 mg discontinued due to hallucinations compared with 0% on placebo
0% of patients treated with NOURIANZ 20 mg discontinued due to hallucinations compared with 0% on placebo

NOURIANZ, in combination with levodopa, may cause dyskinesia or exacerbate pre-existing dyskinesia. The incidence of dyskinesia was 15% for NOURIANZ 20 mg, 17% for NOURIANZ 40 mg, and 8% for placebo, in combination with levodopa¹

^†Four 12-week studies included 734 patients (NOURIANZ 20 mg [n=356] and NOURIANZ 40 mg [n=378]).

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Find out about NOURIANZ dosing DOSING

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Important Safety Information

Warnings and Precautions

Dyskinesia: NOURIANZ in combination with levodopa may cause dyskinesia or exacerbate pre-existing dyskinesia. In clinical trials, 1% of patients treated with either NOURIANZ 20 mg or 40 mg discontinued treatment because of dyskinesia, compared to 0% for placebo.

Hallucinations / Psychotic Behavior: Because of the potential risk of exacerbating psychosis, patients with a major psychotic disorder should not be treated with NOURIANZ. Consider dosage reduction or discontinuation if a patient develops hallucinations or psychotic behaviors while taking NOURIANZ.

Impulse Control / Compulsive Behaviors: Patients treated with NOURIANZ and one or more medication(s) for the treatment of Parkinson’s disease (including levodopa) may experience intense urges to gamble, increased sexual urges, intense urges to spend money, binge or compulsive eating, and/or other intense urges, and the inability to control these urges. In clinical trials, 1 patient treated with NOURIANZ 40 mg was reported to have impulse control disorder, compared to no patient on NOURIANZ 20 mg or placebo.

Drug Interactions

The maximum recommended dosage in patients taking strong CYP3A4 inhibitors is 20 mg once daily. Avoid use of NOURIANZ with strong CYP3A4 inducers.

Specific Populations

Pregnancy: Based on animal data, may cause fetal harm.

Hepatic impairment: The maximum recommended dosage of NOURIANZ in patients with moderate hepatic impairment is 20 mg once daily. Avoid use in patients with severe hepatic impairment.

Adverse Reactions

The most common adverse reactions with an incidence ≥5% and occurring more frequently than with placebo were dyskinesia (15%, 17%, and 8%), dizziness (3%, 6%, and 4%), constipation (5%, 6%, and 3%), nausea (4%, 6%, and 5%), hallucination (2%, 6%, and 3%), and insomnia (1%, 6%, and 4%) for NOURIANZ 20 mg, 40 mg, and placebo, respectively.

Indication

NOURIANZ^® (istradefylline) is an adenosine receptor antagonist indicated as adjunctive treatment to levodopa/carbidopa in adult patients with Parkinson’s disease (PD) experiencing “off” episodes.

You are encouraged to report suspected adverse reactions to Kyowa Kirin, Inc. at 1-844-768-3544 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please see full Prescribing Information for NOURIANZ.

References: 1. NOURIANZ [package insert]. Kyowa Kirin, Inc., Princeton, NJ 08540. 2. Chen J-F, Cunha RA. The belated US FDA approval of the adenosine A_2A receptor antagonist istradefylline for treatment of Parkinson’s disease. Purinergic Signal. 2020;16(2):167-174. 3. Isaacson SH, Betté S, Pahwa R. Istradefylline for OFF episodes in Parkinson’s disease: a US perspective of common clinical scenarios. Degener Neurol Neuromuscul Dis. 2022;12:97-109.

References: 1. Parkinson’s disease. National Institutes of Health. Updated June 26, 2023. Accessed April 9, 2024. https://www.nih.gov/research-training/accelerating-medicines-partnership-amp/parkinsons-disease 2. Olanow CW, Poewe W, Rascol O, Stocchi F. From OFF to ON—treating OFF episodes in Parkinson’s disease. US Neurol. 2020;16(suppl 1):2-10.

