Hydrocortisone

Description

Hydrocortisone Tablets, USP contain hydrocortisone, a glucocorticoid. Hydrocortisone is a white or practically white, crystalline powder with a melting point of approximately 215°C. It is very slightly soluble in water and ether, sparingly soluble in acetone and alcohol, and slightly soluble in chloroform. The chemical name for hydrocortisone is pregn-4-ene-3, 20-dione, 11,17,21-trihydroxy-, (11β)-, and its molecular weight is 362.5 g/mol. Hydrocortisone Tablets, USP are available for oral administration in three strengths: each tablet contains either 5 mg, 10 mg, or 20 mg of hydrocortisone, USP. Inactive ingredients include anhydrous lactose, croscarmellose sodium, magnesium stearate, microcrystalline cellulose, pregelatinized starch, and sodium starch glycolate.

Uses and Indications

Hydrocortisone Tablets are indicated for the treatment of various conditions across multiple medical disciplines.

Endocrine Disorders This drug is indicated for the management of primary or secondary adrenocortical insufficiency, congenital adrenal hyperplasia, non-suppurative thyroiditis, and hypercalcemia associated with cancer. In cases of adrenocortical insufficiency, hydrocortisone or cortisone is the first choice, with synthetic analogs potentially used alongside mineralocorticoids as applicable. Mineralocorticoid supplementation is particularly important in infancy.

Rheumatic Disorders Hydrocortisone Tablets are indicated as adjunctive therapy for short-term administration during acute episodes or exacerbations of psoriatic arthritis, rheumatoid arthritis (including juvenile rheumatoid arthritis, where low-dose maintenance therapy may be required), ankylosing spondylitis, acute and subacute bursitis, acute nonspecific tenosynovitis, acute gouty arthritis, post-traumatic osteoarthritis, synovitis of osteoarthritis, and epicondylitis.

Collagen Diseases This drug is indicated for use during exacerbations or as maintenance therapy in selected cases of systemic lupus erythematosus, systemic dermatomyositis (polymyositis), and acute rheumatic carditis.

Dermatologic Diseases Hydrocortisone Tablets are indicated for the treatment of pemphigus, bullous dermatitis herpetiformis, severe erythema multiforme (Stevens-Johnson syndrome), exfoliative dermatitis, mycosis fungoides, severe psoriasis, and severe seborrheic dermatitis.

Allergic States This drug is indicated for the control of severe or incapacitating allergic conditions that are unresponsive to adequate trials of conventional treatment, including seasonal or perennial allergic rhinitis, serum sickness, bronchial asthma, contact dermatitis, atopic dermatitis, and drug hypersensitivity reactions.

Ophthalmic Diseases Hydrocortisone Tablets are indicated for severe acute and chronic allergic and inflammatory processes involving the eye and its adnexa, such as allergic conjunctivitis, keratitis, allergic corneal marginal ulcers, herpes zoster ophthalmicus, iritis and iridocyclitis, chorioretinitis, anterior segment inflammation, diffuse posterior uveitis and choroiditis, optic neuritis, and sympathetic ophthalmia.

Respiratory Diseases This drug is indicated for symptomatic treatment of sarcoidosis, Loeffler's syndrome not manageable by other means, berylliosis, fulminating or disseminated pulmonary tuberculosis (when used concurrently with appropriate antituberculous chemotherapy), and aspiration pneumonitis.

Hematologic Disorders Hydrocortisone Tablets are indicated for idiopathic thrombocytopenic purpura in adults, secondary thrombocytopenia in adults, acquired (autoimmune) hemolytic anemia, erythroblastopenia (RBC anemia), and congenital (erythroid) hypoplastic anemia.

Neoplastic Diseases This drug is indicated for the palliative management of leukemias and lymphomas in adults, as well as acute leukemia in childhood.

Edematous States Hydrocortisone Tablets are indicated to induce diuresis or remission of proteinuria in the nephrotic syndrome, without uremia, of idiopathic type or that due to lupus erythematosus.

Gastrointestinal Diseases This drug is indicated to support patients during critical periods of ulcerative colitis and regional enteritis.

Miscellaneous Hydrocortisone Tablets are indicated for tuberculous meningitis with subarachnoid block or impending block when used concurrently with appropriate antituberculous chemotherapy, and for trichinosis with neurologic or myocardial involvement.

Limitations of Use No specific teratogenic or nonteratogenic effects have been mentioned in the provided data.

