Mesalamine .375 g Capsule, Extended Release, 120-count
Other active recalls for Mesalamine (different manufacturers) — 1 · tap to view
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Aminosalicylate class.
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🏭 Manufacturer & labeler
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🩺 Clinical
Mesalamine is used to treat ulcerative colitis (a condition which causes swelling and sores in the lining of the colon [large intestine] and rectum) and also to maintain improvement of ulcerative colitis symptoms. Mesalamine is in a class of medications called anti-inflammatory agents. It works by stopping the body from producing a certain substance that may cause inflammation.
Read the full MedlinePlus article ↗- Mesalamine works to reduce inflammation directly in the lining of your colon or rectum. Depending on which product you've been prescribed, it can help bring an active flare of ulce...
- What exactly is mesalamine supposed to do for me?
- It really does matter, and they're not interchangeable. The form your doctor chose depends on where in your bowel the inflammation is. Rectal suppositories (like CANASA) treat infl...
- There are so many different forms — pills, enemas, suppositories. Does it matter which one I use?
Patient education
Supplement & herbal interactions
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💊 What it looks like
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
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Ethylcellulose is a plant-fiber derivative used as a binder and film-coating agent in tablets and capsules. It helps hold ingredients together and can create a protective coating that controls how quickly the medicine dissolves.
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FD&C Blue No. 1 is a synthetic blue dye approved for use in foods and medicines. It serves as a colorant to give the medication its distinctive appearance and help with product identification.
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A dark iron oxide compound that gives medicines their black or dark color. It's used as a colorant in tablets and capsules to help identify the product and make it visually distinctive.
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Gelatin is a protein derived from animal collagen, commonly used in medicines as a gelling agent and capsule material. It helps create soft or hard capsule shells that hold and release medication, and can also thicken liquid formulations.
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Hypromellose 2910 is a plant-derived thickening agent made from cellulose. It serves as a binder that holds tablet ingredients together, a film-coating for pills, and a viscosity controller in liquids.
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A synthetic polymer made by combining two plastic-like chemicals. It forms a coating on tablets or capsules that dissolves at a specific point in the digestive tract, controlling where and when the medicine releases.
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Potassium hydroxide is a strong alkaline chemical used in medicines to adjust and maintain the pH level of liquid formulations, helping keep the product stable and the active ingredients effective.
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Propylene glycol is a clear liquid derived from petroleum or vegetable sources. It acts as a solvent, humectant, and preservative in medicines, helping dissolve active ingredients and maintain product stability.
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Shellac is a natural resin secreted by the lac beetle. It's used as a coating on tablets and capsules to control how quickly the medicine dissolves and to improve appearance and stability.
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A detergent and foaming agent derived from coconut or palm oil. In medications, it helps break down and mix oil and water-based ingredients, aids in tablet disintegration, and improves how the drug dissolves and spreads in the mouth or digestive system.
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A plant-based carbohydrate derived from corn kernels. It acts as a filler to add bulk, a binder to hold ingredients together, and a disintegrant to help the tablet break apart in your stomach for absorption.
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A natural sugar derived from sugar cane or sugar beets. It's used as a sweetener, filler, and binder to improve taste, add bulk, and help hold tablet or capsule ingredients together.
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A powder made from a naturally occurring mineral. In medicines, talc works as a glidant and anti-caking agent, helping tablets and capsules flow smoothly during manufacturing and preventing clumping.
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Titanium dioxide is a bright white mineral powder commonly used as a colorant and opacifying agent. It makes pills and tablets white or lighter in color and helps make coatings non-transparent.
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Triethyl citrate is a clear liquid derived from citric acid. It acts as a plasticizer and solvent in tablet coatings and film formulations, helping the coating remain flexible and adhere properly to the medicine.
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Water is a liquid solvent that dissolves and mixes ingredients together in liquid medicines, syrups, and injections. It helps distribute the active drug evenly throughout the product.
16 inactive ingredients listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per ea | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $0.487 | $58.38 / 120 capsules |
| Medicaid paysCMS SDUD · 12 mo | $0.6237 | $74.84 / 120 capsules |
| Medicare drug plans payPart D · Q2 2026 | $1.16 | $139.36 / 120 capsules |
Where does this data come from?
🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| mesalamine 375 mg 00093-9224-89 | Teva | 120 capsules | $0.487 | AB | Availability likely | — |
| Mesalamine .375 g 00378-1375-78 | Mylan | 120 capsules | $0.487 | AB | Availability likely | — |
| Mesalamine .375 g 00832-6056-12 | Upsher-Smith | 120 capsules | $0.487 | AB | Availability likely | — |
| Mesalamine .375 g 50268-0577-15 | AvPAK | 1 capsule | $0.487 | AB | Availability likely | — |
| Mesalamine .375 g 59651-0397-08 | Aurobindo | 120 capsules | $0.487 | AB | Availability likely | — |
| Mesalamine .375 g 60687-0650-32 | American | 1 capsule | $0.487 | AB | Availability likely | — |
| Mesalamine .375 g 62332-0724-35 | Alembic | 120 capsules | $0.487 | AB | Availability likely | — |
| Mesalamine .375 gthis 68382-0452-19 | Zydus | 120 capsules | $0.487 | AB | Availability likely | — |
| mesalamine 375 mg 68682-0113-20 | Oceanside | 120 capsules | $0.727 | AB | FDA listed | +49% |
| Mesalamine 375 mg 31722-0489-12 | Camber | 120 capsules | — | AB | FDA listed | — |
| Mesalamine .375 g 46708-0724-35 | Alembic | 120 capsules | — | AB | FDA listed | — |
| Mesalamine .375 g 50742-0371-12 | Ingenus | 120 capsules | — | AB | FDA listed | — |
| Mesalamine .375 g 51407-0976-12 | Golden | 120 capsules | — | AB | FDA listed | — |
| Apriso 375 mg 65649-0103-01 | Salix | 4 capsules | — | AB | FDA listed | — |
| Mesalamine .375 g 67877-0717-05 | Ascend | 500 capsules | — | AB | FDA listed | — |
| Mesalamine .375 g 70771-1625-07 | Zydus | 120 capsules | — | AB | FDA listed | — |
Where does this data come from?
⏳ Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
Where does this data come from?
🗺️ Medicaid utilization & spend
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 68382-0452-19 You're viewing this | 120 CAPSULE, EXTENDED RELEASE in 1 BOTTLE (68382-452-19) | 2021-08-13 | Active |
📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Mesalamine extended-release capsules are indicated for the maintenance of remission of ulcerative colitis in adults. Mesalamine extended-release capsules are an aminosalicylate indicated for the maintenance of remission of ulcerative colitis in adults. ( 1 )
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Dosage The recommended dosage in adults is 1.5 g (four 0.375 g capsules) orally once daily in the morning. Administration Instructions Evaluate renal function before initiating therapy with mesalamine extended-release capsules [see Warnings and Precautions ( 5.1 )] . Swallow mesalamine extended-release capsules whole.
Do not cut, break, crush or chew the capsules. Avoid co-administration of mesalamine extended-release capsules with antacids [see Drug Interactions ( 7.1 )] . Drink an adequate amount of fluids [see Warnings and Precautions ( 5.7 )].
Take mesalamine extended-release capsules without regard to meals [see Clinical Pharmacology ( 12.3 )] . Dosage The recommended dosage is 1.5 g (four 0.375 g capsules) once daily in the morning. ( 2 ) Administration Instructions Evaluate renal function before initiating therapy with mesalamine extended-release capsules.
( 2 ) Swallow the capsules whole. Do not cut, break, crush or chew the capsules. ( 2 ) Avoid co-administration with antacids.
( 2 , 7.1 ) Drink an adequate amount of fluids. ( 2 , 5.6 ) Take mesalamine extended-release capsules without regard to meals. ( 2 ) .
