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Radicava Ors Edaravone Kit — NDC 70510-2321-2 (Billing 70510-2321-02)

by Shionogi Inc. · 2 CARTON in 1 CARTON / 1 KIT in 1 CARTON * 1 BOTTLE in 1 KIT / 35 mL in 1 BOTTLE

This is a package of Radicava Ors Edaravone Kit from Shionogi Inc., marketed since May 2022 and currently FDA-listed. It is this product's only package size.

NDC 70510-2321-02
🏷️ FDA NDC (as labeled) 70510-2321-2 billing pads the package segment with a zero
Rx only Brand On market Non-controlled ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 1, 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 70510-2321-2 alone.

Record
FDA NDC Directory package listing · Human prescription drug
Code segments
70510 labeler · 2321 product · 2 package
Package marketed since
May 12, 2022
Sample package
No — commercial package
Listing certified through
Dec 31, 2027
Barcode (UPC)
0370510232414, 0370510217121, 0370510232315
FDA record last changed
Jul 24, 2026

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 70510-2321-2
Product NDC 70510-2321
11-digit billing NDC 70510232102
NCPDP billing unit ML — per mL (volume)
RxCUI 1924316, 1924317, 2602117, 2602122
UPC 0370510232414, 0370510217121, 0370510232315
Application # NDA215446
SPL Set ID 0ce2c1c4-2a40-485c-b7cb-96a9b85d9d11
DEA schedule Non-controlled
Marketing category NDA
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2022-05-12
Dosage form KIT

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

GPI-14 74509030001820
GPI class Radicava ORS Starter Kit
GCN Seq No 083378
GCN 52318
HICL code 044252
Ingredient (HICL) Edaravone
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 H6I
Therapeutic class — specific (HIC3) Amyotrophic Lateral Sclerosis Agents
AHFS code 28:44.00.00
AHFS class Amyotrophic Lateral Sclerosis(Als) Agent
FDB label name RADICAVA ORS STARTER KIT SUSP
FDB brand name Radicava Ors
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 083378
  • GCN: 52318
  • GPI-14 (Medi-Span): 74509030001820
  • HICL (First Databank): 044252
  • AHFS class code: 28:44.00.00
  • RxCUI (RxNorm): 1924316
Why two NDCs? The FDA registers this code as 70510-2321-2 — a 5-4-1 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 package segment → 70510-2321-02. 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 nervous system drugs class.

Drug family (ATC) Other nervous system 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 RADICAVA ORS STARTER KIT SUSP Ingredient Edaravone
📗 Our plain-language guide HelloPharmacist
  • Radicava is approved to treat ALS — amyotrophic lateral sclerosis, sometimes called Lou Gehrig's disease. It's a progressive condition that damages the nerve cells that control you...
  • Radicava is given as an IV infusion, which means it goes directly into a vein through a drip over about 60 minutes. A healthcare professional administers each dose. It follows a cy...
  • How is this medication given — do I take it at home?
  • The most common ones seen in studies were bruising, trouble walking, and headache. Skin reactions like rash or eczema were also reported. The most serious concern is a severe aller...
📖 Read our full Edaravone Injection 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 No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data.
Medicare drug plans payPart D · Q2 2026 $298.41 —
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
70510-2321-02 You're viewing this Main listing 2 CARTON in 1 CARTON / 1 KIT in 1 CARTON * 1 BOTTLE in 1 KIT / 35 mL in 1 BOTTLE 2022-05-12 — Active

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Radicava Orsthis 70510-2321-02 Shionogi 1 kit — — FDA listed —
Radicava Ors 70510-2322-01 Shionogi 1 kit — — 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

🏛️
2022
First FDA approval
May 2022
📍
2026
Currently FDA-listed
4 years listed
🛡️
2041
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 Nov 2041. This may affect when a full generic version becomes widely available, but it is not a guaranteed launch date.
📅 FDA approved May 12, 2022 RLD RS ⏳ ~15.1 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 12310946 — method of use (U-4111)
US 12569469 — method of use (U-4111)
US 12527769 — method of use (U-4111)
US 12194025 — method of use (U-4111)
US 11478450 — method of use (U-3468)
US 12478611 — method of use (U-4111)
US 10987341 — drug product
US 12285409 — drug product
US 12599586 — drug product
US 11241416 — drug product
US 11957660 — drug product
US 11826352 — drug product
Exclusivity ODE-144
2022 2024 2026 2028 2030 2032 2034 2036 2038 2040 2042
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 (12)
PatentTypeUse codeExpires
US 12310946 ↗ Method of use U-4111 Nov 12, 2041
US 12569469 ↗ Method of use U-4111 Nov 12, 2041
US 12527769 ↗ Method of use U-4111 Nov 12, 2041
US 12194025 ↗ Method of use U-4111 Nov 12, 2041
US 11478450 ↗ Method of use U-3468 Nov 1, 2039
US 12478611 ↗ Method of use U-4111 Nov 12, 2041
US 10987341 ↗ Drug product — Nov 1, 2039
US 12285409 ↗ Drug product — Nov 1, 2039
US 12599586 ↗ Drug product — Nov 1, 2039
US 11241416 ↗ Drug product — Nov 1, 2039
US 11957660 ↗ Drug product — Nov 1, 2039
US 11826352 ↗ Drug product — Nov 1, 2039
FDA exclusivity
CodeWhat it grantsExpires
ODE-144Orphan Drug Exclusivity (7-year)May 12, 2029
Common questions
Is there a generic version of RADICAVA ORS STARTER KIT SUSP?
No FDA-approved generic equivalent is currently listed in the FDA Orange Book for RADICAVA ORS STARTER KIT SUSP. Based on the patents and exclusivity currently listed, the Orange Book estimate is that full-label generic entry may be delayed until Nov 2041 — 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 Edaravone Injection 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.

Loading inactive ingredients from the official FDA label in the background. No external source is being called by this page request.
Where does this data come from?
Source: official FDA Structured Product Labeling (SPL) via DailyMed and the openFDA label index. Structured IACT rows and label-wide narrative are kept separate; availability and product-level specificity depend on the submitted label.

