Hydrocortisone

Description

Hydrocortisone tablets contain hydrocortisone, a glucocorticoid classified as an adrenocortical steroid, which can be either naturally occurring or synthetic. Hydrocortisone USP 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 are formulated for oral administration and are available in three strengths: each tablet contains either 5 mg, 10 mg, or 20 mg of hydrocortisone. The inactive ingredients include calcium stearate, corn starch, lactose, mineral oil, sorbic acid, and sucrose.

Uses and Indications

Hydrocortisone tablets are indicated for the treatment of various conditions across multiple medical disciplines.

Endocrine Disorders This drug is indicated for the management of primary or secondary adrenocortical insufficiency, with hydrocortisone or cortisone being the first choice. Synthetic analogs may be used in conjunction with mineralocorticoids where applicable, particularly in infants where mineralocorticoid supplementation is crucial. Additional indications include congenital adrenal hyperplasia, non-suppurative thyroiditis, and hypercalcemia associated with cancer.

Rheumatic Disorders Hydrocortisone is indicated as adjunctive therapy for short-term administration in acute episodes or exacerbations of psoriatic arthritis, rheumatoid arthritis (including juvenile rheumatoid arthritis, with selected cases possibly requiring low-dose maintenance therapy), ankylosing spondylitis, acute and subacute bursitis, acute nonspecific tenosynovitis, acute gouty arthritis, post-traumatic osteoarthritis, synovitis of osteoarthritis, and epicondylitis.

Collagen Diseases This drug is indicated during exacerbations or as maintenance therapy in selected cases of systemic lupus erythematosus, systemic dermatomyositis (polymyositis), and acute rheumatic carditis.

Dermatologic Diseases Hydrocortisone is indicated for the treatment of pemphigus, bullous dermatitis herpetiformis, severe erythema multiforme (Stevens-Johnson syndrome), exfoliative dermatitis, mycosis fungoides, severe psoriasis, and severe seborrheic dermatitis.

Allergic States This drug is indicated for the control of severe or incapacitating allergic conditions that are intractable to adequate trials of conventional treatment, including seasonal or perennial allergic rhinitis, serum sickness, bronchial asthma, contact dermatitis, atopic dermatitis, and drug hypersensitivity reactions.

Ophthalmic Diseases Hydrocortisone is indicated for severe acute and chronic allergic and inflammatory processes involving the eye and its adnexa, such as allergic conjunctivitis, keratitis, allergic corneal marginal ulcers, herpes zoster ophthalmicus, iritis and iridocyclitis, chorioretinitis, anterior segment inflammation, diffuse posterior uveitis and choroiditis, optic neuritis, and sympathetic ophthalmia.

Respiratory Diseases This drug is indicated for symptomatic sarcoidosis, Loeffler's syndrome not manageable by other means, berylliosis, fulminating or disseminated pulmonary tuberculosis when used concurrently with appropriate antituberculous chemotherapy, and aspiration pneumonitis.

Hematologic Disorders Hydrocortisone is indicated for idiopathic thrombocytopenic purpura in adults, secondary thrombocytopenia in adults, acquired (autoimmune) hemolytic anemia, erythroblastopenia (RBC anemia), and congenital (erythroid) hypoplastic anemia.

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

Edematous States Hydrocortisone is indicated to induce diuresis or remission of proteinuria in the nephrotic syndrome, without uremia, of the idiopathic type or that due to lupus erythematosus.

Gastrointestinal Diseases This drug is indicated to support patients during critical periods of ulcerative colitis and regional enteritis.

Miscellaneous Hydrocortisone is indicated for tuberculous meningitis with subarachnoid block or impending block when used concurrently with appropriate antituberculous chemotherapy, and for trichinosis with neurologic or myocardial involvement.

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

Dosage and Administration

The initial dosage of hydrocortisone tablets may range from 20 mg to 240 mg per day, tailored to the specific disease entity being treated. In 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 therapies. 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 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.