References: 1. Kalia LV, Brotchie JM, Fox SH. Novel nondopaminergic targets for motor features of Parkinson's disease: review of recent trials. Mov Disord. 2013;28(2):131-144. 2. Mori A. Mode of action of adenosine A_2A receptor antagonists as symptomatic treatment for Parkinson’s disease. Int Rev Neurobiol. 2014;119:87-116. 3. Varani K, Vincenzi F, Tosi A, et al. A_2A adenosine receptor overexpression and functionality, as well as TNF-α levels, correlate with motor symptoms in Parkinson’s disease. FASEB J. 2010;24(2):587-598. doi:10.1096/fj.09-141044. 4. Fuxe K, Marcellino D, Genedani S, Agnati L. Adenosine A_2A receptors, dopamine D₂ receptors and their interactions in Parkinson's disease. Mov Disord. 2007;22(14):1990-2017. doi: 10.1002/mds.21440. 5. Morelli M, Di Paolo T, Wardas J, Calon F, Xiao D, Schwarzschild MA. Role of adenosine A_2A receptors in parkinsonian motor impairment and L-DOPA-induced motor complications. Prog Neurobiol. 2007;83(5):293-309. 6. Morelli M, Blandini F, Simola N, Hauser RA. A_2A receptor antagonism and dyskinesia in Parkinson's disease. Parkinsons Dis. 2012;2012:489853. doi: 10.1155/2012/489853. 7. Mishina M, Ishiwata K. Adenosine receptor PET imaging in human brain. Int Rev Neurobiol. 2014;119:51-69. doi:10.1016/B978-0-12-801022-8.00002-7. 8. The voice of the patient: Parkinson’s disease. Silver Spring, MD: US Food and Drug Administration; April 2016. https://www.fda.gov/media/124392/download. Accessed June 11, 2019. 9. Hickey P, Stacy M. Available and emerging treatments for Parkinson’s disease: a review. Drug Des Devel Ther. 2011;5:241-254. 10. Stocchi F, Antonini A, Barone P, et al. Early DEtection of wEaring off in Parkinson disease: the DEEP study. Parkinsonism Relat Disord. 2014;20(2):204-211.

References: 1. Kulisevsky J, Poyurovsky M. Adenosine A_2A-receptor antagonism and pathophysiology of Parkinson’s disease and drug-induced movement disorders. Eur Neurol. 2012;67(1):4-11. 2. Mori A. Mode of action of adenosine A_2A receptor antagonists as symptomatic treatment for Parkinson’s disease. Int Rev Neurobiol. 2014;119:87-116. 3. NOURIANZ [package insert]. Kyowa Kirin, Inc., Princeton, NJ 08540. 4. DHIVY [package insert]. Alpharetta, GA: Avion Pharmaceuticals, LLC; 2021. 5. Morelli M, Blandini F, Simola N, Hauser RA. A_2A receptor antagonism and dyskinesia in Parkinson’s disease. Parkinsons Dis. 2012;2012:489853. 6. Liu Y-J, Chen J, Li X, et al. Research progress on adenosine in central nervous system diseases. CNS Neurosci Ther. 2019;25(9):899-910. 7. Mishina M, Ishiwata K. Adenosine receptor PET imaging in human brain. Int Rev Neurobiol. 2014;119:51-69. 8. Isaacson SH, Betté S, Pahwa R. Istradefylline for OFF episodes in Parkinson’s disease: a US perspective of common clinical scenarios. Degener Neurol Neuromuscul Dis. 2022;12:97-109. 9. Chen J-F, Cunha RA. The belated US FDA approval of the adenosine A_2A receptor antagonist istradefylline for treatment of Parkinson’s disease. Purinergic Signal. 2020;16(2):167-174. 10. Brichta L, Greengard P, Flajolet M. Advances in the pharmacological treatment of Parkinson’s disease: targeting neurotransmitter systems. Trends Neurosci. 2013;36(9):543-554. 11. Kaakkola S, Wurtman RJ. Effects of COMT inhibitors on striatal dopamine metabolism: a microdialysis study. Brain Res.1992;587(2):241-249. 12. Kong P, Zhang B, Lei P, et al. Neuroprotection of MAO-B inhibitor and dopamine agonist in Parkinson disease. Int J Clin Exp Med. 2015;8(1):431-439. 13. Barrett MJ, Sargent L, Nawaz H, Weintraub D, Price ET, Willis AW. Antimuscarinic anticholinergic medications in Parkinson disease: to prescribe or deprescribe? Mov Disord Clin Pract. 2021;8(8):1181-1188. 14. Vanle B, Olcott W, Jimenez J, Bashmi L, Danovitch I, IsHak WW. NMDA antagonists for treating the non-motor symptoms in Parkinson’s disease. Transl Psychiatry. 2018;8(1):117. 15. Rascol O, Fabbri M, Poewe W. Amantadine in the treatment of Parkinson’s disease and other movement disorders. Lancet Neurol. 2021;20:1048-1056. 16. Rubí B, Maechler P. Minireview: new roles for peripheral dopamine on metabolic control and tumor growth: let’s seek the balance. Endocrinology. 2010;151(12):5570-5581. 17. Gerlach M, Double K, Arzberger T, Leblhuber F, Tatschner T, Riederer P. Dopamine receptor agonists in current clinical use: comparative dopamine receptor binding profiles defined in the human striatum. J Neural Transm (Vienna). 2003;110(10):1119-1127. 18. Jenner P. Istradefylline, a novel adenosine A_2A receptor antagonist, for the treatment of Parkinson’s disease. Expert Opin Investig Drugs. 2005;14(6):729-738. 19. Ishibashi K, Miura Y, Wagatsuma K, Toyohara J, Ishiwata K, Ishii K. Occupancy of adenosine A_2A receptors by istradefylline in patients with Parkinson’s disease using ¹¹C-preladenant PET. Neuropharmacology. 2018;143:106-112.

