Brand names: Asacol, Canasa, Lialda, Pentasa, Rowasa
Drug class: Anti-inflammatory Agents
VA class: GA900
Chemical name: 5-Amino-2-hydroxybenzoic acid
Molecular formula: C₇H₇NO₃
CAS number: 89-57-6

Medically reviewed by Drugs.com on Jul 22, 2024. Written by ASHP.

Introduction

The 5-amino derivative of salicylic acid; a GI anti-inflammatory agent.

Uses for Mesalamine

Ulcerative Colitis

Used for management of ulcerative colitis (as oral delayed-release tablets or extended-release capsules) and to induce (as extended-release capsules and as 1.2-g delayed-release tablets) and maintain (as 400-mg delayed-release tablets) clinical remission in adults with mildly to moderately active disease.

Management of mildly to moderately active distal ulcerative colitis (as rectal suspension) including ulcerative proctosigmoiditis and ulcerative proctitis.

Management of active ulcerative proctitis (as rectal suppositories).

Oral preparations of the drug may be preferable to rectal preparations in patients with extensive inflammatory bowel disease, since efficacy of rectal preparations may be limited to disease distal to the splenic flexure.

Crohn’s Disease

Has been used (as extended-release oral preparations) for the management of active Crohn’s disease^{† [off-label]} and to induce and maintain clinical remission in adults with mildly to moderately active disease.

Has been used (as rectal preparations) in a limited number of patients for the management of active Crohn’s disease^{† [off-label]}, but the role of such therapy in this condition is not as well defined as in the management of ulcerative colitis.

Mesalamine Dosage and Administration

Administration

Administer orally or rectally.

Oral Administration

Administer orally as delayed-release tablets (Asacol, Lialda) or extended-release capsules (Pentasa).

Delayed-release tablets should be swallowed whole without breaking the outer coating, since the coating is designed to maintain the integrity of the tablets prior to entering the colon, where the drug is released. Intact or partially intact tablets may be present in stools; if this occurs repeatedly, patients should notify their clinician.

1.2-g delayed-release tablets (Lialda): Administer orally with food.

Rectal Administration

Administer rectally as a suspension retention enema or suppositories.

Administer rectal suspension preferably at bedtime and retain for about 8 hours. Best results are achieved if the bowel is emptied just prior to enema administration. Administer according to manufacturer’s instructions.

Retain rectal suppositories for ≥1–3 hours, if possible, to achieve maximum benefit.

Dosage

Pediatric Patients

Ulcerative Colitis† [off-label] or Crohn’s Disease† [off-label]

Oral

Delayed-release tablets have been given in an initial dosage of 20–30 mg/kg daily and then increased up to 60 mg/kg daily.

Adults

Ulcerative Colitis

Management of Mildly to Moderately Active Ulcerative Colitis

Oral

Delayed-release tablets: Usually, 2.4 g daily (given as two 400-mg delayed-release tablets 3 times daily) for 6 weeks.

Induction of Remission of Mildly to Moderately Active Ulcerative Colitis

Oral

Extended-release capsules: Usually, 4 g daily in equally divided doses (given as four 250-mg extended-release capsules or two 500-mg extended-release capsules 4 times daily) for up to 8 weeks. Lower dosages (e.g., 2–4 g daily [in divided doses]) have been used^{† [off-label]}.

Delayed-release tablets: 2.4 or 4.8 g once daily (given as two or four 1.2-g delayed-release tablets). Safety and efficacy beyond 8 weeks of treatment have not been established.

Maintenance of Remission

Oral

Delayed-release tablets: Usually, 1.6 g daily (four 400-mg delayed-release tablets) given in divided doses for 6 months. Dosages of 800 mg to 4.8 g daily (in divided doses) also have been used.

Extended-release capsules: Dosages of 1.5–3 g daily (in divided doses) have been used.

Advise patients that ulcerative colitis rarely remits completely, and continued use of maintenance dosages of mesalamine may substantially decrease the risk of relapse.

Distal Ulcerative Colitis

Rectal

Suppositories: 1 g (using 1-g suppositories) once daily at bedtime.

Enema suspension: Usually, 4 g once daily (preferably at bedtime).

Although clinical response may be apparent within 3–21 days, therapy with rectal mesalamine usually is continued for 3–6 weeks or until clinical and/or sigmoidoscopic remission is achieved.

Efficacy of rectal therapy (in terms of modification of relapse rates) beyond 6 weeks has not been established, but mesalamine has been used rectally for prolonged periods (e.g., >1 year) in some patients.

Lower dosages or less frequent administration of the rectal drug has been used in some patients^†, particularly after initial remission is achieved.

In some patients with distal ulcerative colitis in whom clinical remission occurred following daily administration of 4-g doses of the rectal suspension, dosage was reduced to 4 g every 2 or 3 nights or, occasionally, to less frequent administration. If clinical relapse occurred with such administration, dosage was increased to more frequent use. In some patients with distal ulcerative colitis or ulcerative proctosigmoiditis, the rectal suspension also has been used in dosages of 1–3 g daily.