When discontinuing long-term therapy, it is advised to taper the dosage gradually rather than stopping abruptly to minimize potential withdrawal effects.

Contraindications

Use of this product is contraindicated in patients with systemic fungal infections due to the potential for exacerbation of the condition. Additionally, individuals with known hypersensitivity to any of the components of this product should not use it, as this may lead to severe allergic reactions.

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 CORTEF, 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, with some signs of infection potentially being masked. The incidence of infectious complications correlates with corticosteroid dosage; therefore, vigilant monitoring for infection development is crucial, and consideration should be given to withdrawing CORTEF or reducing its dosage as necessary.

Tuberculosis Patients with latent tuberculosis or tuberculin reactivity who are treated with CORTEF may experience reactivation of tuberculosis. Such patients should be closely monitored for signs of reactivation. During extended CORTEF therapy, chemoprophylaxis is recommended for those with latent tuberculosis or tuberculin reactivity.

Varicella Zoster and Measles Viral Infections Corticosteroid-treated patients who are non-immune to varicella or measles are at risk for severe or fatal outcomes if exposed to these infections. Prophylaxis with varicella zoster immune globulin is advised for patients exposed to varicella, and antiviral treatment should be considered if varicella develops. Similarly, exposure to measles warrants prophylaxis with immunoglobulin.

Hepatitis B Virus Reactivation Reactivation of hepatitis B virus may occur in patients who are carriers and are treated with immunosuppressive doses of corticosteroids, including CORTEF. It can also infrequently occur in patients who appear to have resolved hepatitis B infection. Prior to initiating immunosuppressive treatment with CORTEF, screening for hepatitis B infection is recommended. For those with evidence of hepatitis B infection, consultation with specialists in hepatitis B management is advised regarding monitoring and potential antiviral therapy.

Fungal Infections Corticosteroids may exacerbate systemic fungal infections; thus, CORTEF should be avoided in the presence of such infections unless necessary to control drug reactions. For patients on chronic CORTEF therapy who develop systemic fungal infections, withdrawal or dosage reduction of CORTEF is recommended.

Amebiasis Before initiating CORTEF in patients with a history of travel to tropical regions or unexplained diarrhea, it is prudent to rule out latent or active amebiasis, as corticosteroids may activate latent infections.

Strongyloides Infestation Corticosteroids should be administered with caution in patients with known or suspected Strongyloides infestation, as immunosuppression may lead to hyperinfection and dissemination, potentially resulting in severe enterocolitis and fatal gram-negative septicemia.

Cerebral Malaria Corticosteroids, including CORTEF, should be avoided in patients diagnosed with cerebral malaria.

Ophthalmic Effects Prolonged corticosteroid use may lead to posterior subcapsular cataracts, glaucoma with potential optic nerve damage, and an increased risk of secondary ocular infections due to fungi or viruses.

Kaposi’s Sarcoma Reports indicate that Kaposi’s sarcoma may occur in patients receiving corticosteroid therapy, particularly for chronic conditions. Discontinuation of corticosteroids may lead to clinical improvement of this condition.

Hypertension, Volume Overload, and Hypokalemia Hydrocortisone or cortisone at average to large doses can elevate blood pressure, cause salt and water retention, and increase potassium excretion. These effects are less pronounced with synthetic derivatives unless used in large doses. Dietary salt restriction and potassium supplementation may be necessary, as all corticosteroids increase calcium excretion.

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

Usage in Pregnancy Due to the lack of adequate human reproduction studies, the use of corticosteroids in pregnant women, nursing mothers, or women of childbearing potential requires careful consideration of the potential benefits 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.

General Precautions To minimize drug-induced secondary adrenocortical insufficiency, a gradual reduction in dosage is recommended. This relative insufficiency may persist for months post-therapy; therefore, hormone therapy should be reinstated during any stress events in this period. 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 corticosteroid dose should be utilized, and any dosage reduction should be gradual.

