Drug Monograph
Mesalamine (5-ASA)
mesalamine • 5-aminosalicylic acid
Pharmacokinetic Profile
Half-Life
Mesalamine: ~0.5–10 h (variable); N-Ac-5-ASA: ~2–15 h
Metabolism
N-acetyltransferase (gut wall & liver) → N-acetyl-5-ASA (inactive)
Systemic Absorption
~20–28% (formulation-dependent); action is topical/local
Excretion
Absorbed portion: kidney (as N-Ac-5-ASA); unabsorbed: feces
Clinical Information
Drug Class
5-Aminosalicylate (Aminosalicylate)
Oral Formulations
Lialda, Asacol HD, Delzicol, Pentasa, Apriso
Key Safety Concern
Nephrotoxicity — renal monitoring required
Renal Adjustment
No formal dose adjustment; use caution in renal impairment
Hepatic Adjustment
Caution in hepatic failure (rare reports of hepatic failure)
Pregnancy
Generally considered safe; continue for UC management in pregnancy
Lactation
Present in breast milk in small amounts; monitor infant for diarrhea
Generic Available
Yes (most formulations)
Indications
| Formulation | Indication | Population | Status |
|---|---|---|---|
| Lialda | Induction & maintenance of remission in mild–moderate UC | Adults; pediatrics ≥5 yr (≥24 kg) | FDA Approved |
| Asacol HD | Treatment of moderately active UC | Adults only | FDA Approved |
| Delzicol | Treatment of mild–moderate UC; maintenance of remission | Adults; pediatrics ≥5 yr | FDA Approved |
| Pentasa | Induction of remission in mild–moderate UC | Adults only | FDA Approved |
| Apriso | Maintenance of remission of UC only | Adults only | FDA Approved |
Mesalamine (5-aminosalicylic acid, 5-ASA) is the first-line treatment for mild-to-moderate ulcerative colitis. It has been available in the US since 1987 (first as rectal formulations) and is recommended by both the AGA (2019) and ACG (2019, updated 2025) as initial therapy for induction and maintenance of remission. Guideline-defined dose tiers are: low dose (<2 g/day), standard dose (2–3 g/day), and high dose (>3 g/day). High-dose and standard-dose mesalamine are both superior to low-dose for induction, while standard-dose is sufficient for maintenance. Once-daily dosing is non-inferior to divided dosing for both induction and maintenance. The different oral formulations are considered therapeutically equivalent at comparable doses, but they differ in their release site, food requirements, and pill burden.
Note on Crohn’s Disease
Oral mesalamine is not considered effective for Crohn’s disease in current evidence-based guidelines. Earlier guidelines had conditionally supported use for mild ileal Crohn’s, but the AGA/ACG now recommend against mesalamine for Crohn’s disease induction or maintenance, based on large negative trials.
Dosing
Oral Formulation Comparison — Adult Dosing
| Formulation | Strengths | Induction Dose | Maintenance Dose | Food | Release Site |
|---|---|---|---|---|---|
| Lialda Delayed-release tablet (Multi Matrix System) | 1.2 g | 2.4–4.8 g once daily (2–4 tablets) for up to 8 weeks | 2.4 g once daily (2 tablets) | WITH food | Terminal ileum & colon (pH ≥6.8 + extended-release core) |
| Asacol HD Delayed-release tablet | 800 mg | 1600 mg TID = 4.8 g/day (2 tablets three times daily) for 6 weeks | Not specifically labeled for maintenance | EMPTY stomach ≥1 hr before or 2 hr after meals | Terminal ileum & colon (pH ≥7, Eudragit S+L) |
| Delzicol Delayed-release capsule (4 × 100 mg tablets inside) | 400 mg | 800 mg TID = 2.4 g/day (2 capsules three times daily) for 6 weeks | 1.6 g/day (4 capsules in 2–4 divided doses) | With or without food | Terminal ileum & colon (pH ≥7, Eudragit S) |
| Pentasa Controlled-release capsule (ethylcellulose microgranules) | 250 mg, 500 mg | 1 g QID = 4 g/day for up to 8 weeks | Not specifically labeled for maintenance | With or without food Can sprinkle on applesauce/yogurt | Duodenum through colon (gradual release throughout GI tract) |
| Apriso Extended-release capsule (pH ≥6 coating + retarding polymer) | 0.375 g | Not indicated for induction | 1.5 g once daily (AM) (4 capsules in the morning) | With or without food | Terminal ileum & colon (pH ≥6 coating + extended-release matrix) |
Critical: Non-Interchangeability
One Asacol HD 800 mg tablet is NOT bioequivalent to two Asacol/Delzicol 400 mg tablets (Cmax 36% lower, AUC 25% lower). Do not substitute one for the other. Different formulations have different release mechanisms and should be prescribed by specific brand name or with awareness of the specific formulation being dispensed.
