Hydrocortisone

Description

Hydrocortisone Tablets, USP contain hydrocortisone, a glucocorticoid classified as an adrenocortical steroid, which can be either naturally occurring or synthetic. Hydrocortisone is readily absorbed from the gastrointestinal tract. The compound appears as a white or practically white crystalline powder with a melting point of approximately 215°C. It exhibits very slight solubility in water and ether, sparing solubility in acetone and alcohol, and slight solubility in chloroform. The chemical name for hydrocortisone is pregn-4-ene-3, 20-dione, 11,17,21-trihydroxy-, (11β)-, with a molecular weight of 362.5 g/mol. 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 the following inactive ingredients: 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 Hydrocortisone Tablets are 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 This medication is 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 Hydrocortisone Tablets are 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 This drug 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 Hydrocortisone Tablets are 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 This medication 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 Hydrocortisone Tablets are 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 This drug is indicated for the treatment of idiopathic thrombocytopenic purpura in adults, secondary thrombocytopenia in adults, acquired (autoimmune) hemolytic anemia, erythroblastopenia (RBC anemia), and congenital (erythroid) hypoplastic anemia.

Neoplastic Diseases Hydrocortisone Tablets are indicated for the palliative management of leukemias and lymphomas in adults, as well as acute leukemia in childhood.

Edematous States This medication 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 Hydrocortisone Tablets are indicated to support patients during critical periods of ulcerative colitis and regional enteritis.

Miscellaneous This drug is indicated for the treatment of tuberculous meningitis with subarachnoid block or impending block when used concurrently with appropriate antituberculous chemotherapy, as well as trichinosis with neurologic or myocardial involvement.

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

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, or 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 is contraindicated in patients with systemic fungal infections and in individuals with known hypersensitivity to any components of the product.

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 clinicians should consider hydrocortisone withdrawal or dosage reduction as necessary.

Tuberculosis When hydrocortisone is administered to patients with latent tuberculosis or those exhibiting tuberculin reactivity, there is a risk of reactivation of tuberculosis. Such patients should be closely monitored for signs of reactivation. During extended hydrocortisone therapy, chemoprophylaxis should be provided to 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. In hydrocortisone-treated patients lacking immunity to these diseases, it is crucial to avoid exposure. 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, may experience 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 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 in such cases.

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 euphoria to severe depression, may occur, and existing emotional instability may be exacerbated. Caution is warranted in patients with nonspecific ulcerative colitis, diverticulitis, fresh intestinal anastomoses, 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, as well as the choice between daily or intermittent treatment. In patients with suspected pheochromocytoma, the risk of pheochromocytoma crisis should be considered prior to corticosteroid administration.

In post-marketing experience, 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 Prior to initiating prolonged immunosuppressive treatment with hydrocortisone, screening for hepatitis B infection is essential. 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, encompassing a range of physiological systems.

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 particular, patients with latent tuberculosis or tuberculin reactivity should be closely monitored, and chemoprophylaxis is recommended during prolonged therapy. Severe infections can occur, and the rate of infectious complications correlates with corticosteroid dosage.

Neurological effects may manifest as increased intracranial pressure, leading to conditions such as pseudotumor cerebri, convulsions, and vertigo. Additionally, psychiatric effects can range from euphoria and mood swings to severe depression and psychotic manifestations, particularly in patients with pre-existing emotional instability.

Fluid and electrolyte disturbances are common, including sodium and fluid retention, hypokalemic alkalosis, and hypertension. In susceptible patients, these disturbances may lead to congestive heart failure. Musculoskeletal adverse reactions include muscle weakness, steroid myopathy, osteoporosis, and an increased risk of tendon ruptures, particularly of the Achilles tendon, as well as pathologic fractures.

Gastrointestinal reactions may include peptic ulcers, pancreatitis, and abdominal distention. Laboratory changes such as increases in alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase have been observed, although these changes are typically small and reversible upon discontinuation of therapy.

Ophthalmic effects can include central serous chorioretinopathy, posterior subcapsular cataracts, increased intraocular pressure, and glaucoma. Endocrine effects may involve the development of a Cushingoid state, suppression of growth in children, menstrual irregularities, and increased requirements for insulin or oral hypoglycemic agents in diabetic patients.

