UCERIS

UCERIS^® (budesonide) extended release tablets are designed to target the full length of the colon using multi-matrix (MMX^®) technology.

UCERIS^® (budesonide) tablets are designed to target the full length of the colon

Utilizing multi-matrix (MMX^®) technology, UCERIS contains budesonide in an extended-release core. Therefore, the active compound is not released until it reaches the colon¹
The tablet core is coated with a film that dissolves only after exposure to a pH ≥7¹
After the coating disintegrates, the pill matrix is designed to provide extended release of budesonide throughout the full length of the colon²

MMX technology is designed to target delivery of budesonide throughout the full length of the colon.³

Important Safety Information

UCERIS extended release tablets are contraindicated in patients with hypersensitivity to budesonide or any of the ingredients of UCERIS. When glucocorticosteroids are used chronically, systemic effects such as hypercorticism and adrenal suppression may occur. Since UCERIS extended release tablets are a glucocorticosteroid, general warnings concerning glucocorticoids should be followed.

UCERIS^® (budesonide) tablets:
Pharmacokinetic profile¹

Budesonide has limited systemic glucocorticoid activity¹
Undergoes extensive first-pass metabolism in the liver
Approximately 10% of a dose is available systemically

Important Safety Information

Care is needed in patients who are transferred from glucocorticosteroid treatment with higher systemic effects to glucocorticosteroids with lower systemic effects, such as UCERIS extended release tablets, since symptoms attributed to withdrawal of steroid therapy, including those of acute adrenal suppression or benign intracranial hypertension, may develop. Taper patients slowly from systemic corticosteroids if transferring to UCERIS extended release tablets.

UCERIS^® (budesonide) tablets are effective in inducing clinical and endoscopic remission in patients with active, mild to moderate ulcerative colitis (UC)⁴

Important Safety Information

Patients who are on drugs that suppress the immune system are more susceptible to infection than healthy individuals. Glucocorticosteroids should be used with caution, if at all, in patients with active or quiescent tuberculosis infection, untreated fungal, bacterial, systemic viral or parasitic infections, or ocular herpes simplex. More serious or even fatal courses of chickenpox or measles can occur in susceptible patients.

The CORE study design

Two randomized, double-blind, placebo-controlled trials (CORE I and CORE II) in 899 adult patients with active, mild to moderate UC^1,2,4,5,*
Rigorous primary endpoint assessed after 8 weeks of treatment
Induction of combined clinical and endoscopic remission^1,2,4,5
Remission was defined as an Ulcerative Colitis Disease Activity Index (UCDAI) score of ≤1, with scores of 0 for both rectal bleeding and stool frequency, normal mucosa with no friability on endoscopy, and ≥ 1-point reduction in the endoscopic index (EI) score^1,2,4,5

UCDAI at study entry was ≥4 and ≤10.

Baseline disease severity

Active UC

Active, mild to moderate UC^1,5

(UCDAI score between 4 and 10)

Median disease activity score consistent with mild to moderate UC (UCDAI score of 7 on a scale of 0-12¹)

Primary endpoint

Normal mucosa with no friability

Remission of UC^1,5

(Including UCDAI score of ≤1)^*
Improvement in Endoscopic Index
(≥1-point reduction in EI score)

Rigorous primary endpoint assessed combined clinical and endoscopic remission

Endoscopic images are not from study patients.

Important Safety Information

Patients with moderate to severe liver disease should be monitored for increased signs and/or symptoms of hypercorticism.

UCERIS^® (budesonide) tablets: Efficacy^†

IN STUDY 1

UCERIS 9 mg induced remission in 17.9% of patients (n/N; 22/123) compared with 7.4% (9/121) of patients taking placebo at 8 weeks (P=0.0143)^1,5

IN STUDY 2

UCERIS induced remission in 17.4% (19/109) of patients versus 4.5% (4/89) of placebo-treated patients at 8 weeks (P=0.005)^1,2

Three times more patients taking UCERIS achieved clinical and endoscopic remission versus placebo^4,†

In a pooled analysis of 2 Phase III trials.⁴

PRIMARY ENDPOINT: COMBINED CLINICAL AND ENDOSCOPIC REMISSION AT 8 WEEKS

18%

6%

Sources: UCERIS Prescribing Information¹; Sandborn 2015.⁴

Important Safety Information

Caution should be taken in patients with hypertension, diabetes mellitus, osteoporosis, peptic ulcer, glaucoma or cataracts, or with a family history of diabetes or glaucoma, or with any other condition where glucocorticosteroids may have unwanted effects.

UCERIS^® (budesonide) tablets:
Adverse Event Profile

Overall glucocorticosteroid-related side effects occurred at similar rates with UCERIS 9-mg tablets and placebo at 8 weeks¹

GLUCOCORTICOID-RELATED SIDE EFFECTS WITH UCERIS 9 MG AND PLACEBO^‡

10.2

10.5

3.5

4.3

2.7

4.7

2.4

3.1

2.4

1.9

1.2

1.6

Source: UCERIS Prescribing Information.¹

In a pooled analysis of 2 Phase III trials.

