budesonide
Suspension · Oral, Respiratory (inhalation), Nasal
Uses
Budesonide delayed-release capsules are a corticosteroid indicated for:
• Treatment of mild to moderate active Crohn’s disease involving the ileum and/or the ascending colon, in patients 8 years and older. ( 1.1 )
• Maintenance of clinical remission of mild to moderate Crohn’s disease involving the ileum and/or the ascending colon for up to 3 months in adults. ( 1.2 ) 1.1 Treatment of Mild to Moderate Active Crohn’s Disease Budesonide delayed-release capsules are indicated for the treatment of mild to moderate active Crohn's disease involving the ileum and/or the ascending colon in patients 8 years of age and older. 1.2 Maintenance of Clinical Remission of Mild to Moderate Crohn’s Disease Budesonide delayed-release capsules are indicated for the maintenance of clinical remission of mild to moderate Crohn’s disease involving the ileum and/or the ascending colon for up to 3 months in adults.
Dosage and administration
Administration Instructions ( 2.1 ):
• Take once daily in the morning.
• Swallow whole. Do not chew or crush.
• For patients unable to swallow an intact capsule, open the capsules and empty the granules onto one tablespoonful of applesauce. Mix and consume the entire contents within 30 minutes. Do not chew or crush. Follow with 8 ounces of water.
• Avoid consumption of grapefruit juice for the duration of therapy. Recommended Dosage : Mild to moderate active Crohn’s disease ( 2.2 ):
• Adults: 9 mg once daily for up to 8 weeks; repeat 8 week treatment courses for recurring episodes of active disease.
• Pediatrics 8 to 17 years who weigh more than 25 kg: 9 mg once daily for up to 8 weeks, followed by 6 mg once daily in the morning for 2 weeks. Maintenance of clinical remission of mild to moderate Crohn’s disease ( 2.3 ):
• Adults: 6 mg once daily for up to 3 months; taper to complete cessation after 3 months. Continued treatment for more than 3 months has not been shown to provide substantial clinical benefit.
• When switching from oral prednisolone, begin tapering prednisolone concomitantly with initiating budesonide delayed-release capsules. Hepatic Impairment :
• Consider reducing the dosage to 3 mg once daily in adult patients with moderate hepatic impairment (Child-Pugh Class B). ( 2.4 , 5.1 , 8.6 ) 2.1 Administration Instructions
• Take budesonide delayed-release capsules once daily in the morning.
• Swallow budesonide delayed-release capsules whole. Do not chew or crush.
• For patients unable to swallow an intact capsule, budesonide delayed-release capsules can be opened and administered as follows: 1. Place one tablespoonful of applesauce into a clean container (e.g., empty bowl). The applesauce used should not be hot and should be soft enough to be swallowed without chewing. 2. Open the capsule(s). 3. Carefully empty all the granules inside the capsule(s) on the applesauce. 4. Mix the granules with the applesauce. 5. Consume the entire contents within 30 minutes of mixing. Do not chew or crush the granules. Do not save the applesauce and granules for future use. 6. Follow the applesauce and granules immediately with a glass (8 ounces) of cool water to ensure complete swallowing of the granules.
• Avoid consumption of grapefruit juice for the duration of budesonide delayed-release capsule therapy [see Drug Interactions (7.1)] . 2.2 Treatment of Mild to Moderate Active Crohn’s Disease The recommended dosage of budesonide delayed-release capsules is: Adults : 9 mg orally once daily for up to 8 weeks. Repeated 8 week courses of budesonide delayed-release capsules can be given for recurring episodes of active disease. Pediatric patients 8 to 17 years who weigh more than 25 kg : 9 mg orally once daily for up to 8 weeks, followed by 6 mg once daily for 2 weeks. 2.3 Maintenance of Clinical Remission of Mild to Moderate Crohn’s Disease The recommended dosage in adults, following an 8 week course(s) of treatment for active disease and once the patient’s symptoms are controlled (CDAI less than 150), is budesonide delayed-release capsules 6 mg orally once daily for maintenance of clinical remission up to 3 months. If symptom control is still maintained at 3 months an attempt to taper to complete cessation is recommended. Continued treatment with budesonide delayed-release capsules 6 mg for more than 3 months has not been shown to provide substantial clinical benefit. Patients with mild to moderate active Crohn’s disease involving the ileum and/or ascending colon have been switched from oral prednisolone to budesonide delayed-release capsules with no reported episodes of adrenal insufficiency. Since prednisolone should not be stopped abruptly, tapering should begin concomitantly with initiating budesonide delayed-release capsules treatment. 2.4 Dosage Adjustment in Adult Patients with Hepatic Impairment Consider reducing the dosage of budesonide delayed-release capsules to 3 mg once daily for adult patients with moderate hepatic impairment (Child-Pugh Class B). Avoid use in patients with severe hepatic impairment (Child-Pugh Class C) [see Warnings and Precautions (5.1), Use in Specific Populations (8.6)] .
