Edaravone

Brand names: Radicava; Radicava ORS
Drug class: Antineoplastic Agents

Usage of 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.

There is no cure for ALS and limited treatment options are available that have shown only modest benefits in delaying disease progression and death.

The American Academy of Neurology published an evidence-based guideline for ALS in 2009; however, the only disease-modifying drug available at that time was riluzole. The availability of edaravone offers another option; however, both drugs provide limited improvement in survival.

Relate drugs

How to use Edaravone

General

Patient Monitoring

  • Monitor patients for hypersensitivity Reactions during administration of edaravone; promptly discontinue the drug at the first sign or symptom of such a reaction.

    • Administration

    Administer orally (as an oral suspension) or by IV infusion.

    IV Administration

    Administer by IV infusion.

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

    Do not mix with other drugs.

    Rate of Administration

    Administer each 60-mg dose as 2 consecutive 30-mg IV infusion bags over a total of 60 minutes (infusion rate of approximately 1 mg per minute [3.33 mL per minute]).

    Oral Administration

    Administer by mouth or via feeding tube.

    Administer in the morning on an empty stomach after overnight Fasting. (See Table 1 for specific fasting conditions.) Do not consume food for 1 hour after administration except water.

    Table 1: Administration of Edaravone Oral Suspension Relative to Type of Food Consumption1

    Type of food/caloric supplement consumed

    Fasting time before and after edaravone oral suspension dose administration with regards to meal type

    High-fat meal (800–1000 calories, 50% fat)

    8 hours before administration and 1 hour after administration

    Low-fat meal (400–500 calories, 25% fat)

    4 hours before administration and 1 hour after administration

    Caloric supplement (250 calories; e.g., protein drink)

    2 hours before administration and 1 hour after administration

    Before each use, invert the container and vigorously shake ≥30 seconds. Administer oral suspension using the supplied 5-mL oral syringe; a household teaspoon is not an adequate measuring device.

    Administration via Feeding Tube

    Oral suspension may be administered via nasogastric tubes or percUTAneous endoscopic gastrostomy (PEG) tubes made of silicone, polyvinyl chloride (PVC), or polyurethane. Use a catheter-tip syringe to flush the tube with at least 1 ounce (30 mL) of water before and after administration of the drug.

    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.

    Oral

    105 mg (5 mL) by mouth or via feeding tube using the oral suspension 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.

    Switching from IV to Oral

    Patients receiving IV edaravone 60 mg may be switched to oral edaravone 105 mg (5 mL of the oral suspension) using the SAMe dosing frequency.

    Upon switching to oral therapy, follow dosing recommendations for the oral suspension with regards to food consumption.

    Special Populations

    Hepatic Impairment

    Dosage adjustments not needed.

    Renal Impairment

    Mild or moderate renal impairment: Dosage adjustments not needed. No data on severe renal impairment.

    Geriatric Use

    Dosage adjustments not needed; some older individuals may exhibit greater sensitivity.

    Warnings

    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 individuals with asthma.

    Specific Populations

    Pregnancy

    No adequate data on developmental risk when used 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 breast-fed 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.

    Geriatric Use

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

    Hepatic Impairment

    Changes in exposures observed in patients with mild, moderate, or severe hepatic impairment not considered clinically significant; therefore, dosage adjustments not necessary in patients with hepatic impairment.

    Renal Impairment

    Changes observed in mean peak plasma concentration and AUC in patients with mild to moderate renal impairment not considered clinically important; dosage adjustments therefore not necessary in such patients. The effects of severe renal impairment not studied.

    Common Adverse Effects

    Most common adverse reactions (≥10%): contusion, gait disturbance, headache.

    What other drugs will affect Edaravone

    Metabolized by multiple uridine diphosphate-glucuronosyltransferase (UGT) enzymes (i.e., UGT 1A1, 1A6, 1A7, 1A8, 1A9, 1A10, 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, MATE1, MATE2-K).

    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

    Drug

    Interaction

    Comments

    Furosemide

    No change in peak plasma concentration or AUC of furosemide (OAT3 substrate)

    Riluzole

    Pharmacokinetic interaction not expected; administered concomitantly with edaravone in most patients in clinical studies

    Rosuvastatin

    No change in peak plasma concentration or AUC of rosuvastatin (BCRP substrate)

    Sildenafil

    No change in peak plasma concentration or AUC of sildenafil (CYP3A4 substrate)

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