Prednisone - Drug Monograph

Introduction

Prednisone is a synthetic glucocorticoid medication that belongs to the corticosteroid class of drugs. It is one of the most widely prescribed anti-inflammatory and immunosuppressive agents in clinical practice. First introduced in the 1950s, prednisone remains a cornerstone therapy for numerous inflammatory, autoimmune, and allergic conditions due to its potent anti-inflammatory and immunomodulatory effects.

Mechanism of Action

Prednisone is a prodrug that undergoes hepatic conversion to its active metabolite, prednisolone. The drug exerts its effects primarily through genomic mechanisms by binding to intracellular glucocorticoid receptors. This receptor-ligand complex translocates to the nucleus where it modulates gene transcription by:

• Binding to glucocorticoid response elements (GREs) to upregulate anti-inflammatory genes
• Inhibiting transcription factors such as NF-κB and AP-1 that promote inflammatory gene expression
• Reducing synthesis of pro-inflammatory cytokines (IL-1, IL-2, IL-6, TNF-α)
• Decreasing inflammatory cell migration and activation
• Inhibiting phospholipase A2, reducing prostaglandin and leukotriene production

The net effect is comprehensive suppression of inflammatory and immune responses at multiple levels.

Indications

• Rheumatoid arthritis
• Systemic lupus erythematosus
• Polymyalgia rheumatica
• Dermatologic conditions (pemphigus, severe psoriasis)
• Allergic states (severe allergic reactions, seasonal allergies)
• Ophthalmic inflammation
• Respiratory diseases (asthma, sarcoidosis)
• Hematologic disorders (autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura)
• Neoplastic diseases (palliative management of leukemias and lymphomas)
• Edematous states (nephrotic syndrome)
• Endocrine disorders (adrenal insufficiency)
• Gastrointestinal diseases (ulcerative colitis, Crohn's disease)
• Other inflammatory conditions (tuberculous meningitis, trichinosis)

• Acute gout flares
• COVID-19-related cytokine storm
• Organ transplantation rejection prophylaxis
• Bell's palsy
• Autoimmune hepatitis

Dosage and Administration

• Individualize dosage based on disease severity and patient response
• Use the lowest effective dose for the shortest duration possible
• Administer with food to reduce gastrointestinal irritation

• Anti-inflammatory/immunosuppressive: 5-60 mg daily in single or divided doses
• Adrenal insufficiency: 4-5 mg/m² daily (typically 5-7.5 mg daily)
• Acute exacerbations: Higher doses (40-60 mg daily) followed by taper

• Geriatric patients: Start at lower end of dosing range due to increased susceptibility to adverse effects
• Hepatic impairment: Monitor closely; may require dose adjustment due to impaired conversion to active metabolite
• Renal impairment: No specific dose adjustment required
• Pediatric patients: 0.1-2 mg/kg/day in divided doses (based on condition severity)

• Oral administration only
• Tablets should be swallowed whole with water
• Morning administration preferred to minimize HPA axis suppression
• For long-term therapy, gradual tapering is essential to avoid adrenal insufficiency

Pharmacokinetics

• Well absorbed from gastrointestinal tract (90% bioavailability)
• Peak plasma concentrations reached within 1-2 hours

• Volume of distribution: 0.4-1 L/kg
• Protein binding: 70-90% primarily to transcortin (corticosteroid-binding globulin) and albumin
• Crosses placenta and appears in breast milk

• Hepatic metabolism via CYP3A4 to active metabolite prednisolone
• Also undergoes reduction and conjugation
• First-pass metabolism is minimal

• Half-life: 2-3 hours (prednisone), 2-4 hours (prednisolone)
• Duration of biological effect: 18-36 hours
• Excretion: Primarily renal (metabolites), with some fecal elimination

Contraindications

• Systemic fungal infections (unless concurrent antifungal therapy)
• Known hypersensitivity to prednisone or any component of the formulation
• Live virus vaccinations in immunosuppressed patients
• Absolute contraindications may be relative in life-threatening situations

Warnings and Precautions

• Corticosteroids may cause serious and fatal infections
• Prolonged use may cause hypothalamic-pituitary-adrenal (HPA) axis suppression
• May mask signs of infection and cause new infections

