Hydrocortisone

Description

Hydrocortisone tablets, USP contain hydrocortisone, a glucocorticoid. Hydrocortisone is a white to practically white, odorless, crystalline powder with a melting point of approximately 215º C. It is very slightly soluble in water and ether, 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)-, and its molecular weight is 362.46. Hydrocortisone tablets, USP are available for oral administration in three strengths: each tablet contains either 5 mg, 10 mg, or 20 mg of hydrocortisone. Inactive ingredients include colloidal silicon dioxide, lactose monohydrate, magnesium stearate, and microcrystalline cellulose.

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 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 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 in childhood.

Edematous States Hydrocortisone 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 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, 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.

For patients undergoing long-term therapy, it is advised to withdraw hydrocortisone 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 increase the dosage of rapidly acting corticosteroids before, during, and after the stressful situation 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 Patients with latent tuberculosis or tuberculin reactivity who are treated with hydrocortisone are at risk for reactivation of tuberculosis. Close monitoring for reactivation is advised, and during prolonged hydrocortisone therapy, these patients should receive chemoprophylaxis.

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 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 Reactivation of hepatitis B virus can occur in patients who are carriers and are treated with immunosuppressive doses of corticosteroids, including hydrocortisone. It is recommended to screen for hepatitis B infection prior to initiating prolonged corticosteroid treatment. For patients 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. Therefore, hydrocortisone should be avoided in the presence of such infections unless necessary to control drug reactions. For patients on chronic hydrocortisone therapy who develop systemic fungal infections, withdrawal or dosage reduction 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 lead to clinical improvement.

Hypertension, Volume Overload, and Hypokalemia Hydrocortisone and cortisone can elevate blood pressure, cause salt and water retention, and increase 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 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 potential benefits against risks to the mother and fetus. Infants born to mothers who received substantial 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 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 should be used, and any dosage reduction should be gradual.

Psychiatric effects, ranging from euphoria to severe depression, may occur with corticosteroid use, and existing emotional instability may be exacerbated. 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 therapy should be closely monitored.

The risk of complications from glucocorticoid treatment is dose-dependent, necessitating careful consideration of the risk/benefit ratio for each patient regarding dosage and duration of therapy. In patients with suspected pheochromocytoma, the risk of pheochromocytoma crisis should be evaluated prior to corticosteroid administration.

Finally, tumor lysis syndrome (TLS) has been reported in patients with malignancies following systemic corticosteroid use. Patients at high risk for TLS should be closely monitored, particularly those with high tumor burden or sensitivity to cytotoxic agents.

Side Effects

Patients receiving corticosteroids, including hydrocortisone, may experience a range of adverse reactions, which can be categorized by seriousness and frequency.

Serious adverse reactions include immunosuppression, which significantly 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, reactivation of latent infections, and may mask some signs of infection. The incidence of infectious complications tends to rise with higher corticosteroid dosages. Additionally, psychic derangements may occur, manifesting as euphoria, insomnia, mood swings, personality changes, severe depression, or even psychotic manifestations. Existing emotional instability or psychotic tendencies may be exacerbated by corticosteroid treatment. A pheochromocytoma crisis, which can be fatal, has also been reported following systemic corticosteroid administration, necessitating caution in patients with suspected pheochromocytoma.

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

Gastrointestinal reactions may involve peptic ulcers with potential perforation and hemorrhage, pancreatitis, abdominal distention, and ulcerative esophagitis. Increases in liver enzymes such as alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase have been observed, although these changes are typically small, reversible upon discontinuation, and not associated with clinical syndromes.

Dermatologic reactions can include impaired wound healing, thin fragile skin, petechiae, ecchymoses, facial erythema, increased sweating, and suppression of reactions to skin tests. Neurological effects may consist of increased intracranial pressure with papilledema (pseudotumor cerebri), convulsions, vertigo, headache, and epidural lipomatosis.

Endocrine disturbances may lead to the development of a Cushingoid state, suppression of growth in children, secondary adrenocortical and pituitary unresponsiveness during stress, menstrual irregularities, decreased carbohydrate tolerance, 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 effects may result in a negative nitrogen balance due to protein catabolism, while blood and lymphatic system disorders may present as leukocytosis.

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

Drug Interactions

Phenobarbital, phenytoin, and rifampin are known to increase the clearance of corticosteroids. This interaction may necessitate dosage adjustments to achieve the desired therapeutic response.

Conversely, troleandomycin and ketoconazole can inhibit the metabolism of corticosteroids, resulting in decreased clearance. In such cases, careful dose titration may be required to prevent toxicity.

Corticosteroids may also influence the pharmacokinetics of chronic high-dose aspirin, potentially increasing its clearance. This interaction can lead to decreased salicylate serum levels or an increased risk of salicylate toxicity upon withdrawal of corticosteroids. Therefore, monitoring is advised when corticosteroids are used in conjunction with high-dose aspirin.

