What is the recommended dosing of mesalazine (5‑aminosalicylic acid) for ulcerative colitis in adults, including induction, maintenance, rectal formulations, pediatric dosing, and dose adjustments in renal impairment?

Mesalazine Dosing for Ulcerative Colitis

For adults with mild-to-moderate ulcerative colitis, start with oral mesalazine 2.4–3 g/day for induction, escalate to 4.8 g/day for moderate disease or inadequate response, and add rectal mesalazine (≥1 g/day) for left-sided or extensive disease to maximize remission rates. 1, 2

Induction Therapy (Active Disease)

Standard Dosing by Disease Severity

• Mild disease: Start with 2–3 g/day oral mesalazine 1
• Moderate disease or inadequate response: Escalate to 4.8 g/day, which demonstrates superior efficacy compared to lower doses 1, 2, 3
• Doses <2 g/day are significantly less effective and should be avoided (RR 0.88 vs 0.84 for ≥2 g/day) 2

Once-Daily vs. Divided Dosing

• Once-daily dosing is as effective as divided doses and improves adherence 1, 2
• This applies across all formulations and disease severities 1

Disease-Specific Strategies

Extensive/Pancolitis:

• Oral mesalazine 2.4–4.8 g/day 1, 2
• Add rectal mesalazine ≥1 g/day as enema for superior efficacy compared to oral monotherapy 2

Left-sided colitis (proctosigmoiditis):

• Combination therapy is mandatory: Mesalazine enema ≥1 g/day PLUS oral mesalazine ≥2.4 g/day 2
• Rectal therapy alone is more effective than oral alone for distal disease 1, 2

Proctitis (rectum only):

• First-line: Mesalazine suppositories 1 g/day, not oral therapy 2
• Suppositories reach only 15–20 cm from anal verge; use enemas for disease extending beyond rectum 2

Maintenance Therapy

Standard Maintenance Dosing

• Minimum effective dose: 1.2–2.4 g/day for maintaining remission 1
• Higher maintenance doses (up to 3 g/day) may be needed for patients with frequent relapses or extensive disease 2, 4

Dose Adjustment Based on Induction Response

• Patients achieving remission: Reduce to 1.6 g/day 4
• Partial responders: Continue 3.2 g/day 4
• Non-responders requiring extended induction: Maintain 4.8 g/day 4

Formulation-Specific Maximum Doses

The following maximum doses apply to different mesalazine formulations 1, 2:

• Delayed-release (Delzicol, Asacol-HD): 4.8 g/day 2
• MMX mesalamine (Lialda): 4.8 g/day 2
• Time-dependent release (Pentasa): 4.0 g/day 2
• Apriso: 1.5 g/day (approved only for maintenance, insufficient for active disease) 2

Rectal Formulations

Enemas

• Dose: 1–4 g once daily (typically at bedtime for optimal retention) 2, 5
• Reach sigmoid colon; preferred for left-sided colitis 2

Suppositories

• Dose: 1 g once daily 2
• Only reach rectum (15–20 cm); use exclusively for isolated proctitis 2

Escalation Criteria

When to escalate beyond mesalazine:

• Rectal bleeding persists beyond 10–14 days 2
• No adequate response by day 40 2
• Add oral prednisone 40 mg/day OR budesonide MMX 9 mg/day, taper over 8 weeks 2

When to escalate to immunomodulators/biologics:

• Steroid-dependent disease (≥2 courses/year) 2
• Failure of optimized mesalazine (4.8 g/day oral + rectal) 2

Pediatric Dosing

Active Disease

• 60–80 mg/kg/day (maximum ~4 g/day) given once daily 6
• Doses <50 mg/kg/day are subtherapeutic and delay effective treatment 6

Maintenance

• 30–50 mg/kg/day (approximately 1–2 g/day) once daily 6
• Escalate to 60–80 mg/kg/day for frequent relapses or extensive disease 6

Combination Therapy in Children

• Add rectal mesalazine ≥1 g/day (enemas or suppositories) to oral therapy for left-sided or extensive disease 6

Renal Impairment

• Monitor renal function periodically due to rare risk of interstitial nephritis 2, 6
• No specific dose adjustments are provided in guidelines, but caution is warranted with declining renal function 1

Critical Pitfalls to Avoid

1. Underdosing: Doses <2 g/day have significantly inferior efficacy 1, 2
2. Oral monotherapy for distal disease: Always combine oral + rectal therapy for left-sided colitis 2
3. Using suppositories for proctosigmoiditis: Suppositories only reach rectum; use enemas for sigmoid involvement 2
4. Delayed escalation: Do not wait beyond 40 days without improvement before adding corticosteroids 2
5. Gradual tapering when stopping: Unlike corticosteroids, mesalazine does not require tapering (though stopping may precipitate relapse) 2

Safety Profile

• 4.8 g/day is well-tolerated with adverse event rates similar to lower doses 2
• Up to 15% may develop intolerance (paradoxical diarrhea, headache, nausea, rash) 1, 6
• Serious idiosyncratic reactions (Stevens-Johnson syndrome, pancreatitis, agranulocytosis) are rare 1