Balsalazide
Balsalazide
Generic Name
Balsalazide
Mechanism
Balsalazide is an orally‑administered, enterohepatic‑stable prodrug that relies on colonic bacterial enzymes for activation.
• Prodrug structure: Two mesalamine moieties linked by a disulfide bond.
• Colonic release: In the distal colon, bacterial thiol‑reducing enzymes cleave the disulfide bond, liberating free mesalamine.
• Pharmacological effect: Mesalamine dampens inflammation through
• Inhibition of cyclooxygenase‑2 and 5‑lipoxygenase pathways → ↓ prostaglandin & leukotriene production.
• Suppression of nuclear factor‑κB (NF‑κB) activation → ↓ pro‑inflammatory cytokines (TNF‑α, IL‑1β, IL‑6).
• Free radical scavenging and modulation of leukocyte migration.
• Result: Localized anti‑inflammatory action in the colonic mucosa with minimal systemic exposure.
Pharmacokinetics
| Parameter | Value & Notes |
| Absorption | Poor systemic absorption; primarily intact drug reaches colon |
| Bioavailability | <10 % systemic; ≥80 % delivered to rectosigmoid region |
| First‑pass metabolism | Minimal; hepatic conjugation of a small fraction of mesalamine |
| Half‑life | Mesalamine in plasma ~16‑18 h; prodrug 6‑8 h |
| Metabolism | Cleaved by colonic bacteria → free mesalamine; minor glucuronidation in liver |
| Excretion | Mainly fecal (≈95 %) of unchanged drug; renal excretion <2 % |
| Food interaction | No clinically significant effect; can be taken with or without food |
Indications
- Primary:
- Mild‑to‑moderate ulcerative colitis (induction and maintenance).
- Secondary:
- Crohn’s disease limited to the colon (maintenance).
- Not indicated for acute severe colitis, complicated Crohn’s (penetrating, stricturing), or systemic infections.
Contraindications
- Absolute contraindications
- Hypersensitivity to sulfa drugs, sulfonamides, or mesalamine.
- Severe renal impairment (CrCl < 30 mL/min).
- Severe hepatic disease (Child‑Pugh C).
- Relative cautions
- Pregnancy: Category B; use if clearly needed.
- Lactation: limited data; shared decision.
- Concurrent use of NSAIDs or glucocorticoids may increase GI upset.
- Warnings
- Bone marrow suppression: Rare neutropenia, leukopenia.
- Nephrotoxicity: Rare acute interstitial nephritis.
- Hepatotoxicity: Transient LFT elevations.
Dosing
| Indication | Starting Dose | Titration | Maintenance Dose | Administration Notes |
| Ulcerative colitis induction | 3 g/day (1 g TID) | Increase by 1 g/day as tolerated | 2 – 3 g/day | Take with meals; not crushing tablets |
| Ulcerative colitis maintenance | 1 – 2 g/day | Maintain stable dose | 1 – 2 g/day | Long‑term use; monitor labs |
| Colonic Crohn’s maintenance | 1 – 2 g/day | Same | Same |
• Maximum: 8 g/day (for selected severe UC; monitor for toxicity).
• Dose adjustments for renal impairment: not required unless CrCl < 30 mL/min (stop).
Adverse Effects
Common
• Gastro‑intestinal: nausea, abdominal cramps, flatulence, diarrhea (transient).
• Headache, dizziness.
• Skin rash (maculopapular, rarely bullous).
Serious
• Neutropenia / leukopenia → febrile neutropenia (rare, <0.1 %).
• Interstitial nephritis: oliguria, rash, hematuria.
• Hepatotoxicity: AST/ALT ↑, jaundice.
Monitoring
• Baseline CBC, CMP.
• CBC every 3–4 weeks during dose escalation.
• LFTs every 3–4 weeks during first three months.
• Renal function annually, more often if CrCl < 60 mL/min.
Monitoring
| Parameter | Frequency | Rationale |
| CBC / differential | Every 3–4 weeks (induction) | Detect neutropenia / leukopenia |
| LFT panel | Every 3–4 weeks (first 3 mo) | Identify hepatotoxicity |
| Serum creatinine / BUN | Every 3–4 weeks (first 6 mo) | Monitor for nephrotoxicity |
| Pregnancy test (if applicable) | Once pre‑treatment | Balsalazide is pregnancy category B |
| Stool calprotectin | For disease activity monitoring | Helps assess mucosal healing |
Clinical Pearls
- Better colonic targeting: The disulfide bond in balsalazide makes it less enterohepatic–loop reabsorbed than sulfasalazine, giving a steeper release curve in distal colon—ideal for left‑sided UC.
- Lower sulfa‑related toxicity: Because balsalazide lacks the sulfonamide moiety of sulfasalazine, it rarely triggers sulfa‑drug hypersensitivity (rash, eosinophilia).
- Use as a “bridge” to steroids: In mild‑to‑moderate UC, it can be started concurrently with a short course of oral prednisone to achieve rapid symptom control while 5‑ASA takes effect.
- Avoid splitting tablets: Tablets provide a sustained‑release profile; crushing compromises colonic release and increases GI upset.
- Dietary precautions: Fat‑rich meals slightly delay release; administer with moderately fat meals if GI upset occurs.
- Adjunct therapy: For patients who reach remission but remain symptomatic, adding topical mesalamine suppositories can enhance rectal disease control.
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• Key Takeaway
Balsalazide is a colon‑specific 5‑ASA prodrug that delivers mesalamine with minimal systemic absorption, making it a first‑line agent for mild‑to‑moderate ulcerative colitis with a favorable safety profile in patients intolerant of sulfasalazine.