Pentasa - Drug Monograph

Introduction

Pentasa (mesalamine) is an aminosalicylate medication used primarily in the management of inflammatory bowel diseases. It is specifically formulated with a unique controlled-release delivery system that targets drug release throughout the gastrointestinal tract, making it particularly effective for both colonic and small intestinal inflammation.

Mechanism of Action

Pentasa's active component, mesalamine (5-aminosalicylic acid or 5-ASA), exerts its therapeutic effects through local anti-inflammatory action in the gastrointestinal mucosa. The exact mechanism is multifactorial and includes:

• Inhibition of cyclooxygenase and lipoxygenase pathways
• Scavenging of reactive oxygen species
• Inhibition of cytokine production (particularly TNF-α, IL-1, and IL-6)
• Interference with neutrophil chemotaxis and activation
• Reduction of nuclear factor kappa B (NF-κB) activation

The ethylcellulose-coated microgranules in Pentasa's formulation allow for continuous release of mesalamine throughout the small intestine and colon.

Indications

• Treatment of mildly to moderately active ulcerative colitis
• Maintenance of remission of ulcerative colitis
• Off-label uses may include Crohn's disease (particularly colonic involvement), though evidence is more limited compared to ulcerative colitis

Dosage and Administration

• Adults: 1g orally four times daily (total 4g/day)
• Duration: Typically 8 weeks for active disease

• Adults: 1g orally four times daily (total 4g/day) or 500mg orally three times daily (total 1.5g/day)

• Swallow capsules whole; do not crush or chew
• May be taken with or without food
• For patients who have difficulty swallowing capsules, contents may be sprinkled on applesauce or yogurt

• Renal impairment: Use with caution; dose reduction may be necessary
• Hepatic impairment: No specific dosage adjustment recommended
• Elderly: Use with caution due to potential decreased renal function
• Pediatrics: Safety and effectiveness not established in children

Pharmacokinetics

Contraindications

• Hypersensitivity to mesalamine, salicylates, or any component of the formulation
• Patients with history of hypersensitivity to sulfasalazine

Warnings and Precautions

• Renal impairment: May cause nephrotoxicity; monitor renal function at baseline and periodically during treatment
• Acute intolerance syndrome: May occur with symptoms resembling exacerbation of colitis (cramping, abdominal pain, bloody diarrhea, fever, headache, rash)
• Hepatic effects: Rare reports of hepatitis, liver function abnormalities
• Pulmonary effects: Rare reports of interstitial pneumonitis, fibrosing alveolitis
• Blood dyscrasias: Rare reports of agranulocytosis, aplastic anemia
• Pericarditis: Rare reports, usually reversible upon discontinuation
• Sun sensitivity: May cause photosensitivity reactions

Drug Interactions

• Warfarin: Mesalamine may enhance anticoagulant effect
• Azathioprine/6-mercaptopurine: Potential increased risk of blood dyscrasias
• NSAIDs: May increase risk of nephrotoxicity
• Lactulose: May decrease pH in colon, potentially reducing mesalamine release
• Probenecid: May decrease renal excretion of mesalamine metabolites

Adverse Effects

• Headache (15%)
• Abdominal pain (12%)
• Nausea (8%)
• Diarrhea (7%)
• Flatulence (6%)
• Rash (4%)
• Dizziness (3%)

• Nephrotoxicity (interstitial nephritis, renal failure)
• Pancreatitis
• Hepatic failure
• Pericarditis
• Blood dyscrasias (agranulocytosis, aplastic anemia)
• Severe cutaneous adverse reactions (Stevens-Johnson syndrome)
• Pulmonary fibrosis

Monitoring Parameters

• Baseline: Complete blood count, renal function tests (BUN, creatinine), liver function tests
• Ongoing: Renal function every 3-6 months during first year, then annually; CBC and LFTs periodically
• Clinical monitoring: Symptom improvement, disease activity indices, tolerance to medication
• Therapeutic response: Reduction in bowel frequency, bleeding, and improvement in endoscopic appearance

Patient Education

• Take medication exactly as prescribed; do not stop abruptly
• Swallow capsules whole unless instructed to open them
• Report any of the following immediately:

- Worsening abdominal pain - Bloody diarrhea - Fever - Rash or skin changes - Unusual bruising or bleeding - Signs of kidney problems (decreased urine output, swelling) - Shortness of breath or chest pain

• Use sun protection measures due to potential photosensitivity
• Inform all healthcare providers about Pentasa use, especially before procedures or new prescriptions
• Keep regularly scheduled follow-up appointments for monitoring

References

1. Hanauer SB, Sandborn WJ, Kornbluth A, et al. Delayed-release oral mesalamine at 4.8 g/day (800 mg tablet) for the treatment of moderately active ulcerative colitis: The ASCEND II trial. Am J Gastroenterol. 2005;100(11):2478-2485. 2. Sandborn WJ, Regula J, Feagan BG, et al. Delayed-release oral mesalamine 4.8 g/day (800-mg tablet) is effective for patients with moderately active ulcerative colitis. Gastroenterology. 2009;137(6):1934-1943. 3. Lichtenstein GR, Hanauer SB, Sandborn WJ. Practice Parameters Committee of American College of Gastroenterology. Management of Crohn's disease in adults. Am J Gastroenterol. 2009;104(2):465-483. 4. Pentasa [package insert]. Lexington, MA: Shire US Inc.; 2021. 5. Ford AC, Achkar JP, Khan KJ, et al. Efficacy of 5-aminosalicylates in ulcerative colitis: systematic review and meta-analysis. Am J Gastroenterol. 2011;106(4):601-616. 6. Kornbluth A, Sachar DB. Ulcerative colitis practice guidelines in adults: American College of Gastroenterology, Practice Parameters Committee. Am J Gastroenterol. 2010;105(3):501-523.