Hydrocortisone

Description

Hydrocortisone Tablets, USP contain hydrocortisone, a glucocorticoid classified as an adrenocortical steroid, which can be either naturally occurring or synthetic. Hydrocortisone is presented as a white to practically white, odorless, crystalline powder with a melting point of approximately 215° C. It exhibits very slight solubility in water and ether, is 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)-, 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 calcium stearate, corn starch, lactose monohydrate, sorbic acid, and sucrose. It is important to note that FDA-approved dissolution test specifications may differ from those established by the USP.

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, congenital adrenal hyperplasia, non-suppurative thyroiditis, and hypercalcemia associated with cancer. In infants, mineralocorticoid supplementation is particularly important.

Rheumatic Disorders This medication serves as adjunctive therapy for short-term administration during 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 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 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 is indicated for the control of severe or incapacitating allergic conditions that are unresponsive to conventional treatments, 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 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 This drug 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 Hydrocortisone is 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 is indicated to support patients during critical periods of ulcerative colitis and regional enteritis.

Miscellaneous This drug 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 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 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 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 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 advised that hydrocortisone be withdrawn 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 during periods of unusual stress, it is essential to consider an increased dosage of rapidly acting corticosteroids before, during, and after the stressful event to mitigate potential complications.

Immunosuppression and Infection Risk 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, including reactivation of latent infections. Healthcare professionals should monitor patients for signs of infection and consider hydrocortisone withdrawal or dosage reduction as necessary.

Tuberculosis Monitoring When hydrocortisone is prescribed for 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 is recommended.

Viral Infections Patients receiving corticosteroids who are non-immune to varicella or measles are at risk for severe complications if exposed to these viruses. Prophylaxis with varicella zoster immune globulin should be considered for those exposed to varicella, and antiviral treatment may be warranted if varicella develops. Similarly, exposure to measles may necessitate prophylaxis with immunoglobulin.

Hepatitis B Virus Reactivation Corticosteroids can lead to reactivation of hepatitis B virus in carriers and, less frequently, in patients who appear to have resolved infections. Prior to initiating immunosuppressive treatment with hydrocortisone, screening for hepatitis B infection is crucial. For patients with evidence of hepatitis B infection, consultation with specialists in hepatitis management is advised to discuss monitoring and potential antiviral therapy.

Fungal Infections The use of corticosteroids may exacerbate systemic fungal infections. Therefore, hydrocortisone should be avoided in patients with active systemic fungal infections unless absolutely necessary to manage drug reactions. For those on chronic hydrocortisone therapy who develop such infections, dosage reduction or withdrawal is recommended.

Amebiasis and Strongyloides Infestation 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. Caution is also warranted in patients with known or suspected Strongyloides infestation, as corticosteroid-induced immunosuppression can lead to severe complications, including hyperinfection and dissemination.

Cerebral Malaria Corticosteroids should be avoided in patients diagnosed with cerebral malaria due to the potential for exacerbating the condition.

Ophthalmic Effects Prolonged corticosteroid use may lead to posterior subcapsular cataracts, glaucoma, and an increased risk of secondary ocular infections. Regular ophthalmic evaluations are recommended for patients on long-term corticosteroid therapy.

Kaposi's Sarcoma There have been reports of Kaposi's sarcoma in patients receiving corticosteroid therapy, particularly for chronic conditions. Discontinuation of corticosteroids may lead to clinical improvement in such cases.

Cardiovascular and Electrolyte Effects Hydrocortisone can cause hypertension, volume overload, and hypokalemia, particularly at average and high doses. Dietary salt restriction and potassium supplementation may be necessary. All corticosteroids are associated with increased calcium excretion.

Vaccination Considerations Live or live attenuated vaccines are contraindicated in patients receiving immunosuppressive doses of corticosteroids. Killed or inactivated vaccines may be administered, but the immune response may be diminished. Immunization procedures can be performed in patients receiving non-immunosuppressive doses.

Pregnancy and Fertility The use of corticosteroids during pregnancy, in nursing mothers, or in women of childbearing potential requires careful consideration of the potential benefits versus risks. 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 hormone therapy during periods of stress. Caution is advised in patients with hypothyroidism, cirrhosis, ocular herpes simplex, nonspecific ulcerative colitis, and other specified conditions.

Psychiatric effects, including mood swings and severe depression, may occur with corticosteroid use, and existing emotional instability may be exacerbated. Growth and development in infants and children on prolonged therapy should be closely monitored.

In patients with suspected pheochromocytoma, the risk of pheochromocytoma crisis should be considered prior to corticosteroid administration. Furthermore, tumor lysis syndrome has been reported in patients with malignancies following corticosteroid use, necessitating close monitoring in high-risk patients.

Laboratory Testing Screening for hepatitis B infection is essential 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 immunosuppressive effect can reduce resistance to new infections, exacerbate existing infections, and increase the risk of disseminated infections, as well as the reactivation of latent infections. Signs of infection may also be less apparent in these patients. The incidence of infectious complications tends to rise 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 secondary ocular infections due to fungi or viruses.

Patients may also experience hypertension, volume overload, and hypokalemia, particularly with average to large doses of hydrocortisone or cortisone. These effects include elevated blood pressure, salt and water retention, and increased potassium excretion. Dietary salt restriction and potassium supplementation may be necessary, as all corticosteroids can increase calcium excretion.

