Hydrocortisone

AHFS Class: Adrenals (68:04)

ATC Class: H02AB09
VA Class: HS051

Compound F

Cortisol

View the associated Essentials monograph.

Introduction

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

See Uses in the associated General Statement for more information.

Uses

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.

See Dosage and Administration in the associated General Statement for more information.

Dosage and Administration

The route of administration and dosage of hydrocortisone and its derivatives depend on the condition being treated and the response of the patient. Dosage of hydrocortisone cypionate, sodium phosphate, and 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. The sodium phosphate and sodium succinate esters of hydrocortisone are absorbed rapidly, and peak plasma concentrations are attained within 1 hour following IM administration. Parenteral injection of the soluble esters of hydrocortisone 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. (See the Corticosteroids General Statement 68:04.)

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. 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 Phosphate

Hydrocortisone sodium phosphate may be administered by IM, subcutaneous, or IV injection or by IV infusion. Usually the drug is given parenterally at 12-hour intervals. When hydrocortisone sodium phosphate is administered by IV infusion, the drug can be added to dextrose or sodium chloride injections.

The usual initial adult dosage of hydrocortisone sodium phosphate ranges from 15–240 mg daily depending on the disease being treated. In life-threatening situations, extremely high parenteral dosage may be justified and may be a multiple of the usual oral dosage. Some clinicians state that children are usually given hydrocortisone sodium phosphate 0.16–1 mg/kg or 6–30 mg/m² IM 1 or 2 times daily.

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.

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.

Hydrocortisone Acetate

Hydrocortisone acetate may be administered by intra-articular, intrasynovial, intrabursal, intralesional, or soft tissue injection. Systemic absorption of hydrocortisone acetate from intra-articular injection sites is usually complete within 24–48 hours. A local anesthetic, such as procaine hydrochloride, may be infiltrated into the soft tissue surrounding the joint and/or injected into the joint before the administration of hydrocortisone acetate. Alternatively, the local anesthetic may be mixed in the syringe with hydrocortisone acetate suspension immediately prior to administration.

For intrasynovial, intrabursal, or intra-articular injection, the dosage of hydrocortisone acetate varies with the degree of inflammation and the size and location of the affected area. For large joints such as the knee, 25–50 mg of hydrocortisone acetate may be used. For smaller joints, 10–25 mg may be adequate. The dose for bursae is 25–50 mg and for ganglia 10–25 mg. For soft tissue injection, dosage varies from 5–12.5 mg in tendon sheath inflammation to as much as 25–75 mg for soft tissue infiltration. Injections may be repeated from once every 3–5 days (for bursae) to once every 1–4 weeks (for joints).

See Cautions in the associated General Statement for more information.

See Drug Interactions in the associated General Statement for more information.

See Lab Test Interferences in the associated General Statement for more information.

See Pharmacology in the associated General Statement for more information.

See Pharmacokinetics in the associated General Statement for more information.

See Chemistry and Stability in the associated General Statement for more information.

Chemistry and Stability

Chemistry

Hydrocortisone (cortisol) is a corticosteroid secreted by the adrenal cortex. The corticosteroid is commercially available as hydrocortisone and various derivatives of hydrocortisone. Hydrocortisone and hydrocortisone acetate occur as white to practically white, crystalline powders. Hydrocortisone and hydrocortisone acetate are odorless, and hydrocortisone cypionate is odorless or has a slight odor. Hydrocortisone is very slightly soluble and the acetate and cypionate esters are insoluble in water. Hydrocortisone is sparingly soluble, hydrocortisone acetate is slightly soluble, and hydrocortisone cypionate is soluble in alcohol. Hydrocortisone sodium phosphate occurs as a white to light yellow, odorless or practically odorless powder and is freely soluble in water and slightly 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 phosphate and sodium succinate esters of hydrocortisone are hygroscopic.

Commercially available sterile suspensions of hydrocortisone acetate have a pH of 5–7. Hydrocortisone sodium phosphate injection has a pH of 7.5–8.5. Following reconstitution with bacteriostatic water for injection, hydrocortisone sodium succinate injection has a pH of 7–8. Hydrocortisone cypionate oral suspension has a pH of 2.8–3.2.

Stability

Commercially available preparations of hydrocortisone should be stored at a temperature less than 40°C, preferably between 15–30°C; freezing of the oral suspension and sterile suspensions should be avoided. 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 and suspensions 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.

For further information on chemistry, pharmacology, pharmacokinetics, uses, cautions, drug interactions, laboratory test interferences, and dosage and administration of hydrocortisone, see the Corticosteroids General Statement 68:04. For EENT and topical uses, see 52:08.08 and 84:06, respectively.

Preparations

Hydrocortisone

Routes	Forms	Strengths	Brand Names	Manufacturer
Powder
Oral	Tablets	5 mg	Cortef® (scored)	Pfizer
		10 mg	Cortef® (scored)	Pfizer
			Hydrocortone® (scored)	Merck
		20 mg*	Cortef® (scored)	Pfizer

* available by nonproprietary name

Hydrocortisone Acetate

Routes	Forms	Strengths	Brand Names	Manufacturer
Powder
Parenteral	Injectable suspension	25 mg/mL*
		50 mg/mL*	Hydrocortone® Acetate (with benzyl alcohol)	Merck

* available by nonproprietary name

Hydrocortisone Sodium Phosphate

Routes	Forms	Strengths	Brand Names	Manufacturer
Parenteral	Injection	50 mg (of hydrocortisone) per mL	Hydrocortone® Phosphate (with parabens and sodium bisulfite)	Merck

Hydrocortisone Sodium Succinate

Routes	Forms	Strengths	Brand Names	Manufacturer
Parenteral	For injection	100 mg (of hydrocortisone)*	A-hydroCort® (with benzyl alcohol 18 mg in Univial®)	Hospira
			Solu-Cortef® (preservative-free in vials or with benzyl alcohol 18 mg in Act-O-Vial®)	Pfizer
		250 mg (of hydrocortisone)*	A-hydroCort® (with benzyl alcohol 18 mg in Univial®)	Hospira
			Solu-Cortef® (with benzyl alcohol 16.4 mg in Act-O-Vial®)	Pfizer
		500 mg (of hydrocortisone)*	A-hydroCort® (with benzyl alcohol 36 mg in Univial®)	Hospira
			Solu-Cortef® (with benzyl alcohol 33.4 mg in Act-O-Vial®)	Pfizer
		1 g (of hydrocortisone)*	A-hydroCort® (with benzyl alcohol 72 mg in Univial®)	Hospira
			Solu-Cortef® (with benzyl alcohol 66.9 mg in Act-O-Vial®)	Pfizer

* available by nonproprietary name

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. For the most current and up-to-date pricing information, please visit www.drugstore.com.

Cortef 10MG Tablets (PFIZER U.S.): 30/$25.99 or 90/$53.97

Cortef 20MG Tablets (PFIZER U.S.): 30/$36.65 or 90/$95.32

Cortef 5MG Tablets (PFIZER U.S.): 50/$24.99 or 100/$37.98

Hydrocortisone 10MG Tablets (GLADES PHARMACEUTICALS): 100/$39.99 or 200/$75.98

Hydrocortisone 20MG Tablets (WEST-WARD): 30/$12.99 or 90/$22.97

Hydrocortisone 5MG Tablets (GLADES PHARMACEUTICALS): 50/$19.99 or 100/$29.97

Selected Revisions October 2006, © Copyright, May 1978, American Society of Health-System Pharmacists, Inc. 7272 Wisconsin Avenue, Bethesda, MD 20814.