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 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 the following inactive ingredients: lactose, pregelatinized corn starch, microcrystalline cellulose, croscarmellose sodium, sodium starch glycolate, and magnesium stearate.

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, 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 Hydrocortisone Tablets are 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 This drug is 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 Hydrocortisone Tablets are 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 unresponsive to adequate trials of conventional treatment, including seasonal or perennial allergic rhinitis, serum sickness, bronchial asthma, contact dermatitis, atopic dermatitis, and drug hypersensitivity reactions.

Ophthalmic Diseases Hydrocortisone Tablets are 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 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 Hydrocortisone Tablets are indicated for idiopathic thrombocytopenic purpura in adults, secondary thrombocytopenia in adults, acquired (autoimmune) hemolytic anemia, erythroblastopenia (RBC anemia), and congenital (erythroid) hypoplastic anemia.

Neoplastic Diseases This drug is indicated for the palliative management of leukemias and lymphomas in adults, as well as acute leukemia in childhood.

Edematous States Hydrocortisone Tablets are 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 Tablets are 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 tablets should be discontinued, and the patient should be transitioned to alternative appropriate 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.

When discontinuing long-term therapy, it is recommended 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, it is crucial to recognize that unusual stress may necessitate an increased dosage of rapidly acting corticosteroids before, during, and after the stressful event. Corticosteroids have the potential to mask signs of infection, and new infections may emerge during their use. This includes infections caused by various pathogens—viral, bacterial, fungal, protozoan, or helminthic—either alone or in conjunction with other immunosuppressive agents that impact cellular and humoral immunity, as well as neutrophil function. The risk of infectious complications escalates with higher doses of corticosteroids, leading to decreased resistance and challenges in localizing infections.

Prolonged corticosteroid use is associated with the development of posterior subcapsular cataracts, glaucoma, and an increased risk of secondary ocular infections due to fungi or viruses. Given the lack of adequate human reproduction studies, the use of corticosteroids in pregnant women, nursing mothers, or women of childbearing potential must involve a careful assessment of the potential benefits against the 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.

Patients receiving average to large doses of hydrocortisone or cortisone may experience elevated blood pressure, salt and water retention, and increased potassium excretion. These effects are less pronounced with synthetic derivatives unless administered in large doses. Dietary salt restriction and potassium supplementation may be warranted, as all corticosteroids increase calcium excretion.

Administration of live or live attenuated vaccines is contraindicated in patients receiving immunosuppressive doses of corticosteroids. While killed or inactivated vaccines may be given, the immune response may be diminished. Immunization procedures can be performed in patients on nonimmunosuppressive doses of corticosteroids. The use of hydrocortisone tablets in active tuberculosis should be limited to cases of fulminating or disseminated tuberculosis, where corticosteroids are part of a comprehensive antituberculous regimen. For patients with latent tuberculosis or tuberculin reactivity, close monitoring is essential due to the risk of disease reactivation, and chemoprophylaxis should be administered during prolonged corticosteroid therapy.

Patients on immunosuppressive drugs are at an increased risk for infections, with chickenpox and measles potentially leading to severe or fatal outcomes in non-immune individuals. Careful measures should be taken to avoid exposure to these diseases, and prophylactic treatments such as varicella zoster immune globulin (VZIG) or pooled intramuscular immunoglobulin (IG) may be indicated if exposure occurs. In cases of chickenpox, antiviral treatment may be considered. Caution is also advised in patients with known or suspected Strongyloides infestation.

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 reinstatement of hormone therapy during periods of stress. Enhanced effects of corticosteroids may be observed in patients with hypothyroidism or cirrhosis. Caution is warranted in patients with ocular herpes simplex due to the risk of corneal perforation.

The lowest effective corticosteroid dose should be utilized, with gradual reductions when feasible. Psychiatric effects, ranging from euphoria and mood swings to severe depression and psychosis, may occur, and pre-existing emotional instability may be exacerbated. Caution is also advised in patients with nonspecific ulcerative colitis, diverticulitis, fresh intestinal anastomoses, active or latent peptic ulcer, renal insufficiency, hypertension, osteoporosis, and myasthenia gravis. Growth and development in infants and children on prolonged corticosteroid therapy should be closely monitored.

Kaposi's sarcoma has been reported in patients receiving corticosteroid therapy, and discontinuation may lead to clinical remission. Given that complications from glucocorticoid treatment are dose- and duration-dependent, a thorough risk/benefit analysis is essential for each patient regarding the appropriate dosage and treatment duration, as well as the choice between daily or intermittent therapy. In patients with suspected pheochromocytoma, the risk of a potentially fatal pheochromocytoma crisis should be carefully considered prior to corticosteroid administration.

