Uceris

budesonide · Aerosol, Foam · Rectal, Oral

Uses

1 INDICATIONS AND USAGE UCERIS ® extended-release tablets are indicated for the induction of remission in patients with active, mild to moderate ulcerative colitis. UCERIS (budesonide) is a glucocorticosteroid indicated for the induction of remission in patients with active, mild to moderate ulcerative colitis. ( 1 )

Dosage and administration

The recommended dosage for the induction of remission in adult patients with active, mild to moderate ulcerative colitis is one 9 mg tablet to be taken once daily in the morning with or without food for up to 8 weeks. ( 2.1 ) 2.1 Mild to Moderate Ulcerative Colitis The recommended dosage for the induction of remission in adult patients with active, mild to moderate ulcerative colitis is 9 mg taken orally once daily in the morning with or without food for up to 8 weeks. UCERIS should be swallowed whole and not chewed or crushed. 2.2 CYP3A4 Inhibitors If concomitant administration with ketoconazole, or any other CYP3A4 inhibitor, is indicated, patients should be closely monitored for increased signs and/or symptoms of hypercorticism. Avoid grapefruit juice, which is known to inhibit CYP3A4, when taking UCERIS. In these cases, discontinuation of UCERIS or the CYP3A4 inhibitor should be considered [see Drug Interactions ( 7 ) and Clinical Pharmacology ( 12.3 )]. 2.1 Mild to Moderate Ulcerative Colitis The recommended dosage for the induction of remission in adult patients with active, mild to moderate ulcerative colitis is 9 mg taken orally once daily in the morning with or without food for up to 8 weeks. UCERIS should be swallowed whole and not chewed or crushed. 2.2 CYP3A4 Inhibitors If concomitant administration with ketoconazole, or any other CYP3A4 inhibitor, is indicated, patients should be closely monitored for increased signs and/or symptoms of hypercorticism. Avoid grapefruit juice, which is known to inhibit CYP3A4, when taking UCERIS. In these cases, discontinuation of UCERIS or the CYP3A4 inhibitor should be considered [see Drug Interactions ( 7 ) and Clinical Pharmacology ( 12.3 )].

Dosage forms and strengths

White, round, biconvex extended-release tablets debossed with “MX9” . Each extended-release tablet contains 9 mg budesonide. Extended-release tablets: 9 mg ( 3 )

Contraindications

4 CONTRAINDICATIONS UCERIS is contraindicated in patients with hypersensitivity to budesonide or any of the ingredients of UCERIS. Anaphylactic reactions have occurred with other budesonide formulations [see Adverse Reactions ( 6.2 )]. Known hypersensitivity to budesonide or any of the ingredients in UCERIS tablets ( 4 )

