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Nourianz istradefylline 40 mg Tablet, Film Coated, 90-count — NDC 42747-0604-90 package photo
Label image from the product's FDA listing (DailyMed) — may show a different pack size or an older label revision.

Nourianz istradefylline 40 mg Tablet, Film Coated, 90-count — NDC 42747-604-90 (Billing 42747-0604-90)

by Kyowa Kirin, Inc. · 90 TABLET, FILM COATED in 1 BOTTLE

This is a package of 90 tablets of Nourianz istradefylline 40 mg Tablet, Film Coated from Kyowa Kirin, Inc., marketed since Aug 2019 and currently FDA-listed. It is the main listing for this product, which comes in 2 package sizes.

NDC 42747-0604-90
🏷️ FDA NDC (as labeled) 42747-604-90 billing pads the product segment with a zero
This package
Contains90-count Medicaid pays$66.95 / unit · 12 mo Per package$6,025.15 / 90 tablets · Medicaid Pack sizes2 compare ↓
Also priced by: Part D plans $69.06/unit — full pricing hub ↓
Main listing for product 42747-604 · Also comes in: 7 tablets 42747-604-07
Rx only Brand On market Non-controlled ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 8, 2026 · this listing last changed Jul 24, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

This page is curated, coded, and maintained by

Compiled from public FDA, CMS, DailyMed, NADAC, and related drug data sources. Editorial policy

NDC database record

One package, one record: these facts belong to NDC 42747-604-90 alone.

Record
FDA NDC Directory package listing · Human prescription drug
Code segments
42747 labeler · 604 product · 90 package
Package marketed since
Aug 27, 2019
Sample package
No — commercial package
Listing certified through
Dec 31, 2026
Billing quantity
90 EA per package
Barcode (UPC)
0342747604906, 0342747602902
Medicaid fills, this package
205 prescriptions in the last four reported quarters
FDA record last changed
Jul 24, 2026

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 42747-604-90
Product NDC 42747-604
11-digit billing NDC 42747060490
NCPDP billing unit EA — each (per item)
RxCUI 2199020, 2199026, 2199028, 2199030
UNII 2GZ0LIK7T4
UPC 0342747604906, 0342747602902
Application # NDA022075
SPL Set ID a7d008cb-b273-4049-a5d2-9c6902910d58
DEA schedule Non-controlled
Marketing category NDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2019-08-27
Route ORAL
Dosage form TABLET, FILM COATED
Substance ISTRADEFYLLINE

Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification

GPI-14 73401025000340
GPI class Nourianz
GCN Seq No 080178
GCN 46884
HICL code 045994
Ingredient (HICL) Istradefylline
HIC1 code H
Therapeutic class — broad (HIC1) Nervous System (Except Autonomic)
HIC2 code H6
Therapeutic class — intermediate (HIC2) Drugs Acting Principally On The Midbrain
HIC3 code H6A
Therapeutic class — specific (HIC3) Antiparkinsonism Drugs,Other
AHFS code 28:36.24.00
AHFS class Adenosine A2A Receptor Antagonists
FDB label name NOURIANZ 40 MG TABLET
FDB brand name Nourianz
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 080178
  • GCN: 46884
  • GPI-14 (Medi-Span): 73401025000340
  • HICL (First Databank): 045994
  • AHFS class code: 28:36.24.00
  • RxCUI (RxNorm): 2199020
Why two NDCs? The FDA registers this code as 42747-604-90 — a 5-3-2 layout, and that's what's printed on the package and shown on DailyMed. For insurance claims, every NDC is standardized to a uniform 11-digit 5-4-2 format by adding a zero to the product segment → 42747-0604-90. Same drug, same package — only the format differs.
Where does this data come from?
Identifiers from the FDA openFDA NDC Directory and Structured Product Labeling; RxCUI from RxNorm (NLM); GPI from Medi-Span; GCN / HIC / AHFS / legend from First Databank.

RxNorm drug class

This medicine belongs to the Other antiparkinson drugs class.

Drug family (ATC) Other antiparkinson drugs
Where does this data come from?
Therapeutic classes from RxNorm RxClass (U.S. National Library of Medicine) — Established Pharmacologic Class (FDA), ATC drug family (WHO) and mechanism of action, matched by this product’s RxCUI.

Clinical

Label name NOURIANZ 40 MG TABLET Ingredient Istradefylline
📖 What it is MedlinePlus · NLM

Istradefylline is used along with the combination of levodopa and carbidopa (Duopa, Rytary, Sinemet, others) to treat "off" episodes (times of difficulty moving, walking, and speaking that may happen as medication wears off or at random) in people with Parkinson's disease (PD; a disorder of the nervous system that causes difficulties with movement, muscle control, and balance). Istradefylline is in a class of medications called adenosine receptor antagonists. It works by changing the activity of certain natural substances in the brain.

Read the full MedlinePlus article ↗
📗 Our plain-language guide HelloPharmacist
  • Istradefylline (Nourianz) is an add-on to levodopa/carbidopa for adults with Parkinson’s disease. It is for people who still have “off” episodes, when symptoms come back between le...
  • You take one tablet by mouth once a day. It’s fine with or without food. Follow your prescriber’s directions, since the amount can depend on your liver health, tobacco use, and oth...
  • The most common ones are uncontrolled movements (dyskinesia), dizziness, constipation, nausea, hallucinations, and trouble sleeping. Let your doctor know if any are bothersome or g...
  • Call if you see or hear things that aren’t there, become paranoid, confused or agitated, or have new strong urges to gamble, spend, binge eat, or increased sexual urges. Lowering t...
📖 Read our full Istradefylline guide →
Where does this data come from?
Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

Pricing

A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.

Price systemPer eachPer package
Retail pharmacies payNADAC · weekly Not in the retail survey — common for institutional, discontinued, or low-volume packs.
Medicaid paysCMS SDUD · 12 mo $66.95 $6,025.15 / 90 tablets
Medicare drug plans payPart D · Q2 2026 $69.06 $6,214.95 / 90 tablets
Where does this data come from?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

Packaging — all sizes for this product

Package NDCDescription Marketing startMarketing endStatus
42747-0604-07 42747-604-07 1 BLISTER PACK in 1 BOX / 7 TABLET, FILM COATED in 1 BLISTER PACK Sample 2019-08-27 — Active
42747-0604-90 You're viewing this Main listing 90 TABLET, FILM COATED in 1 BOTTLE 2019-08-27 — Active

In Medicaid, this is the most-dispensed pack of this product — about 100% of fills over the last four reported quarters. See all packs ↓

Pack size FAQ

What quantity is in this package?
This is a 90-count package — 90 tablet, film coated in 1 bottle.
How does this package differ from NDC 42747-0604-07?
Both are Nourianz istradefylline 40 mg Tablet, Film Coated — the drug itself is identical. This page's package is the 90-count one, while NDC 42747-0604-07 is the 7 tablets package.
What NDC number is used to bill for this package of Nourianz istradefylline 40 mg Tablet, Film Coated?
Use the 11-digit billing form listed in the identifiers section of this page. Pharmacy and medical claims use the 11-digit form; the FDA label may print a shorter form of the same code.

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Nourianz 40 mgthis 42747-0604-90 Kyowa 90 tablets — — FDA listed —
About this product: this is the brand-name version. We did not find an FDA-approved generic match for this exact strength, form and route.
Where does this data come from?
Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

Availability & generic status

🏛️
2019
First FDA approval
Aug 2019
📍
2026
Currently FDA-listed
7 years listed
🛡️
2028
Latest patent/protection listed
not a guaranteed launch date
🔒No FDA-approved generic found

We did not find an FDA-approved generic match for this exact strength, form and route. Patent/protection dates below may affect future generic timing.

