Hydrocortisone

Description

Hydrocortisone Cream USP, 2.5% contains 25 mg of hydrocortisone per gram in a cream base composed of cetyl alcohol, methylparaben, propylene glycol, propylparaben, purified water, sodium lauryl sulfate, and stearyl alcohol. Hydrocortisone Ointment USP, 2.5% similarly contains 25 mg of hydrocortisone per gram, formulated in an ointment base of light mineral oil and white petrolatum.

Chemically, hydrocortisone is identified as Pregn-4-ene-3,20-dione,11,17,21-trihydroxy-, (11β)-, with a molecular formula of C21H30O5 and a molecular weight of 362.47. The CAS Registry Number for hydrocortisone is 50-23-7. As a member of the topical corticosteroids class, hydrocortisone serves as an anti-inflammatory and antipruritic agent, primarily utilized in synthetic steroid formulations.

Uses and Indications

Topical corticosteroids are indicated for the relief of the inflammatory and pruritic manifestations associated with corticosteroid-responsive dermatoses. These conditions may include, but are not limited to, eczema, psoriasis, and dermatitis.

Limitations of Use: Topical corticosteroids should be used with caution in patients with a history of hypersensitivity to corticosteroids or in the presence of untreated infections. Prolonged use may lead to skin atrophy and other local adverse effects.

Dosage and Administration

Topical corticosteroids should be applied to the affected area as a thin film, with a frequency of two to four times daily, depending on the severity of the condition being treated. For patients with psoriasis or other recalcitrant conditions, occlusive dressings may be utilized to enhance the efficacy of the treatment.

In cases where an infection develops, it is imperative to discontinue the use of occlusive dressings immediately and to initiate appropriate antimicrobial therapy 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 in these individuals may lead to severe allergic reactions.

Warnings and Precautions

Systemic absorption of topical corticosteroids can lead to reversible hypothalamic-pituitary-adrenal (HPA) axis suppression, as well as manifestations of Cushing's syndrome, hyperglycemia, and glucosuria in certain patients. Factors that may enhance systemic absorption include the use of more potent steroids, application over extensive surface areas, prolonged treatment duration, and the use of occlusive dressings. It is important to note that children may absorb larger amounts of topical corticosteroids relative to their body size, making them more vulnerable to systemic toxicity.

Patients receiving high doses of potent topical steroids, particularly when applied to large areas of the body or under occlusive dressings, should undergo periodic evaluations for signs of HPA axis suppression. Recommended laboratory tests for this assessment include the urinary free cortisol test and the ACTH stimulation test. Should evidence of HPA axis suppression be detected, it is advisable to consider withdrawing the medication, reducing the frequency of application, or substituting with a less potent steroid. Typically, recovery of HPA axis function occurs promptly and completely following discontinuation of the corticosteroid; however, in rare cases, withdrawal symptoms may arise, necessitating the use of supplemental systemic corticosteroids.

In instances of irritation, the use of topical corticosteroids should be halted, and appropriate therapeutic measures should be initiated. Additionally, if dermatological infections are present, it is essential to implement suitable antifungal or antibacterial treatment. Should there be no prompt improvement in the infection, the corticosteroid should be discontinued until adequate control of the infection is achieved.

Side Effects

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

Local adverse reactions are common and may include burning, itching, irritation, dryness, folliculitis, hypertrichosis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, maceration of the skin, secondary infection, skin atrophy, striae, and miliaria. If irritation develops, it is recommended that the topical corticosteroid be discontinued and appropriate therapy instituted. In cases of dermatological infections, the corticosteroid should also be discontinued until the infection has been adequately controlled.

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.

Pediatric patients are particularly susceptible to adverse effects, including greater risk of topical corticosteroid-induced HPA axis suppression and Cushing's syndrome. Manifestations of adrenal suppression in this population may present as linear growth retardation, delayed weight gain, low plasma cortisol levels, and absence of response to ACTH stimulation. Additionally, signs of intracranial hypertension, such as bulging fontanelles, headaches, and bilateral papilledema, may also be observed in pediatric patients.

It is important to note that signs and symptoms of steroid withdrawal may occur, necessitating the use of supplemental systemic corticosteroids.

Drug Interactions

No specific drug interactions have been identified in the available data.

However, for the evaluation of hypothalamic-pituitary-adrenal (HPA) axis suppression, certain laboratory tests may be beneficial. The urinary free cortisol test and the ACTH stimulation test are recommended for assessing HPA axis function. These tests can provide valuable insights into the patient's adrenal function and help guide clinical decision-making.

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 adrenocorticotropic hormone (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 note 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 classified as pregnancy category C, indicating that they may pose risks to fetal development. Animal studies have demonstrated that corticosteroids can be teratogenic when administered systemically at relatively low dosage levels. Additionally, more potent corticosteroids have shown teratogenic effects following dermal application in laboratory animals.

