Schedule H

Oral, Rectal

Oral:

• Delayed-release/Enteric-coated tablets: 400 mg, 800 mg

• Sustained-release/Modified-release tablets: 500 mg, 1 g, 1.2 g

• Delayed-release granules: 1 g, 2 g sachets

Rectal:

• Suppositories: 500 mg, 1 g

• Enema suspension: 1 g/100 mL, 2 g/100 mL, 4 g/60 mL

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

1. Ulcerative Colitis — Induction of Remission

Oral Therapy:

Parameter Mild-Moderate Disease Moderate Disease

Starting dose 2.4 g/day in 2–3 divided doses 4–4.8 g/day in 2–3 divided doses

Titration Assess response at 2–4 weeks; escalate if inadequate Assess at 2–4 weeks

Usual maintenance dose Not applicable (induction phase) Not applicable

Maximum dose 4.8 g/day 4.8 g/day

Rectal Therapy (for distal disease/proctitis/proctosigmoiditis):

Formulation Starting Dose Frequency Maximum Dose

Suppository 500 mg–1 g Once or twice daily 1.5 g/day

Enema 1–2 g at bedtime Once daily (preferably HS) 4 g/day

Key Clinical Notes:

• Combination oral + rectal therapy superior for left-sided colitis and proctosigmoiditis

• Response typically assessed at 4–8 weeks

• Once-daily oral dosing non-inferior to divided doses for mild-moderate disease

1. Ulcerative Colitis — Maintenance of Remission

Oral Therapy:

Parameter Dosing Details

Starting dose 1.2–2.4 g/day (single or divided doses)

Titration Not applicable

Usual maintenance dose 2–2.4 g/day

Maximum dose 4.8 g/day (for frequent relapsers)

Rectal Therapy (adjunct or monotherapy for distal disease):

Formulation Maintenance Dose Frequency

Suppository 500 mg–1 g Once daily or alternate days

Enema 1–2 g Once daily or 2–3 times weekly

Key Clinical Notes:

• Continue maintenance therapy indefinitely to reduce relapse risk

• Once-daily dosing improves adherence with equivalent efficacy

• Combined oral + topical rectal therapy reduces relapse rates in extensive colitis

1. Crohn's Disease — Mild Colonic Involvement

⚠️ Limited role; not first-line therapy

Parameter Dosing Details

Starting dose 2.4–4 g/day orally in divided doses

Titration Assess at 4–8 weeks; consider alternative if no response

Usual maintenance dose 2–3 g/day (if responsive)

Maximum dose 4 g/day

Key Clinical Notes:

• Evidence weaker than for ulcerative colitis

• Most effective for mild colonic or ileocolonic Crohn's disease

• Rectal formulations not routinely used in Crohn's disease

• Consider step-up to immunomodulators or biologics if inadequate response

Secondary Indications — Adults Only (Off-label)

Indication Dose Duration Notes

Radiation Proctitis (OFF-LABEL) 500 mg–1 g suppository once or twice daily OR 1–2 g enema at bedtime 6–8 weeks Specialist only. Based on retrospective case series and expert consensus; limited RCT data.

Microscopic Colitis (OFF-LABEL) 2.4–3 g/day orally 8–12 weeks trial Specialist only. Second-line after budesonide. Limited efficacy data.

PAEDIATRIC DOSING (Specialist Only)

Primary Indications

1. Ulcerative Colitis — Induction of Remission

Age/Weight Oral Dose Rectal Dose

2–6 years (10–20 kg) 30–50 mg/kg/day in 2–3 divided doses Suppository: 250–500 mg once daily

6–12 years (20–40 kg) 40–60 mg/kg/day in 2–3 divided doses (max 2.4 g/day) Suppository: 500 mg once or twice daily; Enema: 1 g at bedtime

12 years (>40 kg) Adult dosing (2.4–4.8 g/day) Adult rectal dosing

Key Clinical Notes:

• Minimum age: 2 years (paediatric gastroenterologist supervision required)

• Suppository size may limit use in younger children

• Assess response at 2–4 weeks

1. Ulcerative Colitis — Maintenance of Remission

Age/Weight Oral Dose Maximum

2–12 years 20–30 mg/kg/day in 1–2 divided doses 2 g/day

12 years 1.2–2.4 g/day 2.4 g/day

Secondary Indications — Paediatric (Off-label)

Indication Dose Notes

Crohn's Disease — Mild colonic (OFF-LABEL) 50–70 mg/kg/day orally (max 4 g/day) Specialist only. Extrapolated from adult data; limited paediatric evidence. Not first-line.