Crohn’s Disease†

Management of Mildly to Moderately Active Crohn’s Disease†

Oral

Adults have received dosages of 3.2–4.8 g daily (as delayed-release tablets) or 4 g daily (as extended-release capsules), generally in divided doses. Lower dosages do not appear to be effective.

Prescribing Limits

Pediatric Patients

Ulcerative Colitis† or Crohn’s Disease†

Oral

Maximum 60 mg/kg daily.

Adults

Ulcerative Colitis

Management of Mildly to Moderately Active Ulcerative Colitis

Oral

Delayed-release tablets (400 mg; Asacol): Maximum 4.8 g daily in divided doses.

Extended-release capsules: Maximum 4 g daily in divided doses.

Induction of Remission of Mildly to Moderately Active Ulcerative Colitis

Oral

Extended-release capsules: Maximum 4 g daily in divided doses.

Delayed-release tablets (1.2 g; Lialda): Safety and efficacy beyond 8 weeks of therapy not established.

Maintenance of Remission

Oral

Delayed-release tablets (400 mg; Asacol): Maximum 4.8 g daily, in divided doses.

Extended-release capsules^†: Maximum 3 g daily in divided doses.

Distal Ulcerative Colitis

Rectal

Enema suspension: Maximum 4 g once daily.

The drug has been used rectally for >1 year.

Crohn’s Disease†

Management of Mildly to Moderately Active Crohn’s Disease

Oral

Delayed-release tablets (400 mg; Asacol): Maximum 4.8 g daily in divided doses.

Extended-release capsules: Maximum 4 g daily in divided doses.

Maintenance of Remission

Oral

Delayed-release tablets (400 mg; Asacol): Maximum 4.8 g daily in divided doses.

Extended-release capsules: Maximum 3 g daily in divided doses.

Special Populations

Geriatric Patients

Careful dosage selection recommended due to possible age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.

Cautions for Mesalamine

Contraindications

• Extended-release capsules (Pentasa), delayed-release tablets (1.2-g; Lialda), rectal suppositories (Canasa): Known hypersensitivity to salicylates (including aspirin, mesalamine) or any ingredient in the respective formulation.

Warnings/Precautions

Sensitivity Reactions

Possible acute intolerance (sensitivity reaction) syndrome (e.g., cramping, abdominal pain, bloody diarrhea, fever, headache, malaise, conjunctivitis, pruritus, rash); may require prompt discontinuance. A history of sulfasalazine intolerance, if any, should be reevaluated.

Use with caution in patients with a history of hypersensitivity to sulfasalazine.

Sulfite Sensitivity

Rectal suspension contains a sulfite, which may cause allergic-type reactions (including anaphylaxis and life-threatening or less severe asthmatic episodes) in certain susceptible individuals.

General Precautions

Renal Impairment

Renal impairment (e.g., minimal change nephropathy, acute and chronic interstitial nephritis, renal failure) and increases in BUN and S_cr reported.

Use with caution and only if the benefits outweigh the risks in patients with renal impairment.

Renal function should be evaluated prior to initiation of therapy and periodically thereafter.

GI Effects

Pancolitis reported rarely in patients receiving rectal mesalamine.

Possible worsening colitis or symptoms of inflammatory bowel disease (e.g., melena, hematochezia) in patients receiving rectal mesalamine.

Potential for prolonged gastric retention of oral delayed-release tablets in patients with pyloric stenosis.

The possibility of acute pancreatitis should be considered in any patient who develops new abdominal complaints while receiving mesalamine therapy.

Cardiac Effects

Use with caution in patients with conditions predisposing them to the development of myocarditis or pericarditis. The possibility of pericarditis should be considered in any patient who develops chest pain or dyspnea during mesalamine therapy. Discontinuance may be needed.

Specific Populations

Pregnancy

Category B.

Lactation

Distributed into milk following oral administration. Use with caution.

Not known whether the rectal drug is distributed into milk. Use of rectal mesalamine usually not recommended, although one manufacturer of rectal suppositories states the preparation may be used with caution.

Pediatric Use

Safety and efficacy not established in children.

Has been used (as oral delayed-release tablets) for the management of inflammatory bowel disease (i.e., mild ileal, ileocecal, ileocolonic, or colonic disease) and (as rectal mesalamine suspension) in those with left-sided colitis in a limited number of pediatric patients^†. (See Pediatric Patients under Dosage.)

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger patients. Response does not appear to differ from that in younger adults; however, drug dosage should be selected cautiously.

Possibility of increased incidence of blood dyscrasias (i.e., agranulocytosis, neutropenia, pancytopenia); CBCs should be monitored closely.

Because mesalamine is substantially eliminated by kidneys, assess renal function prior to initiation of therapy and periodically thereafter since geriatric patients more likely to have decreased renal function.

Hepatic Impairment

Use with caution in patients with hepatic impairment.

