Drug Monograph

Prednisone

Brand names: generic widely available; Rayos (delayed-release tablet); Deltasone, Sterapred (older brands, largely discontinued)
Intermediate-acting synthetic glucocorticoid · Oral
Pharmacokinetic Profile
Oral Bioavailability
~80% (immediate-release)
Tmax
~2 h (IR) · ~6.5 h (delayed-release)
Protein Binding
Prednisolone ~70–95% (concentration-dependent; primarily transcortin)
Metabolism
Hepatic; complete conversion to prednisolone (active); CYP3A4 substrate
Terminal Half-life
~2–3 h (prednisone and prednisolone)
Biological Half-life
~12–36 h (intermediate-acting class)
Clinical Information
Drug Class
Synthetic glucocorticoid (intermediate-acting)
Available Strengths
Tablets: 1, 2.5, 5, 10, 20, 50 mg · Oral solution: 5 mg/5 mL · DR: 1, 2, 5 mg
Glucocorticoid Equivalence
5 mg ≡ 4 mg methylprednisolone ≡ 0.75 mg dexamethasone ≡ 20 mg hydrocortisone
Renal Adjustment
No formal adjustment; use lowest effective dose
Hepatic Adjustment
Severe disease: prednisolone preferred (impaired conversion)
Pregnancy
Small ↑risk of orofacial clefts (1st trimester); IUGR with prolonged use
Lactation
~0.14% of maternal dose to infant; generally compatible
Schedule / Legal Status
Rx only; not a controlled substance
Generic Available
Yes (immediate-release; widely)
Ind

Indications

Prednisone has one of the broadest FDA-approved indication lists of any drug — the labelling spans 13 categories of conditions where corticosteroid anti-inflammatory or immunosuppressive activity is desired, plus replacement therapy for adrenocortical insufficiency. Because the indications cover dozens of distinct diseases, the table below groups them by category. In nearly every indication, prednisone is used as adjunctive therapy or for short-term flare control rather than as monotherapy or definitive treatment.

CategoryFDA-Approved IndicationsStatus
EndocrinePrimary or secondary adrenocortical insufficiency (hydrocortisone or cortisone preferred); congenital adrenal hyperplasia; nonsuppurative thyroiditis; hypercalcemia of malignancyFDA Approved
RheumatologicAcute gouty arthritis (short-term); rheumatoid arthritis (including JRA); psoriatic arthritis; ankylosing spondylitis; SLE; vasculitis; polymyositis/dermatomyositis; polymyalgia rheumatica; Sjögren’s syndrome; relapsing polychondritisFDA Approved
AllergicSevere allergic conditions intractable to conventional therapy: atopic dermatitis, drug hypersensitivity, allergic rhinitis (seasonal/perennial), serum sicknessFDA Approved
DermatologicPemphigus; bullous dermatitis herpetiformis; severe erythema multiforme (Stevens-Johnson syndrome); exfoliative erythroderma; mycosis fungoides; severe psoriasis; severe seborrheic dermatitis; contact dermatitisFDA Approved
PulmonaryAsthma; acute COPD exacerbations; allergic bronchopulmonary aspergillosis; idiopathic eosinophilic pneumonias; idiopathic pulmonary fibrosis; symptomatic sarcoidosis; cryptogenic organizing pneumonia; aspiration pneumonitis; PCP with hypoxemia (HIV+); fulminating/disseminated pulmonary TB (with anti-TB therapy); hypersensitivity pneumonitisFDA Approved
HematologicIdiopathic thrombocytopenic purpura (adults); secondary thrombocytopenia (adults); acquired (autoimmune) hemolytic anemia; pure red cell aplasia; Diamond-Blackfan anemiaFDA Approved
GastrointestinalCrohn’s disease and ulcerative colitis (acute episodes)FDA Approved
NeurologicAcute exacerbations of multiple sclerosis; cerebral edema with primary or metastatic brain tumor, craniotomy, or head injuryFDA Approved
RenalNephrotic syndrome (idiopathic or due to lupus erythematosus, without uremia)FDA Approved
OphthalmicSympathetic ophthalmia; uveitis and ocular inflammation unresponsive to topical steroidsFDA Approved
NeoplasticAcute leukemia; aggressive lymphomas (component of CHOP, R-CHOP, and similar regimens)FDA Approved
TransplantationAcute or chronic solid organ rejectionFDA Approved
Specific Infectious DiseasesTrichinosis with neurologic or myocardial involvement; tuberculous meningitis with subarachnoid block (with anti-TB chemotherapy)FDA Approved
Common Off-Label Uses (Evidence Quality)

Giant cell arteritis (high evidence): 40–60 mg/day initial, taper over 12–24 months — guideline-recommended (ACR/VF 2021), although prednisone itself is not specifically labelled for GCA.

Bell’s palsy within 72 h (high evidence): 50–60 mg/day for 5–10 days — improves recovery rates per multiple RCTs.

Severe COVID-19 with oxygen requirement (high evidence): Dexamethasone 6 mg/day is the standard per RECOVERY trial; prednisone 40 mg/day is an accepted equivalent when dexamethasone is unavailable.

Recurrent pregnancy loss, IVF support, and other reproductive indications (low to moderate evidence): Practice varies; not generally recommended outside specific protocols.

Acute spinal cord injury (very low evidence): High-dose methylprednisolone protocols are no longer routinely recommended; oral prednisone has no role in this setting.

Dose

Dosing

Prednisone dose is individualized to disease activity, response, and risk of toxicity rather than to body weight or tablet strength. The FDA labelling describes the typical initial range as 5 to 60 mg per day, with the actual starting dose chosen by the clinical scenario. After clinical response, doses are tapered to the lowest amount that maintains disease control. Below are common scenario-based regimens drawn from the FDA labelling and major guidelines; doses for chemotherapy and transplantation regimens follow protocol-specific schedules and are not summarized here.