Dosage forms and strengths
Delayed-Release Capsules: 3 mg hard gelatin capsules with an opaque light grey body and an opaque pink cap, coded with ENTOCORT EC 3 mg. Delayed-release Capsules: 3 mg ( 3 )
Contraindications
Budesonide delayed-release capsules are contraindicated in patients with hypersensitivity to budesonide or any of the ingredients of budesonide delayed-release capsules. Serious hypersensitivity reactions, including anaphylaxis have occurred [see Adverse Reactions (6.2)] . Hypersensitivity to budesonide or any of the ingredients in budesonide delayed-release capsules. ( 4 )
Warnings and precautions
• Hypercorticism and Adrenal Axis Suppression : May occur with treatment; monitor for signs and symptoms; pediatrics and patients with hepatic impairment may be at increased risk. ( 2.4 , 5.1 , 8.4 , 8.6 )
• 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). ( 5.2 )
• Immunosuppression and Increased Risk of Infection : Increased risk of viral, bacterial, fungal, protozoal and helminthic infections, including potentially fatal varicella and measles infection. Monitor patients for new or worsening infection and consider drug discontinuation. Avoid use in patients with fungal infections, Strongyloides infestation, cerebral malaria and ocular herpes simplex. Screen for hepatitis B infection. ( 5.3 )
• Karposi’s Sarcoma : Reported to occur in patients receiving corticosteroid therapy, most often for chronic conditions. ( 5.4 )
• Other Corticosteroid Effects : Monitor patients with concomitant conditions where corticosteroids may have unwanted effects (e.g., hypertension, diabetes mellitus). ( 5.5 ) 5.1 Hypercorticism and Adrenal Axis Suppression Systemic effects such as hypercorticism and adrenal axis suppression may occur with use of corticosteroids, including budesonide delayed-release capsules [see Adverse Reactions (6.1), Clinical Pharmacology (12.2)] . Pediatric patients with Crohn’s disease have a slightly higher systemic exposure of budesonide and increased cortisol suppression than adults with Crohn’s disease [see Use in Specific Populations (8.4), Clinical Pharmacology (12.2)] . Monitor patients for signs and symptoms of hypercorticism and adrenal axis suppression during treatment with budesonide delayed-release capsules. 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. Avoid use in patients with severe hepatic impairment (Child-Pugh Class C). Monitor for increased signs and/or symptoms of hypercorticism and consider reducing the dosage in patients with moderate hepatic impairment (Child-Pugh Class B) [see Dosage and Administration (2.4), Use in Specific Populations (8.6), Clinical Pharmacology (12.3)] . Corticosteroids, including budesonide delayed-release capsules, can reduce the response of the hypothalamus-pituitary-adrenal (HPA) axis to stress. In situations where patients are subject to surgery or other stress situations, supplementation with a systemic corticosteroid is recommended. 5.2 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 budesonide delayed-release capsules, 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 budesonide delayed-release capsules may unmask allergies (e.g., rhinitis and eczema), which were previously controlled by the systemic drug. 5.3 Immunosuppression and Increased Risk of Infection Corticosteroids, including budesonide delayed-release capsules, 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 budesonide delayed-release capsules if the patient develops an infection while on treatment. Tuberculosis If budesonide delayed-release capsules is used in patients with latent tuberculosis or tuberculin reactivity, reactivation of tuberculosis may occur. Closely monitor such patients for reactivation. During prolonged budesonide delayed-release capsules therapy, patients with latent tuberculosis or tuberculin reactivity should receive chemoprophylaxis. 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, including budesonide delayed-release capsules. 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 budesonide delayed-release capsules-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 budesonide delayed-release capsules-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, including budesonide delayed-release capsules. Reactivation can also occur infrequently in corticosteroid-treated patients who appear to have resolved hepatitis B infection. Screen patients for hepatitis B infection before initiating immunosuppressive (e.g., prolonged) treatment with budesonide delayed-release capsules.
