Cortef

Description

CORTEF Tablets contain hydrocortisone, a glucocorticoid classified as an adrenocortical steroid, which is readily absorbed from the gastrointestinal tract. 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, 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.

CORTEF 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

CORTEF 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, particularly in infants where mineralocorticoid supplementation is crucial.

Rheumatic Disorders CORTEF is indicated as adjunctive therapy for short-term administration during acute episodes or exacerbations of psoriatic arthritis, rheumatoid arthritis (including juvenile rheumatoid arthritis, where low-dose maintenance therapy may be required), ankylosing spondylitis, acute and subacute bursitis, acute nonspecific tenosynovitis, acute gouty arthritis, post-traumatic osteoarthritis, synovitis of osteoarthritis, and epicondylitis.

Collagen Diseases 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 CORTEF 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 unresponsive to conventional treatments, including seasonal or perennial allergic rhinitis, serum sickness, bronchial asthma, contact dermatitis, atopic dermatitis, and drug hypersensitivity reactions.

Ophthalmic Diseases CORTEF is indicated for severe acute and chronic allergic and inflammatory processes affecting 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 CORTEF is indicated for the treatment of idiopathic thrombocytopenic purpura in adults, secondary thrombocytopenia in adults, acquired (autoimmune) hemolytic anemia, erythroblastopenia (RBC anemia), and congenital (erythroid) hypoplastic anemia.

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

Edematous States CORTEF is indicated to induce diuresis or remission of proteinuria in the nephrotic syndrome, without uremia, of 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 CORTEF is indicated for the treatment of tuberculous meningitis with subarachnoid block or impending block when used concurrently with appropriate antituberculous chemotherapy, as well as trichinosis with neurologic or myocardial involvement.

Limitations of Use No specific teratogenic or nonteratogenic effects have been mentioned in the provided data.

Dosage and Administration

The initial dosage of CORTEF Tablets may range from 20 mg to 240 mg of hydrocortisone per day, tailored to 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, CORTEF 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 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 CORTEF in accordance with the patient's condition.

For patients undergoing long-term therapy, it is advised that CORTEF 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 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, and corticosteroids may mask some signs of infection. 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 When CORTEF 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. During extended CORTEF therapy, chemoprophylaxis is recommended for patients with latent tuberculosis or tuberculin reactivity.

Varicella Zoster and Measles Viral Infections Patients receiving corticosteroids, including CORTEF, who are non-immune to varicella or measles are at risk for severe or potentially fatal courses of these infections. It is imperative to avoid exposure to these viruses. If exposure occurs, prophylaxis with varicella zoster immune globulin or immunoglobulin may be indicated. Should varicella develop, antiviral treatment may be warranted.

Hepatitis B Virus Reactivation Corticosteroids can lead to reactivation of hepatitis B virus in carriers receiving immunosuppressive doses. Reactivation may also occur in patients who appear to have resolved hepatitis B infection. Prior to initiating prolonged treatment with CORTEF, patients should be screened for hepatitis B infection. For those with positive results, consultation with specialists in hepatitis B management is advised to discuss monitoring and potential antiviral therapy.

Fungal Infections The use of corticosteroids, including CORTEF, may exacerbate systemic fungal infections. Therefore, 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 develop systemic fungal infections, dosage reduction or withdrawal of CORTEF is recommended.

Amebiasis Before initiating CORTEF 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 administered with caution in patients with known or suspected Strongyloides infestation, as immunosuppression may lead to hyperinfection and severe complications, including enterocolitis and potentially fatal septicemia.

Cerebral Malaria Corticosteroids, including CORTEF, are contraindicated in patients with cerebral malaria.

Ophthalmic Effects Prolonged corticosteroid use may result in posterior subcapsular cataracts, glaucoma, and an increased risk of secondary ocular infections due to fungi or viruses.

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

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 high doses. Dietary salt restriction and potassium supplementation may be necessary, as all corticosteroids can 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 Due to the lack of adequate human studies, the use of corticosteroids in pregnant or nursing women, or those of childbearing potential, requires careful consideration of the potential benefits against 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 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 corticosteroid dose should be utilized, and any dosage reduction should be gradual.

Psychiatric effects, ranging from euphoria to severe depression, may occur with corticosteroid use, potentially exacerbating existing emotional instability or psychotic tendencies. 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 thorough risk/benefit assessment is essential for each patient regarding the appropriate dosage and treatment duration. In patients with suspected pheochromocytoma, the risk of pheochromocytoma crisis should be considered prior to corticosteroid administration. Additionally, tumor lysis syndrome (TLS) has been reported in patients with malignancies following systemic corticosteroid use, necessitating close monitoring and appropriate precautions for those at high risk of TLS.