Adult Dosing by Clinical Scenario

Clinical ScenarioStarting DoseMaintenance / TaperTypical MaximumNotes
Rheumatoid arthritis flare (adjunct to DMARD)5–10 mg PO dailyTaper to lowest effective dose10 mg/day for routine flare useHigher doses (e.g., 20–60 mg) reserved for severe flare; consider osteoporosis prophylaxis if ≥7.5 mg/day for ≥3 months
RAYOS Phase 3: 5 mg at bedtime improved morning stiffness vs placebo
Polymyalgia rheumatica12.5–25 mg PO dailyTaper by 2.5 mg every 2–4 wk to 10 mg/day, then 1 mg/month25 mg/day initialPer ACR/EULAR 2015. Most patients require 1–2 years of therapy; ~40% relapse during taper
Giant cell arteritis (off-label)40–60 mg PO dailyTaper over 12–24 months60 mg/day (or 1 mg/kg)Higher initial doses (or IV pulse methylprednisolone) for visual involvement. Tocilizumab as steroid-sparing add-on per ACR/VF 2021
Acute asthma exacerbation (adult, outpatient or inpatient)40–60 mg PO dailyContinue × 5–7 days; no taper needed if course ≤7 days60 mg/dayPer GINA 2024. Single morning dose; no tapering required for short courses ≤2–3 weeks
Acute COPD exacerbation40 mg PO daily × 5 daysStop after 5 days (no taper)40 mg/day × 5 days (REDUCE)5-day course non-inferior to 14-day course (Leuppi 2013; GOLD 2024)
IBD flare (Crohn’s, UC)40–60 mg PO dailyTaper by 5–10 mg/wk to 20 mg, then 5 mg/wk to off60 mg/day or 1 mg/kgUse as bridge to a steroid-sparing agent (immunomodulator, biologic). Avoid prolonged use as maintenance
Acute multiple sclerosis exacerbation200 mg PO daily × 1 wk → 80 mg every other day × 1 moStop after the listed regimen200 mg/day × 7 daysPer FDA prednisone labelling. In current practice, IV methylprednisolone 1 g/day × 3–5 days (with or without oral taper) is more commonly used
Idiopathic thrombocytopenic purpura (adults)1 mg/kg/dayTaper based on platelet response over 4–6 weeks80 mg/dayPer ASH 2019. High-dose pulse dexamethasone (40 mg × 4 days) is an alternative
Acute gouty arthritis (when NSAIDs/colchicine contraindicated)30–40 mg PO dailyContinue × 5 days, then taper over 7–10 days40 mg/dayPer ACR 2020. Useful in patients with renal impairment or anticoagulation
Bell’s palsy (off-label, <72 h onset)60 mg PO daily × 5 days, then taper10-day total course60 mg/dayPer AAN 2012; addition of valacyclovir does not improve outcome over steroid alone
Severe COVID-19 (oxygen-dependent, off-label equivalent)40 mg PO daily × up to 10 daysStop at hospital discharge or 10 days40 mg/dayEquivalent to dexamethasone 6 mg (RECOVERY trial). Use dexamethasone first-line where available
Adrenal insufficiency (replacement, when prednisone is selected)3–5 mg PO every morningLong-term physiologic replacement7.5 mg/dayHydrocortisone (15–25 mg/day in 2–3 divided doses) is preferred per Endocrine Society 2016 because of more physiologic profile. Stress-dose coverage required for illness, surgery, trauma

Pediatric Dosing (Selected Indications)

IndicationDoseDurationNotes
Acute asthma exacerbation1–2 mg/kg/day PO (max 60 mg/day)3–10 daysPer NHLBI / NAEPP. No taper needed if ≤7 days
Idiopathic nephrotic syndrome (initial)60 mg/m²/day PO (max 60 mg) in 1–3 divided doses4–6 weeks, then 40 mg/m² every other day × 2–5 monthsPer KDIGO 2021. Follow growth velocity carefully
Aggressive lymphomas / acute lymphoblastic leukemia (induction)Protocol-specific (commonly 40 mg/m²/day or 60 mg/m²/day)Per chemotherapy protocolDoses follow individual induction regimens (e.g., COG ALL protocols). FDA labelling supports use ≥1 month of age
Other pediatric indications0.05–2 mg/kg/day in 1–4 divided dosesDisease- and response-dependentAlways titrate to lowest effective dose; monitor growth velocity

Tapering Principles

Patients on prednisone for >2–3 weeks at supraphysiologic doses (typically >5 mg/day) may have HPA-axis suppression and require tapering before discontinuation. There is no single validated taper schedule; the principles below align with the FDA labelling and clinical consensus:

  • Courses ≤7 days at any dose: No taper required (HPA-axis recovery within days).
  • Courses 1–3 weeks at >20 mg/day: Optional brief taper over 5–7 days.
  • Courses 3 weeks to 3 months: Taper by 5–10 mg every 1–2 weeks above 20 mg/day, then 2.5–5 mg every 1–2 weeks below 20 mg/day, then 1 mg every 1–2 weeks below 10 mg/day.
  • Courses >3 months: Slower tapers (1 mg every 2–4 weeks below 10 mg/day) and consider morning cortisol or ACTH stimulation testing once at physiologic-equivalent dose (≤5 mg/day) before complete withdrawal.
  • Stress-dose coverage may be required for major illness, surgery, or trauma during the taper and for up to 12 months after discontinuation.

