Eohilia

Description

EOHILIA (budesonide oral suspension) is formulated with budesonide, a synthetic corticosteroid. Budesonide is chemically designated as (RS)-11β, 16α, 17,21-tetrahydroxypregna-1,4-diene-3,20-dione cyclic 16,17-acetal with butyraldehyde, existing as a mixture of two epimers (22 R and 22 S). The empirical formula for budesonide is C25H34O6, with a molecular weight of 430.53.

The active ingredient, budesonide, appears as a white or almost-white crystalline powder, which is freely soluble in chloroform, sparingly soluble in alcohol, and practically insoluble in water and heptane. EOHILIA itself is presented as a white to yellow, thixotropic, viscous suspension. Each 10 mL dose of EOHILIA contains 2 mg of budesonide.

The oral suspension includes several inactive ingredients: acesulfame potassium, ascorbic acid, Avicel® RC-591, cherry flavor, citric acid, dextrose, disodium ethylenediaminetetraacetic acid (EDTA), glycerin, Magnasweet® 110, maltodextrin, polysorbate 80, potassium sorbate, sodium ascorbate, sodium benzoate, sodium citrate, and purified water. All excipients are free from ingredients derived from gluten-containing grains (wheat, barley, or rye).

Uses and Indications

EOHILIA is a corticosteroid indicated for the treatment of eosinophilic esophagitis (EoE) in adult and pediatric patients aged 11 years and older. The recommended duration of treatment is 12 weeks.

Limitations of use: EOHILIA has not been demonstrated to be safe and effective for the treatment of EoE beyond 12 weeks. There are no reported teratogenic or nonteratogenic effects associated with EOHILIA.

Dosage and Administration

The recommended dosage for the medication is 2 mg administered orally twice daily for a duration of 12 weeks. Healthcare professionals should ensure that the medication is taken consistently at the same times each day to maintain optimal therapeutic levels. It is important to monitor the patient’s response to therapy throughout the treatment period.

Contraindications

Use of this product is contraindicated in patients with a known hypersensitivity to budesonide. Due to the potential for severe allergic reactions, administration in such cases should be avoided.

Warnings and Precautions

Hypercorticism and adrenal axis suppression may occur with treatment. Healthcare professionals should monitor patients for signs and symptoms indicative of these conditions and consider dosage reduction as necessary.

Immunosuppression is a significant concern, as patients may experience an increased risk of infections, including viral, bacterial, fungal, protozoan, and helminthic infections. Notably, there is a potential risk for severe infections such as varicella and measles. It is essential to monitor patients for any new or worsening localized or systemic infections, including oropharyngeal and esophageal candidiasis. In cases of infection, drug discontinuation should be considered. The use of this medication is contraindicated in patients with active fungal infections, Strongyloides infestation, cerebral malaria, and ocular herpes simplex. Additionally, screening for hepatitis B infection is recommended prior to treatment initiation.

Erosive esophagitis is another potential adverse effect. Patients and caregivers should be advised to report any new or worsening signs or symptoms associated with erosive esophagitis, and endoscopic evaluation should be considered when appropriate.

In pediatric patients, the use of corticosteroids may lead to a reduction in growth velocity. Therefore, it is crucial to monitor growth during the course of treatment.

For patients transitioning from other systemic corticosteroids, it is important to taper the dosage slowly to mitigate the risk of steroid withdrawal symptoms. Healthcare providers should remain vigilant for withdrawal symptoms and the unmasking of allergies, such as rhinitis and eczema.

Patients with concomitant conditions, such as hypertension or diabetes mellitus, should be closely monitored, as corticosteroids may exacerbate these conditions.

Kaposi’s sarcoma has been reported in patients receiving corticosteroid therapy, particularly those being treated for chronic conditions. This potential risk should be communicated to patients.

In summary, healthcare professionals must remain attentive to the aforementioned warnings and precautions, ensuring appropriate monitoring and management strategies are in place to safeguard patient health during treatment.

Side Effects

Common adverse reactions observed in clinical trials include respiratory tract infections, which occurred in 13% of patients and encompass conditions such as acute sinusitis, sinusitis, nasopharyngitis, and viral upper respiratory infections. Gastrointestinal mucosal candidiasis was reported in 8% of patients, including esophageal, oropharyngeal, and oral candidiasis. Headaches, including migraines, were noted in 5% of participants, while gastroenteritis and throat irritation were reported in 3% of patients each. Adrenal suppression and erosive esophagitis were each observed in 2% of subjects, with erosive esophagitis specifically occurring in 4 out of 213 subjects treated with EOHILIA in Study 1, all of whom had no erosions at baseline. Notably, all but one of these subjects were receiving concomitant therapy with a proton pump inhibitor (PPI). No cases of erosive esophagitis were reported in Study 2.

