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. |
| Molecular Weight | 490.42 Da (hydrocortisone sodium phosphate) |
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 | Corticosteroids like hydrocortisone are associated with a small increased risk of oral clefts when used in the first trimester. Use only if clearly needed and weigh risks against benefits. |
| 2nd trimester | May be used for maternal benefit. Monitor fetal growth if used long-term. |
| 3rd trimester | May cause fetal adrenal suppression, particularly with high doses or prolonged use. Use lowest effective dose for shortest duration. |
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 |
| Placental transfer | Hydrocortisone crosses the placenta. The placenta expresses 11β-hydroxysteroid dehydrogenase type 2, which converts active cortisol to inactive cortisone, reducing fetal exposure. However, significant transfer occurs with high maternal doses. |
■ 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 (except when used in life-threatening situations with appropriate antifungal therapy)Hypersensitivity to hydrocortisone or any component of the formulationAdministration of live or live attenuated vaccines (due to immunosuppression)
| 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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| Breastfeeding | Hydrocortisone is excreted into breast milk in small amounts. Doses up to 20 mg/day are considered compatible with breastfeeding. Higher doses may suppress infant cortisol production. Monitor infant for potential adrenal suppression. |
| Lactation Rating | L2 (Safer) |
| 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. |
| 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. |
| Food/Dietary | Avoid grapefruit and grapefruit juice as they may increase drug levels. Limit high-sodium foods to reduce fluid retention and hypertension. Maintain adequate potassium intake through potassium-rich foods (bananas, oranges, spinach) to counteract hypokalemia. Avoid excessive alcohol consumption as it may increase gastrointestinal irritation. |
| Clinical Pearls | Hydrocortisone sodium phosphate is a water-soluble prodrug that is rapidly hydrolyzed to hydrocortisone, providing rapid onset of corticosteroid effects. It is commonly used in acute adrenal insufficiency (Addisonian crisis) for rapid glucocorticoid replacement. Avoid use in patients with systemic fungal infections or known hypersensitivity. Monitor for signs of adrenal suppression if used long-term; taper dose gradually to prevent withdrawal. Because of its mineralocorticoid activity, monitor potassium and sodium levels, especially during prolonged therapy. |
| Patient Advice | Take exactly as prescribed; do not stop abruptly without doctor's guidance. · Report any signs of infection (fever, sore throat) or worsening of existing conditions. · Carry a medical alert card stating you are taking a corticosteroid. · Avoid live vaccines while on this medication. · Inform all healthcare providers of your corticosteroid use before any surgery or emergency treatment. |