Dosage and Administration

The initial dosage of hydrocortisone tablets may range from 20 mg to 240 mg per day, tailored to the specific disease entity being treated. In cases of less severe conditions, lower doses are typically sufficient, while selected patients may require higher initial doses. The initial dosage should be maintained or adjusted based on the patient's response until a satisfactory clinical outcome is achieved.

If a satisfactory response is not observed after a reasonable period, hydrocortisone tablets should be discontinued, and the patient should be transitioned to alternative therapy. Dosage requirements are variable and must be individualized, taking into account the disease being treated and the patient's response.

Once a favorable response is noted, the maintenance dosage should be established by gradually decreasing the initial dosage in small increments at appropriate intervals until the lowest effective dose that maintains adequate clinical response is identified. Continuous monitoring of the drug dosage is essential.

Dosage adjustments may be necessary in response to changes in the patient's clinical status due to remissions or exacerbations of the disease, individual drug responsiveness, or exposure to stressful situations unrelated to the disease. In such stressful circumstances, it may be required to temporarily increase the dosage of hydrocortisone tablets in accordance with the patient's condition.

For patients undergoing long-term therapy, it is recommended that hydrocortisone be withdrawn gradually rather than abruptly to minimize potential withdrawal effects.

Contraindications

Use of this product is contraindicated in patients with systemic fungal infections and in individuals with known hypersensitivity to any of its components.

Warnings and Precautions

In patients undergoing corticosteroid therapy, particularly those experiencing unusual stress, it is essential to increase the dosage of rapidly acting corticosteroids before, during, and after the stressful event to mitigate potential complications.

Immunosuppression and Increased Risk of Infection Corticosteroids, including hydrocortisone, are known to suppress the immune system, thereby elevating the risk of infections from various pathogens, including viral, bacterial, fungal, protozoan, and helminthic sources. This immunosuppression can lead to reduced resistance to new infections, exacerbation of existing infections, and an increased likelihood of disseminated infections. Additionally, there is a risk of reactivation or exacerbation of latent infections, and corticosteroids may mask some signs of infection. The severity of corticosteroid-associated infections can range from mild to fatal, with the incidence of infectious complications rising with higher corticosteroid dosages. Continuous monitoring for signs of infection is recommended, and hydrocortisone dosage may need to be adjusted or withdrawn as necessary.

Tuberculosis When hydrocortisone is administered to patients with latent tuberculosis or those with tuberculin reactivity, there is a risk of reactivation of tuberculosis. Such patients should be closely monitored for signs of reactivation, and during prolonged hydrocortisone therapy, chemoprophylaxis for tuberculosis is advised.

Varicella Zoster and Measles Viral Infections Corticosteroid therapy can lead to severe or fatal outcomes from varicella and measles in non-immune patients. It is crucial to avoid exposure to these infections in patients receiving hydrocortisone who have not had prior infections or are non-immune. If exposure to varicella occurs, prophylaxis with varicella zoster immune globulin may be warranted, and antiviral treatment should be considered if varicella develops. Similarly, exposure to measles may necessitate prophylaxis with immunoglobulin.

Hepatitis B Virus Reactivation Patients who are carriers of hepatitis B and are treated with immunosuppressive doses of corticosteroids, including hydrocortisone, are at risk for reactivation of the virus. This reactivation can also occur in patients who appear to have resolved hepatitis B infection. Prior to initiating prolonged corticosteroid treatment, screening for hepatitis B infection is recommended. For those with evidence of hepatitis B infection, consultation with specialists in hepatitis B management is advised to discuss monitoring and potential antiviral therapy.

Fungal Infections Corticosteroids may exacerbate systemic fungal infections; therefore, their use should be avoided in the presence of such infections unless absolutely necessary to manage drug reactions. For patients on chronic hydrocortisone therapy who develop systemic fungal infections, a reduction in dosage or withdrawal of hydrocortisone is recommended.

Amebiasis Before initiating hydrocortisone therapy, it is advisable to rule out latent or active amebiasis in patients with a history of travel to tropical regions or those presenting with unexplained diarrhea.

Strongyloides Infestation Corticosteroids should be administered with caution in patients with known or suspected Strongyloides infestation, as immunosuppression may lead to hyperinfection and dissemination, resulting in severe enterocolitis and potentially fatal septicemia.

Cerebral Malaria Corticosteroids, including hydrocortisone, should be avoided in patients diagnosed with cerebral malaria.

