Mesalamine (Monograph)

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.¹ ³ ⁴ ⁶ ¹⁵

Uses for Mesalamine

Ulcerative Colitis

Used for management of ulcerative colitis (as oral delayed-release tablets or extended-release capsules)²²⁸ ²²⁹ ²³¹ ²³² ²³³ ²³⁶ and to induce (as extended-release capsules and as 1.2-g delayed-release tablets)²²⁹ ²³⁶ ⁴⁴⁸ and maintain (as 400-mg delayed-release tablets)²²⁸ ²³⁴ ²³⁵ clinical remission in adults with mildly to moderately active disease.

Management of mildly to moderately active distal ulcerative colitis (as rectal suspension) ¹ ² ³ ⁷ ⁷¹ ⁷² ⁷⁴ ⁷⁸ ⁹³ ⁹⁴ ¹⁰⁴ ¹⁵⁴ ¹⁷⁵ ¹⁷⁶ ¹⁷⁷ ²⁰³ ²⁰⁴ ²⁰⁵ including ulcerative proctosigmoiditis ¹ ² ⁷ ¹⁵ ⁹⁷ ⁹⁹ ¹⁰⁰ ¹⁰² ¹²⁰ ¹²² ¹⁵³ ¹⁵⁴ ¹⁷³ ¹⁷⁵ and ulcerative proctitis.¹ ² ⁷ ⁷¹ ⁷² ⁹⁷ ⁹⁸ ¹²² ¹⁵⁴

Management of active ulcerative proctitis (as rectal suppositories).²¹⁷ ²²⁷ ²³⁰ ²³⁷

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.⁸⁶ ¹⁵⁶

Crohn’s Disease

Has been used (as extended-release oral preparations) for the management of active Crohn’s disease^{† [off-label]}¹⁰⁶ ²⁶¹ ³³⁹ ³⁴¹ ³⁴² ³⁴³ ³⁴⁴ ³⁴⁵ and to induce³⁰⁰ ³³⁹ ³⁴¹ and maintain clinical remission²⁴¹ ²⁴⁵ ²⁴⁸ ²⁵⁰ ³³⁹ ³⁴⁸ ³⁴⁹ ³⁵⁰ ³⁵¹ ³⁵² ³⁵³ ³⁵⁴ ³⁵⁵ ³⁵⁶ ³⁵⁷ 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]},⁷⁰ but the role of such therapy in this condition is not as well defined as in the management of ulcerative colitis.⁸⁸ ¹⁹⁹ ²⁰⁰

Mesalamine Dosage and Administration

Administration

Administer orally⁶⁶ ⁷³ ⁸⁰ ⁸¹ ⁸³ ⁸⁵ ⁹⁰ ⁹¹ ⁹⁶ ¹³⁶ ¹⁵⁶ ¹⁶⁴ ¹⁷² ¹⁷⁴ ²²⁸ ²²⁹ ²³¹ ²³³ ²³⁴ ²³⁵ ²³⁶ ⁴⁴⁸ or rectally.¹ ² ⁷ ⁷¹ ⁷² ⁷⁴ ⁸⁶ ⁹³ ⁹⁴ ⁹⁹ ¹⁰⁰ ¹⁰² ¹⁰³ ¹⁰⁴ ¹⁰⁵ ¹ ²²⁷

Oral Administration

Administer orally as delayed-release tablets (Asacol, Lialda)²²⁸ ²³¹ ²³³ ²³⁴ ⁴⁴⁸ or extended-release capsules (Pentasa).²²⁹ ²³⁵ ²³⁶

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.²²⁸ ⁴⁴⁸ Intact or partially intact tablets may be present in stools; if this occurs repeatedly, patients should notify their clinician.²²⁸

1.2-g delayed-release tablets (Lialda): Administer orally with food.⁴⁴⁸

Rectal Administration

Administer rectally as a suspension retention enema¹ ² ⁷ ⁷¹ ⁷² ⁷⁴ ⁸⁶ ⁹³ ⁹⁴ ⁹⁹ ¹⁰⁰ ¹⁰² ¹⁰³ ¹⁰⁴ ¹⁰⁵ or suppositories.²²⁷ ²³⁰

