Hydrocortisone

Cortef includes primary/secondary adrenal insufficiency and congenital adrenal hyperplasia, plus selected endocrine, rheumatic/collagen, dermatologic/allergic, eye, respiratory, hematologic/neoplastic, nephrotic and GI inflammatory conditions. Disease-specific restrictions include adjunctive TB treatment with appropriate antimicrobials. Solu-Cortef IV/IM has its own broad disease list when oral treatment is not feasible and route fits; thrombocytopenic-purpura administration is IV only. Lists are not evidence that systemic steroids are preferred for every condition or safe for ordinary rash/infection.

Alkindi Sprinkle is pediatric adrenocortical-insufficiency replacement. Selected Rx 2.5% skin products relieve inflammatory/itching manifestations of steroid-responsive dermatoses; OTC 1% temporarily relieves minor skin irritation/rash and specified external itching. Cortenema is adjunctive ulcerative-colitis therapy, especially distal disease. Cortifoam is adjunctive distal ulcerative proctitis when corticosteroid enemas cannot be retained. These rectal indications are not automatic skin-cream or systemic uses.

The selected acetate 25 or 30 mg suppository label claims hemorrhoidal/anorectal inflammatory, proctitis and related uses, but its marketing category is unapproved drug other. A DailyMed listing, Rx-only marking and claimed indications do not establish FDA approval, safety/effectiveness findings or therapeutic equivalence. No FDA-approved suppository regimen is inferred.

The 2024 joint guideline for non-endocrine treatment generally permits stopping courses shorter than 3–4 weeks without taper/testing; longer therapy is tapered only when the treated disease is controlled and steroid is no longer required. This does not authorize stopping essential adrenal replacement. Ongoing physiologic-dose withdrawal may use clinical taper or clinician-selected morning cortisol assessment. No single taper, equivalence or stress-dose schedule applies to all formulations.

Cortef/Solu-Cortef: systemic fungal infection and hypersensitivity; Solu-Cortef also intrathecal administration, and IM corticosteroids in idiopathic thrombocytopenic purpura. Alkindi: hydrocortisone/component hypersensitivity; do not transplant the broad anti-inflammatory fungal contraindication into permission to withhold essential replacement. Rx skin products/suppositories: component hypersensitivity. Cortifoam additionally lists local obstruction, abscess, perforation, peritonitis, fresh anastomoses and extensive fistulas/sinus tracts; Cortenema lists systemic fungal infection and immediate/early postoperative ileocolostomy. Live vaccines are contraindicated at immunosuppressive steroid doses.

The reviewed systemic, skin and rectal labels have no boxed warning. Adrenal-crisis, infection, route and systemic-absorption hazards remain clinically serious; the suppository label’s lack of a box does not establish FDA approval.

Systemic reactions include increased appetite/weight, insomnia/mood change, fluid retention, hyperglycemia, hypertension, infection, skin fragility, muscle/bone disease, GI ulcer/bleeding, ocular effects and adrenal suppression. Skin/rectal products can irritate, burn or cause allergic contact dermatitis; absorbed exposure can add systemic effects. Trial frequencies are not comparable across routes, and pediatric Alkindi infections in a small uncontrolled study do not prove replacement-induced immunosuppression. Overexposure requires clinical/Poison Help (1-800-222-1222) review and supportive care; avoid abrupt withdrawal of required replacement or chronic therapy. Swallowed skin/rectal products require prompt professional advice.

CYP3A4 inducers such as rifampin, phenytoin, carbamazepine and phenobarbital can lower exposure and risk adrenal under-replacement; inhibitors such as azole antifungals, macrolides and ritonavir may increase exposure/toxicity. Grapefruit is listed among Alkindi inhibitors. Dose review may be needed. Estrogen wording differs: Alkindi notes increased cortisol-binding globulin and possible replacement-dose increase, while injected/older systemic labels describe increased steroid effects. Assess exact product, clinical response and estrogen change rather than apply one automatic opposite-direction adjustment.

NSAIDs/aspirin increase GI risk; salicylate levels can rise when steroid is withdrawn. Warfarin effects vary: monitor coagulation indices. Potassium-depleting agents/amphotericin B increase hypokalemia risk, with reported cardiac enlargement/HF with hydrocortisone; low potassium can increase digoxin arrhythmia risk. Glucose-lowering therapy may need adjustment. Cyclosporine exposure/activity can increase and seizures have occurred. Anticholinesterases/neuromuscular blockers may aggravate weakness; specialist review. Isoniazid and cholestyramine interactions and suppressed skin-test/vaccine responses also merit review. Local forms are not assumed interaction-free when significant absorption occurs.

Alkindi pediatric replacement includes accurate low-dose granules; monitor growth, weight and under/over-replacement. Do not swallow shells or use feeding tubes. OTC skin age≥2 directions do not erase anal-itching doctor review below 12. Rx skin children need least effective amount and avoidance of unprescribed occlusion. Cortifoam/Cortenema pediatric efficacy/safety are unestablished. Systemic pediatric indications are disease-specific; premature-infant cardiac/growth risks require monitoring. Older adults need cautious selection based on organ disease and concurrent medicines.

