Hydrocortisone

Description

Hydrocortisone tablets, USP contain hydrocortisone, a glucocorticoid. Hydrocortisone is a white to practically white, odorless, crystalline powder with a melting point of approximately 215º 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 362.46. Hydrocortisone tablets, USP are available for oral administration in three strengths: each tablet contains either 5 mg, 10 mg, or 20 mg of hydrocortisone. Inactive ingredients include colloidal silicon dioxide, lactose monohydrate, magnesium stearate, and microcrystalline cellulose.

Uses and Indications

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

Endocrine Disorders Hydrocortisone is indicated for the management of primary or secondary adrenocortical insufficiency, with hydrocortisone or cortisone being the first choice. Synthetic analogs may be utilized in conjunction with mineralocorticoids where applicable, particularly in infants where mineralocorticoid supplementation is crucial. Additional indications include congenital adrenal hyperplasia, non-suppurative thyroiditis, and hypercalcemia associated with cancer.

Rheumatic Disorders This drug serves as adjunctive therapy for short-term administration during acute episodes or exacerbations of rheumatic disorders, including psoriatic arthritis, rheumatoid arthritis (including juvenile rheumatoid arthritis, with selected cases possibly requiring low-dose maintenance therapy), ankylosing spondylitis, acute and subacute bursitis, acute nonspecific tenosynovitis, acute gouty arthritis, post-traumatic osteoarthritis, synovitis of osteoarthritis, and epicondylitis.

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

Dermatologic Diseases Indications include 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 is 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 Indications include symptomatic 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 is 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 is indicated to induce diuresis or remission of proteinuria in the nephrotic syndrome, without uremia, of the idiopathic type or that due to lupus erythematosus.

Gastrointestinal Diseases Indications include the management of ulcerative colitis and regional enteritis during critical periods of the disease.

Miscellaneous Hydrocortisone is 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.

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 adequate, 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 duration, hydrocortisone should be discontinued, and the patient should be transitioned to alternative therapies. Dosage requirements are variable and must be individualized, taking into account the disease being treated and the patient's response.

Upon achieving a favorable response, 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 hydrocortisone dosage in accordance with the patient's condition.

For patients undergoing long-term therapy, it is advised to withdraw hydrocortisone gradually rather than abruptly when discontinuation is necessary.

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 severe, with the potential for fatal outcomes. Therefore, it is crucial to monitor patients for signs of infection and consider hydrocortisone withdrawal or dosage reduction as necessary.

Tuberculosis Patients with latent tuberculosis or tuberculin reactivity who are treated with hydrocortisone are at risk for reactivation of tuberculosis. Close monitoring for reactivation is advised, and during prolonged hydrocortisone therapy, these patients should receive chemoprophylaxis.

Varicella Zoster and Measles Viral Infections Corticosteroid-treated patients who are non-immune to varicella or measles are at risk for serious or fatal outcomes if exposed to these infections. Prophylaxis with varicella zoster immune globulin is recommended for patients exposed to varicella, and antiviral treatment should be considered if varicella develops. Similarly, exposure to measles may necessitate prophylaxis with immunoglobulin.

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

Fungal Infections Corticosteroids may exacerbate systemic fungal infections. Therefore, 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, withdrawal or dosage reduction is recommended.

Amebiasis Before initiating hydrocortisone in patients with a history of travel to tropical regions or unexplained diarrhea, it is advisable to rule out latent or active amebiasis, as corticosteroids may activate latent infections.

Strongyloides Infestation Corticosteroids should be used cautiously in patients with known or suspected Strongyloides infestation due to the risk of hyperinfection and dissemination, which can lead to 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 There have been reports of Kaposi's sarcoma occurring 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 likely with synthetic derivatives unless used in large doses. Dietary salt restriction and potassium supplementation may be necessary, and 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.

Usage in Pregnancy Due to the lack of adequate human reproduction studies, the use of corticosteroids in pregnant women, nursing mothers, or women of childbearing potential requires careful consideration of the potential benefits versus risks to the mother and fetus. Infants born to mothers who received substantial doses of corticosteroids during pregnancy should be monitored for signs of hypoadrenalism. Additionally, corticosteroids have been shown to impair fertility in male rats.

General Precautions To minimize the risk of drug-induced secondary adrenocortical insufficiency, a gradual reduction in dosage is recommended. This relative insufficiency may persist for months post-therapy, necessitating hormone therapy during periods of stress. Enhanced effects of corticosteroids may occur in patients with hypothyroidism or cirrhosis. Caution is advised 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 euphoria to severe depression and psychosis, may occur with corticosteroid use, and existing emotional instability may be exacerbated. Caution is warranted in patients with nonspecific ulcerative colitis, diverticulitis, fresh intestinal anastomoses, active or latent peptic ulcer, renal insufficiency, hypertension, osteoporosis, and myasthenia gravis. Growth and development in infants and children on prolonged corticosteroid therapy should be closely monitored.