Administer rectal suspension preferably at bedtime and retain for about 8 hours.¹ Best results are achieved if the bowel is emptied just prior to enema administration.² Administer according to manufacturer’s instructions.¹

Retain rectal suppositories for ≥1–3 hours, if possible, to achieve maximum benefit.⁷⁰ ²¹⁷ ²²⁷ ²³⁰

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.³³³ ³³⁵

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.²²⁸

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.²²⁹ Lower dosages (e.g., 2–4 g daily [in divided doses]) have been used^{† [off-label]}.²⁵⁰

Delayed-release tablets: 2.4 or 4.8 g once daily (given as two or four 1.2-g delayed-release tablets).⁴⁴⁸ Safety and efficacy beyond 8 weeks of treatment have not been established.⁴⁴⁸

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.²²⁸ Dosages of 800 mg to 4.8 g daily (in divided doses) also have been used.²⁵⁰

Extended-release capsules: Dosages of 1.5–3 g daily (in divided doses) have been used.²⁵⁰

Advise patients that ulcerative colitis rarely remits completely, and continued use of maintenance dosages of mesalamine may substantially decrease the risk of relapse.²²⁸

Distal Ulcerative Colitis

Rectal

Suppositories: 1 g (using 1-g suppositories) once daily at bedtime.²²⁷ ²³⁰

Enema suspension: Usually, 4 g once daily (preferably at bedtime).¹ ² ⁷² ⁷⁸ ⁸⁶ ⁹³ ⁹⁴ ²⁰⁵

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.¹ ²²⁷ ²³⁰

Efficacy of rectal therapy (in terms of modification of relapse rates) beyond 6 weeks has not been established,¹ ²²⁷ but mesalamine has been used rectally for prolonged periods (e.g., >1 year) in some patients.⁹³

Lower dosages⁷ ⁷¹ ⁹⁹ ¹⁰⁰ ¹⁰² ¹⁰⁴ ¹⁰⁵ ¹⁷⁶ ²⁰³ ²⁰⁴ ²⁰⁸ or less frequent administration⁹³ ²⁰⁴ 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.⁹³ ²⁰⁴ If clinical relapse occurred with such administration, dosage was increased to more frequent use.⁹³ In some patients with distal ulcerative colitis or ulcerative proctosigmoiditis, the rectal suspension also has been used in dosages of 1–3 g daily.⁷ ⁷¹ ⁹⁹ ¹⁰⁰ ¹⁰² ¹⁰⁴ ¹⁰⁵ ¹⁷⁶ ²⁰³ ²⁰⁴ ²⁰⁸

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)²⁴¹ ²⁴³ ²⁴⁸ ²⁵⁰ ³³⁹ ³⁴⁰ ³⁴² or 4 g daily (as extended-release capsules), generally in divided doses.³⁰⁰ ³³⁹ Lower dosages do not appear to be effective.¹⁰⁶ ³⁰⁰ ³³⁹ ³⁶⁷ ³⁴¹

Prescribing Limits

Pediatric Patients

Ulcerative Colitis† or Crohn’s Disease†

Oral

Maximum 60 mg/kg daily.³³³ ³³⁵

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.²⁵⁰

Extended-release capsules: Maximum 4 g daily in divided doses.²²⁹ ²⁵⁰

Induction of Remission of Mildly to Moderately Active Ulcerative Colitis

Oral

Extended-release capsules: Maximum 4 g daily in divided doses.²²⁹

Delayed-release tablets (1.2 g; Lialda): Safety and efficacy beyond 8 weeks of therapy not established.⁴⁴⁸

Maintenance of Remission

Oral

Delayed-release tablets (400 mg; Asacol): Maximum 4.8 g daily, in divided doses.²⁵⁰

