How Mesacol (Mesalamine) Enema Works
Mechanism of Action
Mesalamine enema works by delivering the anti-inflammatory drug mesalamine (5-aminosalicylic acid) directly to the inflamed colonic mucosa, where it exerts a topical anti-inflammatory effect primarily by blocking cyclooxygenase and inhibiting prostaglandin production in the colon. 1
The mechanism is not fully understood, but mesalamine appears to have a topical anti-inflammatory effect on colonic epithelial cells 1. In patients with ulcerative colitis, mucosal production of arachidonic acid metabolites is increased through both cyclooxygenase and lipoxygenase pathways, and mesalamine diminishes inflammation by blocking these pathways 1.
Drug Delivery and Distribution
Physical Distribution in the Colon
A standard 60-mL mesalamine enema (4g dose) routinely spreads retrograde from the rectum to the sigmoid colon in all patients, reaches the splenic flexure region in approximately 92% of administrations, but rarely extends beyond the splenic flexure to the transverse colon 2
Most of the enema volume is retained in the sigmoid colon, with the highest drug concentration at the site of administration 2
This distribution pattern supports the use of mesalamine enemas specifically for distal ulcerative colitis extending up to the splenic flexure or within 50 cm from the anal verge 3
Topical vs. Systemic Action
The therapeutic effect is primarily topical rather than systemic, as mesalamine enemas deliver much higher local drug concentrations directly to the inflamed mucosa compared to oral formulations 3
This direct mucosal contact is why rectal mesalamine is superior to oral mesalamine for distal disease (proctitis and proctosigmoiditis) 3
Systemic absorption from rectal administration is minimal, which contributes to the excellent safety profile 4
Clinical Efficacy
Evidence of Effectiveness
Mesalamine enemas (2-4g/day, once nightly) are significantly more effective than placebo for inducing remission in mild-moderate ulcerative proctosigmoiditis, with a relative risk of 0.50 (95% CI 0.35-0.73) 3
Mesalamine enemas are superior to rectal corticosteroids for inducing remission, with a relative risk of 0.74 (95% CI 0.61-0.90) 3
For extensive disease, combining mesalamine enema with oral mesalamine produces earlier and more complete relief of symptoms than either therapy alone 5, 6
Optimal Dosing
The standard effective dose is 4g mesalamine administered once nightly, as there is no dose-response benefit above 1g daily for topical therapy, but 4g is the FDA-approved and most commonly available formulation in the United States 3
Once-daily dosing is as effective as divided doses and improves patient adherence 3
Important Clinical Considerations
When Mesalamine Enemas Are Most Appropriate
Mesalamine enemas are the preferred first-line treatment for mild-moderate ulcerative proctosigmoiditis (disease extending beyond the rectum but not past the splenic flexure) 3
For isolated proctitis (inflammation limited to <15-20 cm from anus), mesalamine suppositories are preferred over enemas as they better target the rectum 3
Critical Pitfall to Avoid
Never use mesalamine enemas in patients with an ileostomy, as the surgical diversion bypasses the colon and rectum completely, making rectal therapy ineffective 7
In ileostomy patients with remaining rectal tissue inflammation, systemic oral therapy is required instead 7
Patient Tolerance Factors
Patients with active disease may have difficulty retaining enemas due to urgency and discomfort 3
Foam formulations may be better tolerated than liquid enemas due to ease of delivery and improved retention, though efficacy is similar 3, 8
Adverse effects are generally limited to local irritation and effects from enema-tip insertion 4