Mechanism of action
Prednisone is a prodrug that is converted by hepatic 11β-hydroxysteroid dehydrogenase to its active metabolite, prednisolone. Prednisolone binds to cytoplasmic glucocorticoid receptors (GR), and the GR-ligand complex translocates to the nucleus where it modulates gene transcription.
Anti-inflammatory effects are mediated by:
- Inhibition of phospholipase A2 via induction of lipocortin-1 (annexin-1), reducing arachidonic acid release and subsequent prostaglandin and leukotriene synthesis
- Decreased production of pro-inflammatory cytokines (IL-1, IL-2, IL-6, TNF-α, IFN-γ)
- Reduction in capillary permeability and leukocyte migration to sites of inflammation
- Stabilization of lysosomal membranes
Immunosuppressive effects include:
- Inhibition of T-cell proliferation and cytokine production
- Reduced B-cell antibody production
- Decreased macrophage and dendritic cell function
- Redistribution of lymphocytes from circulation to lymphoid tissue
Prednisone also has metabolic effects through glucocorticoid activity: increased gluconeogenesis, protein catabolism, lipolysis, and insulin resistance. It exhibits minimal mineralocorticoid activity compared to hydrocortisone.
- Prednisone is a prodrug converted to prednisolone in the liver; use prednisolone in severe hepatic impairment.
- Chronic use (>2-3 weeks) suppresses the HPA axis; taper gradually to prevent adrenal crisis.
- Adverse effects: Cushing syndrome, osteoporosis, avascular necrosis, hyperglycemia, increased infection risk, peptic ulcers.
- Live vaccines are contraindicated during immunosuppressive glucocorticoid therapy.
- Screen for latent tuberculosis before starting chronic glucocorticoid therapy; consider PCP prophylaxis if ≥20 mg/day for ≥1 month.
- CYP3A4 inducers (rifampin, phenytoin) decrease prednisone efficacy; inhibitors (ketoconazole) increase toxicity.
- Combination with NSAIDs significantly increases gastrointestinal bleeding risk; use gastroprotection.
- Morning dosing mimics physiologic cortisol and reduces HPA suppression and insomnia.
Indications
Prednisone is indicated for a wide range of inflammatory, autoimmune, and allergic conditions:
Respiratory
- Asthma exacerbations (acute management)
- Chronic obstructive pulmonary disease (COPD) exacerbations
- Allergic bronchopulmonary aspergillosis
- Sarcoidosis
- Hypersensitivity pneumonitis
Rheumatologic and autoimmune
- Rheumatoid arthritis
- Systemic lupus erythematosus (SLE)
- Polymyalgia rheumatica and giant cell arteritis
- Dermatomyositis and polymyositis
- Vasculitis syndromes
Dermatologic
- Severe atopic dermatitis and eczema
- Pemphigus and bullous pemphigoid
- Severe allergic contact dermatitis
Hematologic and oncologic
- Immune thrombocytopenic purpura (ITP)
- Autoimmune hemolytic anemia
- Lymphomas and leukemias (part of chemotherapy regimens)
- Multiple myeloma
Gastrointestinal
- Inflammatory bowel disease (Crohn disease, ulcerative colitis)
- Autoimmune hepatitis
Renal
- Nephrotic syndrome (minimal change disease)
- Acute interstitial nephritis
Neurologic
- Multiple sclerosis exacerbations
- Cerebral edema (though dexamethasone is preferred)
Other
- Organ transplant rejection prophylaxis and treatment
- Acute gout (when NSAIDs or colchicine contraindicated)
- Severe allergic reactions
- Addison disease (replacement therapy, though hydrocortisone preferred)
Pharmacokinetics
Absorption: Prednisone is well absorbed orally with bioavailability of 80-90%. Peak plasma concentrations occur within 1-2 hours.
Distribution: Prednisone is widely distributed with a volume of distribution of approximately 0.4-1 L/kg. It is 70-90% protein-bound, primarily to albumin and corticosteroid-binding globulin (transcortin).