Side effects
The following clinically significant adverse reactions are described elsewhere in labeling:
• Hypercorticism and adrenal axis suppression [see Warnings and Precautions (5.1)]
• Symptoms of steroid withdrawal in those patients transferred from other systemic corticosteroids [see Warnings and Precautions (5.2)]
• Immunosuppression and increased risk of infection [see Warnings and Precautions (5.3)]
• Kaposi’s sarcoma [see Warnings and Precautions (5.4)]
• Other corticosteroid effects [see Warnings and Precautions (5.5)] Most common adverse reactions (≥5%) in adults are: headache, respiratory infection, nausea, back pain, dyspepsia, dizziness, abdominal pain, flatulence, vomiting, fatigue, and pain. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Padagis ® at 1-866-634-9120 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical 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. Adults The data described below reflect exposure to budesonide delayed-release capsules in 520 patients with Crohn’s disease, including 520 exposed to 9 mg per day (total daily dose) for 8 weeks and 145 exposed to 6 mg per day for one year in placebo controlled clinical trials. Of the 520 patients, 38% were males and the age range was 17 to 74 years. Treatment of Mild to Moderate Active Crohn’s Disease The safety of budesonide delayed-release capsules was evaluated in 651 adult patients in five clinical trials of 8 weeks duration in patients with active mild to moderate Crohn’s disease. The most common adverse reactions, occurring in greater than or equal to 5% of the patients, are listed in Table 1. Table 1: Common Adverse Reactions 1 in 8-Week Treatment Clinical Trials Adverse Reaction Budesonide Delayed-Release Capsules 9 mg n=520 Number (%) Placebo n=107 Number (%) Prednisolone 2 40 mg n=145 Number (%) Comparator 3 n=88 Number (%) Headache 107 (21) 19 (18) 31 (21) 11 (13) Respiratory Infection 55 (11) 7 (7) 20 (14) 5 (6) Nausea 57 (11) 10 (9) 18 (12) 7 (8) Back Pain 36 (7) 10 (9) 17 (12) 5 (6) Dyspepsia 31 (6) 4 (4) 17 (12) 3 (3) Dizziness 38 (7) 5 (5) 18 (12) 5 (6) Abdominal Pain 32 (6) 18 (17) 6 (4) 10 (11) Flatulence 30 (6) 6 (6) 12 (8) 5 (6) Vomiting 29 (6) 6 (6) 6 (4) 6 (7) Fatigue 25 (5) 8 (7) 11 (8) 0 (0) Pain 24 (5) 8 (7) 17 (12) 2 (2) 1. Occurring in greater than or equal to 5% of the patients in any treated group. 2. Prednisolone tapering scheme: either 40 mg in week 1 to 2, thereafter tapering with 5 mg per week; or 40 mg in week 1 to 2, 30 mg in week 3 to 4, thereafter tapering with 5 mg per week. 3. This drug is not approved for the treatment of Crohn’s disease in the United States. The incidence of signs and symptoms of hypercorticism reported by active questioning of patients in 4 of the 5 short-term clinical trials are displayed in Table 2. Table 2: Summary and Incidence of Signs/Symptoms of Hypercorticism in 8-Week Treatment Clinical Trials Signs/Symptom Budesonide Delayed-Release Capsules 9 mg n=427 Number (%) Placebo n=107 Number (%) Prednisolone 1 40 mg n=145 Number (%) Total 145 (34%) 29 (27%) 69 (48%) Acne 63 (15) 14 (13) 33 (23) 2 Bruising Easily 63 (15) 12 (11) 13 (9) Moon Face 46 (11) 4 (4) 53 (37) 2 Swollen Ankles 32 (7) 6 (6) 13 (9) Hirsutism 3 22 (5) 2 (2) 5 (3) Buffalo Hump 6 (1) 2 (2) 5 (3) Skin Striae 4 (1) 2 (2) 0 (0) 1. Prednisolone tapering scheme: either 40 mg in week 1-2, thereafter tapering with 5 mg/week; or 40 mg in week 1 to 2, 30 mg in week 3 to 4, thereafter tapering with 5 mg/week. 2. Statistically significantly different from budesonide delayed-release capsules 9 mg 3. Including hair growth increased, local and hair growth increased, general Maintenance of Clinical Remission of Mild to Moderate Crohn’s Disease The safety of budesonide delayed-release capsules was evaluated in 233 adult patients in four long-term clinical trials (52 weeks) of maintenance of clinical remission in patients with mild to moderate Crohn’s disease. A total of 145 patients were treated with budesonide delayed-release capsules 6 mg once daily. The adverse reaction profile of budesonide delayed-release capsules 6 mg once daily in maintenance of Crohn’s disease was similar to that of short-term treatment with budesonide delayed-release capsules 9 mg once daily in active Crohn’s disease. In the long-term clinical trials, the following adverse reactions occurred in greater than or equal to 5% and are not listed in Table 1: diarrhea (10%); sinusitis (8%); infection viral (6%); and arthralgia (5%). Signs/symptoms of hypercorticism reported by active questioning of patients in the long-term maintenance clinical trials are displayed in Table 3. Table 3: Summary and Incidence of Signs/Symptoms of Hypercorticism in Long-Term Clinical Trials Signs/Symptom Budesonide Delayed-Release Capsules 3 mg n=88 Number (%) Budesonide Delayed-Release Capsules 6 mg n=145 Number (%) Placebo n=143 Number (%) Bruising Easily 4 (5) 15 (10) 5 (4) Acne 4 (5) 14 (10) 3 (2) Moon Face 3 (3) 6 (4) 0 Hirsutism 2 (2) 5 (3) 1(1) Swollen Ankles 2 (2) 3 (2) 3 (2) Buffalo Hump 1 (1) 1 (1) 0 Skin Striae 2 (2) 0 0 The incidence of signs/symptoms of hypercorticism as described above in long-term maintenance clinical trials was similar to that seen in the short-term treatment clinical trials.