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

LabelerShionogi Inc.
Application holderSHIONOGI INC
FDA applicationNDA215446 (NDA)
Labeler code70510
First marketedMay 2022
Product typeHuman Prescription Drug
Portfolio8 products on file

More NDCs from Shionogi Inc. labeler code 70510

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 👥 Use in Specific Populations 🤰 Pregnancy 🧒 Pediatric Use 🧓 Geriatric Use 🧬 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 📖 Instructions for Use 📄 Package Label / Principal Display Panel
🎯 Indications and Usage 35 words ▾

1 INDICATIONS AND USAGE RADICAVA and RADICAVA ORS are indicated for the treatment of amyotrophic lateral sclerosis (ALS). RADICAVA and RADICAVA ORS are indicated for the treatment of amyotrophic lateral sclerosis (ALS). ( 1 )

⏱️ Dosage and Administration ~3 min read ▾

2 DOSAGE AND ADMINISTRATION RADICAVA: The recommended dosage is 60 mg administered as an intravenous infusion over 60 minutes ( 2.1 ) RADICAVA ORS: The recommended dosage is 105 mg (5 mL) taken orally or via feeding tube in the morning after overnight fasting. Food should not be consumed for 1 hour after administration except water ( 2.1 , 2.3 ) For RADICAVA and RADICAVA ORS: Initial treatment cycle: daily dosing for 14 days followed by a 14-day drug-free period ( 2.1 ) Subsequent treatment cycles: daily dosing for 10 days out of 14-day periods, followed by 14-day drug-free periods ( 2.1 )

2.1Dosage Information The recommended dosage of RADICAVA and RADICAVA ORS is as follows: RADICAVA: an intravenous infusion of 60 mg administered over a 60-minute period RADICAVA ORS: 105 mg (5 mL) taken orally or via feeding tube in the morning after overnight fasting [see Dosage and Administration (2.3) ] Administer RADICAVA or RADICAVA ORS according to the following schedule: An initial treatment cycle with daily dosing for 14 days, followed by a 14-day drug-free period Subsequent treatment cycles with daily dosing for 10 days out of 14-day periods, followed by 14-day drug-free periods

2.2Preparation and Administration Information for RADICAVA Injection RADICAVA is for intravenous infusion only. Preparation Do not use if the oxygen indicator has turned blue or purple before opening the package . Once the overwrap package is opened, use within 24 hours [see How Supplied/Storage and Handling (16.1 , 16.2) ].

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Administration Administer each 60 mg dose of RADICAVA injection as two consecutive 30 mg intravenous infusion bags over a total of 60 minutes (infusion rate approximately 1 mg per minute [3.33 mL per minute]). Promptly discontinue the infusion upon the first observation of any signs or symptoms consistent with a hypersensitivity reaction [see Warnings and Precautions (5.1 , 5.2) ] .

Other medications should not be injected into the infusion bag or mixed with RADICAVA.

2.3Preparation and Administration Information for RADICAVA ORS Oral Suspension See the Instruction for Use for further preparation and administration details. Preparation Prior to opening the bottle, turn it upside down (invert) and shake vigorously up and down for at least 30 seconds. Administration RADICAVA ORS can be administered by mouth or via feeding tube (see Feeding Tube Administration ) .

RADICAVA ORS should be taken in the morning on an empty stomach after overnight fasting. Food should not be consumed for 1 hour after administration except water [see Clinical Pharmacology (12.3) ] . See Table 1 for specific fasting conditions.

Table 1: RADICAVA ORS Administration Relative to Type of Food Consumption Type of food/caloric supplement consumed Fasting time before and after RADICAVA ORS dose administration with regards to meal type High-fat meal (800-1,000 calories, 50% fat) 8 hours before administration and one hour after administration Low-fat meal (400-500 calories, 25% fat) 4 hours before administration and one hour after administration Caloric supplement (250 calories, e.g., protein drink) 2 hours before administration and one hour after administration Administer RADICAVA ORS using a 5 mL oral syringe that comes with the product.

A household teaspoon is not an adequate measuring device. Dispose of any RADICAVA ORS that is not used within 15 days after opening the bottle or within the 30 days from the date of shipment indicated on the carton pharmacy label, which ever happens first. Feeding Tube Administration Nasogastric (NG) tubes or percutaneous endoscopic gastrostomy (PEG) tubes made of silicone, polyvinyl chloride (PVC), or polyurethane can be used Before and after administration, use a catheter-tip syringe to flush the tube with at least 1 ounce (30 mL) of water

2.4Switching from RADICAVA to RADIC… [Excerpted — this section continues on DailyMed.]

💊 Dosage Forms and Strengths 77 words ▾

3 DOSAGE FORMS AND STRENGTHS RADICAVA is supplied for intravenous infusion in a single-dose polypropylene bag containing 30 mg of edaravone in 100 mL of clear, colorless aqueous solution. RADICAVA ORS is supplied as an oral suspension in a multi-dose amber glass bottle 105 mg/5 mL of white to off-white color. Injection: 30 mg/100 mL in a single-dose polypropylene bag ( 3 ) Oral suspension: 105 mg/5 mL in a multi-dose amber glass bottle ( 3 )

⛔ Contraindications 63 words ▾

4 CONTRAINDICATIONS RADICAVA and RADICAVA ORS are contraindicated in patients with a history of hypersensitivity to edaravone or any of the inactive ingredients in this product. Hypersensitivity reactions and anaphylactic reactions have occurred [see Warnings and Precautions (5.1 , 5.2) ]. Patients with a history of hypersensitivity to edaravone or any of the inactive ingredients in RADICAVA and/or RADICAVA ORS ( 4 )

⚠️ Warnings and Cautions 159 words ▾

5 WARNINGS AND PRECAUTIONS Hypersensitivity Reactions: Advise patients to seek immediate medical care ( 5.1 ) Sulfite Allergic Reactions: RADICAVA and RADICAVA ORS contain sodium bisulfite, which may cause allergic type reactions, including anaphylactic symptoms and asthmatic episodes in susceptible people ( 5.2 )

5.1Hypersensitivity Reactions Hypersensitivity reactions (redness, wheals, and erythema multiforme) and cases of anaphylaxis (urticaria, decreased blood pressure, and dyspnea) have been reported in spontaneous postmarketing reports with RADICAVA. Patients should be monitored carefully for hypersensitivity reactions. If hypersensitivity reactions occur, discontinue RADICAVA and/or RADICAVA ORS, treat per standard of care, and monitor until the condition resolves [see Contraindications (4) ].