Metabolism: Prednisone undergoes rapid hepatic conversion to its active form, prednisolone, via 11β-hydroxysteroid dehydrogenase type 1. Prednisolone is further metabolized by hepatic enzymes. In severe liver disease, conversion to prednisolone may be impaired, and prednisolone may be preferred.
Excretion: Metabolites are primarily excreted renally. The elimination half-life of prednisone is 2-3 hours, while prednisolone has a half-life of 3-4 hours. The biologic half-life (duration of HPA suppression) is 18-36 hours, longer than the plasma half-life.
Special populations: In hypothyroidism, clearance is decreased; in hyperthyroidism, clearance is increased. Renal impairment does not significantly alter pharmacokinetics.
Adverse effects
Adverse effects are dose- and duration-dependent. Short courses (<2 weeks) generally carry lower risk.
Endocrine and metabolic
- HPA axis suppression with prolonged use (>2-3 weeks), risking adrenal insufficiency upon abrupt withdrawal
- Cushing syndrome: moon facies, buffalo hump, central obesity, striae, easy bruising
- Hyperglycemia and precipitation or worsening of diabetes mellitus
- Dyslipidemia
- Growth retardation in children
Musculoskeletal
- Osteoporosis and increased fracture risk (inhibits osteoblasts, increases osteoclast activity)
- Avascular necrosis (osteonecrosis), especially of femoral and humeral heads
- Myopathy (proximal muscle weakness)
Cardiovascular
- Hypertension (mineralocorticoid effects)
- Fluid retention and edema
- Increased risk of atherosclerosis
Gastrointestinal
- Peptic ulcer disease (especially when combined with NSAIDs)
- Pancreatitis
- Increased appetite and weight gain
- Nausea
Ophthalmic
- Cataracts (posterior subcapsular)
- Glaucoma and increased intraocular pressure
Dermatologic
- Skin thinning and fragility
- Impaired wound healing
- Acne
- Hirsutism
Psychiatric
- Mood changes: euphoria, depression, anxiety
- Psychosis (steroid psychosis)
- Insomnia
- Cognitive impairment
Immunologic and infectious
- Increased susceptibility to infections, including opportunistic infections (Pneumocystis jirovecii, tuberculosis, fungal)
- Reactivation of latent infections (tuberculosis, hepatitis B, strongyloidiasis)
- Impaired vaccine response (live vaccines contraindicated)
Hematologic
- Leukocytosis (neutrophilia with lymphopenia)
- Eosinopenia
Other
- Hypersensitivity reactions (rare)
Contraindications and warnings
Contraindications
- Hypersensitivity to prednisone or any component
- Systemic fungal infections (absolute contraindication)
- Administration of live or live-attenuated vaccines in patients receiving immunosuppressive doses
Warnings and precautions
HPA axis suppression: Prolonged use (>2-3 weeks) suppresses endogenous cortisol production. Taper gradually to allow HPA axis recovery. Abrupt discontinuation can precipitate adrenal crisis (hypotension, shock, hypoglycemia). Patients may require stress-dose steroids during illness, surgery, or trauma for up to 1 year after discontinuation.
Infections: Screen for latent tuberculosis (PPD or IGRA) before initiating therapy. Consider Pneumocystis jirovecii prophylaxis in high-risk patients (e.g., prednisone ≥20 mg/day for >1 month). Avoid live vaccines.
Peptic ulcer disease: Use with caution in patients with history of PUD. Consider gastroprotection with proton pump inhibitors when combined with NSAIDs.
Osteoporosis prevention: For patients on long-term therapy, ensure adequate calcium (1000-1500 mg/day) and vitamin D (800-1000 IU/day). Consider bisphosphonates for high-risk patients.
Diabetes: Monitor blood glucose closely; hyperglycemia is common.
Psychiatric effects: Use with caution in patients with history of psychiatric disorders. Monitor for mood changes and psychosis.