Drug interactions
7 DRUG INTERACTIONS CYP3A4 Inhibitors (e.g., ketoconazole, grapefruit juice) : Can increase systemic budesonide concentrations: avoid use. ( 2.1 , 7.1 ) 7.1 CYP3A4 Inhibitors Budesonide is a substrate for CYP3A4. Avoid use with CYP3A4 inhibitors. Concomitant oral administration of a strong CYP3A4 inhibitor (ketoconazole) caused an eight-fold increase of the systemic exposure to oral budesonide. Inhibitors of CYP3A4 (e.g., ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, erythromycin, and cyclosporine) can increase systemic budesonide concentrations [see Clinical Pharmacology (12.3)] . Grapefruit Juice Avoid ingestion of grapefruit juice with budesonide. Intake of grapefruit juice which inhibits CYP3A4 activity with budesonide can increase the systemic exposure for budesonide [see Clinical Pharmacology (12.3)] .
Use in specific populations
Pregnancy : Based on animal data, may cause fetal harm. ( 8.1 ) 8.1 Pregnancy Risk Summary Limited published studies report on the use of budesonide in pregnant women; however, the data are insufficient to inform a drug-associated risk for major birth defects and miscarriage. There are clinical considerations [see Clinical Considerations] . In animal reproduction studies with pregnant rats and rabbits, administration of subcutaneous budesonide during organogenesis at doses approximately 0.5 times or 0.05 times, respectively, the maximum recommended human dose, 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 estimated background risk of major birth defects and miscarriage of 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 Disease-Associated Maternal and/or Embryo/Fetal Risk Some published epidemiological studies show an association of adverse pregnancy outcomes in women with Crohn’s disease, including preterm birth and low birth weight infants, during periods of increased disease activity (including increased stool frequency and abdominal pain). Pregnant women with Crohn’s disease should be counseled regarding the importance of controlling disease. 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 in rats (approximately 0.5 times the maximum recommended human dose on a body surface area basis). 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 in rabbits (approximately 0.05 times the maximum recommended human dose on a body surface area basis). Maternal toxicity, including reduction in body weight gain, was observed at subcutaneous doses of 5 mcg/kg in rabbits (approximately 0.01 times the maximum recommended human dose on a body surface area basis) and 500 mcg/kg in rats (approximately 0.5 times the maximum recommended human dose on a body surface area basis). 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 0.02 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. 8.2 Lactation Risk Summary Lactation studies have not been conducted with oral budesonide, including budesonide delayed-release capsules, 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 reports 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 budesonide delayed-release capsules and any potential adverse effects on the breastfed infant from budesonide delayed-release capsules, or from the underlying maternal condition. Data One published study reports 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 budesonide delayed-release capsules is higher (up to 9 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 9 mg daily dose (in both single- and repeated-dose pharmacokinetic studies) of oral budesonide is approximately 2.15 to 4.31 ng/mL which is up to 10 times higher than the 0.43 to 0.86 ng/mL for a 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 budesonide delayed-release capsules, budesonide exposure to the nursing child may be up to 10 times higher than that by budesonide inhalation. 8.4 Pediatric Use The safety and effectiveness of budesonide delayed-release capsules have been established in pediatric patients 8 to 17 years of age who weigh more than 25 kg for the treatment of mild to moderate active Crohn’s disease involving the ileum and/or the ascending colon.
