Istradefylline

The precise mechanism by which istradefylline exerts its therapeutic effect in Parkinson’s disease is unknown. In in vitro studies and in in vivo animal studies, istradefylline was demonstrated to be an adenosine A 2A receptor antagonist.

• NOURIANZ is indicated as adjunctive treatment to levodopa/carbidopa in adult patients with Parkinson's disease (PD) experiencing "off" episodes. NOURIANZ is an adenosine receptor antagonist indicated as adjunctive treatment to levodopa/carbidopa in adult patients with Parkinson's disease (PD) experiencing "off" episodes ( 1 ).ICD-10: G20

• None. None ( 4 ).contraindicated

The recommended dosage is 20 mg orally once daily. The dosage may be increased to a maximum of 40 mg once daily ( 2.1 ). May be taken with or without food ( 2.1 ). Patients with hepatic impairment: Maximum recommended dosage with moderate hepatic impairment is 20 mg once daily; use of NOURIANZ in patients with severe hepatic impairment should be avoided ( 2.4 , 8.7 ). Patients who smoke 20 or more cigarettes per day (or the equivalent of another tobacco product): Recommended dosage is 40 mg once daily ( 2.5 , 8.8 ). 2.1 Dosing Information The recommended dosage of NOURIANZ is 20 mg administered orally once daily. The dosage may be increased to a maximum of 40 mg once daily, based on individual need and tolerability. Initial dose titration is not required. NOURIANZ can be taken with or without food [see Clinical Pharmacology (12.3) ] . 2.2 Dosage Adjustment with Strong CYP3A4 Inhibitors The maximum recommended dosage of NOURIANZ with concomitant use of strong CYP3A4 inhibitors is 20 mg once daily [see Drug Interactions (7.1) ] . 2.3 Dosing with Strong CYP3A4 Inducers Avoid use of NOURIANZ with strong CYP3A4 inducers [see Drug Interactions (7.1) ] . 2.4 Dosage Adjustment in Patients with Hepatic Impairment The maximum recommended dosage of NOURIANZ in patients with moderate hepatic impairment (Child-Pugh Class B) is 20 mg once daily. Closely monitor patients with moderate hepatic impairment for adverse reactions when on NOURIANZ treatment [see Adverse Reactions (6.1) ] .

Dyskinesia: Monitor patients for dyskinesia or exacerbation of existing dyskinesia ( 5.1 ). Hallucinations / Psychotic Behavior: Consider dosage reduction or stopping NOURIANZ if occurs ( 5.2 ). Impulse Control / Compulsive Behaviors: Consider dosage reduction or stopping NOURIANZ if occurs ( 5.3 ). 5.1 Dyskinesia NOURIANZ in combination with levodopa may cause dyskinesia or exacerbate pre-existing dyskinesia. In controlled clinical trials (Studies 1, 2, 3, and 4) [see Clinical Studies (14) ] , the incidence of dyskinesia was 15% for NOURIANZ 20 mg, 17% for NOURIANZ 40 mg, and 8% for placebo, in combination with levodopa. One percent of patients treated with either NOURIANZ 20 mg or 40 mg discontinued treatment because of dyskinesia, compared to 0% for placebo. 5.2 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. In controlled clinical trials (Studies 1, 2, 3, and 4) [see Clinical Studies (14) ] , the incidence of hallucinations was 2% for NOURIANZ 20 mg, 6% for NOURIANZ 40 mg, and 3% for placebo. In patients treated with NOURIANZ 40 mg, 1% discontinued because of hallucinations, compared to 0% for placebo and 0% for patients treated with NOURIANZ 20 mg.

The following clinically significant adverse reactions are discussed in greater detail in other sections of the labeling: Dyskinesia [see Warnings and Precautions (5.1) ] Hallucinations / Psychotic Behavior [see Warnings and Precautions (5.2) ] Impulse Control / Compulsive Behaviors [see Warnings and Precautions (5.3) ] The most common adverse reactions (at least 5% and more frequent than placebo) were dyskinesia, dizziness, constipation, nausea, hallucination, and insomnia ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Kyowa Kirin Inc. at 1-844-768-3544 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of NOURIANZ was evaluated in 734 patients with Parkinson's disease (PD) taking a stable dose of levodopa and a DOPA decarboxylase inhibitor, with or without other PD medications, in four randomized, multicenter, double-blind, placebo-controlled trials 12 weeks in duration (Studies 1, 2, 3 and 4) [see Clinical Studies (14) ] . Of the patient population exposed to NOURIANZ, 50% were male, 32% White, 67% Asian, and the mean age was 65 years (range: 33 to 84 years). Of these patients, 356 received NOURIANZ 20 mg and 378 received NOURIANZ 40 mg.

Pregnancy: Based on animal data, may cause fetal harm ( 8.1 ). 8.1 Pregnancy Risk Summary There are no adequate data on the developmental risk associated with the use of NOURIANZ in pregnant women. In animal studies ( see Data ), oral administration of istradefylline during pregnancy resulted in teratogenicity (increased incidences of fetal structural abnormalities, embryofetal and offspring mortality and growth deficits) at clinically relevant exposures and in the absence of maternal toxicity. The teratogenic effects of istradefylline in pregnant rabbits were substantially greater when administered in combination with levodopa/carbidopa than when administered alone. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies are 2-4% and 15-20%, respectively. Data Animal Data Oral administration of istradefylline (0, 40, 200, or 1000 mg/kg/day) to pregnant rats throughout organogenesis resulted in decreased fetal body weight and increased fetal skeletal and visceral variations at the highest dose tested.

