Can prednisolone be administered twice daily (bid)?

Can Prednisolone Be Given Twice Daily (BID)?

Yes, prednisolone can be administered twice daily (BID), but single daily dosing is generally preferred for most conditions because it causes less adrenal suppression while maintaining equal efficacy. 1

Standard Dosing Recommendation

Single daily dosing is the recommended approach for most clinical scenarios:

• The British Society of Gastroenterology explicitly states that single daily dosing is as effective as split-dosing and causes less adrenal suppression for ulcerative colitis treatment. 1
• KDIGO guidelines recommend oral prednisone be administered as a single daily dose for nephrotic syndrome in children. 1
• The FDA label indicates that prednisolone can be given in divided doses (3-4 times daily) for pediatric patients, with dosing ranging from 0.14 to 2 mg/kg/day in three or four divided doses. 2

When BID Dosing May Be Considered

Split dosing can be used in specific clinical situations, though it comes with trade-offs:

Faster Time to Remission in Nephrotic Syndrome

• A 2023 randomized controlled trial demonstrated that split-dose prednisolone (2/3 morning, 1/3 evening) achieved remission significantly faster than single-dose (8.02 days vs 9.74 days, p=0.001) in children with nephrotic syndrome relapses. 3
• However, this same study found no difference in adverse events between the two dosing strategies. 3

Potential for Lower Total Daily Dose

• One observational study in glomerulonephritis and transplant patients suggested that twice-daily fractionated dosing (2 x 1.25 mg = 2.5 mg total) was as effective as once-daily dosing (4.0 mg) with less diabetogenic effect. 4
• This approach resulted in significantly lower proteinuria (-0.12 g/L vs +0.08 g/L, p=0.008). 4

Critical Caveat: Increased HPA Axis Suppression

The major disadvantage of BID dosing is greater hypothalamic-pituitary-adrenal (HPA) axis suppression:

• A 2023 randomized controlled trial in children with first-episode nephrotic syndrome found that divided-dose prednisolone caused 100% HPA suppression compared to 83% with single-dose (p=0.02). 5
• Children on divided doses also had shorter time to first relapse (median 28 days vs 131 days, p=0.002). 5
• The British Society of Gastroenterology emphasizes that single daily dosing minimizes adrenal suppression. 1

Practical Algorithm for Deciding

Use single daily dosing (morning) as default for:

• Ulcerative colitis (40 mg daily). 1
• Nephrotic syndrome initial episodes (60 mg/m² or 2 mg/kg/day, maximum 60 mg). 1
• Asthma exacerbations (40-60 mg daily for adults; 1-2 mg/kg/day for children). 1
• Most inflammatory conditions requiring moderate-to-high dose therapy. 1

Consider BID dosing only when:

• Rapid remission is critical and the patient can tolerate increased HPA suppression risk. 3
• Using very low maintenance doses (total 2.5-5 mg/day) where fractionation may improve efficacy. 4
• Patient has documented poor response to single daily dosing. 4

Never use BID dosing for:

• Short courses (<10 days), where tapering and dosing frequency are irrelevant. 1, 6
• Patients at high risk for adrenal insufficiency complications. 5

Important Warnings

• Splitting doses substantially increases total glucocorticoid exposure (higher AUC), which may increase side effects. 7
• The FDA label allows divided dosing but does not preferentially recommend it over single dosing. 2
• For replacement therapy in adrenal insufficiency, once-daily prednisolone (3-4 mg) is sufficient and mimics circadian rhythm better than multiple daily doses. 8, 7