Generic Name

Pentasa

Brand Names

for the 5‑aminosalicylic acid (5‑ASA) formulation marketed by Pfizer for the treatment of inflammatory bowel disease (IBD). The medication is available in oral capsules and as a delayed‑release powder for direct colonic delivery.

Mechanism

• Topical anti‑inflammatory: 5‑ASA blocks cyclo‑oxygenase (COX) and 5‑lipoxygenase (5‑LOX) pathways, reducing leukotriene, prostaglandin, and thromboxane synthesis.
• NF‑κB inhibition: Direct suppression of the nuclear factor‑kappa B (NF‑κB) transcription factor decreases cytokine production (TNF‑α, IL‑1β, IL‑6).
• Free radical scavenging: 5‑ASA neutralizes reactive oxygen species, limiting mucosal oxidative damage.
• Localized action: The delayed‑release formulation releases mesalamine only in the distal colon, sparing the upper GI tract.

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Pharmacokinetics

• Absorption: Limited systemic absorption (<10%); the drug acts locally in the colon.
• Metabolism: 5‑ASA is glucuronidated and sulfated in the liver and small intestine; metabolites are largely excreted unchanged.
• Distribution: Concentrations are highest in colonic tissue; plasma levels are low (<2 µg/mL).
• Elimination: Primarily via the kidneys; half‑life ≈ 9–12 h (dependent on dosage form).
• Drug interactions: Minimal systemic interactions; may increase risk of NSAID‑induced mucosal injury when co‑administered.

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Indications

• Ulcerative colitis (UC): Maintenance and induction of remission for mild to moderate disease, particularly left‑sided colitis.
• Crohn’s disease (CD): Maintenance therapy for luminal disease; less effective for ileal or small‑bowel disease.
• Colitis associated with systemic diseases: e.g., pouchitis after ileal‑pouch–anal anastomosis.

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Contraindications

• Contraindications
• Hypersensitivity to 5‑ASA, sulfonamides, or any components of Pentasa.
• Severe hepatic impairment (due to higher systemic exposure).
• Warnings
• Renal impairment: Dose adjustment required; monitor creatinine clearance (ClCr >30 mL/min recommended).
• Pregnancy/Breastfeeding: Category B; use only if benefits outweigh risks.
• Drug–Drug Interactions: Chronic sulfasalazine or other 5‑ASA may decrease efficacy; consider desensitization or switching.

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Dosing

• Titration: Begin at lowest effective dose; titrate upward by 1 g increments monthly.
• Long‑term use: Possible risk of *acetaminophen* toxicity if combined with other 5‑ASA containing medications.

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Monitoring

• Baseline: CBC, CMP (renal & hepatic), urinalysis (protein/creatinine), pregnancy test if applicable.
• Follow‑ups:
• Renal function every 3 months.
• Liver enzymes at 3, 6, and 12 months.
• In patients with CD: fecal calprotectin to gauge mucosal healing.
• Special: For patients on chronic NSAIDs or steroids, assess for GI ulceration or bleeding.

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Clinical Pearls

• Delayed‑release design: Ensures >90 % mesalamine delivery to the distal colon—critical for left‑sided UC.
• Low systemic exposure: Reduces risk of NSAID‑like side effects seen with older sulfasalazine regimens.
• Combination therapy: Pairing Pentasa with azathioprine or biologics may benefit steroid‑refractory UC patients; monitor for immunosuppression.
• Renal dose adjustment: For CrCl 30–50 mL/min, reduce to 1.5 g/day; stop if CrCl <30 mL/min.
• Pregnancy safety: Data from registries indicate negligible teratogenic risk; consider switch to oral mesalamine to avoid rectal formulations.
• Adherence: Use pill organizers and set reminders; non‑adherence is a leading cause of flares.
• Drug interactions: Avoid concurrent use of interferon‑α or allopurinol as they may elevate 5‑ASA levels systemically.

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• Pentasa remains a cornerstone in the maintenance and induction of remission for ulcerative colitis, with a favorable safety profile as a locally acting anti‑inflammatory. Understanding its pharmacokinetic nuances and vigilance for renal/hepatic compromise are essential for optimal therapeutic outcomes.