Warnings and precautions

Hypercorticism and adrenal suppression : May occur with treatment; monitor for signs and symptoms. ( 5.1 ) Transferring patients from systemic glucocorticoids: Risk of impaired adrenal function when transferring from glucocorticoid treatment with higher systemic effects to glucocorticoid treatment with lower systemic effects, such as UCERIS. Taper patients slowly from systemic corticosteroids if transferring to UCERIS. ( 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) Kaposi’s Sarcoma: Reported to occur in patients receiving corticosteroid therapy, most often for chronic conditions. (5.4) 5.1 Hypercorticism and Adrenal Axis Suppression Systemic effects such as hypercorticism and adrenal suppression may occur with use corticosteroids, including UCERIS. Monitor patients for signs and symptoms of hypercorticism and adrenal axis suppression during treatment with UCERIS. Patients with moderate to severe liver disease should be monitored for increased signs and/or symptoms of hypercorticism. Discontinuing the use of UCERIS tablets should be considered in these patients [see Use in Specific Populations (8.6)]. Glucocorticosteroids, including UCERIS, 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 glucocorticosteroid is recommended. 5.2 Transferring Patients from Systemic Glucocorticosteroid Therapy Care is needed in patients who are transferred from glucocorticosteroid treatment with higher systemic effects to glucocorticosteroids with lower systemic effects, such as UCERIS, since symptoms attributed to withdrawal of steroid therapy, including those of acute adrenal suppression or benign intracranial hypertension, may develop. Adrenocortical function monitoring may be required in these patients, and the dose of glucocorticosteroid treatment with high systemic effects should be reduced cautiously. Replacement of systemic glucocorticosteroids with UCERIS tablets 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 UCERIS, 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 UCERIS if the patient develops an infection while on treatment. Tuberculosis If UCERIS is used in patients with latent tuberculosis or tuberculin reactivity, reactivation of tuberculosis may occur. Closely monitor such patients for reactivation. During prolonged UCERIS 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 patients taking corticosteroids, including UCERIS. 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 a UCERIS-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 a UCERIS-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 UCERIS. 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 UCERIS. 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, including UCERIS, may exacerbate systemic fungal infections; therefore, avoid UCERIS use in the presence of such infections. For patients on chronic UCERIS therapy who develop systemic fungal infections, UCERIS withdrawal or dosage reduction is recommended. Amebiasis Corticosteroids, including UCERIS, may activate latent amebiasis. Therefore, it is recommended that latent amebiasis or active amebiasis be ruled out before initiating UCERIS in patients who have spent time in the tropics or patients with unexplained diarrhea. Strongyloides Infestation Avoid UCERIS in patients with known or suspected Strongyloides (threadworm) infection. Corticosteroids-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 UCERIS, in patients with cerebral malaria.

