AHFS Class:

• Adrenals 68:04

Generic Name(s):

• Hydrocortisone

• Hydrocortisone Sodium Succinate

Hydrocortisone (cortisol) is a glucocorticoid secreted by the adrenal cortex.

Hydrocortisone or cortisone is usually the corticosteroid of choice for replacement therapy in patients with adrenocortical insufficiency, because these drugs have both glucocorticoid and mineralocorticoid properties. Concomitant administration of a more potent mineralocorticoid (fludrocortisone) may be required in some patients. For anti-inflammatory or immunosuppressive uses, synthetic glucocorticoids which have minimal mineralocorticoid activity are preferred.

Hydrocortisone has been used as adjunctive therapy in the treatment of serious complications from coronavirus disease 2019 (COVID-19)†.1005,1006,1008,1009 Patients with severe COVID-19 may develop a systemic inflammatory response that can result in lung injury and multisystem organ dysfunction.1005 The potent anti-inflammatory effects of corticosteroids (e.g., hydrocortisone) may prevent or mitigate these deleterious effects.1005

Administration

The route of administration and dosage of hydrocortisone and its derivatives depend on the condition being treated and the response of the patient.

Hydrocortisone

Hydrocortisone is administered orally; the drug also was previously administered by IM injection, but absorption of the drug from the injection site is slow (4-8 hours) and a parenteral dosage form currently is not commercially available in the US.

Hydrocortisone Sodium Succinate

Hydrocortisone sodium succinate may be administered by IM or IV injection or by IV infusion. Hydrocortisone sodium succinate is reconstituted for IM or IV injection with bacteriostatic water for injection or bacteriostatic 0.9% sodium chloride injection according to the manufacturer's instructions. When the drug is administered by direct IV injection, it should be administered over a period of at least 30 seconds. For IV infusion, the reconstituted hydrocortisone sodium succinate should be further diluted with 5% dextrose, 0.9% sodium chloride, or 5% dextrose in 0.9% sodium chloride injection to a concentration of 0.1-1 mg/mL.

Extemporaneously Compounded Oral Liquid

Extemporaneously compounded oral suspensions of hydrocortisone have been prepared.133,134

Standardize 4 Safety

Standardized concentrations for an extemporaneously prepared oral suspension of hydrocortisone have been established through Standardize 4 Safety (S4S), a national patient safety initiative to reduce medication errors, especially during transitions of care. 252Multidisciplinary expert panels were convened to determine recommended standard concentrations. Because recommendations from the S4S panels may differ from the manufacturer's prescribing information, caution is advised when using concentrations that differ from labeling, particularly when using rate information from the label. 252 For additional information on S4S (including updates that may be available), see [Web].252

Dosage

General

Dosage of hydrocortisone sodium succinate is expressed in terms of hydrocortisone. IM or IV therapy is generally reserved for patients who are unable to take the drug orally or for use in emergency situations. Hydrocortisone sodium succinate is absorbed rapidly, and peak plasma concentrations are attained within 1 hour following IM administration. Parenteral injection of hydrocortisone sodium succinate must be given at 4- to 6-hour intervals if constant high blood concentrations of hydrocortisone are required. After the initial emergency period, a longer-acting injectable corticosteroid preparation or oral administration of a corticosteroid should be considered. Dosage for infants and children should be based on the severity of the disease and the response of the patient rather than on strict adherence to dosage indicated by age, body weight, or body surface area. After a satisfactory response is obtained, dosage should be decreased in small decrements to the lowest level that maintains an adequate clinical response. Patients should be continually monitored for signs that indicate dosage adjustment is necessary, such as remissions or exacerbations of the disease and stress (surgery, infection, trauma). If hydrocortisone is used orally for prolonged anti-inflammatory therapy, an alternate-day dosage regimen should be considered. Following long-term therapy, hydrocortisone should be withdrawn gradually.

Hydrocortisone

The initial adult oral dosage of hydrocortisone as the free alcohol may range from 10-320 mg daily, depending on the disease being treated, and is usually administered in 3 or 4 divided doses. Some clinicians state that children may be given an oral dosage of 0.56-8 mg/kg daily or 16-240 mg/m² daily, administered in 3 or 4 divided doses.

Hydrocortisone Sodium Succinate

The IM or IV dosage of hydrocortisone as the sodium succinate may range from 100 mg to 8 g daily. The usual dosage is 100-500 mg IM or IV initially and every 2-10 hours as needed. Some clinicians state that the usual IM or IV dosage for children is 0.16-1 mg/kg or 6-30 mg/m² administered 1 or 2 times daily.

In life-threatening shock, massive IV doses of hydrocortisone as the sodium succinate (such as 50 mg/kg initially and repeated in 4 hours and/or every 24 hours if needed, or 0.5-2 g IV initially and repeated at 2- to 6-hour intervals as required) have been recommended by some clinicians. In such cases, the drug is administered by direct IV injection over a period of one to several minutes. High-dose therapy should be continued only until the patient's condition has stabilized and usually should not be continued beyond 48-72 hours. If massive corticosteroid therapy is needed beyond 72 hours, a corticosteroid which causes less sodium retention (such as methylprednisolone sodium succinate or dexamethasone sodium phosphate) should be used to minimize the risk of hypernatremia.