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Mesalamine extended-release capsules USP, 0.375 g are off-white to light brown colored free flowing pellets filled in size '00' hard gelatin capsules having opaque blue color 'cap' without imprint and opaque blue color 'body' printed with '452' in black ink. Extended-release capsules: 0.375 g ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS Mesalamine extended-release capsules are contraindicated in patients with hypersensitivity to salicylates or aminosalicylates or to any of the components of mesalamine extended-release capsules [see Warnings and Precautions ( 5.3 ), Adverse Reactions ( 6.2 ), Description ( 11 )] . Known or suspected hypersensitivity to salicylates, aminosalicylates, or any component of mesalamine extended-release capsules. ( 4 , 5.3 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Renal Impairment: Assess renal function at the beginning of treatment and periodically during treatment. Evaluate the risks and benefits in patients with known renal impairment or taking nephrotoxic drugs; monitor renal function. Discontinue if renal function deteriorates.
( 5.1 , 7.2 , 8.6 ) Mesalamine-Induced Acute Intolerance Syndrome: Symptoms may be difficult to distinguish from an exacerbation of ulcerative colitis; monitor for worsening symptoms; discontinue treatment if acute intolerance syndrome is suspected. ( 5.2 ) Hypersensitivity Reactions, including Myocarditis and Pericarditis: Evaluate patients immediately and discontinue if a hypersensitivity reaction is suspected. ( 5.3 ) Hepatic Failure: Evaluate the risks and benefits in patients with known liver impairment.
( 5.4 ) Severe Cutaneous Adverse Reactions: Discontinue at the first signs or symptoms of severe cutaneous adverse reactions or other signs of hypersensitivity and consider further evaluation. ( 5.5 ) Photosensitivity: Advise patients with pre-existing skin conditions to avoid sun exposure, wear protective clothing, and use a broad-spectrum sunscreen when outdoors. ( 5.6 ) Nephrolithiasis: Mesalamine-containing stones are undetectable by standard radiography or computed tomography (CT).
Ensure adequate fluid intake during treatment. ( 5.7 ) Interference with Laboratory Tests: Use of mesalamine may lead to spuriously elevated test results when measuring urinary normetanephrine by liquid chromatography with electrochemical detection. ( 5.8 )
5.1Renal Impairment Renal impairment, including minimal change disease, acute and chronic interstitial nephritis, and renal failure, has been reported in patients given products such as mesalamine extended-release capsules that contain mesalamine or are converted to mesalamine. In animal studies, the kidney was the principal organ of mesalamine toxicity [see Adverse Reactions ( 6.2 ), Nonclinical Toxicology ( 13.2 )]. Evaluate renal function prior to initiation of mesalamine extended-release capsules therapy and periodically while on therapy.
Evaluate the risks and benefits of using mesalamine extended-release capsules in patients with known renal impairment or a history of renal disease or taking concomitant nephrotoxic drugs. Discontinue if renal function deteriorates while on therapy [see Drug Interactions ( 7.2 ), Use in Specific Populations ( 8.6 )] .
5.2Mesalamine-Induced Acute Intolerance Syndrome Mesalamine has been associated with an acute intolerance syndrome that may be difficult to distinguish from an exacerbation of ulcerative colitis. Although the exact frequency of occurrence has not been determined, it has occurred in 3% of patients in controlled clinical trials of mesalamine or sulfasalazine. Symptoms include cramping, acute abdominal pain and bloody diarrhea, sometimes fever, headache, and rash.
Monitor patients for worsening of these symptoms while on treatment. If acute intolerance syndrome is suspected, promptly discontinue treatment with mesalamine extended-release capsules.
5.3Hypersensitivity Reactions Some patients have experienced a hypersensitivity reaction to sulfasalazine. Some patients may have a similar reaction to mesalamine extended-release capsules or to other compounds that contain or are converted to mesalamine. As with sulfasalazine, mesalamine-induced hypersensitivity reactions may present as internal organ involvement, including myocarditis, pericarditis, nephritis, hepatitis, pneumonitis and hematologic abnormalities.
Evaluate patients immediately if signs or symptoms of a hypersensitivity reaction are present. Discontinue mesalamine extended-release capsules if an alternative etiology for the signs and symptoms cannot be established.