Clinical Pearl: Guideline-Based Dosing Strategy
The AGA 2019 mild-moderate UC guideline recommends standard-dose mesalamine (2–3 g/day) for induction. If response is suboptimal, escalate to high-dose (>3 g/day) combined with rectal mesalamine before adding corticosteroids. The ACG guideline (2019, updated 2025) recommends at least 2 g/day oral mesalamine for mildly active UC, with no difference between once-daily and divided dosing. For maintenance, at least 1.5 g/day is recommended. Once-daily dosing may improve adherence, which is a major determinant of relapse risk.
Pharmacology
Mechanism of Action
Mesalamine (5-aminosalicylic acid) acts as a topical anti-inflammatory agent in the colonic mucosa. Its mechanism is not fully elucidated but involves inhibition of cyclooxygenase and lipoxygenase pathways, reducing prostaglandin and leukotriene synthesis in the inflamed bowel wall. More recent data indicate that mesalamine also inhibits NF-κB activation, a key nuclear transcription factor that regulates transcription of many pro-inflammatory genes. Unlike sulfasalazine, mesalamine does not contain the sulfapyridine moiety responsible for most sulfonamide-related adverse effects. The therapeutic effect is primarily local/topical in the colonic lumen, which is why the various oral formulations are engineered to deliver drug to specific regions of the intestine while minimizing systemic absorption.
ADME Profile
| Parameter | Value | Clinical Implication |
|---|---|---|
| Absorption | ~20–28% absorbed systemically (formulation-dependent); Tmax varies widely: Pentasa ~3 h, Apriso ~4 h, Lialda ~9–12 h, Asacol HD ~10–16 h, Delzicol ~4–16 h | Therapeutic effect is primarily topical, not systemic; different Tmax values reflect different release mechanisms, not efficacy differences |
| Distribution | Limited systemic distribution; protein binding data limited | Drug acts locally on colonic mucosa; systemic levels are a byproduct rather than required for efficacy |
| Metabolism | Rapidly acetylated in gut mucosa and liver by N-acetyltransferase to N-acetyl-5-ASA (inactive); independent of acetylator phenotype; not CYP-mediated | No CYP-mediated drug interactions; the metabolite N-Ac-5-ASA is the predominant form in plasma and urine |
| Elimination | Absorbed mesalamine: excreted as N-Ac-5-ASA mainly by the kidney; unabsorbed mesalamine: excreted in feces; IV t½ ~40 min; oral t½ 2–15 h (variable) | Renal excretion of absorbed drug makes nephrotoxicity the key safety concern; monitor renal function at baseline and periodically |
Side Effects
Mesalamine is generally well tolerated. Adverse reaction rates below are representative from pivotal trials of Asacol HD and Lialda, the two most commonly prescribed oral formulations. Rates are similar across formulations at equivalent doses.
