Cortenema

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 at a concentration of 0.18% as a preservative.

Uses and Indications

CORTENEMA® 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 drug has also demonstrated efficacy in certain cases involving the transverse and ascending colons.

Dosage and Administration

The usual course of therapy with CORTENEMA® is one enema administered 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 through sigmoidoscopic examination, may occur later than the clinical improvements.

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

For optimal administration, patients should be instructed to lie on their left side during the enema administration and to maintain this position for at least 30 minutes post-administration to ensure adequate distribution of the fluid throughout the left colon. Patients are encouraged to retain the enema for a minimum of one hour, and ideally, throughout the night. This retention may be supported by the use of prior sedation and/or antidiarrheal medications, particularly in the early stages of therapy when the urge to evacuate may be pronounced. Detailed patient instructions for the administration of CORTENEMA® are included in each box.

Contraindications

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

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 CORTENEMA® hydrocortisone retention enema, as improper insertion of the enema tip can lead to damage to the rectal wall.

Patients undergoing corticosteroid therapy may require an increased dosage of rapidly acting corticosteroids in situations of unusual stress, both before and during the stressful event, as well as after its resolution. It is important to note that corticosteroids can mask 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 and glaucoma, which may result in optic nerve damage. Additionally, there is an increased risk of secondary ocular infections due to fungi or viruses.

CORTENEMA® 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 warranted in patients with active or latent peptic ulcers, diverticulitis, renal insufficiency, hypertension, osteoporosis, and myasthenia gravis.

The use of corticosteroids may impair surgical prognosis by increasing the risk of infection. In cases where infection is suspected, appropriate antibiotic therapy should be initiated, typically at higher than standard doses. Prolonged use of CORTENEMA® may lead to drug-induced secondary adrenocortical insufficiency, which can persist for months after therapy cessation. To mitigate this risk, a gradual reduction in dosage is recommended, and hormone therapy should be reinstated during periods of stress.

Corticosteroids may exert an enhanced effect in patients with hypothyroidism or cirrhosis, and caution is advised when prescribing corticosteroids to patients with ocular herpes simplex due to the risk of corneal perforation. The lowest effective dose of corticosteroids should be utilized, and any dosage reductions should be implemented gradually.

Psychiatric effects, including euphoria, insomnia, mood swings, personality changes, severe depression, and even psychotic manifestations, may occur with corticosteroid use. Existing emotional instability or psychotic tendencies may be exacerbated. Additionally, caution is advised when using aspirin in conjunction with corticosteroids in patients with hypoprothrombinemia.

No specific laboratory tests are recommended for the safe use of CORTENEMA®, but healthcare professionals should remain vigilant for potential complications associated with corticosteroid therapy.

Side Effects

Adverse reactions associated with CORTENEMA® have been observed in clinical trials and postmarketing experiences, categorized by seriousness and frequency.

Serious adverse reactions include neurological effects such as convulsions and increased intracranial pressure, which may present as papilledema (pseudo-tumor cerebri), typically occurring after treatment. Additionally, patients may experience gastrointestinal complications, including peptic ulcer with potential perforation and hemorrhage, as well as pancreatitis. Endocrine disturbances are also notable, with manifestations such as menstrual irregularities, development of a Cushingoid state, and suppression of growth in pediatric patients. Furthermore, prolonged corticosteroid use may lead to posterior subcapsular cataracts, glaucoma, and increased intraocular pressure, which can result in optic nerve damage and secondary ocular infections.

Common adverse reactions reported include local reactions such as pain or burning and rectal bleeding, which have been noted rarely. Patients may also experience fluid and electrolyte disturbances, including sodium and fluid retention, hypokalemic alkalosis, and hypertension. Musculoskeletal issues such as muscle weakness, steroid myopathy, and osteoporosis, along with the risk of vertebral compression fractures and pathologic fractures of long bones, have been documented. Dermatologic reactions may manifest as impaired wound healing, thin fragile skin, and increased sweating, while neurological symptoms can include vertigo and headache.

Metabolic effects, such as negative nitrogen balance due to protein catabolism, have also been reported. Additionally, psychiatric effects may occur, ranging from euphoria and mood swings to severe depression and psychotic manifestations, particularly in patients with pre-existing emotional instability.

