PENTASA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PENTASA (PENTASA).
Mesalamine, the active ingredient, acts locally in the colon to reduce inflammation by inhibiting prostaglandin production and leukotriene synthesis via blockade of cyclooxygenase and lipoxygenase pathways.
| Metabolism | Primarily metabolized in the liver via N-acetylation to N-acetyl-5-aminosalicylic acid; also undergoes metabolism by gut flora and intestinal mucosa. |
| Excretion | Renal: 50-80% as mesalazine and metabolites; fecal: negligible; biliary: minor enterohepatic cycling. |
| Half-life | Mesalazine: 0.5-1.5 hours; N-acetyl-5-aminosalicylic acid (acetyl metabolite): 5-10 hours. Clinical context: short half-life necessitates controlled-release formulations for sustained colonic delivery. |
| Protein binding | Mesalazine: 40-50% bound, primarily to albumin; N-acetyl metabolite: 80-90% bound. |
| Volume of Distribution | Mesalazine: 1.5-2 L/kg, indicating extensive tissue distribution, particularly to intestinal mucosa. |
| Bioavailability | Oral: 20-30% (systemic), primarily due to extensive presystemic metabolism in gut and liver; rectal: 10-20% (systemic), predominantly local action. |
| Onset of Action | Oral: 3-5 days for clinical improvement in ulcerative colitis; rectal (enema/suppository): 2-4 hours for local effect. |
| Duration of Action | Oral: 24 hours with controlled-release formulation (e.g., Pentasa 4 g/day); rectal: up to 8-12 hours per dose. |
For ulcerative colitis: 4 g orally once daily or 2 g orally twice daily. For maintenance of remission: 2-4 g orally once daily. For proctitis: 1 g rectally once daily. Mesalamine 400 mg; extended-release 1200 mg tablets; 4 g/60 mL enema; 1 g/100 mL suspension; 500 mg and 1000 mg suppositories.
| Dosage form | CAPSULE, EXTENDED RELEASE |
| Renal impairment | eGFR 30-60 mL/min: caution, consider dose reduction; eGFR <30 mL/min: contraindicated. |
| Liver impairment | No specific Child-Pugh based adjustments; use caution in severe hepatic impairment. |
| Pediatric use | Weight-based: 30-50 mg/kg/day orally in 1-2 divided doses; maximum 4 g/day. |
| Geriatric use | Elderly: start at lower end of dosing range due to potential renal impairment; adjust dose based on renal function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PENTASA (PENTASA).
| Breastfeeding | Mesalamine and its metabolite N-acetyl-5-aminosalicylic acid are excreted into human breast milk in low concentrations. The M/P ratio is approximately 0.2-0.3. At maternal doses up to 4 g/day, infant exposure is <2% of maternal weight-adjusted dose. Diarrhea in breastfed infants has been reported rarely. Generally considered compatible with breastfeeding, but monitor infant for loose stools. |
| Teratogenic Risk | PENTASA (mesalamine) is classified as FDA Pregnancy Category B. First trimester: No evidence of increased risk of major malformations in human studies, though data are limited. Second and third trimesters: No known fetal risks, but use only if clearly needed. Animal studies show no teratogenicity at clinically relevant doses. |
■ FDA Black Box Warning
None.
| Common Effects | Rectal discomfort Flatulence Headache Vomiting Diarrhea Nausea Abdominal pain Rash |
| Serious Effects |
["Hypersensitivity to mesalamine or any salicylates","History of salicylate-induced asthma","Severe renal impairment (e.g., GFR <30 mL/min/1.73 m²)"]
| Precautions | ["Renal impairment (acute interstitial nephritis, renal toxicity)","Hypersensitivity reactions (including Stevens-Johnson syndrome)","Exacerbation of colitis symptoms","Hepatic toxicity (elevated liver enzymes)","Blood dyscrasias (leukopenia, neutropenia)","Sulfasalazine allergy cross-sensitivity"] |
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| Fetal Monitoring | Monitor maternal renal function (serum creatinine, BUN) periodically. No specific fetal monitoring required beyond routine prenatal care. In active inflammatory bowel disease, monitor disease activity as it may affect pregnancy outcomes. |
| Fertility Effects | No adverse effects on human fertility reported. Mesalamine does not impair fertility in animal studies. |