5.2Sulfite Allergic Reactions RADICAVA and RADICAVA ORS contain sodium bisulfite, a sulfite that may cause allergic type reactions, including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown. Sulfite sensitivity occurs more frequently in asthmatic than non-asthmatic people.

🤒 Adverse Reactions ~2 min read ▾

6 ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in the labeling: Hypersensitivity Reactions [see Warnings and Precautions (5.1) ] Sulfite Allergic Reactions [see Warnings and Precautions (5.2) ] Most common adverse reactions (at least 10% of patients treated with RADICAVA and greater than placebo) are contusion, gait disturbance, and headache ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Shionogi Inc. at 1-888-292-0058 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. In randomized, placebo-controlled trials, 184 patients with ALS were administered RADICAVA 60 mg in treatment cycles for 6 months. The population consisted of Japanese patients who had a median age of 60 years (range 29-75) and were 59% male.

Most (93%) of these patients were living independently at the time of screening. Most Common Adverse Reactions Observed During Clinical Studies Table 2 lists the adverse reactions that occurred in ≥2% of patients in the RADICAVA-treated group and that occurred at least 2% more frequently than in the placebo-treated group in randomized placebo-controlled ALS trials. The most common adverse reactions that occurred in ≥10% of RADICAVA-treated patients were contusion, gait disturbance, and headache.

Table 2: Adverse Reactions from Pooled Placebo-Controlled Trials Pooled placebo-controlled studies include two additional studies with 231 additional patients, all using the same treatment regimen [see Clinical Studies (14) ]. that Occurred in ≥2% of RADICAVA -Treated Patients and ≥2% More Frequently than in Placebo Patients Adverse Reaction RADICAVA (N=184) % Placebo (N=184) % Contusion 15 9 Gait disturbance 13 9 Headache 10 6 Dermatitis 8 5 Eczema 7 4 Respiratory failure, respiratory disorder, hypoxia 6 4 Glycosuria 4 2 Tinea infection 4 2 Additional Adverse Reactions with RADICAVA ORS In an open-label study in patients with ALS (n=185) treated with RADICAVA ORS for 6 months, fatigue was observed in 7.6% of patients.

6.2Postmarketing Experience The following adverse reactions have been identified during postapproval use of RADICAVA. 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. Skin and subcutaneous tissue disorders: Hypersensitivity reactions and anaphylaxis [see Warnings and Precautions (5.1 , 5.2) ].

👥 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 RADICAVA or RADICAVA ORS in pregnant women. In animal studies, administration of edaravone to pregnant rats and rabbits resulted in adverse developmental effects (increased mortality, decreased growth, delayed sexual development, and altered behavior) at clinically relevant doses. Most of these effects occurred at doses that were also associated with maternal toxicity (see Animal Data ).

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. The background risk for major birth defects and miscarriage in patients with ALS is unknown. Data Animal Data In rats, intravenous administration of edaravone (0, 3, 30, or 300 mg/kg/day) throughout the period of organogenesis resulted in reduced fetal weight at all doses.

In dams allowed to deliver naturally, offspring weight was reduced at the highest dose tested. Maternal toxicity was also observed at the highest dose tested. There were no adverse effects on reproductive function in the offspring.

A no-effect dose for embryofetal developmental toxicity was not identified; the low dose is less than the recommended human dose of 60 mg for RADICAVA on a body surface area (mg/m 2 ) basis. In rabbits, intravenous administration of edaravone (0, 3, 20, or 100 mg/kg/day) throughout the period of organogenesis resulted in embryofetal death at the highest dose tested, which was associated with maternal toxicity. The higher no-effect dose for embryofetal developmental toxicity is approximately 6 times the recommended human dose (RHD) for RADICAVA on a body surface area (mg/m 2 ) basis.

The effects on offspring of edaravone (0, 3, 20, or 200 mg/kg/day), administered by intravenous injection to rats from GD 17 throughout lactation, were assessed in two studies. In the first study, offspring mortality was observed at the high dose and increased activity was observed at the mid and high doses. In the second study, there was an increase in stillbirths, offspring mortality, and delayed physical development (vaginal opening) at the highest dose tested.

Reproduction function in offspring was not affected in either study. Maternal toxicity was evident in both studies at all but the lowest dose tested. The no-effect dose for developmental toxicity (3 mg/kg/day) is less than the RHD on a mg/m 2 basis.

Reproductive and developmental toxicology studies of edaravone using the oral route have not been conducted.

8.2Lactation Risk Summary There are no data on the presence of edaravone in human milk, the effects on the breastfed infant, or the effects of the drug on milk production. Edaravone and its metabolites are excreted in the milk of lactating rats. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for RADICAVA and RADICAVA ORS and any potential adverse effects on the breastfed infant from RADICAVA and RADICAVA ORS or from the underlying maternal condition.

8.4Pediatric Use Safety and effectiveness of RADICAVA or RADICAVA ORS in pediatric patients have not been established.

8.5Geriatric Use Of the 184 patients with ALS who received RADICAVA in 3 placebo-controlled clinical trials, a total of 53 patients were 65 years of age and older, including 2 patients 75 years of age and older. No overall differences in safety or effectiveness were observed between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

🤰 Pregnancy ~2 min read ▾

8.1Pregnancy Risk Summary There are no adequate data on the developmental risk associated with the use of RADICAVA or RADICAVA ORS in pregnant women. In animal studies, administration of edaravone to pregnant rats and rabbits resulted in adverse developmental effects (increased mortality, decreased growth, delayed sexual development, and altered behavior) at clinically relevant doses. Most of these effects occurred at doses that were also associated with maternal toxicity (see Animal Data ).

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. The background risk for major birth defects and miscarriage in patients with ALS is unknown. Data Animal Data In rats, intravenous administration of edaravone (0, 3, 30, or 300 mg/kg/day) throughout the period of organogenesis resulted in reduced fetal weight at all doses.

In dams allowed to deliver naturally, offspring weight was reduced at the highest dose tested. Maternal toxicity was also observed at the highest dose tested. There were no adverse effects on reproductive function in the offspring.

A no-effect dose for embryofetal developmental toxicity was not identified; the low dose is less than the recommended human dose of 60 mg for RADICAVA on a body surface area (mg/m 2 ) basis. In rabbits, intravenous administration of edaravone (0, 3, 20, or 100 mg/kg/day) throughout the period of organogenesis resulted in embryofetal death at the highest dose tested, which was associated with maternal toxicity. The higher no-effect dose for embryofetal developmental toxicity is approximately 6 times the recommended human dose (RHD) for RADICAVA on a body surface area (mg/m 2 ) basis.