Coronavirus Disease 2019 (COVID-19)

When used for adjunctive therapy in adults with coronavirus disease 2019 (COVID-19)†, the National Institutes of Health (NIH) COVID-19 Treatment Guidelines Panel recommends the use of hydrocortisone 160 mg daily given IV in 2-4 divided doses when dexamethasone is not available.1005 The World Health Organization (WHO) Guideline Development Group recommends hydrocortisone 50 mg IV every 8 hours for 7-10 days.1006

When a corticosteroid is used for adjunctive therapy in pediatric patients with COVID-19†, the NIH panel recommends dexamethasone (0.15 mg/kg [maximum dosage 6 mg] given IV or orally for up to 10 days).1005 If dexamethasone is not available, equivalent dosages of an alternative corticosteroid (e.g., hydrocortisone) may be considered.1005

Clinicians also should consult the most recent NIH and WHO COVID-19 treatment guidelines for additional information on use of corticosteroids in patients with COVID-19.1005,1006

Chemistry and Stability

Chemistry

Hydrocortisone (cortisol) is a corticosteroid secreted by the adrenal cortex. The corticosteroid is commercially available as hydrocortisone and hydrocortisone sodium succinate. Hydrocortisone occurs as an odorless, white to practically white, crystalline powder. Hydrocortisone is very slightly soluble in water and sparingly soluble in alcohol. Hydrocortisone sodium succinate occurs as a white or nearly white, odorless, amorphous solid and is very soluble in water and in alcohol. The sodium succinate ester of hydrocortisone is hygroscopic.

Following reconstitution with bacteriostatic water for injection, hydrocortisone sodium succinate injection has a pH of 7-8.

Stability

Commercially available preparations of hydrocortisone should be stored at a temperature less than 40°C, preferably between 15-30°C. Hydrocortisone tablets should be stored in well-closed containers. Reconstituted solutions of hydrocortisone sodium succinate should be stored at 25°C or below. Reconstituted solutions of the drug should not be used unless they are clear, and unused solutions should be discarded after 3 days. Solutions of hydrocortisone and its derivatives are heat labile and must not be autoclaved.

Injections of hydrocortisone and its esters have been reported to be incompatible with various drugs, but the compatibility depends on several factors (e.g., concentration of the drugs, resulting pH, temperatures). Specialized references should be consulted for more specific compatibility information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Only references cited for selected revisions after 1984 are available electronically.

133. Fawcett JP, Boulton DW, Jiang R, Woods DJ. Stability of hydrocortisone oral suspensions prepared from tablets and powder. Ann Pharmacother. 1995 Oct;29(10):987-90. doi: 10.1177/106002809502901005. PMID: 8845559.

134. Manchanda A, Laracy M, Savji T, Bogner RH. Stability of an Alcohol-free, Dye-free Hydrocortisone (2 mg/mL) Compounded Oral Suspension. Int J Pharm Compd. 2018 Jan-Feb;22(1):66-75. PMID: 29385387..

252. ASHP. Standardize 4 Safety: compounded oral liquid standards. Updated 2024 Mar. From ASHP website. Updates may be available at ASHP website. [Web]

1000. Food and Drug Administration. Epidural corticosteroid injection: Drug safety communication - risk of rare but serious neurologic problems. 2014 Apr 23. From FDA website. Accessed 2014 May 19. [Web]

1001. Food and Drug Administration. FDA drug safety communication: FDA requires label changes to warn of rare but serious neurologic problems after epidural corticosteroid injections for pain. 2014 Apr 23. From FDA website. Accessed 2014 May 19. [Web]

1002. Rathmell JP. Toward improving the safety of transforaminal injection. Anesth Analg . 2009; 109:8-10. [PubMed 19535690]

1003. Cohen SP, Bicket MC, Jamison D et al. Epidural steroids: a comprehensive, evidence-based review. Reg Anesth Pain Med . 2013 May-Jun; 38:175-200.

1005. National Institutes of Health. COVID-19 treatment guidelines. Updated 2021 Aug 4. From NIH website. Accessed 2021 Aug 12. Updates may be available at NIH website. [Web]

1006. World Health Organization. Therapeutics and COVID-19: living guideline. 2021 Jul 6. From WHO website. Accessed 2021 Jul 7. [Web]

1008. Dequin PF, Heming N, Meziani F et al. Effect of Hydrocortisone on 21-Day Mortality or Respiratory Support Among Critically Ill Patients With COVID-19: A Randomized Clinical Trial. JAMA . 2020; 324:1298-1306. [PubMed 32876689]

1009. Writing Committee for the REMAP-CAP Investigators., Angus DC, Derde L et al. Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial. JAMA . 2020; 324:1317-29. [PubMed 32876697]

1015. Stauffer WM, Alpern JD, Walker PF. COVID-19 and Dexamethasone: A Potential Strategy to Avoid Steroid-Related Strongyloides Hyperinfection. JAMA . 2020; 324:623-4. [PubMed 32761166]

1016. Liu J, Wang T, Cai Q et al. Longitudinal changes of liver function and hepatitis B reactivation in COVID-19 patients with pre-existing chronic hepatitis B virus infection. Hepatol Res . 2020; 50:1211-21. [PubMed 32761993]