Special Populations

  • Hepatic impairment: Severe liver disease (cirrhosis, fulminant hepatitis) may impair conversion of prednisone to active prednisolone; prednisolone is preferred in this setting. No formal dose adjustment for mild–moderate impairment.
  • Renal impairment: No specific dose adjustment, but elderly patients with reduced renal function may have higher exposures; start at the lower end of the dosing range.
  • Older adults (≥65 years): Higher unbound prednisolone exposures and reduced clearance per the FDA labelling. Osteoporosis risk is the dominant concern; doses ≥7.5 mg/day for ≥3 months warrant bone-protection strategies and DEXA monitoring.
  • Pediatrics: Use lowest effective dose; growth velocity is a sensitive marker of systemic exposure and may decline at low doses without HPA-axis suppression on biochemical testing.
  • Pregnancy: Maternal first-trimester corticosteroid use has been associated with a small increase in orofacial clefts (from ~1/1,000 to 3–5/1,000 infants in observational studies). Intrauterine growth restriction and reduced birth weight have been reported with prolonged use. When prednisone is required during pregnancy, use the lowest effective dose.
  • Lactation: Prednisolone concentrations in human milk are 5–25% of maternal serum levels; total infant daily dose is approximately 0.14% of the maternal daily dose. Generally compatible with breastfeeding; for doses >20 mg/day, some authorities recommend waiting 4 hours after a dose before breastfeeding.
Clinical Pearl — Single Morning Dose Minimizes HPA Suppression

Endogenous cortisol secretion peaks between 2 a.m. and 8 a.m. and is lowest between 4 p.m. and midnight. A single morning dose of prednisone produces the least HPA-axis suppression because it mimics the natural circadian peak; divided dosing or evening dosing produces more suppression for the same total daily dose. The exception is delayed-release prednisone (Rayos), which is taken at bedtime so that drug release coincides with the early-morning rise in disease activity — particularly the morning stiffness of rheumatoid arthritis. For all other regimens, default to a single morning dose unless there is a compelling clinical reason to divide.

Px

Pharmacology

Mechanism of Action

Prednisone is a synthetic glucocorticoid prodrug that is rapidly and almost completely converted by hepatic 11β-hydroxysteroid dehydrogenase to its active metabolite prednisolone. Prednisolone diffuses across the cell membrane and binds the cytosolic glucocorticoid receptor; the activated complex translocates to the nucleus, where it modulates transcription of inflammatory and immune-response genes through two principal mechanisms.

Transactivation upregulates anti-inflammatory genes including lipocortin-1 (annexin A1), which inhibits phospholipase A2 and thereby reduces release of arachidonic acid and downstream prostaglandins and leukotrienes. Transrepression inhibits the activity of pro-inflammatory transcription factors NF-κB and AP-1, producing broad suppression of cytokine synthesis (IL-1, IL-2, IL-6, TNF-α, IFN-γ), adhesion molecule expression, and the recruitment and function of neutrophils, eosinophils, lymphocytes, and macrophages. The clinical anti-inflammatory effect is evident within hours; the immunosuppressive effect — including reduction of circulating lymphocytes through redistribution to lymphoid tissue — develops over days. At higher doses, prednisolone also produces measurable mineralocorticoid activity (sodium retention, potassium loss, increased blood pressure) although less prominently than the parent endogenous hormone hydrocortisone.

The pharmacological effects of prednisone described in the FDA labelling include promotion of gluconeogenesis, increased hepatic glycogen deposition, anti-insulin activity, increased protein catabolism, increased lipolysis and fat redistribution, increased glomerular filtration with elevated urinary urate excretion, and increased calcium excretion. Eosinophil and lymphocyte production is suppressed while erythropoiesis and neutrophil production are stimulated. These metabolic effects underlie much of the toxicity profile (hyperglycemia, muscle wasting, fat redistribution, osteoporosis) observed with prolonged use.

Glucocorticoid Potency Comparison

Prednisone is classed as an intermediate-acting glucocorticoid based on its biological half-life of approximately 12–36 hours. The FDA labelling specifies the following equipotent oral and intravenous doses:

GlucocorticoidEquipotent DoseRelative Anti-inflammatory PotencyRelative Mineralocorticoid PotencyBiological Half-life Class
Hydrocortisone20 mg11Short-acting (8–12 h)
Cortisone25 mg0.80.8Short-acting
Prednisone5 mg40.8Intermediate (12–36 h)
Prednisolone5 mg40.8Intermediate
Methylprednisolone4 mg50.5Intermediate
Triamcinolone4 mg50Intermediate
Dexamethasone0.75 mg25–30~0Long-acting (36–72 h)
Betamethasone0.75 mg25–30~0Long-acting

Pharmacokinetics

ParameterValueComment
Bioavailability~80% (oral)Immediate-release formulation; food does not meaningfully impair absorption of IR tablets
Tmax~2 h (IR); ~6.5 h (DR Rayos)Delayed-release coating delays drug release by approximately 4 hours; must be taken with food
Volume of distribution~0.4–1 L/kg (prednisolone)Distributes into most tissues; crosses placenta and into breast milk
Protein binding~70–95% (concentration-dependent)Primarily transcortin (cortisol-binding globulin) at low concentrations; albumin at higher concentrations. Free fraction increases as transcortin saturates
MetabolismHepatic; CYP3A4 substratePrednisone is rapidly and completely converted to active prednisolone by hepatic 11β-HSD; prednisolone is further metabolized in the liver and excreted as sulfate and glucuronide conjugates. Prednisolone exposure is 4–6× higher than prednisone
Terminal half-life~2–3 hPharmacological/biological half-life is much longer (12–36 h) due to receptor-binding and downstream genomic effects
ExcretionUrine (predominantly as conjugates)Negligible biliary excretion

Prednisone exhibits dose-proportional pharmacokinetics across the 1–5 mg dose range studied for the delayed-release formulation. The pharmacokinetics are not meaningfully altered by mild-to-moderate renal impairment, but elderly patients have higher unbound prednisolone exposures and reduced clearance; the FDA labelling recommends starting at the lower end of the dosing range in older adults. In severe hepatic impairment, conversion of prednisone to prednisolone may be impaired and direct administration of prednisolone is preferred.