1–5%Common
| Adverse Effect | Incidence (Asacol HD) | Clinical Note |
|---|---|---|
| Headache | 4.7% | Most common AE across all formulations; usually mild and transient |
| Nausea | 2.8% | May be reduced by taking with food (formulation permitting) |
| Nasopharyngitis | 2.5% | Common across trial populations; likely coincidental |
| Abdominal pain | 2.3% | Distinguish from mesalamine-induced acute intolerance syndrome |
| Diarrhea | 1.7% | If worsening diarrhea with mesalamine initiation, consider acute intolerance |
| Dyspepsia | 1.7% | More common with formulations taken on empty stomach |
| Flatulence | 1–3% | Related to colonic delivery of drug; usually self-limiting |
SeriousSerious (Regardless of Frequency)
| Adverse Effect | Estimated Frequency | Typical Onset | Required Action |
|---|---|---|---|
| Renal impairment (minimal change nephropathy, interstitial nephritis, renal failure) | Rare (all formulation PIs) | Weeks to years; can occur at any time | Monitor renal function at baseline and periodically; discontinue if renal function deteriorates; kidney is the principal organ of mesalamine toxicity in animals |
| Mesalamine-induced acute intolerance syndrome | ~3% in controlled trials | Within days of starting therapy; may mimic UC flare | Discontinue mesalamine immediately; symptoms include cramping, acute abdominal pain, bloody diarrhea, sometimes fever/headache/rash; distinguish from UC exacerbation |
| Hypersensitivity (myocarditis, pericarditis) | Very rare (postmarketing) | Typically within first few weeks | Discontinue permanently; never rechallenge; cardiac workup required |
| Hepatic failure | Very rare (postmarketing) | Variable | Caution in pre-existing liver disease; monitor LFTs if indicated |
| Nephrolithiasis (mesalamine-containing stones) | Rare (Asacol HD PI) | Variable | Ensure adequate hydration; mesalamine stones are undetectable by standard radiography or CT |
| Blood dyscrasias (agranulocytosis, pancytopenia) | Rare; higher incidence in elderly and with AZA/6-MP | Variable | Monitor CBC, especially in elderly and patients on thiopurines |
| Severe cutaneous adverse reactions | Very rare (Asacol HD PI) | Variable | Discontinue at first signs; patients with pre-existing skin conditions should avoid excess sun exposure |
Drug Interactions
Mesalamine is not metabolized by cytochrome P450 enzymes, limiting PK interactions. However, two important pharmacodynamic interactions exist.
MajorAzathioprine / 6-Mercaptopurine
MechanismMesalamine inhibits thiopurine methyltransferase (TPMT), increasing 6-thioguanine nucleotide levels
EffectIncreased risk of myelosuppression, blood dyscrasias (leukopenia, pancytopenia, agranulocytosis)
ManagementMonitor CBC and platelet counts regularly; particularly important in elderly patients; dose adjustment of thiopurine may be needed
All Mesalamine PIsMajorNephrotoxic agents (NSAIDs, aminoglycosides, tacrolimus, cyclosporine)
MechanismAdditive nephrotoxicity risk; mesalamine independently causes interstitial nephritis and minimal change nephropathy
EffectIncreased risk of renal impairment
ManagementMonitor renal function closely; consider mesalamine-related adverse reactions; discontinue if renal function deteriorates
All Mesalamine PIsMinorUrinary normetanephrine assays
MechanismN-Ac-5-ASA metabolite co-elutes with normetanephrine on liquid chromatography with electrochemical detection
EffectSpuriously elevated urinary normetanephrine results (false positive for pheochromocytoma)
ManagementUse an alternative, selective assay for normetanephrine
All Mesalamine PIsMonitoring
- Renal FunctionBaseline and periodically
RoutineAll mesalamine PIs mandate renal function evaluation prior to initiation and periodically during therapy. Mesalamine can cause minimal change nephropathy, acute and chronic interstitial nephritis, and rarely renal failure. The kidney is the principal organ of mesalamine toxicity in animal studies. Use caution in patients with known renal impairment. Discontinue if renal function deteriorates. - CBC & PlateletsBaseline; regularly if on AZA/6-MP
RoutineMonitor for blood dyscrasias, especially in elderly patients (≥65 years) and those on concomitant thiopurines. Higher incidence of agranulocytosis, neutropenia, and pancytopenia reported in elderly patients. - Acute IntoleranceFirst 2–4 weeks
Trigger-basedWatch for mesalamine-induced acute intolerance syndrome (~3% in trials). Symptoms mimic UC flare: cramping, acute abdominal pain, bloody diarrhea, fever, headache, rash. If symptoms worsen after starting mesalamine, discontinue and reassess before attributing to a UC flare. - Cardiac SymptomsIf chest pain, dyspnea, or palpitations occur
Trigger-basedMyocarditis and pericarditis have been reported as hypersensitivity reactions. Discontinue mesalamine immediately and do not rechallenge. Patients with prior hypersensitivity to sulfasalazine may be at higher risk. - Hydration StatusOngoing
RoutineMesalamine-containing kidney stones are undetectable by standard radiography or CT. Ensure adequate fluid intake throughout treatment. Patients should be advised to drink plenty of fluids.
