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. |
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 | 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.
| Breastfeeding | Enters breast milk in low concentrations; M/P ratio approximately 0.2-0.5. Doses up to 20 mg/day (oral) or physiologic replacement considered compatible. High maternal doses may suppress infant adrenal function; monitor for growth and development. Use lowest effective dose. |
| 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. |
■ 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 infections (except when used for adrenal insufficiency with concomitant antifungal therapy)","Hypersensitivity to hydrocortisone or any component of the formulation","Intrathecal administration (contraindicated due to risk of arachnoiditis)","Administration of live or live-attenuated vaccines in patients receiving immunosuppressive doses","Relative: diabetes mellitus, hypertension, congestive heart failure, osteoporosis, glaucoma, cataracts, peptic ulcer disease, history of tuberculosis, recent surgery, pregnancy (use only if clearly needed)"]
| 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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| 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. |