HYDROCORTISONE SODIUM PHOSPHATE
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 phosphate is a corticosteroid that binds to the glucocorticoid receptor, leading to regulation of gene transcription. It inhibits phospholipase A2, reducing pro-inflammatory mediators such as prostaglandins and leukotrienes. It also suppresses immune cell migration and cytokine production.
| Metabolism | Hydrocortisone is primarily metabolized in the liver via reduction, hydroxylation, and conjugation with glucuronic acid and sulfate. Key enzymes include 11β-hydroxysteroid dehydrogenase (11β-HSD), 5α-reductase, and 3α-hydroxysteroid dehydrogenase. A small fraction is metabolized by CYP3A4. |
| Excretion | Renal: primarily as inactive metabolites, <1% unchanged; hepatic metabolism to tetrahydrocortisone and glucuronide conjugates; biliary/fecal excretion negligible. |
| Half-life | Terminal elimination half-life approximately 1.5–2 hours; in adrenal insufficiency, dose interval is 8 hours due to HPA axis suppression considerations. |
| Protein binding | Approximately 90% bound, primarily to corticosteroid-binding globulin (CBG, transcortin) and albumin. |
| Volume of Distribution | Vd approximately 0.3–0.5 L/kg; reflects distribution into total body water with minimal tissue binding; higher in obese patients. |
| Bioavailability | Oral: 96% (rapidly absorbed); IM: 100% (complete); IV: 100%. |
| Onset of Action | IV: immediate (within minutes); IM: 15–30 minutes; oral: 1–2 hours. |
| Duration of Action | IV/IM: 4–6 hours; oral: 6–8 hours; duration is sufficient for replacement therapy; for anti-inflammatory effects, multiple daily doses or continuous infusion may be needed. |
100-500 mg intravenously or intramuscularly every 2-6 hours as needed for acute conditions; typical dose 100 mg IV/IM every 8 hours.
| Dosage form | Injectable |
| Renal impairment | No dose adjustment required in renal impairment; hemodialysis does not significantly remove hydrocortisone. |
| Liver impairment | In severe hepatic impairment (Child-Pugh C), consider dose reduction by 50% due to reduced clearance. |
| Pediatric use | 0.5-2 mg/kg/day intravenously or intramuscularly divided every 6-12 hours; for acute conditions, up to 1-2 mg/kg/dose every 4-6 hours. |
| Geriatric use | Use lowest effective dose; monitor for electrolyte disturbances, hyperglycemia, and increased susceptibility to infections. |
| 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 | Hydrocortisone enters breast milk with an M/P ratio approximately 0.25. At maternal doses ≤20 mg/day, amount in milk is minimal (<1% of maternal dose) and considered compatible. Higher doses may cause adrenal suppression in infant. |
| Teratogenic Risk | First trimester: Corticosteroids are associated with a small increased risk of cleft palate (odds ratio ~1.3-3.4). Second/third trimester: Chronic use may increase risk of preterm delivery, intrauterine growth restriction, and maternal hypertension. High doses may cause fetal adrenal suppression. |
■ FDA Black Box Warning
There is no FDA black box warning for hydrocortisone sodium phosphate. However, corticosteroids including hydrocortisone are associated with increased risk of infection, masking of infection, and reactivation of latent infections.
| Common Effects | adrenal insufficiency |
| Serious Effects |
["Systemic fungal infections","Known hypersensitivity to hydrocortisone or any component","Administration of live or live-attenuated vaccines in patients receiving immunosuppressive doses","Idiopathic thrombocytopenic purpura (relative)"]
| Precautions | ["Immunosuppression and increased risk of infections","Adrenal suppression with prolonged use (avoid abrupt withdrawal)","Increased cardiovascular risk (hypertension, heart failure)","Osteoporosis and increased fracture risk","Gastrointestinal perforation and peptic ulcer disease","Cushing's syndrome with long-term high doses","Growth suppression in children","Ocular effects: cataracts, glaucoma, central serous chorioretinopathy","Psychiatric disturbances (e.g., euphoria, depression, psychosis)","Electrolyte imbalance: hypokalemia, hypernatremia, fluid retention","Masking of signs of infection","Increased intraocular pressure"] |
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| Fetal Monitoring | Monitor maternal blood pressure, blood glucose, and signs of infection. Fetal growth ultrasound if used chronically. Assess infant for adrenal suppression after delivery if maternal high-dose or prolonged therapy. |
| Fertility Effects | No direct adverse effects on fertility. High doses may cause menstrual irregularities and transient anovulation. Underlying disease (e.g., autoimmune) may impact fertility. |