Edaravone

FDA Drug Information • Also known as: Edaravone, Radicava, Radicava Ors

Brand Names: Edaravone, Radicava, Radicava Ors
Dosage Form: POWDER
Product Type: BULK INGREDIENT

Description

11 DESCRIPTION The active ingredient in edaravone injection 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. Edaravone injection is a clear, colorless liquid provided as a sterile solution. Edaravone injection is supplied for intravenous infusion in a polypropylene bag containing 30 mg edaravone in 100 mL and 60 mg in 100 mL isotonic, sterile, aqueous solution, which is further overwrapped with clear pouch. The overwrapped package also contains an oxygen absorber and oxygen indicator to minimize oxidation. Clear pouch is further overwrapped in PET pouch. Each bag contains the following inactive ingredients: Edaravone Injection, 60 mg/100 mL: L-cysteine hydrochloride hydrate (20 mg), sodium bisulfite (40 mg). Sodium chloride is added for isotonicity and phosphoric acid and sodium hydroxide are added to adjust to pH 4. Edaravone Injection, 30 mg/100 mL: 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. Edaravone-SPL-Structure

What Is Edaravone Used For?

1 INDICATIONS AND USAGE Edaravone injection is indicated for the treatment of amyotrophic lateral sclerosis (ALS). Edaravone injection is indicated for the treatment of amyotrophic lateral sclerosis (ALS) ( 1 )

Dosage and Administration

2 DOSAGE AND ADMINISTRATION Edaravone Injection: The recommended dosage is 60 mg administered as an intravenous infusion over 60 minutes as follows ( 2.1 ) 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 ) 2.1 Dosage Information The recommended dosage of edaravone injection: an intravenous infusion of 60 mg administered over a 60-minute period. Administer Edaravone injection 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. 2.2 Preparation and Administration Information for Edaravone Injection Edaravone injection 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. Discard unused portion. Administration 60 mg/100 mL infusion Bag: Administer a 60 mg dose of edaravone injection as an intravenous infusion bag over a total of 60 minutes (infusion rate approximately 1 mg per minute [1.67 mL per minute]). 30 mg/100 mL infusion Bag: Administer each 60 mg dose of Edaravone 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 edaravone injection. 2.4 Switching from Edaravone Injection to RADICAVA ORS Patients treated with 60 mg of edaravone injection intravenous infusion may be switched to 105 mg (5 mL) Radicava ORS using the same dosing frequency.

Side Effects (Adverse Reactions)

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 edaravone injection and greater than placebo) are contusion, gait disturbance, and headache ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Gland Pharma at 609-250-7990 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. In randomized, placebo-controlled trials, 184 patients with ALS were administered edaravone injection 60 mg in treatment cycles for 6 months. The population consisted of Japanese patients who had a median age of 60 years (range 29 to 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 edaravone injection-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 edaravone injection-treated patients were contusion, gait disturbance, and headache. Table 2: Adverse Reactions from Pooled Placebo-Controlled Trials a that Occurred in ≥ 2% of Edaravone Injection-Treated Patients and ≥ 2% More Frequently than in Placebo Patients Adverse Reaction Edaravone Injection (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 a Pooled placebo-controlled studies include two additional studies with 231 additional patients, all using the same treatment regimen [see Clinical Studies (14) ]. 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of edaravone injection. 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 )].

Contraindications

4 CONTRAINDICATIONS Edaravone injection is 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 edaravone injection ( 4 )

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary There are no adequate data on the developmental risk associated with the use of edaravone injection 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 to 4% and 15 to 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 edaravone injection, 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 edaravone injection 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...

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING 16.1 How Supplied Edaravone injection is supplied as a 30 mg/10 mL (0.3 mg/mL) and 60 mg/100 mL (0.6 mg/mL) clear, colorless, sterile solution for intravenous infusion in a single-dose polypropylene bags, each overwrapped with clear pouch secondary packaging containing an oxygen absorber and oxygen indicator, which should be pink to reflect appropriate oxygen levels and clear pouch is further overwrapped in PET pouch [see Dosage and Administration (2.2) and How Supplied/Storage and Handling (16.2) ] . These are supplied in cartons as listed below. NDC 68083-501-01 60 mg/100 mL (0.6 mg/mL) single-dose bag NDC 68083-501-01 1 bag per carton NDC 68083-500-01 30 mg/100 mL (0.3 mg/mL) single-dose bag NDC 68083-500-02 2 bags per carton 16.2 Storage and Handling Store Edaravone Injection at 20º to 25ºC (68º to 77ºF); excursions permitted from 15° to 30°C (59° 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.

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.