🛡️ Latest patent/protection date listed: FDA patent/protection data lists protections through Jan 2028. This may affect when a full generic version becomes widely available, but it is not a guaranteed launch date.
📅 FDA approved Aug 27, 2019 RLD RS ⏳ ~1.3 yr to latest listed protection

Why the date isn’t exact: Generic timing can change because patents may be challenged, settled, licensed, added, removed, or worked around with a narrower label — and FDA approval does not always mean a pharmacy can get the generic today.

Patents & exclusivity — FDA Orange Book
US 7727993 — method of use (U-2623)
US 7727993 — method of use (U-2623)
US 8318201 — drug product
US 8318201 — drug product
2019 2021 2023 2025 2027
Today
LOE
Substance patent Formulation patent Method-of-use patent Exclusivity Pediatric +6mo
🏛️FDA exclusivity
FDA-granted marketing protection. It’s separate from patents and may be shorter than patent protection.
🧪Product / substance patents
Patents covering the active ingredient, product, formulation, or related drug features.
🎯Method-of-use patents
Patents covering specific approved uses. These can sometimes be carved out with a “skinny label,” but not always.
🛈 What do these terms mean?
Patent
Legal protection listed in the Orange Book that may delay generic approval or launch. Issued by the U.S. Patent & Trademark Office.
Substance patent
Covers the active drug molecule itself — the hardest to design around. A generic generally can’t launch until it expires.
Formulation (product) patent
Covers a specific formulation or dosage form. A generic can sometimes work around it with a different formulation.
Method-of-use patent
A patent covering one specific approved use of the drug — not necessarily the whole molecule. A generic can sometimes launch with a “skinny label” that carves out the protected use and keeps the others.
Skinny label
A generic label that omits a still-patented use when the FDA allows it — letting a generic reach the market for the unprotected uses.
Exclusivity
FDA-granted marketing protection, separate from patents — e.g. 5-yr new chemical entity, 7-yr orphan drug, or a +6-month pediatric extension.
Paragraph IV
A generic applicant’s formal challenge to a listed patent. It can potentially lead to earlier generic entry, but often involves litigation or a settlement.
RLD / RS
Reference Listed Drug — the brand product the FDA uses as the reference for generic applications. Reference Standard — the product the FDA expects generics to compare against in bioequivalence testing.
TE / AB rating
FDA therapeutic-equivalence rating. An AB rating generally means the FDA considers a generic therapeutically equivalent to — and substitutable for — the brand.
LOE (loss of exclusivity)
The latest patent or exclusivity currently listed — the loss-of-exclusivity / latest-listed-protection date shown on this page. Paragraph-IV challenges and settlements can move the real date earlier; FDA approval and a manufacturer’s decision to market can move it later.

Built from the FDA Orange Book. The bars above are scaled to each protection’s expiry; the red LOE marker is the last one to lapse.

Listed patents (4)
PatentTypeUse codeExpires
US 7727993 ↗ Method of use U-2623 Jan 28, 2028
US 7727993 ↗ Method of use U-2623 Jan 28, 2028
US 8318201 ↗ Drug product — Sep 5, 2027
US 8318201 ↗ Drug product — Sep 5, 2027
Common questions
Is there a generic version of NOURIANZ 40 MG TABLET?
No FDA-approved generic equivalent is currently listed in the FDA Orange Book for NOURIANZ 40 MG TABLET. Based on the patents and exclusivity currently listed, the Orange Book estimate is that full-label generic entry may be delayed until Jan 2028 — an estimate, not a guaranteed launch date.
The FDA approved a generic — why can’t I get it at my pharmacy yet?
FDA approval and pharmacy availability are two different things. The FDA can approve a generic years before it actually reaches pharmacies, because the brand company may still hold patents or have a settlement that delays the launch. A manufacturer also has to choose to make and sell it, and have supply ready. So a drug can be “FDA-approved generic exists” and still be brand-only at the counter today.
Why do different websites show different generic release dates?
Generic availability is not based on one single date. Some sources use the first exclusivity expiration, some use the last product patent, and others use the latest method-of-use patent. Patent challenges, settlements, licenses, and label carve-outs can also change the real-world launch date. This page shows the underlying Orange Book dates so you can see why estimates may differ.
What does “FDA listed” mean?
It means the product appears in the FDA’s official NDC directory. That’s a good sign a product exists and is intended for the U.S. market, but on its own it does not confirm a pharmacy can fill it today. Where we have recent retail pricing data (NADAC) for a product, we label it “Availability likely” instead.
What does a patent or protection date mean here?
It’s the latest date currently listed in the FDA Orange Book for a patent or exclusivity on the brand product. It can affect when a full generic version becomes widely available — but it is not a guaranteed generic launch date. Generics sometimes arrive earlier (through a settlement or patent challenge) or later (a manufacturer still has to make and sell one).
What does “current Orange Book estimate” mean?
It means we are using the latest patent and exclusivity dates currently listed in the FDA Orange Book. It is not a guaranteed launch date.
Can a generic come out before the last patent expires?
Sometimes. A generic company may challenge a patent, settle with the brand manufacturer, receive a license, or obtain approval with a narrower label that avoids a patented use. In other cases, the last listed protection may delay full-label generic competition.
Can a generic come out after the listed dates?
Yes. Even after patents or exclusivity expire, a generic still needs FDA approval and a manufacturer must choose to market it. Supply, litigation, business decisions, or regulatory issues can delay actual availability.
What is the difference between patents and exclusivity?
Patents are legal protections usually issued by the U.S. Patent and Trademark Office. FDA exclusivity is marketing protection granted by the FDA. They are separate, and either one can affect generic timing.
Why are there multiple patent dates?
One drug can have several patents covering different things: the active ingredient, a formulation, a manufacturing process, or a specific approved use. That is why a page may show several expiration dates instead of one simple generic date.
Built from FDA Orange Book patent and exclusivity data. Dates are refreshed from public FDA data when available; the marker is max(latest patent expiry, latest exclusivity expiry). Paragraph-IV settlements and first-filer 180-day exclusivity can shift the real date; a method-of-use patent may allow an earlier skinny-label generic for non-protected indications. Generic launch timing is an estimate, not a guarantee.
Where does this data come from?
Patents and exclusivity from the FDA Orange Book (small-molecule drugs), refreshed from public FDA data. Generic launch timing is an estimate, not a guarantee.

Inactive Ingredients / Excipients

Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.

🧪 Avoiding an ingredient? See Istradefylline inactive ingredients by manufacturer: every current product's list side by side, so you can ask your pharmacy for the version that does not list it.

💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.

  • UNII R12CBM0EIZ
    A natural wax derived from a Brazilian palm tree, used as a coating and polish on tablets and capsules. It creates a smooth, shiny finish that protects the medicine and improves appearance.
  • UNII 2S7830E561
    Crospovidone is a synthetic polymer derived from povidone. It acts as a disintegrant, helping the tablet or capsule break apart quickly in the stomach so the active ingredient can be absorbed.
  • UNII EWQ57Q8I5X
    Lactose monohydrate is a natural sugar derived from milk. It serves as a filler and binder in tablets and capsules, helping create the proper size, texture, and consistency of the medicine.
  • UNII 70097M6I30
    Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
  • UNII OP1R32D61U
    Microcrystalline cellulose is a purified form of cellulose, a natural fiber from plant sources. It acts as a binder and filler in tablets and capsules, helping hold ingredients together and give the medicine its shape and size.
  • UNII 532B59J990
    Polyvinyl alcohol is a synthetic polymer made from plant-derived materials. It's used as a binder to hold ingredients together, a film-former in coatings, and a thickener in liquid formulations.

