Hydrocortisone

Description

Hydrocortisone is a white to practically white, odorless, crystalline powder that is very slightly soluble in water. The chemical name is Pregn-4-ene-3,20-dione,11,17,21-tri-hydroxy,(11β)-, with a molecular formula of C₂₁H₃₀O₅ and a molecular weight of 362.47. Hydrocortisone Rectal Suspension, USP is formulated as a convenient disposable single-dose enema, designed to facilitate self-administration. Each 60 mL unit contains 100 mg of hydrocortisone in an aqueous solution, which includes carbomer 934P, polysorbate 80, purified water, sodium hydroxide, and methylparaben (0.18% as a preservative).

Uses and Indications

Hydrocortisone Rectal Suspension, USP is indicated as adjunctive therapy in the treatment of ulcerative colitis, particularly in distal forms such as ulcerative proctitis, ulcerative proctosigmoiditis, and left-sided ulcerative colitis. This formulation has also demonstrated efficacy in certain cases involving the transverse and ascending colons.

There are no teratogenic or nonteratogenic effects associated with the use of this drug.

Dosage and Administration

The usual course of therapy with Hydrocortisone Rectal Suspension, USP is one administration nightly for a duration of 21 days, or until the patient achieves clinical and proctological remission. Clinical symptoms typically show improvement within 3 to 5 days; however, enhancement in mucosal appearance, as assessed by sigmoidoscopic examination, may occur later than the clinical improvement.

In challenging cases, treatment may be extended to 2 or 3 months. If the therapy needs to continue beyond 21 days, it is essential to taper the dosage gradually by reducing the administration frequency to every other night for a period of 2 to 3 weeks.

For optimal administration, patients are advised to lie on their left side during the administration of Hydrocortisone Rectal Suspension, USP and to maintain this position for at least 30 minutes post-administration to ensure adequate distribution of the fluid throughout the left colon. Patients should be instructed to retain the enema for a minimum of one hour, and ideally overnight. This retention may be aided by the use of prior sedation and/or antidiarrheal medication, particularly in the initial stages of therapy when the urge to evacuate may be pronounced.

Detailed patient instructions for the administration of Hydrocortisone Rectal Suspension, USP are included in each package.

Contraindications

Use of this product is contraindicated in patients with systemic fungal infections due to the potential for exacerbation of the condition. Additionally, it should not be administered to individuals who have undergone ileocolostomy during the immediate or early post-operative period, as this may pose significant health risks.

Warnings and Precautions

In patients with severe ulcerative colitis, it is critical to avoid delaying necessary surgical intervention while awaiting the response to medical treatment, as this may pose significant risks.

Care must be taken during the administration of enemas, as improper or careless insertion of the enema tip can lead to damage to the rectal wall.

For patients undergoing corticosteroid therapy, it is essential 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 certain signs of infection, and new infections may emerge during their use. Consequently, there may be a decreased resistance to infections and an impaired ability to localize infections in patients receiving corticosteroids.

Prolonged corticosteroid use is associated with the development of posterior subcapsular cataracts and glaucoma, which may result in optic nerve damage. Additionally, long-term corticosteroid therapy can facilitate the establishment of secondary ocular infections caused by fungi or viruses.

Vaccination against smallpox is contraindicated in patients receiving corticosteroid therapy. Furthermore, other immunization procedures should be approached with caution in patients on corticosteroids, particularly those on high doses, due to the potential for neurological complications and an inadequate antibody response.

Patients on immunosuppressive medications, including corticosteroids, are at an increased risk of infections compared to healthy individuals. In particular, chickenpox and measles can present with more severe or even fatal outcomes in non-immune pediatric patients or adults on corticosteroids. Therefore, it is imperative to take special precautions to avoid exposure to these infections in such individuals.

In the event of exposure to chickenpox, prophylactic treatment with varicella zoster immune globulin (VZIG) may be warranted. Similarly, exposure to measles may require prophylaxis with pooled intramuscular immunoglobulin (IG).

