Hydrocortisone

Description

Hydrocortisone is a white to practically white crystalline powder. Chemically, it is identified as pregn-4-ene-3,20-dione, 11,17,21-trihydroxy-, (11ß)-. The molecular formula of hydrocortisone is C21H30O5, and it has a molecular weight of 362.47 g/mol. Hydrocortisone Cream USP is available in two strengths: 1% and 2.5%. Each gram of the 1% cream contains 10 mg of hydrocortisone, while each gram of the 2.5% cream contains 25 mg of hydrocortisone. The base of Hydrocortisone Cream includes cetyl alcohol, isopropyl palmitate, methylparaben, mineral oil, lanolin alcohol, polyoxyl 40 stearate, polysorbate 60, propylene glycol monostearate, propylene glycol, propylparaben, purified water, sorbic acid, and sorbitan monostearate.

Uses and Indications

This drug is indicated for the relief of the inflammatory and pruritic manifestations associated with corticosteroid-responsive dermatoses.

There are no teratogenic or nonteratogenic effects reported for this medication.

Dosage and Administration

The medication should be applied to the affected area as a thin film, with a frequency of 2 to 4 times daily, contingent upon the severity of the condition being treated. For patients with psoriasis or other recalcitrant conditions, occlusive dressings may be utilized to enhance the therapeutic effect.

In the event that an infection develops, the use of occlusive dressings must be discontinued immediately, and appropriate antimicrobial therapy should be initiated to address the infection.

Contraindications

Topical corticosteroids are contraindicated in patients with a history of hypersensitivity to any of the components of the preparation.

Use of topical corticosteroids should be discontinued if irritation develops, and appropriate therapy should be initiated. Additionally, these corticosteroids are contraindicated in the presence of dermatological infections; treatment should not resume until the infection has been adequately controlled.

Systemic absorption of topical corticosteroids may lead to reversible hypothalamic-pituitary-adrenal (HPA) axis suppression, as well as manifestations of Cushing's syndrome, hyperglycemia, and glucosuria in some patients, warranting caution in their use.

Warnings and Precautions

Systemic absorption of topical corticosteroids has been associated with reversible hypothalamic-pituitary-adrenal (HPA) axis suppression, which may manifest as Cushing's syndrome, hyperglycemia, and glucosuria in certain patients. Factors that can enhance systemic absorption include the use of more potent steroids, application over extensive surface areas, prolonged treatment duration, and the use of occlusive dressings. Should irritation occur, the application of topical corticosteroids must be discontinued, and appropriate alternative therapy should be initiated.

In cases where dermatological infections are present, it is imperative to employ an appropriate antifungal or antibacterial agent. If there is no prompt favorable response, the corticosteroid treatment should be halted until the infection is adequately managed.

Patients receiving high doses of potent topical steroids, particularly when applied to large areas or under occlusive dressings, should undergo periodic evaluations for signs of HPA axis suppression. This can be assessed through urinary free cortisol and ACTH stimulation tests. If evidence of HPA axis suppression is detected, it is recommended to withdraw the corticosteroid, reduce the frequency of application, or consider switching to a less potent steroid. Typically, recovery of HPA axis function occurs rapidly and completely upon discontinuation of the corticosteroid; however, in rare instances, withdrawal symptoms may arise, necessitating the use of supplemental systemic corticosteroids.

It is important to note that children may absorb larger amounts of topical corticosteroids relative to their body size, rendering them more susceptible to systemic toxicity. Therefore, careful monitoring and consideration of dosage are essential in this population.

For monitoring purposes, the following laboratory tests are recommended: urinary free cortisol test and ACTH stimulation test.

Side Effects

Patients may experience a range of local and systemic adverse reactions associated with the use of this medication.

Local adverse reactions are commonly reported and include burning, itching, irritation, and dryness. Other local effects may consist of folliculitis, hypertrichosis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, maceration of the skin, secondary infections, skin atrophy, striae, and miliaria. In cases where irritation develops, it is recommended that the topical corticosteroids be discontinued and appropriate therapy instituted.

Systemic adverse reactions, although less common, can occur and include reversible hypothalamic-pituitary-adrenal (HPA) axis suppression, manifestations of Cushing's syndrome, hyperglycemia, and glucosuria.

In pediatric populations, there is an increased risk of HPA axis suppression and Cushing's syndrome, as well as intracranial hypertension. Manifestations of adrenal suppression in children may include linear growth retardation, delayed weight gain, low plasma cortisol levels, and an absence of response to ACTH stimulation. Signs of intracranial hypertension may present as bulging fontanelles, headaches, and bilateral papilledema.