The effects on offspring of edaravone (0, 3, 20, or 200 mg/kg/day), administered by intravenous injection to rats from GD 17 throughout lactation, were assessed in two studies. In the first study, offspring mortality was observed at the high dose and increased activity was observed at the mid and high doses. In the second study, there was an increase in stillbirths, offspring mortality, and delayed physical development (vaginal opening) at the highest dose tested.

Reproduction function in offspring was not affected in either study. Maternal toxicity was evident in both studies at all but the lowest dose tested. The no-effect dose for developmental toxicity (3 mg/kg/day) is less than the RHD on a mg/m 2 basis.

Reproductive and developmental toxicology studies of edaravone using the oral route have not been conducted.

🧒 Pediatric Use 18 words ▾

8.4Pediatric Use Safety and effectiveness of RADICAVA or RADICAVA ORS in pediatric patients have not been established.

🧓 Geriatric Use 64 words ▾

8.5Geriatric Use Of the 184 patients with ALS who received RADICAVA in 3 placebo-controlled clinical trials, a total of 53 patients were 65 years of age and older, including 2 patients 75 years of age and older. No overall differences in safety or effectiveness were observed between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action The mechanism by which RADICAVA and RADICAVA ORS exert their therapeutic effect in patients with ALS is unknown.

12.2Pharmacodynamics Cardiac Electrophysiology At exposures at least 5 times higher than that of the recommended doses of RADICAVA and RADICAVA ORS, edaravone does not prolong the QT interval to any clinically relevant extent.

12.3Pharmacokinetics RADICAVA is administered by IV infusion. The maximum plasma concentration (C max ) of edaravone was reached by the end of infusion. There was a trend of more than dose-proportional increase in area under the concentration-time curve (AUC) and C max of edaravone.

With multiple-dose administration, edaravone does not accumulate in plasma. RADICAVA ORS administered orally at the dose of 105 mg, under fasted conditions, was shown to demonstrate an equivalent AUC with RADICAVA (60 mg administered intravenously for 60 min) and C max not less than that of RADICAVA. RADICAVA ORS demonstrated similar pharmacokinetics following administration via feeding tubes and oral administration.

In healthy subjects, RADICAVA ORS does not accumulate with once-daily administration, and the maximum plasma concentration (C max ) and area under the concentration-time curve (AUC) of edaravone is more than dose-proportional over the dose range of 30 to 300 mg (approximately 0.3 and 3 times the recommended dosage, respectively). Absorption RADICAVA ORS has a median time to maximum concentration (T max ) occurring at approximately 0.5 hour (range, 0.25 to 0.75 hours) after fasted oral administration. The absolute oral bioavailability is about 57% because of first-pass effect when comparing RADICAVA ORS (105 mg oral suspension) and RADICAVA (60 mg intravenous formulation).

Effect of Food Following oral administration of RADICAVA ORS to healthy subjects 1 hour before or 8 hours after high-fat meals (800-1000 calories, 50% fat), 4 hours after low-fat meals (400-500 calories, 25% fat), or 2 hours after caloric supplement (250 calories, e.g., protein drink), the C max and AUC did not decrease significantly (less than 20% and 10% changes in C max and AUC, respectively) [see Dosage and Administration (2.3) ] . Following oral administration of RADICAVA ORS to healthy subjects, the C max decreased by 82%, and the AUC decreased by 61% with a high-fat meal compared to fasted conditions.

Following administration of RADICAVA ORS 4 hours after high-fat meals, the C max and AUC decreased by 44% and 24%, respectively. Following administration of RADICAVA ORS 2 hours after low-fat meals, the C max and AUC decreased by 45% and 21%, respectively. Distribution Edaravone is bound to human serum proteins (92%), mainly to albumin, with no concentration dependence in the range of 0.1 to 50 micromol/L.

Edaravone has a mean volume of distribution after intravenous administration of

63.1L. Elimination The mean terminal elimination half-life of edaravone is approximately 4.5 to 9 hours. The half-lives of its metabolites are 3 to 6 hours. Following intravenous administration, the total clearance of edaravone is estimated to be

35.9L/h. Metabolism Edaravone is metabolized to a sulfate conjugate and a glucuronide conjugate, which are not pharmacologically active. The glucuronide conjugation of edaravone involves multiple uridine diphosphate glucuronosyltransferase (UGT) isoforms (UGT1A1, UGT1A6, UGT1A7, UGT1A8, UGT1A9, UGT1A10, UGT2B7, and UGT2B17).

In human plasma, edaravone is mainly detected as the sulfate conjugate, which is presumed to be formed by sulfotransferases. RADICAVA ORS results in 1.3- and 1.7-fold higher exposures for both sulfate and glucuronide metabolites, respectively, when compared to RADICAVA because of first-pass metabolism. Excretion In Japanese and Caucasian healthy volunteer studies, edaravone was excreted mainly in the urine as its glucuronide conjugate (60-80% of the dose up to 48 hours).

Approximately 6-8% of the dose was recovered in the urine as the… [Excerpted — this section continues on DailyMed.]

🧬 Mechanism of Action 22 words ▾

12.1Mechanism of Action The mechanism by which RADICAVA and RADICAVA ORS exert their therapeutic effect in patients with ALS is unknown.

📦 How Supplied / Storage and Handling ~2 min read ▾

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1How Supplied RADICAVA RADICAVA is supplied as a 30 mg/100 mL (0.3 mg/mL) clear, colorless, sterile solution for intravenous infusion in single-dose polypropylene bags, each overwrapped with polyvinyl alcohol (PVA) secondary packaging containing an oxygen absorber and oxygen indicator, which should be pink to reflect appropriate oxygen levels [see Dosage and Administration (2.2) and How Supplied/Storage and Handling (16.2) ] . These are supplied in cartons as listed below. NDC 70510-2171-1 30 mg/100 mL (0.3 mg/mL) single-dose bag NDC 70510-2171-2 2 bags per carton RADICAVA ORS RADICAVA ORS is supplied in a white to off-white suspension in multi-dose child resistant 60 mL amber glass bottle which is supplied as two configurations: RADICAVA ORS Starter Kit (14-day treatment cycle), including two (2) inner cartons, each containing one (1) bottle of 735 mg/35mL (105 mg/5 mL dose), two oral dosing syringes and one bottle adapter.