Less common adverse reactions include cardiac disorders such as palpitations, gastrointestinal disorders including dry mouth and dyspepsia, and general disorders like fatigue and feelings of abnormality. Infections and infestations such as fungal skin infections, pneumonia, and sepsis were also reported. Investigations revealed increased transaminases and hyperkalemia, while metabolic disorders included dyslipidemia. Musculoskeletal issues such as arthralgia and muscle spasms, nervous system disorders like dysgeusia and tremor, and psychiatric disorders including depression and irritability were also noted. Respiratory disorders such as nasal congestion and skin conditions like hirsutism and dermatitis acneiform were observed, along with vascular disorders including hypertension.

Postmarketing experience has revealed hypersensitivity reactions, including anaphylaxis, and nervous system disorders such as benign intracranial hypertension. Additionally, psychiatric disorders characterized by mood swings have been reported.

It is important to monitor for hypercorticism and adrenal axis suppression, which may occur with treatment, and to consider dosage reduction if signs and symptoms arise. Patients are at an increased risk of infections, including potentially fatal varicella and measles, necessitating careful monitoring for new or worsening infections. The use of corticosteroids may also affect growth velocity in pediatric patients, warranting regular growth assessments during treatment. Symptoms of steroid withdrawal should be monitored in patients transitioning from other systemic corticosteroids, and patients with pre-existing conditions that may be exacerbated by corticosteroids should be closely observed. Lastly, Kaposi’s sarcoma has been reported in patients receiving corticosteroid therapy, particularly for chronic conditions.

Drug Interactions

Concomitant use of CYP3A4 inhibitors, such as ketoconazole and grapefruit juice, may lead to increased systemic concentrations of budesonide. It is advisable to avoid the use of these inhibitors alongside budesonide to prevent potential adverse effects associated with elevated drug levels. Monitoring for signs of increased systemic effects is recommended if avoidance is not possible.

Packaging & NDC

The table below lists all NDC Code configurations of Eohilia (budesonide), the U.S. brand-name prescription product. Columns show Packaging, Formulation Type, and Active Ingredient Strength.

Pediatric Use

The safety and effectiveness of EOHILIA for the treatment of eosinophilic esophagitis (EoE) have been established in pediatric patients aged 11 years and older, supported by adequate and well-controlled studies in both adults and this age group (Studies 1 and 2). Pharmacokinetic data are available for pediatric subjects aged 11 to 17 years. In these studies, the safety profile of EOHILIA in pediatric patients aged 11 to 17 years was found to be similar to that observed in adults.

It is important to note that the safety and effectiveness of EOHILIA have not been established in pediatric patients younger than 11 years of age. Additionally, the use of corticosteroids, which may be part of the treatment regimen, can lead to a reduction in growth velocity in pediatric patients. Therefore, monitoring the growth of pediatric patients receiving EOHILIA is recommended. The recommended duration of treatment with EOHILIA is 12 weeks.

Geriatric Use

Clinical studies of EOHILIA did not include a sufficient number of subjects aged 65 years and older to determine whether this population responds differently from younger adult subjects. Therefore, healthcare providers should exercise caution when prescribing EOHILIA to elderly patients.

In general, EOHILIA should be used with caution in geriatric patients due to the potential for decreased hepatic function, which may affect drug metabolism and clearance. It is advisable to monitor these patients closely for any adverse effects and to consider dose adjustments as necessary based on individual patient assessments.

Pregnancy

The available data from published case series, epidemiological studies, and reviews indicate that oral budesonide use in pregnant women has not been associated with an increased risk of major birth defects, miscarriage, or other adverse maternal outcomes. However, infants exposed to in-utero corticosteroids, including EOHILIA, may be at risk for hypoadrenalism.

Animal reproduction studies have demonstrated that subcutaneous administration of budesonide during organogenesis in pregnant rats and rabbits resulted in increased fetal loss, decreased pup weights, and skeletal abnormalities. Maternal toxicity was also observed in both species at these dose levels. Therefore, based on animal data, healthcare professionals should advise pregnant women of the potential risks to the fetus.

The background risk of major birth defects and miscarriage in the general population is unknown; however, it is estimated that the background risk of major birth defects and miscarriage in clinically recognized pregnancies is approximately 2% to 4% and 15% to 20%, respectively.