5.4Hepatic Failure There have been reports of hepatic failure in patients with pre-existing liver disease who have been administered mesalamine. Evaluate the risks and benefits of using mesalamine extended-release cap…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in labeling: Renal Impairment [see Warnings and Precautions ( 5.1 )] Mesalamine-Induced Acute Intolerance Syndrome [see Warnings and Precautions ( 5.2 )] Hypersensitivity Reactions [see Warnings and Precautions ( 5.3 )] Hepatic Failure [see Warnings and Precautions ( 5.4 )] Severe Cutaneous Adverse Reactions [see Warnings and Precautions ( 5.5 )] Photosensitivity [see Warnings and Precautions ( 5.6 )] Nephrolithiasis [see Warnings and Precautions ( 5.7 )] Most common adverse reactions (≥3%) are: headache, diarrhea, upper abdominal pain, nausea, and nasopharyngitis.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Zydus Pharmaceuticals (USA) Inc. at 1-877-993-8779 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical Trials Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The data described below reflect exposure to mesalamine extended-release capsules in 557 patients, including 354 exposed for at least 6 months and 250 exposed for greater than one year. Mesalamine extended-release capsules was studied in two placebo-controlled trials (n=367 treated with mesalamine extended-release capsules) and in one open-label, long-term study (n=190 additional patients).
The population consisted of patients with ulcerative colitis; the mean age was 47 years, 54% were female, and 93% were white. Patients received doses of mesalamine extended-release capsules 1.5 g administered orally once per day for six months in the placebo-controlled trials and for up to 24 months in the open-label study. In the two placebo-controlled trials, the most common reactions reported in at least 3% of mesalamine extended-release capsules-treated patients and at a greater rate than placebo are shown in Table 1 below.
Table 1 Common Adverse Reactions * in Clinical Trials of Adults with Ulcerative Colitis * Reported in at least 3% of mesalamine extended-release capsules-treated patients and at a greater rate than with placebo Mesalamine Extended-Release Capsules 1.5 g once daily N=367 Placebo N=185 Headache 11% 8% Diarrhea 8% 7% Upper Abdominal Pain 5% 3% Nausea 4% 3% Nasopharyngitis 4% 3% The following adverse reactions, presented by body system, were reported at a frequency less than 3% in patients treated with mesalamine extended-release capsules for up to 24 months in controlled and open-label trials.
Ear and Labyrinth Disorders: tinnitus, vertigo Dermatological Disorder: alopecia Gastrointestinal: lower abdominal pain, rectal hemorrhage Laboratory Abnormalities: increased triglycerides, decreased hematocrit and hemoglobin General Disorders and Administration Site Disorders: fatigue Hepatic: hepatitis cholestatic, transaminases increased Renal Disorders: creatinine clearance decreased, hematuria Musculoskeletal: pain, arthralgia Respiratory: dyspnea
6.2Postmarketing Experience The following adverse reactions have been identified during post approval use of mesalamine extended-release capsules or other mesalamine-containing products. Because many of these reactions are reported voluntarily from a population of unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Body as a Whole: lupus-like syndrome, drug fever Cardiovascular: pericarditis, pericardial effusion, myocarditis [see Warnings and Precautions ( 5.3 )] Gastrointestinal: pancreatitis, cholecystitis, gastritis, gastroenteritis, gastrointestinal bleeding, perforated peptic ulcer Hepatic: jaundice, cholestatic jaundice, hepatitis, liver necrosis, liver failure, Kawasaki-like syndrome including changes in liver enzymes Hematologic: agranulocytosis, aplastic anemia Nervous System: intracranial hype…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Nephrotoxic Agents including NSAIDs: Increased risk of nephrotoxicity; monitor for changes in renal function and mesalamine-related adverse reactions. ( 7.2 ) Azathioprine or 6-Mercaptopurine: Increased risk of blood disorders; monitor complete blood cell counts and platelet counts. ( 7.3 )
7.1Antacids Because the dissolution of the coating of the granules in mesalamine extended-release capsules depends on pH, avoid co-administration of mesalamine extended-release capsules with antacids [see Dosage and Administration ( 2 )].
7.2Nephrotoxic Agents, Including Non-Steroidal Anti-Inflammatory Drugs The concurrent use of mesalamine with known nephrotoxic agents, including non-steroidal anti-inflammatory drugs (NSAIDs) may increase the risk of nephrotoxicity. Monitor patients taking nephrotoxic drugs for changes in renal function and mesalamine-related adverse reactions [see Warnings and Precautions ( 5.1 )].
