Hospital Pharmacy - December 2017 - 735

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Ali and Baker
Animal study data showed adverse developmental effects,
including increased mortality, decreased growth, delayed
sexual development, and altered behavior, as well as maternal toxicity, at clinically relevant doses of edaravone.1
There are currently no data regarding the presence of
edaravone or its metabolites in human breast milk or its
effects on breastfeeding infants or milk production; however, the drug and its metabolites were detected in the milk
of lactating rats. The developmental and health benefits of
breastfeeding should be weighed against the mother's clinical need for the drug and potential for adverse effects in
breastfeeding infants due to edaravone or the underlying
maternal condition.1
The safety and efficacy of edaravone in pediatric patients
have not been established.1

Adverse Reactions
In pooled clinical trials of Japanese patients with ALS (184
patients received edaravone, 184 received placebo; median
age, 60 years [range, 29-75 years]), the most commonly
reported adverse effects associated with edaravone and
occurring at least 2% more frequently than with placebo
were contusion (15% vs 9%), gait disturbance (13% vs 9%),
and headache (10% vs 6%). Other adverse effects include
dermatitis, eczema, respiratory failure (hypoxia), glycosuria,
and tinea infections.1

Drug Interactions
In vitro studies suggest that edaravone does not significantly
inhibit cytochrome P450 enzymes (CYP1A2, 2B6, 2C8,
2C9, 2C19, 2D6, 3A4), UGT1A1 or 2B7, or transporters
(P-glycoprotein; BCRP; OATP1B1, OATP1B3, OAT1, and
OAT3; and OCT2), nor is it expected to induce CYP1A2,
2B6, or 3A4 metabolic enzymes. Edaravone is a substrate of
UGT1A6, 1A9, 2B7, and 2B17.1

Recommended Monitoring
Patients should be monitored for hypersensitivity reactions.1

Dosing
The recommended dose of edaravone is 60 mg given by IV
infusion over 60 minutes once daily using a 28-day cycle. For
the initial treatment cycle, 60 mg is administered once daily
for 14 days, followed by a 14-day drug-free period. For subsequent cycles, patients should receive once-daily edaravone
for 10 days of the 14-day period, followed by a 14-day drugfree period.1
The 60 mg dose should be administered as 2 consecutive 30 mg IV infusion bags over a total of 60 minutes
(infusion rate approximately 1 mg/minute [3.33 mL/minute]). Discontinue the infusion if the patient exhibits signs

or symptoms of a hypersensitivity reaction. Other medications should not be injected into the infusion bag or mixed
with edaravone.1

Product Availability
Edaravone was approved on May 5, 2017.2 It is available as
a 30 mg per 100 mL aqueous solution for injection in a single-dose polypropylene bag.1
The solution for injection should be stored at 25°C (77°F),
with excursions permitted to between 15°C and 30°C (59°F
and 86°F). The medication should be protected from light
and from oxygen degradation until time of use [the oxygen
indicator will turn blue or purple if the oxygen levels exceed
acceptable levels; if this occurs, the product should not be
used]. The medication should be used within 24 hours of
opening the protective packaging.1

Drug Safety/Risk Evaluation and
Mitigation Strategy (REMS)
No REMS is required for edaravone.1,2

Conclusion
Edaravone is FDA approved for the treatment of ALS based
on evidence from clinical trials conducted in Japan. Patients
with well-defined, advanced disease may be more likely to
benefit from treatment. Common adverse effects include gait
disturbance, contusion, and headache, and severe adverse
effects include hypersensitivity reactions, especially in
patients with sulfite allergy. Edaravone offers marginal benefit in slowing disease progression, and does not reverse disease modality.
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect
to the research, authorship, and/or publication of this article.

Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.

References
1. Radicava (edaravone) [prescribing information]. Jersey City,
NJ: MT Pharma America Inc; May 2017.
2. Unger EF. NDA approval letter: Radicava (edaravone NDA
209176). Food and Drug Administration. https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2017/209176Orig1s00
0ltr.pdf. Published May 5, 2017. Accessed June 14, 2017
3. Abe K, Itoyama Y, Sobue G, et al; Edaravone ALS Study
Group. Confirmatory double-blind, parallel-group, placebocontrolled study of efficacy and safety of edaravone (MCI-186)
in amyotrophic lateral sclerosis patients. Amyotroph Lateral
Scler Frontotemporal Degener. 2014;15(7-8):610-617.

https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2017/209176Orig1s000ltr.pdf https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2017/209176Orig1s000ltr.pdf https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2017/209176Orig1s000ltr.pdf

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