Eohilia
(budesonide)Dosage & Administration
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Eohilia Prescribing Information
EOHILIA™ is indicated for 12 weeks of treatment in adult and pediatric patients 11 years of age and older with eosinophilic esophagitis (EoE).
Limitations of Use
EOHILIA has not been shown to be safe and effective for the treatment of EoE for longer than 12 weeks [see Dosage and Administration (2.1), Clinical Studies (14)].
Recommended Dosage
- The recommended dosage is 2 mg orally twice daily for 12 weeks.
Preparation and Important Administration Instructions
- Do NOT take EOHILIA with food or liquid at the time of ingestion. Wait for at least 30 minutes to eat or drink after taking EOHILIA.
- Administer EOHILIA as follows:
- Do NOT mix EOHILIA with food or liquid.
- Shake the EOHILIA packet for at least 10 seconds prior to opening.
- Squeeze the packet from the bottom to the top directly into the mouth. Repeat 2 to 3 times until the EOHILIA packet is empty.
- Swallow all the EOHILIA suspension.
- Do not eat or drink for 30 minutes after taking EOHILIA. After 30 minutes, rinse mouth with water and spit out the contents without swallowing [see Warnings and Precautions (5.2)].
- Avoid consumption of grapefruit juice for the duration of therapy with EOHILIA [see Drug Interactions (7.1)].
Oral suspension: 2 mg/10 mL unit-dose packets of a white to yellow viscous suspension with cherry flavoring.
Pregnancy
Risk Summary
The available data from published case series, epidemiological studies, and reviews with oral budesonide use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or other adverse maternal outcomes. Infants exposed to in-utero corticosteroids, including EOHILIA, are at risk for hypoadrenalism (see Clinical Considerations). In animal reproduction studies, subcutaneous administration of budesonide during organogenesis in pregnant rats (at doses up to approximately 1.2 times the maximum recommended human dose, based on body surface area [BSA]) or pregnant rabbits (at doses approximately 0.14 times the maximum recommended human dose, based on body surface area [BSA]) resulted in increased fetal loss, decreased pup weights, and skeletal abnormalities. Maternal toxicity was observed in both rats and rabbits at these dose levels (see Data). Based on animal data, advise pregnant women of the potential risk to a fetus.
The background risk of major birth defects and miscarriage in the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Clinical Considerations
Fetal/Neonatal Adverse Reactions
Hypoadrenalism may occur in infants born of mothers receiving corticosteroids during pregnancy. Infants should be carefully observed for signs of hypoadrenalism, such as poor feeding, irritability, weakness, and vomiting, and managed accordingly [see Warnings and Precautions (5.1)].
Data
Animal Data
Budesonide was teratogenic and embryolethal in rabbits and rats.
In an embryo-fetal development study in pregnant rats dosed subcutaneously with budesonide during the period of organogenesis from gestation days 6-15, there were effects on fetal development and survival at subcutaneous doses up to approximately 500 mcg/kg/day in rats (approximately 1.2 times the maximum recommended human dose [MRHD], based on body surface area [BSA]). In an embryo-fetal development study in pregnant rabbits dosed during the period of organogenesis from gestation days 6-18, there was an increase in maternal abortion, and effects on fetal development and reduction in litter weights at subcutaneous doses up to approximately 25 mcg/kg/day (approximately 0.14 times the MRHD, based on BSA). Maternal toxicity, including reduction in body weight gain, was observed at subcutaneous doses of 5 mcg/kg in rabbits (approximately 0.03 times the MRHD, based on BSA) and 500 mcg/kg in rats (approximately 1.2 times the MRHD, based on BSA).
In a peri- and post-natal development study, rats dosed subcutaneously with budesonide during the period of Day 15 post coitum to Day 21 postpartum, budesonide had no effects on delivery but did have an effect on growth and development of offspring. In addition, offspring survival was reduced and surviving offspring had decreased mean body weights at birth and during lactation at exposures 0.05 times the MRHD (on a mg/m2 basis at maternal subcutaneous doses of 20 mcg/kg/day and higher). These findings occurred in the presence of maternal toxicity.