Side Effects

Adverse reactions associated with corticosteroid use can be categorized based on their 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, potassium loss and hypokalemic alkalosis have been reported.

Musculoskeletal adverse reactions are also significant, with reports of muscle weakness, steroid myopathy, loss of muscle mass, and osteoporosis. Serious complications such as tendon rupture, particularly of the Achilles tendon, vertebral compression fractures, aseptic necrosis of the femoral and humeral heads, and pathologic fractures of long bones have been observed.

Gastrointestinal adverse reactions include the potential for peptic ulceration, which may lead to perforation and hemorrhage, as well as pancreatitis and abdominal distention. Participants in clinical trials have shown increases in alanine transaminase (ALT, SGPT), aspartate transaminase (AST, SGOT), and alkaline phosphatase following corticosteroid treatment; these changes are typically small, not associated with clinical syndromes, and reversible upon discontinuation.

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

Neurological adverse reactions include increased intracranial pressure with papilledema (pseudotumor cerebri), convulsions, vertigo, headache, and epidural lipomatosis.

Endocrine effects can lead to the development of a Cushingoid state, suppression of growth in children, and secondary adrenocortical and pituitary unresponsiveness, particularly during periods of stress such as trauma, surgery, or illness. Other endocrine-related adverse reactions include menstrual irregularities, decreased carbohydrate tolerance, manifestations of latent diabetes mellitus, and increased requirements for insulin or oral hypoglycemic agents in diabetic patients.

Ophthalmic adverse reactions include central serous chorioretinopathy, posterior subcapsular cataracts, increased intraocular pressure, glaucoma, and exophthalmos.

Metabolic disturbances such as negative nitrogen balance due to protein catabolism and leukocytosis in the blood and lymphatic system have also been reported.

Warnings associated with corticosteroid use indicate that these medications may mask signs of infection, with new infections potentially arising during treatment. Infections caused by various pathogens, including viral, bacterial, fungal, protozoan, or helminthic agents, may occur, and the risk of infectious complications increases with higher doses of corticosteroids. Prolonged use may lead to posterior subcapsular cataracts, glaucoma with possible optic nerve damage, and an increased risk of secondary ocular infections due to fungi or viruses.

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 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.

Packaging & NDC

The table below lists all NDC Code configurations of Hydrocortisone, the U.S. brand-name prescription product. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

Pediatric Use

Hydrocortisone is indicated for the treatment of juvenile rheumatoid arthritis, with some cases potentially requiring low-dose maintenance therapy. In pediatric patients, particularly infants and children receiving prolonged corticosteroid therapy, careful monitoring of growth and development is essential.

Infants born to mothers who received substantial doses of corticosteroids during pregnancy should be closely observed for signs of hypoadrenalism. Additionally, caution is warranted in children who have not had chicken pox or measles, as these patients may experience a more severe or even fatal course if exposed to these infections while on corticosteroids.

For children exposed to chicken pox, prophylaxis with varicella zoster immune globulin (VZIG) may be indicated, while pooled intramuscular immunoglobulin (IG) may be necessary for those exposed to measles. It is important to note that corticosteroids can suppress growth in children, necessitating ongoing assessment of growth parameters during treatment.

Geriatric Use

Caution is advised when using corticosteroids in elderly patients due to the potential for increased sensitivity to side effects. It is important to recognize that elderly patients may have reduced kidney function, which can significantly affect drug metabolism and clearance. Therefore, the lowest effective dose should be utilized in this population to minimize the risk of adverse effects.

Close monitoring of elderly patients is recommended to detect any signs of complications or adverse reactions. Additionally, dosage adjustments may be necessary based on the individual response and clinical status of elderly patients. This approach ensures that treatment is both safe and effective while addressing the unique considerations associated with geriatric care.

Pregnancy

The use of corticosteroids during pregnancy requires careful consideration of the potential benefits and risks to both the mother and the developing embryo or fetus, as adequate human reproduction studies have not been conducted. Healthcare professionals should weigh the therapeutic advantages against the possible hazards associated with corticosteroid use in pregnant patients, nursing mothers, or women of childbearing potential.

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 implications for reproductive health that warrant further investigation.

In summary, the decision to use corticosteroids in pregnant patients should be made with caution, considering both maternal health needs and fetal safety.

