Schedule H

Oral

• Capsules: 250 mg (Olsalazine sodium)

Note: Limited availability in India; mesalazine and sulfasalazine are more widely stocked

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India):

1. Ulcerative Colitis — Maintenance of Remission

Parameter Recommendation

Starting dose 500 mg orally twice daily (with meals)

Titration May adjust after 4–6 weeks based on symptom control and tolerance

Usual maintenance dose 500 mg orally twice daily

Maximum dose 1.5 g/day in divided doses (specialist discretion)

Clinical notes:

• Initiated after achieving remission with corticosteroids or other induction agents

• Not suitable for acute exacerbations — may worsen diarrhoea due to pro-secretory effects

• Prodrug converted to mesalazine in the colon by bacterial azo-reductases

• Take with food to reduce GI intolerance

Secondary Indications – Adults Only (Off-label, if any):

Indication Dose Duration Evidence Basis Notes

Crohn's Colitis (OFF-LABEL) Starting: 500 mg BD; Maintenance: 500 mg BD; Max: 1.5 g/day Specialist-guided Limited observational studies; extrapolated from mesalazine class Specialist only; consider if mesalazine not tolerated

Radiation Proctitis (OFF-LABEL) Starting: 500 mg BD; Maintenance: 500 mg BD Minimum 4 weeks; assess response Indian specialist practice; extrapolated from mesalazine data Specialist only

PAEDIATRIC DOSING (Specialist Only)

Primary Indications:

Ulcerative Colitis — Maintenance of Remission

Below 12 years Not recommended — — Use mesalazine preferred per IAP guidance

12–18 years 250 mg orally twice daily 500 mg orally twice daily if tolerated 1.5 g/day Gastroenterology supervision required

Safety Monitoring:

• Monitor for diarrhoea and weight loss

• Baseline and periodic CBC, renal function, LFTs

• Mesalazine is preferred first-line agent in paediatric IBD per Indian IAP guidelines

Safety Statement: Not recommended below 12 years of age except under specialist supervision.

Secondary Indications – Paediatric Doses (Off-label, if any):

Not applicable — no well-validated off-label uses in Indian paediatric practice.

Mild impairment (eGFR 60–89) Use with caution; monitor renal function

Moderate impairment (eGFR 30–59) Avoid use; consider mesalazine alternatives with closer monitoring

Severe impairment (eGFR <30) Contraindicated

Haemodialysis Avoid use; insufficient data

• Monitor serum creatinine every 3 months if prolonged use in patients with any degree of renal impairment

• Known hypersensitivity to olsalazine, salicylates, or other 5-ASA derivatives

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

• Severe hepatic impairment

• Acute flare of ulcerative colitis (may exacerbate diarrhoea)

• Known salicylate hypersensitivity

• History of bronchial asthma — increased risk of hypersensitivity reactions

• Sulfonamide allergy — cross-reactivity possible though olsalazine is sulfa-free

• Elderly patients — higher susceptibility to diarrhoea and dehydration

• Pre-existing renal impairment — monitor function closely

• Paradoxical worsening of diarrhoea in 10–20% of patients — may require drug discontinuation

• Blood dyscrasias — monitor CBC periodically

• Concomitant nephrotoxic drugs — increased renal risk

Parameter Information

Safety category Likely safe (based on 5-ASA class experience); limited olsalazine-specific human data

Preferred alternatives Mesalazine (broader safety data in pregnancy)

Use recommendation May be used if mesalazine not tolerated and benefit clearly outweighs risk; specialist input essential

Monitoring Fetal growth monitoring if used long-term; maternal renal function

Parameter Information

Compatibility Compatible with breastfeeding

Drug levels in milk Low to negligible (parent drug poorly absorbed systemically)