6 inactive ingredients listed in the exact product block matched to this NDC.

Where does this data come from?
Data sourced from official FDA Structured Product Labeling (SPL) via DailyMed — ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.

Inactive ingredient FAQ

Are inactive ingredients the same for every manufacturer?
No. Inactive ingredients can differ by manufacturer, dosage form, strength, and package / product version.
Why might an inactive ingredient be missing?
Some SPLs do not provide a complete structured inactive-ingredient list, and older or unusual labels may only include the information in narrative text.
Can inactive ingredients matter?
Yes. They can matter for allergies, intolerances, dyes, gluten / lactose concerns, preservatives, and formulation differences — but confirm with a pharmacist or the manufacturer when it’s clinically important.

Manufacturer & labeler

LabelerKyowa Kirin, Inc.
Application holderKYOWA KIRIN INC
FDA applicationNDA022075 (NDA)
Labeler code42747
First marketedAug 2019
Product typeHuman Prescription Drug
Portfolio7 products on file

More NDCs from Kyowa Kirin, Inc. labeler code 42747

The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Very long sections are excerpted here and marked; the full text is on DailyMed (linked in the sources below). Jump with a chip, search within the label, or expand everything.
🎯 Indications and Usage ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications ⚠️ Warnings and Cautions 🤒 Adverse Reactions 🔄 Drug Interactions 👥 Use in Specific Populations 🤰 Pregnancy 🧒 Pediatric Use 🧓 Geriatric Use 🆘 Overdosage 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📦 Storage and Handling 📋 Description 💬 Information for Patients 🧬 Pharmacokinetics 🧬 Pharmacodynamics 🔬 Clinical Studies 🧪 Nonclinical Toxicology 📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 📄 Patient Package Insert 📄 Package Label / Principal Display Panel
🎯 Indications and Usage 47 words ▾

1 INDICATIONS AND USAGE 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 ).

⏱️ Dosage and Administration ~1 min read ▾

2 DOSAGE AND ADMINISTRATION 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 ).

2.1Dosing 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) ] .

2.2Dosage 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) ] .

2.3Dosing with Strong CYP3A4 Inducers Avoid use of NOURIANZ with strong CYP3A4 inducers [see Drug Interactions (7.1) ] .

2.4Dosage 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) ] . Avoid use of NOURIANZ in patients with severe hepatic impairment (Child-Pugh Class C) [see Use in Specific Populations (8.7) ] .

2.5Dosage Adjustment for Tobacco Smokers The recommended dosage of NOURIANZ in patients who use tobacco in amounts of 20 or more cigarettes per day (or the equivalent of another tobacco product) is 40 mg once daily [see Use in Specific Populations (8.8) and Clinical Pharmacology (12.3) ] .

💊 Dosage Forms and Strengths 40 words ▾

3 DOSAGE FORMS AND STRENGTHS 20 mg tablets: Peach-colored, pillow-shaped, film-coated tablets with "20" debossed on one side. 40 mg tablets: Peach-colored, almond-shaped, film-coated tablets with "40" debossed on one side. Tablets: 20 mg and 40 mg ( 3 ).

⛔ Contraindications 7 words ▾

4 CONTRAINDICATIONS None. None ( 4 ).

⚠️ Warnings and Cautions ~2 min read ▾

5 WARNINGS AND PRECAUTIONS 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 ).

5.1Dyskinesia 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.

5.2Hallucinations / 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 incidence of "abnormal thinking and behavior" (paranoid ideation, delusions, confusion, mania, disorientation, aggressive behavior, agitation, or delirium) reported as an adverse reaction was 1% for NOURIANZ 20 mg, 2% for NOURIANZ 40 mg, and 1% for placebo.

5.3Impulse 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 controlled clinical trials (Studies 1, 2, 3 and 4) [see Clinical Studies (14) ] , one patient treated with NOURIANZ 40 mg was reported to have impulse control disorder, compared to no patient on placebo or NOURIANZ 20 mg.

In some postmarketing cases, these urges were reported to have stopped when the dose was reduced, or the medication was discontinued. Because patients may not recognize these behaviors as abnormal, it is important for prescribers to specifically ask patients or their caregivers about the development of new or increased gambling urges, sexual urges, uncontrolled spending, binge or compulsive eating, or other urges while being treated with NOURIANZ. Consider dose reduction or discontinuation if a patient develops such urges while taking NOURIANZ [see Adverse Reactions (6.2) ] .

🤒 Adverse Reactions ~2 min read ▾

6 ADVERSE REACTIONS 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.

6.1Clinical 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. Adverse Reactions Leading to Discontinuation of Treatment The incidence of patients discontinuing for any adverse reaction was 5% for NOURIANZ 20 mg, 6% for NOURIANZ 40 mg, and 5% for placebo.

The most frequently reported adverse reaction causing study discontinuation was dyskinesia [see Warnings and Precautions (5.1) ] . Common Adverse Reactions in Pooled Placebo-Controlled Trials Table 1 shows adverse reactions with a frequency of at least 2% in patients treated with NOURIANZ 20 mg or 40 mg once daily. The most common adverse reactions in which the frequency for NOURIANZ was at least 5%, and greater than the incidence on placebo, were dyskinesia, dizziness, constipation, nausea, hallucination, and insomnia.

Table 1: Adverse Reactions with an Incidence of at Least 2% in Patients Treated with NOURIANZ, and Greater than on Placebo, in Pooled Studies 1, 2, 3, and 4 Adverse Reactions NOURIANZ 20 mg/day (N=356) % NOURIANZ 40 mg/day (N=378) % Placebo N=426 (%) Nervous system disorders Dyskinesia 15 17 8 Dizziness 3 6 4 Gastrointestinal disorders Constipation 5 6 3 Nausea 4 6 5 Diarrhea 1 2 1 Psychiatric disorders Hallucination Includes hallucinations, hallucinations visual, hallucinations olfactory, hallucinations somatic, hallucinations auditory.

2 6 3 Insomnia 1 6 4 Metabolism and nutrition disorders Decreased appetite 1 3 1 Investigations Blood alkaline phosphatase increased 1 2 1 Blood glucose increased 1 2 0 Blood urea increased 1 2 0 Respiratory, thoracic and mediastinal disorders Upper Respiratory Tract Inflammation 1 2 0 Skin and subcutaneous tissue disorders Rash 1 2 1

6.2Postmarketing Experience The following adverse reaction has been identified during post approval use of istradefylline outside of the United States. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure: increased libido.

🔄 Drug Interactions ~1 min read ▾

7 DRUG INTERACTIONS Strong CYP3A4 inhibitors: Recommended maximum dosage with concomitant use is 20 mg once daily ( 2.2 , 7.1 ). Strong CYP3A4 inducers: Avoid use ( 2.3 , 7.1 ).

7.1Effect of Other Drugs on NOURIANZ Strong CYP3A4 Inhibitors Coadministration of NOURIANZ with a strong CYP3A4 inhibitor (ketoconazole) increased istradefylline AUC inf by 2.5-fold [see Clinical Pharmacology (12.3) ] . Therefore, the recommended maximum dosage of NOURIANZ in patients concomitantly using strong CYP3A4 inhibitors (e.g., itraconazole, ketoconazole, clarithromycin) is 20 mg once daily [see Dosage and Administration (2.2) ]. Strong CYP3A4 Inducers Coadministration of NOURIANZ with a strong CYP3A4 inducer (rifampin) decreased istradefylline C max and AUC inf by 45% and 81%, respectively [see Clinical Pharmacology (12.3) ] .