Pregnancy
8.1 Pregnancy Risk Summary Limited published studies report on the use of budesonide in pregnant women; however, the data are insufficient to inform a drug-associated risk for major birth defects and miscarriage. There are clinical considerations [see Clinical Considerations] . In animal reproduction studies with pregnant rats and rabbits, administration of subcutaneous budesonide during organogenesis at doses approximately 0.5 times or 0.05 times, respectively, the maximum recommended human dose, 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 estimated background risk of major birth defects and miscarriage of 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 Disease-Associated Maternal and/or Embryo/Fetal Risk Some published epidemiological studies show an association of adverse pregnancy outcomes in women with Crohn’s disease, including preterm birth and low birth weight infants, during periods of increased disease activity (including increased stool frequency and abdominal pain). Pregnant women with Crohn’s disease should be counseled regarding the importance of controlling disease. 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 in rats (approximately 0.5 times the maximum recommended human dose on a body surface area basis). 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 in rabbits (approximately 0.05 times the maximum recommended human dose on a body surface area basis). Maternal toxicity, including reduction in body weight gain, was observed at subcutaneous doses of 5 mcg/kg in rabbits (approximately 0.01 times the maximum recommended human dose on a body surface area basis) and 500 mcg/kg in rats (approximately 0.5 times the maximum recommended human dose on a body surface area basis). 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 0.02 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.
Pediatric use
8.4 Pediatric Use The safety and effectiveness of budesonide delayed-release capsules have been established in pediatric patients 8 to 17 years of age who weigh more than 25 kg for the treatment of mild to moderate active Crohn’s disease involving the ileum and/or the ascending colon. Use of budesonide delayed-release capsules in this age group is supported by evidence from adequate and well controlled studies of budesonide delayed-release capsules in adults, with additional data from 2 clinical studies in 149 pediatric patients treated up to 8 weeks and one pharmacokinetic study in 8 pediatric patients [see Adverse Reactions (6.1), Clinical Pharmacology (12.3), and Clinical Studies (14.1)] . The observed safety profile of budesonide delayed-release capsules in pediatric patients is consistent with its known safety profile in adults and no new safety concerns were identified [see Adverse Reactions (6.1)] . The safety and effectiveness of budesonide delayed-release capsules have not been established in pediatric patients less than 8 years of age for the treatment of mild to moderate active Crohn’s disease involving the ileum and/or the ascending colon. The safety and effectiveness of budesonide delayed-release capsules have not been established in pediatric patients for the maintenance of clinical remission of mild to moderate Crohn’s disease. An open-label study to evaluate the safety and tolerability of budesonide delayed-release capsules as maintenance treatment in pediatric patients aged 5 to 17 years was conducted, and did not establish the safety and efficacy of maintenance of clinical remission. Systemic corticosteroids, including budesonide delayed-release capsules, may cause a reduction of growth velocity in pediatric patients. Pediatric patients with Crohn’s disease have a 17% higher mean systemic exposure and cortisol suppression than adults with Crohn’s disease [see Warnings and Precautions (5.1) and Clinical Pharmacology (12.2)] .
Geriatric use
8.5 Geriatric Use Clinical studies of budesonide delayed-release capsules did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients. Of the 651 patients treated with budesonide delayed-release capsules in clinical studies, 17 (3%) were greater than or equal to 65 years of age and none were greater than 74 years of age. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
Overdosage
Reports of acute toxicity and/or death following overdosage of glucocorticoids are rare. Treatment consists of immediate gastric lavage or emesis followed by supportive and symptomatic therapy. If corticosteroids are used at excessive doses for prolonged periods, systemic corticosteroid effects such as hypercorticism and adrenal axis suppression may occur. For chronic overdosage in the case of severe disease requiring continuous steroid therapy, the dosage may be reduced temporarily. Single oral doses of 200 and 400 mg/kg were lethal in female and male mice, respectively. The signs of acute toxicity were decreased motor activity, piloerection and generalized edema.
