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. |
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 | 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 is excreted into breast milk in small amounts with an estimated M/P ratio of 0.2-0.4 (low). At maternal doses ≤20 mg/day, infant exposure is negligible and considered compatible with breastfeeding. Higher doses (>40 mg/day) may warrant monitoring infant adrenal function. |
| Teratogenic Risk |
■ FDA Black Box Warning
No FDA mandated black box warning.
| Common Effects | adrenal insufficiency |
| Serious Effects |
["Systemic fungal infection (absolute)","Hypersensitivity to hydrocortisone or components","Intrathecal administration (contraindicated)","Live or live-attenuated vaccines (relative)","Peptic ulcer disease (relative)"]
| 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. |
Loading safety data…
| 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. |