Therefore, it is recommended to avoid use of NOURIANZ with strong CYP3A4 inducers (e.g., carbamazepine, rifampin, phenytoin, St. John's wort) [see Dosage and Administration (2.3) ].

7.2Effect of NOURIANZ on Other Drugs CYP3A4 Substrates Coadministration of NOURIANZ 20 mg with a CYP3A4 substrate (midazolam) did not affect the CYP3A4 substrate exposure, while concomitant administration of NOURIANZ 40 mg increased the CYP3A4 substrate (atorvastatin) C max and AUC inf by 1.5-fold [see Clinical Pharmacology (12.3) ] . Monitor for an increase in adverse reactions of concomitant drugs that are CYP3A4 substrates when coadministering with NOURIANZ 40 mg. P-glycoprotein (P-gp) Substrates Coadministration of NOURIANZ with a P-gp substrate (digoxin) increased the P-gp substrate C max and AUC inf by 33% and 21%, respectively [see Clinical Pharmacology (12.3) ] .

Monitor for an increase in adverse reactions of concomitant drugs that are P-gp substrates when coadministering with NOURIANZ.

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS Pregnancy: Based on animal data, may cause fetal harm ( 8.1 ).

8.1Pregnancy 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.

Plasma exposure (AUC) at the no-effect dose for adverse effects on embryofetal development in rats (200 mg/kg/day) is approximately 4 times that in humans at the maximum recommended human dose (MRHD) of 40 mg. Oral administration of istradefylline (0, 50, 200, or 800 mg/kg/day) to pregnant rabbits throughout organogenesis resulted in increased embryofetal mortality at the mid and high doses, increased fetal malformations (external, visceral, skeletal) at all doses, and reduced fetal body weight at the highest dose tested.

A no-effect dose for adverse effects on embryofetal development in rabbits was not identified. Plasma exposure (AUC) at the lowest dose tested (50 mg/kg/day) is less than that in humans at the MRHD. In pregnant rabbits, oral administration of istradefylline (0, 50, 200, or 400 mg/kg/day) alone or in combination with oral levodopa/carbidopa (80/20 mg/kg/day) throughout the period of organogenesis resulted in an increase in embryofetal mortality and an increase (marked at the high dose) in malformations (including limb reduction, craniofacial, and cardiovascular) in fetuses from rats administered istradefylline at all doses in combination with levodopa/carbidopa.

Istradefylline alone resulted in an increase in embryofetal mortality and visceral malformations; no increase in fetal malformations was observed with levodopa/carbidopa alone. Fetal body weight was reduced by istradefylline alone (400 mg/kg/day) and in combination (200 and 400 mg/kg/day) with levodopa/carbidopa. A no-effect dose for adverse effects on embryofetal development in rabbits when istradefylline was administered in combination with levodopa/carbidopa was not identified.

Plasma exposure (AUC) at the lowest dose of istradefylline tested (50 mg/kg/day) in combination with levodopa/carbidopa is less than that in humans at the MRHD. Oral administration of istradefylline (0, 6, 25, 100, or 400 mg/kg/day) to female rats throughout gestation and lactation resulted in decreased pup survival and reduced pup body weight (which persisted into adulthood) at all but the lowest dose tested. Exposure to drug in the milk may have contributed to these effects, as demonstrated in pups of untreated (control) dams reared by dams receiving istradefylline (400 mg/kg/day).

No adverse effects were observed on physical or neurobehavioral development, or reproductive function. Plasma exposure at the no-effect dose for adverse effects on pre- and postnatal development in rats (6 mg/kg/day) is less than that in humans at the MRHD.

8.2Lactation Risk Summary There are no data on the presence of istradefylline in human milk, the effects of istradefylline on the breastfed infant, or the effects of istradefylline on milk production. Istradefylline was presen… [Excerpted — this section continues on DailyMed.]

🤰 Pregnancy ~2 min read ▾

8.1Pregnancy 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.

Plasma exposure (AUC) at the no-effect dose for adverse effects on embryofetal development in rats (200 mg/kg/day) is approximately 4 times that in humans at the maximum recommended human dose (MRHD) of 40 mg. Oral administration of istradefylline (0, 50, 200, or 800 mg/kg/day) to pregnant rabbits throughout organogenesis resulted in increased embryofetal mortality at the mid and high doses, increased fetal malformations (external, visceral, skeletal) at all doses, and reduced fetal body weight at the highest dose tested.

A no-effect dose for adverse effects on embryofetal development in rabbits was not identified. Plasma exposure (AUC) at the lowest dose tested (50 mg/kg/day) is less than that in humans at the MRHD. In pregnant rabbits, oral administration of istradefylline (0, 50, 200, or 400 mg/kg/day) alone or in combination with oral levodopa/carbidopa (80/20 mg/kg/day) throughout the period of organogenesis resulted in an increase in embryofetal mortality and an increase (marked at the high dose) in malformations (including limb reduction, craniofacial, and cardiovascular) in fetuses from rats administered istradefylline at all doses in combination with levodopa/carbidopa.

Istradefylline alone resulted in an increase in embryofetal mortality and visceral malformations; no increase in fetal malformations was observed with levodopa/carbidopa alone. Fetal body weight was reduced by istradefylline alone (400 mg/kg/day) and in combination (200 and 400 mg/kg/day) with levodopa/carbidopa. A no-effect dose for adverse effects on embryofetal development in rabbits when istradefylline was administered in combination with levodopa/carbidopa was not identified.

Plasma exposure (AUC) at the lowest dose of istradefylline tested (50 mg/kg/day) in combination with levodopa/carbidopa is less than that in humans at the MRHD. Oral administration of istradefylline (0, 6, 25, 100, or 400 mg/kg/day) to female rats throughout gestation and lactation resulted in decreased pup survival and reduced pup body weight (which persisted into adulthood) at all but the lowest dose tested. Exposure to drug in the milk may have contributed to these effects, as demonstrated in pups of untreated (control) dams reared by dams receiving istradefylline (400 mg/kg/day).

No adverse effects were observed on physical or neurobehavioral development, or reproductive function. Plasma exposure at the no-effect dose for adverse effects on pre- and postnatal development in rats (6 mg/kg/day) is less than that in humans at the MRHD.

🧒 Pediatric Use 13 words ▾

8.4Pediatric Use Safety and effectiveness in pediatric patients have not been established.

🧓 Geriatric Use 52 words ▾

8.5Geriatric Use No adjustment of NOURIANZ dosage is recommended on the basis of age. Of the total number of PD patients who received NOURIANZ in clinical trials, 53% were ≥65 years and 13% were ≥75 years of age. No overall differences in effectiveness were observed between these patients and younger patients.

🆘 Overdosage 108 words ▾

10 OVERDOSAGE

10.1Human 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.

10.2Management 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.

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action 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.

12.2Pharmacodynamics Cardiac Electrophysiology The effect of NOURIANZ (40 mg or 160 mg [4 times the maximum recommended dosage] once daily for 14 days) on the QTc interval was evaluated in a randomized, placebo and moxifloxacin-controlled, multiple-dose, blinded, parallel group study. There was no clinically significant prolongation of QTc interval or relationship between changes in QTc and concentrations of istradefylline.

12.3Pharmacokinetics 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. The pharmacokinetics of istradefylline were similar in PD patients and healthy subjects.