Psychiatric effects, ranging from euphoria to severe depression and psychosis, may occur with corticosteroid use, potentially exacerbating existing emotional instability. Caution is warranted 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.

Given that complications from glucocorticoid treatment are dose- and duration-dependent, a careful risk/benefit assessment is necessary for each patient regarding the appropriate dose and treatment duration. In patients with suspected pheochromocytoma, the risk of pheochromocytoma crisis should be considered prior to corticosteroid administration.

Laboratory Tests Screening for hepatitis B infection is recommended before initiating immunosuppressive treatment with CORTEF to ensure patient safety.

Side Effects

Patients receiving corticosteroids, including CORTEF, 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 an increased risk of tendon rupture, particularly of the Achilles tendon. Patients may also experience vertebral compression fractures and aseptic necrosis of the femoral and humeral heads, as well as pathologic fractures of long bones.

Gastrointestinal complications may arise, including peptic ulcer with potential perforation and hemorrhage, 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, reversible upon discontinuation, and not associated with clinical symptoms.

Neurological adverse reactions can include increased intracranial pressure with papilledema (pseudotumor cerebri), convulsions, vertigo, headache, and epidural lipomatosis. Endocrine effects may 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 are notable, with risks of 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.

Corticosteroids are associated with immunosuppression, increasing the risk of infections from various pathogens, including viral, bacterial, fungal, protozoan, and helminthic sources. This immunosuppression can reduce resistance to new infections, exacerbate existing infections, and increase the risk of disseminated infections, including reactivation of latent infections. Specific concerns include the reactivation of tuberculosis in patients with latent tuberculosis, serious courses of varicella and measles in non-immune patients, and hepatitis B virus reactivation in carriers. Fungal infections may be exacerbated, and latent amebiasis may be activated. Caution is advised in patients with known or suspected Strongyloides infestation and in those with cerebral malaria.

Prolonged use of corticosteroids may lead to posterior subcapsular cataracts, glaucoma, and an increased risk of secondary ocular infections. Additionally, Kaposi’s sarcoma has been reported in patients undergoing corticosteroid therapy.

Overall, the use of corticosteroids requires careful consideration of these potential adverse reactions, particularly in patients with pre-existing conditions or those receiving high doses.

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 pharmacokinetics 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 in patients receiving corticosteroids, particularly those with hypoprothrombinemia, due to the potential for increased bleeding risk.

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

Packaging & NDC

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

Pediatric Use

Hydrocortisone is indicated for selected cases of juvenile rheumatoid arthritis in pediatric patients, which may necessitate low-dose maintenance therapy. Dosage requirements for hydrocortisone are variable and must be individualized based on the specific disease being treated and the response of the pediatric patient.

Careful monitoring of growth and development is essential for infants and children undergoing prolonged corticosteroid therapy, as corticosteroids can suppress growth. This suppression should be closely observed throughout the treatment period. Additionally, in infants, the importance of mineralocorticoid supplementation should be emphasized when hydrocortisone or cortisone is used for the management of adrenocortical insufficiency.

Geriatric Use

Elderly patients may not require specific dosage adjustments or age considerations when prescribed corticosteroids; however, caution is advised due to the increased prevalence of certain conditions within this population. In particular, elderly patients often present with renal insufficiency, which may necessitate careful monitoring when corticosteroids are administered, as these medications can exacerbate renal issues.

Additionally, the use of corticosteroids in patients with hypertension and osteoporosis should be approached with caution, given that these conditions are more common among geriatric patients. The potential for increased sensitivity to side effects in elderly patients is a consideration that healthcare providers should keep in mind, even though it is not explicitly stated in the available data.

Furthermore, while the need for careful monitoring of growth and development in infants and children on prolonged corticosteroid therapy is highlighted, this principle of vigilance may also be applicable to elderly patients. Regular assessment and monitoring are recommended to ensure the safe and effective use of corticosteroids in this vulnerable population.

