What oral steroid has less fluid retention?

Oral Steroids with Reduced Fluid Retention

Budesonide MMX is the oral corticosteroid with the least fluid retention, as it has low systemic bioavailability and fewer systemic corticosteroid adverse effects compared to traditional oral steroids like prednisone. 1

Why Budesonide MMX Has Less Fluid Retention

Pharmacological Basis

• Budesonide MMX and other second-generation corticosteroids (such as beclomethasone dipropionate) have demonstrated efficacy for induction of remission with significantly fewer systemic corticosteroid adverse effects compared to prednisone. 1

• The Toronto Consensus guidelines specifically note that oral corticosteroid preparations with low systemic bioavailability, such as budesonide MMX, show efficacy while minimizing systemic adverse effects including edema. 1

• Pooled results from three trials comparing second-generation corticosteroids to oral prednisone showed no significant difference in inducing remission (RR 1.04,95% CI 0.96-1.13), but rates of steroid-related adverse events were significantly lower with second-generation corticosteroids (RR 0.32,95% CI 0.16-0.64). 1

Mechanism of Reduced Fluid Retention

• Traditional corticosteroids like prednisone have mineralocorticoid activity that stimulates sodium entry into cells and potassium loss, particularly evident in the kidney where rapid ion exchange leads to sodium retention and hypertension. 2

• Prednisolone has "slight mineralocorticoid activity" that causes sodium retention and hypertension through stimulation of ion exchange in the kidney. 2

• Budesonide MMX undergoes extensive first-pass hepatic metabolism, resulting in lower systemic bioavailability and therefore less mineralocorticoid effect compared to systemically absorbed corticosteroids. 1

Clinical Evidence on Fluid Retention

Prednisone/Prednisolone Side Effect Profile

• In a prospective study of 101 patients treated with prednisone, fluid retention or bloating was the most common adverse symptom, particularly in those receiving treatment for more than two weeks. 3

• Approximately 50% of patients experience short-term corticosteroid-related adverse events including edema when treated with traditional oral corticosteroids. 1

• Despite known mineralocorticoid activity, a 2021 study of 945 ICU patients found that glucocorticoids themselves appear not to contribute substantially to fluid retention when confounding variables are properly controlled. 4

Practical Clinical Algorithm

When to Choose Budesonide MMX Over Prednisone

1. For mild to moderate ulcerative colitis of any disease extent, budesonide MMX is suggested as an alternative first-line therapy to induce complete remission (GRADE: Weak recommendation, high-quality evidence). 1

2. For patients with relative contraindications to high-dose corticosteroids (including conditions where fluid retention would be particularly problematic such as uncontrolled hypertension or heart failure), budesonide MMX should be strongly considered. 1

3. For patients requiring corticosteroid therapy who have pre-existing fluid retention, hypertension, congestive heart failure, or renal insufficiency, budesonide MMX is preferable to minimize sodium retention. 2

Important Caveats

• Not all budesonide formulations are equivalent—the ileal-release preparations of budesonide (Entocort and Budenofalk) were inferior to placebo and 5-ASA respectively, so specifically the MMX formulation should be used. 1

• Budesonide MMX is primarily studied and indicated for inflammatory bowel disease; for other conditions requiring systemic corticosteroid therapy, traditional steroids may still be necessary despite their fluid retention effects. 1

• The lowest possible dose of any corticosteroid should be used to control the condition, and when reduction in dosage is possible, the reduction should be gradual. 2

Monitoring Considerations

• When using traditional oral corticosteroids like prednisone, parameters to monitor include weight, blood pressure, triglycerides, glucose, and urea and electrolytes. 5

• Corticosteroids should be used with caution in patients with hypertension, congestive heart failure, or renal insufficiency due to sodium retention with resultant edema and potassium loss. 2

• Blood pressure and weight should be monitored regularly in all patients receiving oral corticosteroids, regardless of formulation. 5