Contraindications & Cautions
Absolute Contraindications
- Known or suspected hypersensitivity to salicylates, aminosalicylates, or any ingredients in the specific formulation.
Use with Caution
- Renal impairment or history of renal disease: The kidney is the principal organ of mesalamine toxicity. Evaluate renal function before starting and periodically during therapy. Use caution with concomitant nephrotoxic drugs.
- Hepatic impairment: Hepatic failure has been reported in patients with pre-existing liver disease receiving mesalamine.
- Sulfasalazine allergy: Some patients with prior sulfasalazine hypersensitivity may cross-react with mesalamine; monitor closely.
- Phenylketonuria (PKU): Apriso capsules contain aspartame, which generates phenylalanine.
- Elderly patients (≥65 years): Higher incidence of blood dyscrasias reported; monitor CBC regularly.
- Upper GI obstruction (Asacol HD): The delayed-release coating may result in prolonged gastric retention and delayed onset of action.
No Boxed Warning
Mesalamine does not carry an FDA boxed warning. The primary safety concern is nephrotoxicity, which requires baseline and periodic renal function monitoring across all formulations.
Patient Counselling
Purpose of Therapy
Mesalamine is an anti-inflammatory medication that works directly on the lining of your colon to reduce inflammation caused by ulcerative colitis. It is not a steroid and does not suppress your immune system. It is typically the first medication used for mild-to-moderate UC and is taken long-term to keep the disease in remission.
How to Take Your Specific Formulation
LialdaTake with food, once daily. Swallow tablets whole; do not split or crush.
Asacol HDTake on an empty stomach (at least 1 hour before or 2 hours after a meal). Swallow whole; do not crush, break, or chew.
DelzicolTake with or without food. If you cannot swallow capsules, open and swallow the 4 small tablets inside — do not chew them.
PentasaTake with or without food, four times daily. If you cannot swallow capsules, sprinkle contents on applesauce or yogurt and swallow immediately without chewing.
AprisoTake once daily in the morning, with or without food. Swallow capsules whole.
Worsening Symptoms on Starting Treatment
Tell patientIn about 3 out of 100 patients, mesalamine can cause an acute intolerance reaction that looks like a worsening of your UC — stomach cramping, bloody diarrhea, and sometimes fever. This is actually a reaction to the medication itself, not a flare of your disease.
Call prescriberIf your symptoms get worse within the first few weeks of starting mesalamine, stop the medication and call your doctor right away. Do not assume it is a UC flare.
Kidney Health & Hydration
Tell patientMesalamine can rarely affect your kidneys. Drink plenty of fluids throughout the day. Your doctor will check your kidney function before you start and periodically during treatment.
Call prescriberReport any changes in urination (amount, frequency, pain), swelling in your legs or feet, or unusual fatigue.
Tablet Shells in Stool
Tell patientYou may occasionally see intact or partially intact tablet shells in your stool. This is normal for delayed-release formulations — the medication has already been released. However, if you see this happening frequently, tell your doctor.
Sources
Regulatory (Prescribing Information)
- LIALDA (mesalamine) delayed-release tablets. Full Prescribing Information. Takeda Pharmaceuticals. Revised October 2023. DailyMedSource for Lialda dosing (induction 2.4–4.8 g QD with food; maintenance 2.4 g QD), pediatric dosing, AE rates, and renal warnings.
