EDARAVONE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for EDARAVONE (EDARAVONE).
Edaravone is a free radical scavenger that reduces oxidative stress by trapping hydroxyl radicals, peroxynitrite, and other reactive oxygen species, thereby protecting neuronal cells from oxidative damage.
| Metabolism | Edaravone is metabolized primarily via glucuronidation by UGT1A6, UGT1A9, and UGT2B7, and also undergoes sulfation. It is not significantly metabolized by CYP450 enzymes. |
| Excretion | Primarily renal excretion as unchanged drug and metabolites (approximately 60-70% unchanged edaravone in urine). Minor fecal elimination (<10%). |
| Half-life | Terminal elimination half-life is 4.5-6 hours. In patients with moderate hepatic impairment, half-life may be prolonged up to 9 hours. No significant accumulation with twice-daily dosing. |
| Protein binding | Approximately 90-92% bound to plasma proteins, primarily to albumin. |
| Volume of Distribution | Volume of distribution is approximately 0.2-0.3 L/kg, indicating limited extravascular distribution. Predominantly distributes in extracellular fluid. |
| Bioavailability | Oral bioavailability is approximately 50-60% due to first-pass metabolism. For the intravenous formulation (approved), bioavailability is 100% by definition. |
| Onset of Action | Intravenous infusion: Clinical effects observed within 2-4 hours after start of infusion based on reduction of free radical markers. Oral formulation (not approved in US): Onset within 1-2 hours. |
| Duration of Action | Duration of action is approximately 6-8 hours corresponding to plasma concentrations above therapeutic threshold. Administered as 60 mg IV infusion over 60 minutes twice daily for 14 days in acute ischemic stroke. Clinical trials show sustained efficacy over treatment period. |
60 mg intravenously over 60 minutes once daily for 14 days, followed by a 14-day drug-free period, then 60 mg intravenously over 60 minutes once daily for 14 days.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for GFR ≥30 mL/min/1.73 m². Safety and efficacy not established for GFR <30 mL/min/1.73 m²; use with caution. |
| Liver impairment | No specific guidelines for Child-Pugh classification. Use with caution in severe hepatic impairment due to lack of data. |
| Pediatric use | Not approved for use in pediatric patients; safety and efficacy not established. |
| Geriatric use | No specific dose adjustment required; pharmacokinetic studies show no significant differences in elderly patients. Monitor renal function as age-related decline may occur. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for EDARAVONE (EDARAVONE).
| Breastfeeding | No data on edaravone excretion in human milk. M/P ratio unknown. Due to potential for adverse effects in nursing infants, breastfeeding is not recommended during treatment and for at least 2 weeks after last dose. |
| Teratogenic Risk | Edaravone is not recommended during pregnancy due to lack of adequate human data. In animal studies, intravenous administration during organogenesis resulted in increased fetal malformations (e.g., skeletal abnormalities) at doses below the human equivalent. Risk cannot be excluded for all trimesters. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Hypersensitivity to edaravone or any of its excipients.","Severe renal impairment (CrCl <30 mL/min)."]
| Precautions | ["Hypersensitivity reactions (e.g., urticaria, dyspnea) have been reported; discontinue if severe.","Monitor for sulfite sensitivity in patients with asthma (contains sodium bisulfite).","Renal impairment: Not recommended in severe renal impairment (CrCl <30 mL/min).","Hepatic impairment: Use with caution in moderate to severe hepatic impairment."] |
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| Fetal Monitoring |
| Pregnancy testing before initiation in women of childbearing potential. Monitor fetal growth and amniotic fluid volume via ultrasound if exposure occurs. No specific maternal monitoring beyond standard pregnancy care. |
| Fertility Effects | Edaravone did not impair fertility in animal studies at clinically relevant doses. Human data on fertility effects are absent. No effect on spermatogenesis observed in male rats. |