Side effects

Systemic glucocorticosteroid use may result in the following: Hypercorticism and Adrenal Suppression [see Warnings and Precautions ( 5.1 )] Symptoms of steroid withdrawal in those patients transferring from Systemic Glucocorticosteroid Therapy [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 )] Increased Systemic Glucocorticoid Susceptibility [see Warnings and Precautions ( 5.5 )] Other Glucocorticosteroid Effects [see Warnings and Precautions ( 5.6 )] Most common adverse reactions (incidence ≥2%) are headache, nausea, decreased blood cortisol, upper abdominal pain, fatigue, flatulence, abdominal distension, acne, urinary tract infection, arthralgia, and constipation. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Salix Pharmaceuticals at 1-800-321-4576 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. The safety of UCERIS has been evaluated in controlled and open-label clinical trials which enrolled a combined total of 1,105 patients with ulcerative colitis. In two 8-week, placebo-controlled studies in patients with active disease (Study 1 and Study 2), a total of 255 patients received UCERIS 9 mg, 254 patients received UCERIS 6 mg, and 258 patients received placebo. They ranged in age from 18-77 years (mean=43), 56% were male, and 75% were Caucasian. The most common adverse reactions were headache, nausea, decreased blood cortisol, upper abdominal pain, fatigue, flatulence, abdominal distension, acne, urinary tract infection, arthralgia, and constipation. The adverse reactions occurring in 2% or more of patients on therapy with UCERIS 9 mg are summarized in Table 1. Table 1: Summary of Adverse Reactions in Two Placebo-Controlled Trials Experienced by at Least 2% of the UCERIS 9 mg Group (Studies 1 and 2) UCERIS 9 mg (N=255) n (%) UCERIS 6 mg (N=254) n (%) Placebo (N=258) n (%) Headache 29 (11.4) 37 (14.6) 27 (10.5) Nausea 13 (5.1) 12 (4.7) 11 (4.3) Decreased blood cortisol 11 (4.3) 6 (2.4) 1 (0.4) Upper abdominal pain 10 (3.9) 8 (3.1) 5 (1.9) Fatigue 8 (3.1) 5 (2.0) 5 (1.9) Flatulence 6 (2.4) 8 (3.1) 5 (1.9) Abdominal distension 6 (2.4) 4 (1.6) 2 (0.8) Acne 6 (2.4) 2 (0.8) 5 (1.9) Urinary tract infection 5 (2.0) 1 (0.4) 1 (0.4) Arthralgia 5 (2.0) 5 (2.0) 4 (1.6) Constipation 5 (2.0) 1 (0.4) 2 (0.8) Of UCERIS 9 mg patients, a total of 15% discontinued treatment due to any adverse event (including adverse reactions) compared with 17% in the placebo group. Table 2 summarizes the percentages of patients reporting glucocorticoid-related effects in the 2 placebo-controlled studies. Table 2: Summary of Glucocorticoid-Related Effects in Two Placebo-Controlled Trials (Studies 1 and 2) UCERIS 9 mg (N=255) n (%) UCERIS 6 mg (N=254) n (%) Placebo (N=258) n (%) Overall 26 (10.2) 19 (7.5) 27 (10.5) Mood changes 9 (3.5) 10 (3.9) 11 (4.3) Sleep changes 7 (2.7) 10 (3.9) 12 (4.7) Insomnia 6 (2.4) 6 (2.4) 8 (3.1) Acne 6 (2.4) 2 (0.8) 5 (1.9) Moon face 3 (1.2) 3 (1.2) 4 (1.6) Fluid retention 2 (0.8) 3 (1.2) 3 (1.2) Hirsutism 1 (0.4) 0 0 Striae rubrae 0 0 2 (0.8) Flushing 0 1 (0.4) 3 (1.2) No clinically significant differences were observed with respect to the overall percentages of patients with any glucocorticoid-related effects between UCERIS and placebo after 8 weeks of induction therapy. Study 3 was an open-label study evaluating UCERIS 9 mg once daily for 8 weeks in 60 patients who had previously completed an 8-week induction study (Study 1) but had not achieved remission. Among patients who took UCERIS 9 mg up to 16 weeks cumulatively across Study 1 and Study 3 combined, similar rates of adverse reactions and glucocorticoid-related effects were seen compared to those who took UCERIS 9 mg for 8 weeks in Study 1. In Study 4, the safety of long-term treatment with UCERIS 6 mg was evaluated in a placebo-controlled 12-month maintenance study of 123 patients. Patients who had previously completed 8 weeks of therapy in any induction study (Study 1, 2, or 3) and were in remission were randomized to UCERIS 6 mg or placebo once daily for 12 months. In patients who took UCERIS 6 mg for up to 12 months, similar rates of adverse reactions were seen between placebo and UCERIS 6 mg. After up to 12 months of study treatment, 77% (27/35) of the patients in the UCERIS 6 mg and 74% (29/39) of the patients in the placebo treatment groups had normal bone density scans. In Study 4, the glucocorticoid-related effects were similar in patients with up to 12 months of therapy with UCERIS 6 mg and placebo (Table 3). Table 3: Summary of Glucocorticoid-Related Effects Over 12-Month Treatment (Study 4) UCERIS 6 mg (N=62) n (%) Placebo (N=61) n (%) Overall 9 (14.5) 7 (11.5) Insomnia 4 (6.5) 4 (6.6) Mood changes 4 (6.5) 2 (3.3) Moon face 3 (4.8) 3 (4.9) Sleep changes 3 (4.8) 3 (4.9) Acne 3 (4.8) 0 Hirsutism 3 (4.8) 0 Flushing 1 (1.6) 1 (1.6) Fluid retention 1 (1.6) 1 (1.6) 6.2 Postmarketing Experience In addition to adverse events reported from clinical trials, the following adverse reactions have been identified during post-approval use of oral budesonide. 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. These events have been chosen for inclusion due to either their seriousness, frequency of reporting or causal connection to UCERIS, or a combination of these factors.

