Is it better to take prednisone (corticosteroid) in the morning or evening?

Prednisone Administration Timing: Morning vs Evening

Prednisone should be administered in the morning prior to 9 am to minimize adrenal suppression and better mimic the natural cortisol circadian rhythm. 1

Rationale for Morning Administration

• The maximal activity of the adrenal cortex occurs between 2 am and 8 am, with minimal activity between 4 pm and midnight 1
• Exogenous corticosteroids suppress adrenocortical activity the least when given at the time of maximal natural cortisol activity (morning) 1
• Morning administration helps recreate the natural diurnal rhythm of cortisol, which is important for metabolic health 2
• Taking prednisone in the morning allows cortisol levels to decrease throughout the day, reaching their lowest point at midnight, similar to the natural pattern 1

Dosing Recommendations

• For single daily dose regimens, prednisone should be taken upon awakening (before 9 am) 1, 3
• For divided dose regimens, the largest portion (typically 2/3) should be given in the morning and the remainder in early afternoon (not later than 4-6 hours before bedtime) 3
• Typical prednisolone dosing for adrenal insufficiency is 4-5 mg on awakening, or 3 mg on awakening and 1-2 mg at 14:00h 3, 4

Benefits of Morning Administration

• Reduces risk of insomnia, a common side effect when corticosteroids are taken in the evening 3
• Better mimics the natural cortisol rhythm, which may improve overall treatment outcomes 2, 5
• Results in less adrenal suppression compared to evening dosing or divided doses throughout the day 6, 7
• May help prevent weight gain and other cushingoid features associated with disruption of normal cortisol patterns 1

Special Considerations

• For patients experiencing morning nausea or lack of appetite (common in adrenal insufficiency), waking up earlier to take the first dose and then going back to sleep may help relieve symptoms 3
• Night shift workers should adjust their dosing schedule according to their sleep-wake pattern (e.g., taking the first dose upon awakening before going to work) 3
• For rheumatoid arthritis specifically, a modified-release prednisone taken at bedtime (designed to release medication 4 hours after ingestion) may be beneficial for reducing morning stiffness 8
• Patients with severe symptoms may benefit from divided doses, but the last dose should be taken no later than 4-6 hours before bedtime 3

Monitoring and Adjustment

• Clinical assessment is the primary method for monitoring glucocorticoid replacement adequacy rather than laboratory values 3
• Signs of over-replacement include weight gain, insomnia, and peripheral edema 3
• Signs of under-replacement include lethargy, nausea, poor appetite, weight loss, and increased pigmentation 3
• Dose adjustments should be made based on patient symptoms, energy levels, and overall well-being 3

Patient Education

• All patients on long-term prednisone should be educated on stress dosing for illness or injury 3
• Patients should be advised not to stop prednisone abruptly 1
• Taking prednisone with food or milk may reduce gastric irritation 1
• Patients should be aware of medication interactions that may affect prednisone metabolism (e.g., anticonvulsants may increase prednisone requirements) 3, 4

In conclusion, morning administration of prednisone is generally preferred to align with the body's natural cortisol rhythm, minimize adrenal suppression, and reduce side effects like insomnia.