Edaravone Dosing for Amyotrophic Lateral Sclerosis
The recommended dose of edaravone for ALS is 60 mg administered as an intravenous infusion over 60 minutes, following a specific cyclical schedule: an initial 14-day treatment cycle followed by subsequent 10-day treatment cycles within 14-day periods, each separated by 14-day drug-free intervals. 1
Intravenous Formulation Dosing Schedule
Initial Treatment Cycle
- 60 mg IV infusion over 60 minutes (infusion rate approximately 1 mg per minute or 3.33 mL per minute) 1
- Daily dosing for 14 consecutive days 1
- Followed by a 14-day drug-free period 1
Subsequent Treatment Cycles
- 60 mg IV infusion over 60 minutes 1
- Daily dosing for 10 days out of each 14-day period 1
- Followed by 14-day drug-free periods between cycles 1
- This pattern continues for ongoing treatment 1
Administration Details
Preparation and Infusion
- Administer each 60 mg dose as two consecutive 30 mg intravenous infusion bags over a total of 60 minutes 1
- 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 prior to administration 1
- Do not inject other medications into the infusion bag or mix with edaravone 1
Oral Suspension Alternative
Switching from IV to Oral
- Patients treated with 60 mg IV edaravone may be switched to 105 mg (5 mL) oral suspension using the same dosing frequency 1
- The oral suspension has a bioavailability of 57% when compared with the 60 mg IV dose 2
- Must be taken on an empty stomach in the morning, with water and no food or beverages for 1 hour 2
Oral Administration Routes
- Can be self-administered or administered by a caregiver 2
- Can be administered via percutaneous endoscopic gastrostomy (PEG) tube with similar pharmacokinetics to oral administration 3
Critical Safety Monitoring
Immediate Discontinuation Required
- Promptly discontinue the infusion upon the first observation of any signs or symptoms consistent with a hypersensitivity reaction 1
- Monitor carefully for hypersensitivity reactions including redness, wheals, erythema multiforme, urticaria, decreased blood pressure, and dyspnea 1
Contraindications
- Absolutely contraindicated in patients with a history of hypersensitivity to edaravone or any inactive ingredients 1
- Contains sodium bisulfite, which may cause allergic-type reactions including anaphylactic symptoms and life-threatening asthmatic episodes, particularly in asthmatic patients 1
Clinical Context
Evidence Base
- FDA approval was based on Japanese clinical trials involving 368 ALS patients 4
- The drug has been shown to slow the loss of physical function in ALS patients by 33% compared to placebo 4
- A phase II study showed the decline in ALSFRS-R score during six-month treatment (2.3±3.6 points) was significantly less than the six months prior to edaravone administration (4.7±2.1 points), with p=0.039 5
- However, a confirmatory phase III study showed changes in ALSFRS-R of -5.70±0.85 in the edaravone group versus -6.35±0.84 in placebo (difference 0.65±0.78, p=0.411), not reaching statistical significance 6
Common Adverse Events
- Most common adverse reactions (≥10% and greater than placebo) are contusion, gait disturbance, and headache 1
- In the oral suspension study, the most reported treatment-emergent adverse events were falls, muscular weakness, and constipation 2
Mechanism of Action
- Acts as a potent free radical scavenger with neuroprotective effects through antioxidant properties 2, 4
- Markedly reduces cerebrospinal fluid 3-nitrotyrosine (a marker for oxidative stress) to almost undetectable levels 5
Important Clinical Pitfall
Never deviate from the prescribed cyclical schedule - the drug-free periods are integral to the dosing regimen and should not be eliminated or shortened 1. The alternating treatment and drug-free periods distinguish this medication from continuous daily dosing regimens used for other neurological conditions.