For patients with latent tuberculosis or those exhibiting tuberculin reactivity who require corticosteroid treatment, close monitoring is essential, as there is a risk of disease reactivation. During extended corticosteroid therapy, these patients should be placed on chemoprophylaxis to mitigate this risk.

Side Effects

Adverse reactions associated with Hydrocortisone Rectal Suspension, USP, can be categorized based on their seriousness and frequency of occurrence.

Local reactions, although rare, may include local pain or burning sensations and rectal bleeding. Additionally, some patients may experience apparent exacerbations or sensitivity reactions.

Fluid and electrolyte disturbances have been noted, including sodium retention, fluid retention, and congestive heart failure in susceptible patients. Other disturbances may involve potassium loss, hypokalemic alkalosis, and hypertension.

Musculoskeletal adverse reactions can manifest as muscle weakness, steroid myopathy, loss of muscle mass, osteoporosis, vertebral compression fractures, aseptic necrosis of the femoral and humeral heads, and pathologic fractures of long bones.

Gastrointestinal effects may include peptic ulcers with potential perforation and hemorrhage, pancreatitis, abdominal distention, and ulcerative esophagitis.

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

Neurological adverse reactions reported include convulsions, increased intracranial pressure with papilledema (pseudo-tumor cerebri), vertigo, and headache.

Endocrine effects may involve menstrual irregularities, the development of a Cushingoid state, suppression of growth in pediatric patients, secondary adrenocortical and pituitary unresponsiveness—particularly during times of stress such as trauma, surgery, or illness—decreased carbohydrate tolerance, manifestations of latent diabetes, and increased requirements for insulin or oral hypoglycemic agents in diabetic patients.

Ophthalmic adverse reactions can include posterior subcapsular cataracts, increased intraocular pressure, glaucoma, and exophthalmos.

Metabolic effects may lead to a negative nitrogen balance due to protein catabolism.

Corticosteroids, including Hydrocortisone Rectal Suspension, USP, may mask signs of infection, potentially leading to decreased resistance and difficulty localizing infections. Prolonged use can result in posterior subcapsular cataracts, glaucoma with possible optic nerve damage, and an increased risk of secondary ocular infections due to fungi or viruses.

Care should be taken to avoid damage to the rectal wall from improper insertion of the enema tip. In patients undergoing corticosteroid therapy who experience unusual stress, an increased dosage of rapidly acting corticosteroids is recommended before, during, and after the stressful event.

Drug-induced secondary adrenocortical insufficiency may occur with prolonged therapy, which can be minimized by gradual dosage reduction. This relative insufficiency may persist for months after discontinuation, necessitating the reinstitution of hormone therapy during any stress occurring in that period.

Corticosteroids may have an enhanced effect in patients with hypothyroidism or cirrhosis and should be used cautiously in those with ocular herpes simplex due to the risk of corneal perforation. Additionally, psychic derangements ranging from euphoria, insomnia, mood swings, and personality changes to severe depression and psychotic manifestations may occur. Existing emotional instability or psychotic tendencies may be exacerbated by corticosteroid use.

Drug Interactions

Aspirin should be administered with caution when used concurrently with corticosteroids in patients with hypoprothrombinemia due to the potential for increased bleeding risk.

Corticosteroids may exhibit an enhanced pharmacological effect in patients with hypothyroidism and those with cirrhosis, necessitating careful monitoring of therapeutic outcomes and potential dosage adjustments.

In terms of drug and laboratory test interactions, corticosteroids have the potential to mask signs of infection, which may lead to the emergence of new infections during treatment. Additionally, corticosteroids can suppress reactions to skin tests, which may affect the interpretation of allergy or infection assessments. Monitoring for signs of infection and considering alternative diagnostic approaches may be warranted in patients receiving corticosteroid therapy.

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

Safety and effectiveness in pediatric patients have not been established. Therefore, caution is advised when considering the use of this medication in children and adolescents.

