edaravone (Rx)

>10%

Contusion (15%)

Gait disturbance (13%)

1-10%

Headache (10%)

Dermatitis (8%)

Eczema (7%)

Respiratory failure, respiratory disorder, hypoxia (6%)

Glycosuria (4%)

Tinea infection (4%)

Postmarketing Reports

Skin and subcutaneous tissue disorders: Hypersensitivity reactions and anaphylaxis

Contraindications

Hypersensitivity to drug or any of its excipients

Cautions

Hypersensitivity reactions (redness, wheals, and erythema multiforme) and cases of anaphylaxis (urticaria, decreased blood pressure, and dyspnea) reported; monitor for hypersensitivity reactions; if hypersensitivity reactions occur, discontinue drug, treat per standard of care, and monitor until condition resolves

Contains sodium bisulfite, which may cause allergic type-reactions, including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in susceptible people; sulfite sensitivity occurs more often with history of asthma

Pregnancy

There are no adequate data on the developmental risk associated with use in pregnant women

In animal studies, administration 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

Lactation

Unknown if distributed in human breast milk

Excreted in the milk of lactating rats

Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Pyrazolone free radical scavenger; mechanism of action for ALS is unknown

Theorized to decrease effects of oxidative stress, a likely factor in the onset and progression of ALS

Absorption

Oral bioavailability: 57%

Peak plasma concentration

• IV: At end of infusion time
• PO: 0.5 hr (fasting conditions)

Effect of food on oral suspension

• Peak plasma concentration and AUC decreased by 82% and 61%, respectively, with a high-fat meal compared with fasted conditions
• Peak plasma concentration and AUC decreased by 44% and 24%, respectively, 4 hr after a high-fat meal
• Peak plasma concentration and AUC decreased by 45% and 21%, respectively 2 hr after low-fat meals
• Peak plasma concentration and AUC did not decrease significantly when administered 1 hr before (or 8 hr after) high-fat meals; 4 hr after low-fat meals, or 2 hr after caloric supplement

Distribution

Protein bound: 92% (mainly albumin)

Vd (IV): 63.1 L

Metabolism

Metabolized to a sulfate conjugate and a glucuronide conjugate, which are not pharmacologically active

Elimination

Half-life: 4.5-9 hr; 3-6 hr (metabolites)

Total clearance (IV): 35.9 L/hr

Excretion (urine)

• Glucuronide conjugate: 60-80%
• Sulfate conjugate: 6-8%
• Unchanged drug: <1%

IV Preparation

Do not use if oxygen indicator has turned blue or purple before opening package

Once overwrap is opened, use within 24 hr

Inspect visually for particulate matter and discoloration before administration

Clear, colorless, aqueous solution

Do not mix with other medications in infusion bag

IV Administration

For IV infusion only

Administer each 60-mg dose as 2 consecutive 30-mg IV infusion bags over total of 60 minutes (infusion rate ~1 mg/min)

Discontinue infusion upon first observation of any signs or symptoms consistent with hypersensitivity reaction

Oral Preparation

Before opening bottle, invert and shake vigorously up and down for at least 30 seconds

Use 5-mL oral syringe to measure dose (provided with product)

Oral Administration

May give orally or by feeding tube

Take in morning on empty stomach after overnight fasting; do not consume food for 1 hr after administration except water

Fasting time before and after dose relative to type of food consumption

• High-fat meal (800-1000 calories, 50% fat): 8 hr before administration and 1 hr after
• Low-fat meal (400-500 calories, 25% fat): 4 hr before administration and 1 hr after administration
• Caloric supplement (250 calories [eg, protein drink]): 2 hr before administration and 1 hr after administration

Feeding tube

• May administer by nasogastric tubes or percutaneous endoscopic gastrostomy tubes made of silicone, polyvinyl chloride or polyurethane
• Before and after administration, use a catheter-tip syringe to flush tube with at least 30 mL of water

Storage

IV

• Store at up to 25°C (77°F); excursions permitted from 15-30°C (59-86°F)
• Protect from light
• Supplied in single-dose polypropylene bags, each overwrapped with polyvinyl alcohol (PVA) secondary packaging containing an oxygen absorber and oxygen indicator, which should be pink to reflect appropriate oxygen levels
• Store in PVA overwrapped package to protect from oxygen degradation until time of use
• Oxygen indicator turns blue or purple if oxygen has exceeded acceptable levels
• Once overwrap is opened, use within 24 hr

PO

• Pharmacy

  • Refrigerate at 2-8ºC (36-46ºF)
  • Protect from light
  • Do not freeze

• Patient

  • Store bottle upright at 20-25ºC (68-77ºF)
  • Protect from light
  • Discard 15 days after opening bottle, or if unopened, 30 days from date of shipment indicated on carton pharmacy label