What is the dosage and administration of Edaravone (MCI-186) for treating amyotrophic lateral sclerosis (ALS) and acute ischemic stroke?

Edaravone Dosage and Administration

For Amyotrophic Lateral Sclerosis (ALS)

Administer edaravone 60 mg intravenously over 60 minutes according to a specific cyclical schedule: an initial 14-day treatment cycle followed by subsequent 10-day cycles, each separated by 14-day drug-free periods. 1

Detailed Dosing Schedule

Initial Treatment Cycle:

• Administer 60 mg IV infusion daily for 14 consecutive days 1
• Follow with a 14-day drug-free period 1

Subsequent Treatment Cycles (Cycles 2-6 and beyond):

• Administer 60 mg IV infusion daily for 10 days out of each 14-day period 1
• Follow each treatment period with a 14-day drug-free period 1

Administration Technique

• Each 60 mg dose is given as two consecutive 30 mg infusion bags over a total of 60 minutes 1
• Infusion rate: approximately 1 mg per minute (3.33 mL per minute) 1
• Do not mix other medications with edaravone or inject into the infusion bag 1

Preparation Requirements

• Do not use if the oxygen indicator has turned blue or purple before opening the package 1
• Once the overwrap package is opened, use within 24 hours 1
• Inspect visually for particulate matter and discoloration before administration 1
• Discard any unused solution 1

Clinical Evidence for ALS

The FDA approval was based on clinical trials in 368 ALS patients in Japan, demonstrating that edaravone slows the loss of physical function by approximately 33% compared to placebo 2. In a Phase II study, the decline in ALSFRS-R score over 6 months was significantly less during edaravone treatment (2.3±3.6 points) compared to the 6 months prior to treatment (4.7±2.1 points), with p=0.039 3. A meta-analysis of 367 patients showed a mean difference in ALSFRS-R score of 1.63 points (95% CI 0.26-3.00, P=0.02) favoring edaravone 4.

Important Safety Considerations

Contraindications:

• History of hypersensitivity to edaravone or any inactive ingredients 1
• Edaravone contains sodium bisulfite, which may cause allergic reactions including anaphylaxis, particularly in asthmatic patients 1

Monitoring:

• Monitor carefully for hypersensitivity reactions (redness, wheals, erythema multiforme, urticaria, decreased blood pressure, dyspnea) 1
• Discontinue immediately if hypersensitivity reactions occur 1

Common Adverse Events:

• Most common (≥10%): contusion, gait disturbance, and headache 1
• Overall adverse event rates are similar to placebo (approximately 89%) 5

For Acute Ischemic Stroke

Edaravone is NOT approved by the FDA for acute ischemic stroke in the United States, though it is approved for this indication in Japan. 2

In Japan, edaravone (marketed as Radicut) was launched in 2015 for stroke treatment 2. The drug acts as a potent free radical scavenger and has been shown to prevent oxidative stress-induced motor neuron death 2. However, the evidence provided does not contain specific FDA-approved dosing guidelines for stroke, as this indication has not been approved in the United States.

Clinical Context

The primary evidence base for edaravone focuses on ALS treatment in the U.S. market 1. While edaravone has neuroprotective properties through free radical scavenging that could theoretically benefit stroke patients 2, clinicians in the United States should follow established stroke guidelines that recommend IV alteplase (0.9 mg/kg, maximum 90 mg) within 3-4.5 hours of symptom onset 6, along with early aspirin therapy (160-325 mg within 48 hours) 6, 7.