Absorption The median time to reach the maximum concentration (T max ) for istradefylline was about 4 hours under fasted dosing conditions. Effect of Food Istradefylline exposure, represented by the area under the curve over time to infinity (AUC inf ), increased 1.25-fold when NOURIANZ was coadministered with a standard high-fat meal, compared with administration in a fasted state. Istradefylline maximum plasma concentrations (C max ) increased by 1.64-fold and T max was shortened by 1 hour when NOURIANZ was administered with a high-fat meal.

These differences in pharmacokinetic parameters are not expected to be clinically significant [see Dosage and Administration (2.1) ]. Distribution The plasma protein binding of istradefylline was approximately 98%. The apparent volume of distribution (V d /F) of istradefylline is approximately 557 liters.

Elimination The total clearance of istradefylline is approximately

4.6L/hour. The mean terminal half-life (t 1/2 ) for istradefylline at steady-state is approximately 83 hours. Metabolism In humans, istradefylline is exclusively eliminated via metabolism.

In vitro studies indicate that istradefylline is primarily metabolized via CYP1A1 and CYP3A4, with minor contribution from CYP1A2, 2B6, 2C8, CYP2C9, CYP2C18, and 2D6. Six metabolites have been identified in human plasma. These metabolites each account for less than 10% of the exposure of the parent drug.

Excretion Approximately 48% of a 40-mg oral dose of 14 C-istradefylline was eliminated in feces, and 39% in urine. Unchanged istradefylline was not detected in urine. Specific Populations In patients with moderate hepatic impairment (Child-Pugh Class B), the steady-state exposure (AUC 0-24 ) of istradefylline is predicted to be 3.3-fold higher relative to healthy subjects, based on the estimated mean terminal half-life [see Use in Specific Populations (8.7) ].

Based on population pharmacokinetic analyses, no clinically relevant changes in the pharmacokinetics of istradefylline were observed based on age, sex, weight, or race. No clinically relevant changes in istradefylline exposure were observed in patients with severe renal impairment (CrCL 15-29 mL/min) or mild hepatic impairment. NOURIANZ has not been studied in patients with ESRD (CrCL < 15 mL/min), ESRD patients requiring hemodialysis, or severe hepatic impairment (Child-Pugh Class C) [see Use in Specific Populations (8.6 , 8.7) ] .

Steady-state systemic exposure to istradefylline (40 mg) is 38% to 54% lower in tobacco smokers (who smoke 20 or more cigarettes per day) when compared with non-smokers matched for age, gender, and body weight [see Specific Populations (8.8) ] . Drug Interaction Studies In Vitro Assessment of Drug Interactions Drug-Metabolizing Enzyme Inhibition Istradefylline is a weak inhibitor of CYP3A4, but not an inhibitor of CYP1A2, 2B6, 2C9, 2C19, or 2D6 in vitro . Drug-Metabolizing Enzyme Induction Istradefylline was a weak inducer of CYP3A4… [Excerpted — this section continues on DailyMed.]

🧬 Mechanism of Action 40 words ▾

12.1Mechanism of Action 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.

📦 How Supplied / Storage and Handling 76 words ▾

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1How Supplied NOURIANZ (istradefylline) tablets are available as: 20 mg Tablets: Peach-colored, pillow-shaped, film-coated tablets with "20" debossed on one side. Bottle of 90: NDC 42747-602-90 40 mg Tablets: Peach-colored, almond-shaped, film-coated tablets with "40" debossed on one side. Bottle of 90: NDC 42747-604-90

16.2Storage and Handling Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F to 86°F) [see USP Controlled Room Temperature].

📦 Storage and Handling 26 words ▾

16.2Storage and Handling Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F to 86°F) [see USP Controlled Room Temperature].

📋 Description 149 words ▾

11 DESCRIPTION NOURIANZ contains istradefylline, an adenosine receptor antagonist, which has a xanthine derivative structure. The chemical name is ( E )-8-(3,4-dimethoxystyryl)-1,3-diethyl-7-methyl-3,7-dihydro-1 H -purine-2,6-dione. Its molecular formula is C 20 H 24 N 4 O 4 .

The molecular weight is 384.43. Istradefylline has the following structural formula: Istradefylline is a light yellow-green crystalline powder. Istradefylline has a dissociation constant (p K a ) of 0.78.

The aqueous solubility of istradefylline is ~0.5 µg/mL across the physiological pH range and 0.6 µg/mL in water. NOURIANZ tablets are intended for oral administration only. Each tablet contains 20 mg or 40 mg of istradefylline and the following inactive ingredients: crospovidone, lactose monohydrate, magnesium stearate, microcrystalline cellulose, and polyvinyl alcohol.

The film coating contains hypromellose, lactose monohydrate, polyethylene glycol 3350, titanium dioxide, triacetin, and the following dyes: iron oxide red and iron oxide yellow. Carnauba wax is used for polishing. Chemical Structure

💬 Information for Patients 189 words ▾

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information). Dyskinesia Advise patients that NOURIANZ may cause dyskinesia or exacerbate pre-existing dyskinesia [see Warnings and Precautions (5.1) ] . Hallucinations / Psychotic Behavior Advise patients that NOURIANZ may cause hallucinations or psychotic behavior and they should report any of these adverse reactions to their healthcare provider [see Warnings and Precautions (5.2) ].

Impulse Control / Compulsive Behaviors Inform patients that they may experience intense urges to gamble, increased sexual urges, and other intense urges and the inability to control these urges while taking NOURIANZ and one or more medication(s) for the treatment of Parkinson's disease (including levodopa). Advise patients that they should report any of these adverse reactions to their healthcare provider [see Warnings and Precautions (5.3) ]. Concomitant Medications Certain medications can cause an interaction with NOURIANZ.

Advise patients to inform their healthcare provider about their smoking status and about all of the medicines they are taking or plan to take, including over-the-counter medicines, dietary supplements, and herbal products [see Drug Interactions (7.1 , 7.2) and Use in Specific Populations (8.8) ] .

🧬 Pharmacokinetics ~3 min read ▾

12.3Pharmacokinetics 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. The pharmacokinetics of istradefylline were similar in PD patients and healthy subjects.

Absorption The median time to reach the maximum concentration (T max ) for istradefylline was about 4 hours under fasted dosing conditions. Effect of Food Istradefylline exposure, represented by the area under the curve over time to infinity (AUC inf ), increased 1.25-fold when NOURIANZ was coadministered with a standard high-fat meal, compared with administration in a fasted state. Istradefylline maximum plasma concentrations (C max ) increased by 1.64-fold and T max was shortened by 1 hour when NOURIANZ was administered with a high-fat meal.

These differences in pharmacokinetic parameters are not expected to be clinically significant [see Dosage and Administration (2.1) ]. Distribution The plasma protein binding of istradefylline was approximately 98%. The apparent volume of distribution (V d /F) of istradefylline is approximately 557 liters.

Elimination The total clearance of istradefylline is approximately

4.6L/hour. The mean terminal half-life (t 1/2 ) for istradefylline at steady-state is approximately 83 hours. Metabolism In humans, istradefylline is exclusively eliminated via metabolism.

In vitro studies indicate that istradefylline is primarily metabolized via CYP1A1 and CYP3A4, with minor contribution from CYP1A2, 2B6, 2C8, CYP2C9, CYP2C18, and 2D6. Six metabolites have been identified in human plasma. These metabolites each account for less than 10% of the exposure of the parent drug.

Excretion Approximately 48% of a 40-mg oral dose of 14 C-istradefylline was eliminated in feces, and 39% in urine. Unchanged istradefylline was not detected in urine. Specific Populations In patients with moderate hepatic impairment (Child-Pugh Class B), the steady-state exposure (AUC 0-24 ) of istradefylline is predicted to be 3.3-fold higher relative to healthy subjects, based on the estimated mean terminal half-life [see Use in Specific Populations (8.7) ].