SE

Side Effects

Prednisone has been in clinical use since 1955 and its adverse-effect profile is among the most thoroughly characterized of any drug. Because the FDA labelling lists adverse reactions by organ system without modern RCT-derived incidence rates, the frequencies below are drawn from the FDA labelling combined with systematic reviews of low-to-medium dose chronic glucocorticoid therapy in inflammatory diseases (Da Silva 2006; Hoes 2009) and the ACR 2017 guideline on glucocorticoid-induced osteoporosis. The single most important factor governing toxicity is cumulative dose × duration: most adverse effects are minimal with short courses (≤3 weeks) at any reasonable dose, increase substantially with chronic use, and become near-universal with long-term doses ≥10 mg/day. The RAYOS Phase 3 RA trial (350 patients, 12 weeks, doses 3–10 mg/day) did not raise new safety concerns beyond the well-established profile of immediate-release prednisone.

Tier 1 — Very Common Expected during chronic use; dose- and duration-dependent
EffectFrequency / OnsetClinical Action
Increased appetite & weight gainVery common
Within weeks; cumulative
Counsel on portion control, regular weighing; weight gain >5% body weight should prompt dose review
Cushingoid features (moon face, central obesity, dorsocervical fat pad, striae)Very common with ≥10 mg/day chronic use
Weeks to months
Largely cosmetic; reverses with dose reduction. Counsel patients in advance to set expectations
HPA-axis suppressionCommon after >3 weeks at >5 mg/day
Days to weeks
Taper after prolonged use; consider stress-dose coverage for surgery/illness; recovery may take months
Fluid retention and mild lower-extremity edemaCommon
Days to weeks
Reduce dietary sodium; usually resolves on dose reduction. More prominent with hydrocortisone than with prednisone
Hyperglycemia / impaired glucose toleranceCommon; near-universal in pre-diabetes
Days to weeks
Check fasting and 2-hour postprandial glucose at baseline and during chronic therapy. May unmask latent diabetes; insulin requirements rise in known diabetics
Mood changes (euphoria, irritability, mood swings, insomnia)Common, especially at higher doses
Days; may begin with the first dose
Warn all patients prospectively. Take dose in the morning to reduce insomnia. Severe mood disturbance warrants dose reduction or discontinuation
Hypertension / blood pressure elevationCommon
Weeks
Monitor BP at each visit during chronic therapy; may require initiation or intensification of antihypertensives
Skin changes (thinning, easy bruising, acne, striae, impaired wound healing)Common with chronic use
Months
Counsel; partially reversible with dose reduction. Striae may be permanent
Tier 2 — Common with Higher Doses or Prolonged Use Increasingly likely with cumulative exposure
EffectFrequency / OnsetClinical Action
Decreased bone density / osteoporotic fractureSignificant fracture risk at ≥7.5 mg/day for ≥3 months
Greatest bone loss in first 3–6 months
Per ACR 2017 GIO guideline: assess fracture risk and initiate bone-protective therapy (calcium 1,000–1,200 mg/day, vitamin D 600–800 IU/day, plus bisphosphonate if at moderate-to-high risk). DEXA at baseline and every 1–3 years
Cataracts (posterior subcapsular)Common with prolonged use; dose- and duration-dependent
Months to years
Annual ophthalmologic exam during chronic therapy; cataracts are largely irreversible but surgically treatable
Glaucoma / increased intraocular pressure~5% of chronic users; higher in steroid-responders
Weeks to months
Monitor IOP if therapy continues >6 weeks (FDA recommendation). Higher risk with personal or family history of open-angle glaucoma
Increased infection risk (bacterial, viral, fungal, opportunistic)Risk increases with dose and duration
Throughout therapy
Screen for latent TB and hepatitis B before chronic therapy. Consider PCP prophylaxis at sustained doses ≥20 mg/day for ≥4 weeks. Avoid live vaccines at immunosuppressive doses
Hypokalemia and metabolic alkalosisCommon with high doses or concomitant diuretics/amphotericin
Days to weeks
Monitor potassium during chronic therapy; supplement as needed. Particularly important in patients on digoxin or with cardiac arrhythmias
Myopathy (proximal muscle weakness)Common with chronic high doses
Weeks to months
Counsel on resistance exercise; CK is typically normal in steroid myopathy. Reverses slowly with dose reduction
Menstrual irregularitiesCommon
Variable
Reassure; resolves with discontinuation
Growth suppression (pediatric)Common with chronic use
Detectable within months
Monitor growth velocity (more sensitive than HPA testing). Use lowest effective dose; alternate-day dosing when feasible
Tier 3 — Serious or Life-Threatening Less common but require urgent recognition and intervention
EffectFrequency / OnsetClinical Action
Adrenal crisis (during withdrawal or stress)Uncommon but life-threatening
Onset within hours of stress in suppressed patient
Provide MedicAlert identification, written stress-dose plan, and emergency hydrocortisone for any patient on chronic supraphysiologic doses or prolonged taper. Treat with IV hydrocortisone 100 mg + saline for hypotension/shock during stress
Steroid-induced psychosis or severe depression~3–6% with high-dose use
Days to weeks; higher risk at >40 mg/day prednisone-equivalent
Discontinue or rapidly reduce dose under cover of antipsychotic if needed. Symptoms typically resolve within 6 weeks of discontinuation
Gastrointestinal perforationUncommon overall; higher in IBD, diverticulitis, recent intestinal anastomosis, active peptic ulcer
During therapy; signs may be masked
Maintain low threshold for imaging in chronically treated patients with new abdominal pain. Coadministration with NSAIDs further increases risk
Reactivation of latent infection (TB, hepatitis B, Strongyloides, herpes zoster)Uncommon but potentially fatal
Weeks to months into therapy
Screen for latent TB (IGRA or TST) and hepatitis B before chronic immunosuppressive therapy. Consider Strongyloides screening in patients from endemic areas. Treat reactivations promptly
Cardiovascular events (MI, heart failure exacerbation)Increased risk at higher doses; LV free wall rupture has been reported after recent MI
During therapy
Use with great caution within 30 days of MI per the FDA labelling. Address cardiovascular risk factors aggressively in chronic users
Osteonecrosis (avascular necrosis) of the femoral or humeral headUncommon but well-described; risk increases with cumulative dose and pulse therapy
Months to years
MRI for new persistent hip or shoulder pain in chronic users. Discontinuation does not reverse established osteonecrosis
Acute myopathy (high-dose, neuromuscular disease)Rare
Days to weeks at very high doses, especially with concomitant neuromuscular blockers
Generalized weakness involving ocular and respiratory muscles; CK may be elevated. Discontinue corticosteroid; recovery takes weeks to years
Anaphylaxis / angioedemaRare
Minutes to hours of exposure
Discontinue immediately; treat with epinephrine and supportive care. True hypersensitivity is rare but documented
Tier 4 — Withdrawal Effects Distinct from disease relapse; due to HPA-axis suppression and abrupt cortisol deprivation