Additionally, the growth and development of pediatric patients undergoing prolonged corticosteroid therapy should be carefully monitored to assess any potential impacts on their overall health and development.

Geriatric Use

Elderly patients may exhibit increased sensitivity to the side effects of corticosteroids, necessitating careful consideration when prescribing Hydrocortisone Rectal Suspension, USP. Caution is advised due to the potential for reduced kidney function and other age-related health issues that may affect drug metabolism and clearance.

Dosage adjustments may be necessary for geriatric patients, particularly for those with renal insufficiency or other comorbidities that could influence the pharmacokinetics of the medication. It is essential to evaluate each patient's individual health status and adjust the dosage accordingly to minimize the risk of adverse effects.

Close monitoring is recommended for elderly patients receiving corticosteroid therapy. This vigilance is crucial to effectively manage potential adverse effects and complications that may arise during treatment. Regular assessments can help ensure the safety and efficacy of the therapy in this population.

Pregnancy

The use of corticosteroids during pregnancy, nursing, or in women of childbearing potential requires careful consideration of the potential benefits against the possible risks to the mother and the developing embryo or fetus, as adequate human reproduction studies have not been conducted.

Neonates born to mothers who have received substantial doses of corticosteroids during pregnancy should be closely monitored for signs of hypoadrenalism. This precaution is essential to ensure timely identification and management of any potential complications arising from in utero exposure to corticosteroids.

Lactation

Lactating mothers should consider the potential benefits of the drug against the possible hazards to themselves and their breastfed infants. The use of these drugs during lactation requires careful evaluation.

Neonates born to mothers who have received substantial doses of corticosteroids during pregnancy should be closely monitored for signs of hypoadrenalism.

Renal Impairment

There is no specific information available regarding dosage adjustments, special monitoring, or safety considerations for patients with renal impairment. Healthcare professionals should exercise caution when prescribing to patients with reduced kidney function, as the absence of detailed guidance necessitates careful clinical judgment. Regular monitoring of renal function may be advisable in this patient population.

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

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

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

In the event of an overdose, the following management procedures are recommended:

1. Assessment: Conduct a thorough assessment of the patient's clinical status, including vital signs and level of consciousness.

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

3. Consultation: Engage with a poison control center or toxicology specialist for guidance on specific interventions and antidotes, if applicable.

4. Documentation: Document all findings, interventions, and the patient's response to treatment meticulously.

Healthcare professionals should remain vigilant and prepared to implement these measures in the event of an overdose, despite the lack of specific information regarding the substance in question.

Nonclinical Toxicology

The use of corticosteroids during pregnancy, nursing, or in women of child-bearing potential necessitates careful consideration of the potential benefits against the risks to the mother and the developing embryo or fetus, as adequate human reproduction studies have not been conducted. Neonates born to mothers who received substantial doses of corticosteroids during pregnancy should be closely monitored for signs of hypoadrenalism.

Corticosteroids, including hydrocortisone and cortisone, can lead to non-teratogenic effects such as elevated blood pressure, salt and water retention, and increased potassium excretion, particularly at average and high doses. These effects are generally less pronounced with synthetic derivatives unless administered in large doses. Additionally, all corticosteroids are known to increase calcium excretion.

Prolonged therapy with Hydrocortisone Rectal Suspension, USP, may result in drug-induced secondary adrenocortical insufficiency, which can be mitigated through a gradual reduction in dosage. This relative insufficiency may persist for months following the cessation of therapy; therefore, in instances of stress during this period, it is advisable to reinstate hormone therapy. Due to the potential impairment of mineralocorticoid secretion, concurrent administration of salt and/or a mineralocorticoid is recommended. Furthermore, corticosteroids may exhibit enhanced effects in patients with hypothyroidism and those with cirrhosis.

No specific information regarding animal pharmacology and toxicology is available.

