Hydrocortisone

Description

Hydrocortisone Tablets, USP contain hydrocortisone, a glucocorticoid classified as an adrenocortical steroid, which is readily absorbed from the gastrointestinal tract. 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, 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 362.46. 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 lactose monohydrate, microcrystalline cellulose, colloidal silicon dioxide, and magnesium stearate. The FDA-approved dissolution test and specifications differ from those outlined in 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, 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 This drug 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 Indications include 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 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 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 Indications include use 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.

No specific teratogenic or nonteratogenic effects have been mentioned in the provided information.

Dosage and Administration

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

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

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

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

For patients undergoing long-term therapy, it is recommended 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 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. It is crucial to monitor patients for signs of infection and 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, and during prolonged hydrocortisone therapy, chemoprophylaxis for tuberculosis is recommended.

Varicella Zoster and Measles Viral Infections Patients receiving corticosteroids who are non-immune to varicella or measles are at risk for severe or fatal outcomes if exposed to these viruses. Prophylaxis with varicella zoster immune globulin may be indicated 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 Corticosteroids can lead to reactivation of hepatitis B virus in carriers and, less frequently, in patients who appear to have resolved hepatitis B infection. Prior to initiating immunosuppressive treatment with hydrocortisone, it is imperative to screen patients for hepatitis B infection. For those with evidence of hepatitis B, consultation with specialists in hepatitis management is advised regarding monitoring and potential antiviral therapy.

Fungal Infections Corticosteroids may exacerbate systemic fungal infections. Therefore, hydrocortisone should be avoided in patients with such infections unless it is necessary to control 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 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 are contraindicated in patients 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 in patients receiving corticosteroid therapy, particularly for chronic conditions. Discontinuation of corticosteroids may result in clinical improvement of this condition.

Hypertension, Volume Overload, and Hypokalemia Hydrocortisone and cortisone can cause hypertension, salt and water retention, and increased potassium excretion. Dietary salt restriction and potassium supplementation may be necessary. All corticosteroids also increase calcium excretion.

Vaccinations 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 may be performed in patients receiving non-immunosuppressive doses.

Usage in Pregnancy The use of corticosteroids during pregnancy, in nursing mothers, or in women of childbearing potential should be carefully considered, weighing the potential benefits against 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 corticosteroid should be used, and any dosage reduction should be gradual.

Psychiatric effects, including mood swings and severe depression, may occur with corticosteroid use, and existing emotional instability may be exacerbated. 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.

The risk of pheochromocytoma crisis, which can be fatal, should be considered before administering corticosteroids to patients with suspected pheochromocytoma. Additionally, tumor lysis syndrome (TLS) has been reported in patients with malignancies following systemic corticosteroid use. Patients at high risk for TLS should be monitored closely, and appropriate precautions should be taken.

Laboratory Tests Screening for hepatitis B infection is recommended prior to 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 fluid and electrolyte disturbances such as sodium retention, fluid retention, and hypertension. In susceptible patients, these disturbances may lead to congestive heart failure. Additionally, corticosteroids can cause significant musculoskeletal effects, including muscle weakness, steroid myopathy, loss of muscle mass, osteoporosis, and tendon rupture, particularly of the Achilles tendon. Other serious musculoskeletal complications may include vertebral compression fractures and aseptic necrosis of the femoral and humeral heads.

Gastrointestinal adverse reactions can be severe, with reports of peptic ulceration that may lead to perforation and hemorrhage, as well as pancreatitis. Patients may also experience abdominal distention and ulcerative esophagitis. Laboratory changes, such as increases in alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase, have been observed following corticosteroid treatment; these changes are typically small, reversible upon discontinuation, and not associated with clinical syndromes.

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

Ophthalmic effects associated with corticosteroid use include central serous chorioretinopathy, posterior subcapsular cataracts, increased intraocular pressure, glaucoma, and exophthalmos. Metabolic effects may present as a negative nitrogen balance due to protein catabolism, while blood and lymphatic system disorders may include leukocytosis.

Corticosteroids are known to suppress the immune system, increasing the risk of infections from various pathogens, including viral, bacterial, fungal, protozoan, and helminthic sources. This immunosuppression can lead to the exacerbation of existing infections, reactivation of latent infections, and may mask signs of infection. The risk of infectious complications is dose-dependent.

Specific warnings include the potential for reactivation of latent tuberculosis in patients with tuberculin reactivity, as well as serious complications from varicella and measles in non-immune patients. Hepatitis B virus reactivation has been reported in carriers receiving immunosuppressive doses of corticosteroids. Additionally, corticosteroids may exacerbate systemic fungal infections and should be used cautiously in patients with known or suspected Strongyloides infestation, as this can lead to severe complications.

Psychiatric effects may range from euphoria and mood swings to severe depression and psychotic manifestations. Pheochromocytoma crisis has been reported following systemic corticosteroid administration, necessitating caution in patients with suspected pheochromocytoma. In postmarketing experiences, tumor lysis syndrome has been observed in patients with malignancies following corticosteroid use, highlighting the need for close monitoring in high-risk patients.

Overall, the adverse reactions associated with corticosteroids necessitate careful consideration and monitoring during treatment.

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, careful monitoring is recommended.

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

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.

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 for pediatric patients can range from 20 mg to 240 mg per day, depending on the specific disease being treated. Dosage requirements are variable and must be individualized based on the disease entity and the patient's response.

Healthcare professionals should closely 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 carefully observed for signs of hypoadrenalism.

Geriatric Use

Elderly patients may not require specific dosage adjustments or have unique safety concerns when using Hydrocortisone Tablets, as the prescribing information does not indicate any particular 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 potential reproductive risks that warrant consideration in the context of treatment decisions for 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 crucial to ensure the well-being of the infant during the breastfeeding 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 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, corticosteroid-induced immunosuppression can lead to Strongyloides hyperinfection and dissemination, which may result in severe enterocolitis and potentially fatal gram-negative septicemia. Thus, careful monitoring and management are crucial for patients with hepatic impairment receiving hydrocortisone therapy.

Overdosage

In the absence of specific information regarding overdosage, healthcare professionals are advised to exercise caution and adhere to general principles of management in cases of suspected overdose.

It is essential to monitor the patient closely for any potential symptoms that may arise from excessive dosing. Symptoms of overdosage can vary widely depending on the substance involved and the individual patient's response.

In the event of an overdose, immediate medical attention should be sought. Healthcare providers should implement supportive care measures, which may include monitoring vital signs, providing symptomatic treatment, and ensuring the patient's safety.

If available, consultation with a poison control center or a medical toxicologist is recommended to guide the management of the overdose. Additionally, healthcare professionals should refer to local protocols and guidelines for the management of overdose situations, as these may provide specific recommendations based on the substance involved.

Documentation of the incident, including the amount ingested and the time of ingestion, is crucial for effective management and follow-up care.

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.

No specific details regarding nonclinical toxicology or animal pharmacology and toxicology are provided in the insert.

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 this patient population.

Patient Counseling

Healthcare providers should advise patients on the importance of avoiding exposure to chicken pox or measles, particularly for those receiving immunosuppressant doses of corticosteroids. It is crucial for patients to understand that their immune response may be compromised, increasing their risk of severe illness from these infections.

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

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° to 30°C (59° to 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 conjunction 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 implement appropriate precautions.

FDA Insert (PDF)

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

View full prescribing information (PDF)