Based on population pharmacokinetic analyses, no clinically relevant changes in the pharmacokinetics of istradefylline were observed based on age, sex, weight, or race. No clinically relevant changes in istradefylline exposure were observed in patients with severe renal impairment (CrCL 15-29 mL/min) or mild hepatic impairment. NOURIANZ has not been studied in patients with ESRD (CrCL < 15 mL/min), ESRD patients requiring hemodialysis, or severe hepatic impairment (Child-Pugh Class C) [see Use in Specific Populations (8.6 , 8.7) ] .

Steady-state systemic exposure to istradefylline (40 mg) is 38% to 54% lower in tobacco smokers (who smoke 20 or more cigarettes per day) when compared with non-smokers matched for age, gender, and body weight [see Specific Populations (8.8) ] . Drug Interaction Studies In Vitro Assessment of Drug Interactions Drug-Metabolizing Enzyme Inhibition Istradefylline is a weak inhibitor of CYP3A4, but not an inhibitor of CYP1A2, 2B6, 2C9, 2C19, or 2D6 in vitro . Drug-Metabolizing Enzyme Induction Istradefylline was a weak inducer of CYP3A4 but not an inducer of CYP1A2 and 2B6 when tested in vitro .

However, clinical drug-drug interaction studies with a CYP3A4 substrate (i.e., midazolam) showed no induction of CYP3A4. Transporters Istradefylline was not a substrate for drug transporters P-gp, BCRP, OATP1B1, or OATP1B3 when tested in vitro . Istradefylline was a weak inhibitor for P-gp, BCRP, OATP1B1, OATP1B3, OAT1, OCT2, MATE1, and MATE2-K, but not an inhibitor of OAT3 when tested in vitro .

In Vivo Assessment of Drug Interactions Effect of Other Drugs on Istradefylline Strong CYP3A4 Inhibitors Coadministration of ketoconazole (200 mg twice daily for 4 days) with a single dose of istradefylline (40 mg) increased the AUC inf of istradefylline by… [Excerpted — this section continues on DailyMed.]

🧬 Pharmacodynamics 60 words ▾

12.2Pharmacodynamics Cardiac Electrophysiology The effect of NOURIANZ (40 mg or 160 mg [4 times the maximum recommended dosage] once daily for 14 days) on the QTc interval was evaluated in a randomized, placebo and moxifloxacin-controlled, multiple-dose, blinded, parallel group study. There was no clinically significant prolongation of QTc interval or relationship between changes in QTc and concentrations of istradefylline.

🔬 Clinical Studies ~3 min read ▾

14 CLINICAL STUDIES The efficacy of NOURIANZ for the adjunctive treatment to levodopa/carbidopa in patients with Parkinson's disease experiencing "off" episodes was shown in four randomized, multicenter, double-blind, 12-week, placebo-controlled studies (Study 1, NCT00456586; Study 2, NCT00199407; Study 3, NCT00455507; and Study 4, NCT00955526). The studies enrolled patients with a mean duration of Parkinson's disease of 9 years (range: 1 month to 37 years) that were Hoehn and Yahr Stage II to IV, experiencing at least 2 hours (mean approximately 6 hours) of "off" time per day, and were treated with levodopa for at least one year, with stable dosage for at least 4 weeks before screening (mean total daily dosage range: 416 to 785 mg).

Patients continued levodopa treatment with or without concomitant PD medications, including dopamine agonists (85%), COMT inhibitors (38%), MAO-B inhibitors (40%), anticholinergics (13%), and/or amantadine (33%), provided the medications were stable for at least 4 weeks before screening and throughout the study period. The studies excluded patients who had received a neurosurgical treatment for PD (e.g., pallidotomy, thalamotomy, deep brain stimulation). The primary efficacy endpoint was the change from baseline in the daily awake percentage of "off" time, or the change from baseline in total daily "off" time, based on 24-hour diaries completed by patients.

A change from baseline in "on" time without troublesome dyskinesia (i.e., "on" time without dyskinesia plus "on" time with non-troublesome dyskinesia) was a secondary efficacy endpoint. Study 1 was conducted in the U.S. and Canada, and Study 2 was conducted in the U.S. In these studies, patients were randomized to once-daily treatment with NOURIANZ 20 mg, 40 mg, or placebo.

Patients treated with NOURIANZ 20 mg or NOURIANZ 40 mg once daily experienced a statistically significant decrease from baseline in percentage of daily awake "off" time, compared with patients on placebo, as summarized in Table 2. Table 2: Studies 1 and 2: Change From Baseline in Daily Awake OFF Time Baseline Change from Baseline to Endpoint N (mean ± SD) % of awake "off" hours N (LSMD LSMD: Least squares mean difference; a negative value indicates a greater reduction from baseline in Percentage Daily Awake "off" time for NOURIANZ, relative to placebo. vs. placebo), % awake "off" hours, (p-value) SD: Standard Deviation Study 1 Placebo 66 37.2 ± 13.8 65 -- NOURIANZ 40 mg 129 38.4 ± 16.2 126 - 6.78 ( p =0.007) Study 2 Placebo 113 38.7 ± 11.6 113 -- NOURIANZ 20 mg 112 39.8 ± 14.0 112 - 4.57 ( p =0.025) Compared with patients on placebo, patients treated with NOURIANZ experienced an additional increase from baseline in "on" time without troublesome dyskinesia of 0.96 hours (nominal p =0.026) in Study 1, and of 0.55 hours (nominal p =0.135) in Study 2.

Study 3 and Study 4 were conducted in Japan. In these studies, patients were randomized equally to treatment with NOURIANZ 20 mg, 40 mg, or placebo. Patients treated with NOURIANZ 20 mg or NOURIANZ 40 mg once daily experienced a statistically significant decrease from baseline in "off" time compared with patients on placebo, as summarized in Table 3.

Table 3: Studies 3 and 4: Change From Baseline in Daily OFF Time Baseline Change from Baseline to Endpoint N (mean ± SD) hours N (LSMD LSMD: Least squares mean difference; a negative value indicates a greater reduction from baseline in "off" time for NOURIANZ, relative to placebo. vs. placebo) hours ( p-value) SD: Standard Deviation Study 3 Placebo 118 6.4 ± 2.7 118 -- NOURIANZ 20 mg 115 6.8 ± 2.9 115 -0.65 ( p =0.028) NOURIANZ 40 mg 124 6.6 ± 2.5 124 -0.92 ( p =0.002) Study 4 Placebo 123 6.3 ± 2.5 123 -- NOURIANZ 20 mg 120 6.6 ± 2.7 120 -0.76 ( p =0.006) NOURIANZ 40 mg 123 6.0 ± 2.5 123 -0.74 ( p =0.008) In Study 3, compared with placebo, an additional increase from baseline in "on" time without troublesome dyskinesia of 0.57 hours (nominal p =0.085) and of 0.65 hours (nominal p =0.04… [Excerpted — this section continues on DailyMed.]

🧪 Nonclinical Toxicology ~1 min read ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, and Impairment of Fertility Carcinogenesis In lifetime oral carcinogenicity studies, there was no evidence of carcinogenicity in mouse (0, 25, 125, or 250 mg/kg) or rat (0, 30, 100, or 320 mg/kg). Plasma exposures (AUC) at the highest doses tested were approximately 20 (mouse) and 10 (rat) times that in humans at the maximum recommended human dose (MRHD) of 40 mg/day. Mutagenesis Istradefylline was negative in in vitro (bacterial reverse mutation assay, chromosomal aberration in mammalian cells) and in vivo (mouse bone marrow micronucleus) assays.