Given that complications from glucocorticoid treatment are dose- and duration-dependent, a careful risk/benefit assessment is necessary for each patient regarding the appropriate dose and treatment duration. In patients with suspected pheochromocytoma, the risk of pheochromocytoma crisis should be considered prior to corticosteroid administration.

Finally, tumor lysis syndrome (TLS) has been reported in patients with malignancies following systemic corticosteroid use. Patients at high risk for TLS should be closely monitored, particularly those with high tumor burden or sensitivity to cytotoxic agents.

Laboratory Tests Screening for hepatitis B infection is recommended before initiating prolonged immunosuppressive treatment with hydrocortisone to ensure patient safety.

Side Effects

Patients receiving corticosteroids, including hydrocortisone, may experience a range of adverse reactions, which can be categorized by seriousness and frequency.

Serious adverse reactions include immunosuppression, which increases the risk of infections from various pathogens, including viral, bacterial, fungal, protozoan, and helminthic sources. This immunosuppression can reduce resistance to new infections, exacerbate existing infections, and increase the risk of disseminated infections, as well as the reactivation of latent infections. Infections associated with corticosteroid use can vary in severity, with some cases being fatal. The likelihood of infectious complications rises with higher corticosteroid dosages.

Ophthalmic effects are also significant, with prolonged corticosteroid use potentially leading to posterior subcapsular cataracts, glaucoma, and increased intraocular pressure, which may damage the optic nerves. Additionally, there is a risk of enhancing secondary ocular infections due to fungi or viruses.

Hypertension, volume overload, and hypokalemia are common concerns, particularly with average and large doses of hydrocortisone or cortisone, which can elevate blood pressure, cause salt and water retention, and increase potassium excretion. These effects are less pronounced with synthetic derivatives unless used in large doses. Dietary salt restriction and potassium supplementation may be necessary.

Fluid and electrolyte disturbances may manifest as sodium retention, fluid retention, and hypokalemic alkalosis, potentially leading to congestive heart failure in susceptible patients. Patients may also experience muscle weakness, steroid myopathy, and loss of muscle mass, alongside osteoporosis and an increased risk of tendon rupture, particularly of the Achilles tendon. Other musculoskeletal concerns include vertebral compression fractures, aseptic necrosis of the femoral and humeral heads, and pathologic fractures of long bones.

Gastrointestinal adverse reactions can include peptic ulcers with possible perforation and hemorrhage, pancreatitis, abdominal distention, and ulcerative esophagitis. Increases in liver enzymes such as alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase have been observed, although these changes are typically small, reversible upon discontinuation, and not associated with clinical syndromes.

Dermatologic reactions may involve impaired wound healing, thin fragile skin, petechiae, ecchymoses, facial erythema, and increased sweating. Corticosteroids may also suppress reactions to skin tests.

Neurological effects can include increased intracranial pressure with papilledema (pseudotumor cerebri), convulsions, vertigo, headaches, and epidural lipomatosis.

Endocrine effects may manifest as 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.

Metabolic disturbances may lead to a negative nitrogen balance due to protein catabolism, while blood and lymphatic system disorders may present as leukocytosis.

Psychic derangements, ranging from euphoria and insomnia to severe depression and psychotic manifestations, may occur. Existing emotional instability or psychotic tendencies may be exacerbated by corticosteroid therapy.

In postmarketing experience, tumor lysis syndrome (TLS) has been reported in patients with malignancies following the use of systemic corticosteroids, either alone or in combination with chemotherapeutic agents. Patients at high risk for TLS should be closely monitored, especially those with tumors characterized by a high proliferative rate, high tumor burden, and high sensitivity to cytotoxic agents.

Kaposi's sarcoma has also been reported in patients receiving corticosteroid therapy, particularly for chronic conditions, with clinical improvement noted upon discontinuation of corticosteroids.

Drug Interactions

Phenobarbital, phenytoin, and rifampin are known to increase the clearance of corticosteroids. This interaction may necessitate dosage adjustments to achieve the desired therapeutic response.

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

Corticosteroids may also influence the pharmacokinetics of chronic high-dose aspirin, potentially increasing its clearance. This interaction can lead to decreased salicylate serum levels or an increased risk of salicylate toxicity 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 maintain 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

Hydrocortisone is indicated for the treatment of juvenile rheumatoid arthritis, with some selected cases requiring low-dose maintenance therapy. The initial dosage of hydrocortisone tablets for pediatric patients may range from 20 mg to 240 mg per day, depending on the specific disease entity being treated. Dosage requirements are variable and must be individualized based on the disease under treatment and the patient's response.

