Uceris - Drug Monograph

Introduction

Uceris (budesonide) is a locally acting corticosteroid specifically formulated for targeted delivery in the gastrointestinal tract. It represents a significant advancement in the treatment of inflammatory bowel diseases, offering the anti-inflammatory benefits of corticosteroids with reduced systemic exposure. The unique multi-matrix (MMX) delivery system allows for controlled release throughout the colon, making it particularly valuable for ulcerative colitis management.

Mechanism of Action

Budesonide, the active ingredient in Uceris, exerts its therapeutic effects through potent glucocorticoid receptor agonism. The drug binds to cytoplasmic glucocorticoid receptors, forming complexes that translocate to the cell nucleus. These complexes modulate gene transcription by binding to glucocorticoid response elements, ultimately leading to:

• Downregulation of pro-inflammatory cytokine production (IL-1, IL-6, TNF-α)
• Inhibition of inflammatory cell migration and activation
• Stabilization of lysosomal membranes
• Reduction in capillary permeability

The MMX technology ensures that budesonide is released primarily in the distal ileum and colon, maximizing local anti-inflammatory effects while minimizing systemic absorption.

Indications

Uceris is FDA-approved for:

• Induction of remission in patients with active, mild to moderate ulcerative colitis

Off-label uses (with varying evidence):

• Microscopic colitis (lymphocytic and collagenous colitis)
• Crohn's disease (limited evidence, not first-line)

Dosage and Administration

• Ulcerative colitis: 9 mg orally once daily in the morning
• Treatment duration: Up to 8 weeks for induction therapy

• Take tablet whole with water; do not crush, chew, or break
• Administer in the morning, with or without food
• Swallow tablet whole; do not consume grapefruit juice concurrently

• Hepatic impairment: Use with caution in severe impairment
• Renal impairment: No dosage adjustment necessary
• Elderly: No specific dosage adjustment required
• Pediatrics: Safety and effectiveness not established

Pharmacokinetics

• Minimal systemic absorption (approximately 9-21% of administered dose)
• Extensive first-pass metabolism (approximately 90%)

• Protein binding: 85-90%
• Volume of distribution: 2.2-3.9 L/kg

• Extensive hepatic metabolism via CYP3A4
• Primary metabolites: 16α-hydroxyprednisolone and 6β-hydroxybudesonide

• Half-life: 2-3 hours
• Excretion: Primarily fecal (60%), renal (≤10%)
• Clearance: 0.9-1.8 L/min

Contraindications

• Hypersensitivity to budesonide or any component of the formulation
• Untreated systemic fungal, bacterial, viral, or parasitic infections
• Active or latent tuberculosis (unless receiving appropriate anti-tuberculosis treatment)

Warnings and Precautions

Drug Interactions

• Ketoconazole, itraconazole, clarithromycin, ritonavir
• May significantly increase budesonide exposure
• Avoid concomitant use or consider dosage reduction

• Erythromycin, fluconazole, diltiazem
• Monitor for increased corticosteroid effects

• Warfarin: May alter anticoagulant effect
• Live vaccines: Avoid administration during treatment
• Potassium-depleting agents: Enhanced hypokalemia risk

Adverse Effects

• Headache (15%)
• Nausea (8%)
• Fatigue (5%)
• Abdominal pain (5%)
• Flatulence (5%)

• Insomnia
• Anxiety
• Acne
• Tremor
• Peripheral edema

• Adrenal suppression
• Hypercorticism
• Severe infections
• Anaphylaxis
• Osteoporosis with long-term use
• Ophthalmic complications

Monitoring Parameters

• Complete blood count
• Electrolytes, glucose
• Blood pressure
• Bone density (if long-term use anticipated)
• Tuberculosis screening (if indicated)

• Clinical symptoms improvement
• Signs of adrenal insufficiency (fatigue, weakness, hypotension)
• Blood glucose levels (in diabetic patients)
• Blood pressure monitoring
• Signs of infection
• Ophthalmic examinations with prolonged use

• Adrenal function assessment if symptoms suggest insufficiency
• Clinical relapse monitoring

Patient Education

• Take exactly as prescribed; do not exceed recommended duration
• Swallow tablet whole with water; do not crush or chew
• Take in the morning with or without food

• Avoid grapefruit and grapefruit juice during treatment
• Inform all healthcare providers about Uceris use
• Report any signs of infection (fever, sore throat) immediately
• Notify physician if surgery or emergency care is needed

• Maintain adequate calcium and vitamin D intake
• Regular weight-bearing exercise to support bone health
• Monitor for mood changes or sleep disturbances

• Severe abdominal pain
• Bloody stools worsening
• Signs of allergic reaction
• Unexplained weight gain or swelling
• Vision changes

• Discuss with healthcare provider before conception
• Use during pregnancy only if clearly needed
• Budesonide excreted in breast milk; use caution while nursing

References

1. Sandborn WJ, Travis S, Danese S, et al. Once-daily budesonide MMX® extends time to relapse in patients with mild-to-moderate ulcerative colitis: a combined analysis of two phase 3 studies. Aliment Pharmacol Ther. 2019;50(5):519-531.

2. Lichtenstein GR, Travis S, Danese S, et al. Budesonide MMX for the induction of remission of mild to moderate ulcerative colitis: a pooled safety analysis. J Crohns Colitis. 2015;9(9):738-746.

3. Uceris [package insert]. Raleigh, NC: Salix Pharmaceuticals; 2023.

4. Travis SPL, 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.

5. Kane SV, Bjorkman DJ. The efficacy and safety of budesonide MMX in ulcerative colitis. Expert Rev Gastroenterol Hepatol. 2015;9(6):721-727.

6. FDA Approved Drug Products: Uceris (budesonide) extended-release tablets. Accessed January 2024.