HYDROCORTISONE ACETATE
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 acetate is a synthetic glucocorticoid that binds to the glucocorticoid receptor, leading to modulation of gene expression. It exerts anti-inflammatory, immunosuppressive, and vasoconstrictive effects by inhibiting phospholipase A2, reducing prostaglandin and leukotriene synthesis, and suppressing cytokine production.
| Metabolism | Hepatic metabolism via CYP3A4, also reduction by 20-ketosteroid reductases; major metabolites include tetrahydrocortisone and tetrahydrocortisol. |
| Excretion | Renal: ~80% as metabolites (glucuronide and sulfate conjugates) and <1% unchanged; fecal: <5% via biliary elimination. |
| Half-life | Terminal elimination half-life: 1-2 hours for endogenous hydrocortisone; with acetate ester, extended to ~2-4 hours due to slower absorption and hydrolysis. Clinical context: Duration of action exceeds half-life due to intracellular receptor binding. |
| Protein binding | 90-95% bound primarily to corticosteroid-binding globulin (CBG, transcortin) and albumin; hydrocortisone acetate has similar binding profile as free hydrocortisone. |
| Volume of Distribution | 0.3-0.4 L/kg (for hydrocortisone base). Vd is relatively small, consistent with extensive protein binding and limited tissue penetration; distributes into extracellular fluid and poorly into CNS. |
| Bioavailability | Oral: not applicable (acetate form not for oral use); intramuscular: 100% (administered as suspension); topical: minimal systemic absorption (~1-2% with intact skin, higher with damaged skin); rectal: 20-30% (enema preparation). |
| Onset of Action | Intravenous: minutes (as free alcohol); intramuscular: 1-2 hours; topical: variable, typically 3-5 days for anti-inflammatory effect; intra-articular: 1-2 days; rectal (enema): within 2-4 hours. |
| Duration of Action | Intramuscular: 8-12 hours; intra-articular: up to 2-4 weeks; topical: 1-2 weeks with repeated application; rectal: 6-12 hours. Clinical notes: Duration is prolonged with depot formulations due to slow ester hydrolysis. |
Hydrocortisone acetate is typically administered as a topical, intra-articular, intradermal, or rectal preparation. For intra-articular use, adult dose: 5-50 mg (depending on joint size) every 1-2 weeks. For rectal use, 25 mg (one suppository) twice daily or 1 application of foam or enema (10% or 1% respectively) once or twice daily. For intradermal injection, 1-2 mL (25 mg/mL) into lesion every 1-2 weeks. Note: Systemic dosing is not applicable as it is not used for systemic effects due to low bioavailability.
| Dosage form | OINTMENT |
| Renal impairment | No dosage adjustment required for topical, intra-articular, or rectal formulations due to minimal systemic absorption. For extensive or prolonged use in renal impairment, monitor for systemic effects (e.g., fluid retention). No specific GFR-based guidelines. |
| Liver impairment | No dosage adjustment required for topical, intra-articular, or rectal formulations due to minimal systemic absorption. In severe hepatic impairment (Child-Pugh C), consider potential for increased systemic exposure if used on large areas or damaged skin; monitor for adverse effects. |
| Pediatric use | Topical: Apply sparingly to affected area once or twice daily. Rectal: Children 2-12 years: 25 mg suppository once daily (or half adult dose depending on formulation). Intra-articular: Not typically recommended; consult specialist. Doses should be based on body surface area and severity; avoid prolonged use. |
| 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 acetate is excreted into breast milk in low amounts (M/P ratio approximately 0.25). Doses up to 40 mg/day are considered compatible with breastfeeding. Higher doses may require monitoring for infant adrenal suppression. |
| Teratogenic Risk | First trimester: Increased risk of cleft palate (odds ratio ~1.3-3.4) with systemic use. Second and third trimesters: Possible fetal growth restriction, adrenal suppression, and oligohydramnios with prolonged high-dose therapy. |
■ FDA Black Box Warning
None
| Common Effects | adrenal insufficiency |
| Serious Effects |
["Hypersensitivity to hydrocortisone acetate or any component","Systemic fungal infections","Untreated localized infections (topical use)","Administration of live virus vaccines (systemic use at immunosuppressive doses)","Idiopathic thrombocytopenic purpura (intramuscular use)"]
| Precautions | ["Systemic absorption from topical application may produce reversible HPA axis suppression, Cushing's syndrome, hyperglycemia, and glucosuria.","Use with caution in patients with diabetes, osteoporosis, hypertension, congestive heart failure, or tuberculosis.","May mask signs of infection; increased susceptibility to infections.","Live or attenuated vaccines contraindicated with high doses.","Abrupt withdrawal may cause adrenal insufficiency.","Pediatric patients may be more susceptible to systemic toxicity."] |
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| Geriatric use | Use with caution due to increased risk of skin atrophy with topical use. Intra-articular: Use lowest effective dose. Rectal: No specific adjustment, but monitor for fluid retention and electrolyte imbalance. Consider age-related renal and hepatic function decline. |
| Fetal Monitoring | Monitor maternal blood pressure, blood glucose, and signs of infection. Fetal growth ultrasound if prolonged use. Newborns exposed in utero should be monitored for adrenal insufficiency. |
| Fertility Effects | No direct impairment of fertility reported. Indirect effects from underlying condition (e.g., autoimmune disease) may affect fertility. |