Impairment of Fertility Oral administration of istradefylline (0, 160, 360, or 800 mg/kg/day) to male and female rats prior to and during mating and continuing in females to gestation day 7 resulted in a decrease in fertility at the highest dose tested and an increase in preimplantation loss at the mid and high doses. Sperm motility was reduced at the highest dose tested. Plasma exposure (AUC) at the no-effect dose (160 mg/kg) for adverse effects on reproductive function is approximately 3 times that in humans at the MRHD.

13.2Animal Toxicology and/or Pharmacology Oral administration of istradefylline (0, 30, 100, or 320 mg/kg/day) to rats for two years resulted in an increase in the incidence and severity of vascular mineralization in the brain (including in the caudate/putamen, globus pallidus, thalamus, and nucleus accumbens) at all doses tested. The vascular mineralization was composed of calcium and phosphorus and, at higher doses, were reported to partially or completely occlude the blood vessels. There was no evidence of neuronal degeneration, inflammation, or glial response associated with the foci of mineralization.

Brain mineralization was not detected in mice administered istradefylline (0, 25, 125, or 250 mg/kg/day) orally for two years or in dogs administered istradefylline (0, 10, 30, or 100 mg/kg/day) orally for 52 weeks.

📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 176 words ▾

13.1Carcinogenesis, Mutagenesis, and Impairment of Fertility Carcinogenesis In lifetime oral carcinogenicity studies, there was no evidence of carcinogenicity in mouse (0, 25, 125, or 250 mg/kg) or rat (0, 30, 100, or 320 mg/kg). Plasma exposures (AUC) at the highest doses tested were approximately 20 (mouse) and 10 (rat) times that in humans at the maximum recommended human dose (MRHD) of 40 mg/day. Mutagenesis Istradefylline was negative in in vitro (bacterial reverse mutation assay, chromosomal aberration in mammalian cells) and in vivo (mouse bone marrow micronucleus) assays.

Impairment of Fertility Oral administration of istradefylline (0, 160, 360, or 800 mg/kg/day) to male and female rats prior to and during mating and continuing in females to gestation day 7 resulted in a decrease in fertility at the highest dose tested and an increase in preimplantation loss at the mid and high doses. Sperm motility was reduced at the highest dose tested. Plasma exposure (AUC) at the no-effect dose (160 mg/kg) for adverse effects on reproductive function is approximately 3 times that in humans at the MRHD.

📄 Patient Package Insert ~3 min read ▾

This Patient Information has been approved by the U.S. Food and Drug Administration Issued: 3/2023 Patient Information NOURIANZ ® ( nue'–ree–anz ) (istradefylline) tablets, for oral use What is NOURIANZ? NOURIANZ is a prescription medicine used with levodopa and carbidopa to treat adults with Parkinson's disease (PD) who are having "off" episodes.

It is not known if NOURIANZ is safe and effective in children. Before you take NOURIANZ, tell your healthcare provider about all your medical conditions, including if you: have a history of abnormal movement (dyskinesia). have reduced liver function. smoke cigarettes. are pregnant or plan to become pregnant. NOURIANZ may harm your unborn baby. are breastfeeding or plan to breastfeed.

It is not known if NOURIANZ passes into breast milk. You and your healthcare provider should decide if you will take NOURIANZ or breastfeed. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

NOURIANZ and other medicines may affect each other causing side effects. NOURIANZ may affect the way other medicines work, and other medicines may affect how NOURIANZ works. Know the medicines you take.

Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine. How should I take NOURIANZ? Take NOURIANZ exactly as your healthcare provider tells you to.

Take NOURIANZ one time each day. You can take NOURIANZ with or without food. If you take too much NOURIANZ, call your health care provider or go to the nearest hospital emergency room right away.

What are the possible side effects of NOURIANZ? NOURIANZ may cause serious side effects, including: uncontrolled sudden movements (dyskinesia). Uncontrolled sudden movements is one of the most common side effects.

NOURIANZ may cause uncontrolled sudden movements or make such movements you already have worse or more frequent. Tell your healthcare provider if this happens. hallucinations and other symptoms of psychosis. NOURIANZ can cause abnormal thinking and behavior including: being overly suspicious or feeling people want to harm you (paranoid ideation) believing things that are not real (delusions) seeing or hearing things that are not real (hallucinations) confusion increase activity or talking (mania) disorientation aggressive behavior agitation delirium (decreased awareness of things around you) If you have hallucinations or any other abnormal thinking or behavior, talk with your healthcare provider. unusual urges (impulse control or compulsive behaviors).

Some people taking NOURIANZ get urges to behave in a way unusual for them. Examples of this are unusual urges to gamble, increased sexual urges, strong urges to spend money, binge eating, and the inability to control these urges. If you notice or your family notices that you are developing any unusual behaviors, talk to your healthcare provider.

The most common side effects of NOURIANZ include uncontrolled movements (dyskinesia), dizziness, constipation, nausea, hallucinations, and problems sleeping (insomnia). These are not all the possible side effects of NOURIANZ. Call your doctor for medical advice about side effects.

You may report side effects to FDA at 1-800-FDA-1088. How should I store NOURIANZ? Store NOURIANZ at room temperature between 68°F to 77°F (20°C to 25°C).

Keep NOURIANZ and all medicines out of the reach of children. General information about the safe and effective use of NOURIANZ. Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet.

Do not use NOURIANZ for a condition for which it was not prescribed. Do not give NOURIANZ to other people, even if they have the same symptoms that you have. It may harm them.

You can ask your healthcare provider or pharmacist for information about NOURIANZ that is written for health professionals. What are the ingredients in NOURIANZ? Active ingredient: istradefylline Inactive ingr… [Excerpted — this section continues on DailyMed.]

📄 Package Label / Principal Display Panel 131 words ▾

PRINCIPAL DISPLAY PANEL - 20 mg Tablet Label NDC 42747-602-90 NOURIANZ ® (istradefylline) tablets 20 mg 90 tablets Rx Only KYOWA KIRIN PRINCIPAL DISPLAY PANEL - 20 mg Label

PRINCIPAL DISPLAY PANEL - 20 mg Tablet Carton Label NDC 42747-602-07 Rx Only NOURIANZ ® (istradefylline) tablets 20 mg per tablet 7 tablets (7-count blister card) KYOWA KIRIN PRINCIPAL DISPLAY PANEL - 20 mg Carton Label

PRINCIPAL DISPLAY PANEL - 40 mg Tablet Label NDC 42747-604-90 NOURIANZ ® (istradefylline) tablets 40 mg 90 tablets Rx Only KYOWA KIRIN PRINCIPAL DISPLAY PANEL - 40 mg Carton Label

PRINCIPAL DISPLAY PANEL - 40 mg Tablet Carton Label NDC 42747-604-07 Rx Only NOURIANZ ® (istradefylline) tablets 40 mg per tablet 7 tablets (7-count blister card) KYOWA KIRIN PRINCIPAL DISPLAY PANEL - 40 mg Carton Label