Patients who have received supraphysiologic doses (typically >5 mg/day) for more than 2–3 weeks are at risk for HPA-axis suppression. Abrupt discontinuation in a suppressed patient can produce a withdrawal syndrome that overlaps with — but is not identical to — adrenal insufficiency, characterized by fatigue, anorexia, nausea, weight loss, arthralgia, myalgia, headache, and orthostatic hypotension. The syndrome is typically self-limited but may unmask frank adrenal crisis under physiologic stress. There is no validated biochemical test that perfectly predicts who will become symptomatic on withdrawal; clinical judgement and gradual tapering (see Dosing) remain the cornerstones of safe discontinuation.

Risk Threshold
>5 mg/day for >3 weeks
Below this threshold, HPA-axis suppression is unlikely and abrupt discontinuation is generally safe. Above it, taper before discontinuation and consider stress-dose coverage during illness or surgery
HPA Recovery Time
Up to 12 months after long-term use
Pituitary corticotroph axis recovers first (weeks); adrenal cortisol response may take 6–12 months. Stress-dose coverage may be needed throughout this window
DI

Drug Interactions

Prednisone has a large number of clinically relevant interactions, mediated primarily through (1) CYP3A4 metabolism of the active metabolite prednisolone, (2) glucocorticoid effects on glucose, potassium, and the GI tract, and (3) immunosuppressive effects altering vaccine response. The cards below summarize the most important interactions from the FDA labelling, organized by clinical management priority.

Major Live or live-attenuated vaccines
Mechanism: Immunosuppression at higher doses → potential for vaccine-strain disseminated infection
Effect: Risk of disseminated infection; reduced vaccine response
Action: Contraindicated at immunosuppressive doses (≥20 mg/day prednisone-equivalent for ≥2 weeks). Defer live vaccines (MMR, varicella, yellow fever, BCG, oral polio, oral typhoid, intranasal influenza, live zoster) until ≥1 month after discontinuation. Inactivated/recombinant vaccines (e.g., Shingrix, inactivated influenza) are acceptable but immune response may be reduced
FDA Label §5.8, §7.16
Major Strong CYP3A4 inducers (rifampin, phenytoin, carbamazepine, phenobarbital)
Mechanism: Induction of hepatic CYP3A4 → ↑ prednisolone clearance
Effect: Reduced corticosteroid efficacy; loss of disease control
Action: Anticipate increased corticosteroid dose requirement (often 50–100% higher). Monitor disease activity. If treating refractory adrenal insufficiency on rifampin, dose may need doubling
FDA Label §7.7
Moderate Strong CYP3A4 inhibitors (ketoconazole, itraconazole, ritonavir, clarithromycin, erythromycin)
Mechanism: Inhibition of hepatic CYP3A4 → ↓ prednisolone clearance
Effect: ↑ Corticosteroid exposure (ketoconazole reduces metabolism by up to 60%); higher risk of toxicity
Action: Consider dose reduction during co-administration; monitor for Cushingoid features, hyperglycemia, hypertension. Avoid concurrent inhaled fluticasone with ritonavir (risk of iatrogenic Cushing’s syndrome)
FDA Label §7.8
Moderate Antidiabetic agents (insulin, sulfonylureas, metformin)
Mechanism: Glucocorticoid-induced gluconeogenesis and insulin resistance
Effect: ↑ Blood glucose; loss of glycemic control; ↑ insulin requirements
Action: Increase home glucose monitoring frequency; anticipate insulin dose increases of 25–50% with prednisone ≥20 mg/day. Reduce insulin proportionally during taper to prevent hypoglycemia
FDA Label §7.5
Moderate Warfarin / coumarin anticoagulants
Mechanism: Variable; may inhibit anticoagulant response, but conflicting reports
Effect: Unpredictable INR change; some patients develop ↑INR, others ↓INR
Action: Check INR within 3–5 days of starting or stopping prednisone; recheck during dose changes. Concomitant GI risk with NSAID/aspirin compounds the bleeding hazard
FDA Label §7.4
Moderate NSAIDs and aspirin
Mechanism: Additive GI mucosal injury; corticosteroids increase salicylate clearance
Effect: ↑ Risk of gastric ulcer and GI bleeding (~4× with combination); ↓ salicylate levels during prednisone therapy with risk of toxicity on prednisone withdrawal
Action: Avoid combination when possible. If unavoidable, add PPI gastroprotection. Adjust salicylate dose if used for therapeutic levels (e.g., in rheumatic conditions)
FDA Label §7.13
Moderate Potassium-depleting agents (loop and thiazide diuretics, amphotericin B)
Mechanism: Additive renal potassium wasting
Effect: Hypokalemia; ↑ risk of cardiac arrhythmias (especially if also on digoxin)
Action: Monitor potassium; supplement as needed. Cases of cardiac enlargement and CHF reported with amphotericin B + corticosteroid
FDA Label §7.14
Moderate Cyclosporine
Mechanism: Mutual inhibition of metabolism via CYP3A4
Effect: ↑ Activity of both drugs; convulsions reported with concurrent use
Action: Frequent in transplant medicine; monitor cyclosporine levels and clinical response. Be alert to neurotoxicity
FDA Label §7.10
Moderate Anticholinesterases (pyridostigmine, neostigmine) in myasthenia gravis
Mechanism: Corticosteroid-induced transient myasthenic worsening
Effect: Severe weakness can occur in the first 1–2 weeks of corticosteroid initiation
Action: If feasible, withdraw anticholinesterases ≥24 h before initiating corticosteroids. Initiate corticosteroids in a monitored setting in severe myasthenia
FDA Label §7.3
Minor Digoxin
Mechanism: Indirect — corticosteroid-induced hypokalemia sensitizes the myocardium to digitalis
Effect: ↑ Risk of digitalis toxicity and arrhythmia
Action: Monitor potassium; supplement to keep ≥4.0 mmol/L in digitalized patients
FDA Label §7.11
Minor Estrogens / oral contraceptives
Mechanism: Estrogens decrease hepatic metabolism of corticosteroids
Effect: ↑ Corticosteroid exposure and prolonged half-life
Action: Generally clinically modest; consider when titrating doses in patients on combined hormonal contraceptives or HRT
FDA Label §7.12
Minor Cholestyramine and isoniazid
Mechanism: Cholestyramine: ↑ corticosteroid clearance via reduced enterohepatic recirculation. Isoniazid: prednisone reduces serum INH levels
Effect: Reduced efficacy of corticosteroid (cholestyramine); reduced INH levels (potential efficacy reduction in TB)
Action: Separate dosing. Monitor TB therapy response when corticosteroid is co-administered (e.g., in TB meningitis)
FDA Label §7.6, §7.9
Mon