It is important to note that signs and symptoms of steroid withdrawal may occur, necessitating the use of supplemental systemic corticosteroids. Children may absorb proportionally larger amounts of topical corticosteroids, making them more susceptible to systemic toxicity. In the presence of dermatological infections, the use of an appropriate antifungal or antibacterial agent should be initiated. If a favorable response does not occur promptly, the corticosteroid should be discontinued until the infection is adequately controlled.

Drug Interactions

There are currently no documented drug interactions associated with this medication. Additionally, there is no information available regarding interactions with laboratory tests. As such, no specific recommendations for dosage adjustments or monitoring are warranted at this time.

Packaging & NDC

The table below lists all NDC Code configurations of Hydrocortisone, the U.S. brand-name prescription product. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

Pediatric Use

Pediatric patients may exhibit increased susceptibility to topical corticosteroid-induced hypothalamic-pituitary-adrenal (HPA) axis suppression and Cushing's syndrome compared to mature patients, primarily due to a larger skin surface area relative to body weight. Reports indicate that HPA axis suppression, Cushing's syndrome, and intracranial hypertension have occurred in this population following the use of topical corticosteroids.

Manifestations of adrenal suppression in pediatric patients can include linear growth retardation, delayed weight gain, low plasma cortisol levels, and a lack of response to ACTH stimulation. Additionally, signs of intracranial hypertension may present as bulging fontanelles, headaches, and bilateral papilledema.

To mitigate these risks, the administration of topical corticosteroids in pediatric patients should be restricted to the minimum amount necessary to achieve an effective therapeutic outcome. It is important to consider that chronic corticosteroid therapy may adversely affect the growth and development of pediatric patients.

Geriatric Use

Elderly patients may not have specific information regarding the use of this medication, including dosage adjustments, safety concerns, or special precautions. Therefore, healthcare providers should exercise caution when prescribing this medication to geriatric patients. It is advisable to monitor these patients closely for any adverse effects or changes in therapeutic response, given the lack of targeted data for this population.

Pregnancy

Corticosteroids are generally considered teratogenic in laboratory animals when administered systemically at relatively low dosage levels. Additionally, more potent corticosteroids have demonstrated teratogenic effects following dermal application in these animal studies. However, there are no adequate and well-controlled studies in pregnant women to assess the teratogenic effects of topically applied corticosteroids.

Given the potential risks, topical corticosteroids should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is advised that drugs of this class not be used extensively on pregnant patients, in large amounts, or for prolonged periods of time to minimize any potential adverse fetal outcomes.

Lactation

It is not known whether topical administration of corticosteroids could result in sufficient systemic absorption to produce detectable quantities in breast milk. However, systemically administered corticosteroids are secreted into breast milk in quantities not likely to have a deleterious effect on the breastfed infant.

Caution should be exercised when topical corticosteroids are administered to lactating mothers.

Renal Impairment

Patients with renal impairment may experience altered pharmacokinetics of corticosteroids, which are primarily metabolized in the liver and excreted by the kidneys. Systemic absorption of topical corticosteroids can lead to reversible hypothalamic-pituitary-adrenal (HPA) axis suppression, necessitating careful monitoring in this population.

For patients receiving large doses of potent topical steroids, particularly when applied to extensive areas of skin or under occlusive dressings, periodic evaluation for signs of HPA axis suppression is recommended. This can be assessed through urinary free cortisol and ACTH stimulation tests. Should HPA axis suppression be detected, it is advisable to consider withdrawing the corticosteroid, reducing the frequency of application, or substituting with a less potent steroid.

Typically, recovery of HPA axis function occurs promptly and completely following the discontinuation of the corticosteroid.

Hepatic Impairment

Corticosteroids are primarily metabolized in the liver and subsequently excreted by the kidneys. In patients with hepatic impairment, the metabolism of corticosteroids may be altered, necessitating caution in their use. Some topical corticosteroids and their metabolites are also excreted into the bile, which may further complicate their pharmacokinetics in this population.

Systemic absorption of topical corticosteroids has been associated with reversible hypothalamic-pituitary-adrenal (HPA) axis suppression. This effect is particularly concerning for patients with compromised liver function. Therefore, patients receiving a large dose of a potent topical steroid, especially when applied to a large surface area or under an occlusive dressing, should be evaluated periodically for signs of HPA axis suppression. Monitoring should include urinary free cortisol and ACTH stimulation tests to assess adrenal function.

While recovery of HPA axis function is generally prompt and complete upon discontinuation of the corticosteroid, caution is advised in patients with hepatic impairment due to the potential for altered metabolism. Adjustments to dosing and careful monitoring are recommended to mitigate risks associated with corticosteroid therapy in this patient population.

