What is the equivalent dose and administration regimen of hydrocortisone (corticosteroid) to methylprednisolone (glucocorticoid) 40 mg, in terms of effectiveness and duration of action, and is it better to administer it as a single 200 mg intravenous (IV) dose or divided into multiple doses?

From the Guidelines

The equivalent dose of hydrocortisone to 40 mg of methylprednisolone is approximately 200 mg, as hydrocortisone has about one-fifth the potency of methylprednisolone. For most clinical situations, dividing the 200 mg hydrocortisone into multiple doses (typically 50 mg every 6 hours) is preferable to a single 200 mg IV dose, as this approach better mimics the body's natural cortisol secretion pattern and provides more consistent anti-inflammatory effects throughout the day 1.

Administration Regimen

When considering the administration regimen of hydrocortisone, it's crucial to note that the plasma elimination half-time of exogenously administered hydrocortisone is approximately 90 min, which may be shorter in patients taking inducers of liver enzyme CYP3A4 or suffering from hyperthyroidism, and longer in critically ill patients 1. Given this, dividing the dose into multiple administrations, such as 100 mg IV every 8 hours or 50 mg every 6 hours, may be more effective in maintaining therapeutic levels.

Route of Administration

The route of administration is also an important consideration. Intravenous (IV) infusion is recommended for maintaining plasma cortisol concentrations seen in a normal stress response, especially in the peri-operative period until normal enteral function returns 1. However, intramuscular (IM) administration has a long tradition of safety and clinical effectiveness and may be prescribed in circumstances where IV infusion therapy is impractical.

Clinical Considerations

It's also important to consider that some patients, such as those taking drugs that induce CYP3A4 or obese adults, may require higher doses of hydrocortisone, and clinicians should maintain a high index of suspicion for adrenal crises in these patients and be prepared to immediately increase the dose if necessary 1. In such cases, commencing on a continuous infusion of hydrocortisone may reduce the risks of decompensation.

Monitoring and Side Effects

Regardless of the dosing regimen selected, monitoring for electrolyte imbalances, blood glucose elevations, and other steroid-related side effects is recommended. This is particularly important when switching between hydrocortisone and methylprednisolone, as hydrocortisone has more mineralocorticoid activity than methylprednisolone, which may lead to more sodium retention and potassium loss.

From the FDA Drug Label

For the purpose of comparison, the following is the equivalent milligram dosage of the various glucocorticoids: These dose relationships apply only to oral or intravenous administration of these compounds When these substances or their derivatives are injected intramuscularly or into joint spaces, their relative properties may be greatly altered.

The equivalent dose of hydrocortisone to methylprednisolone 40 mg is not directly stated in the provided drug label. However, based on general knowledge of glucocorticoid potency, methylprednisolone is approximately 1.25 times more potent than hydrocortisone.

• The dose of hydrocortisone equivalent to methylprednisolone 40 mg can be estimated to be around 50 mg.
• The best method for injection of hydrocortisone in this situation is intravenous (IV) administration.
• The label suggests that high-dose corticosteroid therapy should be continued only until the patient's condition has stabilized, usually not beyond 48 to 72 hours.
• The initial dose of SOLU-CORTEF Sterile Powder is 100 mg to 500 mg, depending on the specific disease entity being treated.
• The dose may be repeated at intervals of 2,4, or 6 hours as indicated by the patient's response and clinical condition.
• It is recommended to individualize the dosage based on the disease under treatment and the response of the patient.
• Regarding the administration of 200 mg of hydrocortisone, it may be better to divide the dose into 2 doses of 100 mg each, administered at intervals of 2 to 4 hours, to minimize potential side effects and optimize efficacy 2.

From the Research

Equivalent Dose of Methylprednisolone and Hydrocortisone

• The equivalent dose of methylprednisolone to hydrocortisone is not directly stated in the provided studies, but it can be inferred from the study 3 that the equivalent dose of methylprednisolone in 24 hours is compared to hydrocortisone doses.
• The study 4 provides information on the antirheumatic potencies of different corticosteroids, including methylprednisolone and hydrocortisone, but does not provide a direct equivalent dose.

Effectiveness and Duration of Action

• The study 5 compares the efficacy of methylprednisolone, dexamethasone, and hydrocortisone in patients with COVID-19-related acute respiratory distress syndrome, and finds that dexamethasone may have a better clinical status at 28-day follow-up compared to methylprednisolone and hydrocortisone at an equivalent dose.
• The study 6 compares the efficacy of intravenous methylprednisolone followed by oral methylprednisolone with intravenous hydrocortisone followed by oral prednisolone in patients with acute bronchial asthma, and finds that the methylprednisolone regimen is more efficacious and safer.
• The study 7 compares the efficacy of intravenous methylprednisolone followed by oral methylprednisolone with intravenous hydrocortisone followed by oral prednisolone in patients with acute exacerbation of chronic obstructive pulmonary disease, and finds that the methylprednisolone regimen produces greater improvement in lung function.

Administration Regimen of Hydrocortisone

• The study 6 administers hydrocortisone 200 mg intravenously 6-hourly until discharge, followed by oral prednisolone 0.75 mg/kg daily for 2 weeks.
• The study 7 administers hydrocortisone 200 mg 6-hourly until discharge, followed by oral prednisolone 0.75 mg/kg/day for 2 weeks.
• The study 3 suggests that low dose corticosteroids (< or = 80 mg/day of methylprednisolone or < or = 400 mg/day of hydrocortisone) appear to be adequate in the initial management of acute severe asthma requiring hospital admission.

Route of Administration and Dose

• The study 6 compares the efficacy of intravenous methylprednisolone followed by oral methylprednisolone with intravenous hydrocortisone followed by oral prednisolone, and finds that the methylprednisolone regimen is more efficacious and safer.
• The study 7 compares the efficacy of intravenous methylprednisolone followed by oral methylprednisolone with intravenous hydrocortisone followed by oral prednisolone, and finds that the methylprednisolone regimen produces greater improvement in lung function.
• The study 3 suggests that there are no significant differences in side effects or rates of respiratory failure among the varying doses of corticosteroids, and that low dose corticosteroids appear to be adequate in the initial management of acute severe asthma requiring hospital admission.

Intervals for Divided Doses

• The study 6 administers hydrocortisone 200 mg intravenously 6-hourly until discharge.
• The study 7 administers hydrocortisone 200 mg 6-hourly until discharge.
• The study 3 does not provide information on the intervals for divided doses.