HYDROCORTISONE
Clinical safety rating: avoid
Positive evidence of fetus risks but benefits may outweigh risks in some cases
Hydrocortisone is a glucocorticoid that binds to the glucocorticoid receptor (GR), leading to altered gene expression. This results in anti-inflammatory, immunosuppressive, anti-proliferative, and vasoconstrictive effects. It also modulates carbohydrate, protein, and lipid metabolism.
| Metabolism | Hydrocortisone is metabolized primarily in the liver via reduction and conjugation, mainly by CYP3A4. The metabolites are glucuronidated and sulfated, then excreted renally. |
| Excretion | Renal: primarily as inactive metabolites (cortisone, tetrahydrocortisone) and unchanged drug (<1%). Biliary/fecal: minimal (<5%). |
| Half-life | Terminal half-life: 1.5–2 hours (plasma). In tissues, biologic half-life is 8–12 hours due to intracellular activity. Half-life prolonged in hepatic impairment. |
| Protein binding | ~90% bound, primarily to corticosteroid-binding globulin (CBG, transcortin) and albumin. In pregnancy/inflammation, CBG increases; binding may decrease. |
| Volume of Distribution | Vd: 0.4–0.6 L/kg. Distributes well into tissues; crosses placenta; enters breast milk. |
| Bioavailability | Oral: 80–100% (rapid absorption). IM: 70–90%. Rectal: 20–60% (variable). Topical: minimal systemic absorption (except with damaged skin or occlusive dressings). |
| Onset of Action | IV: immediate (minutes). Oral: 1–2 hours. IM: 2–4 hours. Topical: variable (hours to days). Rectal: 2–4 hours. |
| Duration of Action | Duration of HPA axis suppression: 1.5–2 days after single dose. Plasma glucocorticoid effects last 8–12 hours. Duration of anti-inflammatory effect may persist beyond plasma half-life. |
| Molecular Weight | 362.46 |
Oral: 10-20 mg every 6-8 hours; IV/IM: 100-500 mg every 2-6 hours for acute conditions; typical maintenance: 20-240 mg/day divided every 8-12 hours.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for GFR >30 mL/min; for GFR 10-30 mL/min: use with caution and consider every 12-hour dosing; for GFR <10 mL/min: avoid or reduce dose by 50%. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: reduce dose by 75% or avoid. |
| Pediatric use | Oral/IV/IM: 0.5-2 mg/kg/day divided every 6-8 hours; maximum 60 mg/m²/day; for acute conditions: loading dose 1-2 mg/kg followed by 0.5-1 mg/kg every 6 hours. |
| Geriatric use | Initiate at lower end of dosing range (e.g., 5-10 mg orally every 12 hours) due to increased risk of osteoporosis, hyperglycemia, and immunosuppression; monitor glucose and bone density. |
| 1st trimester | Hydrocortisone is a glucocorticoid. Use in first trimester should be restricted to conditions where benefit outweighs risk. Associated with a small increase in risk of cleft palate (absolute risk increase ~0.1%) and possibly intrauterine growth restriction. Consider lowest effective dose. |
| 2nd trimester | May cause fetal adrenal suppression if used long-term. Monitor fetal growth. Risk of preterm birth and premature rupture of membranes with prolonged use. |
| 3rd trimester | Prolonged use may lead to neonatal adrenal suppression. Use with caution; taper dose if possible before delivery. May cause neonatal hypoglycemia. |
Clinical note
CYP3A4 inducers (eg phenytoin) may decrease efficacy and inhibitors may increase effects Can cause hyperglycemia and adrenal suppression with prolonged use.
| Placental transfer | Hydrocortisone crosses the placenta. The placenta expresses 11β-hydroxysteroid dehydrogenase type 2 which converts cortisol to inactive cortisone, limiting fetal exposure. However, at high maternal doses, this barrier may be overwhelmed. |
■ FDA Black Box Warning
None (no FDA black box warning for systemic hydrocortisone; however, intrathecal administration is contraindicated due to risk of arachnoiditis).
| Common Effects | adrenal insufficiency |
| Serious Effects |
systemic fungal infectionsknown hypersensitivity to hydrocortisone or any excipient
| Precautions | Adrenal suppression: prolonged therapy can lead to secondary adrenocortical insufficiency; taper dosage gradually after long-term use., Increased susceptibility to infections: corticosteroids mask signs of infection; avoid live vaccines during immunosuppressive doses., Osteoporosis: long-term use increases risk; recommend calcium and vitamin D supplementation., Gastrointestinal effects: may cause peptic ulcers; use with caution in patients with ulcerative colitis, diverticulitis, or recent intestinal anastomoses., Ocular effects: risk of glaucoma, cataracts; monitor intraocular pressure with prolonged use., Psychiatric disturbances: may cause euphoria, insomnia, mood swings, or psychosis., Growth suppression in children: monitor growth in pediatric patients., Metabolic effects: hyperglycemia, sodium and fluid retention, hypokalemia, increased appetite, weight gain., Myopathy: acute myopathy with high doses, especially in patients with neuromuscular disorders., Vaccination: avoid live vaccines during immunosuppressive therapy. |
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| Breastfeeding |
| Hydrocortisone is excreted into breast milk in trace amounts (less than 1% of maternal dose). At typical anti-inflammatory doses, it is considered compatible with breastfeeding. However, high maternal doses (e.g., >40 mg/day) may potentially cause adrenal suppression in the infant; monitor infant for growth and development. |
| Lactation Rating | L2 |
| Teratogenic Risk | First trimester: Oral clefts slightly increased with first trimester exposure (odds ratio ~1.3-1.7). Second/third trimester: Fetal adrenal suppression, intrauterine growth restriction, premature rupture of membranes. Chronic high doses: Risk of adrenal insufficiency in neonate. Overall, benefits often outweigh risks for maternal conditions. |
| Fetal Monitoring | Maternal: Blood pressure, blood glucose, electrolyte levels, signs of infection. Fetal/neonatal: Ultrasound for growth restriction (especially in third trimester), assess for adrenal suppression (hypoglycemia, hypotension, poor feeding) in neonates exposed to high doses. |
| Fertility Effects | May cause menstrual irregularities and ovulatory dysfunction at high doses, potentially impairing fertility. Low or physiologic doses have minimal impact. Reversible upon dose reduction or discontinuation. |
| Food/Dietary | Avoid grapefruit juice as it may increase hydrocortisone levels. Limit sodium intake to reduce fluid retention. Maintain adequate potassium intake (e.g., bananas, oranges) to counter hypokalemia. |
| Clinical Pearls | Hydrocortisone is a short-acting glucocorticoid with mild mineralocorticoid activity. In adrenal crisis, administer IV hydrocortisone 100 mg stat, then 200 mg/day continuous infusion or divided doses. Taper gradually to avoid adrenal insufficiency. Monitor for hyperglycemia, hypokalemia, and osteoporosis with long-term use. Avoid abrupt withdrawal. |
| Patient Advice | Take with food or milk to reduce stomach upset. · Do not stop suddenly; follow doctor's tapering schedule to prevent withdrawal symptoms. · Report signs of infection (fever, sore throat) promptly as hydrocortisone can mask symptoms. · Avoid live vaccines while on therapy. · Carry a medical alert card if on long-term treatment. |