References: 1. NOURIANZ [package insert]. Kyowa Kirin, Inc. Princeton, NJ 08540. 2. Data on file. Kyowa Kirin Pharmaceutical Development, Inc., Princeton, NJ. 3. Wadhwa RR, Cascella M. Steady state concentration. StatPearls Publishing; 2023.

References: 1. NOURIANZ [package insert]. Kyowa Kirin, Inc. Princeton, NJ 08540. 2. Data on file. Kyowa Kirin Pharmaceutical Development, Inc., Princeton, NJ. 3. Hauser RA, Hattori N, Fernandez H, et al. Efficacy of istradefylline, an adenosine A_2A receptor antagonist, as adjunctive therapy to levodopa in Parkinson’s disease: a pooled analysis of 8 phase 2b/3 trials. J Park Dis. 2021;11:1663-1675.

Reference: 1. NOURIANZ [package insert]. Kyowa Kirin, Inc., Princeton, NJ 08540.

References: 1. NOURIANZ [package insert]. Kyowa Kirin, Inc., Princeton, NJ 08540. 2. Isaacson SH, Betté S, Pahwa R. Istradefylline for OFF episodes in Parkinson’s disease: a US perspective of common clinical scenarios. Degener Neurol Neuromuscul Dis. 2022;12:97-109. 3. Kulisevsky J, Poyurovsky M. Adenosine A_2A-receptor antagonism and pathophysiology of Parkinson’s disease and drug-induced movement disorders. Eur Neurol. 2012;67(1):4-11. 4. Mori A. Mode of action of adenosine A_2A receptor antagonists as symptomatic treatment for Parkinson’s disease. Int Rev Neurobiol. 2014;119:87-116. 5. DHIVY [package insert]. Alpharetta, GA: Avion Pharmaceuticals, LLC; 2021. 6. Olanow CW, Poewe W, Rascol O, Stocchi F. From OFF to ON—treating OFF episodes in Parkinson’s disease. US Neurol. 2020;16(suppl 1):2-10. 7. Chou KL, Stacy M, Simuni T, et al. The spectrum of “off” in Parkinson’s disease: what have we learned over 40 years? Parkinsonism Relat Disord. 2018;51:9-16.

Reference: 1. NOURIANZ. Prescribing Information. Kyowa Kirin, Inc; 2020. Accessed April 1, 2021. https://www.nourianzhcp.com/assets/pdf/nourianz-full-prescribing-information.pdf

NOURIANZ® (istradefylline) safety profile1,2

Clinical trial details

NOURIANZ: Safety data1

Incidence of adverse reactions ≥2% with either dose of NOURIANZ and greater than placebo1*

Treatment-emergent adverse reactions of special interest2,3

NOURIANZ: Low rates of discontinuation due to adverse events compared with placebo1†