In an adult without known comorbidities, what are the adverse effects of taking 20 mg prednisone once weekly and how do they compare to taking 20 mg prednisone every two days?

Risks of 20 mg Prednisone Once Weekly vs. Every 2 Days

Taking 20 mg prednisone once weekly carries minimal immunosuppression risk and negligible adverse effects, whereas taking 20 mg every 2 days (averaging 70 mg/week) poses substantially higher risks of infection, metabolic complications, and bone loss due to cumulative glucocorticoid exposure.

Weekly Dosing (20 mg once weekly)

Immunosuppression Risk

• The CDC defines clinically significant immunosuppression as prednisone ≥20 mg/day for at least 2 weeks, not intermittent weekly dosing 1
• A single 20 mg dose once weekly does not meet criteria for immunosuppression requiring live vaccine precautions 1
• This dosing pattern falls well below the threshold for HPA axis suppression, which requires >3 weeks at >7.5 mg/day 2

Adverse Effect Profile

• Minimal risk of systemic adverse effects since cumulative weekly exposure (20 mg/week) is far below therapeutic daily doses 3
• No meaningful risk of cushingoid features, metabolic disturbances, or bone loss at this exposure level 3
• Short-term effects like insomnia or mood changes may occur transiently on dosing day but resolve quickly 4, 5

Clinical Context

• This dosing pattern has no established therapeutic role in rheumatic diseases and provides insufficient anti-inflammatory effect 1, 2
• Doses <7.5 mg/day are generally discouraged for inflammatory conditions due to inadequate efficacy 1, and weekly dosing provides even less sustained exposure

Every-Other-Day Dosing (20 mg every 2 days)

Cumulative Exposure and Risk Profile

• This regimen delivers 70 mg prednisone per week (10 mg/day average), placing patients at moderate risk for glucocorticoid-related adverse effects 3
• Alternate-day dosing of 20 mg is considered "low-level immunosuppression" by ACR guidelines 1

Specific Adverse Effects by Dose Threshold

Linear Dose-Dependent Effects (present at all doses, worse with higher exposure):

• Cushingoid phenotype, ecchymosis, leg edema, parchment-like skin, and sleep disturbance increase progressively with cumulative exposure 3
• Weight gain and hyperphagia occur frequently, reported in 49% of patients on chronic therapy 4
• Insomnia affects 58% of patients and occurs early in treatment 4

Threshold Effects (manifest above specific dose levels):

• At doses ≥5 mg/day equivalent: Increased risk of epistaxis, weight gain, and cataract formation 3
• At doses >7.5 mg/day: Elevated risk of glaucoma, depression/listlessness, and hypertension 3
• At doses ≥10 mg/day: Substantially higher risk of infections, fractures, and GI bleeding 2

Infection Risk

• Doses averaging 10 mg/day increase perioperative infection risk in surgical patients 1
• Observational studies demonstrate increased infection risk at doses >15 mg/day, with the every-other-day regimen approaching this threshold 1

Bone Health

• Doses ≥7.5 mg/day for ≥3 months require bone protection with calcium, vitamin D, and bisphosphonates 1, 2
• The 10 mg/day average from alternate-day dosing mandates osteoporosis prophylaxis 1

Metabolic and Cardiovascular Effects

• Approximately 50% of patients experience mood disturbances, glucose intolerance, and dyspepsia on chronic therapy 1
• Blood pressure, blood glucose, and weight require monitoring at every visit 2

Direct Comparison

Parameter	20 mg once weekly	20 mg every 2 days
Weekly cumulative dose	20 mg	70 mg
Daily average	2.9 mg	10 mg
Immunosuppression	None [1]	Moderate [1]
Bone protection needed	No [1]	Yes [1,2]
HPA axis suppression	No [2]	Possible with prolonged use [2]
Infection risk	Minimal [1]	Moderate [1,2]
Metabolic effects	Negligible [3]	Significant [1,3]
GI prophylaxis	Not required [2]	Recommended [2]

Critical Clinical Implications

For Weekly Dosing

• No established therapeutic benefit for any inflammatory condition at this exposure level 1, 2
• Does not require routine monitoring, bone protection, or GI prophylaxis 1, 2
• Safe from immunosuppression standpoint but clinically ineffective 1

For Every-Other-Day Dosing

• Requires comprehensive monitoring: blood pressure, glucose, weight, and bone density 2
• Mandatory prophylaxis: PPI for GI protection, calcium/vitamin D for bone health 1, 2
• Cannot be stopped abruptly after >1 month of use due to adrenal suppression risk 2
• Should be limited to <3 months when possible to minimize cumulative toxicity 2

Common Pitfalls to Avoid

• Do not assume alternate-day dosing eliminates adverse effects—cumulative weekly exposure determines risk, not dosing frequency 3
• Do not use weekly dosing expecting therapeutic benefit—it provides insufficient anti-inflammatory effect for any established indication 1, 2
• Do not forget stress-dose coverage for patients on alternate-day therapy who develop acute illness or require surgery 2
• Do not overlook bone protection in patients averaging ≥7.5 mg/day, regardless of dosing schedule 1, 2