Metabolism

Istradefylline exhibits dose-proportional pharmacokinetics after multiple oral doses from 20 mg to 80 mg (2 times the maximum recommended dosage). Steady-state was reached within 2 weeks of once-daily dosing.

10.1 Human Experience There is limited clinical experience regarding human overdosage with NOURIANZ. In clinical trials, one patient took 6 tablets (120 mg, 3 times the maximum recommended dosage) of istradefylline with alcoholic beverages and developed hallucinations, agitation, and worsening dyskinesia. 10.2 Management of Overdose There are no known specific antidotes for NOURIANZ nor any specific treatment for istradefylline overdose. If an overdose occurs, NOURIANZ treatment should be discontinued and supportive treatment should be administered as clinically indicated. Consider the long terminal half-life of istradefylline (about 83 hours) and the possibility of multiple drug involvement. Consult a Certified Poison Control Center for up-to-date guidance and advice.

• Aug 27, 2019NDANDA022075Kyowa Kirin

1. 1Death70612%
2. 2Drug Ineffective62411%
3. 3Hallucination60310%
4. 4Dyskinesia4798.2%
5. 5Condition Aggravated4467.6%
6. 6Dizziness4197.2%
7. 7Product Dose Omission Issue3596.1%
8. 8Constipation3536.0%
9. 9Fall3335.7%
10. 10Tremor2614.5%
11. 11Therapy Non-responder2524.3%
12. 12Insomnia2253.8%
13. 13Fatigue2013.4%
14. 14Nausea1963.3%
15. 15Parkinson^s Disease1783.0%

The 10 most recently updated of 27 ClinicalTrials.gov registrations naming Istradefylline as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Adenosine 2A Receptor Antagonism and AIH in ALS
  Active not recruiting · Phase 1 · Phase 2 · Interventional · 40 enrolled · University of Florida
  NCT05377424updated 2026-03-27
• Combining Low Oxygen Therapy and an Adenosine A2a Receptor Antagonist to Improve Functional Mobility After Spinal Cord Injury
  Not yet recruiting · Phase 1 · Phase 2 · Interventional · 40 enrolled · Randy Trumbower, PT, PhD
  NCT05217498updated 2026-03-20
• Effect of Istradefylline Treatment on Behavioral Measures of Apathy in Parkinson's Disease.
  Terminated · Observational · 8 enrolled · Medical University of South Carolina
  NCT05182151updated 2026-02-02
• Istradefylline for Parkinson Disease With Cognitive Impairment
  Completed · Phase 2 · Interventional · 15 enrolled · Virginia Commonwealth University
  NCT05333549updated 2025-07-28
• Istradefylline Effect Protocol on Parkinson's Disease Tremor
  Completed · Phase 4 · Interventional · 27 enrolled · Georgetown University
  NCT05885360updated 2025-03-13
• An Extension of Istradefylline in North American Parkinson's Disease Patients Who Have Completed Study 6002-INT-001
  Terminated · Phase 3 · Interventional · 504 enrolled · Kyowa Kirin, Inc.
  NCT00199381updated 2024-05-17
• An Extension of Istradefylline in Parkinson's Disease Patients Who Have Completed Studies 6002-EU-007, 6002-US-013 or 6002-US-018
  Completed · Phase 3 · Interventional · 1,100 enrolled · Kyowa Kirin, Inc.
  NCT00199368updated 2024-04-25
• A Study of Istradefylline (KW-6002) for the Treatment of Parkinson's Disease in Patients Taking Levodopa
  Completed · Phase 3 · Interventional · 230 enrolled · Kyowa Kirin, Inc.
  NCT00199407updated 2024-04-25
• Effect of Mild Hepatic Impairment on the Pharmacokinetics of Istradefylline
  Completed · Phase 1 · Interventional · 20 enrolled · Kyowa Kirin Co., Ltd.
  NCT02256033updated 2024-04-25
• Long Term Study of Istradefylline in Subjects With Moderate to Severe Parkinson's Disease
  Completed · Phase 3 · Interventional · 239 enrolled · Kyowa Kirin Co., Ltd.
  NCT02610231updated 2024-04-25

Frequently asked questions

How does Istradefylline work?

The precise mechanism by which istradefylline exerts its therapeutic effect in Parkinson’s disease is unknown. In in vitro studies and in in vivo animal studies, istradefylline was demonstrated to be an adenosine A 2A receptor antagonist.

What is Istradefylline used for?

According to FDA labeling, Istradefylline carries indications including: NOURIANZ is indicated as adjunctive treatment to levodopa/carbidopa in adult patients with Parkinson's disease (PD) experiencing "off" episodes. NOURIANZ is an adenosine receptor antagonist indicated as adjunctive treatment to levodopa/carbidopa in adult patients with Parkinson's disease (PD) experiencing "off" episodes ( 1 ).. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Istradefylline?

Istradefylline is classified as Other antiparkinson drugs, Adenosine Receptor Antagonists.

What are the brand names for Istradefylline?

Istradefylline is marketed under brand names including Nourianz.

What are the contraindications for Istradefylline?

Istradefylline labeling lists contraindications including: None. None ( 4 ).. Always consult the full prescribing information and a clinician.