Aspirin should be administered with caution alongside corticosteroids in patients with hypoprothrombinemia due to the potential for significant interactions.

The interaction between corticosteroids and oral anticoagulants is variable, with some reports indicating both enhanced and diminished anticoagulant effects. 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

Pediatric patients with juvenile rheumatoid arthritis may require low-dose maintenance therapy with hydrocortisone in selected cases. The initial dosage of hydrocortisone tablets can range from 20 mg to 240 mg per day, depending on the specific disease entity being treated. Dosage requirements are variable and must be individualized based on the disease and the patient's response.

It is essential to carefully monitor the growth and development of infants and children undergoing prolonged corticosteroid therapy, as corticosteroids can suppress growth in this population. Additionally, infants born to mothers who received substantial doses of corticosteroids during pregnancy should be closely observed for signs of hypoadrenalism.

Geriatric Use

Elderly patients may not require specific dosage adjustments or safety considerations when using hydrocortisone, as the provided drug insert 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.

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 patients.

Given these considerations, healthcare providers should carefully evaluate the necessity of corticosteroid treatment in pregnant patients and those planning to conceive, ensuring that the potential risks are clearly communicated and managed.

Lactation

The use of hydrocortisone in lactating mothers necessitates a careful evaluation of the potential benefits of the medication 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 data regarding dosage adjustments, special monitoring, or safety considerations. Therefore, healthcare professionals should exercise caution when prescribing this medication to individuals with reduced kidney function, as the lack of information necessitates careful clinical judgment and monitoring.

Hepatic Impairment

Patients with hepatic impairment may experience an increased risk of hepatitis B virus reactivation when treated with immunosuppressive dosages of corticosteroids, including hydrocortisone. This reactivation can also occur 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 demonstrate evidence of hepatitis B infection, it is recommended to consult with healthcare professionals who specialize in managing hepatitis B. This consultation should focus on appropriate monitoring and the potential need for hepatitis B antiviral therapy.

Additionally, corticosteroids, including hydrocortisone, have the potential to 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 of hydrocortisone or a reduction in dosage is advised to mitigate risks associated with hepatic impairment.

Overdosage

In the absence of specific overdosage information, it is essential for healthcare professionals to remain vigilant and prepared for potential scenarios involving overdose.

Healthcare providers should be aware that the clinical presentation of an overdose may vary depending on the substance involved and the individual patient’s characteristics. Symptoms of overdose can range from mild to severe and may include altered mental status, cardiovascular instability, respiratory distress, and gastrointestinal disturbances.

In the event of suspected overdosage, immediate assessment of the patient’s condition is crucial. Recommended actions include:

1. Assessment: Conduct a thorough evaluation of the patient, including vital signs and level of consciousness.

2. Supportive Care: Initiate supportive measures as necessary, which may include airway management, oxygen supplementation, and intravenous fluids.

3. Decontamination: If the overdose is recent and the patient is alert, consider activated charcoal administration, provided there are no contraindications.

4. Specific Antidotes: If applicable, administer specific antidotes based on the substance involved in the overdose.

5. Monitoring: Continuous monitoring of the patient’s vital signs and clinical status is essential to detect any deterioration promptly.

Healthcare professionals should consult local poison control centers or toxicology experts for guidance on managing specific overdose cases. Documentation of the incident and any interventions performed is also critical for ongoing patient care and legal purposes.

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 information is available regarding other aspects of nonclinical toxicology or animal pharmacology and toxicology.

Postmarketing Experience

In postmarketing experience, tumor lysis syndrome (TLS) has been reported in patients with malignancies, including both hematological malignancies and solid tumors, following the use of systemic corticosteroids, either alone or in combination with other chemotherapeutic agents. It is noted that patients at high risk for TLS, such as those with tumors characterized by a high proliferative rate, significant tumor burden, and heightened sensitivity to cytotoxic agents, should be monitored closely. Appropriate precautions are recommended for these patients to mitigate potential risks associated with TLS.

Patient Counseling

Patients receiving immunosuppressant doses of corticosteroids should be informed about the importance of avoiding exposure to chicken pox or measles. Healthcare providers should emphasize that these infections can pose significant risks to individuals with compromised immune systems.

Additionally, patients should be advised that if they are exposed to either chicken pox or measles, it is crucial to seek medical advice promptly. This proactive approach can help in managing potential complications and ensuring appropriate care.

Storage and Handling

The product is supplied in accordance with the National Drug Code (NDC) specifications. It should be stored at a temperature range of 20° to 25°C (68° to 77°F), in compliance with USP Controlled Room Temperature guidelines. Proper storage conditions are essential to maintain the integrity and efficacy of the product.

Additional Clinical Information

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 to mitigate risks.

FDA Insert (PDF)

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

View full prescribing information (PDF)