MESALAMINE Drug Interactions: What You Need to Know

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 <span class="opacity-50 text-xs">[see Dosage and Administration ( 2 )]</span>.

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 <span class="opacity-50 text-xs">[see Warnings and Precautions ( 5.1 )]</span>.

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 extended-release capsules 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 extended-release capsules may lead to spuriously elevated test results when measuring urinary normetanephrine by liquid chromatography with electrochemical detection <span class="opacity-50 text-xs">[see Warnings and Precautions ( 5.9 )]</span> . Consider an alternative, selective assay for normetanephrine.

Mesalamine delayed-release tablets are contraindicated in patients with known or suspected hypersensitivity to salicylates or aminosalicylates or to any of the ingredients of mesalamine delayed-release tablets [see Warnings and Precautions ( 5.3 ), Adverse Reactions ( 6.2 ), and Description ( 11 )] . Known or suspected hypersensitivity to salicylates or aminosalicylates or to any of the ingredients of mesalamine delayed-release tablets. ( 4 , 5.3 )

AND PRECAUTIONS Renal Impairment: Assess renal function at the beginning of treatment and periodically during treatment. Evaluate the risks and benefits of using MESALAMINE delayed-release capsules in patients with known renal impairment or taking nephrotoxic drugs; monitor renal function. Discontinue MESALAMINE delayed-release capsules if renal function deteriorates. ( 5.1 , 7.1 , 8.6 , 13.2 ) Mesalamine-induced Acute Intolerance Syndrome: Symptoms may be difficult to distinguish from an ulcerative colitis exacerbation; monitor for worsening symptoms while on treatment; discontinue treatment, if acute intolerance syndrome is suspected. ( 5.2 )

Hypersensitivity

Reactions , including myocarditis and pericarditis : Evaluate patients immediately and discontinue MESALAMINE delayed-release capsules, if a hypersensitivity reaction is suspected. ( 5.3 )

Hepatic

Failur e : Evaluate the risks and benefits of using MESALAMINE delayed-release capsules 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 undetectable by standard radiography or computed tomography (CT). Ensure adequate fluid intake during treatment. ( 5.7 )

Iron

Content of MESALAMINE d elayed- r elease c apsules : Consider the iron content of MESALAMINE delayed-release capsules in patients taking iron supplementation and those at risk of iron overload. ( 5.8 ) 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 taking products such as MESALAMINE delayed-release capsules that contain mesalamine or are converted to mesalamine. In animal studies, the kidney was the principal organ of mesalamine toxicity <span class="opacity-50 text-xs">[see Adverse Reactions ( 6.2 ) , Nonclinical Toxicology ( 13.2 ) ]</span> . Evaluate renal function prior to initiation of MESALAMINE delayed-release capsules and periodically while on therapy. Discontinue MESALAMINE delayed-release capsules if renal function deteriorates while on therapy. Evaluate the risks and benefits of using MESALAMINE delayed-release capsules in patients with known renal impairment or history of renal disease or taking concomitant nephrotoxic drugs <span class="opacity-50 text-xs">[see Drug Interactions ( 7.1 ), Use in Specific Populations ( 8.6 ) ]</span> .

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 controlled clinical trials of mesalamine or sulfasalazine. Symptoms include cramping, abdominal pain, bloody diarrhea, and sometimes fever, headache, malaise, pruritus, conjunctivitis and rash. Monitor patients closely for worsening of these symptoms while on treatment. If acute intolerance syndrome is suspected, promptly discontinue treatment with MESALAMINE delayed-release capsules.

5.3 Hypersensitivity Reactions Hypersensitivity reactions have been reported in patients taking sulfasalazine. Some patients may have a similar reaction to MESALAMINE delayed-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 delayed-release capsules 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 risk and benefits of using MESALAMINE delayed-release capsules 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 <span class="opacity-50 text-xs">[see Adverse Reactions ( 6.2 )]</span> . Discontinue MESALAMINE delayed-release capsules 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 capsules. 5. 8 Iron Content of Mesalamine Delayed-Release Capsules MESALAMINE delayed-release capsules contains iron oxide as a colorant in the coating of the delayed-release capsules.

Each

400 mg delayed-release capsule contains 2.7 mg of iron. The total content of iron is 16.4 mg at the maximum recommended daily dosage in adults [see Dosage and Administration ( 2.2 )]. Before prescribing MESALAMINE delayed-release capsules to patients receiving iron supplementation or those at risk of developing iron overload, consider the combined daily amount of iron from all sources, including MESALAMINE delayed-release capsules. 5. 9 Interference with Laboratory Tests Use of MESALAMINE delayed-release capsules 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.