edaravone 21 MG/ML Oral Suspension [Radicava]

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 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 ) 2.1 Dosage 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 2.2 Preparation 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. 2.3 Preparation 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 2.4 Switching from RADICAVA to RADICAVA ORS Patients treated with 60 mg of RADICAVA intravenous infusion may be switched to 105 mg (5 mL) RADICAVA ORS using the same dosing frequency. Upon switching to RADICAVA ORS, patients should follow RADICAVA ORS dosing recommendations with regards to food consumption [see Dosage and Administration (2.3) ] .

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 ) 5.1 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 (4) ]. 5.2 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.

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 )

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