7.3Azathioprine or 6-Mercaptopurine The concurrent use of mesalamine with azathioprine or 6-mercaptopurine and/or other drugs known to cause myelotoxicity may increase the risk for blood disorders, bone marrow failure, and associated complications. If concomitant use of mesalamine extended-release capsules and azathioprine or 6-mercaptopurine cannot be avoided, monitor blood tests, including complete blood cell counts and platelet counts.
7.4Interference with Urinary Normetanephrine Measurements Use of mesalamine extended-release capsules may lead to spuriously elevated test results when measuring urinary normetanephrine by liquid chromatography with electrochemical detection [see Warnings and Precautions ( 5.8 )] . Consider an alternative, selective assay for normetanephrine.
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Geriatric Patients: Increased risk of blood dyscrasias; monitor blood cell counts and platelet counts. ( 8.5 )
8.1Pregnancy Risk Summary Published data from meta-analyses, cohort studies and case series on the use of mesalamine during pregnancy have not reliably informed an association with mesalamine and major birth defects, miscarriage, or adverse maternal or fetal outcomes (see Data) . In animal reproduction studies, there were no adverse developmental outcomes with administration of oral mesalamine during organogenesis to pregnant rats and rabbits at doses 1.7 times and 5.4 times, respectively, the maximum recommended human dose (see Data) .
The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. Adverse outcomes in pregnancy occur regardless of the health of the mother or the use of medications. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Clinical Considerations Disease-associated maternal and embryo/fetal risk Published data suggest that increased disease activity is associated with the risk of developing adverse pregnancy outcomes in women with ulcerative colitis. Adverse pregnancy outcomes include preterm delivery (before 37 weeks of gestation), low birth weight (less than 2,500 g) infants, and small for gestational age at birth. Data Human Data Published data from meta-analyses, cohort studies and case series on the use of mesalamine during early pregnancy (first trimester) and throughout pregnancy have not reliably informed an association of mesalamine and major birth defects, miscarriage, or adverse maternal or fetal outcomes.
There is no clear evidence that mesalamine exposure in early pregnancy is associated with an increased risk in major congenital malformations, including cardiac malformations. Published epidemiologic studies have important methodological limitations which hinder interpretation of the data, including inability to control for confounders, such as underlying maternal disease, and maternal use of concomitant medications, and missing information on the dose and duration of use for mesalamine products. Animal Data Reproduction studies with mesalamine during organogenesis have been performed in rats at oral doses up to 320 mg/kg/day (about 1.7 times the recommended human dose based on a body surface area comparison) and rabbits at doses up to 495 mg/kg/day (about 5.4 times the recommended human dose based on a body surface area comparison) and have revealed no evidence of harm to the fetus due to mesalamine.
8.2Lactation Risk Summary Data from published literature report the presence of mesalamine and its metabolite, N-acetyl 5-aminosalicylic acid in human milk in small amounts with relative infant doses (RID) of 2% or less (see Data) . There are case reports of diarrhea in breastfed infants exposed to mesalamine (see Clinical Considerations) . There is no information on the effects of the drug on milk production.
The lack of clinical data during lactation precludes a clear determination of the risk of mesalamine extended-release capsules to an infant during lactation; therefore, the developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for mesalamine extended-release capsules and any potential adverse effects on the breastfed child from mesalamine extended-release capsules or from the underlying maternal condition. Clinical Considerations Advise the caregiver to monitor the breastfed infant for diarrhea.
Data In published lactation studies, maternal mesalamine doses from various oral and rectal formulations and products ranged from 500 mg to 4.8 g daily. The average concentration of mesalamine in milk ranged from non-detectable to 0.5 mg/L. The average concentration of the N-acetyl-5-aminosalicylic acid in milk ranged from 0.…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary Published data from meta-analyses, cohort studies and case series on the use of mesalamine during pregnancy have not reliably informed an association with mesalamine and major birth defects, miscarriage, or adverse maternal or fetal outcomes (see Data) . In animal reproduction studies, there were no adverse developmental outcomes with administration of oral mesalamine during organogenesis to pregnant rats and rabbits at doses 1.7 times and 5.4 times, respectively, the maximum recommended human dose (see Data) .
