Edaravone

Edaravone may be found in some form under the following brand names:

• Radicava

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

Edaravone is a central nervous system agent.

Edaravone has the following uses:

Edaravone is indicated for the treatment of amyotrophic lateral sclerosis (ALS).1

Contraindications

• Patients with a history of hypersensitivity to edaravone or any of the inactive ingredients in the formulation.1

Warnings/Precautions

Hypersensitivity Reactions

Hypersensitivity reactions (redness, wheals, and erythema multiforme) and cases of anaphylaxis (urticaria, decreased blood pressure, and dyspnea) have been reported in spontaneous postmarketing reports with edaravone.1

Patients should be monitored carefully for hypersensitivity reactions. If hypersensitivity reactions occur, discontinue edaravone, treat per standard of care, and monitor until the condition resolves.1

Sulfite Allergic Reactions

Edaravone contains sodium bisulfite, a sulfite that may cause allergic type reactions, including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown. Sulfite sensitivity occurs more frequently in asthmatic people.1

Specific Populations

Risk Summary: There are no adequate data on the developmental risk associated with the use of edaravone in pregnant women. In animal studies, administration of edaravone 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.1

In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2–4% and 15–20%, respectively. The background risk for major birth defects and miscarriage in patients with ALS is unknown.1

Animal Data: In rats, intravenous administration of edaravone (0, 3, 30, or 300 mg/kg/day) throughout the period of organogenesis resulted in reduced fetal weight at all doses. In dams allowed to deliver naturally, offspring weight was reduced at the highest dose tested. Maternal toxicity was also observed at the highest dose tested. There were no adverse effects on reproductive function in the offspring. A no-effect dose for embryofetal developmental toxicity was not identified; the low dose is less than the recommended human dose of 60 mg, on a body surface area (mg/m2) basis.1

In rabbits, intravenous administration of edaravone (0, 3, 20, or 100 mg/kg/day) throughout the period of organogenesis resulted in embryofetal death at the highest dose tested, which was associated with maternal toxicity. The higher no-effect dose for embryofetal developmental toxicity is approximately 6 times the recommended human dose (RHD) on a body surface area (mg/m2) basis.1

The effects on offspring of edaravone (0, 3, 20, or 200 mg/kg/day), administered by intravenous injection to rats from GD 17 throughout lactation, were assessed in two studies. In the first study, offspring mortality was observed at the high dose and increased activity was observed at the mid and high doses. In the second study, there was an increase in stillbirths, offspring mortality, and delayed physical development (vaginal opening) at the highest dose tested. Reproduction function in offspring was not affected in either study. Maternal toxicity was evident in both studies at all but the lowest dose tested. The no-effect dose for developmental toxicity (3 mg/kg/day) is less than the RHD on a mg/m2 basis.1

There are no data on the presence of edaravone in human milk, the effects on the breast-fed infant, or the effects of the drug on milk production. Edaravone and its metabolites are excreted in the milk of lactating rats. The developmental and health benefits of breast-feeding should be considered along with the mother’s clinical need for edaravone and any potential adverse effects on the breastfed infant from edaravone or from the underlying maternal condition.1

Safety and effectiveness of edaravone in pediatric patients have not been established.1

Of the 184 patients with ALS who received edaravone in 3 placebo-controlled clinical trials, a total of 53 patients were 65 years of age or older, including 2 patients 75 years of age or older. No overall differences in safety or effectiveness were observed between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out.1

The effect of renal impairment on the pharmacokinetics of edaravone has not been studied. However, renal impairment is not expected to significantly affect the exposure to edaravone. No dose adjustment is needed in these patients.1

The effect of hepatic impairment on the pharmacokinetics of edaravone has not been studied. No dose adjustment is needed for patients with mild or moderate hepatic impairment. No specific dosing recommendation can be provided for patients with severe hepatic impairment.1

Common Adverse Effects

Most common adverse reactions (at least 10% and greater than placebo) are contusion, gait disturbance, and headache.1

AHFS First Release. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Use this medicine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• It is given as an infusion into a vein over a period of time.

What do I do if I miss a dose?

• Call your doctor to find out what to do.

• MCI-186

Adverse events were observed in some animal reproduction studies.

Edaravone can cause serious allergic reactions. The symptoms may not appear until after your IV infusion is finished.

Get emergency medical help if you have signs of an allergic reaction: hives, itching; wheezing, difficult breathing; feeling light-headed; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• bronchospasm (wheezing, chest tightness, trouble breathing); or
• a light-headed feeling, like you might pass out.

Common side effects may include:

• bruising;
• headache; or
• trouble walking.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

-Initial Treatment Cycle: 60 mg once a day as IV infusion for 14 days followed by a 14-day drug-free period.

-Subsequent Treatment Cycles: 60 mg once a day as IV infusion for 10 days out of 14-day periods, followed by 14-day drug-free periods.

Comments:
-Administer each 60 mg dose as 2 consecutive 30 mg IV infusion bags over a total of 60 minutes (infusion rate approximately 1 mg per minute [3.33 mL per minute]).
-Upon the first observation of any signs or symptoms of a hypersensitivity reaction, promptly discontinue the infusion.

Use: Treatment of amyotrophic lateral sclerosis (ALS)

Administration Advice:
-The oxygen indicator will turn blue or purple if the oxygen has exceeded acceptable levels; avoid use in such cases.
-Use within 24 hours once the overwrap package is opened.
-Inspect visually for particulate matter and discoloration prior to administration.

Storage Requirements:
-Store at up to 25 degrees Celsius (77 degrees Fahrenheit); excursions permitted from 15 to 30 degrees Celsius (59 to 86 degrees Fahrenheit).
-Protect from light, and keep in overwrapped package to protect from oxygen degradation until time of use.

IV Compatibility:
-Do not inject other medications into the infusion bag or mixed with this drug.

General:
-The efficacy of this drug was established in a 6-month clinical study of Japanese patients with ALS duration of 2 years or less who had normal respiratory function (forced vital capacity of 80% or more); 93% of these patients were living independently and retained most activities of daily living (2 points or better on each item of the ALS Functional Rating Scale - Revised).

Monitoring:
-Hypersensitivity/allergic reactions, anaphylaxis, asthmatic episodes (throughout treatment)