RADICAVA ORS Kit (10-day treatment cycle), including one (1) bottle of 1050 mg/50 mL (105 mg/5 mL dose) with two oral dosing syringes and one bottle adapter. These are supplied in cartons as listed below: Unit of sale NDC number Package configuration RADICAVA ORS Starter Kit NDC 70510-2321-1 Carton of One (1) bottle of 35mL (105 mg/5 mL dose) NDC 70510-2321-2 Carton of two (2) NDC 70510-2321-1 RADICAVA ORS Kit NDC 70510-2322-1 Carton of One (1) bottle of 50 mL (105 mg/5 mL dose)

16.2Storage and Handling RADICAVA Store RADICAVA at up to 25°C (77°F). Excursions permitted from 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Protect from light.

Store in overwrapped package to protect from oxygen degradation until time of use. The oxygen indicator will turn blue or purple if the oxygen has exceeded acceptable levels. Once the overwrap package is opened, use within 24 hours.

RADICAVA ORS Pharmacy Store RADICAVA ORS refrigerated between 2°C to 8°C (36°F to 46°F) and protect from light. Do not freeze. Store upright.

Patient Store RADICAVA ORS upright at room temperature between 20°C to 25°C (68°F to 77°F). Protect from light. Discard 15 days after opening bottle or if unopened 30 days from date of shipment indicated on the carton pharmacy label.

📦 Storage and Handling 129 words ▾

16.2Storage and Handling RADICAVA Store RADICAVA at up to 25°C (77°F). Excursions permitted from 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Protect from light.

Store in overwrapped package to protect from oxygen degradation until time of use. The oxygen indicator will turn blue or purple if the oxygen has exceeded acceptable levels. Once the overwrap package is opened, use within 24 hours.

RADICAVA ORS Pharmacy Store RADICAVA ORS refrigerated between 2°C to 8°C (36°F to 46°F) and protect from light. Do not freeze. Store upright.

Patient Store RADICAVA ORS upright at room temperature between 20°C to 25°C (68°F to 77°F). Protect from light. Discard 15 days after opening bottle or if unopened 30 days from date of shipment indicated on the carton pharmacy label.

📋 Description ~1 min read ▾

11 DESCRIPTION The active ingredient in RADICAVA and RADICAVA ORS is edaravone, which is a member of the substituted 2-pyrazolin-5-one class. The chemical name of edaravone is [3-methyl-1-phenyl-2-pyrazolin-5-one]. The molecular formula is C 10 H 10 N 2 O and the molecular weight is 174.20.

The chemical structure is: Edaravone is a white crystalline powder with a melting point of 129.7°C. It is freely soluble in acetic acid, methanol, or ethanol and slightly soluble in water or diethyl ether. RADICAVA injection is a clear, colorless liquid provided as a sterile solution.

RADICAVA injection is supplied for intravenous infusion in a polypropylene bag containing 30 mg edaravone in 100 mL isotonic, sterile, aqueous solution, which is further overwrapped with polyvinyl alcohol (PVA) secondary packaging. The overwrapped package also contains an oxygen absorber and oxygen indicator to minimize oxidation. Each bag contains the following inactive ingredients: L-cysteine hydrochloride hydrate (10 mg), sodium bisulfite (20 mg).

Sodium chloride is added for isotonicity and phosphoric acid and sodium hydroxide are added to adjust to pH 4. RADICAVA ORS (edaravone) oral suspension is a white to off-white color, opaque, homogenous suspension containing 105 mg of edaravone per 5 mL of suspension. RADICAVA ORS contains the following inactive ingredients: L-cysteine hydrochloride hydrate, polyvinyl alcohol, simethicone emulsion, sodium bisulfite, sorbitol, and xanthan gum.

Phosphoric acid and sodium hydroxide are added to adjust to pH 4. Chemical Structure

💬 Information for Patients ~1 min read ▾

17 PATIENT COUNSELING INFORMATION Advise the patients to read the FDA-approved patient labeling (Patient Information and Instructions for Use). Hypersensitivity Reactions Advise patients to seek immediate medical care if they experience signs or symptoms of a hypersensitivity reaction [see Warnings and Precautions (5.1) ]. Sulfite Allergic Reactions Advise patients about potential for sulfite sensitivity.

Inform patients that RADICAVA and RADICAVA ORS contain sodium bisulfite, which may cause allergic type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes, and to seek immediate medical care if they experience these signs or symptoms [see Warnings and Precautions (5.2) ]. Pregnancy and Breastfeeding Advise patients to notify their healthcare provider if they become pregnant or intend to become pregnant during RADICAVA or RADICAVA ORS therapy [see Use in Specific Populations (8.1) ] .

Advise patients to notify their healthcare provider if they intend to breastfeed or are breastfeeding an infant [see Use in Specific Populations (8.2) ] . RADICAVA ORS Administration Advise patients to take RADICAVA ORS in the morning on an empty stomach. Instruct patients to fast 8 hours before each dose if they consume a high-fat meal, 4 hours before each dose if they consume a low-fat meal, or 2 hours before each dose if they consume a caloric supplement [see Dosage and Administration (2.3) and Clinical Pharmacology (12.3) ] .

Also instruct patients to not to consume food for 1 hour after each dose. Advise caregivers, if administering RADICAVA ORS via feeding tube, to use a catheter-tip syringe and flush the feeding tube with approximately 1 ounce (30 mL) of water before and after use (see Instructions for Use ) .

🧬 Pharmacokinetics ~3 min read ▾

12.3Pharmacokinetics RADICAVA is administered by IV infusion. The maximum plasma concentration (C max ) of edaravone was reached by the end of infusion. There was a trend of more than dose-proportional increase in area under the concentration-time curve (AUC) and C max of edaravone.

With multiple-dose administration, edaravone does not accumulate in plasma. RADICAVA ORS administered orally at the dose of 105 mg, under fasted conditions, was shown to demonstrate an equivalent AUC with RADICAVA (60 mg administered intravenously for 60 min) and C max not less than that of RADICAVA. RADICAVA ORS demonstrated similar pharmacokinetics following administration via feeding tubes and oral administration.

