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 mesalamine if renal function deteriorates. (5.1 , 7.1 , 8.6) Mesalamine-induced Acute Intolerance Syndrome: Symptoms may be difficult to distinguish from an ulcerative colitis exacerbation; monitor for worsening symptoms; discontinue if acute intolerance syndrome 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 preexisting 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) 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, rarely, renal failure, has been reported in patients taking products such as mesalamine delayed-release tablets that contain or are converted to mesalamine [see Adverse Reactions (6.2) ]. 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 delayed-release tablets and periodically while on therapy. Evaluate the risks and benefits of using mesalamine delayed-release tablets in patients with known renal impairment or history of renal disease or taking concomitant nephrotoxic drugs. Discontinue mesalamine 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. Exacerbation of the symptoms of colitis has been reported in 2.3% of mesalamine-treated patients in controlled clinical trials. This acute reaction, characterized by cramping, abdominal pain, bloody diarrhea, and occasionally by fever, headache, malaise, pruritus, rash, and conjunctivitis, has been reported after the initiation of mesalamine delayed-release tablets as well as other mesalamine products. Symptoms usually abate when mesalamine delayed-release tablets are discontinued. Monitor patients for worsening of these symptoms while on treatment. If acute intolerance syndrome is suspected, promptly discontinue treatment with mesalamine delayed-release tablets. 5.3 Hypersensitivity Reactions Hypersensitivity reactions have been reported in patients taking sulfasalazine. Some patients may have a similar reaction to mesalamine delayed-release tablets 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 delayed-release tablets if an alternative etiology for the signs or 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 delayed-release tablets 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 use of mesalamine [see Adverse Reactions (6.2) ]. Discontinue mesalamine delayed-release tablets at the first appearance of signs or symptoms of severe cutaneous adverse reactions, or other signs of hypersensitivity and consider further evaluation. 5.6 Photosensitivity 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 fluid intake during treatment with mesalamine delayed-release tablets. 5.9 Interference with Laboratory Tests Use of mesalamine delayed-release tablets 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.