Uceris Tablets

White, round, biconvex extended release tablets debossed with “MX9”. Each extended release tablet contains 9 mg budesonide.

Systemic glucocorticosteroid use may result in the following:

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)

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)

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)

Postmarketing Experience

In addition to adverse events reported from clinical trials, the following adverse reactions have been identified during postapproval 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.

Gastrointestinal Disorders: diarrhea, rectal bleeding

General Disorders and Administrative Site Conditions: peripheral edema

Immune System Disorders: anaphylactic reactions

Musculoskeletal and Connective Tissue Disorders: muscle cramps/spasms

Nervous System Disorders: benign intracranial hypertension, dizziness

Psychiatric Disorders: mood swings

Skin and Subcutaneous Tissue Disorders: rash

Vascular Disorders: increased blood pressure

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)].

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), H2-blockers and antacids).

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 C25H34O6  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, 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 7.0. 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.

Induction of Remission in Active, Mild to Moderate Ulcerative Colitis

Two similarly-designed, randomized, double-blind, placebo-controlled studies were conducted in a total of 970 adult patients with active, mild to moderate ulcerative colitis (UC) which was defined as an Ulcerative Colitis Disease Activity Index (UCDAI of  ≥4 and ≤10).  Eight hundred ninety-nine of these patients had histology consistent with active UC; this was considered the primary analysis population. UCDAI is a four-component scale (total score of 0 to 12) that encompasses the clinical assessments of stool frequency, rectal bleeding, mucosal appearance and physician’s rating of disease activity (score of 0 to 3 for each of the components).

The baseline median UCDAI score in both studies was 7.

In Study 1, 56% of patients were male, and the median age was 42 years. In Study 2, 57% of patients were male, and the median age was 44 years. In Study 1, 50% of patients were Caucasian, 7% were African American, and 34% were Asian. In Study 2, more than 99% were Caucasian.

Both studies compared UCERIS 9 mg and 6 mg with placebo and included an active reference arm (a mesalamine 2.4 g in Study 1 and a budesonide* 9 mg not approved for the treatment of UC in Study 2). The primary endpoint was induction of remission after 8 weeks of treatment. Remission was defined as a UCDAI score of ≤1, with subscores of 0 for rectal bleeding, stool frequency, and mucosal appearance and with a ≥1 point reduction in an endoscopy-only score.2 In both studies, UCERIS 9 mg extended release tablets demonstrated superiority to placebo in inducing remission (Table 4).

Table 4.          Induction of Remission in Studies 1 and 2

Remission is defined as a UCDAI score of ≤1, with subscores of 0 for rectal bleeding, stool frequency, and mucosal appearance and with a ≥1 point reduction in an endoscopy-only score.2

The primary analysis population included only patients that had histology consistent with active UC.

CI=Confidence Interval

*The reference arm in Study 1 is a delayed release mesalamine 2.4 g; the reference arm in Study 2 is a budesonide 9 mg not approved for the treatment of UC.

†p<0.025 for UCERIS 9 mg vs. placebo in both Studies 1 and 2 based on the Chi-square test (alpha = 0.025)

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° to 30°C (59° to 86°F). [See USP Controlled Room Temperature].

Keep container tightly closed. Protect from light and moisture.