MESALAMINE
Clinical safety rating: safe
Animal studies have demonstrated safety
Mesalamine is a 5-aminosalicylic acid (5-ASA) that acts locally in the colon to reduce inflammation. Its exact mechanism is not fully understood, but it is thought to inhibit cyclooxygenase and lipoxygenase pathways, reduce prostaglandin and leukotriene synthesis, and scavenge reactive oxygen species.
| Metabolism | Mesalamine is metabolized in the liver and intestinal mucosa via N-acetylation to N-acetyl-5-aminosalicylic acid. The enzyme involved is N-acetyltransferase 1 (NAT1). |
| Excretion | Renal 20-30% as acetyl-5-ASA; fecal 40-50% as unabsorbed mesalamine; biliary <1%. |
| Half-life | Terminal half-life of mesalamine is 0.5-1.5 hours; N-acetyl-5-ASA half-life 5-10 hours. Short half-life necessitates multiple daily dosing or sustained-release formulations. |
| Protein binding | Mesalamine: 43% bound (primarily to albumin); N-acetyl-5-ASA: 78% bound. |
| Volume of Distribution | 0.5-1 L/kg; suggests distribution into total body water with limited tissue binding. |
| Bioavailability | Oral conventional: 20-30%; oral delayed-release (Asacol): 20-30%; oral sustained-release (Pentasa): 20-30%; rectal (enema/suppository): 10-35% (systemic absorption). |
| Onset of Action | Oral: 3-21 days for clinical response in ulcerative colitis; rectal: 3-21 days; topical: 2-4 weeks. |
| Duration of Action | Oral conventional: 4-6 hours; sustained-release (Pentasa): 8-12 hours; delayed-release (Asacol, Lialda): 12-24 hours; rectal: systemic effects minimal, local action duration 6-12 hours. |
800 mg orally three times daily or 1 g orally four times daily for ulcerative colitis; 4 g rectally once daily as retention enema or 500 mg rectally twice daily as suppository.
| Dosage form | CAPSULE, EXTENDED RELEASE |
| Renal impairment | GFR 30-60 mL/min: reduce dose by 50%; GFR <30 mL/min: contraindicated or avoid use. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: avoid use. |
| Pediatric use | Children ≥5 years: 25-50 mg/kg/day in 2-4 divided doses, maximum 4 g/day; rectal dosing per adult guidelines. |
| Geriatric use | Use lowest effective dose; monitor renal function frequently; dose adjustment per renal function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
No significant drug interactions Can cause renal impairment and acute intolerance syndrome.
| Breastfeeding | Mesalamine and its metabolite N-acetyl-5-aminosalicylic acid are excreted into breast milk in low concentrations. The milk-to-plasma ratio is approximately 0.1-0.4. Based on limited data, the infant dose is estimated to be <1% of the maternal weight-adjusted dose. No adverse effects have been reported in breastfed infants, but caution is advised, particularly in premature infants or those with renal impairment. |
| Teratogenic Risk | Mesalamine is classified as FDA Pregnancy Category B. Data from human studies do not indicate an increased risk of major congenital abnormalities or adverse fetal outcomes. However, oral mesalamine use in the third trimester may be associated with an increased risk of preterm birth and low birth weight. Cases of mesalamine-induced renal impairment in neonates have been reported, likely due to oligohydramnios from prostaglandin inhibition. Therefore, use during pregnancy should be cautious, especially in later trimesters. |
■ FDA Black Box Warning
No FDA black box warning.
| Common Effects | Headache |
| Serious Effects |
["Hypersensitivity to mesalamine, salicylates, or any component of the formulation.","Severe renal impairment (e.g., GFR <30 mL/min/1.73 m²).","Hypersensitivity to sulfites (for certain formulations)."]
| Precautions | ["Renal impairment: monitor renal function; mesalamine may cause interstitial nephritis.","Mesalamine-induced acute intolerance syndrome (cramping, abdominal pain, bloody diarrhea) in patients with inflammatory bowel disease.","Possibility of sulfite sensitivity reactions (for formulations containing sulfites).","Exacerbation of symptoms of colitis.","Hepatic failure (rare).","Blood dyscrasias (rare)."] |
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| Fetal Monitoring | During pregnancy, monitor renal function (serum creatinine, BUN, urine output) periodically, as mesalamine can cause renal toxicity. Assess for signs of oligohydramnios via ultrasound in the third trimester. Monitor fetal growth and well-being. After delivery, observe the neonate for signs of renal impairment. |
| Fertility Effects | Animal studies have not shown impaired fertility with mesalamine. Human data are limited; however, mesalamine is not known to adversely affect fertility in either males or females. Inflammatory bowel disease itself may impact fertility, and disease control with mesalamine may improve fertility outcomes. |