ENDARI
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ENDARI (ENDARI).
L-arginine is a precursor to nitric oxide, which causes vasodilation and reduces endothelial dysfunction. In sickle cell disease, it decreases red blood cell adhesion to endothelium and reduces hemolysis.
| Metabolism | L-arginine is metabolized primarily in the liver and kidney via arginase to ornithine and urea, and via nitric oxide synthase to citrulline and nitric oxide. Minor pathways include transamination and decarboxylation. |
| Excretion | Primarily renal elimination; approximately 90% of a dose is excreted unchanged in urine within 24 hours. |
| Half-life | 0.5–1 hour; short half-life necessitates continuous or frequent dosing for sustained effect. |
| Protein binding | <5%; minimally bound to plasma proteins. |
| Volume of Distribution | 0.3–0.5 L/kg; distributes primarily in extracellular fluid. |
| Bioavailability | Intravenous: 100%; not available orally. |
| Onset of Action | Intravenous: within minutes; peak effect in 15–30 minutes. |
| Duration of Action | 2–4 hours; clinical effect correlates with plasma levels, requiring repeated doses or infusion. |
0.5 g/kg intravenous infusion over 30-60 minutes once daily.
| Dosage form | FOR SOLUTION |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (GFR >= 30 mL/min/1.73 m^2). Not studied in severe renal impairment (GFR < 30 mL/min/1.73 m^2) or on dialysis, use with caution. |
| Liver impairment | No dose adjustment required for mild hepatic impairment (Child-Pugh A). Not studied in moderate to severe hepatic impairment (Child-Pugh B or C), use with caution. |
| Pediatric use | <30 kg: 3 g/m^2 intravenous infusion over 30-60 minutes once daily; >=30 kg: same as adult dose (0.5 g/kg once daily). |
| Geriatric use | No specific dose adjustments recommended; use with consideration of age-related decline in renal function and increased comorbidity. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ENDARI (ENDARI).
| Breastfeeding | Unknown if excreted in human milk; M/P ratio not available. Caution advised due to potential adverse reactions in nursing infants. |
| Teratogenic Risk | FDA Pregnancy Category B. No evidence of teratogenicity in animal studies; no adequate human studies in first trimester. Second and third trimester: no known fetal risks. |
| Fetal Monitoring | Monitor maternal hemoglobin and reticulocyte count; fetal monitoring if maternal anemia worsens. |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to L-arginine or any component; patients with known urea cycle disorders; severe hepatic or renal failure.
| Precautions | Use with caution in patients with hepatic or renal impairment; may cause electrolyte imbalances; monitor for hypersensitivity reactions; not recommended in patients with argininosuccinic aciduria or other urea cycle disorders; potential for drug interactions with agents affecting nitric oxide synthesis. |
Loading safety data…
| Fertility Effects | No data on fertility impairment in humans; animal studies show no effect on fertility. |