In healthy subjects, RADICAVA ORS does not accumulate with once-daily administration, and the maximum plasma concentration (C max ) and area under the concentration-time curve (AUC) of edaravone is more than dose-proportional over the dose range of 30 to 300 mg (approximately 0.3 and 3 times the recommended dosage, respectively). Absorption RADICAVA ORS has a median time to maximum concentration (T max ) occurring at approximately 0.5 hour (range, 0.25 to 0.75 hours) after fasted oral administration. The absolute oral bioavailability is about 57% because of first-pass effect when comparing RADICAVA ORS (105 mg oral suspension) and RADICAVA (60 mg intravenous formulation).

Effect of Food Following oral administration of RADICAVA ORS to healthy subjects 1 hour before or 8 hours after high-fat meals (800-1000 calories, 50% fat), 4 hours after low-fat meals (400-500 calories, 25% fat), or 2 hours after caloric supplement (250 calories, e.g., protein drink), the C max and AUC did not decrease significantly (less than 20% and 10% changes in C max and AUC, respectively) [see Dosage and Administration (2.3) ] . Following oral administration of RADICAVA ORS to healthy subjects, the C max decreased by 82%, and the AUC decreased by 61% with a high-fat meal compared to fasted conditions.

Following administration of RADICAVA ORS 4 hours after high-fat meals, the C max and AUC decreased by 44% and 24%, respectively. Following administration of RADICAVA ORS 2 hours after low-fat meals, the C max and AUC decreased by 45% and 21%, respectively. Distribution Edaravone is bound to human serum proteins (92%), mainly to albumin, with no concentration dependence in the range of 0.1 to 50 micromol/L.

Edaravone has a mean volume of distribution after intravenous administration of

63.1L. Elimination The mean terminal elimination half-life of edaravone is approximately 4.5 to 9 hours. The half-lives of its metabolites are 3 to 6 hours. Following intravenous administration, the total clearance of edaravone is estimated to be

35.9L/h. Metabolism Edaravone is metabolized to a sulfate conjugate and a glucuronide conjugate, which are not pharmacologically active. The glucuronide conjugation of edaravone involves multiple uridine diphosphate glucuronosyltransferase (UGT) isoforms (UGT1A1, UGT1A6, UGT1A7, UGT1A8, UGT1A9, UGT1A10, UGT2B7, and UGT2B17).

In human plasma, edaravone is mainly detected as the sulfate conjugate, which is presumed to be formed by sulfotransferases. RADICAVA ORS results in 1.3- and 1.7-fold higher exposures for both sulfate and glucuronide metabolites, respectively, when compared to RADICAVA because of first-pass metabolism. Excretion In Japanese and Caucasian healthy volunteer studies, edaravone was excreted mainly in the urine as its glucuronide conjugate (60-80% of the dose up to 48 hours).

Approximately 6-8% of the dose was recovered in the urine as the sulfate conjugate, and < 1% of the dose was recovered in the urine as the unchanged drug. In vitro studies suggest that the sulfate conjugate of edaravone is hydrolyzed back to edaravone, which is then converted to the glucuronide conjugate in the kidney before excretion into the urine. Specific Populations Geriatric Patients No age effect on edaravone pharmacokinetics has been found [se… [Excerpted — this section continues on DailyMed.]

🧬 Pharmacodynamics 34 words ▾

12.2Pharmacodynamics Cardiac Electrophysiology At exposures at least 5 times higher than that of the recommended doses of RADICAVA and RADICAVA ORS, edaravone does not prolong the QT interval to any clinically relevant extent.

🔬 Clinical Studies ~2 min read ▾

14 CLINICAL STUDIES The efficacy of RADICAVA ORS is based on a bioavailability study comparing RADICAVA and RADICAVA ORS [see Clinical Pharmacology (12.3) ] . The efficacy of RADICAVA for the treatment of ALS was established in a 6-month, randomized, placebo- controlled, double-blind study conducted in Japanese patients with ALS who were living independently and met the following criteria at screening: 1 Functionality retained most activities of daily living (defined as scores of 2 points or better on each individual item of the ALS Functional Rating Scale-Revised [ALSFRS-R; described below]) 2 Normal respiratory function (defined as percent-predicted forced vital capacity values of [%FVC] ≥80%) 3 Definite or Probable ALS based on El Escorial revised criteria 4 Disease duration of 2 years or less The study enrolled 69 patients in the RADICAVA arm and 68 in the placebo arm.

Baseline characteristics were similar between these groups, with over 90% of patients in each group being treated with riluzole. RADICAVA was administered as an intravenous infusion of 60 mg given over a 60-minute period according to the following schedule: An initial treatment cycle with daily dosing for 14 days, followed by a 14-day drug-free period (Cycle 1). Subsequent treatment cycles with daily dosing for 10 days out of 14-day periods, followed by 14-day drug-free periods (Cycles 2-6).

The primary efficacy endpoint was a comparison of the change between treatment arms in the ALSFRS-R total scores from baseline to Week 24. The ALSFRS-R scale consists of 12 questions that evaluate the fine motor, gross motor, bulbar, and respiratory function of patients with ALS (speech, salivation, swallowing, handwriting, cutting food, dressing/hygiene, turning in bed, walking, climbing stairs, dyspnea, orthopnea, and respiratory insufficiency). Each item is scored from 0-4, with higher scores representing greater functional ability.

The decline in ALSFRS-R scores from baseline was significantly less in the RADICAVA-treated patients as compared to placebo (see Table 3 ). The distribution of change in ALSFRS-R scores from baseline to Week 24 by percent of patients is shown in Figure 1. Table 3: Analysis of Change from Baseline to Week 24 in ALSFRS-R Scores Treatment Change from Baseline LS Mean ± SE (95% CI) Treatment Difference (RADICAVA – placebo [95% CI]) p -value RADICAVA −5.01±0.64 2.49 (0.99, 3.98) 0.0013 Placebo −7.50±0.66 Figure 1 Distribution of Change from Baseline to Week 24 in ALSFRS-R Scores Figure 1

🧪 Nonclinical Toxicology ~1 min read ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis In a 26-week carcinogenicity study in male and female transgenic (Tg rasH2) mice, oral administration of edaravone (0 [water control], 0 [vehicle control], 100, 150, or 350 mg/kg) resulted in no increase in tumors. In a 2-year carcinogenicity study in rats, oral administration of edaravone (0, 50, 100, or 200 mg/kg in males; 0, 50, 100, or 250 mg/kg in females) resulted in no increase in tumors. Carcinogenicity studies of edaravone using the intravenous route have not been conducted.