Hypoadrenalism may occur in infants born to mothers receiving corticosteroids during pregnancy. These infants should be carefully monitored for signs of hypoadrenalism, which may include poor feeding, irritability, weakness, and vomiting, and managed accordingly.

Budesonide has been shown to be teratogenic and embryolethal in animal studies. In an embryo-fetal development study involving pregnant rats dosed subcutaneously with budesonide during the organogenesis period, there were notable effects on fetal development and survival at doses up to approximately 500 mcg/kg/day. Similarly, in pregnant rabbits, there was an increase in maternal abortion and adverse effects on fetal development and litter weights at doses up to approximately 25 mcg/kg/day. Maternal toxicity, including reduced body weight gain, was observed at subcutaneous doses of 5 mcg/kg in rabbits and 500 mcg/kg in rats.

In a peri- and post-natal development study, budesonide did not affect delivery; however, it did impact the growth and development of offspring, resulting in reduced survival and decreased mean body weights at birth and during lactation at exposures as low as 0.05 times the maximum recommended human dose (MRHD).

Lactation

Lactation studies have not been conducted with oral budesonide, including EOHILIA, and no information is available on the effects of the drug on the breastfed infant or on milk production. One published study reported that budesonide is present in human milk following maternal inhalation, with infant doses approximately 0.3% to 1% of the maternal weight-adjusted dosage and a milk/plasma ratio ranging between 0.4 and 0.5.

Budesonide plasma concentrations were not detected, and no adverse events were noted in breastfed infants following maternal use of inhaled budesonide. However, the recommended daily dose of EOHILIA (4 mg daily) is higher compared to inhaled budesonide (up to 800 mcg daily) used in the aforementioned study. Assuming the coefficient of extrapolation between inhaled and oral doses is constant across all dose levels, at therapeutic doses of EOHILIA, budesonide exposure to the nursing child may be up to 2.5 times higher than that from budesonide inhalation.

The developmental and health benefits of breastfeeding should be considered alongside the mother’s clinical need for EOHILIA and any potential adverse effects on the breastfed infant from EOHILIA or from the underlying maternal condition.

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. Regular monitoring of renal function may be advisable in these patients to ensure safety and efficacy.

Hepatic Impairment

Patients with moderate to severe hepatic impairment (Child-Pugh Class B or Class C, respectively) may experience an increased risk of hypercorticism and adrenal axis suppression due to heightened systemic exposure to budesonide. Therefore, the use of budesonide is not recommended in patients with severe hepatic impairment (Child-Pugh Class C).

For patients with mild or moderate hepatic impairment (Child-Pugh Class A or Class B), the recommended dosage remains the same as that for patients with normal hepatic function. However, in patients with moderate hepatic impairment (Child-Pugh Class B), it is essential to monitor for signs and/or symptoms of hypercorticism to ensure patient safety and effective management of potential adverse effects.

Overdosage

In cases of acute overdosage, immediate intervention is critical. The recommended initial treatment involves gastric lavage or the induction of emesis to reduce the absorption of the substance. Following these procedures, supportive and symptomatic therapy should be administered to manage any arising complications.

Healthcare professionals should be aware that the excessive use of corticosteroids, including EOHILIA, can lead to significant adverse effects. Prolonged or high-dose administration increases the risk of systemic corticosteroid effects, which may manifest as hypercorticism and adrenal axis suppression. Monitoring for these potential symptoms is essential in the management of patients experiencing overdosage.

In summary, prompt gastric decontamination followed by vigilant supportive care is essential in the management of overdosage, particularly with corticosteroids, to mitigate the risk of serious systemic effects.

Nonclinical Toxicology

Carcinogenicity studies with budesonide were conducted in rats and mice. In a 2-year study involving Sprague-Dawley rats, a statistically significant increase in the incidence of gliomas was observed in male rats at an oral dose of 50 mcg/kg/day, which is approximately 0.1 times the maximum recommended human dose (MRHD) based on body surface area (BSA). Additionally, increased incidences of primary hepatocellular tumors were noted in male rats at doses of 25 mcg/kg (approximately 0.06 times the MRHD) and above. No tumorigenicity was observed in female rats at oral doses up to 50 mcg/kg/day (approximately 0.1 times the MRHD, based on BSA). In a separate 2-year study in male Sprague-Dawley rats, no gliomas were detected at the same oral dose of 50 mcg/kg/day; however, a statistically significant increase in the incidence of hepatocellular tumors was reported. Concurrent reference corticosteroids, including prednisolone and triamcinolone acetonide, exhibited similar findings. In a 91-week study in mice, budesonide did not demonstrate treatment-related carcinogenicity at oral doses up to 200 mcg/kg/day (approximately 0.2 times the MRHD, based on BSA).