Lactation
Risk Summary
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 the effects of the drug on milk production. One published study reported that budesonide is present in human milk following maternal inhalation of budesonide (see Data). The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for EOHILIA and any potential adverse effects on the breastfed infant from EOHILIA, or from the underlying maternal condition.
Data
One published study reported that budesonide is present in human milk following maternal inhalation of budesonide which resulted in 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 the breastfed infants following maternal use of inhaled budesonide. The recommended daily dose of EOHILIA is higher (4 mg daily) compared with inhaled budesonide (up to 800 mcg daily) given to mothers in the above-described study.
The maximum budesonide plasma concentration following a 2 mg single dose and twice a day repeat dose of oral budesonide is approximately 0.92 ng/mL to 1.1 ng/mL which is up to 2.5 times higher than the 0.43 to 0.86 ng/mL for an 800 mcg daily dose of inhaled budesonide at steady state in the above inhalation study.
Assuming the coefficient of extrapolation between the 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 by budesonide inhalation.
Pediatric Use
The safety and effectiveness of EOHILIA for 12 weeks of treatment for EoE have been established in pediatric patients 11 years of age and older. Use of EOHILIA for this indication is supported by adequate and well controlled studies in adults and pediatric subjects 11 years of age and older (Studies 1 and 2) with pharmacokinetic data in pediatric subjects aged 11 to 17 years of age. In Studies 1 and 2, the safety of EOHILIA in pediatric subjects 11 to 17 years of age was similar to the safety profile in adults [see Adverse Reactions (6.1), Clinical Pharmacology (12.3), and Clinical Studies (14)].
Systemic effects such as hypercorticism and adrenal axis suppression may occur with use of corticosteroids, including EOHILIA [see Warnings and Precautions (5.1), Adverse Reactions (6.1), and Clinical Pharmacology (12.2)].
Use of corticosteroids may cause a reduction of growth velocity in pediatric patients. Monitor the growth of pediatric patients on EOHILIA. The recommended duration of treatment with EOHILIA is 12 weeks [see Dosage and Administration (2.1)].
The safety and effectiveness of EOHILIA in pediatric patients less than 11 years of age have not been established.
Juvenile Animal Toxicity Data
In a juvenile rat study, budesonide was administered orally at doses of 0.05, 0.2, 0.6, and 1.5 mg/kg/day starting on postnatal day (PND) 22 for 91 consecutive days. All of the effects noted were associated with the pharmacology of the drug and manifested in a dose related manner, typical of corticosteroids. These included decreased body weight gain, adrenal atrophy, and effects on bone (decreased cellularity and bone length) and lymphoid tissues (decreased cellularity). The no observed adverse effect level (NOAEL) in juvenile rats was determined to be the 0.05 mg/kg/day. Plasma exposure (AUC) in rats at the NOAEL (0.05 mg/kg/day) was lower (approximately 0.8 times) than that in pediatric subjects (11 years to 17 years of age) at the MRHD.
In a juvenile toxicity study in dogs, budesonide was orally administered at doses of 0.05, 0.2, and 0.6 mg/kg/day (starting at approximately 7 weeks of age) for 91 consecutive days. The observations were dose-related and consistent with corticosteroid treatment. The effects included decreased body weight gain, distended abdomen and swelling associated with inguinal hernias, lymphocytic and leukocytic changes, adrenal atrophy, depletion in lymphoid organs (lymph nodes, spleen, thymus), and effects on skeletal development (decreased cellularity in bone marrow, bone growth, and skeletal muscle atrophy). The incidence and severity of the majority of the pharmacologically mediated effects decreased or resolved completely following the recovery period. A NOAEL could not be defined in juvenile dogs. Plasma exposure (AUC) at the lowest dose tested (0.05 mg/kg/day) was lower (approximately 0.4 times) than that in pediatric subjects (11 years to 17 years of age) at the MRHD.