The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. Adverse outcomes in pregnancy occur regardless of the health of the mother or the use of medications. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Clinical Considerations Disease-associated maternal and embryo/fetal risk Published data suggest that increased disease activity is associated with the risk of developing adverse pregnancy outcomes in women with ulcerative colitis. Adverse pregnancy outcomes include preterm delivery (before 37 weeks of gestation), low birth weight (less than 2,500 g) infants, and small for gestational age at birth. Data Human Data Published data from meta-analyses, cohort studies and case series on the use of mesalamine during early pregnancy (first trimester) and throughout pregnancy have not reliably informed an association of mesalamine and major birth defects, miscarriage, or adverse maternal or fetal outcomes.
There is no clear evidence that mesalamine exposure in early pregnancy is associated with an increased risk in major congenital malformations, including cardiac malformations. Published epidemiologic studies have important methodological limitations which hinder interpretation of the data, including inability to control for confounders, such as underlying maternal disease, and maternal use of concomitant medications, and missing information on the dose and duration of use for mesalamine products. Animal Data Reproduction studies with mesalamine during organogenesis have been performed in rats at oral doses up to 320 mg/kg/day (about 1.7 times the recommended human dose based on a body surface area comparison) and rabbits at doses up to 495 mg/kg/day (about 5.4 times the recommended human dose based on a body surface area comparison) and have revealed no evidence of harm to the fetus due to mesalamine.
🧒 Pediatric Use ▾
8.4Pediatric Use Safety and effectiveness of mesalamine extended-release capsules in pediatric patients have not been established.
🧓 Geriatric Use ▾
8.5Geriatric Use Clinical studies of mesalamine extended-release capsules did not include sufficient numbers of subjects aged 65 years and over to determine whether they respond differently than younger subjects. Reports from uncontrolled clinical studies and postmarketing reporting systems suggested a higher incidence of blood dyscrasias (i.e., agranulocytosis, neutropenia and pancytopenia) in patients who were 65 years or older compared to younger patients taking mesalamine-containing products such as mesalamine extended-release capsules.
Monitor complete blood cell counts and platelet counts in elderly patients during treatment with mesalamine extended-release capsules. In general, consider the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy in elderly patients when prescribing mesalamine extended-release capsules [see Use in Specific Populations ( 8.6 )] .
🆘 Overdosage ▾
10 OVERDOSAGE Mesalamine extended-release capsules are an aminosalicylate, and symptoms of salicylate toxicity include nausea, vomiting and abdominal pain, tachypnea, hyperpnea, tinnitus, and neurologic symptoms (headache, dizziness, confusion, seizures). Severe salicylate intoxication may lead to electrolyte and blood pH imbalance and potentially to other organ (e.g., renal and liver) damage. There is no specific antidote for mesalamine overdose; however, conventional therapy for salicylate toxicity may be beneficial in the event of acute overdosage and may include gastrointestinal tract decontamination to prevent further absorption.
Correct fluid and electrolyte imbalance by the administration of appropriate intravenous therapy and maintain adequate renal function. Mesalamine extended-release capsules are a pH-dependent delayed-release product and this factor should be considered when treating a suspected overdose.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action The mechanism of action of mesalamine (5-ASA) is not fully understood, but appears to be a local anti-inflammatory effect on colonic epithelial cells. Mucosal production of arachidonic acid metabolites, both through the cyclooxygenase pathways, i.e., prostanoids, and through the lipoxygenase pathways, i.e., leukotrienes and hydroxyeicosatetraenoic acids, is increased in patients with ulcerative colitis, and it is possible that 5-ASA diminishes inflammation by blocking production of arachidonic acid metabolites.
12.3Pharmacokinetics Absorption The pharmacokinetics of 5-ASA and its metabolite, N-acetyl-5-aminosalicylic acid (N-Ac-5-ASA), were studied after a single and multiple oral doses of 1.5 g mesalamine extended-release capsules in a crossover study in healthy subjects under fasting conditions. In the multiple-dose period, each subject received mesalamine extended-release capsules 1.5 g (four 0.375 g capsules) once daily for 7 consecutive days. Steady state was reached on Day 6 of once daily dosing based on trough concentrations.
