HYDROCORTISONE SODIUM SUCCINATE
Clinical safety rating: avoid
CYP3A4 inducers (eg phenytoin) may decrease efficacy and inhibitors may increase effects Can cause hyperglycemia and adrenal suppression with prolonged use.
Hydrocortisone sodium succinate is a corticosteroid that binds to glucocorticoid receptors, modulating gene expression to produce anti-inflammatory, immunosuppressive, and anti-stress responses. It inhibits phospholipase A2, reducing prostaglandin and leukotriene synthesis.
| Metabolism | Hepatic metabolism primarily via 11β-hydroxysteroid dehydrogenase and CYP3A4, producing inactive metabolites (tetrahydrocortisol, cortisone, tetrahydrocortisone) that are conjugated and excreted renally. |
| Excretion | Renal (90-95% as metabolites, <5% unchanged); biliary/fecal <5% |
| Half-life | 1.5-2 hours (plasma terminal); biological half-life 8-12 hours (due to intracellular effects), requiring q6-8h dosing in adrenal insufficiency |
| Protein binding | 90-95% (corticosteroid-binding globulin and albumin) |
| Volume of Distribution | 0.4-0.6 L/kg; distributes into total body water, low tissue binding |
| Bioavailability | IV: 100%; IM: ~80-90% (succinate ester hydrolyzed to active cortisol); not available orally |
| Onset of Action | IV: immediate (minutes); IM: 1-2 hours; oral: 2-4 hours (not applicable as succinate ester is only IV/IM) |
| Duration of Action | IV/IM: 12-24 hours (duration of HPA suppression); clinical effects persist beyond plasma half-life due to genomic actions |
100–500 mg IV or IM every 2–6 hours, as needed; typical initial dose 100–250 mg IV bolus followed by 100–250 mg IV every 4–6 hours for acute conditions.
| Dosage form | INJECTABLE |
| Renal impairment | No specific dose adjustment required for acute dosing; monitor for fluid retention and hypertension in severe renal impairment (GFR <30 mL/min). |
| Liver impairment | For Child-Pugh Class C, reduce dose by 50% and monitor for signs of glucocorticoid excess; Class A/B no adjustment necessary. |
| Pediatric use | Children: 0.56–8 mg/kg/day IV or IM divided every 6–8 hours; status asthmaticus: loading dose 4–8 mg/kg IV then 1–2 mg/kg every 6 hours. |
| Geriatric use | Initiate at low end of adult dose (e.g., 100 mg IV) due to increased risk of osteoporosis, hyperglycemia, and immunosuppression; monitor for fluid and electrolyte disturbances. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
CYP3A4 inducers (eg phenytoin) may decrease efficacy and inhibitors may increase effects Can cause hyperglycemia and adrenal suppression with prolonged use.
| FDA category | Positive |
| Breastfeeding | Low levels in breast milk; M/P ratio unknown but minimal. Compatible with breastfeeding at maternal doses up to 80 mg/day prednisone equivalent; monitor infant for adrenal suppression. |
| Teratogenic Risk | First trimester: Increased risk of cleft palate at doses >10 mg/day prednisone equivalent; second/third trimester: Fetal adrenal suppression, intrauterine growth restriction, premature birth with chronic high doses. |
■ FDA Black Box Warning
No FDA black box warning specifically for hydrocortisone sodium succinate. However, systemic corticosteroids are associated with increased risk of serious infections, suppression of the hypothalamic-pituitary-adrenal (HPA) axis, and growth retardation in children.
| Common Effects | adrenal insufficiency |
| Serious Effects |
["Systemic fungal infections (except in the presence of antifungal therapy)","Administration of live or live-attenuated vaccines in immunosuppressed patients","Idiopathic thrombocytopenic purpura (intramuscular use)","Hypersensitivity to hydrocortisone or any component of the formulation"]
| Precautions | ["HPA axis suppression and adrenal crisis upon withdrawal after prolonged therapy","Increased risk of infections (bacterial, viral, fungal, parasitic) and reactivation of latent tuberculosis","Masking of signs of infection (suppression of inflammation)","Cushing's syndrome with prolonged use","Osteoporosis, avascular necrosis of bone","Gastrointestinal perforation (especially in diverticulitis, peptic ulcer, colitis)","Psychiatric disturbances (euphoria, depression, psychosis)","Increased intraocular pressure, glaucoma, cataracts","Thrombotic events (including thrombophlebitis)","Growth suppression in children","Fluid and electrolyte disturbances (sodium retention, potassium loss)"] |
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| Fetal Monitoring | Monitor maternal blood pressure, blood glucose, electrolytes; fetal growth ultrasound for IUGR; fetal heart rate monitoring; assess for signs of adrenal suppression in newborn after prolonged exposure. |
| Fertility Effects | May impair ovulation and spermatogenesis at high doses; reversible upon dose reduction or discontinuation. |