Hydrocortisone

Description

Hydrocortisone is a white to practically white, odorless, crystalline powder that is very slightly soluble in water. Its chemical name is Pregn-4-ene-3,20-dione,11,17,21-trihydroxy-,(11β)-. Each disposable unit (60 mL) contains 100 mg of Hydrocortisone in an aqueous solution that includes carbomer 934P, polysorbate 80, purified water, sodium hydroxide, and methylparaben, with 0.18% serving 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 remission both clinically and proctologically. Clinical symptoms typically show improvement within 3 to 5 days; however, enhancement in the appearance of the mucosa, 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 preferably overnight, to maximize therapeutic effect. 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 box.

Contraindications

Use is contraindicated in patients with systemic fungal infections due to the potential for exacerbation of the condition. Additionally, the use of this product is contraindicated in individuals who have undergone ileocolostomy during the immediate or early post-operative period, as it may interfere with recovery and healing processes.

Warnings and Precautions

In the management of patients with severe ulcerative colitis, it is critical to avoid delaying necessary surgical intervention while awaiting a response to medical treatment, as this may pose significant risks. Care must be taken during the administration of enemas, as improper insertion of the enema tip can lead to damage of 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. It is important to note that corticosteroids can mask certain signs of infection, potentially leading to decreased resistance and difficulty in localizing infections. New infections may emerge during corticosteroid use, necessitating vigilant monitoring.

Prolonged corticosteroid therapy is associated with the development of posterior subcapsular cataracts, glaucoma, and an increased risk of secondary ocular infections due to fungi or viruses. Therefore, careful consideration of the duration and dosage of corticosteroid treatment is warranted.

Hydrocortisone Rectal Suspension, USP should be administered with caution in patients with conditions that may predispose them to complications, including impending perforation, abscess, or other pyogenic infections, as well as fresh intestinal anastomoses, obstruction, or extensive fistulas and sinus tracts. Caution is also advised in patients with active or latent peptic ulcers, diverticulitis, renal insufficiency, hypertension, osteoporosis, and myasthenia gravis.

The use of steroid therapy may complicate surgical outcomes by increasing the risk of infection. In cases where infection is suspected, appropriate antibiotic therapy should be initiated, often at higher than standard doses. Prolonged use of Hydrocortisone Rectal Suspension, USP may lead to drug-induced secondary adrenocortical insufficiency, which can persist for months after discontinuation of therapy. To mitigate this risk, a gradual reduction in dosage is recommended, and hormone therapy should be reinstated during periods of stress.

Patients with hypothyroidism or cirrhosis may experience an enhanced effect from corticosteroids, necessitating careful monitoring. Additionally, corticosteroids should be used cautiously in patients with ocular herpes simplex due to the risk of corneal perforation. The lowest effective dose of corticosteroids should be employed, and any dosage reductions should be made gradually.

Psychiatric effects, ranging from euphoria and mood swings to severe depression and psychotic manifestations, may occur with corticosteroid use. Existing emotional instability or psychotic tendencies may be exacerbated. Caution is also advised when using aspirin in conjunction with corticosteroids in patients with hypoprothrombinemia.

No specific laboratory tests are recommended for monitoring during the use of Hydrocortisone Rectal Suspension, USP; however, healthcare professionals should remain vigilant for potential complications associated with corticosteroid therapy.

Side Effects

Patients receiving Hydrocortisone Rectal Suspension, USP may experience a range of adverse reactions, which can be categorized by seriousness and frequency.

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

Fluid and electrolyte disturbances are notable, with occurrences of sodium retention, fluid retention, and congestive heart failure in susceptible patients. Other disturbances include potassium loss, hypokalemic alkalosis, and hypertension.

Musculoskeletal adverse reactions may 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 can be serious, including peptic ulcer with potential perforation and hemorrhage, pancreatitis, abdominal distention, and ulcerative esophagitis.

Dermatologic reactions may include impaired wound healing, thin fragile skin, petechiae and ecchymoses, facial erythema, increased sweating, and suppression of reactions to skin tests.

Neurological adverse reactions have been observed, such as convulsions, increased intracranial pressure with papilledema (pseudo-tumor cerebri), vertigo, and headache.

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

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

Metabolic effects may present as negative nitrogen balance due to protein catabolism.

Corticosteroids, including Hydrocortisone, may mask signs of infection, leading to decreased resistance and an inability to localize infections. Prolonged use can result in posterior subcapsular cataracts, glaucoma with potential optic nerve damage, and an increased risk of secondary ocular infections due to fungi or viruses.

Psychic derangements may occur, ranging from euphoria, insomnia, mood swings, and personality changes to severe depression and frank psychotic manifestations. Existing emotional instability or psychotic tendencies may be exacerbated by corticosteroid use.

Drug Interactions

There are currently no documented drug interactions associated with this medication. Additionally, there is no information available regarding interactions with laboratory tests. As such, no specific recommendations for dosage adjustments or monitoring are warranted at this time.

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.

Particular attention should be given to the growth and development of pediatric patients undergoing prolonged corticosteroid therapy, as these factors may be adversely affected. Regular monitoring is recommended to ensure appropriate management of any potential impacts on growth.

Geriatric Use

Elderly patients may exhibit increased sensitivity to the effects of corticosteroids, necessitating caution when administering hydrocortisone. This sensitivity can be attributed to age-related physiological changes, including potential reductions in kidney function.

Dosage adjustments may be required for geriatric patients, particularly those with renal insufficiency or other comorbidities. It is advisable to utilize the lowest effective dose of hydrocortisone in this population to minimize the risk of adverse effects.

Furthermore, close monitoring for side effects is recommended for elderly patients undergoing hydrocortisone therapy to ensure their safety and well-being.