After single and multiple doses of mesalamine extended-release capsules, peak plasma concentrations were observed at about 4 hours post-dose. At steady state, moderate increases (1.5-fold and 1.7-fold) in systemic exposure (AUC 0-24 ) to 5-ASA and N-Ac-5-ASA were observed when compared with a single-dose of mesalamine extended-release capsules. Pharmacokinetic parameters after a single dose of 1.5 g mesalamine extended-release capsules and at steady state in healthy subjects under fasting condition are shown in Table 2.
Table 2 Single Dose and Multiple Dose Mean (±SD) Plasma Pharmacokinetic Parameters of Mesalamine (5-ASA) and N-Ac-5-ASA After 1.5 g Mesalamine Extended-Release Capsules Administration in Healthy Subjects a Median (range); b Harmonic mean (pseudo SD); c after 7 days of treatment Mesalamine (5-ASA) Single Dose (n=24) Multiple Dose c (n=24) AUC 0-24 (mcg * h/mL) 11±5 17±6 AUC 0-inf (mcg * h/mL) 14±5 - C max (mcg/mL) 2.1±1.1 2.7±1.1 T max (h) a 4 (2, 16) 4 (2, 8) t ½ (h) b 9±7 10±8 N-Ac-5-ASA AUC 0-24 (mcg * h/mL) 26±6 37±9 AUC 0-inf (mcg * h/mL) 51±23 - C max (mcg/mL) 2.8±0.8 3.4±0.9 T max (h) a 4 (4, 12) 5 (2, 8) t ½ (h) b 12±11 14±10 In a separate study (n=30), it was observed that under fasting conditions about 32%±11% (mean±SD) of the administered dose was systemically absorbed based on the combined cumulative urinary excretion of 5-ASA and N-Ac-5-ASA over 96 hours post-dose.
Food Effects The effect of a high fat meal intake on absorption of mesalamine granules (the same granules contained in mesalamine extended-release capsules) was evaluated in 30 healthy subjects. Subjects received 1.6 g of mesalamine granules in sachet (2 x 0.8 g) following an overnight fast or a high fat meal in a crossover study. Under fed conditions, T max for both 5-ASA and N-Ac-5-ASA was prolonged by 4 hours and 2 hours, respectively.
A high fat meal did not affect C max for 5-ASA, but a 27% increase in the cumulative urinary excretion of 5-ASA was observed with a high fat meal. The overall extent of absorption of N-Ac-5-ASA was not affected by a high fat meal [see Dosage and Administration ( 2 )]. Distribution In an in vitro study, at 2.5 mcg/mL, mesalamine and N-Ac-5-ASA are 43±6% and 78±1% bound, respectively, to plasma proteins.
Protein binding of N-Ac-5-ASA does not appear to be concentration dependent at concentrations ranging from 1 mcg/mL to 10 mcg/mL. Elimination Metabolism The major metabolite of mesalamine is N-acetyl-5-aminosalicylic acid (N-Ac-5-ASA). It is formed by N-acetyltransferase activity in the liver and intestinal mucosa.
Excretion Following single and multiple doses of mesalamine extended-release capsules, the mean half-lives were 9 hours to 10 hours for 5-ASA, and 12 hours to 14 hours for N-Ac-5-ASA. Of the approximately 32% of the dose absorbed, about 2% of the dose was excreted unchanged in the urine, compared with about 30% of th…
🧬 Mechanism of Action ▾
12.1Mechanism of Action The mechanism of action of mesalamine (5-ASA) is not fully understood, but appears to be a local anti-inflammatory effect on colonic epithelial cells. Mucosal production of arachidonic acid metabolites, both through the cyclooxygenase pathways, i.e., prostanoids, and through the lipoxygenase pathways, i.e., leukotrienes and hydroxyeicosatetraenoic acids, is increased in patients with ulcerative colitis, and it is possible that 5-ASA diminishes inflammation by blocking production of arachidonic acid metabolites.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING Mesalamine extended-release capsules USP, 0.375 g are off-white to light brown colored free flowing pellets filled in size '00' hard gelatin capsules having opaque blue color 'cap' without imprint and opaque blue color 'body' printed with '452' in black ink and are supplied as follows: NDC 68382-452-19 in bottle of 120 capsules with child-resistant closure. Storage Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature].