Extended-release capsules^†: Maximum 3 g daily in divided doses.²⁵⁰

Distal Ulcerative Colitis

Rectal

Enema suspension: Maximum 4 g once daily.¹ ² ⁷² ⁷⁸ ⁸⁶ ⁹³ ⁹⁴ ²⁰⁵

The drug has been used rectally for >1 year.⁹³

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.²⁵⁰

Extended-release capsules: Maximum 4 g daily in divided doses.²⁵⁰

Maintenance of Remission

Oral

Delayed-release tablets (400 mg; Asacol): Maximum 4.8 g daily in divided doses.²⁵⁰

Extended-release capsules: Maximum 3 g daily in divided doses.²⁵⁰

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.²²⁸ ²³⁰ ⁴⁴⁸

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)²²⁹ ²³⁰ ⁴⁴⁸ or any ingredient in the respective formulation.¹ ²²⁷ ²²⁸ ²²⁹ ²³⁰ ⁴⁴⁸

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.¹ ² ⁷⁸ ¹¹² ¹¹⁴ ¹²¹ ¹⁵⁶ ¹⁸⁰ ¹⁹⁸ ²¹³ ²²⁷ ²²⁸ ²²⁹ ²³⁰ ⁴⁴⁸ A history of sulfasalazine intolerance, if any, should be reevaluated.¹ ² ¹⁹⁸ ²²⁷ ²²⁸ ²³⁰

Use with caution in patients with a history of hypersensitivity to sulfasalazine.¹ ²²⁷ ²²⁸ ²³⁰ ⁴⁴⁸

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.¹

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.²²⁸ ²²⁹

Use with caution and only if the benefits outweigh the risks⁴⁴⁸ in patients with renal impairment.¹ ²²⁸ ²²⁹ ²³⁰ ⁴⁴⁸

Renal function should be evaluated prior to initiation of therapy and periodically thereafter.¹ ²²⁸ ⁴⁴⁸

GI Effects

Pancolitis reported rarely in patients receiving rectal mesalamine.¹ ² ²²⁷ ²³⁰

Possible worsening colitis or symptoms of inflammatory bowel disease (e.g., melena, hematochezia) in patients receiving rectal mesalamine.¹

Potential for prolonged gastric retention of oral delayed-release tablets in patients with pyloric stenosis.²²⁸ ⁴⁴⁸

The possibility of acute pancreatitis should be considered in any patient who develops new abdominal complaints while receiving mesalamine therapy.²²⁰

Cardiac Effects

Use with caution in patients with conditions predisposing them to the development of myocarditis or pericarditis.⁴⁴⁸ The possibility of pericarditis should be considered in any patient who develops chest pain or dyspnea during mesalamine therapy.¹ Discontinuance may be needed.²²⁷

Specific Populations

Pregnancy

Category B.¹ ²²⁸ ²²⁹ ²³⁰ ⁴⁴⁸

Lactation

Distributed into milk following oral administration.²²⁸ ²²⁹ Use with caution.²²⁸ ²²⁹ ⁴⁴⁸

Not known whether the rectal drug is distributed into milk.¹ ²²⁷ ²³⁰ Use of rectal mesalamine usually not recommended,¹ ²²⁷ although one manufacturer of rectal suppositories states the preparation may be used with caution.²³⁰

Pediatric Use

Safety and efficacy not established in children.¹ ²²⁸ ²²⁹ ²³⁰ ⁴⁴⁸

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^†.⁵⁹ ¹⁹⁹ ²⁰⁰ ³³³ ³³⁵ (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.²²⁸ ²³⁰ ⁴⁴⁸ Response does not appear to differ from that in younger adults; however, drug dosage should be selected cautiously.²³⁰ ⁴⁴⁸

Possibility of increased incidence of blood dyscrasias (i.e., agranulocytosis, neutropenia, pancytopenia); CBCs should be monitored closely.²²⁸