Postmarketing Experience

Reports of local pain or burning, as well as rectal bleeding, attributed to Hydrocortisone Rectal Suspension, USP, have been documented rarely. Additionally, instances of apparent exacerbations or sensitivity reactions have also been reported infrequently.

When corticosteroids are administered rectally, the following adverse reactions should be considered:

Fluid and Electrolyte Disturbances: Sodium retention, fluid retention, congestive heart failure in susceptible patients, potassium loss, hypokalemic alkalosis, and hypertension.

Musculoskeletal Effects: Muscle weakness, steroid myopathy, loss of muscle mass, osteoporosis, vertebral compression fractures, aseptic necrosis of femoral and humeral heads, and pathologic fractures of long bones.

Gastrointestinal Reactions: Peptic ulcer with potential perforation and hemorrhage, pancreatitis, abdominal distention, and ulcerative esophagitis.

Dermatologic Effects: Impaired wound healing, thin fragile skin, petechiae and ecchymoses, facial erythema, increased sweating, and possible suppression of reactions to skin tests.

Neurological Effects: Convulsions, increased intracranial pressure with papilledema (pseudo-tumor cerebri) typically following treatment, vertigo, and headache.

Endocrine Effects: Menstrual irregularities, development of a Cushingoid state, suppression of growth in pediatric patients, secondary adrenocortical and pituitary unresponsiveness, particularly during periods of stress such as trauma, surgery, or illness, decreased carbohydrate tolerance, manifestations of latent diabetes, and increased requirements for insulin or oral hypoglycemic agents in diabetic patients.

Ophthalmic Effects: Posterior subcapsular cataracts, increased intraocular pressure, glaucoma, and exophthalmos.

Metabolic Effects: Negative nitrogen balance due to protein catabolism.

Patient Counseling

Patients should be advised to avoid exposure to chicken pox or measles while on immunosuppressant doses of corticosteroids. In the event of exposure to either chicken pox or measles, patients should seek medical advice without delay.

Instructions for administering Hydrocortisone Rectal Suspension, USP are enclosed in each box and should be reviewed with the patient. It is recommended that the patient lie on their left side during administration and for at least 30 minutes thereafter to ensure proper distribution of the fluid throughout the left colon.

Patients should be encouraged to retain the enema for a minimum of one hour, and preferably overnight. This may be facilitated by the use of prior sedation and/or antidiarrheal medication, particularly early in therapy when the urge to evacuate may be more pronounced.

For optimal results, patients should empty their bowels immediately before administering the enema. They should shake the bottle well to ensure that the suspension is homogeneous prior to administration.

Patients should remove the protective sheath from the applicator tip and hold the bottle at the neck to prevent discharging any medication inadvertently. The best position for administration is lying on the left side with the left leg extended and the right leg flexed forward for balance, or alternatively, in the "knee-chest" position.

Patients should gently insert the lubricated applicator tip into the rectum, directing it slightly toward the navel (umbilicus). They should grasp the bottle firmly, tilt it slightly so that the nozzle is aimed toward the back, and squeeze slowly to instill the medication.

After administration, patients should remain in position for at least 30 minutes to allow for thorough internal distribution of the medication. Finally, they should withdraw and discard the used unit after administering the enema.

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 ranging from 20° to 25°C (68° to 77°F) to ensure optimal stability and efficacy. Proper handling practices should be observed to maintain the integrity of the product during storage.

Additional Clinical Information

The usual course of therapy for Hydrocortisone Rectal Suspension, USP involves administration of one dose nightly for 21 days, or until the patient achieves clinical and proctological remission. If treatment needs to extend beyond 21 days, it is recommended that the suspension be gradually discontinued by reducing the frequency to every other night for 2 to 3 weeks.

Clinicians should counsel patients on the importance of avoiding exposure to chicken pox or measles, particularly for those receiving immunosuppressant doses of corticosteroids. Patients should be advised to seek medical advice promptly if they are exposed to these infections.

FDA Insert (PDF)

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

View full prescribing information (PDF)