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, healthcare providers are advised to carefully assess the necessity of corticosteroid treatment in pregnant patients and to discuss potential risks with 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 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 experience an increased risk of complications when treated with CORTEF, 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 CORTEF. It is important to screen patients for hepatitis B infection prior to initiating prolonged treatment with CORTEF. For those who test positive for hepatitis B, consultation with specialists experienced in managing hepatitis B is recommended to discuss appropriate monitoring and the potential need for antiviral therapy.

Additionally, corticosteroids, including CORTEF, have the potential to exacerbate systemic fungal infections. Therefore, the use of CORTEF should be avoided in patients with active systemic fungal infections unless it is necessary to manage drug reactions. For patients on chronic CORTEF therapy who subsequently develop systemic fungal infections, it is advisable to consider withdrawal of CORTEF or a reduction in dosage to mitigate risks associated with hepatic impairment and infection. Regular monitoring of liver function and clinical status is recommended for patients with compromised liver function receiving CORTEF.

Overdosage

Overdosage of corticosteroids, including CORTEF, can lead to significant adverse effects that require careful monitoring and management.

Symptoms of Overdosage Healthcare professionals should be vigilant for symptoms indicative of overdosage, which may include hypertension, hyperglycemia, and an increased risk of infections. These symptoms can manifest shortly after an overdose and may necessitate immediate medical attention.

Long-term Effects Prolonged overdosage can result in Cushing's syndrome, a serious condition characterized by obesity, hypertension, diabetes, and various metabolic disturbances. The development of such complications underscores the importance of adhering to prescribed dosages and monitoring patients closely.

Monitoring and Management Patients receiving corticosteroid therapy should be regularly monitored for signs of overdosage. If symptoms arise, healthcare providers should consider making dosage adjustments as necessary to mitigate risks. In cases of suspected overdosage, it is imperative to seek appropriate medical intervention promptly to address any adverse effects and prevent further complications.

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—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

Healthcare providers should advise patients on the importance of avoiding exposure to chicken pox or measles, particularly for those receiving immunosuppressant doses of corticosteroids. Patients should be informed that if they are exposed to these infections, they must seek medical advice without delay.

In cases where patients are undergoing corticosteroid therapy and are subjected to unusual stress, it is essential to discuss the need for an increased dosage of rapidly acting corticosteroids before, during, and after the stressful situation.

Healthcare providers should monitor patients for the development of infections and consider the withdrawal or dosage reduction of CORTEF as necessary. If a patient treated with CORTEF is exposed to varicella, prophylaxis with varicella zoster immune globulin may be indicated. Should varicella develop, treatment with antiviral agents should be considered. Similarly, if a CORTEF-treated patient is exposed to measles, prophylaxis with immunoglobulin may be warranted.

Prior to initiating immunosuppressive treatment with CORTEF, it is crucial to screen patients for hepatitis B infection. For those who show evidence of hepatitis B infection, healthcare providers should recommend consultation with specialists experienced in managing hepatitis B for appropriate monitoring and consideration of hepatitis B antiviral therapy.

Providers should emphasize the importance of using the lowest possible dose of corticosteroids to control the condition being treated. When a reduction in dosage is feasible, it should be done gradually to minimize the risk of drug-induced secondary adrenocortical insufficiency, which may persist for months after therapy discontinuation. In situations of stress during this period, hormone therapy should be reinstated.

Additionally, healthcare providers should carefully observe the growth and development of infants and children on prolonged corticosteroid therapy. Patients should be informed that corticosteroids may lead to psychic derangements, which can range from euphoria, insomnia, mood swings, and personality changes to severe depression and even psychotic manifestations. It is important to note that existing emotional instability or psychotic tendencies may be exacerbated by corticosteroid treatment.

Storage and Handling

The product is supplied in various package configurations, with specific NDC numbers available for identification. It should be stored at a controlled room temperature of 20° to 25°C (68° to 77°F), in accordance with USP 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 postmarketing 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 Mylan Pharmaceuticals Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)