HC (HYDROCORTISONE)
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 is a glucocorticoid that binds to the glucocorticoid receptor, leading to modulation of gene transcription. It inhibits phospholipase A2, reducing prostaglandin and leukotriene synthesis; suppresses inflammatory cytokine production; and causes vasoconstriction and immunosuppression.
| Metabolism | Primarily hepatic via 11β-hydroxysteroid dehydrogenase (11β-HSD) and other reductases; also metabolized in peripheral tissues. Main metabolite is tetrahydrocortisone. Substrate of CYP3A4 (minor). |
| Excretion | Renal: predominantly as conjugated metabolites and a small fraction of unchanged drug. Biliary/fecal: minor, <5%. Total renal clearance accounts for >95% of elimination. |
| Half-life | 1.5–2.5 hours (terminal half-life). In clinical context, the biological half-life (duration of HPA suppression) is longer (8–12 hours) due to tissue binding and active metabolites. |
| Protein binding | 90–95% bound to corticosteroid-binding globulin (CBG) and albumin; binding is saturable. |
| Volume of Distribution | 0.4–0.6 L/kg. Low Vd reflects extensive plasma protein binding and limited tissue penetration, except for high-permeability tissues. |
| Bioavailability | Oral: approximately 96% (rapidly absorbed); IM: 100% (complete absorption); Topical: variable, typically <1% systemic absorption depending on skin integrity and formulation. |
| Onset of Action | Oral: 1–2 hours; IV: immediate (within minutes); IM: 1–2 hours; Topical: varies with formulation, typically within hours for anti-inflammatory effect. |
| Duration of Action | Oral/IV/IM: 8–12 hours (HPA suppression lasts up to 24–36 hours). Short-acting glucocorticoid with less mineralocorticoid activity. Duration of clinical effect for anti-inflammatory/immunosuppressive purposes is approximately 8–12 hours. |
| Molecular Weight | 362.47 |
Hydrocortisone 100-500 mg IV/IM every 2-6 hours as needed for acute adrenal insufficiency or severe inflammation. Maintenance: 20-30 mg/day PO divided every 8-12 hours.
| Dosage form | OINTMENT |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. For severe renal impairment (GFR < 30 mL/min), consider reducing dose by 25-50% due to prolonged half-life, but clinical monitoring is primary. |
| Liver impairment | In Child-Pugh Class B or C, reduce dose by 50% and monitor for signs of hypercorticism. Start at lowest effective dose and titrate carefully. |
| Pediatric use | Acute adrenal insufficiency: 100 mg/m² IV/IM once, then 50-100 mg/m²/day divided every 6 hours. Anti-inflammatory: 2-8 mg/kg/day PO or IV divided every 6-8 hours; max 240 mg/day. Doses based on body surface area or weight. |
| Geriatric use | Use lowest effective dose; initiate at 10-20 mg/day PO divided every 12 hours. Monitor for fluid retention, hypertension, and hyperglycemia. Avoid prolonged use due to increased risk of osteoporosis and muscle wasting. |
| 1st trimester | Corticosteroids including hydrocortisone are associated with a small increased risk of cleft palate when used in the first trimester. However, hydrocortisone is often used in conditions that require systemic treatment, and the benefits may outweigh risks. Use only if clearly needed. |
| 2nd trimester | Use during second trimester may be associated with fetal growth restriction and adrenal suppression. Monitor fetal growth if prolonged use. Generally, use lowest effective dose for shortest duration. |
| 3rd trimester | Use in third trimester may cause neonatal adrenal suppression if used near term. Withdrawal symptoms in neonate possible. Avoid high doses near delivery if possible. |
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 |
■ FDA Black Box Warning
No FDA mandated black box warning.
| Common Effects | adrenal insufficiency |
| Serious Effects |
Systemic fungal infectionHypersensitivity to hydrocortisone or any componentAdministration of live or live-attenuated vaccines (especially immunosuppressive doses)
| Precautions | Adrenal suppression with prolonged use or abrupt withdrawal, Increased risk of infections due to immunosuppression, Osteoporosis with long-term use, Hyperglycemia, diabetes mellitus, Cataracts and glaucoma, Hypertension, fluid retention, Gastrointestinal perforation (especially with NSAIDs), Growth suppression in children, Cushing's syndrome with high doses |
| Food/Dietary | Avoid grapefruit and grapefruit juice as they may increase hydrocortisone levels. Limit sodium intake to reduce fluid retention and hypertension. Increase potassium-rich foods (bananas, oranges) to counteract hypokalemia. Avoid alcohol as it may increase gastrointestinal side effects. |
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| Hydrocortisone crosses the placenta. Approximately 60-70% of maternal hydrocortisone is inactivated by placental 11β-HSD2 to cortisone, but substantial active drug reaches the fetus at high maternal doses. |
| Breastfeeding | Hydrocortisone is excreted into breast milk in small amounts. At maternal doses up to 20 mg/day, amounts are unlikely to affect the infant. For higher doses (e.g., > 40 mg/day), consider waiting 4 hours after dose to breastfeed or alternative therapy. Monitor infant for growth and adrenal function if prolonged high-dose maternal therapy. |
| Lactation Rating | L2 |
| Teratogenic Risk | First trimester: Increased risk of cleft palate (odds ratio ~1.5-3.0) with systemic use, particularly during weeks 6-11. Second/third trimesters: Risk of fetal growth restriction, adrenal suppression, and possibly preterm birth. High doses may cause maternal glucose intolerance, preeclampsia, or premature rupture of membranes. |
| Fetal Monitoring | Monitor maternal blood pressure, glucose levels (gestational diabetes risk), and fetal growth via ultrasound. Assess for signs of adrenal suppression in both mother and neonate (e.g., lethargy, poor feeding). Consider weekly fetal testing in third trimester if prolonged high-dose therapy. |
| Fertility Effects | May suppress ovulation or reduce fertility via inhibition of gonadotropin release at high doses. Up to 10 mg/day generally has minimal impact. Reversible upon discontinuation. |
| Clinical Pearls | Hydrocortisone has weak mineralocorticoid activity; for adrenal crisis, use high-dose IV hydrocortisone (100 mg bolus) rather than dexamethasone. Taper dose gradually after prolonged use to avoid adrenal suppression. Topical hydrocortisone is low potency; avoid on face, groin, or axillae. In sepsis, stress-dose steroids (200-300 mg/day) may be used in vasopressor-refractory shock. |
| Patient Advice | Do not stop taking this medication abruptly; follow your doctor's tapering schedule. · Avoid live vaccines while on this medication. · Report signs of infection (fever, sore throat) or unusual bruising/bleeding. · For topical use: avoid covering with bandages or plastic unless directed. · Take with food or milk to reduce stomach upset. · Wear a medical alert bracelet if on long-term therapy. |