Ophthalmic: Monitor for cataracts and glaucoma with chronic use.
Pregnancy and lactation: Pregnancy category C (FDA). Prednisone crosses the placenta but is partially inactivated. May be used when benefits outweigh risks; preferred over fluorinated corticosteroids (betamethasone, dexamethasone) which cross placenta more readily. Monitor newborns for adrenal insufficiency. Small amounts enter breast milk; generally considered compatible with breastfeeding at low-to-moderate doses.
Hepatic impairment: Since prednisone requires hepatic conversion to prednisolone, patients with severe liver disease may have reduced drug efficacy. Consider using prednisolone instead.
Pediatric: Growth monitoring is essential; long-term use can cause growth retardation.
Drug interactions
CYP3A4 interactions
Prednisone and prednisolone are metabolized by CYP3A4.
- CYP3A4 inducers (rifampin, phenytoin, carbamazepine, phenobarbital): decrease prednisone levels, reducing efficacy
- CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir, clarithromycin, grapefruit juice): increase prednisone levels, increasing toxicity risk
NSAIDs and antiplatelet agents
Combination increases risk of gastrointestinal bleeding and peptic ulceration. Use gastroprotection if co-administration necessary.
Vaccines
- Live vaccines (MMR, varicella, yellow fever, intranasal influenza) are contraindicated during immunosuppressive therapy
- Inactivated vaccines may have reduced immunogenicity
Diuretics (thiazides, loop diuretics)
Glucocorticoids cause potassium loss; concurrent use increases hypokalemia risk. Monitor potassium levels.
Antidiabetic agents
Prednisone causes hyperglycemia; may require dose adjustment of insulin or oral hypoglycemic agents.
Anticoagulants (warfarin)
Variable effect on INR. Monitor INR closely and adjust warfarin dosing as needed.
Fluoroquinolones
Combination increases risk of tendon rupture, particularly Achilles tendon.
Anticholinesterases
Glucocorticoids may antagonize anticholinesterase effects in myasthenia gravis, potentially worsening muscle weakness.
Other immunosuppressants
Additive immunosuppression increases infection risk. Use caution with combinations (e.g., azathioprine, methotrexate, cyclosporine).
Clinical pearls
- Tapering is essential after >2-3 weeks of use to prevent adrenal crisis. Common taper: reduce by 5-10 mg every 1-2 weeks until reaching physiologic dose (~5 mg), then taper more slowly.
- Morning dosing mimics physiologic cortisol secretion and may reduce HPA suppression and insomnia.
- Prednisone requires hepatic activation to prednisolone. In severe liver disease, prednisolone is preferred as it is already active.
- "Steroid-sparing" agents (methotrexate, azathioprine, mycophenolate) are often used in chronic inflammatory conditions to allow lower prednisone doses and reduce toxicity.
- Stress-dose steroids may be needed during surgery, severe illness, or trauma in patients currently on or recently discontinued from chronic glucocorticoid therapy, as the HPA axis may not respond adequately to stress.
- Pneumocystis jirovecii pneumonia (PCP) prophylaxis (trimethoprim-sulfamethoxazole) should be considered in patients on prednisone ≥20 mg/day for ≥1 month, especially with other immunosuppression.
- Osteoporosis prophylaxis: All patients on long-term glucocorticoids should receive calcium, vitamin D, and weight-bearing exercise counseling. DEXA scan and bisphosphonate therapy should be considered.
- Alternate-day dosing may reduce HPA suppression and growth effects in children requiring chronic therapy, though not suitable for all conditions.
- Moon facies, buffalo hump, and central obesity are classic Cushingoid features that develop with chronic supraphysiologic dosing.
- Avascular necrosis can occur even with short courses; highest risk with high doses and in patients with SLE, sickle cell disease, or alcohol use.
- In COPD exacerbations, a 5-day course of prednisone (40 mg daily) is as effective as longer courses and reduces adverse effects.
