warnings and cautions
5 WARNINGS AND PRECAUTIONS • Renal Impairment : Evaluate the risks and benefits in patients with known renal impairment or taking nephrotoxic drugs; monitor renal function. Discontinue mesalamine if renal function deteriorates. ( 5.1 , 7.1 , 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 hydration during treatment. ( 5.7 ) • Interaction with Laboratory Test for Urinary Normetanephrine: Spuriously elevated test results may occur with liquid chromatography with electrochemical detection in patients receiving mesalamine suppositories; use alternative, selective assay for normetanephrine. ( 5.8 ) 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 suppositories 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 suppository and periodically while on therapy. Evaluate the risks and benefits of using mesalamine suppositories in patients with known renal impairment or a history of renal disease or taking concomitant nephrotoxic drugs. Discontinue mesalamine suppositories if renal function deteriorates while on therapy. [see Drug Interactions ( 7.1 ), 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, and sometimes fever, headache, malaise, pruritus, conjunctivitis, and rash. Monitor patients for worsening of these symptoms while on treatment. If acute intolerance syndrome is suspected, promptly discontinue treatment with mesalamine suppositories. 5.3 Hypersensitivity Reactions Hypersensitivity reactions have been reported in patients taking sulfasalazine. Some patients may have a similar reaction to mesalamine suppositories 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 suppositories 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 other products containing mesalamine. Evaluate the risks and benefits of using mesalamine suppositories in patients with known liver impairment. 5.5 Severe Cutaneous Adverse Reactions Severecutaneous adverse reactions, including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), drug reaction with eosinophilia andsystemicsymptoms (DRESS), and acute generalized exanthematous pustulosis (AGEP) have been reported in association with the use ofmesalamine [see Adverse Reactions ( 6.2 )]. Discontinue mesalamine suppositories at the first signs or symptoms of severe cutaneous adverse reactions or other signs of hypersensitivity and considerfurtherevaluation. 5.6 Photosensitivity In patients treated with mesalamine or sulfasalazine who have 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 of 100% mesalamine content. Mesalamine-containing stones are radiotransparent and undetectable by standard radiography or computed tomography (CT). Ensure adequate hydration during treatment with mesalamine suppositories. 5.8 Interaction with Laboratory Test for Urinary Normetanephrine 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 mesalamine's main metabolite, N-acetylaminosalicylic acid. Consider an alternative, selective assay for normetanephrine.