Mistsubishi Radicava page 2 of 2 4C (near ALS Symptoms) BRIEF SUMMARY OF PRESCRIBING INFORMATION RADICAVA® (edaravone) injection, for intravenous use RADICAVA ORS® (edaravone) oral suspension INDICATIONS AND USAGE RADICAVA and RADICAVA ORS are indicated for the treatment of amyotrophic lateral sclerosis (ALS). 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]. WARNINGS AND PRECAUTIONS Hypersensitivity 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]. Sulfite 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 The following serious adverse reactions are described elsewhere in the labeling: • Hypersensitivity Reactions [see Warnings and Precautions] • Sulfite Allergic Reactions [see Warnings and Precautions] 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 ALS patients 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 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 were as follows for RADICAVA (N=184) versus placebo (N=184), respectively: contusion (15% vs 9%); gait disturbance (13% vs 9%); headache (10% vs 6%); dermatitis (8% vs 5%); eczema (7% vs 4%); respiratory failure, respiratory disorder, hypoxia (6% vs 4%); glycosuria (4% vs 2%); tinea infection (4% vs 2%). Results are from pooled placebo-controlled studies including 2 additional studies with 231 additional patients, all using the same treatment regimen. The most common adverse reactions that occurred in ≥10% of RADICAVA-treated patients were contusion, gait disturbance, and headache. Additional Adverse Reactions with RADICAVA ORS In an open-label study in patients with ALS (n=185) who were treated with RADICAVA ORS for 6 months, fatigue was observed in 7.6% of patients. Postmarketing 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]. USE IN SPECIFIC POPULATIONS Pregnancy 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/m2) 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/m2) 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 2 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/m2 basis. Reproductive and development toxicology studies of edaravone using the oral route have not been conducted. Lactation 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. Pediatric Use Safety and effectiveness of RADICAVA or RADICAVA ORS in pediatric patients have not been established. Geriatric 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. Animal 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 2 highest doses tested. The microscopic findings were accompanied by gait abnormalities, loss of patellar reflex, and inability to rise. Plasma edaravone exposures (Cmax and AUC) at the higher no-effect dose for neurotoxicity (30 mg/kg/day) were 10 times or more those in humans at the recommended human dose of RADICAVA ORS (105 mg). Marketed and distributed by: Tanabe Pharma America, Inc., a US subsidiary of Tanabe Pharma Corporation Jersey City, NJ 07310 RADICAVA, RADICAVA ORS and the RADICAVA ORS logo are registered trademarks of Shionogi Inc. The corporate symbol of Shionogi is a registered trademark of Shionogi Inc. For US healthcare professionals only. © 2026 Shionogi Inc. All rights reserved. CP-OE-US-1662 04/26
View this content as a flipbook by clicking here.