- ASACOL HD (mesalamine) delayed-release tablets. Full Prescribing Information. Allergan USA, Inc. Revised November 2022. Drugs.com PISource for Asacol HD dosing (1600 mg TID = 4.8 g/day for moderately active UC), AE rates (headache 4.7%, nausea 2.8%), and non-interchangeability warning.
- DELZICOL (mesalamine) delayed-release capsules. Full Prescribing Information. Allergan USA, Inc. Drugs.com PISource for Delzicol dosing (800 mg TID induction, 1.6 g/day maintenance), pediatric dosing, and capsule opening instructions.
- PENTASA (mesalamine) controlled-release capsules. Full Prescribing Information. Shire US Inc. Drugs.com PISource for Pentasa dosing (1 g QID = 4 g/day), ethylcellulose microgranule release mechanism, and applesauce/yogurt administration.
- APRISO (mesalamine) extended-release capsules. Full Prescribing Information. Salix Pharmaceuticals. Drugs.com PISource for Apriso dosing (1.5 g once daily maintenance only), PKU/aspartame warning, and release mechanism (pH ≥6 + polymer matrix).
Guidelines
- Ko CW, Singh S, Feuerstein JD, et al. AGA Clinical Practice Guidelines on the management of mild-to-moderate ulcerative colitis. Gastroenterology. 2019;156(3):748–764. DOIAGA guideline recommending standard-dose mesalamine (2–3 g/day) for extensive mild-moderate UC (strong, moderate); once-daily dosing non-inferior to divided dosing.
- Rubin DT, Ananthakrishnan AN, Siegel CA, et al. ACG Clinical Guideline: ulcerative colitis in adults. Am J Gastroenterol. 2019;114(3):384–413. DOIACG guideline recommending mesalamine as first-line for mild-to-moderate UC induction and maintenance; oral ≥2.0 g/day.
- Singh S, Loftus EV Jr, Limketkai BN, et al. AGA Living Clinical Practice Guideline on pharmacological management of moderate-to-severe ulcerative colitis. Gastroenterology. 2024;167(7):1307–1343. DOIAGA living guideline for moderate-to-severe UC; positions advanced therapies after 5-ASA failure.
Key Clinical Trials
- Hanauer SB, Sandborn WJ, Kornbluth A, et al. Delayed-release oral mesalamine at 4.8 g/day (800 mg tablet) for the treatment of moderately active ulcerative colitis: the ASCEND II trial. Am J Gastroenterol. 2005;100(11):2478–2485. DOIPivotal trial for Asacol HD establishing 4.8 g/day dosing; 72% improvement rate vs 59% with 2.4 g/day in moderately active UC.
- Kamm MA, Sandborn WJ, Gassull M, et al. Once-daily, high-concentration MMX mesalamine in active ulcerative colitis. Gastroenterology. 2007;132(1):66–75. DOIPhase 3 pivotal trial for Lialda demonstrating superiority of both 2.4 g and 4.8 g once daily over placebo for induction of remission.
- Ford AC, Khan KJ, Achkar JP, et al. Efficacy of oral vs. topical, or combined oral and topical 5-aminosalicylates, in ulcerative colitis: systematic review and meta-analysis. Am J Gastroenterol. 2012;107(2):167–176. DOIMeta-analysis demonstrating superiority of combined oral + rectal 5-ASA over oral alone for UC induction and maintenance.
Mechanistic / Basic Science
- Desreumaux P, Ghosh S. Review article: mode of action and delivery of 5-aminosalicylic acid — new evidence. Aliment Pharmacol Ther. 2006;24(Suppl 1):2–9. DOIComprehensive review of mesalamine’s local anti-inflammatory mechanisms including COX/LOX inhibition, NF-κB suppression, and PPAR-γ activation.
Pharmacokinetics / Special Populations
- Lichtenstein GR, Kamm MA, Boddu P, et al. Effect of once- or twice-daily MMX mesalamine (SPD476) for the induction of remission of mild to moderately active ulcerative colitis. Clin Gastroenterol Hepatol. 2007;5(1):95–102. DOIPhase 3 once- vs twice-daily Lialda trial supporting once-daily dosing convenience with comparable efficacy.