UCERIS^® (budesonide) tablets:
Adverse reactions at 8 weeks

summary of adverse reactions experienced by ≥3% of patients taking uceris 9 mg in 2 placebo-controlled trials

	UCERIS 9 mg (n=255) n (%)	PLACEBO (n=258) n (%)
Headache	29(11.4)	27(10.5)
Nausea	13 (5.1)	11 (4.3)
Decreased blood cortisol	11 (4.3)	1 (0.4)
Upper abdominal pain	10 (3.9)	5 (1.9)
Fatigue	8 (3.1)	5 (1.9)

Source: UCERIS Prescribing Information.¹

Important Safety Information

Concomitant use of inhibitors of Cytochrome P450 3A4 (for example ketoconazole and erythromycin) should be avoided and 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.

Glucocorticoid-related side effects of UCERIS^® (budesonide) tablets 6 mg from a 12-month safety study^§

Glucocorticoid-related side effects occurred at similar rates with UCERIS 6 mg tablets and placebo¹

GLUCOCORTICOID-RELATED SIDE EFFECTS WITH UCERIS 6 MG AND PLACEBO

14.5

11.5

6.5

3.3

4.8

4.9

6.5

6.6

4.8

0

4.8

4.9

Source: UCERIS Prescribing Information.¹

The recommended dosage for the induction of remission in adult patients with active, mild to moderate UC is one 9-mg tablet to be taken once daily for up to 8 weeks¹
The UCERIS long-term safety data were evaluated in a placebo-controlled 12-month study and used the 6-mg dose. The 6-mg dose is not currently approved in the United States^1,§

Normal bone density was reported in 77% (27/35) and 74% (29/39) of patients taking UCERIS 6 mg and placebo, respectively.¹

Important Safety Information

In clinical studies, the most common adverse reactions (incidence ≥ 2%) were headache, nausea, decreased blood cortisol, upper abdominal pain, fatigue, flatulence, abdominal distension, acne, urinary tract infection, arthralgia, and constipation.

Emily H^||

Physical Exam

Temp: 97.6°F

BP: 110/72 mm Hg

UCDAI Score: 5

Laboratory Results

CBC/Differential: Within normal limits

ESR/CRP: 20 mm/hr; 4 mg/dL

CrCL : 125 mL/min

LFT panel: Within normal limits

Lipid panel: Within normal limits

Stool test:(-) Escherichia coli;
(-) Clostridium difficile; (-) RBC

Pregnancy test: hCG level:<5mlU/mL; negative

Background

Emily is a 29-year-old entrepreneur who owns a catering business and travels frequently for personal deliveries. She is newly married and is looking forward to her next vacation with her husband.

Chief Complaints

Fatigue, nausea, abdominal pain with mild diarrhea, unexplained weight loss.

Past Medical History

Anemia

Current Medications

Iron
Vitamin B₁₂ supplement

Treatment Decision

Colonoscopy reveals that Emily has mildly active UC
Emily will be started on one UCERIS 9-mg tablet daily in the morning for up to 8 weeks to induce remission
Emily prefers taking oral medication with her busy travel schedule

BP = blood pressure; CBC = complete blood count; CrCL = creatinine clearance; CRP = c-reactive protein; ESR = erythrocyte sedimentation rate; hCG = human chorionic gonadotropin; LFT = liver function test; RBC = red blood cells; Temp = temperature; UC = ulcerative colitis; UCDAI = Ulcerative Colitis Disease Activity Index.

Fictitious patient. This case study is not intended to instruct any healthcare provider in the treatment of any illness nor is it meant to substitute for medical training or to be relied upon in treating any individual patient.

Ray S^||

Physical Exam

Temp: 98.6°F

BP: 140/82 mm Hg

UCDAI Score: 8

Laboratory Results

CBC/Differential:

Hgb: 12.1 g/dL;

WBC > 10,000 cells/mL

ESR/CRP: 25 mm/hr; 8 mg/dL

CrCL: 102 mL/min

LFT panel: Within normal limits

Lipid panel:

TC: 174 mmol/L

TG: 155 mmol/L

HDL: 45 mmol/L

LDL: 98 mmol/L

Stool test: (-) Escherichia coli; (-) Clostridium difficile; (+) RBC

Background

Ray is a 52-year-old insurance agent who works long hours. He likes to eat out and drink socially.

Chief Complaints

Abdominal pain and diarrhea a few times per day for the past 2 weeks. These symptoms had occurred briefly a few months prior to the office visit, but resolved on their own. Recently, streaks of blood in his stools have been noted more frequently.

