Edaravone Drug Information

Edaravone injection is indicated for the treatment of amyotrophic lateral sclerosis (ALS).

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.

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.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Discard unused portion. Promptly discontinue the infusion upon the first observation of any signs or symptoms consistent with a hypersensitivity reaction.

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

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.

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. 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 4 2 a Pooled placebo-controlled studies include two additional studies with 231 additional patients, all using the same treatment regimen.

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.

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 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 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 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 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.

Pediatric Use Safety and effectiveness of edaravone injection in pediatric patients have not been established.

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.