Geriatric Use
Clinical studies of EOHILIA did not include sufficient numbers of subjects 65 years of age and older to determine whether they respond differently from younger adult subjects. In general, EOHILIA should be used with caution due to the potential for decreased hepatic function [see Warnings and Precautions (5.1)].
Hepatic Impairment
Patients with moderate to severe hepatic impairment (Child-Pugh Class B or Class C, respectively) could be at an increased risk of hypercorticism and adrenal axis suppression due to an increased systemic exposure to budesonide. Use is not recommended in patients with severe hepatic impairment (Child-Pugh Class C). The recommended dosage in patients with mild or moderate hepatic impairment (Child-Pugh Class A or Class B) is the same as the recommended dosage in patients with normal hepatic function. In patients with moderate hepatic impairment (Child-Pugh Class B), monitor for signs and/or symptoms of hypercorticism [see Warnings and Precautions (5.1), Clinical Pharmacology (12.3)].
EOHILIA is contraindicated in patients with hypersensitivity to budesonide. Serious hypersensitivity reactions, including anaphylaxis, have occurred with oral budesonide products [see Adverse Reactions (6.2)].
Hypercorticism and Adrenal Axis Suppression
Systemic effects such as hypercorticism and adrenal axis suppression may occur with use of corticosteroids, including EOHILIA. Monitor patients for signs and symptoms of hypercorticism and adrenal axis suppression and consider reducing the dosage of EOHILIA [see Adverse Reactions (6.1), Clinical Pharmacology (12.2)].
Patients with moderate to severe hepatic impairment (Child-Pugh Class B and C, respectively) could be at an increased risk of hypercorticism and adrenal axis suppression due to an increased systemic exposure of oral budesonide. Use is not recommended in patients with severe hepatic impairment (Child-Pugh Class C) and monitoring for signs and/or symptoms of hypercorticism is recommended in patients with moderate hepatic impairment (Child-Pugh Class B) [see Use in Specific Populations (8.6), Clinical Pharmacology (12.3)].
Corticosteroids, including EOHILIA, can reduce the response of the hypothalamus-pituitary-adrenal (HPA) axis to stress. In situations where patients are subject to trauma, surgery, infection, or other stress situations, supplementation with a systemic corticosteroid is recommended.
Immunosuppression and Increased Risk of Infection
Corticosteroids, including EOHILIA, suppress the immune system and increase the risk of infection with any pathogen, including viral, bacterial, fungal, protozoan, or helminthic pathogens. Corticosteroids can:
- Reduce resistance to new infections
- Exacerbate existing infections
- Increase the risk of disseminated infections
- Increase the risk of reactivation or exacerbation of latent infections
- Mask some signs of infection
Corticosteroid-associated infections can be mild but can be severe and at times fatal. The rate of infectious complications increases with increasing corticosteroid dosages.
Monitor patients for the development of infection and consider discontinuation of EOHILIA if the patient develops an infection while on treatment.
Tuberculosis
If corticosteroids are used in patients with latent tuberculosis or tuberculin reactivity, reactivation of tuberculosis may occur. Closely monitor such patients for reactivation while receiving EOHILIA.
Varicella Zoster and Measles Viral Infections
Varicella and measles can have a serious or even fatal course in non-immune pediatric and adult patients taking corticosteroids. In corticosteroid-treated patients who have not had these diseases or are non-immune, particular care should be taken to avoid exposure to varicella and measles:
- If an EOHILIA-treated patient is exposed to varicella, prophylaxis with varicella zoster immune globulin may be indicated. If varicella develops, treatment with antiviral agents may be considered.
- If an EOHILIA-treated patient is exposed to measles, prophylaxis with immunoglobulin may be indicated.