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗

Medicaid utilization & spend

📍 This exact package only: Medicaid data is reported per full 11-digit NDC — labeler, product and pack size — so every number here is for this package alone, not the drug overall. Other pack sizes report separately.
💊 Pharmacy benefit only: These are Medicaid outpatient pharmacy claims, billed by NDC. They exclude the medical benefit — clinic- or hospital-administered drugs billed under HCPCS J-codes — so drugs used mostly that way (e.g. Avastin, Lucentis, Keytruda) can look low or missing here. That’s expected, not an error.
📅 Q1 2025 – Q1 2026 · 5 quarters of data
ⓘ The newest quarter is usually incomplete when first published; states restate recent quarters in later CMS releases, so the latest figures typically revise upward. State coverage-policy changes can also shift quarter-to-quarter totals.
Prescriptions last 4 qtrs
205
Units reimbursed last 4 qtrs
8.7K
Gross reimbursed last 4 qtrs
$580.4K
Avg / prescription
$2,831.33
Avg / unit
$66.9461
Latest quarter Q1 2026
43Rx
Fee-for-service vs managed care ⓘ
95% FFS
Fee-for-service · 194 Rx Managed care · 11 Rx
State Medicaid map
Alaska: no data reported AK Maine: no data reported ME Washington: no data reported WA Idaho: no data reported ID Montana: no data reported MT North Dakota: no data reported ND Minnesota: no data reported MN Wisconsin: no data reported WI Michigan: no data reported MI New York: 3,210 units · 16.4 per 100k residents NY Vermont: no data reported VT New Hampshire: no data reported NH Oregon: no data reported OR Nevada: no data reported NV Wyoming: no data reported WY South Dakota: no data reported SD Iowa: no data reported IA Illinois: no data reported IL Indiana: no data reported IN Ohio: no data reported OH Pennsylvania: no data reported PA New Jersey: no data reported NJ Massachusetts: no data reported MA California: 5,130 units · 13.2 per 100k residents CA Utah: no data reported UT Colorado: no data reported CO Nebraska: no data reported NE Missouri: no data reported MO Kentucky: no data reported KY West Virginia: no data reported WV Virginia: no data reported VA Maryland: no data reported MD Connecticut: no data reported CT Rhode Island: no data reported RI Arizona: no data reported AZ New Mexico: no data reported NM Kansas: no data reported KS Arkansas: no data reported AR Tennessee: no data reported TN North Carolina: no data reported NC South Carolina: no data reported SC Delaware: no data reported DE Oklahoma: no data reported OK Louisiana: 330 units · 7.2 per 100k residents LA Mississippi: no data reported MS Alabama: no data reported AL Georgia: no data reported GA D.C.: no data reported DC Hawaii: no data reported HI Texas: no data reported TX Florida: no data reported FL
Units reimbursed · per 100k residents
7.216.4
gray = no data reported ⓘ
Colors are per 100,000 residents, so big states don’t automatically dominate. Tap or hover a state for its actual totals.
Tap or hover a state
…for its Medicaid breakdown
🏆 Top states by units · per 100k residents
1 New York 16.4 /100k
2 California 13.2 /100k
3 Louisiana 7.2 /100k
National units — by quarter
💵 About the dollar figures: “reimbursed” is what Medicaid paid pharmacies before confidential manufacturer rebates, so the program’s real net cost is lower than these numbers. Fee-for-service and managed-care claims are combined unless split above. Source: CMS State Drug Utilization Data; per-100k rates use 2023 Census population estimates.

Medicaid utilization by pack size

Medicaid (SDUD) totals over the four most recent reported quarters for every package size of this drug — handy when a specific package (e.g. a starter/titration pack) carries little or no Medicaid volume on its own.
90 tablets this page42747-0604-90 205 Rx · $580,422
7 tablets42747-0604-07 No Medicaid data
Drug total (last 4 qtrs): 205 Rx · 8,670 units · $580,422 gross reimbursed
Tap a pack size to open its page. Source: CMS State Drug Utilization Data, last 4 quarters.

Medicare Part D spend CMS · PART D · 2026 (Q1)

Medicare Part D (outpatient prescription) spending for Nourianz — the program that covers self-administered drugs. 1 manufacturer.
⚠️ Drug-level data: CMS publishes Part D spending by drug, not by NDC — these figures combine every manufacturer, strength and package size sold under the name Nourianz. That’s a different level of aggregation than the Medicaid card above, which is specific to this exact 11-digit NDC (pack size included), so the two aren’t directly comparable.
Period
Total Part D spend
$11.74M
Claims incl. refills
4.4K
Beneficiaries
2.1K
Spend / beneficiary
$5,483.51
Spend / claim
$2,659.16
Trend by period
💵 About the dollar figures: spending is what Part D plans paid before confidential manufacturer rebates, so the program’s real net cost is lower. A blank patient count means fewer than 11 people — CMS hides counts that small to protect privacy. Source: CMS Medicare Quarterly Part D Spending by Drug (data.cms.gov), updated quarterly.

About this NDC listing & data coverage

Finished prescription product
What data is (and isn’t) available for this NDC — tap to expand
NDC identity (package / product / labeler codes) ✓ Available
Labeler ✓ Available
Product & package description ✓ Available
Marketing category & status ✓ Available
Active ingredient / dosage form / route ✓ Available
FDA label (SPL via DailyMed) ✓ Available
Package photos ✓ Available
Inactive ingredients (structured) ✓ Available
NADAC pharmacy acquisition price (CMS) — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey.
Orange Book / therapeutic-equivalence data ✓ Available
HCPCS J-code billing crosswalk — Not published for this NDC Most self-administered / retail products have no J-code — that is normal.
Medicaid utilization (CMS SDUD) ✓ Available
“Not published” reflects what the public FDA / CMS / NLM sources provide for this exact package code — it is a property of the data feeds, not a judgment about the product.

Questions about this listing

Why is there no price listed?
The pricing shown on our NDC pages comes from CMS NADAC, a voluntary survey of retail community pharmacy invoices. CMS does not publish a NADAC for every NDC — packages outside the retail survey (institutional and hospital products, bulk packages, discontinued items, and many OTC items) may never receive one. A missing price reflects the survey's scope, not this product's actual cost, and does not mean the product is free or unavailable.
Is the NDC printed on the package the same as the 11-digit billing NDC?
Yes, they identify this exact package in different formats. The form printed on the packaging and shown on DailyMed is the one the FDA registered. Insurance claims use a fixed 11-digit 5-4-2 format, so the short segment is padded with a leading zero and the dashes are dropped. The Identity section at the top of this page lists each form of this code.
Is this package still being marketed?
Yes, per the latest FDA NDC Directory data on this page: this package is listed as actively marketed, with no marketing end date reported by Kyowa Kirin, Inc.. Listing status can change — the directory data on this page refreshes weekly.
Does this product come in other package sizes?
Yes — the FDA directory lists 1 other package presentation of this same product, including 7 tablets (42747-0604-07). Each has its own NDC and its own page — see the package list near the top of this page.
Who lists this product with the FDA?
Kyowa Kirin, Inc. is the labeler of record for this NDC — the company under whose FDA-assigned code the package is listed. The labeler may be the manufacturer itself or a distributor marketing the product under its own code.
Do I need a prescription for this product?
This NDC is listed with FDA as a prescription product, so it is dispensed under a prescriber's order. Your pharmacist can tell you whether any over-the-counter forms of the same medication exist.
This page identifies an FDA-listed package (the NDC) and reports public regulatory and pricing data about the listing. It is reference information, not a medical recommendation — talk to your pharmacist or prescriber about your own medication.
Where does this data come from?
Listing facts (marketing category, packager status, marketing dates) from the FDA openFDA NDC Directory; label availability from DailyMed; pricing coverage from CMS NADAC; equivalence scope from the FDA Orange Book.
← 42747-0602-07 · Kyowa 42747-0761-01 · Kyowa →
For educational and professional reference only — not medical advice. Pricing reflects published NADAC and CMS ASP (free public data) and may differ from your acquisition cost; always verify before billing or dispensing.