Healthcare professionals should carefully monitor the growth and development of infants and children undergoing prolonged corticosteroid therapy. Additionally, infants born to mothers who received substantial doses of corticosteroids during pregnancy should be closely observed for signs of hypoadrenalism.

Geriatric Use

Elderly patients may exhibit increased sensitivity to the side effects of corticosteroids, including hydrocortisone. Caution is advised when prescribing hydrocortisone to this population due to the potential for reduced kidney function and other age-related physiological changes that may affect drug metabolism and clearance.

To minimize the risk of adverse effects, it is recommended that the lowest effective dose of hydrocortisone be utilized in geriatric patients. Additionally, regular monitoring for side effects and therapeutic effectiveness is essential for elderly patients receiving hydrocortisone therapy, ensuring that any adverse reactions are promptly identified and managed.

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, healthcare providers are advised to carefully assess the necessity of corticosteroid treatment in pregnant patients and to discuss potential risks with women of childbearing potential.

Lactation

The use of hydrocortisone in lactating mothers necessitates a careful evaluation of the potential benefits against the possible risks to both the mother and the breastfed infant.

Infants born to mothers who have received substantial doses of corticosteroids during pregnancy should be closely monitored for signs of hypoadrenalism. This observation is critical to ensure the well-being of the infant during the postpartum period.

Renal Impairment

Patients with renal impairment may not have specific information regarding dosage adjustments, special monitoring, or safety considerations outlined in the prescribing information. Therefore, healthcare professionals should exercise caution when prescribing to patients with reduced kidney function, as the lack of data necessitates careful clinical judgment and individualized patient assessment. Regular monitoring of renal function is advisable to ensure patient safety and optimal therapeutic outcomes.

Hepatic Impairment

Patients with hepatic impairment may experience an increased risk of hepatitis B virus reactivation when treated with immunosuppressive dosages of corticosteroids, including hydrocortisone. This reactivation can occur in patients who are carriers of the hepatitis B virus as well as in those who appear to have resolved hepatitis B infection.

Prior to initiating prolonged treatment with hydrocortisone, it is essential to screen patients for hepatitis B infection. For those who test positive for hepatitis B, it is recommended to consult with healthcare professionals who specialize in hepatitis B management. These specialists can provide guidance on appropriate monitoring and the potential need for hepatitis B antiviral therapy.

Additionally, corticosteroids, including hydrocortisone, may exacerbate systemic fungal infections. Therefore, the use of hydrocortisone should be avoided in patients with such infections unless it is necessary to manage drug reactions. For patients on chronic hydrocortisone therapy who subsequently develop systemic fungal infections, a withdrawal or dosage reduction of hydrocortisone is advised to mitigate potential complications.

Overdosage

There is currently no specific information available regarding overdosage for this medication. In the absence of documented overdosage data, healthcare professionals are advised to exercise caution and monitor patients closely for any unusual symptoms or adverse effects that may arise following administration.

In the event of suspected overdosage, it is recommended that healthcare providers initiate supportive care and symptomatic treatment as necessary. Continuous monitoring of vital signs and clinical status is essential. If symptoms of overdosage are observed, appropriate interventions should be implemented based on the patient's condition.

Healthcare professionals should also consider contacting a poison control center or a medical toxicologist for guidance on management strategies tailored to the specific situation.

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 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.

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

Postmarketing Experience

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, 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 potential risks associated with TLS.

Patient Counseling

Healthcare providers should advise patients on immunosuppressant doses of corticosteroids to avoid exposure to chicken pox or measles. It is important for patients to understand the risks associated with these infections, particularly in the context of their immunocompromised status.

Additionally, healthcare providers should instruct patients that if they are exposed to chicken pox or measles, they should seek medical advice promptly. This proactive approach is crucial in managing their health and preventing potential complications related to these infections.

Storage and Handling

The product is supplied in various package configurations, with specific NDC numbers available for identification. It is essential to store the product at a temperature range of 20° to 25°C (68° to 77°F), in accordance with USP Controlled Room Temperature guidelines. Proper storage conditions must be maintained to ensure the integrity and efficacy of the product.

Additional Clinical Information

Tumor lysis syndrome (TLS) has been reported in patients with malignancies, including both hematological malignancies and solid tumors, following the administration of systemic corticosteroids, either 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 to mitigate this risk.

FDA Insert (PDF)

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

View full prescribing information (PDF)