The NOURIANZ Difference: Mechanism of Action

Only NOURIANZ^® lifts the brake of adenosine in Parkinson’s disease (PD)^1,2

NOURIANZ is a first-of-its-kind adenosine receptor antagonist indicated as adjunctive treatment to
levodopa/carbidopa in adults for reducing "off" time in PD.¹

The precise mechanism by which NOURIANZ exerts its therapeutic effect in PD is unknown.¹

In in vitro studies and in vivo animal studies, NOURIANZ was demonstrated to be an adenosine A_2A receptor antagonist.¹

Watch the NOURIANZ mechanism of action

With a novel MOA, NOURIANZ works differently than other adjunct treatments for “off” time in PD^1,4-7

The precise mechanism of action by which NOURIANZ exerts its therapeutic effect in PD is unknown.¹

NOURIANZ blocks A_2A receptors.^1,4-7

Table with drug class and dopamine and A2A receptor activity and how NOURIANZ® (istradefylline) is different than other adjunctive treatments for “off” episodes in Parkinson’s disease

COMT, catechol-o-methyl transferase; MAO, monoamine oxidase. ^aIncludes other classes of medication for PD, like anticholinergics and N-methyl-D-aspartate (NMDA) receptor antagonists, including amantadine, which may have effects on dopamine neurons.

Dopaminergic treatments affect dopamine receptors in the striatum and in other areas of the brain and peripheral system^{8, 9}
NOURIANZ is highly selective for adenosine A_2A receptors³
In in vitro studies and in vivo animal studies, NOURIANZ was demonstrated to be an adenosine A_2A receptor antagonist

The NOURIANZ Difference: PET Scans

Positron-emission tomography (PET) imaging of adenosine A_2A
receptors in basal ganglia¹⁰

The rainbow-colored scale represents the magnitude of BP_ND values. Adapted from Ishibashi K, et al. Adenosine A_2A Receptor Occupancy by Long-Term Istradefylline Administration in Parkinson’s Disease. Mov Disord. 2021;36(1):268-269. BP_ND, binding potential.

BP_ND maps in 4 patients with PD and relationship between adenosine A_2A receptor occupancy and dose of istradefylline.

Patients 1 and 3 received a 20 mg dose of istradefylline
Patients 2 and 4 received a 40 mg dose of istradefylline

Help your patients lift
the brake of adenosine
with NOURIANZ.

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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.

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.

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. Prescribing Information. Kyowa Kirin, Inc; 2023. Accessed November 1, 2023. https://www.nourianzhcp.com/assets/pdf/nourianz-full-prescribing-information.pdf. 2. 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.

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. NOURIANZ. Prescribing Information. Kyowa Kirin, Inc; 2020. Accessed April 1, 2021. https://www.nourianzhcp.com/assets/pdf/nourianz-full-prescribing-information.pdf 2. 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. 3. 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. 4. 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. 5. Kaakkola S, Wurtman RJ. Effects of COMT inhibitors on striatal dopamine metabolism: a microdialysis study. Brain Res. 1992;587(2):241-249. 6. 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. 7. Ossola B, Schendzielorz N, Chen SH, et al. Amantadine protects dopamine neurons by a dual action: reducing activation of microglia and inducing expression of GDNF in astroglia. Neuropharmacology. 2011;61(4):574-582. 8. 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. doi:10.1210/en.2010-0745. 9. 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. 10. Ishibashi K, Miura Y, Wagatsuma K, Toyohara J, Ishiwata K, Ishii K. Adenosine A_2A receptor occupancy by long-term istradefylline administration in Parkinson’s disease. Mov Disord. 2021;36(1):268-269. doi:10.1002/mds.28378.

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

The NOURIANZ Difference: Mechanism of Action

Only NOURIANZ® lifts the brake of adenosine in Parkinson’s disease (PD)1,2

NOURIANZ is a first-of-its-kind adenosine receptor antagonist indicated as adjunctive treatment to levodopa/carbidopa in adults for reducing "off" time in PD.1