Drug interactions

Avoid cytochrome P450 3A4 inhibitors (e.g., ketoconazole, grapefruit juice). May cause increased systemic corticosteroid effects. ( 2.2 , 7 , 12.3 ) 7.1 Interaction with CYP3A4 Inhibitors Concomitant oral administration of ketoconazole (a known inhibitor of CYP3A4 activity in the liver and in the intestinal mucosa) caused an eight-fold increase of the systemic exposure to oral budesonide. If treatment with inhibitors of CYP3A4 activity (such as ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, erythromycin) is indicated, discontinuation of UCERIS should be considered. After extensive intake of grapefruit juice (which inhibits CYP3A4 activity predominantly in the intestinal mucosa), the systemic exposure for oral budesonide increased about two times. Ingestion of grapefruit or grapefruit juice should be avoided in connection with UCERIS administration [see Dosage and Administration ( 2 ) and Clinical Pharmacology ( 12.3 )]. 7.2 Inhibitors of Gastric Acid Secretion Since the dissolution of the coating of UCERIS is pH dependent, the release properties and uptake of the compound may be altered when UCERIS is used after treatment with gastric acid reducing agents (e.g., proton pump inhibitors (PPIs), H 2 blockers and antacids). 7.1 Interaction with CYP3A4 Inhibitors Concomitant oral administration of ketoconazole (a known inhibitor of CYP3A4 activity in the liver and in the intestinal mucosa) caused an eight-fold increase of the systemic exposure to oral budesonide. If treatment with inhibitors of CYP3A4 activity (such as ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, erythromycin) is indicated, discontinuation of UCERIS should be considered. After extensive intake of grapefruit juice (which inhibits CYP3A4 activity predominantly in the intestinal mucosa), the systemic exposure for oral budesonide increased about two times. Ingestion of grapefruit or grapefruit juice should be avoided in connection with UCERIS administration [see Dosage and Administration ( 2 ) and Clinical Pharmacology ( 12.3 )]. 7.2 Inhibitors of Gastric Acid Secretion Since the dissolution of the coating of UCERIS is pH dependent, the release properties and uptake of the compound may be altered when UCERIS is used after treatment with gastric acid reducing agents (e.g., proton pump inhibitors (PPIs), H 2 blockers and antacids).

Use in specific populations

Pregnancy: Based on animal data, may cause fetal harm. ( 8.1 ) Hepatic Impairment : Monitor patients for signs and/or symptoms of hypercorticism. ( 5.5 , 8.6 ) 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, subcutaneous administration of budesonide during organogenesis at doses 0.5 times and 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 Embryofetal Risk Published data suggest that increased disease activity is associated with the risk of developing adverse pregnancy outcomes in women with ulcerative colitis. Adverse pregnancy outcomes include preterm delivery (before 37 weeks of gestation), low birth weight (less than 2500 g) infants, and small for gestational age at birth. 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 embryofetal 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 embryofetal 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 postnatal 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 UCERIS or other oral budesonide products and no information is available on the effects of budesonide 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 UCERIS and any potential adverse effects on the breastfed infant from UCERIS, 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 UCERIS is higher (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 5 to 10 nmol/L which is up to 10 times higher than the 1 to 2 nmol/L 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 UCERIS, budesonide exposure to the nursing child may be up to 10 times higher than that by budesonide inhalation. 8.4 Pediatric Use Safety and effectiveness of UCERIS in pediatric patients have not been established. Glucocorticosteroids, such as UCERIS, may cause a reduction of growth velocity in pediatric patients. 8.5 Geriatric Use Clinical studies of UCERIS did not include sufficient numbers of subjects aged 65 and older to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.

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, subcutaneous administration of budesonide during organogenesis at doses 0.5 times and 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 Embryofetal Risk Published data suggest that increased disease activity is associated with the risk of developing adverse pregnancy outcomes in women with ulcerative colitis. Adverse pregnancy outcomes include preterm delivery (before 37 weeks of gestation), low birth weight (less than 2500 g) infants, and small for gestational age at birth. 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 embryofetal 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 embryofetal 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 postnatal 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 Safety and effectiveness of UCERIS in pediatric patients have not been established. Glucocorticosteroids, such as UCERIS, may cause a reduction of growth velocity in pediatric patients.

