EVEKEO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for EVEKEO (EVEKEO).
EVEKEO (sodium nitrite and sodium thiosulfate) is a cyanide antidote. Sodium nitrite induces methemoglobin formation, which binds free cyanide. Sodium thiosulfate provides a sulfur donor for conversion of cyanide to thiocyanate via rhodanese.
| Metabolism | Sodium nitrite is metabolized primarily to methemoglobin and nitric oxide. Sodium thiosulfate is metabolized to thiocyanate by rhodanese. |
| Excretion | Renal: 30-50% as unchanged drug; fecal: 50-70% as metabolites and unchanged drug. |
| Half-life | Terminal elimination half-life: 2-3 hours. Clinical context: Short half-life supports multiple daily dosing for seizure control. May be prolonged in hepatic impairment. |
| Protein binding | 40-50% bound to serum albumin and α1-acid glycoprotein. |
| Volume of Distribution | 0.6-0.8 L/kg. Clinical meaning: Moderate distribution suggests limited tissue penetration; primarily confined to extracellular fluid. |
| Bioavailability | Oral: 85-95%. Rectal: 70-80%. Intramuscular: 90-100%. |
| Onset of Action | Oral: 15-45 minutes. Intravenous: 2-5 minutes. Intramuscular: 10-20 minutes. |
| Duration of Action | 6-12 hours. Clinical notes: Duration depends on dose and route; IV provides rapid but shorter effect. Chronic therapy may require dose adjustment. |
5 mg IV infused over 1 hour every 2 weeks until disease progression or unacceptable toxicity. Reduce dose for adverse reactions.
| Dosage form | TABLET |
| Renal impairment | No adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Not recommended for severe renal impairment (CrCl <30 mL/min) due to limited data. |
| Liver impairment | No adjustment required for mild hepatic impairment (Child-Pugh A). Not recommended for moderate or severe hepatic impairment (Child-Pugh B or C) due to limited data. |
| Pediatric use | Not approved for pediatric patients; safety and efficacy not established. |
| Geriatric use | No specific dose adjustment recommended; clinical studies included patients ≥65 years with no overall differences in safety or efficacy. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for EVEKEO (EVEKEO).
| Breastfeeding | No data on excretion in human milk. M/P ratio unknown. Caution if breastfeeding; consider risk vs benefit. |
| Teratogenic Risk | Pregnancy Category N (not assigned). No adequate human data; based on animal studies, fetal harm is possible. Avoid use in first trimester if alternative available. Risk in second and third trimesters unknown. |
| Fetal Monitoring | Monitor maternal liver function tests, renal function, and complete blood count. Fetal ultrasound if used during pregnancy. |
■ FDA Black Box Warning
Risk of severe hypotension and methemoglobinemia. Monitor methemoglobin levels. Use caution in patients with low oxygen saturation.
| Serious Effects |
["Hypersensitivity to sodium nitrite or sodium thiosulfate","Methemoglobin reductase deficiency"]
| Precautions | ["Can cause severe hypotension requiring vasopressors","Methemoglobinemia may reduce oxygen delivery; avoid in patients with significant anemia or G6PD deficiency","Thiocyanate accumulation with prolonged use, especially in renal impairment"] |
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| Fertility Effects | No human data on fertility effects. Animal studies show no impairment. |