• Adrenal suppression: May occur with prolonged therapy (>2 weeks); requires gradual withdrawal
• Infections: Increased susceptibility to infections; may reactivate latent infections (TB, herpes)
• Osteoporosis: Significant risk with prolonged therapy; consider prophylaxis
• Ocular effects: May cause cataracts, glaucoma; regular ophthalmologic exams recommended
• Psychiatric effects: May cause euphoria, insomnia, mood swings, depression, or psychosis
• Cardiovascular risk: May cause fluid retention, hypertension, hypokalemia
• Metabolic effects: Hyperglycemia, weight gain, lipid abnormalities
• Gastrointestinal: Increased risk of peptic ulcer disease, pancreatitis
• Musculoskeletal: Myopathy, muscle weakness, osteonecrosis (particularly femoral head)
• Dermatologic: Impaired wound healing, skin fragility, purpura

Drug Interactions

• Anticoagulants: Altered anticoagulant effect (increased or decreased)
• Antidiabetic agents: Reduced hypoglycemic effect
• CYP3A4 inducers (rifampin, phenytoin, carbamazepine): Reduced prednisone efficacy
• CYP3A4 inhibitors (ketoconazole, itraconazole): Increased prednisone exposure
• Diuretics: Enhanced potassium-wasting effects
• NSAIDs: Increased risk of GI ulceration
• Vaccines: Reduced immune response to vaccines; avoid live vaccines
• Digitalis glycosides: Increased risk of arrhythmias due to hypokalemia

Adverse Effects

• Insomnia
• Increased appetite
• Weight gain
• Fluid retention
• Mood changes
• Hyperglycemia
• Dyspepsia

• Hypertension
• Hirsutism
• Acne
• Moon facies
• Buffalo hump
• Easy bruising
• Striae

• Adrenal insufficiency
• Severe infections
• Osteoporosis with fractures
• Aseptic necrosis of bone
• Peptic ulcer disease with hemorrhage
• Pancreatitis
• Posterior subcapsular cataracts
• Glaucoma
• Psychosis
• Severe hyperglycemia
• Myopathy
• Thromboembolic events

Monitoring Parameters

• Complete medical history and physical examination
• Blood pressure, weight, height (in children)
• CBC with differential
• Electrolytes, glucose, lipid profile
• Bone density scan (if long-term therapy anticipated)
• Tuberculosis screening
• Ophthalmologic examination

• Blood pressure at each visit
• Weight regularly
• Fasting blood glucose periodically
• Electrolytes (particularly potassium)
• Bone density annually if long-term therapy
• Growth velocity in children
• Signs of infection
• Ophthalmologic exams every 6-12 months with long-term use
• Assessment for adrenal insufficiency during and after taper

Patient Education

• Take exactly as prescribed; do not stop abruptly
• Take with food to minimize stomach upset
• Report any signs of infection (fever, sore throat)
• Monitor for weight gain, swelling, or mood changes
• Inform all healthcare providers about prednisone use
• Carry medical identification indicating steroid use
• Regular follow-up appointments are essential

• Maintain calcium-rich diet (1500 mg daily) and vitamin D supplementation
• Regular weight-bearing exercise to maintain bone health
• Sodium restriction to minimize fluid retention
• Carbohydrate-controlled diet to manage blood glucose
• Avoid alcohol and NSAIDs to reduce GI risk

• Severe abdominal pain
• Black or tarry stools
• Vision changes
• Shortness of breath or chest pain
• Severe headache
• Signs of adrenal insufficiency (weakness, fatigue, nausea, vomiting)

References

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2. Fardet L, Petersen I, Nazareth I. Monitoring of patients on long-term glucocorticoid therapy: A population-based cohort study. Medicine (Baltimore). 2015;94(15):e647.

3. Coutinho AE, Chapman KE. The anti-inflammatory and immunosuppressive effects of glucocorticoids, recent developments and mechanistic insights. Mol Cell Endocrinol. 2011;335(1):2-13.

4. Prednisone [package insert]. U.S. Food and Drug Administration; 2022.

5. Axelrod L, Koch-Weser J, Williams TF. Glucocorticoid therapy. Medicine (Baltimore). 1978;57(1):39-59.

6. American College of Rheumatology. Guidelines for glucocorticoid-induced osteoporosis. Arthritis Care Res. 2017;69(8):1095-1110.

7. Waljee AK, Rogers MAM, Lin P, et al. Short term use of oral corticosteroids and related harms among adults in the United States: population based cohort study. BMJ. 2017;357:j1415.

8. Strehl C, Bijlsma JW, de Wit M, et al. Defining conditions where long-term glucocorticoid treatment has an acceptably low level of harm to facilitate implementation of existing recommendations: viewpoints from an EULAR task force. Ann Rheum Dis. 2016;75(6):952-957.