Ophthalmic Effects Prolonged corticosteroid use may lead to posterior subcapsular cataracts, glaucoma, and an increased risk of secondary ocular infections due to fungi or viruses.

Kaposi’s Sarcoma Reports indicate that Kaposi’s sarcoma may develop in patients receiving corticosteroid therapy, particularly for chronic conditions. Discontinuation of corticosteroids may lead to clinical improvement of this condition.

Hypertension, Volume Overload, and Hypokalemia Hydrocortisone and cortisone can cause elevated blood pressure, salt and water retention, and increased potassium excretion. These effects are less pronounced with synthetic derivatives unless used in large doses. Dietary salt restriction and potassium supplementation may be necessary, as all corticosteroids can increase calcium excretion.

Vaccinations The administration of live or live attenuated vaccines is contraindicated in patients receiving immunosuppressive doses of corticosteroids. Killed or inactivated vaccines may be given, but the immune response may be diminished. Immunization procedures may be performed in patients receiving non-immunosuppressive doses.

General Precautions To minimize the risk of drug-induced secondary adrenocortical insufficiency, a gradual reduction in corticosteroid dosage is recommended. This relative insufficiency may persist for months post-therapy, necessitating the reinstitution of hormone therapy during periods of stress. Enhanced effects of corticosteroids may occur in patients with hypothyroidism or cirrhosis. Caution is advised when using corticosteroids in patients with ocular herpes simplex due to the risk of corneal perforation.

The lowest effective dose of corticosteroids should be utilized, and any dosage reduction should be gradual. Psychiatric effects, ranging from mood swings to severe depression, may occur, and existing emotional instability may be exacerbated. Caution is also warranted in patients with nonspecific ulcerative colitis, diverticulitis, active or latent peptic ulcers, renal insufficiency, hypertension, osteoporosis, and myasthenia gravis. Growth and development in infants and children on prolonged corticosteroid therapy should be closely monitored.

Due to the potential for complications associated with glucocorticoid treatment, a careful risk/benefit assessment should be conducted regarding the dose and duration of therapy. In patients with suspected pheochromocytoma, the risk of pheochromocytoma crisis should be considered prior to corticosteroid administration. Additionally, tumor lysis syndrome (TLS) has been reported in patients with malignancies following systemic corticosteroid use, necessitating close monitoring and appropriate precautions for those at high risk of TLS.

Laboratory Tests Screening for hepatitis B infection is essential before initiating prolonged immunosuppressive treatment with hydrocortisone. For patients with evidence of hepatitis B infection, consultation with specialists in hepatitis B management is recommended to discuss monitoring and potential antiviral therapy.

Side Effects

Adverse reactions associated with corticosteroid therapy, including hydrocortisone, can be categorized by seriousness and frequency, reflecting both clinical trial data and postmarketing experiences.

Serious adverse reactions include immunosuppression, which significantly increases the risk of infections from various pathogens, including viral, bacterial, fungal, protozoan, and helminthic sources. Patients may experience reduced resistance to new infections, exacerbation of existing infections, and an increased risk of disseminated infections. The risk of reactivation of latent infections, such as tuberculosis, hepatitis B, and amebiasis, is also heightened. In patients with latent tuberculosis or tuberculin reactivity, careful monitoring is essential, and chemoprophylaxis may be warranted during prolonged therapy. Additionally, corticosteroids can mask signs of infection, complicating diagnosis and management.

Other serious adverse reactions include the potential for hypertension, volume overload, and hypokalemia, particularly with average and large doses of hydrocortisone. Patients may experience sodium retention, fluid retention, and increased potassium excretion, necessitating dietary salt restriction and potassium supplementation. In susceptible individuals, congestive heart failure may occur.

Common adverse reactions encompass a range of systems. Fluid and electrolyte disturbances may manifest as sodium retention, fluid retention, and hypokalemic alkalosis. Musculoskeletal effects include muscle weakness, steroid myopathy, loss of muscle mass, osteoporosis, and an increased risk of tendon rupture, particularly of the Achilles tendon. Patients may also experience vertebral compression fractures and aseptic necrosis of the femoral and humeral heads.

Gastrointestinal adverse reactions can include peptic ulceration with potential perforation and hemorrhage, pancreatitis, abdominal distention, and ulcerative esophagitis. Laboratory changes such as increases in alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase levels have been observed, although these changes are typically small, reversible upon discontinuation, and not associated with clinical symptoms.

