Introduction

Free radical scavenger.

Uses for Edaravone

Amyotrophic Lateral Sclerosis

Treatment of amyotrophic lateral sclerosis (ALS; Lou Gehrig disease, Charcot's sclerosis); designated an orphan drug by FDA for this use.

Has been shown to slow decline in functioning (e.g., fine motor, gross motor, bulbar, and respiratory function) as assessed by a standard rating scale (ALSFRS-R) used in patients with ALS.

Long-term efficacy and effects on survival remain to be established. Some evidence indicates that benefits may be decreased in patients with more advanced disease.

Edaravone Dosage and Administration

Administration

IV Administration

Administer by IV infusion.

Commercially available in polypropylene infusion bags overwrapped with secondary packaging containing an oxygen absorber and indicator; designed to protect the drug from oxidation. Indicator should be pink when acceptable oxygen levels present; do not use if indicator has turned blue or purple prior to opening the package. (See Storage under Stability.)

Monitor for hypersensitivity reactions during administration; immediately discontinue infusion at first sign or symptom of such a reaction.

Do not mix with other drugs.

Rate of Administration

Administer over 60 minutes (approximately 1 mg/minute).

Dosage

Adults

ALS

IV

60 mg (given as 2 consecutive 30-mg infusions over a total of 60 minutes) in 28-day treatment cycles according to the following schedule:

Initial treatment cycle: Administer on days 1–14, followed by 14-day drug-free period.

Subsequent treatment cycles: Administer for 10 out of the first 14 days, followed by 14-day drug-free period.

Special Populations

Hepatic Impairment

Mild or moderate hepatic impairment: Dosage adjustments not needed. (See Hepatic Impairment under Cautions.)

Severe hepatic impairment: Manufacturer makes no specific dosage recommendation.

Renal Impairment

Dosage adjustments not needed. (See Renal Impairment under Cautions.)

Contraindications

• History of hypersensitivity to edaravone or any ingredient in the formulation.

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity Reactions

Hypersensitivity reactions (e.g., redness, wheals, erythema multiforme), including cases of anaphylaxis (e.g., urticaria, hypotension, dyspnea), reported during postmarketing experience.

Monitor patients carefully. If a hypersensitivity reaction occurs, discontinue drug and initiate appropriate treatment; monitor patient until condition resolves.

Sulfite Sensitivity

Contains sodium bisulfite; may cause allergic-type reactions (e.g., anaphylactic symptoms, life-threatening or less severe asthmatic episodes) in susceptible individuals.

Overall prevalence of sulfite sensitivity in general population unknown. Sulfite sensitivity occurs more frequently in asthmatic individuals.

Specific Populations

Pregnancy

No adequate data on developmental risk in pregnant women. In animal studies, adverse developmental effects (e.g., increased mortality, decreased growth, delayed sexual development, altered behavior) and maternal toxicity observed at clinically relevant doses.

Lactation

Not known whether edaravone is distributed into human milk or if the drug has any effects on the breastfed infant or milk production. Distributed into milk in rats.

Consider known benefits of breast-feeding along with the woman's clinical need for edaravone and any potential adverse effects of the drug or disease on the infant.

Pediatric Use

Efficacy and safety not established in pediatric patients.

Geriatric Use

No overall differences in efficacy or safety compared with younger adults. However, increased sensitivity cannot be ruled out.

Hepatic Impairment

Pharmacokinetics not evaluated in patients with hepatic impairment. (See Hepatic Impairment under Dosage and Administration.)

Renal Impairment

Pharmacokinetics not evaluated in patients with renal impairment; however, not expected to substantially affect edaravone exposure. (See Renal Impairment under Dosage and Administration.)

Common Adverse Effects

Contusion, gait disturbance, headache, dermatitis, eczema, upper respiratory tract inflammation, respiratory failure, respiratory disorder/hypoxia, back pain, myalgia, glycosuria, tinea infection.

Administration

IV Administration

Administer by IV infusion.

Commercially available in polypropylene infusion bags overwrapped with secondary packaging containing an oxygen absorber and indicator; designed to protect the drug from oxidation. Indicator should be pink when acceptable oxygen levels present; do not use if indicator has turned blue or purple prior to opening the package. (See Storage under Stability.)

Monitor for hypersensitivity reactions during administration; immediately discontinue infusion at first sign or symptom of such a reaction.

Do not mix with other drugs.

Rate of Administration

Administer over 60 minutes (approximately 1 mg/minute).

Dosage

Adults

ALS

IV

60 mg (given as 2 consecutive 30-mg infusions over a total of 60 minutes) in 28-day treatment cycles according to the following schedule:

Initial treatment cycle: Administer on days 1–14, followed by 14-day drug-free period.

Subsequent treatment cycles: Administer for 10 out of the first 14 days, followed by 14-day drug-free period.

Special Populations

Hepatic Impairment

Mild or moderate hepatic impairment: Dosage adjustments not needed. (See Hepatic Impairment under Cautions.)

Severe hepatic impairment: Manufacturer makes no specific dosage recommendation.

Renal Impairment

Dosage adjustments not needed. (See Renal Impairment under Cautions.)

Metabolized by multiple uridine diphosphate-glucuronosyltransferase (UGT) enzymes (i.e., UGT 1A6, 1A9, 2B7, and 2B17). Not expected to substantially inhibit UGT 1A1 or 2B7.

Not expected to substantially inhibit major CYP isoenzymes (i.e., CYP isoenzymes 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, or 3A4) nor induce CYP isoenzymes 1A2, 2B6, or 3A4 at clinically relevant concentrations.

Not expected to substantially inhibit major transporters (i.e., P-glycoprotein [P-gp], breast cancer resistance protein [BCRP], organic anion transporting polypeptide [OATP] 1B1, OATP1B3, organic anion transporter [OAT] 1, OAT3, organic cation transporter [OCT] 2).

Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes

Pharmacokinetic interactions unlikely.

Drugs Affecting or Metabolized by UGT Enzymes

Pharmacokinetic interactions unlikely.

Drugs Affecting or Affected by Membrane Transporters

Pharmacokinetic interactions unlikely.

Specific Drugs