Renal Impairment

Use with caution in patients with renal impairment.

Common Adverse Effects

Oral therapy: Headache, rash, vomiting, diarrhea, flatulence, constipation, nausea, dyspepsia, abdominal pain, fever, arthralgia, flu syndrome.

Rectal therapy: Headache, abdominal pain, nausea, diarrhea, gas/flatulence, fever, dizziness, rectal pain, rash, leg/joint pain, flu syndrome.

No known drug interactions.

Specific Drugs

Mesalamine Pharmacokinetics

Absorption

Bioavailability

Following oral administration of the 400-mg delayed-release tablets (Asacol), approximately 28% of mesalamine is absorbed and the remainder of the dose is available for topical activity and fecal excretion.

Following oral administration of extended-release capsules (Pentasa), about 20–30% of the drug is absorbed.

Following oral administration of the 1.2-g delayed-release tablets (Lialda), about 21–22% of the drug is absorbed.

Rectally administered suspension is poorly absorbed from the GI tract (about 15% [range: 5–35%]). The rectal suspension usually is retained for about 3.5–12 hours after administration as an enema; prolonged retention may increase absorption of the drug.

Variably absorbed following rectal administration of the suppositories. Rectal suppositories usually are retained for 1–3 hours after administration.

Food

Food does not appear to affect absorption of the 400-mg delayed-release tablets (Asacol).

Food decreases rate of absorption and increases extent of absorption of the 1.2-g delayed-release tablets (Lialda).

Distribution

Extent

Following oral or IV (IV preparation currently not available in the US) administration, the drug may be distributed into kidneys.

Rectal suspension distributes from the rectum into the colon, generally reaching the splenic flexure and possibly the ascending colon. Rectal suppositories distribute to some extent in rectal tissues.

Oral mesalamine crosses the placenta; serum concentrations of mesalamine in umbilical cord and amniotic fluid are very low.

Not known whether rectal mesalamine crosses the placenta.

Oral mesalamine is distributed into milk.

Not known whether rectal mesalamine is distributed into milk.

Plasma Protein Binding

Approximately 44–55% (as unchanged drug).

Approximately 43% at a concentration of 2.5 mcg/mL.

Elimination

Metabolism

Rapidly metabolized, principally in the liver to form N-acetyl-5-aminosalicylic acid.

Elimination Route

Following oral administration, excreted in urine (about 20%) mainly as metabolites and in feces.

Following rectal administration, principally excreted in feces (about 50%), as unchanged drug and metabolites, and in urine (about 10–35%).

Half-life

400-mg delayed-release tablets (Asacol): 12 hours (range: 2–15 hours).

1.2-g delayed-release tablets (Lialda): 7–9 hours (for mesalamine) and 8–12 hours (for N-acetyl-5-aminosalicylic acid metabolite).

Rectal suspension: 0.5–1.5 hours (for mesalamine) and 5–10 hours (for N-acetyl-5-aminosalicylic acid metabolite).

Rectal suppositories: 0.5–7 hours (for mesalamine) and 5–10 hours (for N-acetyl-5-aminosalicylic acid metabolite).

Stability

Storage

Oral

Extended-release Capsules

25°C (may be exposed to 15–30°C).

Delayed-release Tablets

400-mg tablets: 20–25°C.

1.2-g tablets: 15–25°C (may be exposed to 30°C).

Rectal

Suppositories

<25°C. Do not freeze; keep out of reach of children.

Suspension

20–25°C (may be exposed to 15–30°C); keep out of reach of children. May darken with time once the container has been removed from the foil wrap; dark brown suspensions should be discarded.

Actions

• Exerts local (rather than systemic) anti-inflammatory effects in the GI tract.

• May reduce inflammation in the colon by inhibiting cyclooxygenase and lipoxygenase, which catalyze the formation of prostaglandin precursors (endoperoxides) and of leukotrienes and hydroxyeicosatetraenoic acids, respectively, from arachidonic acid and/or its metabolites.

Advice to Patients

• Importance of swallowing delayed-release tablets whole without breaking the outer coating.

• Importance of taking 1.2-g delayed-release tablets with food.

• Importance of informing patients that intact or partially intact tablets may be present in stools and if this occurs repeatedly, they should notify their clinician.

• Importance of informing patients that the rectal suspension and suppositories will cause staining of direct contact surfaces, including, but not limited to, fabrics, flooring, painted surfaces, marble, granite, vinyl, and enamel and therefore, they should carefully choose a suitable location for administration of the rectal suspension.

• Importance of informing patients with sulfasalazine sensitivity to discontinue mesalamine therapy and contact their clinician if signs of sensitivity (e.g., rash, fever) develop or increased diarrhea or rectal bleeding occurs.

• Importance of informing clinicians of existing pancreatitis.

• Importance informing patients that ulcerative colitis rarely remits completely and that continued use of maintenance dosages of mesalamine may substantially decrease the risk of relapse.

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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Frequently asked questions

• What are 7 mesalamine side effects to be aware of?

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