- GI bleeding risk is highest when prednisone is combined with NSAIDs or anticoagulants. Consider PPI prophylaxis.
- Hyperglycemia can be severe; some patients develop steroid-induced diabetes requiring insulin.
- Psychiatric side effects (mood lability, insomnia, psychosis) are more common at higher doses and can occur even with short courses. Warn patients and families.
CUSHINGOID for adverse effects: Cataracts, Ulcers (peptic), Skin thinning/Striae, Hypertension/Hyperglycemia, Infections, Necrosis (avascular), Growth retardation, Osteoporosis, Immunosuppression, Depression/psychosis.
Practice questions
1. A 35-year-old woman with systemic lupus erythematosus has been taking prednisone 60 mg daily for 6 weeks for a severe flare. Her symptoms have improved, and her physician plans to taper the dose. She is concerned about stopping the medication. Which of the following is the primary reason for tapering prednisone rather than abruptly discontinuing it?
2. A 58-year-old man with rheumatoid arthritis has been on prednisone 15 mg daily for 8 months. He now complains of progressive hip pain that worsens with weight-bearing. Physical examination reveals limited internal rotation of the right hip. X-ray shows a crescent sign and flattening of the femoral head. Which adverse effect of chronic glucocorticoid therapy is most likely responsible?
3. A 42-year-old man with newly diagnosed sarcoidosis is started on prednisone 40 mg daily. Two weeks later, he presents with severe epigastric pain and hematemesis. Endoscopy reveals multiple gastric ulcers. He reports also taking ibuprofen 800 mg three times daily for chronic back pain. Which of the following best explains his presentation?
Frequently asked questions
How does prednisone work?
Prednisone is converted to prednisolone in the liver, which binds glucocorticoid receptors and suppresses inflammation by inhibiting cytokine production, reducing leukocyte migration, and blocking arachidonic acid metabolism. It also has immunosuppressive effects by inhibiting T-cell and B-cell function. These actions make it effective for treating autoimmune, inflammatory, and allergic conditions.
What are the side effects of prednisone?
Common side effects include weight gain, increased appetite, insomnia, mood changes, and hyperglycemia. Long-term use causes osteoporosis, Cushing syndrome (moon facies, buffalo hump, central obesity), cataracts, glaucoma, increased infection risk, peptic ulcers, and HPA axis suppression. Avascular necrosis and myopathy can also occur. Abrupt discontinuation after prolonged use may cause adrenal crisis.
Why do you have to taper prednisone?
Tapering is necessary because prolonged prednisone use (typically >2-3 weeks) suppresses the hypothalamic-pituitary-adrenal (HPA) axis, reducing endogenous cortisol production. Abrupt discontinuation can lead to adrenal insufficiency or adrenal crisis, characterized by hypotension, shock, hypoglycemia, and potentially death. Gradual tapering allows the HPA axis to recover and resume normal cortisol production.
Is prednisone a controlled substance?
No, prednisone is not a controlled substance. It is a prescription glucocorticoid medication used for anti-inflammatory and immunosuppressive purposes. While it requires a prescription, it is not classified under the Controlled Substances Act because it does not have significant abuse potential like opioids, benzodiazepines, or stimulants.
Prednisone vs prednisolone — what is the difference?
Prednisone is a prodrug that must be converted by the liver to prednisolone, its active form. Prednisolone is already active and does not require hepatic conversion. In patients with severe liver disease, prednisolone is preferred because prednisone conversion may be impaired, reducing efficacy. Otherwise, they have similar anti-inflammatory potency, indications, and side effect profiles.
Conditions it is used for
Related drugs
Sources and further reading
DailyMed (FDA labels)StatPearls (NCBI Bookshelf)MedlinePlusWHO ATC/DDD index: H02AB07WHO ATC/DDD index: A07EA03
Educational content for medical students, prepared by the WhiteCoat Pro editorial team with AI assistance; every page is reviewed by a second AI model for factual errors. It is not medical advice and does not replace the product label, local guidelines or a clinician.