Laboratory Tests Prior to initiating prolonged treatment with CORTEF, patients should be screened for hepatitis B infection. For those with evidence of hepatitis B, consultation with specialists in hepatitis B management is recommended to discuss monitoring and potential antiviral therapy.

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 immunosuppression, which increases 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, as well as the reactivation of latent infections. Notably, patients with latent tuberculosis or tuberculin reactivity may experience reactivation of tuberculosis. Additionally, hepatitis B virus reactivation has been reported in carriers treated with immunosuppressive doses of corticosteroids. Other serious infections, such as varicella and measles, can have severe or fatal outcomes in non-immune patients. Fungal infections may also be exacerbated, and caution is advised in patients with known or suspected Strongyloides infestation and those with cerebral malaria.

Fluid and electrolyte disturbances are common, manifesting as sodium and fluid retention, hypertension, potassium loss, hypokalemic alkalosis, and congestive heart failure in susceptible patients. Musculoskeletal adverse reactions include 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, aseptic necrosis of the femoral and humeral heads, and pathologic fractures of long bones.

Gastrointestinal reactions can be serious, including peptic ulcer 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 effects may include impaired wound healing, thin fragile skin, petechiae, ecchymoses, facial erythema, increased sweating, and suppression of reactions to skin tests. Neurological adverse reactions can involve 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 include central serous chorioretinopathy, posterior subcapsular cataracts, increased intraocular pressure, glaucoma, and exophthalmos.

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

Prolonged use of corticosteroids can lead to significant ophthalmic effects, including posterior subcapsular cataracts and glaucoma, which may damage the optic nerves and enhance the risk of secondary ocular infections. The use of live or live attenuated vaccines is contraindicated in patients receiving immunosuppressive doses of corticosteroids.

In summary, the adverse reactions associated with corticosteroids, including CORTEF, are diverse and can range from mild to severe, necessitating careful monitoring and management in affected patients.

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 Cortef (hydrocortisone), the U.S. brand-name prescription product. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

Pediatric Use

Pediatric patients with juvenile rheumatoid arthritis may be treated with CORTEF, which is indicated for this condition. In selected cases, low-dose maintenance therapy may be necessary. The initial dosage of CORTEF Tablets can range from 20 mg to 240 mg of hydrocortisone per day, depending on the specific disease being treated. Dosing requirements are variable and should be individualized based on the patient's response and the disease entity.

It is essential to monitor the growth and development of infants and children undergoing prolonged corticosteroid therapy, as corticosteroids can suppress growth in this population. If long-term therapy is to be discontinued, it is recommended that the medication be withdrawn gradually to avoid potential withdrawal effects.

Geriatric Use

Elderly patients may exhibit increased sensitivity to the effects of corticosteroids, including hydrocortisone. Due to potential reductions in kidney function and alterations in pharmacokinetics, dosage adjustments may be necessary for this population. It is recommended that the lowest effective dose be utilized in geriatric patients to minimize the risk of adverse effects.

Close monitoring for side effects and therapeutic response is essential for elderly patients receiving corticosteroid therapy. This population may also be at a heightened risk for complications such as osteoporosis, hypertension, and infections when treated with corticosteroids. Therefore, careful consideration and management are advised to ensure the safety and efficacy of treatment in geriatric patients.

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 CORTEF in lactating mothers requires careful consideration of the potential benefits of the drug against the possible hazards 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 data regarding dosage adjustments, special monitoring, or safety considerations. Therefore, healthcare professionals should exercise caution when prescribing this medication to patients with reduced kidney function, as the lack of information necessitates careful clinical judgment and monitoring of these patients.

Hepatic Impairment

Patients with hepatic impairment may experience 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 infection, a consultation with a physician 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 either withdrawing CORTEF or reducing the dosage to mitigate risks associated with hepatic impairment and infection.

Overdosage

Overdosage of corticosteroids, including CORTEF, can lead to significant adverse effects that require prompt attention.

Symptoms of Overdosage Healthcare professionals should be vigilant for symptoms associated with corticosteroid overdosage, which may include hypertension, edema, and hypokalemia. These manifestations can indicate the need for immediate intervention.

Long-term Effects Prolonged overdosage may result in Cushing's syndrome, a condition characterized by obesity, moon facies, and various metabolic disturbances. Awareness of these potential long-term effects is crucial for effective patient management.

Management Procedures In the event of overdosage, it is essential to initiate symptomatic treatment promptly. The dosage of CORTEF should be carefully evaluated and may need to be reduced or discontinued based on the severity of the symptoms and the clinical judgment of the healthcare provider. Regular monitoring and supportive care are recommended to mitigate adverse effects and ensure patient safety.

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 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 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 use 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 Cortef as submitted by Pharmacia & Upjohn Company LLC. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)