EDARAVONE
Clinical safety rating
cautionComprehensive 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. |
| Molecular Weight | 174.16 |
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 | Edaravone is contraindicated in the first trimester due to teratogenic effects observed in animal studies. |
| 2nd trimester | Edaravone is contraindicated in the second trimester due to potential fetal harm; avoid use unless no safer alternative. |
| 3rd trimester | Edaravone is contraindicated in the third trimester due to risks of fetal toxicity. |
Clinical note
Comprehensive clinical and safety monograph for EDARAVONE (EDARAVONE).
| Placental transfer | Edaravone is known to cross the placenta in animal studies, with detectable levels in fetal tissues; human data are lacking but expected similar transfer. |
| Breastfeeding | It is unknown whether edaravone is excreted in human milk. Due to potential adverse effects in nursing infants, breastfeeding should be discontinued during therapy. |
| Lactation Rating | L5 - Contraindicated |
| 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. |
| 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. |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to edaravone or any excipientPregnancy
| 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. |
| Food/Dietary | No significant food interactions reported. No dietary restrictions known. |
| Clinical Pearls | Monitor for hypersensitivity reactions, including anaphylaxis; edema and gait disturbance are common adverse effects. Avoid use in patients with severe hepatic impairment. Administer intravenous infusion over 60 minutes; do not mix with other medications in the same bag. Renal function monitoring recommended. |
| Patient Advice | This medication is used to slow the progression of ALS symptoms. · Report any signs of allergic reaction such as rash, itching, or difficulty breathing immediately. · You may experience swelling in the legs or difficulty walking; notify your doctor if these become severe. · Do not drive or operate heavy machinery until you know how the medication affects you. · Keep all appointments for infusion and blood tests to monitor your kidney function. |
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