Mutagenesis Edaravone was negative in in vitro (bacterial reverse mutation and Chinese hamster lung chromosomal aberration) and in vivo (mouse micronucleus) assays. Impairment of Fertility Intravenous administration of edaravone (0, 3, 20, or 200 mg/kg) prior to and throughout mating in male and female rats and continuing in females to gestation day 7 had no effect on fertility; however, disruption of the estrus cycle and mating behavior was observed at the highest dose tested. No effects on reproductive function were observed at the lower doses, which are up to approximately 3 times the RHD for RADICAVA (60 mg) on a body surface area (mg/m 2 ) basis.

Fertility studies of edaravone using the oral route have not been conducted.

13.2Animal Toxicology and/or Pharmacology Oral administration of edaravone (0, 10, 30, 100, or 300 mg/kg/day) in dogs for 39 weeks resulted in neurotoxicity, characterized by white matter vacuolation in the spinal cord and vacuolation and nerve fiber atrophy in the sciatic nerve, at the two highest doses tested. The microscopic findings were accompanied by gait abnormalities, loss of patellar reflex, and inability to rise. Plasma edaravone exposures (C max and AUC) at the higher no-effect dose for neurotoxicity (30 mg/kg/day) were approximately 2 times those in humans at the recommended human dose of RADICAVA ORS (105 mg).

📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 205 words ▾

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis In a 26-week carcinogenicity study in male and female transgenic (Tg rasH2) mice, oral administration of edaravone (0 [water control], 0 [vehicle control], 100, 150, or 350 mg/kg) resulted in no increase in tumors. In a 2-year carcinogenicity study in rats, oral administration of edaravone (0, 50, 100, or 200 mg/kg in males; 0, 50, 100, or 250 mg/kg in females) resulted in no increase in tumors. Carcinogenicity studies of edaravone using the intravenous route have not been conducted.

Mutagenesis Edaravone was negative in in vitro (bacterial reverse mutation and Chinese hamster lung chromosomal aberration) and in vivo (mouse micronucleus) assays. Impairment of Fertility Intravenous administration of edaravone (0, 3, 20, or 200 mg/kg) prior to and throughout mating in male and female rats and continuing in females to gestation day 7 had no effect on fertility; however, disruption of the estrus cycle and mating behavior was observed at the highest dose tested. No effects on reproductive function were observed at the lower doses, which are up to approximately 3 times the RHD for RADICAVA (60 mg) on a body surface area (mg/m 2 ) basis.

Fertility studies of edaravone using the oral route have not been conducted.

📄 Patient Package Insert ~3 min read ▾

This Patient Information has been approved by the U.S. Food and Drug Administration 22022-4 Issued: 05/2026 PATIENT INFORMATION RADICAVA (ra di ká vah) (edaravone) injection for intravenous use RADICAVA ORS (ra di ká vah o r s) (edaravone) oral suspension What are RADICAVA ® and RADICAVA ORS ® ? RADICAVA and RADICAVA ORS are prescription medicines used to treat people with amyotrophic lateral sclerosis (ALS).

It is not known if RADICAVA or RADICAVA ORS are safe and effective in children. Do not receive RADICAVA or RADICAVA ORS if you are allergic to edaravone or any of the ingredients in RADICAVA and RADICAVA ORS. See the end of this leaflet for a complete list of ingredients in RADICAVA and RADICAVA ORS.

Before you take RADICAVA or RADICAVA ORS, tell your healthcare provider about all of your medical conditions, including if you: have asthma. are allergic to other medicines. are pregnant or plan to become pregnant. It is not known if RADICAVA or RADICAVA ORS will harm your unborn baby. are breastfeeding or plan to breastfeed. It is not known if RADICAVA or RADICAVA ORS passes into your breastmilk.

You and your healthcare provider should decide if you will receive RADICAVA or RADICAVA ORS or breastfeed. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. How will I receive RADICAVA?

You will be prescribed RADICAVA by a healthcare provider and told how often you will receive RADICAVA. RADICAVA will be given by intravenous (IV) infusion into your vein. It takes about 1 hour to receive the full dose of RADICAVA.

Your healthcare provider will monitor you closely during your treatment with RADICAVA. How will I take RADICAVA ORS? See the detailed Instructions for Use on how to take RADICAVA ORS at the end of this Patient Information leaflet.

You will be prescribed RADICAVA ORS by a healthcare provider and told how often you will take RADICAVA ORS. RADICAVA ORS is to be taken by mouth or by using a feeding tube. RADICAVA ORS should be taken in the morning on an empty stomach.

You should stop eating at bedtime. Do not eat or drink anything 8 hours before each dose of RADICAVA ORS if you eat a high-fat meal. Do not eat or drink anything 4 hours before each dose of RADICAVA ORS if you eat a low-fat meal.

Do not eat or drink anything 2 hours before each dose of RADICAVA ORS if you take a calorie supplement. You should wait at least 1 hour after taking your medicine before eating or drinking anything except water. What are the possible side effects of RADICAVA and RADICAVA ORS?

RADICAVA and RADICAVA ORS may cause serious side effects including: 1. Hypersensitivity (allergic) reactions. Hypersensitivity reactions have happened in people receiving RADICAVA or taking RADICAVA ORS and can happen after your medicine has been given.

Tell your healthcare provider right away or go to the nearest emergency room if you have any of the following symptoms: hives breathing problems itching swelling of the lips, tongue, face dizziness wheezing fainting 2. Sulfite allergic reactions. RADICAVA and RADICAVA ORS contain sodium bisulfite, a sulfite that may cause a type of allergic reaction that can be serious and life-threatening.

Sodium bisulfite can also cause less severe allergic reactions, for example, asthma episodes, in certain people. Sulfite sensitivity can happen more often in people who have asthma than in people who do not have asthma. Tell your healthcare provider right away or go to the nearest emergency room if you have any of the following symptoms: hives trouble breathing or swallowing itching swelling of the lips, tongue, face dizziness asthma attack (in people with asthma) wheezing fainting Your healthcare provider will monitor you during treatment to watch for signs and symptoms of all the serious side effects and allergic reactions.

The most common side effects of RADICAVA and RADICAVA ORS include bruising (contusion), problems walking (… [Excerpted — this section continues on DailyMed.]