Pregnancy

The use of corticosteroids during pregnancy, nursing, or in women of childbearing potential requires 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 have received substantial doses of corticosteroids during pregnancy should be closely monitored for signs of hypoadrenalism. Additionally, the administration of average and large doses of hydrocortisone or cortisone may lead to elevated blood pressure, salt and water retention, and increased potassium excretion. These adverse effects are less likely to occur with synthetic derivatives, except when administered in large doses.

Healthcare professionals should consider dietary salt restriction and potassium supplementation as necessary interventions for pregnant patients receiving corticosteroids. It is also important to note that all corticosteroids are associated with increased calcium excretion, which may have implications for maternal and fetal health.

Lactation

The use of these drugs in lactating mothers requires careful consideration of the potential benefits versus the risks to both the mother and the breastfed infant. It is essential to evaluate the possible hazards to the nursing mother and the infant when prescribing these medications.

Neonates 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 health and safety of the breastfed infant.

Renal Impairment

There is no specific information 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 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 significantly 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 medical evaluation is recommended. Healthcare professionals should assess the patient's vital signs and conduct a thorough clinical examination. Supportive care should be initiated as necessary, including airway management, oxygen supplementation, and intravenous fluids.

If the specific agent involved in the overdose is known, appropriate antidotes or specific treatments should be administered as indicated. Continuous monitoring of the patient’s condition is crucial, and healthcare providers should be prepared to manage complications that may arise during the course of treatment.

In all cases of suspected overdose, it is advisable to contact a poison control center or consult relevant clinical guidelines for further management recommendations.

Nonclinical Toxicology

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

Administration of average and large doses of hydrocortisone or cortisone may lead to elevated blood pressure, salt and water retention, and increased potassium excretion. These effects are less likely to occur with synthetic derivatives, except when administered in large doses. All corticosteroids are known to increase calcium excretion.

Prolonged therapy with Hydrocortisone Rectal Suspension, USP, may result in drug-induced secondary adrenocortical insufficiency. This risk can be mitigated through a gradual reduction in dosage. It is important to note that this relative insufficiency may persist for several months following the discontinuation of therapy; therefore, in the event of stress during this period, hormone therapy should be reinstated. Additionally, as mineralocorticoid secretion may be compromised, concurrent administration of salt and/or a mineralocorticoid is recommended. The effects of corticosteroids may be enhanced in patients with hypothyroidism and those with cirrhosis.

Postmarketing Experience

Rare cases of local pain or burning and rectal bleeding have been reported in association with the use of Hydrocortisone Rectal Suspension, USP. Additionally, instances of apparent exacerbations or sensitivity reactions have been noted 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

• Hypertension

Musculoskeletal

• Muscle weakness

• Steroid myopathy

• Loss of muscle mass

• Osteoporosis

• Vertebral compression fractures

• Aseptic necrosis of femoral and humeral heads

• Pathologic fracture of long bones

Gastrointestinal

• Peptic ulcer with possible perforation and hemorrhage

• Pancreatitis

• Abdominal distention

• Ulcerative esophagitis

Dermatologic

• Impaired wound healing

• Thin fragile skin

• Petechiae and ecchymoses

• Facial erythema

• Increased sweating

• Possible suppression of reactions to skin tests

Neurological

• Convulsions

• Increased intracranial pressure with papilledema (pseudo-tumor cerebri), usually after treatment

• Vertigo

• Headache

Endocrine

• Menstrual irregularities

• Development of Cushingoid state

• Suppression of growth in pediatric patients

• Secondary adrenocortical and pituitary unresponsiveness, particularly in times of stress, such as trauma, surgery, or illness

• Decreased carbohydrate tolerance

• Manifestations of latent diabetes

• Increased requirements for insulin or oral hypoglycemic agents in diabetics

Ophthalmic

• Posterior subcapsular cataracts

• Increased intraocular pressure

• Glaucoma

• Exophthalmos

Metabolic

• Negative nitrogen balance due to protein catabolism

To report suspected adverse reactions, individuals are encouraged to contact ANI Pharmaceuticals, Inc. at 1-855-204-1431 or the FDA at 1-800-FDA-1088 or visit www.fda.gov/medwatch.

Patient Counseling

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

Instructions for administering Hydrocortisone Rectal Suspension, USP, are provided in each box. Patients should be informed that lying on their left side during administration and for 30 minutes afterward will help the fluid distribute throughout the left colon. They should be encouraged to retain the enema for at least an hour, and preferably overnight. This may be easier if they use prior sedation and/or antidiarrheal medication, particularly in the early stages of therapy when the urge to evacuate may be strong.

For optimal results, patients should empty their bowels immediately before administering the enema.

When preparing the medication for administration, patients should shake the bottle well to ensure the suspension is homogeneous. They should remove the protective sheath from the applicator tip and hold the bottle at the neck to prevent any medication from discharging prematurely.

To assume the correct body position, patients are advised to lie on their left side with the left leg extended and the right leg flexed forward for balance. An alternative position is the “knee-chest” position.

During the administration of the retention enema, patients should gently insert the lubricated applicator tip into the rectum, pointing it slightly toward the navel. 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. Steady hand pressure will help discharge most of the solution. After administering, they should withdraw and discard the used unit. It is essential for patients to remain in position for at least 30 minutes to allow for thorough internal distribution of the medication and to retain the enema overnight if possible.

Storage and Handling

The product is supplied in various package configurations, with specific NDC numbers available upon request. It should be stored at a controlled room temperature of 20° to 25°C (68° to 77°F). Care should be taken to ensure that the storage environment maintains these temperature conditions to preserve product integrity.

Additional Clinical Information

No further data are available.

FDA Insert (PDF)

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

View full prescribing information (PDF)