Lactation

Lactating mothers should consider the potential benefits of the drug against the possible hazards to themselves and their breastfed infants. It is important to monitor breastfed infants born to mothers who have received substantial doses of corticosteroids during pregnancy for signs of hypoadrenalism.

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.

Hepatic Impairment

Patients with hepatic impairment have not been specifically studied in relation to the use of this medication. Consequently, there are no established dosage adjustments, special monitoring requirements, or precautions outlined for individuals with compromised liver function. It is recommended that healthcare providers exercise caution when prescribing this medication to patients with hepatic impairment, given the lack of data on its safety and efficacy in this population. Regular monitoring of liver function may be prudent in these cases, although specific parameters are not defined in the available information.

Overdosage

Overdosage of corticosteroids can result in significant clinical manifestations, including hypertension, salt and water retention, and increased excretion of potassium. These symptoms are particularly associated with the administration of average and large doses of hydrocortisone or cortisone. In contrast, synthetic derivatives are less likely to induce these effects unless administered in substantial quantities.

In the event of corticosteroid overdosage, it may be necessary to implement dietary salt restrictions and consider potassium supplementation to mitigate the associated electrolyte imbalances.

Additionally, it is important to note that drug-induced secondary adrenocortical insufficiency may develop as a consequence of overdosage. This condition can persist for several months following the cessation of corticosteroid therapy. Therefore, in any situation of physiological stress during this recovery period, it is crucial to reinstitute hormone therapy to support the patient's adrenal function adequately.

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.

Postmarketing Experience

Postmarketing experience has identified several adverse reactions reported voluntarily or through surveillance programs. These include sodium and fluid retention, which may lead to congestive heart failure in susceptible patients. Electrolyte imbalances such as potassium loss and hypokalemic alkalosis have also been noted. Hypertension, muscle weakness, steroid myopathy, and loss of muscle mass are additional concerns.

Skeletal complications include osteoporosis, tendon rupture—particularly of the Achilles tendon—vertebral compression fractures, aseptic necrosis of the femoral and humeral heads, and pathologic fractures of long bones. Gastrointestinal events such as peptic ulcer with potential perforation and hemorrhage, pancreatitis, and abdominal distention have been reported. Ulcerative esophagitis has also been observed.

Hepatic enzyme elevations, specifically increases in alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase, have been documented following corticosteroid treatment. These changes are typically minor, not associated with clinical symptoms, and are reversible upon discontinuation. Impaired wound healing, thin fragile skin, petechiae, ecchymoses, and facial erythema have been noted as well.

Other reported effects include increased sweating, suppression of reactions to skin tests, and increased intracranial pressure with papilledema (pseudotumor cerebri), usually following treatment. Neurological events such as convulsions, vertigo, and headache have been documented, along with epidural lipomatosis.

Endocrine effects include the development of a Cushingoid state, suppression of growth in children, and secondary adrenocortical and pituitary unresponsiveness, particularly during stress. Menstrual irregularities, decreased carbohydrate tolerance, and manifestations of latent diabetes mellitus have also been reported, along with increased requirements for insulin or oral hypoglycemic agents in diabetic patients.

Ocular effects such as central serous chorioretinopathy, posterior subcapsular cataracts, increased intraocular pressure, glaucoma, and exophthalmos have been observed. Additionally, a negative nitrogen balance due to protein catabolism and leukocytosis have been noted in the postmarketing experience.

To report suspected adverse reactions, healthcare professionals are encouraged to contact AvKARE at 1-855-361-3993, via email at drugsafety@avkare.com, or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Patient Counseling

Healthcare providers should advise patients on the importance of avoiding exposure to chicken pox or measles, particularly for those who are receiving immunosuppressant doses of corticosteroids. It is crucial for patients to understand that their immune system may be compromised, increasing their susceptibility to infections.

In the event of exposure to either 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 potential complications associated with these infections.

Storage and Handling

The product is dispensed in Unit Dose Packaging and is intended for institutional use only. It should be stored at a temperature range of 20° to 25°C (68° to 77°F), in accordance with USP Controlled Room Temperature guidelines. Proper storage conditions are essential to maintain the integrity and efficacy of the product.

Additional Clinical Information

Patients on immunosuppressant doses of corticosteroids should be cautioned to avoid exposure to chicken pox or measles. It is important for these patients to seek medical advice promptly if they are exposed to either of these infections.

FDA Insert (PDF)

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

View full prescribing information (PDF)