5-aminosalicylates

Overview

5-Aminosalicylates (5-ASAs) are a group of anti-inflammatory drugs structurally related to salicylic acid, used to reduce inflammation in the gastrointestinal (GI) tract, especially the colonic mucosa. These drugs are designed to deliver 5-aminosalicylic acid (5-ASA)—also known as mesalazine—directly to the intestinal site of inflammation, with varying release mechanisms and formulations to optimize delivery.

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Approved Generic Names

1. Mesalazine (also known as Mesalamine or 5-ASA)

• Primary Drug in the class

• Delivered in multiple formulations (pH-dependent, time-dependent, delayed-release, enemas, suppositories)

2. Sulfasalazine

• Prodrug composed of sulfapyridine + 5-ASA

• Cleaved by colonic bacteria to release active 5-ASA

• Used in ulcerative colitis and sometimes in rheumatoid arthritis

3. Olsalazine

• A dimer of two 5-ASA molecules linked by an azo bond

• Cleaved in colon to release 2 molecules of 5-ASA

4. Balsalazide

• A prodrug where 5-ASA is linked to an inert carrier molecule via an azo bond

• Released in the colon after bacterial azo-reduction

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1. Mesalazine (Mesalamine, 5-ASA)

Formulations

• Oral tablets (e.g., Pentasa, Asacol, Lialda)

• Rectal enema

• Rectal suppository

• Granules and capsules

Mechanism of Action

• Acts topically on the colonic mucosa to inhibit inflammatory mediators (e.g., prostaglandins, leukotrienes)

• Reduces cytokine production and neutrophil activation

Indications

• Induction and maintenance of remission in ulcerative colitis

• Occasionally used in mild Crohn’s disease affecting the colon

Pharmacokinetics

• Absorption: Depends on formulation (some systemic, some topical)

• Metabolism: Acetylated in liver and intestinal mucosa

• Excretion: Renal and fecal routes

Common Doses

• Induction: 2–4.8 g/day orally in divided doses

• Maintenance: 1.2–2.4 g/day

• Rectal Enema: 1–4 g/day

• Suppository: 1 g once or twice daily

Adverse Effects

• Headache

• Nausea

• Abdominal pain

• Rare: Interstitial nephritis, pancreatitis, myocarditis

Contraindications

• Hypersensitivity to salicylates

• Severe renal impairment

Monitoring

• Renal function (baseline and periodically)

• Complete blood count (CBC) in long-term therapy

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2. Sulfasalazine

Formulations

• Oral tablets (500 mg)

Mechanism of Action

• Prodrug cleaved by colonic bacteria to release sulfapyridine and 5-ASA

• Sulfapyridine is systemically absorbed and responsible for many side effects

Indications

• Mild to moderate ulcerative colitis

• Rheumatoid arthritis (as a DMARD)

Pharmacokinetics

• Bioavailability: ~20–30% systemic absorption

• Metabolism: Hepatic acetylation of sulfapyridine

• Excretion: Renal

Common Doses

• Ulcerative colitis:

  • Induction: 2–4 g/day in divided doses

  • Maintenance: 1–2 g/day

• Rheumatoid arthritis: Up to 3 g/day

Adverse Effects

• Headache

• Anorexia

• Nausea, vomiting

• Rash, fever

• Reversible oligospermia

• Hemolytic anemia

• Hepatotoxicity

Contraindications

• Sulfonamide or salicylate hypersensitivity

• G6PD deficiency (risk of hemolysis)

• Severe hepatic or renal impairment

Monitoring

• LFTs, CBC, renal function

• Monitor for allergic reactions or hematologic toxicity

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3. Olsalazine

Formulations

• Oral capsule (250 mg)

Mechanism of Action

• Dimer of two 5-ASA molecules linked by azo bond

• Activated by colonic bacteria, releasing 5-ASA locally

Indications

• Maintenance of remission in ulcerative colitis

Pharmacokinetics

• Not systemically absorbed; acts locally in colon

• Metabolized in colon by bacterial azo-reduction

Common Doses

• 500 mg twice daily (maintenance therapy)

Adverse Effects

• Secretory diarrhea (most common, dose-limiting)

• Abdominal cramps

• Headache

• Rash (rare)

Contraindications

• Hypersensitivity to salicylates

• Severe renal impairment

Monitoring

• Renal function tests

• CBC during long-term use

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4. Balsalazide

Formulations

• Oral capsules or tablets (750 mg)

Mechanism of Action

• Prodrug cleaved by bacterial azo-reduction to release active 5-ASA

• Designed for targeted colonic delivery

Indications

• Induction and maintenance of remission in mild to moderate ulcerative colitis

Pharmacokinetics

• Minimal systemic absorption

• Metabolized in the colon to 5-ASA and inert carrier molecule

Common Doses

• Induction: 2.25 g three times daily (6.75 g/day)

• Maintenance: 2.25 g twice daily

Adverse Effects

• Headache

• Abdominal pain

• Arthralgia

• Nausea

• Rare: Interstitial nephritis

Contraindications

• Hypersensitivity to salicylates

• Severe renal or hepatic impairment

Monitoring

• Renal and hepatic function

• Blood counts during long-term therapy

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Comparison Table of 5-ASA Generic Drugs

Generic Name	Form	Mechanism	Main Use	Systemic Absorption	Notable ADRs
Mesalazine	Oral, enema, suppository	Direct anti-inflammatory (5-ASA)	UC, mild Crohn’s	Variable by form	Headache, renal issues
Sulfasalazine	Oral	Prodrug: releases 5-ASA + sulfapyridine	UC, RA	Yes (sulfapyridine)	Rash, anemia, infertility
Olsalazine	Oral	Prodrug: 2 × 5-ASA	UC maintenance	Minimal	Diarrhea, cramping
Balsalazide	Oral	Prodrug: 5-ASA + carrier	UC	Minimal	GI discomfort, arthralgia

Regulatory Approvals

All the above generic drugs are approved by:

• FDA (U.S. Food and Drug Administration)

• EMA (European Medicines Agency)

• MHRA (UK Medicines & Healthcare products Regulatory Agency)

• TGA (Australia)

• Health Canada

• PMDA (Japan)

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Key Clinical Practice Guidelines

• First-line treatment for mild-to-moderate ulcerative colitis

• Preferred over corticosteroids for maintenance due to superior safety

• Rectal 5-ASAs more effective for proctitis

• Sulfasalazine still used in rheumatoid arthritis but less preferred in IBD due to side effects

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Patient Counseling Points

• Take medication as prescribed even during remission

• Do not crush delayed-release tablets

• Report symptoms like rash, fever, or dark urine

• Monitor renal function periodically

• Suppositories/enemas are to be retained for several hours for effectiveness