Past Medical History

UC (diagnosed at age 43)
Hyperlipidemia
GERD

Current Medications

Statin
OTC proton pump inhibitor
Multivitamin

Treatment Decision

Colonoscopy confirmed marked erythema and erosions; biopsy confirms moderately active UC
Ray will be started on one UCERIS 9-mg tablet daily in the morning for up to 8 weeks to induce remission
Ray's doctor advised him to keep a food diary to see what foods might affect symptoms and to limit stress as much as possible

BP = blood pressure; CBC = complete blood count; CrCL = creatinine clearance; CRP = c-reactive protein; ESR = erythrocyte sedimentation rate; GERD = gastroesophageal reflux disease; hCG = human chorionic gonadotropin; HDL = high density lipoprotein; Hgb = hemoglobin; LDL = low density lipoprotein; LFT = liver function test; OTC = over-the-counter; RBC = red blood cells; TC = total cholesterol; Temp = temperature; TG = triglycerides; UC = ulcerative colitis; UCDAI = Ulcerative Colitis Disease Activity Index; WBC = white blood cell count.

Fictitious patient. This case study is not intended to instruct any healthcare provider in the treatment of any illness nor is it meant to substitute for medical training or to be relied upon in treating any individual patient.

Important Safety Information

UCERIS extended release tablets are contraindicated in patients with hypersensitivity to budesonide or any of the ingredients of UCERIS. When glucocorticosteroids are used chronically, systemic effects such as hypercorticism and adrenal suppression may occur. Since UCERIS extended release tablets are a glucocorticosteroid, general warnings concerning glucocorticoids should be followed.

UCERIS^® (budesonide) TABLETS
ARE A LOW-COST OPTION

Most eligible patients
with commercial insurance
will pay only

^$25^¶

Some restrictions apply. Please see the eVoucherRx^™ and Instant Savings Card Program brochure for Terms and Conditions. Salix Pharmaceuticals, Inc. reserves the right to modify or cancel these offerings at any time.

MPR MONOGRAPH

Company:	Santarus, Inc.^#
Pharmacologic class:	Glucocorticosteroid
Active IngRedient:	Budesonide 9 mg; extended release tablets.
Indication:	Induction of remission in patients with active, mild to moderate ulcerative colitis.
Adults:	Swallow whole. 9 mg once daily in the AM for up to 8 weeks.
Children:	Not established.
Contraindications:	Known hypersensitivity to budesonide or any of the ingredients in UCERIS tablets.
WARNINGS AND PRECAUTIONS:	Hypercorticism and adrenal suppression. Supplement with systemic glucocorticosteroid in surgery or other stress situations. Caution when transferring from steroids with high systemic availability (monitor). May unmask allergies previously controlled by systemic corticosteroids. Immunosuppression. Potential worsening of infections. Active or quiescent tuberculosis, untreated fungal, bacterial, systemic viral or parasitic infections. If exposed to chickenpox or measles, consider immune globulin or antiviral prophylactic therapies. Hypertension. Diabetes. Osteoporosis. Peptic ulcer. Glaucoma. Cataracts. Moderate-to-severe liver disease: monitor for hypercorticism; consider discontinuing. Elderly. Pregnancy (Cat. C). Nursing mothers: not recommended.
Interactions:	May be potentiated by CYP3A4 inhibitors (eg, ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, erythromycin); consider discontinuing. Avoid grapefruit or grapefruit juice. May be affected by gastric acid reducing agents (eg, PPIs, H₂-blockers, antacids).
Adverse reactions:	Headache, nausea, decreased blood cortisol, upper abdominal pain, fatigue, flatulence, abdominal distension, acne, urinary tract infection, arthralgia, constipation.
How Supplied:	Tablets—30/bottle

Santarus, Inc. is a wholly owned subsidiary of Salix Pharmaceuticals, Inc

REFERENCES

UCERIS [prescribing information]. Raleigh, NC: Salix Pharmaceuticals, Inc.; 2013
Travis SP, Danese S, Kupcinskas L, et al. Once-daily budesonide MMX in active, mild-to-moderate ulcerative colitis: results from the randomised CORE II study. Gut. 2014;63(3):433-441.
Brunner M, Ziegler S, Di Stefano AF, et al. Gastrointestinal transit, release and plasma pharmacokinetics of a new oral budesonide formulation. Br J Clin Pharmacol. 2006;61(1):31-38.
Sandborn WJ, Danese S, D'Haens G, et al. Induction of clinical and colonoscopic remission of mild-to-moderate ulcerative colitis with budesonide MMX 9 mg: pooled analysis of two phase 3 studies. Aliment Pharmacol Ther. 2015;41(5):409-418.
Sandborn WJ, Travis S, Moro L, et al. Once-daily budesonide MMX^® extended-release tablets induce remission in patients with mild to moderate ulcerative colitis: results from the CORE I study. Gastroenterology. 2012;143(5):1218-1226.

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This MPR Prescribing Alert is produced as a basic reminder of important information for healthcare professionals. Readers are advised to consult manufacturers and specialists if questions arise about specific products, treatments, or diseases. The publisher and editors do not assume liability for any errors or omissions. MPR and MPR Prescribing Alert are registered trademarks of Haymarket Media, Inc.

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UCERIS® (budesonide) tablets are effective in inducing clinical and endoscopic remission in patients with active, mild to moderate ulcerative colitis (UC)4

UCERIS^® (budesonide) tablets are effective in inducing clinical and endoscopic remission in patients with active, mild to moderate ulcerative colitis (UC)⁴