Overdosage

There is currently no specific information available regarding overdosage for this medication. Healthcare professionals are advised to monitor patients closely for any unusual symptoms or adverse effects that may arise. In the event of suspected overdosage, it is recommended to initiate supportive care and symptomatic treatment as necessary.

Healthcare providers should consider contacting a poison control center or a medical toxicologist for guidance on management strategies tailored to the specific situation. Continuous assessment of the patient's clinical status is essential to ensure appropriate interventions are implemented promptly.

Nonclinical Toxicology

Corticosteroids have been shown to exhibit teratogenic effects in laboratory animals when administered systemically at relatively low dosage levels. Additionally, more potent corticosteroids have demonstrated teratogenicity following dermal application in these animal models. However, there are no adequate and well-controlled studies in pregnant women regarding the teratogenic effects of topically applied corticosteroids. Consequently, the use of topical corticosteroids during pregnancy should be considered only when the potential benefits outweigh the risks to the fetus. It is advised that drugs within this class not be used extensively, in large amounts, or for prolonged periods in pregnant patients.

Long-term animal studies have not been conducted to assess the carcinogenic potential or the effects on fertility associated with topical corticosteroids. Furthermore, studies evaluating the mutagenicity of prednisolone and hydrocortisone have yielded negative results.

Postmarketing Experience

Systemic absorption of topical corticosteroids has been associated with reversible hypothalamic-pituitary-adrenal (HPA) axis suppression, manifestations of Cushing's syndrome, hyperglycemia, and glucosuria in some patients. Factors that may enhance systemic absorption include the use of more potent steroids, application over large surface areas, prolonged use, and the application of occlusive dressings.

Patients receiving high doses of potent topical steroids, particularly when applied to extensive areas or under occlusive dressings, should be periodically evaluated for signs of HPA axis suppression. This evaluation can be conducted using urinary free cortisol and ACTH stimulation tests. In cases where HPA axis suppression is identified, it is recommended to withdraw the drug, reduce the frequency of application, or switch to a less potent steroid. Recovery of HPA axis function is typically prompt and complete following discontinuation of the drug; however, in rare instances, signs and symptoms of steroid withdrawal may necessitate the use of supplemental systemic corticosteroids.

Pediatric patients may exhibit a heightened susceptibility to HPA axis suppression and Cushing's syndrome induced by topical corticosteroids, attributed to a larger skin surface area relative to body weight. Reports indicate that pediatric patients have experienced HPA axis suppression, Cushing's syndrome, and intracranial hypertension. Manifestations of adrenal suppression in this population may include linear growth retardation, delayed weight gain, low plasma cortisol levels, and a lack of response to ACTH stimulation. Symptoms of intracranial hypertension may present as bulging fontanelles, headaches, and bilateral papilledema.

Infrequent local adverse reactions associated with topical corticosteroids may occur, particularly with the use of occlusive dressings. These reactions include burning, itching, irritation, dryness, folliculitis, hypertrichosis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, maceration of the skin, secondary infections, skin atrophy, striae, and miliaria.

Patient Counseling

Patients should be informed that this medication is to be used strictly as directed by their physician and is intended for external use only. They must be cautioned to avoid contact with the eyes to prevent irritation or injury.

It is essential for patients to understand that this medication should not be used for any condition other than the one for which it was prescribed. Healthcare providers should emphasize the importance of adhering to the prescribed use to ensure safety and efficacy.

Patients should be advised that the treated skin area should not be bandaged or covered in a manner that creates an occlusive dressing unless specifically directed by their physician. This is crucial to avoid potential complications or adverse reactions.

Healthcare providers should encourage patients to report any signs of local adverse reactions, particularly if they occur under occlusive dressings. Prompt reporting can facilitate timely management of any issues that may arise.

For parents of pediatric patients, it is important to advise against the use of tight-fitting diapers or plastic pants on children being treated in the diaper area. These garments may act as occlusive dressings, which could lead to increased risk of adverse effects.

Storage and Handling

The product is supplied in accordance with the National Drug Code (NDC) specifications. It should be stored at a temperature range of 20° to 25°C (68° to 77°F), in compliance with USP Controlled Room Temperature guidelines. It is essential to protect the product from freezing to maintain its integrity and efficacy. Proper handling and storage conditions are crucial to ensure the product remains within the specified temperature range.

Additional Clinical Information

The evaluation of hypothalamic-pituitary-adrenal (HPA) axis suppression in patients may be supported by specific diagnostic tests. Clinicians may consider utilizing the urinary free cortisol test and the ACTH stimulation test as part of the assessment process. These tests can provide valuable insights into the functioning of the HPA axis in affected subjects.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Hydrocortisone as submitted by Sun Pharmaceutical Industries, Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)