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There is more to consider with Parkinson’s disease (PD) than dopamine...1,2

...there is also adenosine
  • In addition to the degeneration of dopaminergic neurons, there is also an increased density of A2A receptors3,4
  • The resulting overactivity of the indirect “STOP” pathway may further impact motor functionality3
  • There is only one available treatment for PD that specifically targets adenosine A2A receptors1,4
Parkinson's Mechanism of Disease
Choose NOURIANZ for your patients with PD who are experiencing “off” episodes while being treated with levodopa/carbidopa1
+

NOURIANZ: First and only adenosine A2A receptor antagonist for PD1

Learn more about this novel approach to PD therapy

NOURIANZ is an adenosine receptor antagonist
indicated as adjunctive treatment to levodopa/carbidopa
in adult patients with PD experiencing “off” episodes1
  • In PD, A2A receptor stimulation by adenosine, coupled with the dysfunction of dopamine D2 receptors due to the loss of dopamine, may lead to abnormality in signals for motor
    control3,4
  • The density of A2A receptors may increase over time5
  • Treatment with levodopa/carbidopa improves dopamine levels6,7

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

GPe, globus pallidus externa; GPi, globus pallidus interna; STN, subthalamic
nucleus; Str, striatum.

NOURIANZ:
First-in-class A2A receptor antagonist used with levodopa/ carbidopalevodopa/carbidopa for adults with PD experiencing “off” episodes1

Positron-emission tomography (PET) imaging of adenosine A2A receptors in basal ganglia8

PET Scan
Reprinted from Neuropharmacology, vol 143, Ishibashi K et al, Occupancy of adenosine
A2A receptors by istradefylline in patients with Parkinson's disease using 11C-preladenant PET, pp. 106-112, copyright 2018, with permission from Elsevier.

11C-preladenant PET scans were conducted in 10 patients with PD taking levodopa treatment,
then divided evenly into a NOURIANZ low-dose and NOURIANZ high-dose group.

Scans depict PET imaging of adenosine A2A receptors in:

  • Controls (A, n=6)
  • Patients with PD at baseline (B, n=10)
  • Patients with PD on 20 mg istradefylline (C, n=5)
  • Patients with PD on 40 mg istradefylline (D, n=5)

Images C and D illustrate occupancy of adenosine A2A receptors by istradefylline in patients with PD.

Images are displayed on the Montreal Neurological Institute standard brain. Legend displays magnitude of binding potential (red=high, purple=low).

With a novel mechanism of action, nondopaminergic NOURIANZ works differently than
other treatments for PD1,6,7,9-12

NOURIANZ blocks A2A receptors

NOURIANZ Drug Class Table

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.7,12

  • Dopaminergic treatments affect dopamine receptors in the striatum and in other areas of the brain and peripheral system13,14
  • NOURIANZ is highly selective for adenosine A2A receptors15

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

 
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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.

Reference: 1. NOURIANZ [package insert]. Kyowa Kirin, Inc., Bedminster, NJ, USA.

References: 1. Hickey P, Stacy M. Available and emerging treatments for Parkinson’s disease: a review. Drug Des Devel Ther. 2011;5:241-254. 2. 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. 3. Parkinson’s Foundation. Statistics. https://parkinson.org/Understanding-Parkinsons/Statistics. Accessed May 5, 2019. 4. 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. 5. NOURIANZ [package insert]. Kyowa Kirin, Inc., Bedminster, NJ, USA.

References: 1. NOURIANZ [package insert]. Kyowa Kirin, Inc., Bedminster, NJ, USA. 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. Morelli M, Di Paolo T, Wardas J, Calon F, Xiao D, Schwarzschild MA. Role of adenosine A2A receptors in parkinsonian motor impairment and L-DOPA-induced motor complications. Prog Neurobiol. 2007;83(5):293-309. 4. Mishina M, Ishiwata K, Naganawa M, et al. Adenosine A2A receptors measured with [11C]TMSX PET in the striata of Parkinson's disease patients. PLoS One. 2011;6(2):e17338. doi:10.1371/journal.pone.0017338. 5. Varani K, Vincenzi F, Tosi A, et al. A2A 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. 6. Brooks DJ. Dopamine agonists: their role in the treatment of Parkinson’s disease [editorial]. J Neurol Neurosurg Psychiatry. 2000;68(6):685-689. 7. 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. 8. Ishibashi K, Miura Y, Wagatsuma K, Toyohara J, Ishiwata K, Ishii K. Occupancy of adenosine A2A receptors by istradefylline in patients with Parkinson’s disease using 11C-preladenant PET. Neuropharmacology. 2018;143:106-112. 9. 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. 10. Kaakkola S, Wurtman RJ. Effects of COMT inhibitors on striatal dopamine metabolism: a microdialysis study. Brain Res. 1992;587(2):241-249. 11. 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. 12. GOCOVRI® (amantadine) [Prescribing Information]. Emeryville, CA: Adamas Pharma LLC; 2017. 13. 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. 14. 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. 15. Jenner P. Istradefylline, a novel adenosine A2A receptor antagonist, for the treatment of Parkinson's disease. Expert Opin Investig Drugs. 2005;14(6):729-738.

References: 1. NOURIANZ [package insert]. Kyowa Kirin, Inc., Bedminster, NJ, USA. 2. Data on file. Kyowa Kirin Pharmaceutical Development, Inc., Princeton, NJ.

References: 1. Data on file. Kyowa Kirin Pharmaceutical Development, Inc., Princeton, NJ. 2. NOURIANZ [package insert]. Kyowa Kirin, Inc., Bedminster, NJ, USA.

Reference: 1. NOURIANZ [package insert]. Kyowa Kirin, Inc., Bedminster, NJ, USA.