Dermatologic reactions may present as impaired wound healing, thin fragile skin, petechiae, ecchymoses, and facial erythema. Patients may also experience increased sweating and suppressed reactions to skin tests.

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

It is important to note that the use of corticosteroids is contraindicated for live or live attenuated vaccinations in patients receiving immunosuppressive doses. Additionally, drug-induced secondary adrenocortical insufficiency may persist for months after therapy discontinuation, necessitating hormone therapy during periods of stress.

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. Consequently, it may be necessary to increase the corticosteroid dosage to achieve the desired therapeutic response.

Conversely, drugs like troleandomycin and ketoconazole can inhibit the metabolism of corticosteroids, leading to decreased clearance. In such cases, it is advisable to titrate the corticosteroid dose to prevent the risk of steroid toxicity.

Corticosteroids may also affect the clearance of chronic high-dose aspirin, potentially resulting in decreased salicylate serum levels or an increased risk of salicylate toxicity upon withdrawal of corticosteroids. Therefore, caution is warranted when using corticosteroids in conjunction with aspirin, particularly in patients with hypoprothrombinemia.

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 corticosteroids are administered concurrently with these agents.

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. In cases of juvenile rheumatoid arthritis, selected patients may benefit from low-dose maintenance therapy. Additionally, infants born to mothers who received substantial doses of corticosteroids during pregnancy require careful observation for signs of hypoadrenalism. It is important to note that corticosteroids have been shown to impair fertility in male rats, which may have implications for pediatric patients as they mature.

Geriatric Use

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

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

Furthermore, elderly patients may be at a higher risk for complications associated with corticosteroid therapy, including infections and cardiovascular events. Therefore, healthcare providers should remain vigilant in assessing the risks and benefits of treatment in this demographic.

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

Patients with renal impairment have not been specifically addressed in the available data regarding dosage adjustments, special monitoring, or safety considerations. Therefore, healthcare professionals should exercise caution when prescribing this medication to patients with reduced kidney function, as the lack of information necessitates careful clinical judgment and monitoring of these patients.

Hepatic Impairment

Patients with hepatic impairment may experience specific risks and require careful management when treated with hydrocortisone. Hepatitis B virus reactivation is a significant concern for patients who are carriers of the virus and are receiving immunosuppressive dosages of corticosteroids, including hydrocortisone. Reactivation can also occur, albeit infrequently, in patients 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 monitoring strategies 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.

Caution is also warranted in patients with known or suspected Strongyloides (threadworm) infestation. In these individuals, the immunosuppressive effects of corticosteroids may lead to Strongyloides hyperinfection and dissemination, which can result in severe enterocolitis and potentially fatal gram-negative septicemia. Thus, careful consideration and monitoring are essential when administering hydrocortisone to patients with hepatic impairment and associated conditions.

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 generally exhibit a lower risk of 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 the effects of sodium retention. Additionally, potassium supplementation should be considered to address hypokalemia. It is important to note that all corticosteroids, including hydrocortisone, are known to increase calcium excretion, which may necessitate monitoring and management of calcium levels in affected patients.

Healthcare professionals should remain vigilant for these symptoms and implement appropriate interventions to manage the consequences of hydrocortisone overdosage effectively.

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 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 potential risks associated with TLS.

Patient Counseling

Patients receiving immunosuppressant doses of corticosteroids should be informed about the importance of avoiding exposure to chicken pox or measles. Healthcare providers should emphasize that these patients are at an increased risk of severe complications if they contract these infections.

Additionally, patients should be advised that in the event of exposure to chicken pox or measles, it is crucial to seek medical advice promptly. This proactive approach can help ensure appropriate management and reduce the risk of serious health issues.

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

Patients receiving immunosuppressant doses of corticosteroids should be counseled to avoid exposure to chicken pox or measles. In the event of exposure, it is crucial for patients to seek medical advice promptly.

In post-marketing experience, 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.

FDA Insert (PDF)

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

View full prescribing information (PDF)