Hydrocortisone - Drug Monograph

Introduction

Hydrocortisone is a naturally occurring corticosteroid hormone produced by the adrenal cortex. As a pharmaceutical agent, it represents the synthetic version of cortisol and serves as a fundamental anti-inflammatory and immunosuppressive medication. Hydrocortisone is available in multiple formulations including oral tablets, topical creams/ointments, injectable solutions, and rectal preparations, making it one of the most versatile corticosteroids in clinical practice.

Mechanism of Action

Hydrocortisone exerts its effects through binding to intracellular glucocorticoid receptors, forming complexes that migrate to the cell nucleus. These complexes bind to glucocorticoid response elements on DNA, modulating gene transcription. This results in:

• Inhibition of inflammatory cytokine production (IL-1, IL-2, IL-6, TNF-α)
• Decreased migration of inflammatory cells to sites of inflammation
• Stabilization of lysosomal membranes
• Inhibition of phospholipase A2 activity, reducing prostaglandin and leukotriene synthesis
• Suppression of immune cell function and antibody production

Indications

• Adrenal insufficiency (replacement therapy)
• Inflammatory disorders (rheumatoid arthritis, collagen diseases)
• Dermatological conditions (eczema, psoriasis, contact dermatitis)
• Allergic states (severe allergic reactions, angioedema)
• Ophthalmic inflammation
• Ulcerative colitis (rectal formulations)
• Shock (hemodynamic support in septic shock)

• Prevention of antiemetic-induced nausea
• Adjunct in bacterial meningitis
• Thyroid storm
• Acute spinal cord injury

Dosage and Administration

• Adults: 15-25 mg daily in 2-3 divided doses (2/3 in morning, 1/3 in afternoon)
• Children: 8-12 mg/m²/day in 3 divided doses

• Adults: 20-240 mg daily in divided doses
• Children: 2-8 mg/kg/day in 3-4 divided doses

• Apply thin film to affected area 2-4 times daily

• Initial dose: 100-500 mg IV, repeated every 2-6 hours as needed

• Hepatic impairment: Dose reduction may be necessary
• Renal impairment: No specific dose adjustment required
• Elderly: Use lowest effective dose due to increased susceptibility to adverse effects

Pharmacokinetics

Contraindications

• Systemic fungal infections (unless treating adrenal insufficiency)
• Known hypersensitivity to hydrocortisone or components
• Live virus vaccinations during immunosuppressive therapy
• Idiopathic thrombocytopenic purpura (IM administration)
• Intrathecal administration

Warnings and Precautions

• Increased mortality in patients with septic shock
• Adrenal suppression with prolonged use (>2 weeks)
• Increased intraocular pressure with ophthalmic use
• Psychiatric reactions including euphoria, insomnia, mood swings
• Kaposi's sarcoma reported with corticosteroid therapy
• Avoid abrupt withdrawal after prolonged therapy
• Monitor for hyperglycemia, hypertension, and fluid retention
• Increased risk of gastrointestinal perforation in patients with GI disorders
• Reduced growth velocity in pediatric patients

Drug Interactions

• Enzyme inducers (phenytoin, rifampin, carbamazepine): Increased hydrocortisone clearance → reduced efficacy
• Enzyme inhibitors (ketoconazole, itraconazole): Decreased hydrocortisone clearance → increased toxicity risk
• Anticoagulants: Altered response to anticoagulants
• Diuretics: Enhanced potassium wasting
• NSAIDs: Increased risk of GI ulceration
• Vaccines: Reduced antibody response; increased risk of infection with live vaccines
• Diabetes medications: May require dose adjustment due to hyperglycemic effects

Adverse Effects

• Fluid retention
• Weight gain
• Hypertension
• Glucose intolerance
• Mood changes
• Insomnia
• Increased appetite

• Adrenal suppression
• Opportunistic infections
• Osteoporosis/vertebral fractures
• Avascular necrosis
• Peptic ulcer disease
• Cataracts/glaucoma
• Hypokalemia
• Myopathy
• Anaphylaxis (rare)

• Skin atrophy
• Striae
• Telangiectasia
• Hypopigmentation
• Contact dermatitis

Monitoring Parameters

• Blood pressure
• Weight
• Serum electrolytes
• Blood glucose
• Bone density (if long-term therapy anticipated)
• Ophthalmologic exam

• Blood pressure regularly
• Serum glucose (especially in diabetics)
• Weight changes
• Signs of infection
• Growth monitoring in children
• Mood/behavior changes
• Signs of adrenal insufficiency upon withdrawal

• Bone density scans annually
• Ophthalmologic exams annually
• HgbA1c every 3-6 months

Patient Education

• Take with food to minimize GI upset
• Do not stop medication abruptly; follow tapering schedule precisely
• Report signs of infection (fever, sore throat) immediately
• Monitor blood sugar regularly if diabetic
• Report vision changes, significant weight gain, or swelling
• Use lowest effective dose for shortest duration possible
• Carry medical identification indicating steroid use
• Topical: Use sparingly; avoid occlusive dressings unless directed
• Avoid live vaccines during therapy
• Inform all healthcare providers of hydrocortisone use
• Report mood changes, depression, or sleep disturbances

References

1. NIH National Library of Medicine. Hydrocortisone - Drug Information. StatPearls [Internet]. 2023. 2. American Society of Health-System Pharmacists. AHFS Drug Information. Hydrocortisone monograph. 2023. 3. Joint Formulary Committee. British National Formulary. London: BMJ Group and Pharmaceutical Press; 2023. 4. Czock D, Keller F, Rasche FM, et al. Pharmacokinetics and pharmacodynamics of systemically administered glucocorticoids. Clin Pharmacokinet. 2005;44(1):61-98. 5. Liu D, Ahmet A, Ward L, et al. A practical guide to the monitoring and management of the complications of systemic corticosteroid therapy. Allergy Asthma Clin Immunol. 2013;9(1):30. 6. FDA prescribing information: Hydrocortisone tablets, injection, and topical formulations. 2023. 7. Bornstein SR, Allolio B, Arlt W, et al. Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2016;101(2):364-389.