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.²²⁸

Hepatic Impairment

Use with caution in patients with hepatic impairment.²²⁹ ⁴⁴⁸

Renal Impairment

Use with caution in patients with renal impairment.¹ ²²⁸ ²²⁹ ²³⁰

Common Adverse Effects

Oral therapy: Headache, rash, vomiting, diarrhea, flatulence, constipation, nausea, dyspepsia, abdominal pain, fever, arthralgia, flu syndrome.²²⁸ ²²⁹ ⁴⁴⁸

Rectal therapy: Headache, abdominal pain, nausea, diarrhea, gas/flatulence, fever, dizziness, rectal pain, rash, leg/joint pain, flu syndrome.¹ ²²⁷ ²³⁰

No known drug interactions.²²⁸ ²²⁹

Specific Drugs

Drug	Interaction
Azathioprine	Possible increased risk of hematologic toxicity⁴⁴⁸
Digoxin	Decreased GI absorption of digoxin with concomitant sulfasalazine or aminosalicylic acid;¹¹⁵ ¹⁴³ ¹⁹⁵ not known whether mesalamine alters digoxin absorption¹⁹⁹ ²⁰⁰
Mercaptopurine	Possible increased risk of hematologic toxicity⁴⁴⁸
Nephrotoxic drugs (e.g., NSAIAs)	Possible increased nephrotoxicity⁴⁴⁸

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.²²⁸

Following oral administration of extended-release capsules (Pentasa), about 20–30% of the drug is absorbed.²²⁹

Following oral administration of the 1.2-g delayed-release tablets (Lialda), about 21–22% of the drug is absorbed.⁴⁴⁸

Rectally administered suspension is poorly absorbed from the GI tract (about 15% [range: 5–35%]).¹ ² ¹⁵ ⁴³ ⁴⁷ ⁴⁹ ⁶⁵ ⁶⁸ ²¹⁰ ²²⁷ The rectal suspension usually is retained for about 3.5–12 hours after administration as an enema;¹ ² ⁴² ⁴⁷ prolonged retention may increase absorption of the drug.¹⁹⁹ ²⁰⁰

Variably absorbed following rectal administration of the suppositories.²³⁰ Rectal suppositories usually are retained for 1–3 hours after administration.²²⁷

Food

Food does not appear to affect absorption of the 400-mg delayed-release tablets (Asacol).²²⁸

Food decreases rate of absorption and increases extent of absorption of the 1.2-g delayed-release tablets (Lialda).⁴⁴⁸

Distribution

Extent

Following oral or IV (IV preparation currently not available in the US) administration, the drug may be distributed into kidneys.¹ ¹⁹⁹

Rectal suspension distributes from the rectum into the colon, generally reaching the splenic flexure⁷ ⁴² ⁹⁵ ²⁰⁷ and possibly the ascending colon.²⁰⁷ Rectal suppositories distribute to some extent in rectal tissues.²³⁰

Oral mesalamine crosses the placenta;³ ⁴⁷ ¹⁰⁸ ²²⁹ ⁴⁴⁸ serum concentrations of mesalamine in umbilical cord and amniotic fluid are very low.¹⁰⁸

Not known whether rectal mesalamine crosses the placenta.³

Oral mesalamine is distributed into milk.²²⁸ ²²⁹

Not known whether rectal mesalamine is distributed into milk.¹ ² ⁶

Plasma Protein Binding

Approximately 44–55% (as unchanged drug).³ ⁵⁴ ⁶⁰

Approximately 43% at a concentration of 2.5 mcg/mL.⁴⁴⁸

Elimination

Metabolism

Rapidly metabolized, principally in the liver to form N-acetyl-5-aminosalicylic acid.³ ⁴⁷ ⁶³ ⁷⁰ ²²⁸ ⁴⁴⁸

Elimination Route

Following oral administration, excreted in urine (about 20%) mainly as metabolites⁴⁶ ²²⁸ ²²⁹ and in feces.²²⁹

Following rectal administration, principally excreted in feces (about 50%),⁴⁷ ⁷¹ as unchanged drug and metabolites,¹ ⁶ and in urine¹ ² ³ ⁶ ⁴² (about 10–35%).¹ ² ³ ⁶ ⁴² ⁶⁸ ⁷¹