📋 Description ▾
11 DESCRIPTION Each mesalamine capsule is a delayed- and extended-release dosage form for oral administration. Each extended-release capsule contains 0.375 g of mesalamine, USP (5-aminosalicylic acid, 5-ASA), an aminosalicylate. The structural formula of mesalamine is: Molecular Weight: 153.14 Molecular Formula: C 7 H 7 NO 3 Each extended-release capsule contains pellets composed of mesalamine in a polymer matrix with an enteric coating that dissolves at pH 6 and above.
The inactive ingredients of mesalamine extended-release capsules, USP are: ethyl cellulose, hypromellose, methacrylic acid copolymer, starch (source: maize), sucrose, talc and triethyl citrate. The capsule shell contains FD&C blue #1, gelatin, purified water, sodium lauryl sulfate and titanium dioxide. The capsule is imprinted with black pharmaceutical ink and contains following inactive ingredients: black iron oxide, potassium hydroxide, propylene glycol, purified water and shellac.
FDA approved dissolution test specifications differ from USP. Image
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Administration Instruct patients Swallow the capsules whole. Do not cut, break, crush or chew the capsules. Avoid co-administration of mesalamine extended-release capsules with antacids.
Drink an adequate amount of fluids. Mesalamine extended-release capsules can be taken without regard to meals [see Dosage and Administration ( 2 )] . Urine may become discolored reddish-brown while taking Mesalamine extended-release capsules when it comes in contact with surfaces or water treated with hypochlorite-containing bleach.
If discolored urine is observed, advise patients to observe their urine flow. Report to the healthcare provider only if urine is discolored on leaving the body, before contact with any surface or water (e.g., in the toilet). Renal Impairment Inform patients that mesalamine extended-release capsules may decrease their renal function, especially if they have known renal impairment or are taking nephrotoxic drugs, including NSAIDs, and periodic monitoring of renal function will be performed while they are on therapy.
Advise patients to complete all blood tests ordered by their healthcare provider [see Warnings and Precautions ( 5.1 ), Drug Interactions ( 7.2 )] . Mesalamine-Induced Acute Intolerance Syndrome and Other Hypersensitivity Reactions Inform patients of the signs and symptoms of hypersensitivity reactions. Instruct patients to stop taking mesalamine extended-release capsules and report to their healthcare provider if they experience new or worsening symptoms of Acute Intolerance Syndrome (cramping, abdominal pain, bloody diarrhea, fever, headache, and rash) or other symptoms suggestive of mesalamineinduced hypersensitivity [see Warnings and Precautions ( 5.2 , 5.3 )] .
Hepatic Failure Inform patients with known liver disease of the signs and symptoms of worsening liver function and advise them to report to their healthcare provider if they experience such signs or symptoms [see Warnings and Precautions ( 5.4 )] . Severe Cutaneous Adverse Reactions Inform patients of the signs and symptoms of severe cutaneous adverse reactions. Instruct patients to stop taking mesalamine extended-release capsules and report to their healthcare provider at first appearance of a severe cutaneous adverse reaction or other sign of hypersensitivity [see Warnings and Precautions ( 5.5 )] .
Photosensitivity Advise patients with pre-existing skin conditions to avoid sun exposure, wear protective clothing, and use a broad-spectrum sunscreen when outdoors [see Warnings and Precautions ( 5.6 )] . Nephrolithiasis Instruct patients to drink an adequate amount of fluids during treatment in order to minimize the risk of kidney stone formation and to contact their healthcare provider if they experience signs or symptoms of a kidney stone (e.g., severe side or back pain, blood in the urine) [see Warnings and Precautions ( 5.7 )] .
Blood Disorders Inform elderly patients and those taking azathioprine or 6-mercaptopurine of the risk for blood disorders and the need for periodic monitoring of complete blood cell counts and platelet counts while on therapy. Advise patients to complete all blood tests ordered by their healthcare provider [see Drug Interactions ( 7.3 ), Use in Specific Populations ( 8.5 )] . Call your doctor for medical advice about side effects.
You may report side effects to FDA at 1-800-FDA-1088. Please address medical inquiries to, [email protected] or Tel.: 1-877-993-8779.