Hydrocortisone

Description

Hydrocortisone Tablets USP contain hydrocortisone, a glucocorticoid classified as an adrenocortical steroid, which is both naturally occurring and synthetic. Hydrocortisone is a white to practically white, odorless, crystalline powder with a melting point of approximately 215°C. It exhibits sparing solubility in acetone and alcohol, slight solubility in chloroform, and is practically insoluble in water and ether. The chemical name for hydrocortisone is pregn-4-ene-3,20-dione, 11,17,21-trihydroxy-, (11β)-, with a molecular weight of 362.46. The structural formula is provided below.

Hydrocortisone Tablets USP are formulated for oral administration and are available in three strengths: each tablet contains either 5 mg, 10 mg, or 20 mg of hydrocortisone USP. The tablets include inactive ingredients such as colloidal silicon dioxide, copovidone, lactose monohydrate, magnesium stearate, microcrystalline cellulose, pregelatinized starch (maize), 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, with hydrocortisone or cortisone being the first choice. Synthetic analogs may be used 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 Hydrocortisone is indicated as adjunctive therapy for short-term administration in acute episodes or exacerbations of 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 This drug is indicated during exacerbations or as maintenance therapy in selected cases of systemic lupus erythematosus, systemic dermatomyositis (polymyositis), and acute rheumatic carditis.

Dermatologic Diseases Hydrocortisone is 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 intractable 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 This drug is indicated for 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 of 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 This drug is indicated to support patients during critical periods of ulcerative colitis and regional enteritis.

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.

Limitations of Use No specific teratogenic or nonteratogenic effects have been mentioned.

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 less severe cases, 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.

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 disease remissions or exacerbations, individual drug responsiveness, and exposure to stressful situations unrelated to the disease. In instances of stress, 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 advised 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 increasing 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 risk of disseminated infections. Additionally, there is a heightened risk of reactivation or exacerbation of latent infections, and corticosteroids may mask some signs of infection. The likelihood of infectious complications escalates with higher corticosteroid dosages. Continuous monitoring for signs of infection is recommended, and clinicians should consider hydrocortisone withdrawal or dosage reduction 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. During prolonged hydrocortisone therapy, chemoprophylaxis is advised for patients with latent tuberculosis or tuberculin reactivity.

Varicella Zoster and Measles Viral Infections Corticosteroid therapy can lead to severe or fatal outcomes from varicella and measles in non-immune patients. Special precautions should be taken to avoid exposure to these infections in patients receiving hydrocortisone. 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 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, the use of hydrocortisone should be avoided in the presence of such infections unless it is 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 the development of 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 occur in patients receiving corticosteroid therapy, particularly for chronic conditions. Discontinuation of corticosteroids may lead to clinical improvement in such cases.

Hypertension, Volume Overload, and Hypokalemia Hydrocortisone and cortisone 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, 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.

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 corticosteroid doses 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 the reinstatement 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 should be utilized, and any dosage reductions should be gradual.

Psychiatric effects, including euphoria, insomnia, mood swings, and severe depression, may occur with corticosteroid use, potentially exacerbating existing emotional instability or psychotic tendencies. Caution is warranted in patients with nonspecific ulcerative colitis, diverticulitis, 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 the potential complications associated with glucocorticoid treatment, which are dose and duration-dependent, a thorough risk/benefit assessment should be conducted for each patient regarding the appropriate dosage and treatment duration. 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 Patients receiving immunosuppressive doses of corticosteroids should be advised to avoid exposure to chickenpox or measles and to seek medical advice promptly if exposure occurs.

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. In particular, patients with latent tuberculosis or tuberculin reactivity may experience reactivation of tuberculosis. Additionally, hepatitis B virus reactivation has been noted in carriers treated with immunosuppressive dosages of corticosteroids. Fungal infections may also be exacerbated, and caution is advised in patients with known or suspected Strongyloides infestation. Prolonged use of corticosteroids can lead to ocular complications such as posterior subcapsular cataracts and glaucoma, which may damage the optic nerves and increase the risk of secondary ocular infections.

Other serious adverse reactions include psychiatric effects, which can range from euphoria and mood swings to severe depression and psychotic manifestations. Existing emotional instability may be aggravated. Pheochromocytoma crisis, which can be fatal, has also been reported following systemic corticosteroid administration. In postmarketing experience, tumor lysis syndrome has been observed in patients with malignancies after the use of systemic corticosteroids.

Common adverse reactions encompass fluid and electrolyte disturbances, such as sodium and fluid retention, hypokalemic alkalosis, and hypertension. Patients may also experience muscle-related issues, including muscle weakness, steroid myopathy, loss of muscle mass, osteoporosis, and an increased risk of tendon rupture, particularly of the Achilles tendon. Gastrointestinal reactions may include peptic ulcers with potential perforation and hemorrhage, pancreatitis, and abdominal distention. Liver enzyme elevations (ALT, AST, alkaline phosphatase) have been observed, although these changes are typically small, reversible upon discontinuation, and not associated with clinical syndromes.