Preferred alternatives Mesalazine generally preferred in nursing mothers

Infant monitoring Observe for loose stools, feeding intolerance

Parameter Recommendation

Starting dose 250 mg twice daily

Titration Slow titration over 2–4 weeks to 500 mg twice daily if tolerated

Extra risks Diarrhoea (dose-limiting), dehydration, electrolyte imbalance, reduced renal reserve

Monitoring Renal function, hydration status, electrolytes; higher sensitivity to GI adverse effects

Drug Interaction Mechanism Management

Azathioprine / 6-Mercaptopurine Increased myelotoxicity risk Inhibition of TPMT enzyme by 5-ASA metabolites Requires regular CBC monitoring; consider dose reduction of thiopurines

Methotrexate Increased methotrexate toxicity Competition for renal tubular secretion Avoid combination or use with extreme caution; monitor methotrexate levels

Warfarin Enhanced anticoagulant effect Possible displacement from protein binding Monitor INR closely; adjust warfarin dose as needed

Drug Interaction Management

NSAIDs Increased nephrotoxicity risk Monitor renal function; use lowest effective NSAID dose

Diuretics Additive risk of renal impairment and volume depletion Monitor hydration and renal function

Antacids May impair GI absorption of olsalazine Space doses by at least 2 hours

Digoxin Possible reduced digoxin absorption Monitor digoxin levels if clinically indicated

• Diarrhoea (dose-related; occurs in 10–20%)

• Abdominal cramps

• Nausea

• Headache

• Dyspepsia

• Rash

Severe diarrhoea (secretory) Uncommon Discontinue drug; rehydrate

Interstitial nephritis Rare Discontinue immediately; nephrology referral

Hepatitis (idiosyncratic) Rare Discontinue; monitor LFTs; hepatology input

Blood dyscrasias (agranulocytosis, thrombocytopenia) Rare Discontinue; urgent haematology referral

Hypersensitivity reactions (systemic, cutaneous) Rare Discontinue immediately

Pancreatitis Very rare Discontinue; supportive care

Phase Parameters

Baseline CBC, serum creatinine, LFTs, urinalysis

After initiation (2–4 weeks) Renal function, LFTs; assess for diarrhoea

Long-term (every 3–6 months) CBC, renal function, LFTs

Clinical monitoring Stool frequency, weight, signs of dehydration or drug intolerance

• Dipentum (imported; limited availability)

Note: Olsalazine has very limited availability in India. Mesalazine and sulfasalazine are more commonly available and widely used alternatives.

NPPA Status Not under NLEM price control —

Government supply Limited; mesalazine more commonly stocked —

• Prodrug mechanism: Olsalazine consists of two mesalazine molecules linked by azo bond — cleaved by colonic bacteria to release active drug locally

• Diarrhoea risk: Paradoxical secretory diarrhoea occurs in 10–20% of patients; if persistent, switch to mesalazine or sulfasalazine

• Acute flare avoidance: Not indicated for acute ulcerative colitis — pro-secretory effect may worsen symptoms

• Sulfasalazine alternative: Consider olsalazine in patients intolerant to sulfasalazine (headache, nausea) or mesalazine

• Renal vigilance: Essential to monitor renal function in long-term use — interstitial nephritis is a class effect

• Limited availability: In India, mesalazine is preferred and more accessible; olsalazine may require special procurement

Olsalazine; ulcerative colitis; IBD; 5-ASA; mesalazine alternative; diarrhoea risk; renal monitoring; maintenance therapy; sulfa-free; gastroenterology

RxIndia v1.0 — 10 Jan 2025

• CDSCO Product Database

• National Formulary of India (NFI)

• Indian Pharmacopoeia (IP)

• API Textbook of Medicine

• Indian Society of Gastroenterology Practice Guidelines

• AIIMS Formulary and IBD protocols

• IAP Guidelines (paediatric IBD)

• Goodman & Gilman's The Pharmacological Basis of Therapeutics, 14th edition

• Harrison's Principles of Internal Medicine, 21st edition

• NLEM (checked for inclusion status — not currently included)