Corticosteroids acting locally

Eohilia

Approved 9 Feb 2024OralSuspension

Indications

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) ]. EOHILIA is a corticosteroid indicated for 12 weeks of treatment in adult and pediatric patients 11 years of age and older with eosinophilic esophagitis (EoE).

( 1 ) Limitations of Use EOHILIA has not been shown to be safe and effective for the treatment of EoE for longer than 12 weeks. ( 1 , 2.1 , 14 )

Contraindications

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) ] . Hypersensitivity to budesonide. ( 4 )

Warnings and precautions

Hypercorticism and Adrenal Axis Suppression : May occur with treatment; monitor for signs and symptoms and consider reducing the dosage. ( 5.1 , 8.6 ) Immunosuppression and Increased Risk of Infection : Increased risk of viral, bacterial, fungal, protozoan, and helminthic infections, including potentially fatal varicella and measles infection. Monitor patients for new or worsening localized or systemic infection, including oropharyngeal and esophageal candidiasis and consider drug discontinuation.

Avoid use in patients with fungal infections, Strongyloides infestation, cerebral malaria, and ocular herpes simplex. Screen for hepatitis B infection. ( 5.2 ) Erosive Esophagitis : Advise patients or caregivers to report new or worsening signs or symptoms of erosive esophagitis; consider endoscopic evaluation as appropriate. ( 5.3 ) Effect on Growth : Use of corticosteroids may cause a reduction in growth velocity in pediatric patients; monitor growth during treatment.

( 5.4 ) Symptoms of Steroid Withdrawal in Patients Transferred from Other Systemic Corticosteroids : Taper slowly from corticosteroids with high systemic effects; monitor for withdrawal symptoms and unmasking of allergies (rhinitis, eczema). ( 5.5 ) Other Corticosteroid Effects : Monitor patients with concomitant conditions where corticosteroids may have unwanted effects (e.g., hypertension, diabetes mellitus). ( 5.6 ) Kaposi’s Sarcoma : Reported to occur in patients receiving corticosteroid therapy, most often for chronic conditions.

Pregnancy and breastfeeding

8.1Pregnancy 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/m 2 basis at maternal subcutaneous doses of 20 mcg/kg/day and higher). These findings occurred in the presence of maternal toxicity.

Adverse reactions

The following serious adverse reactions are described in greater detail in other sections of the labeling: Hypercorticism and adrenal axis suppression [see Warnings and Precautions (5.1) ] Immunosuppression and increased risk of infections [see Warnings and Precautions (5.2) ] Erosive esophagitis [see Warnings and Precautions (5.3) ] Effect on growth [see Warnings and Precautions (5.4) ] Symptoms of steroid withdrawal in those patients transferred from other systemic corticosteroids [see Warnings and Precautions (5.5) ] Other corticosteroid effects [see Warnings and Precautions (5.6) ] Kaposi’s sarcoma [see Warnings and Precautions (5.7) ] Most common adverse reactions (≥2%) are: respiratory tract infection, gastrointestinal mucosal candidiasis, headache, gastroenteritis, throat irritation, adrenal suppression, and erosive esophagitis.

( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Takeda Pharmaceuticals America, Inc. at 1-877-TAKEDA-7 (1-877-825-3327) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

6.1Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of EOHILIA in 410 adults and pediatric subjects 11 years of age and older with EoE was evaluated in two 12-week, double-blind, placebo-controlled studies (Study 1 and Study 2).

In these studies, 263 subjects received EOHILIA [see Clinical Studies (14) ] . Common Adverse Reactions The most common adverse reactions reported in Study 1 are shown in Table 1. Table 1: Common Adverse Reactions reported in at least 2% of subjects in the EOHILIA group and at a rate greater than placebo. in Adult and Pediatric Subjects 11 Years of Age and Older with EoE in Study 1 ADVERSE REACTIONS EOHILIA 2 mg Twice Daily N = 213 Placebo N = 105 Respiratory tract infection includes acute sinusitis, sinusitis, nasopharyngitis, respiratory tract infection, respiratory tract infection viral, upper respiratory tract infection, viral upper respiratory tract infection, rhinitis 13% 11% Gastrointestinal mucosal candidiasis includes esophageal candidiasis, oropharyngeal candidiasis, oral candidiasis 8% 2% Headache includes headache, migraine 5% 2% Gastroenteritis 3% 1% Throat irritation includes throat irritation, oropharyngeal pain 3% 2% Adrenal suppression includes adrenal suppression, adrenal insufficiency 2% 0 Erosive esophagitis includes esophagitis only where erosions were present at the esophagogastroduodenoscopy conducted after 12 weeks of treatment 2% 0 Specific Adverse Reactions Erosive Esophagitis Erosive esophagitis occurred in 4/213 (2%) of EOHILIA-treated subjects in Study 1.

These subjects had no erosions present at the baseline esophagogastroduodenoscopy (EGD). At EGD after 12 weeks of treatment with EOHILIA, 2 subjects had Los Angeles (LA) classification grade A, 1 subject had LA grade B, and 1 subject had LA grade C erosive esophagitis. All but one of the four subjects developed erosive esophagitis while receiving concomitant therapy with a PPI. No cases of erosive esophagitis were reported in Study 2 [see Warnings and Precautions (5.3) ] .

Less Common Adverse Reactions Adverse reactions reported in less than 2% of subjects treated with EOHILIA and at a greater rate than placebo in Study 1 are listed below: Cardiac disorders: Palpitations Gastrointestinal disorders: Dry mouth, dyspepsia, erosive duodenitis, gastrointestinal motility disorder, esophageal food impaction, palatal swelling General disorders and administration site conditions: Fatigue, feeling abnormal Infections and infestations: Fungal skin infection, paronychia, pneumonia, sepsis, bronchitis Investigations: Transaminases increased, hyperkalemia Metabolism and nutrition disorders: Dyslipidemia Musculoskeletal and connective tissue disorders: Arthralgia, muscle spasms Nervous system disorders: Dysgeusia, syncope, tremor Psychiatric disorders: Depression, irritability, restlessness Respiratory, thoracic, and mediastinal disorders: Nasal congestion Skin and subcutaneous tissue disorders: Hirsutism, dermatitis acneiform Vascular disorders: Hypertension The safety profile of EOHILIA in Study 2 was generally similar to Study 1.

6.2Postmarketing Experience

The following adverse reactions have been reported during post-approval use of oral budesonide products. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Hypersensitivity Reactions: Anaphylaxis Nervous System Disorders: Benign intracranial hypertension Psychiatric Disorders: Mood swings

Eohilia

Indications

Contraindications

Warnings and precautions

Two medicines in one question?

5.1Hypercorticism and Adrenal Axis Suppression

5.2Immunosuppression and Increased Risk of Infection

5.3Erosive Esophagitis

5.4Effect on Growth Use

5.5Symptoms of Steroid Withdrawal in Patients Transferred from Other Systemic Corticosteroids

5.6Other Corticosteroid Effects

Interactions

7.1CYP3A4 Inhibitors

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

Adverse reactions

6.1Clinical Trials Experience

6.2Postmarketing Experience

Composition

Official product information

At a glance

Guidelines