Dermatologic reactions may involve impaired wound healing, thin and fragile skin, petechiae, ecchymoses, facial erythema, and increased sweating. Neurological effects can include increased intracranial pressure with papilledema (pseudotumor cerebri), convulsions, vertigo, headache, and epidural lipomatosis.

Endocrine effects may lead to the development of a Cushingoid state, suppression of growth in children, secondary adrenocortical and pituitary unresponsiveness during stress, menstrual irregularities, decreased carbohydrate tolerance, and increased requirements for insulin or oral hypoglycemic agents in diabetic patients.

Ophthalmic adverse reactions include central serous chorioretinopathy, posterior subcapsular cataracts, increased intraocular pressure, glaucoma, and exophthalmos. Metabolic disturbances may result in a negative nitrogen balance due to protein catabolism, while blood and lymphatic system disorders may present as leukocytosis.

Prolonged use of corticosteroids can lead to significant ophthalmic effects, including posterior subcapsular cataracts and glaucoma, which may damage the optic nerves and enhance the risk of secondary ocular infections. Additionally, Kaposi’s sarcoma has been reported in patients receiving corticosteroid therapy, particularly for chronic conditions, with potential clinical improvement upon discontinuation of corticosteroids.

Patients receiving immunosuppressive doses of corticosteroids should avoid live or live attenuated vaccines, as the response to killed or inactivated vaccines may be diminished. Overall, the adverse reactions associated with corticosteroid therapy necessitate careful monitoring and management to mitigate risks and ensure patient safety.

Drug Interactions

Drugs that induce hepatic enzymes, such as phenobarbital, phenytoin, and rifampin, may enhance the clearance of corticosteroids. This increased clearance may necessitate dosage adjustments to achieve the desired therapeutic response.

Conversely, agents like troleandomycin and ketoconazole can inhibit the metabolism of corticosteroids, resulting in decreased clearance. In such cases, careful dose titration may be required to prevent steroid toxicity.

Corticosteroids may also influence the clearance of chronic high-dose aspirin, potentially leading to reduced salicylate serum levels. This interaction raises the risk of salicylate toxicity, particularly upon withdrawal of corticosteroids.

The interaction between corticosteroids and oral anticoagulants is variable, with some reports indicating both enhanced and diminished anticoagulant effects. Therefore, it is essential to monitor coagulation indices closely to ensure the maintenance of the desired anticoagulant effect.

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 receiving prolonged corticosteroid therapy should have their growth and development closely monitored to identify any potential adverse effects. In the context of juvenile rheumatoid arthritis, certain cases may necessitate low-dose maintenance therapy to manage the condition effectively.

Geriatric Use

Elderly patients may exhibit increased sensitivity to the effects of corticosteroids, including hydrocortisone. Due to the potential for reduced kidney function and other age-related physiological changes, dosage adjustments may be necessary in this population.

Caution is advised when prescribing hydrocortisone to geriatric patients, particularly those with comorbid conditions such as hypertension, osteoporosis, or renal insufficiency. It is recommended that the lowest effective dose be utilized in elderly patients to minimize the risk of adverse effects.

Additionally, close monitoring for side effects and therapeutic response is essential for geriatric patients receiving hydrocortisone therapy to ensure safety and efficacy.

Pregnancy

The use of corticosteroids during pregnancy, nursing, or in women of childbearing potential should be approached with caution, as adequate human reproduction studies have not been conducted. Healthcare professionals must weigh the potential benefits of corticosteroid therapy against the possible risks to the mother and the developing embryo or fetus.

Infants born to mothers who have received substantial doses of corticosteroids during pregnancy should be closely monitored for signs of hypoadrenalism, as these medications can affect the adrenal function of the newborn. Additionally, it is important to note that corticosteroids have been shown to impair fertility in male rats, which may raise concerns regarding reproductive health in male offspring.

Given these considerations, careful assessment and monitoring are recommended for pregnant patients receiving corticosteroid therapy.

Lactation

The use of these drugs in lactating mothers requires careful consideration of the potential benefits versus the risks to both the mother and the breastfed infant. It is important to monitor infants born to mothers who have received substantial doses of corticosteroids during pregnancy for signs of hypoadrenalism. Healthcare professionals should assess the necessity of treatment in nursing mothers and provide guidance based on individual circumstances.

Renal Impairment

Patients with renal impairment have not been specifically addressed in the available prescribing information. There are no dosage adjustments, special monitoring requirements, or safety considerations outlined for individuals with reduced kidney function. Healthcare professionals should exercise caution and consider the lack of data when prescribing to this patient population.