Budesonide showed no evidence of genotoxic potential in several assays, including the Ames test, the mouse lymphoma cell forward gene mutation (TK+/-) test, the human lymphocyte chromosome aberration test, the Drosophila melanogaster sex-linked recessive lethality test, the rat hepatocyte UDS test, and the mouse micronucleus test.

In terms of fertility, budesonide had no effect on fertility in rats at subcutaneous doses up to 80 mcg/kg/day (approximately 0.1 times the MRHD, based on BSA). However, a decrease in prenatal viability and viability in pups at birth and during lactation was observed, along with a reduction in maternal body weight gain, at subcutaneous doses of 20 mcg/kg/day (approximately 0.04 times the MRHD, based on BSA) and above. No such effects were noted at a dose of 5 mcg/kg/day (approximately 0.01 times the MRHD on a body surface area basis).

Postmarketing Experience

During post-approval use of oral budesonide products, various adverse reactions have been reported voluntarily from a population of uncertain size. As a result, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Hypersensitivity reactions, including anaphylaxis, have been documented. Additionally, cases of benign intracranial hypertension have been reported under nervous system disorders. Furthermore, mood swings have been noted as part of psychiatric disorders associated with the use of these products.

Patient Counseling

Patients and caregivers should be advised to read the FDA-approved patient labeling, which includes the Patient Information and Instructions for Use. It is important to inform them that EOHILIA may lead to hypercorticism and adrenal axis suppression. They should be instructed to report any signs or symptoms of these conditions to their healthcare provider, including but not limited to acne, easy bruising, ankle swelling, increased body and facial hair, pink or purple stretch marks, fatigue, weakness, nausea, vomiting, and low blood pressure.

Patients and caregivers must be made aware of the importance of notifying their healthcare provider if they develop a new or worsening infection. They should also be instructed to contact their healthcare provider immediately if they are exposed to varicella or measles.

Additionally, patients and caregivers should be informed that localized infections with Candida albicans may occur in the mouth, throat, and esophagus. They should be instructed to rinse their mouth with water 30 minutes after administration of EOHILIA and to spit out the contents without swallowing. It is crucial to advise them to contact their healthcare provider if they experience signs or symptoms of oropharyngeal or esophageal candidiasis.

Patients and caregivers should also be advised to report any new onset or worsening signs or symptoms of erosive esophagitis, such as heartburn, chest pain, or difficulty swallowing, to their healthcare provider. Furthermore, it is important to inform them that corticosteroids can impact growth in pediatric patients, and any concerns regarding growth while taking EOHILIA should be communicated to the healthcare provider.

For patients transitioning to EOHILIA from corticosteroid treatment with high systemic effects, they should be advised to follow a taper schedule for systemic corticosteroids as instructed by their healthcare provider. It should be noted that replacing other systemic corticosteroids with EOHILIA may unmask previously controlled allergies, such as rhinitis and eczema.

Lastly, patients and caregivers should be informed that Kaposi’s sarcoma has been reported in patients receiving corticosteroids for chronic conditions. They should be instructed to inform their healthcare provider if they experience any signs or symptoms of Kaposi’s sarcoma.

Storage and Handling

The product is supplied in various package configurations, with specific NDC numbers available upon request. It should be stored refrigerated or at controlled room temperature within the range of 2°C to 25°C (36°F to 77°F). Temporary excursions up to 30°C (86°F) are permissible; however, freezing the product is strictly prohibited to maintain its integrity and efficacy. Proper handling and storage conditions are essential to ensure the product remains effective throughout its shelf life.

Additional Clinical Information

Postmarketing experience has revealed several important safety concerns associated with the use of the medication. Clinicians should be aware of the potential for hypersensitivity reactions, including anaphylaxis, which may occur in some patients. Additionally, there have been reports of nervous system disorders, specifically benign intracranial hypertension, as well as psychiatric disorders characterized by mood swings. These findings underscore the need for careful monitoring of patients for these adverse effects during treatment.

FDA Insert (PDF)

This document is the official FDA-approved prescribing information for Eohilia as submitted by TAKEDA PHARMACEUTICALS AMERICA, INC.. It includes detailed information about indications, dosage, contraindications, warnings, and clinical pharmacology.

View full prescribing information (PDF)