Clear Statement: Not recommended below 2 years of age except under paediatric gastroenterologist supervision.

Safety Monitoring in Children:

• Baseline and periodic CBC, LFT, serum creatinine (every 3–6 months)

• Monitor growth velocity with prolonged therapy

• Assess for intolerance symptoms (diarrhoea, abdominal pain, rash)

60 No dose adjustment required

30–60 Use with caution; monitor renal function more frequently (every 1–3 months)

<30 Avoid use — risk of drug accumulation and nephrotoxicity

Dialysis Not significantly dialysed; avoid use due to nephrotoxicity risk

Note: Monitor serum creatinine and urinalysis at baseline and every 3–6 months during therapy. Mesalazine-induced interstitial nephritis can occur at any dose.

• Known hypersensitivity to mesalazine, other salicylates (including aspirin), or any excipient

• History of mesalazine-induced nephrotoxicity or interstitial nephritis

• Severe renal impairment (eGFR <30 mL/min/1.73m²)

• Severe hepatic impairment

• Active peptic ulcer disease (for oral formulations)

• Salicylate hypersensitivity with bronchospasm

• Blood dyscrasias

• Pre-existing renal impairment — increased nephrotoxicity risk; monitor closely

• Pre-existing hepatic disease — monitor LFTs

• History of drug-induced myocarditis, pericarditis, or pancreatitis (5-ASA class effect)

• History of blood dyscrasias — monitor CBC

• Elderly patients — reduced renal reserve; start at lower dose range

• Concurrent use of other nephrotoxic agents (NSAIDs, aminoglycosides)

• Possible cross-sensitivity with sulfasalazine (though mesalazine lacks sulfa moiety)

• Pulmonary disease — rare mesalazine-induced pulmonary toxicity reported

Parameter Details

Risk Category Generally considered safe; extensive human data supporting use

Preferred alternatives Mesalazine is the preferred 5-ASA in pregnancy (sulfasalazine acceptable alternative)

When may be used Recommended for maintaining IBD remission during pregnancy; uncontrolled IBD poses greater fetal risk

Dose consideration Avoid doses >3 g/day unless essential for disease control

Monitoring Maternal renal function; fetal growth surveillance; supplement folic acid 5 mg/day (especially first trimester)

Parameter Details

Compatibility Compatible with breastfeeding

Preferred alternatives None required; mesalazine is preferred 5-ASA during lactation

Drug levels in milk Low (small amounts of acetyl-mesalazine detected)

Infant monitoring Monitor for diarrhoea (rare); no other specific monitoring required

Parameter Recommendation

Starting dose Start at lower end of dose range (e.g., 1.6–2.4 g/day oral for induction)

Titration Slower dose escalation; assess response before increasing

Special risks Increased nephrotoxicity risk due to reduced renal reserve; higher bleeding risk; dehydration may increase toxicity

Rectal administration May have difficulty with self-administration of enemas; suppositories may be more practical

Monitoring More frequent renal function monitoring (every 1–3 months)

Interacting Drug Mechanism & Effect Management

Azathioprine / 6-Mercaptopurine Mesalazine inhibits TPMT, increasing thiopurine metabolite levels → increased myelosuppression risk Monitor CBC closely (weekly initially, then monthly); consider dose reduction of thiopurine

NSAIDs (ibuprofen, diclofenac, naproxen) Additive nephrotoxicity Avoid concurrent use if possible; if essential, monitor renal function frequently

Warfarin / Acenocoumarol May enhance anticoagulant effect; mechanism unclear Monitor INR closely; adjust anticoagulant dose as needed

Interacting Drug Effect Management

Antacids / Proton pump inhibitors May alter release of pH-dependent mesalazine formulations Clinical significance unclear; monitor therapeutic response

Lactulose / Other pH-altering agents May affect rectal mesalazine bioavailability Separate administration if possible

Methotrexate Additive hepatotoxicity; possible reduced methotrexate clearance Monitor LFTs more frequently

Digoxin May reduce digoxin absorption Monitor digoxin levels if initiating or stopping mesalazine

Rifampicin May reduce mesalazine efficacy (enzyme induction) Monitor disease control

• Headache (most common)

• Nausea, vomiting

• Abdominal pain/cramps

• Diarrhoea (may mimic disease flare)

• Flatulence

• Dyspepsia

• Arthralgia/myalgia

• Rash

• Rectal discomfort (with rectal formulations)

Adverse Effect Clinical Notes

Acute interstitial nephritis May occur at any time during therapy; presents with rising creatinine, proteinuria, sterile pyuria. Requires immediate discontinuation.