Monitoring

The intensity of monitoring scales with dose and intended duration of therapy. Short courses (≤7 days) at any reasonable dose require essentially no laboratory monitoring beyond routine clinical assessment. Chronic therapy at supraphysiologic doses requires structured surveillance for the well-described metabolic, cardiovascular, ophthalmologic, infectious, and skeletal complications.

  • Blood Pressure
    Baseline, every visit during chronic useRoutine
    FDA labelling specifies regular BP monitoring during prolonged therapy. Initiate or adjust antihypertensive therapy as needed. Sodium restriction may help in marginal cases
  • Body Weight
    Baseline, every visitRoutine
    Track to detect rapid fluid retention and Cushingoid weight gain. Counsel proactively on diet
  • Glucose (Fasting + 2-hour Postprandial)
    Baseline; routinely during chronic useRoutine
    FDA labelling specifies 2-hour postprandial glucose during prolonged therapy. HbA1c is less sensitive to steroid-induced hyperglycemia. In known diabetics, intensify home glucose monitoring
  • Serum Potassium
    Baseline; periodically during chronic useRoutine
    FDA labelling specifies regular potassium monitoring during prolonged therapy. More frequent monitoring on diuretics, amphotericin B, or digoxin
  • Bone Mineral Density (DEXA)
    Baseline if ≥7.5 mg/day expected for ≥3 months; every 1–3 yearsRoutine
    Per ACR 2017 GIO guideline. Pair with calcium 1,000–1,200 mg/day, vitamin D 600–800 IU/day, and consider bisphosphonate therapy for moderate-to-high fracture risk patients on chronic glucocorticoids
  • Intraocular Pressure
    If therapy ≥6 weeksRoutine
    Per FDA labelling. Annual ophthalmologic exam during chronic therapy includes IOP measurement and slit-lamp evaluation for posterior subcapsular cataracts
  • Latent TB Screening (IGRA or TST)
    Before chronic immunosuppressive therapyTriggered
    Per FDA labelling. Treat latent TB before or concurrent with prolonged corticosteroid therapy in any patient with a positive screen
  • Hepatitis B Serology (HBsAg, anti-HBc)
    Before chronic immunosuppressive therapyTriggered
    Per FDA labelling. HBV reactivation can occur in carriers and even in patients with apparently resolved infection; consult hepatology for prophylactic antiviral consideration
  • Growth Velocity (Pediatric)
    Every visit during chronic therapyRoutine
    More sensitive than HPA-axis testing per FDA labelling. Plot height velocity on growth curve; titrate to lowest effective dose
  • Morning Cortisol or ACTH (Cosyntropin) Stimulation Test
    Before stopping after long-term high-dose useTriggered
    Per Endocrine Society 2016. Consider once tapered to physiologic-equivalent dose (≤5 mg/day) and held for 24 h. Morning cortisol >10 µg/dL or normal ACTH-stim response generally indicates HPA recovery; intermediate values warrant continued precaution
  • Mood / Mental Health
    Every visit; especially first monthRoutine
    Inquire about insomnia, mood elevation, depression, suicidal ideation. Higher risk at doses ≥40 mg/day prednisone-equivalent or in patients with prior psychiatric history
  • Signs of Infection
    Every visitRoutine
    Counsel patient to report fever, productive cough, dysuria, or new abdominal pain promptly. Corticosteroids may mask classic infection signs (fever, leukocytosis pattern)
CI

Contraindications

The FDA labelling for prednisone lists only one absolute contraindication. The labelling otherwise describes a long list of conditions in which corticosteroid therapy carries elevated risk and warrants either avoidance or careful clinical judgement; these are framed as cautions rather than contraindications because the benefit may outweigh the risk in selected scenarios. The lists below organize this distinction.

Absolute Contraindications

Per FDA Labelling §4 Hypersensitivity

Known hypersensitivity to prednisone or to any component of the formulation. Rare instances of anaphylaxis have occurred in patients receiving corticosteroid therapy.

Relative Contraindications and Significant Cautions

Avoid unless benefit clearly outweighs risk

Systemic fungal infections — corticosteroids may exacerbate. Use only if needed to control drug reactions and consider antifungal coverage.