Other serious adverse reactions include the potential for a pheochromocytoma crisis, which can be fatal, particularly in patients with suspected pheochromocytoma. The risk of this crisis should be carefully considered before administering corticosteroids in such cases.

Common adverse reactions encompass a variety of systems. Fluid and electrolyte disturbances may manifest as sodium and fluid retention, hypokalemic alkalosis, and hypertension, with congestive heart failure occurring in susceptible patients. Musculoskeletal effects include muscle weakness, steroid myopathy, loss of muscle mass, osteoporosis, tendon rupture (especially of the Achilles tendon), vertebral compression fractures, aseptic necrosis of the femoral and humeral heads, and pathologic fractures of long bones.

Gastrointestinal reactions can include peptic ulcers with potential 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 and fragile skin, petechiae, ecchymoses, facial erythema, increased sweating, and suppression of reactions to skin tests. 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 manifestations of latent diabetes mellitus. Diabetic patients may require increased insulin or oral hypoglycemic agents.

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

Psychic derangements can occur, ranging from euphoria, insomnia, mood swings, and personality changes to severe depression and psychotic manifestations. Existing emotional instability or psychotic tendencies may be exacerbated by corticosteroid use.

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

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 potential steroid toxicity.

Corticosteroids may also affect the clearance of chronic high-dose aspirin, potentially resulting in decreased salicylate serum levels. This interaction could increase the risk of salicylate toxicity upon withdrawal of corticosteroids. Therefore, caution is warranted when using aspirin in conjunction with corticosteroids, 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 during concurrent therapy.

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, which may necessitate low-dose maintenance therapy in select cases. The initial dosage of hydrocortisone tablets can 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, as corticosteroids can suppress growth in this population. 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 not require specific dosage adjustments or safety considerations when using Hydrocortisone Tablets, as the prescribing information does not indicate any unique recommendations for this population. However, healthcare providers should remain vigilant in monitoring for potential adverse effects, as the pharmacokinetics and pharmacodynamics of medications can differ in geriatric patients. It is advisable to assess the overall health status and concurrent medications of elderly patients to ensure safe and effective use of Hydrocortisone Tablets.

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, animal studies have indicated that corticosteroids may impair fertility in male rats, suggesting a potential risk that warrants consideration in discussions with patients regarding family planning and reproductive health.

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 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 be at an increased risk for complications when treated with hydrocortisone, particularly those who are carriers of the hepatitis B virus. Hepatitis B virus reactivation can occur in these patients when treated with immunosuppressive dosages of corticosteroids, including hydrocortisone. Additionally, reactivation may infrequently occur in patients who have previously resolved hepatitis B infection but are still receiving corticosteroid treatment.

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 managing hepatitis B. This consultation should focus on appropriate monitoring strategies and the potential need for hepatitis B antiviral therapy.

In patients on chronic hydrocortisone therapy who subsequently develop systemic fungal infections, it is advisable to consider hydrocortisone withdrawal or dosage reduction to mitigate further risks associated with hepatic impairment. Regular monitoring of liver function and clinical status is recommended to ensure patient safety and effective management of therapy.

Overdosage

Overdosage of hydrocortisone can manifest through a range of symptoms, including hypertension, edema, and hypokalemia. These clinical signs necessitate careful monitoring and management to mitigate potential complications.

Chronic overdosage may lead to the development of Cushing's syndrome, which is characterized by obesity, moon facies, and various metabolic alterations. Healthcare professionals should be vigilant in recognizing these symptoms, as they indicate prolonged exposure to elevated levels of hydrocortisone.

In the event of an overdosage, it is imperative to initiate symptomatic treatment promptly. Given that there is no specific antidote for hydrocortisone overdosage, management should focus on alleviating symptoms and preventing further complications. Continuous assessment and supportive care are essential components of the treatment strategy.

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 additional specific details regarding nonclinical toxicology or animal pharmacology and toxicology are available.

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, such as 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.

Patient Counseling

Healthcare providers should advise patients on the importance of avoiding exposure to chicken pox or measles, particularly for those who are on immunosuppressant doses of corticosteroids. It is crucial for these patients to understand that if they are exposed to either of these infections, they should seek medical advice promptly to mitigate potential health risks.

Additionally, healthcare providers should inform patients about the implications for infants born to mothers who have received substantial doses of corticosteroids during pregnancy. These infants should be carefully monitored for signs of hypoadrenalism, as early detection and management are essential for their health and well-being.

Storage and Handling

The product is supplied in various package configurations, with specific NDC numbers available for identification. It should be stored at a temperature range of 20° to 25°C (68° to 77°F). Temporary excursions outside this range are permissible, provided they remain between 15° and 30°C (59° and 86°F), in accordance with USP controlled room temperature guidelines. Proper container requirements must be adhered to, and special handling needs should be observed to maintain product integrity.

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.

Additionally, postmarketing experience has indicated that tumor lysis syndrome (TLS) may occur in patients with malignancies, including both hematological malignancies and solid tumors, following the administration of systemic corticosteroids, whether 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 Eywa Pharma Inc. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)