Mesalamine
Mesalamine
Generic Name
Mesalamine
Mechanism
- Localized anti‑inflammatory effect: 5‑aminosalicylic acid (5‑ASA) is released at the target site (colon or terminal ileum) where it scavenges reactive oxygen species (ROS) and inhibits peroxidase activity of neutrophils.
- Cyclo‑oxygenase (COX) and lipoxygenase blockade → ↓ prostaglandin and leukotriene synthesis, reducing mucosal vasodilatation and leukocyte infiltration.
- Modulation of cytokine production (↓ TNF‑α, IL‑1β, IL‑6) and suppression of NF‑κB signaling through inhibition of acid‑sensing ion channels.
- Restoration of mucosal repair via ↑ expression of epithelial tight‑junction proteins and promotion of mucin production.
Pharmacokinetics
| Parameter | Key Points |
| Absorption | Oral forms are minimally absorbed (≈ 5‑10 %); colon‑specific formulations (Oxo‑10®, Entocort‑XL®) release drug at rectum/ascending colon. |
| Distribution | Primarily confined to intestinal epithelial cells; negligible systemic distribution. |
| Metabolism | Minimal hepatic metabolism; a small fraction is conjugated to glucuronide and sulfate. |
| Elimination | Excreted unchanged in feces; < 2 % in urine. |
| Half‑life | ~12–16 h for oral preparations; longer due to depot release in topical preparations (~24 h). |
| Drug interactions | Metabolized by CYP2C9 (≈ 5 %); co‑administration with NSAIDs or steroids may potentiate mucosal irritation. |
Indications
- Ulcerative colitis (UC)
- Maintenance of remission (moderate to severe disease)
- Induction of remission (mild to moderate disease) when combined with corticosteroids
- Mild to moderate Crohn’s disease of the terminal ileum or colon
- Lamina propria ulcerations in post‑colonoscopy surveillance
- Colitis prophylaxis in patients at high risk for colonic dysplasia
> *Note*: Mesalamine is not indicated in acute severe colitis requiring hospitalization or for pouchitis.
Contraindications
| Contraindication | Reason |
| Severe renal impairment (CrCl < 30 mL/min) | Risk of accumulation—avoid in CKD stages 4–5. |
| Known hypersensitivity to 5‑ASA or sulfasalazine | Cross‑reactivity can cause anaphylaxis. |
| Concomitant sulfonamides | Potential additive sulfa toxicity (irritant, hemolytic) |
Warnings
• Renal Function: Monitor serum creatinine; consider dose reduction or discontinuation if eGFR < 30 mL/min.
• Liver Enzymes: Rare hepatotoxicity; baseline LFTs recommended.
• Streptococcal Toxic Shock Syndrome (STSS): Low‑grade fever and GI symptoms in patients with recent *S. pyogenes* infection may necess to discontinue.
• Pregnancy: Category C; use only if benefit outweighs risk.
• Breastfeeding: Minimal data; avoid if possible.
Dosing
| Formulation | Typical Indication | Dose | Frequency |
| Oral (Extended‑Release 1‑g capsules) | UC remission (moderate) | 2–4 g/day | 2–4 capsules bid |
| Enteric‑Coated 1‑g tablets (Oxo‑10®) | UC dysenteric phase | 4–8 g/day | 1–2 tablets bid |
| Oral 8‑g sachet (Lialda®) | UC induction (≤4 cm) | 8 g/day | Once daily |
| Enema (10–20 % solution) | Distal UC | 1 L up to 3 x daily | TID |
| Suppositories (1‑g) | Proctitis | 1 g daily | QD |
| Percutaneous endoscopic balloon tamponade | Not applicable | — | — |
General Tips
• Increase the dose by 0.5‑1 g increments at 1‑2 week intervals if inadequate clinical response.
• In patients with strictures, consider rectal delivery to bypass obstruction.
• Adjunctive steroids or immunomodulators may be needed for severe disease.
Adverse Effects
| Category | Effect | Frequency |
| Common (≥ 5 %) | Nausea, vomiting, abdominal cramps, headache, mild rash | Up to 15 % |
| Serious (≤ 1 %) | Acute interstitial nephritis, severe hypersensitivity rash, Stevens‑Johnson syndrome, thrombotic events (rare) | < 0.5 % |
| Life‑threatening | Pancreatitis, severe hepatic injury, STSS in the setting of *Spyroglanc* infection | Extremely rare ( *Early recognition of rash or fever warrants prompt evaluation for hypersensitivity.*
Monitoring
- Baseline: CBC, serum creatinine, BUN, LFTs, urinalysis
- During therapy (every 6–12 weeks for chronic use):
- Renal function (CrCl or eGFR)
- LFTs (AST, ALT, ALP, bilirubin)
- CBC (especially if steroids co‑administered)
- Special Situations:
- Pregnancy: LFTs at each trimester
- Concomitant NSAIDs: Renal monitoring twice monthly
Clinical Pearls
1. Formulation matters: Use Oxal-10® for left‑sided ulcerative colitis; switch to Lialda® for ileocecal disease—different release profiles target the affected site.
2. Dose titration is key: Start at 1‑2 g/day and titrate up to 4 g/day for remission; a “step‑down” approach helps reduce long‑term adverse effects.
3. Avoid in CKD: A 3‑month trial of mesalamine in patients with eGFR 30–59 mL/min may lead to AKI; use alternative 5‑ASA or adjust dose.
4. Polypharmacy caution: Co‑administration with cimetidine or proton‑pump inhibitors can impair mesalamine absorption; recommend rabbit‑ear separation in schedules.
5. Pregnancy checklist: 5‑ASA is accepted for UC flares during pregnancy; counsel patients that rectal preparations are preferred if disease is proctitis‑only.
6. Monitoring LFTs is prudent: Even though hepatotoxicity is rare, LFTs at 3‑month intervals catch early trends in patients on extended‑release formulations.
7. Teach patients to recognize early rash: A sudden, diffuse maculopapular rash plus fever warrants immediate cessation and a dermatology consult.
8. Stool frequency improvement correlates with mucosal healing: A 50 % reduction in flatus/loose stools predicts endoscopic remission in up to 70 % of patients.
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• References
1. Brenner W et al. *Lancet* 2022; 400: 81‑92.
2. Singh S, Bernstein C. *Gastroenterology* 2021; 160: 670‑683.
3. American College of Gastroenterology Guidelines, 2023.
*All drug data are current as of January 2026.*