Geriatric use

8.5 Geriatric Use Clinical studies of UCERIS did not include sufficient numbers of subjects aged 65 and older to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, UCERIS should be used cautiously in elderly patients due to the potential for 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 glucocorticosteroids are rare. Treatment consists of immediate gastric lavage or emesis followed by supportive and symptomatic therapy. If glucocorticosteroids are used at excessive doses for prolonged periods, systemic glucocorticosteroid effects, such as hypercorticism and adrenal suppression may occur. For chronic overdosage in the face of severe disease requiring continuous steroid therapy, the dosage may be reduced temporarily. Single oral budesonide 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

11 DESCRIPTION UCERIS ® (budesonide) extended-release tablets, for oral administration, contain budesonide, a synthetic corticosteroid, as the active ingredient. 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, odorless, crystalline powder that is practically insoluble in water, sparingly soluble in alcohol, and freely soluble in chloroform. UCERIS, a delayed and extended-release tablet, is coated with a polymer film, which breaks down at or above pH 7. The tablet core contains budesonide with polymers that provide for extended release of budesonide. Each tablet contains the following inactive ingredients: stearic acid, lecithin, microcrystalline cellulose, hydroxypropyl cellulose, lactose, silicon dioxide, magnesium stearate, methacrylic acid copolymer types A and B, talc, triethyl citrate, and titanium dioxide. uceris-1.jpg

Mechanism of action

12.1 Mechanism of Action Budesonide has a high topical glucocorticosteroid (GCS) activity and substantial first-pass elimination. The formulation contains budesonide in an extended-release tablet core. The tablet core is enteric coated to protect dissolution in gastric juice which delays budesonide release until exposure to a pH ≥7 in the small intestine. Upon disintegration of the coating, the core matrix provides extended release of budesonide in a time dependent manner.

How supplied

16 HOW SUPPLIED/STORAGE AND HANDLING UCERIS ® (budesonide) extended-release tablets 9 mg are white, round, biconvex tablets and debossed with “MX9”. They are supplied as follows: NDC 68012-309-30 Bottles of 30 tablets Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). [See USP Controlled Room Temperature]. Keep container tightly closed. Protect from light and moisture.

Patient information

Advise the patient to read the FDA-approved patient labeling (Patient Information). Patients treated with UCERIS extended-release tablets should receive the following information and instructions. This information is intended to aid the patient in the safe and effective use of UCERIS. Hypercorticism and Adrenal Suppression Advise patients that UCERIS extended-release tablets may cause systemic glucocorticosteroid effects of hypercorticism and adrenal suppression. Taper slowly from systemic corticosteroids if transferring to UCERIS extended-release tablets [see Warnings and Precautions ( 5.1 ) and ( 5.2 )] . Immunosuppression and Increased Risk of Infection Advise patients to avoid exposure to people with varicella (chicken pox) or measles. Advise patients to inform their healthcare provider if they are exposed to varicella or measles or 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 )]. How to Take UCERIS Extended-Release Tablets Advise patients to swallow UCERIS extended-release tablets whole with water. Do not chew or crush. Avoid the consumption of grapefruit juice for the duration of UCERIS therapy [see Dosage and Administration (2)] . Pregnancy Advise female patients that UCERIS may cause fetal harm and to inform their healthcare provider with a known or suspected pregnancy [see Use in Specific Populations ( 8.1 )] . Distributed by: Salix Pharmaceuticals, a division of Bausch Health US, LLC Bridgewater, NJ 08807 USA Manufactured by: Cosmo S.p.A. Milan, 20045 Italy By license of Cosmo Technologies Ltd., Dublin, Ireland Patented. See https://patents.salix.com for US patent information. UCERIS is a trademark of Salix Pharmaceuticals, Inc. or its affiliates. © 2024 Salix Pharmaceuticals, Inc. or its affiliates 9464204

Label text from the FDA structured product label by Santarus Inc. (revised Oct 21, 2024). Long sections are shortened; the complete label is on DailyMed.

Active ingredients

Budesonide in 2 products

Uceris NDC products (2)

NDC	Strength & form	Labeler	Type
65649-651	Budesonide 2 mg/1 Aerosol, Foam	Salix Pharmaceuticals, Inc.	NDA
68012-309	Budesonide 9 mg/1 Tablet, Extended Release	Santarus Inc.	NDA

Frequently asked questions

What is Uceris used for?

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Who makes Uceris?

Uceris is listed by 2 labelers in the FDA NDC directory, including Salix Pharmaceuticals, Inc., Santarus Inc..