Live or live-attenuated vaccines at immunosuppressive doses — risk of disseminated vaccine-strain disease (FDA §5.8).

Cerebral malaria — corticosteroid use is associated with worse outcomes and should be avoided (FDA §5.2).

Active untreated tuberculosis — corticosteroids may permit dissemination. Use only with concurrent appropriate anti-TB chemotherapy as in tuberculous meningitis.

Recent myocardial infarction — literature reports of left-ventricular free-wall rupture with corticosteroid use after recent MI; use with great caution within 30 days (FDA §5.3).

Untreated active ocular herpes simplex — risk of corneal perforation (FDA §5.7).

Use with caution

Existing peptic ulcer disease, diverticulitis, recent intestinal anastomosis — increased GI perforation risk (FDA §5.4).

Latent tuberculosis or tuberculin reactivity — provide chemoprophylaxis during prolonged therapy.

Hepatitis B carriers or resolved hepatitis B — risk of viral reactivation; co-management with hepatology.

Patients from tropical regions, unexplained eosinophilia, or unexplained diarrhea — rule out latent Strongyloides infestation; risk of fatal hyperinfection.

Myasthenia gravis — risk of severe weakness during initiation; introduce in monitored setting (FDA §7.3).

Uncontrolled hypertension, congestive heart failure, or significant renal impairment — sodium retention and BP elevation may worsen disease (FDA §5.3).

Pregnancy — small increased risk of orofacial clefts with first-trimester use; intrauterine growth restriction with prolonged use (FDA §5.10).

Diabetes mellitus — anticipate worsening glycemic control; intensify monitoring and therapy.

Psychiatric history — particularly bipolar disorder, prior steroid-induced psychosis; involve mental-health expertise for prolonged or high-dose therapy.

PC

Patient Counselling

Patient understanding is central to safe use of prednisone. The FDA-required counselling points below should be reinforced at initiation and at each follow-up visit, particularly for patients on chronic therapy. A written patient information sheet and MedicAlert identification (for chronic users) substantially reduce the risk of catastrophic events such as adrenal crisis under stress.

“Never stop suddenly”
Why: After more than 2–3 weeks of therapy, your body’s natural cortisol production is suppressed. Stopping suddenly can cause a life-threatening drop in blood pressure, severe fatigue, nausea, and shock — particularly during illness, injury, or surgery.
What to do: Always reduce the dose gradually as instructed. Never discontinue prednisone without speaking to your clinician. Carry a list of your medications and contact your doctor if any pharmacy ever refuses to fill a refill.
MedicAlert identification and stress-dose plan
Who needs this: Anyone taking prednisone >5 mg/day for more than a few weeks, anyone on long-term replacement therapy for adrenal insufficiency, and anyone in the first year after stopping long-term prednisone.
What to wear/carry: A MedicAlert bracelet or wallet card identifying steroid use. Keep an emergency hydrocortisone injection at home if your doctor recommends one. Inform every healthcare provider, dentist, and surgeon that you are taking — or have recently taken — prednisone.
Infections and live vaccines
Why: Prednisone weakens your immune defences against infections, and steroids can mask the usual fever and inflammation of an infection until it becomes serious.
What to do: Seek medical attention promptly for any fever, unusual cough, painful urination, or new severe abdominal pain. Avoid people with chickenpox, measles, or shingles unless you are known immune. Do not receive live vaccines (yellow fever, MMR, varicella, intranasal flu) while on immunosuppressive doses; ask your clinician before any vaccination.
Bone health and fall prevention
Why: Prednisone reduces bone density most rapidly during the first 3–6 months. Fractures can occur even at low doses (≥7.5 mg/day) used for more than 3 months.
What to do: Take calcium 1,000–1,200 mg/day and vitamin D 600–800 IU/day. Engage in weight-bearing exercise. Avoid smoking and limit alcohol. If your clinician prescribes a bone-protection medication (e.g., a bisphosphonate), take it as directed.
Mood and sleep changes
Why: Prednisone can cause insomnia, irritability, mood swings, anxiety, or — in rare cases — severe depression or psychosis, especially at higher doses.
What to do: Take your dose in the morning to reduce insomnia. Tell your clinician immediately about thoughts of self-harm, severe mood changes, or feelings of confusion. These typically resolve within a few weeks of dose reduction or discontinuation.
Eye and dental care
Why: Long-term use can cause cataracts and glaucoma. Wound healing is slower, which matters for tooth extractions and surgical procedures.
What to do: Annual eye exams during chronic therapy. Tell your dentist before any procedure that you are on prednisone — they may need to check whether stress-dose coverage is appropriate.
Glucose monitoring (especially if diabetic or pre-diabetic)
Why: Prednisone consistently raises blood glucose and may unmask diabetes or destabilize known diabetes.
What to do: If you have diabetes, increase home glucose checks while on prednisone. Be prepared for insulin or oral medication doses to rise — and to fall again as you taper down. If you do not have diabetes, ask your clinician whether glucose testing is needed.
How to take this medication
Timing: Take immediate-release prednisone as a single morning dose with food, unless your clinician specifies otherwise. Take delayed-release prednisone (Rayos) at bedtime with food; do not break, divide, or chew the tablet.
Missed dose: Take it as soon as you remember unless it is almost time for the next dose, in which case skip it. Do not double up.
Storage: Store at room temperature, protected from light and moisture. Keep out of reach of children.
Ref

