Hydrocortisone Acetate

Hydrocortisone acetate is a synthetic corticosteroid, specifically the 21-acetate ester of hydrocortisone, the adrenal hormone better known as cortisol. It belongs to the glucocorticoid family of steroids and has the molecular formula C23H32O6. Placing an acetate group on the 21-hydroxyl makes the molecule more lipophilic and only sparingly soluble in water, and this ester is gradually split within tissue to liberate active hydrocortisone ^[1]. How much drug is released and absorbed depends strongly on the carrier; hydrophilic microemulsions and gels behave differently from ointments, and hydrophobic bases tend to hold the steroid near the surface so that it stays where it is applied and less passes into the circulation ^[1].

Classed as a mild or low-potency topical corticosteroid, hydrocortisone acetate is used to ease the redness, swelling, itching and scaling of eczema, contact dermatitis, insect bites and other inflammatory skin complaints. In dermatology trials it is often the reference mild treatment against which newer drugs are judged; a meta-analysis in atopic dermatitis found that topical tacrolimus was more effective than hydrocortisone acetate on the face and body ^[2], and the compound still serves as the background low-potency steroid in current pediatric eczema studies of biologic therapies ^[3]. Beyond the skin it is compounded into rectal creams and suppositories for hemorrhoids and anorectal inflammation, and prepared as a sterile microcrystalline suspension for injection into joints, bursae and inflamed soft tissue.

The parent hormone hydrocortisone was patented in the 1930s and approved for medical use in the early 1940s, growing out of the corticosteroid research that earned Kendall, Reichstein and Hench a share of the 1950 Nobel Prize; hydrocortisone itself appears on the World Health Organization's List of Essential Medicines. The acetate ester is manufactured as a fine, light-sensitive powder, and pharmacopeias require it to be shielded from light, since ultraviolet exposure breaks the steroid into several photoproducts and can strip away its anti-inflammatory activity ^[4]. In much of the world low-strength hydrocortisone preparations are sold over the counter for short-term skin use, while stronger creams, rectal products and injectable suspensions are prescription or pharmacy-supervised items.

Mild hydrocortisone is one of the safest steroids, and low strengths are available without a prescription. Used briefly it rarely causes trouble, but overuse or long use, especially on thin skin like the face or under a dressing, can thin the skin, cause stretch marks, spider veins, or acne-like bumps. It should not be put on infected or broken skin without advice, since steroids can mask or worsen infection. On large areas or with heavy use, enough can absorb to affect the body, though this is uncommon at low potency. Avoid getting it in the eyes, and check with a clinician before using it on young children for more than a few days.

Hydrocortisone acetate is the weakest of the commonly used glucocorticoids and is mostly given topically, rectally or into a joint, so systemic interactions depend on how much actually reaches the circulation. Absorption is higher across inflamed or eroded skin and rectal mucosa, under occlusion, and over large surface areas, which is when the interactions below start to matter.

Hydrocortisone is a CYP3A4 substrate. Strong inhibitors such as ritonavir, cobicistat, itraconazole and clarithromycin raise systemic exposure, and that same route has produced adrenal suppression with other corticosteroids; inducers such as rifampicin, phenytoin and carbamazepine reduce it.

The pharmacodynamic interactions are the usual glucocorticoid set: additive gastrointestinal ulceration risk with NSAIDs, deeper potassium loss with thiazide and loop diuretics or amphotericin B, opposition to insulin and oral antidiabetic drugs, and a weakened response to vaccination.

Checking a whole stack? Run it through interactions + stacks.