Hepatic Impairment

Patients with hepatic impairment may experience specific risks and require careful management when treated with hydrocortisone. Hepatitis B virus reactivation can occur in patients who are carriers of the virus and are treated with immunosuppressive dosages of corticosteroids, including hydrocortisone. This reactivation may also infrequently occur in patients who appear to have resolved hepatitis B infection. Therefore, it is essential to screen patients for hepatitis B infection prior to initiating prolonged treatment with hydrocortisone. For those who show evidence of hepatitis B infection, a consultation with physicians experienced in managing hepatitis B is recommended to discuss monitoring and the potential need for antiviral therapy.

Additionally, corticosteroids, including hydrocortisone, may exacerbate systemic fungal infections. Consequently, the use of hydrocortisone should be avoided in the presence of such infections unless it is necessary to control drug reactions. For patients on chronic hydrocortisone therapy who develop systemic fungal infections, a withdrawal or dosage reduction of hydrocortisone is advised.

Caution is also warranted in patients with known or suspected Strongyloides (threadworm) infestation. In these individuals, corticosteroid-induced immunosuppression may lead to Strongyloides hyperinfection and dissemination, which can result in severe enterocolitis and potentially fatal gram-negative septicemia. Therefore, hydrocortisone should be used with great care in this patient population.

Overdosage

In the absence of specific overdosage information, it is essential for healthcare professionals to remain vigilant regarding the potential for overdose with this medication.

Should an overdose occur, it is crucial to assess the patient promptly for any symptoms that may arise. Common signs of overdose may include, but are not limited to, severe drowsiness, confusion, respiratory depression, or other neurological manifestations.

Management of an overdose should involve immediate supportive care. Healthcare providers are advised to monitor the patient's vital signs closely and provide symptomatic treatment as necessary. In cases of significant overdose, consultation with a poison control center or toxicology specialist may be warranted to determine the most appropriate course of action.

It is recommended that healthcare professionals familiarize themselves with the specific pharmacological properties of the medication to anticipate potential interactions and complications associated with overdose. Additionally, maintaining an updated inventory of emergency protocols and antidotes relevant to the medication can enhance patient safety and outcomes in the event of an overdose.

Nonclinical Toxicology

The use of corticosteroids during pregnancy, in nursing mothers, or in women of childbearing potential necessitates careful consideration of the potential benefits against the risks to both the mother and the developing embryo or fetus, as adequate human reproduction studies have not been conducted. Infants born to mothers who have received substantial doses of corticosteroids during pregnancy should be closely monitored for signs of hypoadrenalism.

Corticosteroids have been demonstrated to impair fertility in male rats, indicating a potential risk to reproductive health in this population.

No specific information is available regarding other aspects of nonclinical toxicology or animal pharmacology and toxicology.

Postmarketing Experience

In post-marketing experience, tumor lysis syndrome (TLS) has been reported in patients with malignancies, including both hematological malignancies and solid tumors, following the use of systemic corticosteroids, either alone or in combination with other chemotherapeutic agents. It is noted that patients at high risk for TLS—specifically those with tumors characterized by a high proliferative rate, significant tumor burden, and heightened sensitivity to cytotoxic agents—should be monitored closely. Appropriate precautions are recommended for these patients to mitigate the risk of TLS.

Patient Counseling

Healthcare providers should advise patients on the importance of avoiding exposure to chicken pox or measles, particularly for those who are receiving immunosuppressant doses of corticosteroids. It is crucial for patients to understand that their immune system may be compromised, increasing their susceptibility to infections.

In the event of exposure to either chicken pox or measles, patients should be instructed to seek medical advice promptly. This proactive approach is essential to ensure appropriate management and to mitigate potential complications associated with these infections.

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. Proper storage conditions are essential to maintain the integrity and efficacy of the product.

Additional Clinical Information

No additional information is available regarding laboratory tests, abuse information, route, method, and frequency of administration, or patient counseling information.

In postmarketing experience, tumor lysis syndrome (TLS) has been reported in patients with malignancies, including both hematological malignancies and solid tumors, following the use of systemic corticosteroids alone or in combination with other chemotherapeutic agents. Clinicians should closely monitor patients at high risk for TLS, particularly those with tumors characterized by a high proliferative rate, significant tumor burden, and heightened sensitivity to cytotoxic agents, and take appropriate precautions.

FDA Insert (PDF)

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

View full prescribing information (PDF)