Description
Budesonide, the active ingredient of budesonide delayed-release capsules, is a synthetic corticosteroid. Budesonide is designated chemically as (RS)-11β, 16α, 17,21-tetrahydroxypregna-1,4-diene-3,20-dione cyclic 16,17-acetal with butyraldehyde. Budesonide is provided as a mixture of two epimers (22R and 22S). The empirical formula of budesonide is C 25 H 34 O 6 and its molecular weight is 430.5. Its structural formula is: Budesonide is a white to off-white, tasteless, odorless powder that is practically insoluble in water and heptane, sparingly soluble in ethanol, and freely soluble in chloroform. Its partition coefficient between octanol and water at pH 5 is 1.6 x 10 3 ionic strength 0.01. Budesonide delayed-release capsules are formulated as hard gelatin capsules filled with enteric-coated granules that dissolve at pH greater than 5.5. Each capsule for oral administration contains 3 mg of micronized budesonide with the following inactive ingredients: ethylcellulose, acetyltributyl citrate, methacrylic acid copolymer type C, triethyl citrate, antifoam M, polysorbate 80, talc, and sugar spheres. The capsule shells have the following inactive ingredients: gelatin, iron oxide, and titanium dioxide. epimer-22r epimer-22s
Mechanism of action
12.1 Mechanism of Action Budesonide is an anti-inflammatory corticosteroid and has a high glucocorticoid effect and a weak mineralocorticoid effect, and the affinity of budesonide to glucocorticoid receptors, which reflects the intrinsic potency of the drug, is about 200-fold that of cortisol and 15-fold that of prednisolone.
How supplied
Budesonide 3 mg delayed-release capsules are hard gelatin capsules with an opaque light grey body and an opaque pink cap, coded with ENTOCORT EC 3 mg on the capsule and are supplied as follows: NDC 0574–9855–10 Bottles of 100 Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F) [See USP Controlled Room Temperature]. Keep container tightly closed.
Patient information
Advise Patients to read the FDA-Approved patient labeling (Patient Information). Hypercorticism and Adrenal Axis Suppression Advise patients that budesonide delayed-release capsules may cause hypercorticism and adrenal axis suppression and to follow a taper schedule, as instructed by their healthcare provider if transferring to budesonide delayed-release capsules from systemic corticosteroids [see Warnings and Precautions (5.1), (5.2)] . Advise patients that replacement of systemic corticosteroids with budesonide delayed-release capsules may unmask allergies (e.g., rhinitis and eczema), which were previously controlled by the systemic drug. Immunosuppression and Increased Risk of Infection Advise patients to avoid exposure to people with varicella (chicken pox) or measles. Advise patients inform their healthcare provider if they are exposed to varicella or measles or if they develop a new or worsening infection [see Warnings and Precautions (5.3)] . Kaposi’s Sarcoma Advise patients that Kaposi’s sarcoma has been reported in patients receiving corticosteroids for chronic conditions and to inform their healthcare provider if they experience signs or symptoms of Kaposi’s sarcoma [see Warnings and Precautions (5.4)] . Pregnancy Advise female patients that budesonide delayed-release capsules may cause fetal harm and to inform their healthcare provider with a known or suspected pregnancy [see Use in Specific Populations (8.1)] . Administration
• Take budesonide delayed-release capsules once daily in the morning.
• Swallow budesonide delayed-release capsules whole. Do not chew or crush.
• For patients unable to swallow an intact capsule, budesonide delayed-release capsules can be opened and administered as follows: 1. Place one tablespoonful of applesauce into a clean container (e.g., empty bowl). The applesauce used should not be hot and should be soft enough to be swallowed without chewing. 2. Open the capsule(s). 3. Carefully empty all the granules inside the capsule(s) on the applesauce. 4. Mix the granules with the applesauce. 5. Consume the entire contents within 30 minutes of mixing. Do not chew or crush the granules. Do not save the applesauce and granules for future use. 6. Follow the applesauce and granules immediately with a glass (8 ounces) of cool water to ensure complete swallowing of the granules.