📖 Instructions for Use ~3 min read ▾

INSTRUCTIONS FOR USE RADICAVA (ra di ká vah) ORS (edaravone) oral suspension Read this Instructions for Use before you take RADICAVA ORS ® for the first time and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or treatment.

Important information about measuring RADICAVA ORS: Always measure your prescribed dose of RADICAVA ORS using the oral syringe provided. Ask your healthcare provider or pharmacist who provided the medicine any questions you have about how to measure your prescribed dose. If you miss a dose, do not take 2 doses of RADICAVA ORS the next day.

Do not take a dose of RADICAVA ORS on days 15 through 28. How to prepare RADICAVA ORS : Keep this Instructions for Use handy when preparing the treatment. If your healthcare provider prescribes a Starter Kit, you will receive 2 bottles of RADICAVA ORS.

Each bottle will contain 35 mL of RADICAVA ORS for a total of 70 mL to be used for your first treatment cycle of 14 days. Only open the second bottle when you have finished the first bottle. If you were not prescribed the Starter Kit, for each treatment cycle you will receive 1 bottle of RADICAVA ORS that contains a total of 50 mL of RADICAVA ORS.

After the first treatment cycle, RADICAVA ORS is to be used for 10 days out of 14-day periods. Only use the bottle adapter and the 2 reusable 5 mL oral syringes provided with the bottle. Do not use a household teaspoon to measure your medicine.

How to store RADICAVA ORS: Store RADICAVA ORS upright at room temperature between 68°F to 77°F (20°C to 25°C). Protect from light. Opening the bottle: When you open the bottle of RADICAVA ORS for the first use, write the date you open the bottle on the bottle label.

After opening the bottle of RADICAVA ORS, use within 15 days. After a bottle of Radicava ORS has been opened and used, a white crust may form on the neck or on the side of the bottle. This is due to normal use and RADICAVA ORS can continue to be used as prescribed.

Keep bottle tightly closed between each use. Throw away (discard) any RADICAVA ORS that is not used within 15 days after opening the bottle or within 30 days from the date of shipment shown on the carton pharmacy label, whichever happens first. Ask your pharmacist how to properly throw away (discard) RADICAVA ORS you are no longer able to use.

Keep RADICAVA ORS and all medicines out of the reach of children. Each RADICAVA ORS carton contains: 1 RADICAVA ORS bottle 1 bottle adapter 2 (5 mL) reusable oral syringes Use a new 5 mL oral syringe and bottle adapter when using a new bottle of RADICAVA ORS (see Figure A ). Figure A Important information: Keep these instructions for future use.

Do not share RADICAVA ORS with anyone else. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

People who have problems using their hands may need assistance to draw up and give the correct dose of RADICAVA ORS. How to take RADICAVA ORS: Take RADICAVA ORS as prescribed by your healthcare provider. Dosing information: RADICAVA ORS has 2 different dosing schedules: For the first treatment cycle, you will take RADICAVA ORS every day for 14 days, followed by 14 days without the medicine.

For the cycles after the first treatment cycle, you will take RADICAVA ORS daily for 10 out of 14 days, followed by 14 days without the medicine. How RADICAVA ORS will be provided: If your healthcare provider prescribes the Starter Kit, you will receive 2 bottles of RADICAVA ORS. Each bottle contains 35 mL of RADICAVA ORS for a total of 70 mL to deliver 14 doses.

There may be some medicine that remains in each bottle after the dose on day 7 and day 14 of the first treatment cycle. Throw away (discard) any medicine that remains. If you were not prescribed the Starter Kit, for each treatment cycle, you will receive 1 bottle of RADICAVA ORS that contains a total of 50 mL of RADICAVA ORS… [Excerpted — this section continues on DailyMed.]

📄 Package Label / Principal Display Panel 35 words ▾

PACKAGE/LABEL PRINCIPAL DISPLAY PANEL radicava-soft-bag

PACKAGE/LABEL PRINCIPAL DISPLAY PANEL radicava-carton

PACKAGE/LABEL PRINCIPAL DISPLAY PANEL radicava-ors-starter-label

PACKAGE/LABEL PRINCIPAL DISPLAY PANEL radicava-ors-starter-inner-carton

PACKAGE/LABEL PRINCIPAL DISPLAY PANEL radicava-ors-starter-carton-outer

PACKAGE/LABEL PRINCIPAL DISPLAY PANEL radicava-ors-maintenance-kit-label

PACKAGE/LABEL PRINCIPAL DISPLAY PANEL radicava-ors-maintenance-carton

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

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

Medicare Part D (outpatient prescription) spending for Radicava Ors — 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 Radicava Ors. 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
$103.22M
Claims incl. refills
7K
Beneficiaries
2.5K
Spend / beneficiary
$40,509.02
Spend / claim
$14,665.67
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.

Reported adverse events (FAERS)

Read carefully: FAERS reports are voluntary and unverified. Counts are not incidence, do not establish causation, are subject to reporting bias, and cannot be used to compare one drug to another. Shown for signal context only. Reports for RADICAVA ORS (this brand).

Top reported reactions

Death196
Cerebral Infarction97
Amyotrophic Lateral Sclerosis78
Disease Progression72
Dyspnoea49
Muscular Weakness45
Diarrhoea43

Reporter sex

1,540 reports
Male · 61%
Female · 39%

Serious outcomes

Death438
Life-threatening60
Disabling22
Reports over time (by year) — tap or hover for the count & year
2023 2024 2025 2026 363 154
Most recent year is provisional (FAERS lags ~3 months).
Where does this data come from?
Adverse-event reports from the FDA Adverse Event Reporting System (FAERS) via openFDA. FAERS reports are voluntary and unverified — counts are not incidence and don’t establish causation.

About this NDC listing & data coverage

Finished prescription product Kit / multi-component package

Kit / multi-component package

This NDC identifies a kit — a package containing more than one component. Structured data (pricing, ingredients, equivalents) is often reported per component rather than for the kit NDC itself, which can make this page look thinner than the components' own pages.

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 — Not published for this NDC No photo available yet for this listing.
Inactive ingredients (structured) — Not published for this NDC The labeler did not submit a structured excipient list, or no SPL is 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) — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold.
“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 Shionogi Inc.. Listing status can change — the directory data on this page refreshes weekly.
Who lists this product with the FDA?
Shionogi 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.
← 70510-2191-01 · Shionogi 70510-2322-01 · Shionogi →
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.