Half-life

400-mg delayed-release tablets (Asacol): 12 hours (range: 2–15 hours).²²⁸

1.2-g delayed-release tablets (Lialda): 7–9 hours (for mesalamine) and 8–12 hours (for N-acetyl-5-aminosalicylic acid metabolite).⁴⁴⁸

Rectal suspension: 0.5–1.5 hours (for mesalamine) and 5–10 hours (for N-acetyl-5-aminosalicylic acid metabolite).¹ ³ ⁴⁷ ⁵⁶ ⁶⁰ ⁶³

Rectal suppositories: 0.5–7 hours (for mesalamine) and 5–10 hours (for N-acetyl-5-aminosalicylic acid metabolite).²²⁷ ²³⁰

Stability

Storage

Oral

Extended-release Capsules

25°C (may be exposed to 15–30°C).²²⁹

Delayed-release Tablets

400-mg tablets: 20–25°C.²²⁸

1.2-g tablets: 15–25°C (may be exposed to 30°C).⁴⁴⁸

Rectal

Suppositories

<25°C.²³⁰ Do not freeze; keep out of reach of children.²³⁰

Suspension

20–25°C (may be exposed to 15–30°C); keep out of reach of children.¹ ⁶ May darken with time once the container has been removed from the foil wrap;¹ dark brown suspensions should be discarded.¹ ¹⁹⁹

Actions

Exerts local (rather than systemic)¹ ² ³ ⁵ ⁷ ⁴² ⁴⁷ ⁴⁹ ⁶⁵ ⁶⁸ ⁶⁹ ⁷⁰ ⁹⁵ ¹⁵⁶ ¹⁷³ ²²⁸ ²²⁹ ²³⁰ ⁴⁴⁸ anti-inflammatory effects in the GI tract.¹ ² ³ ⁴ ⁵ ⁷ ⁹ ¹⁰ ¹³ ²⁶ ⁷⁶ ¹⁶⁸ ¹⁸³
May reduce inflammation in the colon by inhibiting cyclooxygenase and lipoxygenase,¹ ² ³ ¹⁰ ¹² ¹³ ¹⁴ ¹⁶⁸ ²²⁸ ²²⁹ which catalyze the formation of prostaglandin precursors (endoperoxides) and of leukotrienes¹ ² ³ ⁵ ⁹ ¹⁰ ¹² ¹³ ²⁶ ³⁹ ⁷⁶ ¹⁶⁸ ¹⁸³ ²¹⁰ and hydroxyeicosatetraenoic acids, respectively, from arachidonic acid and/or its metabolites.⁵ ¹⁰ ¹³ ²¹⁰

Advice to Patients

Importance of swallowing delayed-release tablets whole without breaking the outer coating.²²⁸ ⁴⁴⁸
Importance of taking 1.2-g delayed-release tablets with food.⁴⁴⁸
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.²²⁸
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 enamel¹ and therefore, they should carefully choose a suitable location for administration of the rectal suspension.¹ ²³⁰
Importance of informing patients with sulfasalazine sensitivity¹ ² ⁷⁸ ⁸⁷ ¹²¹ ¹⁸⁰ ²²⁸ ²³⁰ to discontinue mesalamine therapy and contact their clinician if signs of sensitivity (e.g., rash, fever) develop¹ ² ¹⁹⁸ ²³⁰ or increased diarrhea or rectal bleeding occurs.²⁰⁰
Importance of informing clinicians of existing pancreatitis.²³⁰
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.²²⁸
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹
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.

Mesalamine
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Capsules, extended-release	250 mg	Pentasa	Shire
		500 mg	Pentasa	Shire
	Tablets, delayed-release	400 mg	Asacol	Procter & Gamble
		1.2 g	Lialda	Shire
Rectal	Suppositories	1 g	Canasa	Axcan
	Suspension	4 g/60 mL	Mesalamine Suspension Enema
			Rowasa Suspension Enema	Alaven

† Off-label: Use is not currently included in the labeling approved by the US Food and Drug Administration.

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