• Avoid consumption of grapefruit juice for the duration of their budesonide delayed-release capsules therapy [see Drug Interactions (7.1)] . ENTOCORT is a registered trademark of Padagis US LLC. © Padagis LLC 2024 Manufactured for Padagis ® Minneapolis, MN 55427 Rev 06-24 5V000 RC PH8 2204932
Label text from the FDA structured product label by Padagis US LLC (revised Jun 5, 2024). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Budesonide in 49 products
budesonide NDC products (49)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 50090-7173 | Budesonide .25 mg/2mL Inhalant | A-S Medication Solutions | ANDA |
| 50090-6590 | Budesonide .25 mg/2mL Suspension | A-S Medication Solutions | ANDA |
| 50090-6586 | Budesonide .5 mg/2mL Suspension | A-S Medication Solutions | ANDA |
| 50090-1467 | Budesonide .25 mg/2mL Suspension | A-S Medication Solutions | ANDA |
| 0591-2510 | Budesonide 9 mg/1 Tablet, Film Coated, Extended Release | Actavis Pharma, Inc. | ANDA |
| 60687-889 | Budesonide .25 mg/2mL Suspension | American Health Packaging | ANDA |
| 60687-596 | Budesonide 3 mg/1 Capsule, Coated Pellets | American Health Packaging | ANDA |
| 65162-778 | Budesonide 3 mg/1 Capsule, Delayed Release | Amneal Pharmaceuticals LLC | ANDA |
| 53746-778 | Budesonide 3 mg/1 Capsule, Delayed Release | Amneal Pharmaceuticals of New York LLC | ANDA |
| 60505-6129 | Budesonide 32 ug/1 Spray, Metered | Apotex Corp. | ANDA |
| 59651-585 | Budesonide .5 mg/2mL Suspension | Aurobindo Pharma Limited | ANDA |
| 63629-8294 | Budesonide 3 mg/1 Capsule, Delayed Release | Bryant Ranch Prepack | ANDA |
| 55154-4849 | Budesonide .5 mg/2mL Suspension | Cardinal Health 107, LLC | ANDA |
| 62135-822 | Budesonide .25 mg/2mL Suspension | Chartwell RX, LLC | ANDA |
| 62135-823 | Budesonide .5 mg/2mL Suspension | Chartwell RX, LLC | ANDA |
| 69097-318 | Budesonide .25 mg/2mL Inhalant | Cipla USA Inc. | ANDA |
| 69097-319 | Budesonide .5 mg/2mL Inhalant | Cipla USA Inc. | ANDA |
| 69097-321 | Budesonide 1 mg/2mL Inhalant | Cipla USA Inc. | ANDA |
| 69842-001 | Budesonide 32 ug/1 Spray, Metered | CVS Pharmacy | ANDA |
| 49035-703 | Budesonide 32 ug/1 Spray, Metered | EQUATE (Wal-Mart Stores, Inc.) (see also WAL-MART INC) | ANDA |
| 76282-642 | Budesonide 1 mg/2mL Inhalant | Exelan Pharmaceuticals, Inc. | ANDA |
| 76282-640 | Budesonide .25 mg/2mL Inhalant | Exelan Pharmaceuticals, Inc. | ANDA |
| 76282-641 | Budesonide .5 mg/2mL Inhalant | Exelan Pharmaceuticals, Inc. | ANDA |
| 0904-7313 | Budesonide 3 mg/1 Capsule, Coated Pellets | Major Pharmaceuticals | ANDA |
| 0378-4500 | Budesonide 9 mg/1 Tablet, Film Coated, Extended Release | Mylan Pharmaceuticals Inc. | ANDA |
| 0487-9601 | Budesonide .25 mg/2mL Inhalant | Nephron Pharmaceuticals Corporation | ANDA |
| 0487-9701 | Budesonide .5 mg/2mL Inhalant | Nephron Pharmaceuticals Corporation | ANDA |
| 16714-829 | Budesonide 3 mg/1 Capsule, Coated Pellets | Northstar Rx LLC. | ANDA |
| 45802-627 | Budesonide 2 mg/1 Aerosol, Foam | Padagis Israel Pharmaceuticals Ltd | ANDA |
| 68788-7314 | Budesonide .5 mg/2mL Inhalant | Preferred Pharmaceuticals Inc. | ANDA |
| 70518-4613 | Budesonide 3 mg/1 Capsule, Coated Pellets | REMEDYREPACK INC. | ANDA |
| 64980-638 | Budesonide .25 mg/2mL Inhalant | Rising Pharma Holdings, Inc. | ANDA |
| 64980-639 | Budesonide .5 mg/2mL Inhalant | Rising Pharma Holdings, Inc. | ANDA |