Reviewed labels do not provide one fixed renal/hepatic dose table. Renal insufficiency, hypertension/HF and sodium/potassium changes require careful monitoring; cirrhosis and hypothyroidism can enhance effects. Local skin/rectal absorption does not establish safety in advanced disease. Adjust to indication, clinical response and exact product rather than invent a universal renal percentage reduction.

Untreated adrenal insufficiency is dangerous; physiologic hydrocortisone replacement is not expected to produce major adverse pregnancy outcomes, with limited observational evidence. This does not establish safety of all supraphysiologic/local regimens. Higher systemic exposure carries fetal/neonatal adrenal-suppression concerns; substantial maternal courses warrant neonatal assessment. Cortisol occurs naturally in milk; replacement doses are not expected to harm infant/milk production, while high-dose systemic and local-label data require individualized assessment. Topical pregnancy use should avoid extensive/prolonged high exposure. Do not replace essential therapy or invent a universal milk-discard interval.

Hydrocortisone replaces deficient endogenous glucocorticoid activity and modifies metabolism/immune responses; pharmacologic exposure provides anti-inflammatory effects. It also has mineralocorticoid/salt-retaining properties. Primary adrenal insufficiency with aldosterone deficiency can require separate mineralocorticoid treatment; hydrocortisone is not automatically sufficient for every deficiency.

Alkindi adult study: oral bioavailability about 87%, median peak 0.75 hour; terminal half-life about 1.5 hours, protein binding≥90%. Liver/body metabolism and urinary conjugate elimination occur; plasma half-life is not duration of all steroid effects. IV sodium succinate is a soluble injected preparation, distinct from skin/rectal acetate. Skin absorption depends on vehicle, barrier integrity, inflammation and occlusion; rectal products can have substantial absorption. No percentage-to-systemic-milligram conversion or identical exposure between local forms inferred.

Review replacement versus inflammatory intent, exact product/route, duration and all steroid/interacting medicines. Assess adrenal adequacy, BP/edema, weight/glucose/electrolytes, infection, mood, growth and bone/eye risks as relevant. Alkindi monitors Cushing signs every 6 months, infants may need 3–4 month review; Solu-Cortef/Cortifoam advise IOP monitoring beyond 6 weeks. Skin extensive/occluded exposure may need urinary cortisol/ACTH evaluation; colitis efficacy requires clinical and proctologic assessment. PAI guidance favors clinical replacement assessment rather than routine hormonal dose titration; no universal lab schedule supplied.

Essential replacement patients need an individualized sick-day plan, emergency steroid identification/card and training with their prescribed injection kit. Persistent vomiting/severe illness or hypotension warrants urgent parenteral treatment and emergency evaluation. Do not independently stop prolonged systemic therapy. Use only intended skin/rectal route and supplied device; avoid unprescribed occlusion, eye contact and OTC rectal insertion. Report infection exposure, visual symptoms, severe mood change, GI bleeding or worsening colitis. Guidance for withdrawal of anti-inflammatory steroids is separate from lifelong replacement.

Tablet

5 mg white round scored, CORTEF 5; bottle 50, NDC 0009-0012-01.

Other tablet strengths

10 mg CORTEF 10, NDC 0009-0031-01; 20 mg CORTEF 20, NDC 0009-0044-01; bottles of 100.

Status

Prescription oral NDA product; current served PI revisedFebruary 2024, not a stock claim.

Pediatric granules

Alkindi 0.5, 1, 2, 5 mg in openable capsules; strengths refer to granule dose, not swallowed shell.

Injection

Solu-Cortef sodium succinate equivalent 100 mg plain powder or 100, 250, 500 or 1000 mg Act-O-Vial; reconstituted 100 or 250 mg in 2 mL, 500 mg in 4 mL, 1000 mg in 8 mL.

Skin

Selected OTC 1% base cream 10 mg/g; Rx 2.5% base cream/ointment 25 mg/g. Exact skin-only labeling, not ophthalmic/rectal preparations.

Rectal

Cortenema 100 mg base in 60 mL; Cortifoam 10% acetate, about 90 mg acetate/80 mg hydrocortisone per applicator.

Suppository status

Selected 25 or 30 mg acetate products explicitly unapproved drug other; no FDA approval/equivalence claim.

Scope

Reviewed U.S. products only; OTC monograph marketing is distinct from NDA/ANDA approval. Other esters, modified-release/non-U.S. products and combination preparations excluded.

Cortef/Solu-Cortef/Alkindi/Cortenema/Cortifoam generally 20–25°C; Rx skin 15–30°C, selected OTC 20–25°C. Alkindi original light-protective bottle, use within 60 days after opening. Solu-Cortef use promptly after aseptic preparation; full label limits room-temperature reconstituted/diluted use to 12 hours protected from light, refrigerated to 24 hours, then discard; exact microbiological preparation instructions govern. Cortifoam do not refrigerate, burn/puncture or expose to excessive heat. Suppositories 20–25°C, permitted 15–30°C excursions, protect from freezing/heat. Follow exact package/device instructions, not one shared expiry.