Dermatologic reactions may manifest as impaired wound healing, thin fragile skin, petechiae, ecchymoses, facial erythema, and increased sweating. Neurological effects can include increased intracranial pressure, convulsions, vertigo, headache, and epidural lipomatosis. Endocrine disturbances may lead to a Cushingoid state, suppression of growth in children, menstrual irregularities, and increased requirements for insulin or oral hypoglycemic agents in diabetic patients. Metabolic effects may result in a negative nitrogen balance due to protein catabolism, while blood and lymphatic system disorders may present as leukocytosis.

Patients should be monitored closely for these adverse reactions, particularly when initiating or adjusting corticosteroid therapy.

Drug Interactions

Drugs that induce hepatic enzymes, such as phenobarbital, phenytoin, and rifampin, may enhance the clearance of corticosteroids. Consequently, it may be necessary to increase the corticosteroid dosage to achieve the desired therapeutic response.

Conversely, drugs that inhibit corticosteroid metabolism, including troleandomycin and ketoconazole, can decrease the clearance of corticosteroids. In such cases, it is advisable to titrate the corticosteroid dose to prevent potential steroid toxicity.

Corticosteroids may also influence the clearance of chronic high-dose aspirin, potentially leading to reduced salicylate serum levels. This effect may increase the risk of salicylate toxicity upon withdrawal of corticosteroids. Therefore, careful monitoring is recommended.

Aspirin should be administered with caution alongside corticosteroids in patients with hypoprothrombinemia due to the potential for increased bleeding risk.

The interaction between corticosteroids and oral anticoagulants is variable, with instances of both enhanced and diminished anticoagulant effects reported. It is essential to monitor coagulation indices closely to ensure the maintenance of the desired anticoagulant effect when these medications are used concurrently.

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 in selected pediatric cases, which may necessitate low-dose maintenance therapy.

Healthcare professionals should closely monitor the growth and development of infants and children undergoing prolonged corticosteroid therapy, as corticosteroids have been associated with growth suppression in this population. Additionally, infants born to mothers who received substantial doses of corticosteroids during pregnancy should be carefully observed for signs of hypoadrenalism.

Geriatric Use

Caution is advised when administering corticosteroids, including hydrocortisone, to elderly patients, particularly those with comorbid conditions such as renal insufficiency, hypertension, and osteoporosis, which are more prevalent in this population. Although there are no specific dosage adjustments or age considerations outlined for geriatric patients, it is recommended that the lowest effective dose of corticosteroid be utilized to manage the condition being treated. If a dosage reduction is feasible, it should be implemented gradually to minimize potential adverse effects.

Elderly patients should be closely monitored for the development of infections, as corticosteroids can suppress the immune system, thereby increasing the risk of infections. This is particularly pertinent in older adults, who may already be at an elevated risk for such complications. Additionally, the effects of corticosteroids may be potentiated in patients with hypothyroidism or cirrhosis, conditions that are more commonly observed in geriatric patients.

Furthermore, existing emotional instability or psychotic tendencies in elderly patients may be exacerbated by corticosteroid therapy. This consideration is especially important for those with a prior history of mental health issues, necessitating careful evaluation and monitoring throughout the course of treatment.

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 essential when corticosteroids are prescribed to pregnant patients or those planning to conceive.

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

There is no specific information regarding dosage adjustments, special monitoring, or safety considerations for patients with renal impairment. Healthcare professionals should exercise caution when prescribing to patients with reduced kidney function, as the absence of detailed guidance necessitates careful clinical judgment. Regular monitoring of renal function may be advisable in this patient population.

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. This consultation should focus 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 active systemic fungal 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

Overdosage of hydrocortisone can result in significant clinical manifestations, necessitating prompt recognition and management.

Symptoms of Overdosage Patients experiencing hydrocortisone overdosage may present with hypertension, volume overload, and hypokalemia. The administration of average to large doses of hydrocortisone or cortisone is particularly associated with elevated blood pressure, salt and water retention, and increased potassium excretion. While synthetic derivatives of corticosteroids are generally less likely to induce these effects, they may still pose a risk when administered in large doses.

Management Recommendations In cases of hydrocortisone overdosage, dietary salt restriction may be warranted to mitigate fluid retention. Additionally, potassium supplementation should be considered to address hypokalemia. It is important to monitor electrolyte levels and adjust treatment accordingly, as all corticosteroids are known to increase calcium excretion, which may further complicate the clinical picture.

Healthcare professionals should remain vigilant for these symptoms and implement appropriate management strategies to ensure patient safety and optimal outcomes.

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 for reproductive health in this population.

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

Patients receiving immunosuppressant doses of corticosteroids should be informed about the increased risk of infections, particularly chicken pox and measles. Healthcare providers should emphasize the importance of avoiding exposure to these infections.

In the event of potential exposure, patients should be advised to seek medical advice promptly. It is crucial for patients to understand the significance of this precaution to ensure their health and safety while undergoing treatment.

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 further data are available.

FDA Insert (PDF)

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

View full prescribing information (PDF)