| 0536-1112 | Budesonide 32 ug/1 Spray, Metered | Rugby Laboratories | ANDA |
| 0536-1456 | Budesonide 32 ug/1 Spray, Metered | Rugby Laboratories | ANDA |
| 47335-631 | Budesonide .25 mg/2mL Suspension | Sun Pharmaceutical Industries, Inc. | ANDA |
| 47335-632 | Budesonide .5 mg/2mL Suspension | Sun Pharmaceutical Industries, Inc. | ANDA |
| 47335-633 | Budesonide 1 mg/2mL Suspension | Sun Pharmaceutical Industries, Inc. | ANDA |
| 0093-6815 | Budesonide .25 mg/2mL Suspension | Teva Pharmaceuticals USA, Inc. | ANDA |
| 0093-6817 | Budesonide 1 mg/2mL Suspension | Teva Pharmaceuticals USA, Inc. | ANDA |
| 0093-6816 | Budesonide .5 mg/2mL Suspension | Teva Pharmaceuticals USA, Inc. | ANDA |
| 0363-0048 | Budesonide 32 ug/1 Spray, Metered | Walgreens | ANDA |
| 70771-1075 | Budesonide 3 mg/1 Capsule, Coated Pellets | Zydus Lifesciences Limited | ANDA |
| 68382-720 | Budesonide 3 mg/1 Capsule, Coated Pellets | Zydus Pharmaceuticals USA Inc. | ANDA |
| 72162-2473 | Budesonide 3 mg/1 Capsule | Bryant Ranch Prepack | NDA |
| 51407-591 | Budesonide 3 mg/1 Capsule | Golden State Medical Supply, Inc. | NDA |
| 68682-658 | Budesonide 2 mg/1 Aerosol, Foam | Oceanside Pharmaceuticals | NDA |
| 0574-9855 | Budesonide 3 mg/1 Capsule | Padagis US LLC | NDA |
| 68682-309 | Budesonide 9 mg/1 Tablet, Extended Release | Oceanside Pharmaceuticals | NDA AUTHORIZED GENERIC |
budesonide recalls
- D-0607-2026 Jun 17, 2026 · Class II · Ongoing
Presence of Foreign Substance:This recall has been initiated in response to a product quality complaint reported for black/brown specs and particles within the ampoule solution - D-0541-2025 Jul 30, 2025 · Class II · Ongoing
Lack of Assurance of Sterility: A market complaint was received for leakage and empty ampoule. - D-0275-2024 Feb 7, 2024 · Class II · Ongoing
Failed Dissolution Specifications - D-1545-2022 Oct 5, 2022 · Class II · Terminated
Lack of Assurance of Sterility
Frequently asked questions
What is budesonide used for?
Budesonide delayed-release capsules are a corticosteroid indicated for: • Treatment of mild to moderate active Crohn’s disease involving the ileum and/or the ascending colon, in patients 8 years and older. ( 1.1 ) • Maintenance of clinical remission of mild to moderate Crohn’s disease involving the ileum and/or the ascending colon for up to 3 months in adults. ( 1.2 ) 1.1 Treatment of Mild to…
What are the side effects of budesonide?
The following clinically significant adverse reactions are described elsewhere in labeling: • Hypercorticism and adrenal axis suppression [see Warnings and Precautions (5.1)] • Symptoms of steroid withdrawal in those patients transferred from other systemic corticosteroids [see Warnings and Precautions (5.2)] • Immunosuppression and increased risk of infection [see Warnings and Precautions (5.3)]… See the full label for the complete list.
Who makes budesonide?
budesonide is listed by 31 labelers in the FDA NDC directory, including A-S Medication Solutions, Actavis Pharma, Inc., American Health Packaging, Amneal Pharmaceuticals LLC.
Has budesonide been recalled?
The FDA enforcement database lists 4 recalls for budesonide, most recently D-0607-2026 (class ii): Presence of Foreign Substance:This recall has been initiated in response to a product quality complaint reported for black/brown specs and particles within the…