Drug Facts
Composition & Profile
Identifiers & Packaging
16 HOW SUPPLIED/STORAGE AND HANDLING Mesalamine extended-release capsules, USP are available as opaque light blue cap / opaque light blue body, hard gelatin capsules size ‘00’ having imprinting “A” on cap in black ink and “255” on body in black ink on either side of a black band filled with light grey to grey color granules and are supplied as follows: Bottle of 120 capsules with child resistant closure, NDC 46708-724-35 Bottle of 1000 capsules, NDC 46708-724-91 Storage : Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].; PACKAGE LABEL.PRINCIPAL DISPLAY PANEL NDC 46708-724-35 Mesalamine Extended-Release Capsules, USP 0.375 g Rx only 120 Capsules Alembic 120 capsules
- 16 HOW SUPPLIED/STORAGE AND HANDLING Mesalamine extended-release capsules, USP are available as opaque light blue cap / opaque light blue body, hard gelatin capsules size ‘00’ having imprinting “A” on cap in black ink and “255” on body in black ink on either side of a black band filled with light grey to grey color granules and are supplied as follows: Bottle of 120 capsules with child resistant closure, NDC 46708-724-35 Bottle of 1000 capsules, NDC 46708-724-91 Storage : Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].
- PACKAGE LABEL.PRINCIPAL DISPLAY PANEL NDC 46708-724-35 Mesalamine Extended-Release Capsules, USP 0.375 g Rx only 120 Capsules Alembic 120 capsules
Overview
Each mesalamine capsule is a delayed- and extended-release dosage form for oral administration. Each 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 mesalamine extended-release capsule contains granules 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 are: microcrystalline cellulose, hypromellose, colloidal silicon dioxide, ethyl acrylate and methyl methacrylate 2:1 copolymer, magnesium stearate, methacrylic acid and methyl methacrylate 1:1 copolymer, talc, triethyl citrate, titanium dioxide and hypromellose phthalate. The capsule shell contains titanium dioxide, FD&C Blue 1, FD&C Red 40 and gelatin. The capsule shells are printed with edible black ink containing shellac, black iron oxide and potassium hydroxide. FDA approved dissolution test specifications differ from USP. structure
Indications & Usage
Mesalamine extended-release capsules are indicated for the maintenance of remission of ulcerative colitis in adults. Mesalamine extended-release capsule is an aminosalicylate indicated for the maintenance of remission of ulcerative colitis in adults. (1)
Dosage & 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 (5.6)]. • 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)
Warnings & 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. (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. (5.9) 5.1 Renal 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 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 therapy and periodically while on therapy. Evaluate the risks and benefits of using mesalamine in patients with known renal impairment or a history of renal disease or taking concomitant nephrotoxic drugs [see Drug Interactions (7.2), Use in Specific Populations (8.6)]. 5.2 Mesalamine-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. 5.3 Hypersensitivity Reactions Some patients have experienced a hypersensitivity reaction to sulfasalazine. Some patients may have a similar reaction to mesalamine 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 if an alternative etiology for the signs and symptoms cannot be established. 5.4 Hepatic 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 in patients with known liver impairment. 5.5 Severe Cutaneous Adverse Reactions Severe cutaneous adverse reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP) have been reported with the use of mesalamine [see Adverse Reactions (6.2)]. Discontinue mesalamine at the first signs or symptoms of severe cutaneous adverse reactions or other signs of hypersensitivity and consider further evaluation. 5.6 Photosensitivity Patients with pre-existing skin conditions such as atopic dermatitis and atopic eczema have reported more severe photosensitivity reactions. Advise patients to avoid sun exposure, wear protective clothing, and use a broad-spectrum sunscreen when outdoors. 5.7 Nephrolithiasis Cases of nephrolithiasis have been reported with the use of mesalamine, including stones with 100% mesalamine content. Mesalamine-containing stones are radiotransparent and undetectable by standard radiography or computed tomography (CT). Ensure adequate fluid intake during treatment with mesalamine. 5.9 Interference with Laboratory Tests Use of mesalamine may lead to spuriously elevated test results when measuring urinary normetanephrine by liquid chromatography with electrochemical detection because of the similarity in the chromatograms of normetanephrine and the main metabolite of mesalamine, N-acetyl-5-aminosalicylic acid (N-Ac-5-ASA). Consider an alternative, selective assay for normetanephrine.
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 capsule. (4, 5.3)
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 FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical 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 in 557 patients, including 354 exposed for at least 6 months and 250 exposed for greater than one year. Mesalamine was studied in two placebo-controlled trials (n=367 treated with mesalamine) 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 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-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 Mesalamine 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% * Reported in at least 3% of mesalamine-treated patients and at a greater rate than with placebo The following adverse reactions, presented by body system, were reported at a frequency less than 3% in patients treated with mesalamine 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 6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of mesalamine or other mesalaminecontaining 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 hypertension Neurological/Psychiatric : peripheral neuropathy, Guillain-Barré syndrome, transverse myelitis Renal and Urinary : nephrogenic diabetes insipidus, interstitial nephritis, renal failure, minimal change disease, nephrolithiasis [see Warnings and Precautions (5.1, 5.7)] Respiratory/Pulmonary : eosinophilic pneumonia, interstitial pneumonitis, pleurisy/pleuritis Skin : psoriasis, pyoderma gangrenosum, erythema nodosum, SJS/TEN, DRESS, and AGEP [see Warnings and Precautions (5.5)] Renal/Urogenital : reversible oligospermia
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) 7.1 Antacids 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)] . 7.2 Nephrotoxic 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)]. 7.3 Azathioprine 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 and azathioprine or 6-mercaptopurine cannot be avoided, monitor blood tests, including complete blood cell counts and platelet counts. 7.4 Interference with Urinary Normetanephrine Measurements Use of mesalamine may lead to spuriously elevated test results when measuring urinary normetanephrine by liquid chromatography with electrochemical detection [see Warnings and Precautions (5.9)] . Consider an alternative, selective assay for normetanephrine.
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