Hepatitis B Virus Reactivation
Hepatitis B virus reactivation can occur in patients who are hepatitis B carriers treated with immunosuppressive dosages of corticosteroids. Reactivation can also occur infrequently in corticosteroid-treated patients who appear to have resolved hepatitis B infection.
Prior to starting treatment with EOHILIA, for patients who show evidence of hepatitis B infection, recommend consultation with physicians with expertise in managing hepatitis B regarding monitoring and consideration for hepatitis B antiviral therapy.
Fungal Infections
Corticosteroids may exacerbate systemic fungal infections; therefore, avoid EOHILIA use in the presence of such infections.
Amebiasis
Corticosteroids may activate latent amebiasis. Therefore, it is recommended that latent amebiasis or active amebiasis be ruled out before initiating EOHILIA in patients who have spent time in the tropics or patients with unexplained diarrhea.
Strongyloides Infestation
Avoid EOHILIA in patients with known or suspected Strongyloides (threadworm) infection. Corticosteroid-induced immunosuppression may lead to Strongyloides superinfection and dissemination with widespread larval migration, often accompanied by severe enterocolitis and potentially fatal gram-negative septicemia.
Cerebral Malaria
Avoid corticosteroids, including EOHILIA, in patients with cerebral malaria.
Ocular Herpes Simplex
Avoid corticosteroids, including EOHILIA, in patients with active ocular herpes simplex.
Localized Infections
In clinical trials with EOHILIA, localized infections with Candida albicans occurred in the mouth, throat, and esophagus in some subjects [see Adverse Reactions (6.1)]. Do not eat or drink for 30 minutes after taking EOHILIA. After 30 minutes, rinse mouth with water and spit without swallowing [see Dosage and Administration (2.2)]. If oropharyngeal or esophageal candidiasis develops, treat with appropriate local or systemic antifungal therapy and consider discontinuing treatment with EOHILIA.
Erosive Esophagitis
Erosive esophagitis occurred in subjects who received EOHILIA in a 12-week clinical trial. None of the subjects had erosions at baseline esophagogastroduodenoscopy (EGD), and most were receiving concomitant therapy with a proton pump inhibitor (PPI) during the trial [see Adverse Reactions (6.1)].
Advise patients or caregivers to report new onset or worsening signs or symptoms of erosive esophagitis to their healthcare provider. Consider endoscopic evaluation as appropriate.
Effect on Growth
Use of corticosteroids may cause a reduction of growth velocity in pediatric patients. Monitor the growth of pediatric patients on EOHILIA. The maximum recommended duration of treatment with EOHILIA is 12 weeks [see Dosage and Administration (2.1)].
Symptoms of Steroid Withdrawal in Patients Transferred from Other Systemic Corticosteroids
Monitor patients who are transferred from corticosteroid treatment with high systemic effects to corticosteroids with lower systemic availability, such as EOHILIA, since symptoms attributed to withdrawal of steroid therapy, including those of acute adrenal axis suppression or benign intracranial hypertension, may develop. Adrenocortical function monitoring may be required in these patients and the dose of corticosteroid treatment with high systemic effects should be reduced cautiously.
Replacement of systemic corticosteroids with EOHILIA may unmask allergies (e.g., rhinitis and eczema), which were previously controlled by the systemic drug.
Other Corticosteroid Effects
Monitor patients with hypertension, diabetes mellitus, osteoporosis, peptic ulcer, glaucoma or cataracts, or with a family history of diabetes or glaucoma, or with any other condition where corticosteroids may have unwanted effects.
Kaposi’s Sarcoma
Kaposi’s sarcoma has been reported to occur in patients receiving corticosteroid therapy, most often for chronic conditions. Discontinuation of corticosteroids may result in clinical improvement of Kaposi’s sarcoma. The maximum recommended duration of treatment with EOHILIA is 12 weeks [see Dosage and Administration (2.1)].