Sources

FDA Prescribing Information
  1. RAYOS (prednisone) delayed-release tablets — US prescribing information. Horizon Therapeutics USA, Inc. NDA 202020. Revised March 2024. accessdata.fda.gov/drugsatfda_docs/label/2024/202020s013lbl.pdf Most recent FDA-approved labelling for prednisone (delayed-release formulation). The IR-tablet labelling (e.g., DailyMed setid 10fe5a3b-84dc-4600-87c2-b80c97ce18cf for generic prednisone) reflects the same indications and warnings.
  2. Prednisone tablets, USP — generic prescribing information. DailyMed (US National Library of Medicine). dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=10fe5a3b-84dc-4600-87c2-b80c97ce18cf FDA-approved labelling for generic immediate-release prednisone tablets, covering the full historical indication list that long predates the modern Highlights format.
Pivotal Trial
  1. Buttgereit F, Doering G, Schaeffler A, et al. Efficacy of modified-release versus standard prednisone to reduce duration of morning stiffness of the joints in rheumatoid arthritis (CAPRA-1): a double-blind, randomised controlled trial. Lancet. 2008;371(9608):205–214. doi.org/10.1016/S0140-6736(08)60132-4 Pivotal CAPRA-1 trial supporting the bedtime delayed-release Rayos formulation; demonstrated reduction in morning stiffness duration vs immediate-release prednisone at the same total daily dose.
Major Clinical Practice Guidelines
  1. Buckley L, Guyatt G, Fink HA, et al. 2017 American College of Rheumatology guideline for the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis Rheumatol. 2017;69(8):1521–1537. doi.org/10.1002/art.40137 ACR guideline establishing the ≥7.5 mg/day for ≥3 months threshold for fracture-risk assessment and the bone-protection treatment algorithm for chronic glucocorticoid users.
  2. 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. doi.org/10.1210/jc.2015-1710 Endocrine Society reference for replacement-dose corticosteroid regimens and stress-dose coverage; widely applied to glucocorticoid-induced secondary adrenal insufficiency.
  3. FitzGerald JD, Dalbeth N, Mikuls T, et al. 2020 American College of Rheumatology guideline for the management of gout. Arthritis Care Res. 2020;72(6):744–760. doi.org/10.1002/acr.24180 ACR gout guideline supporting oral glucocorticoids (e.g., prednisone 30–40 mg/day for 5 days) as first-line therapy for acute flares when NSAIDs and colchicine are contraindicated.
  4. Maz M, Chung SA, Abril A, et al. 2021 American College of Rheumatology / Vasculitis Foundation guideline for the management of giant cell arteritis and Takayasu arteritis. Arthritis Rheumatol. 2021;73(8):1349–1365. doi.org/10.1002/art.41774 ACR/VF guideline endorsing high-dose oral glucocorticoids (40–60 mg/day prednisone-equivalent) as initial therapy for GCA, with tocilizumab as steroid-sparing add-on.
  5. Neunert C, Terrell DR, Arnold DM, et al. American Society of Hematology 2019 guidelines for immune thrombocytopenia. Blood Adv. 2019;3(23):3829–3866. doi.org/10.1182/bloodadvances.2019000966 ASH guideline on initial corticosteroid therapy for adult immune thrombocytopenia, including dexamethasone pulse and prednisone 1 mg/kg/day options.
  6. Rovin BH, Adler SG, Barratt J, et al. KDIGO 2021 clinical practice guideline for the management of glomerular diseases. Kidney Int. 2021;100(4S):S1–S276. doi.org/10.1016/j.kint.2021.05.021 KDIGO guideline supporting prednisone-based regimens for childhood and adult nephrotic syndrome (e.g., 60 mg/m²/day initial pediatric dose).
Key Clinical Trials and Systematic Reviews
  1. Leuppi JD, Schuetz P, Bingisser R, et al. Short-term vs conventional glucocorticoid therapy in acute exacerbations of chronic obstructive pulmonary disease: the REDUCE randomized clinical trial. JAMA. 2013;309(21):2223–2231. doi.org/10.1001/jama.2013.5023 REDUCE trial establishing non-inferiority of a 5-day vs 14-day prednisone 40 mg/day course in acute COPD exacerbations; basis of the GOLD recommendation.
  2. RECOVERY Collaborative Group. Dexamethasone in hospitalized patients with Covid-19. N Engl J Med. 2021;384(8):693–704. doi.org/10.1056/NEJMoa2021436 RECOVERY trial demonstrating mortality benefit of dexamethasone 6 mg/day in oxygen-requiring or ventilated COVID-19; prednisone 40 mg/day is the accepted equivalent regimen.
  3. Da Silva JA, Jacobs JW, Kirwan JR, et al. Safety of low dose glucocorticoid treatment in rheumatoid arthritis: published evidence and prospective trial data. Ann Rheum Dis. 2006;65(3):285–293. doi.org/10.1136/ard.2005.038638 Systematic review demonstrating that adverse effects of low-dose glucocorticoid therapy in RA are modest and frequently not statistically different from placebo when assessed in randomized trials.
  4. Hoes JN, Jacobs JW, Verstappen SM, Bijlsma JW, Van der Heijden GJ. Adverse events of low- to medium-dose oral glucocorticoids in inflammatory diseases: a meta-analysis. Ann Rheum Dis. 2009;68(12):1833–1838. doi.org/10.1136/ard.2008.100008 Meta-analysis quantifying adverse-event rates with low-to-medium-dose glucocorticoid therapy in inflammatory disease; primary source for the descriptive frequency tiers used in this monograph.
Regulatory & Reference Resources
  1. Sullivan PJ, Sullivan PB. National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group. 2020 focused updates to the asthma management guidelines: a report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group. J Allergy Clin Immunol. 2020;146(6):1217–1270. doi.org/10.1016/j.jaci.2020.10.003 NHLBI/NAEPP 2020 asthma guideline update; supports systemic glucocorticoid bursts (1–2 mg/kg/day in pediatrics, 40–60 mg/day in adults) for asthma exacerbations.
  2. Gronseth GS, Paduga R; American Academy of Neurology. Evidence-based guideline update: steroids and antivirals for Bell palsy. Neurology. 2012;79(22):2209–2213. doi.org/10.1212/WNL.0b013e318275978c AAN guideline supporting oral corticosteroids (prednisone 60 mg/day for 5 days then taper) initiated within 72 hours of Bell’s palsy onset.