Hydrocortisone

Hydrocortisone is a naturally occurring glucocorticoid hormone (cortisol) and a widely used corticosteroid medication with anti-inflammatory, immunosuppressive, anti-pruritic, and anti-allergic effects. It is available in multiple formulations including oral tablets, topical creams and ointments, injectables, rectal foams and suppositories, eye/ear/nose drops, and buccal tablets, making it one of the most versatile corticosteroids in clinical medicine.

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Pharmacological Classification

• Drug Class: Corticosteroid

• Sub-class: Glucocorticoid

• ATC code: H02AB09 (systemic), D07AA02 (dermatologic), S01BA02 (ophthalmic)

• Molecular formula: C₂₁H₃₀O₅

• Synonyms: Cortisol, Hydrocortisone acetate (topical/injectable), Hydrocortisone sodium succinate (injectable)

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Mechanism of Action

Hydrocortisone binds to cytoplasmic glucocorticoid receptors, forming a complex that translocates into the nucleus. It modulates gene transcription, leading to:

• Downregulation of pro-inflammatory cytokines (IL-1, IL-2, TNF-α)

• Inhibition of COX-2 enzyme, reducing prostaglandin synthesis

• Decreased capillary permeability and leukocyte migration

• Suppression of T-lymphocyte proliferation and macrophage activation

• Reduced histamine release from mast cells

These actions result in potent anti-inflammatory, anti-proliferative, and immunosuppressive effects across tissues.

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Pharmaceutical Forms and Indications

1. Oral Tablets

• Hydrocortisone 10 mg / 20 mg tablets

• Indications:

  • Adrenal insufficiency (e.g., Addison’s disease)

  • Congenital adrenal hyperplasia (CAH)

  • Severe inflammation unresponsive to NSAIDs

  • Replacement therapy in secondary adrenal insufficiency

2. Injectable Forms

• Hydrocortisone sodium succinate (e.g., Solu-Cortef®)

• IV or IM for:

  • Acute adrenal crisis

  • Septic shock

  • Anaphylaxis (with antihistamines and epinephrine)

  • Status asthmaticus

  • Preoperative coverage in adrenal insufficiency

3. Topical Creams/Ointments

• Hydrocortisone 0.5%, 1%, 2.5% (e.g., Cortef®, Hytone®)

• Used for:

  • Eczema, dermatitis

  • Psoriasis (mild)

  • Insect bites

  • Allergic skin reactions

  • Pruritus ani or vulvae

4. Rectal Formulations

• Suppositories, foams, enemas

• Indications:

  • Ulcerative colitis (distal)

  • Proctitis

  • Hemorrhoids

5. Ophthalmic/Nasal/Ear Drops

• Hydrocortisone + antibiotics

• Indications:

  • Allergic conjunctivitis

  • Otitis externa

  • Inflammatory eye diseases

6. Buccal Tablets

• Corlan® 2.5 mg (UK)

• Used in:

  • Oral lichen planus

  • Aphthous ulcers

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Medical Uses

Endocrine Disorders

• Adrenal insufficiency (primary or secondary)

• Congenital adrenal hyperplasia

• Hypopituitarism

Inflammatory and Autoimmune Conditions

• Rheumatoid arthritis

• Systemic lupus erythematosus

• Dermatitis/eczema

• Severe asthma or COPD exacerbations

• Ulcerative colitis

• Temporal arteritis

• Severe allergic reactions

Emergency Situations

• Anaphylaxis (as adjunct)

• Acute adrenal crisis

• Sepsis (shock component)

Dermatological Applications

• Contact dermatitis

• Seborrheic dermatitis

• Insect bites

• Atopic eczema

• Lichen simplex

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Dosage and Administration

Oral

• Adrenal insufficiency:

  • 15–30 mg/day in divided doses (e.g., 10 mg morning, 5 mg early afternoon)

• Anti-inflammatory:

  • 20–240 mg/day, individualized

• Dosing considerations:

  • Circadian dosing preferred

  • Taper slowly after prolonged use

IV/IM

• 100–500 mg initially in emergencies

• Maintenance: 50–100 mg every 6–8 hours

• Mix with sterile water for injection

Topical

• Apply thinly 1–2 times/day

• Limit use to 7 days unless advised

Rectal

• Foam: 1–2 applications/day

• Suppository: once or twice daily

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Contraindications

• Untreated systemic infections (fungal, TB) without appropriate antimicrobials

• Known hypersensitivity to hydrocortisone

• Viral infections (e.g., herpes simplex, chickenpox) in the eye or skin

• Live vaccine administration during systemic use

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Precautions

• Tapering: Long-term users should taper gradually to avoid adrenal insufficiency

• Immunosuppression: Increased risk of infection (especially fungal, TB, herpes)

• Hypertension, diabetes, osteoporosis: Use cautiously

• Pediatric use: May suppress growth; monitor height and weight

• Geriatric patients: Higher risk of skin thinning, glaucoma, or osteoporosis

• Ocular: Avoid prolonged use due to risk of glaucoma or cataracts

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Adverse Effects

Systemic (oral/injectable)

• Adrenal suppression

• Cushingoid features (moon face, buffalo hump)

• Hyperglycemia

• Hypertension

• Gastric ulcer

• Osteoporosis

• Mood disturbances (euphoria, psychosis)

• Myopathy

• Immunosuppression

Topical

• Skin thinning

• Telangiectasia

• Perioral dermatitis

• Hypopigmentation

• Secondary infections (fungal, bacterial)

• Acneiform eruptions

Ocular

• Elevated intraocular pressure

• Posterior subcapsular cataracts

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Drug Interactions

• NSAIDs: Increased risk of GI ulceration and bleeding

• Diuretics: Additive risk of hypokalemia

• Antidiabetic agents: Decreased efficacy due to hyperglycemic effect

• Vaccines: Reduced efficacy and increased risk of infection with live vaccines

• CYP3A4 inducers/inhibitors:

  • Rifampin, phenytoin → ↓ hydrocortisone effect

  • Ketoconazole, erythromycin → ↑ levels of hydrocortisone

• Warfarin: Potential interaction affecting INR levels

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Use in Special Populations

Pregnancy

• Category C (US): Use if benefits outweigh risks

• Risk of low birth weight or fetal adrenal suppression with prolonged high doses

Breastfeeding

• Short-term use is acceptable

• High doses may suppress infant adrenal function

Pediatrics

• Risk of growth suppression with prolonged systemic use

• Use lowest effective dose for the shortest time

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Monitoring Parameters

• Blood pressure

• Blood glucose

• Serum potassium

• Bone mineral density (chronic use)

• Ophthalmologic exams (with prolonged use)

• Adrenal function (ACTH stimulation test if needed)

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Withdrawal and Tapering

Sudden discontinuation after prolonged use can lead to adrenal insufficiency:

Symptoms of withdrawal:

• Fatigue

• Hypotension

• Anorexia

• Nausea

• Hypoglycemia

• Arthralgia

Tapering protocols vary by duration of treatment:

• <3 weeks of use: taper may not be needed

• 3 weeks or high doses: gradual taper over weeks/months

• Assess morning cortisol levels or ACTH response

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Brand Names

• Oral: Hydrocortisone (generic), Cortef®

• Injectable: Solu-Cortef®, A-Hydrocort®, Hydrocortone®

• Topical: Hytone®, Locoid®, Cortaid®, Dermacort®

• Rectal: Anusol HC®, Colifoam®, Proctocort®

• Ophthalmic: Otosporin-HC®, Maxidex-HC®

• Buccal: Corlan® (UK)

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Storage

• Oral and injectable: Store at 20–25°C (68–77°F)

• Topical creams: Room temperature, avoid excess heat

• Rectal forms: Cool dry place

• Reconstituted vials (injectables): Use immediately or within 24 hours if refrigerated

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Summary

Hydrocortisone remains a first-line corticosteroid for both local and systemic inflammatory conditions. Its broad application, predictable pharmacodynamics, and availability in multiple formulations make it an essential drug in various therapeutic settings. Clinicians must, however, monitor closely for side effects, especially in chronic use, and educate patients on appropriate usage to minimize complications