Mesalazine-induced myocarditis/pericarditis Usually occurs within 2–4 weeks of initiation; presents with chest pain, dyspnoea, fever. Discontinue immediately; do not rechallenge.

Hepatotoxicity Cholestatic or hepatocellular pattern; monitor LFTs. Discontinue if significant elevation.

Blood dyscrasias Leucopenia, thrombocytopenia, aplastic anaemia (rare). Monitor CBC.

Pancreatitis Usually within first few weeks; presents with abdominal pain, elevated amylase/lipase. Discontinue and do not rechallenge.

Stevens-Johnson Syndrome / TEN Rare; requires immediate discontinuation and hospitalisation

Pulmonary toxicity Eosinophilic pneumonia, alveolitis (rare); presents with dyspnoea, cough, fever

Paradoxical worsening of colitis May indicate mesalazine intolerance; consider discontinuation

After initiation (2–4 weeks) Serum creatinine, urinalysis; clinical assessment for hypersensitivity (chest pain, rash, fever)

Short-term (first 3 months) CBC, LFT, renal function at 4–8 weeks, then at 3 months

Long-term CBC, LFT, serum creatinine, urinalysis every 6–12 months; more frequent if high dose or risk factors

Clinical monitoring Symptom control (stool frequency, bleeding, urgency); watch for signs of intolerance

Oral Formulations:

• Mesacol® (Sun Pharma) — tablets 400 mg, 800 mg

• Pentasa® (Ferring) — tablets 500 mg, 1 g; granules 1 g, 2 g

• Asacol® (Zydus) — delayed-release tablets 400 mg, 800 mg

• Mesasal® (Glenmark)

• Mesalamine® (various generics)

• Rowasa® (Dr. Reddy's)

Rectal Formulations:

• Mesacol® Enema (Sun Pharma) — 2 g/100 mL, 4 g/60 mL

• Mesacol® Suppository — 500 mg

• Pentasa® Suppository — 1 g

• Pentasa® Enema — 1 g/100 mL

Note: Mesalazine is NOT currently listed in NLEM 2022. Prices vary significantly between brands.

1. Combination therapy is key for distal disease — oral + rectal mesalazine together is superior to either alone for left-sided colitis and proctosigmoiditis

1. Once-daily dosing is non-inferior — improves adherence without compromising efficacy for mild-moderate disease; consider for maintenance

1. Do NOT crush or chew modified-release formulations — instruct patients clearly; crushing destroys the delivery mechanism

1. Silent nephrotoxicity can occur — monitor renal function even in asymptomatic patients; interstitial nephritis may present without symptoms

1. Watch for intolerance mimicking flare — paradoxical diarrhoea, abdominal pain, or fever within weeks of starting may indicate mesalazine intolerance, not disease relapse

1. Cross-sensitivity with sulfasalazine is rare but possible — mesalazine lacks the sulfa moiety but caution still warranted in patients with documented sulfasalazine hypersensitivity

1. Long-term maintenance prevents relapse and reduces colorectal cancer risk — continue indefinitely in ulcerative colitis; do not stop after remission achieved

ulcerative-colitis; Crohn's-disease; IBD; 5-ASA; mesalamine; rectal-enema; nephrotoxicity-risk; pregnancy-safe; paediatric-gastroenterology; maintenance-therapy

RxIndia v1.0 — 06 Jun 2025

• CDSCO Approved Drug Formulations List

• Indian Pharmacopoeia 2022

• National Formulary of India (NFI) 2021

• API Textbook of Medicine (11th Edition)

• ICMR Guidelines — Inflammatory Bowel Disease Management

• AIIMS Gastroenterology Treatment Protocols

• IAP Guidelines for Paediatric IBD

• Goodman & Gilman's The Pharmacological Basis of Therapeutics (14th Edition)

• Indian Journal of Gastroenterology — Expert Consensus Statements

• Harrison's Principles of Internal Medicine (21st Edition)