It is important to note that in patients with severe ulcerative colitis, delaying necessary surgery while awaiting a response to medical treatment poses significant risks. Careful administration is crucial, as improper insertion of the enema tip can damage the rectal wall. In patients undergoing corticosteroid therapy, particularly during periods of unusual stress, an increased dosage of rapidly acting corticosteroids may be required. Corticosteroids can mask signs of infection, potentially leading to decreased resistance and the emergence of new infections.

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 Cortenema (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 identify any potential adverse effects.

Geriatric Use

CORTENEMA® hydrocortisone retention enema should be administered with caution in elderly patients, particularly those aged 65 and older, as they may present with conditions such as renal insufficiency, hypertension, osteoporosis, and myasthenia gravis. It is recommended that the lowest effective dose of corticosteroid be utilized to manage the conditions being treated in this population. Should a dosage reduction be warranted, it should be implemented gradually to minimize potential adverse effects.

Elderly patients may exhibit increased sensitivity to the side effects associated with corticosteroid therapy. Additionally, there is a risk of drug-induced secondary adrenocortical insufficiency with prolonged use of CORTENEMA®, which is particularly concerning for geriatric patients who may be more susceptible to complications arising from this condition.

Due to the potential for prolonged effects of corticosteroids following the cessation of therapy, close monitoring of elderly patients is essential, especially during periods of stress. This vigilance is crucial to ensure patient safety and to mitigate any adverse outcomes associated with corticosteroid treatment.

Pregnancy

The use of corticosteroids during pregnancy, nursing, or in women of childbearing potential requires careful consideration of the potential benefits versus the risks to both 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 for pregnant patients receiving corticosteroids. It is also important to note that all corticosteroids can increase 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 critical to ensure the health and safety of the breastfed infant.

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.

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

There is currently no specific information available regarding overdosage for this medication. In the absence of documented overdosage data, healthcare professionals are advised to exercise caution and monitor patients closely for any unusual symptoms or adverse effects that may arise following administration.

In the event of suspected overdosage, it is recommended that healthcare providers initiate supportive care and symptomatic treatment as necessary. Continuous monitoring of vital signs and clinical status is essential to ensure patient safety.

Healthcare professionals should also consider consulting a poison control center or relevant toxicology resources for guidance on management strategies tailored to the specific circumstances of the overdosage event.

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 are lacking. 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 generally less pronounced with synthetic derivatives, except when administered in high doses. Dietary salt restriction and potassium supplementation may be required, as all corticosteroids are known to increase calcium excretion.

Prolonged therapy with CORTENEMA® may result in drug-induced secondary adrenocortical insufficiency, which can be mitigated by a gradual tapering of the dosage. This relative insufficiency may persist for several months following the cessation of therapy; therefore, in the event of stress during this period, it is advisable to reinstate hormone therapy. Additionally, due to the potential impairment of mineralocorticoid secretion, concurrent administration of salt and/or a mineralocorticoid may be necessary.

No specific details regarding animal pharmacology and toxicology are available.

Postmarketing Experience

Rare cases of local pain or burning, as well as rectal bleeding, have been reported in association with CORTENEMA®. Additionally, instances of apparent exacerbations or sensitivity reactions have been noted infrequently.

Healthcare professionals should be aware of the following adverse reactions that may occur with corticosteroids administered rectally:

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 during 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, healthcare professionals 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

Healthcare providers should advise patients that optimal results from the enema are achieved when the bowel is emptied immediately prior to administration. It is important for patients to shake the bottle well to ensure that the suspension is homogeneous before use.

Patients should be instructed to remove the protective sheath from the applicator tip and to hold the bottle at the neck to prevent any discharge of the medication during preparation. For administration, the best position is lying on the left side with the left leg extended and the right leg flexed forward for balance. Alternatively, patients may use the “knee-chest” position if preferred.

When inserting the lubricated applicator tip into the rectum, patients should be guided to point 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 then squeeze slowly to instill the medication. Steady hand pressure will help discharge most of the solution. After administering the enema, patients should withdraw the applicator and discard the used unit.

It is crucial to inform patients to remain in the chosen position for at least 30 minutes to allow for thorough distribution of the medication internally. If possible, they should retain the enema throughout the night for maximum effectiveness.

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 Cortenema as submitted by ANI Pharmaceuticals, Inc.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)