Currently, there are no adequate and well-controlled studies in pregnant women to assess the teratogenic effects of topically applied corticosteroids. Therefore, the use of topical corticosteroids during pregnancy should be considered only when the potential benefits outweigh the potential risks to the fetus.

Healthcare professionals are advised to avoid extensive use of corticosteroids in pregnant patients, particularly in large amounts or for prolonged periods, 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

Topical corticosteroids are primarily metabolized in the liver and subsequently excreted by the kidneys, with some metabolites also eliminated via bile. In patients with renal impairment, systemic absorption of these corticosteroids may lead to reversible hypothalamic-pituitary-adrenal (HPA) axis suppression, necessitating careful monitoring.

For patients receiving large doses of potent topical steroids, particularly when applied to extensive areas or under occlusive dressings, periodic evaluation for 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 medication, reducing the application frequency, or substituting with a less potent steroid. Notably, recovery of HPA axis function is typically prompt and complete following discontinuation of the corticosteroid.

Hepatic Impairment

Topical corticosteroids are primarily metabolized in the liver, and some of these corticosteroids and their metabolites are excreted into the bile. In patients with hepatic impairment, systemic absorption of topical corticosteroids may lead to reversible hypothalamic-pituitary-adrenal (HPA) axis suppression. Therefore, it is essential to monitor these patients for signs of HPA axis suppression, particularly when they are receiving large doses of potent topical steroids applied to extensive areas of the skin or under occlusive dressings.

Patients with compromised liver function should be evaluated periodically for evidence of HPA axis suppression, as this effect may be more pronounced in this population. If HPA axis suppression is observed, it is recommended to withdraw the drug, reduce the frequency of application, or substitute a less potent steroid. These measures are particularly important for patients with hepatic impairment to ensure their safety and minimize potential adverse effects.

Overdosage

Topically applied corticosteroids have the potential to be absorbed in amounts sufficient to elicit systemic effects. Healthcare professionals should be aware of this possibility when prescribing or recommending these medications.

In the event of overdosage, it is crucial to monitor for potential symptoms associated with systemic corticosteroid effects. These may include, but are not limited to, signs of adrenal suppression, Cushing's syndrome, or other hormonal imbalances.

Management of corticosteroid overdosage primarily involves discontinuation of the topical agent and supportive care tailored to the symptoms presented. In cases of significant systemic effects, further evaluation and intervention may be necessary, including the consideration of corticosteroid tapering if long-term use has occurred.

Healthcare providers are advised to consult relevant clinical guidelines and consider individual patient factors when addressing overdosage situations.

Nonclinical Toxicology

Corticosteroids are generally recognized as 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 animals. There is a lack of 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 potential risks to the fetus. It is advised that drugs within this class not be used extensively on pregnant patients, in large quantities, or for prolonged durations.

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

Postmarketing Experience

Postmarketing experience has identified several adverse events associated with the use of topical corticosteroids, particularly in pediatric patients. Reports indicate occurrences of hypothalamic-pituitary-adrenal (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 an absence of response to ACTH stimulation.

Intracranial hypertension has been characterized by symptoms such as bulging fontanelles, headaches, and bilateral papilledema. Additionally, local adverse reactions have been reported infrequently, with a potential increase in frequency when occlusive dressings are used. These reactions include burning, itching, irritation, dryness, folliculitis, hypertrichosis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, maceration of the skin, secondary infection, 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 to advise patients not to use this medication for any condition other than the specific disorder for which it was prescribed. This ensures the medication's efficacy and safety.

Patients should also be instructed that the treated skin area should not be bandaged or otherwise covered in a manner that creates an occlusive environment, unless specifically directed by their physician. This is important to minimize the risk of local adverse reactions.

In the event of any signs of local adverse reactions, particularly when using occlusive dressings, patients should be encouraged to report these symptoms to their healthcare provider promptly.

For parents of pediatric patients, it is crucial to advise against the use of tight-fitting diapers or plastic pants on children being treated in the diaper area. Such garments may act as occlusive dressings, potentially exacerbating any 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 20-25°C (68-77°F), adhering to the guidelines set forth by the United States Pharmacopeia (USP) for Controlled Room Temperature.

It is essential to keep the product out of the reach of children to ensure safety. Proper handling and storage conditions must be maintained to preserve the integrity of the product.

Additional Clinical Information

Patients may undergo a urinary free cortisol test and an ACTH stimulation test as part of the diagnostic process. These tests are utilized to assess adrenal function and cortisol levels, providing clinicians with essential information for evaluating conditions related to adrenal insufficiency or hypercortisolism.

FDA Insert (PDF)

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

View full prescribing information (PDF)