Mesalamine

MESALAMINE- mesalamine capsule, extended release
Teva Pharmaceuticals USA, Inc.

1 INDICATIONS AND USAGE

Mesalamine extended-release capsules are indicated for the maintenance of remission of ulcerative colitis in adults.

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

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Evaluate renal function before initiating therapy with mesalamine extended-release capsules [see Warnings and Precautions (5.1)].

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Swallow mesalamine extended-release capsules whole. Do not cut, break, crush or chew the capsules.

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Avoid co-administration of mesalamine extended-release capsules with antacids [ see Drug Interactions (7.1) ].

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Drink an adequate amount of fluids [see Warnings and Precautions (5.7)].

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Take mesalamine extended-release capsules without regard to meals [see Clinical Pharmacology (12.3)].

3 DOSAGE FORMS AND STRENGTHS

Extended-release capsules: 0.375 g mesalamine in a light blue opaque gelatin capsule with the letters “G” and “M” imprinted on either side of a black band.

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)].

5 WARNINGS AND PRECAUTIONS

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 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 mesalamine extended-release capsules if renal function deteriorates while on therapy [see Drug Interactions (7.2), Use inSpecific 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 extended-release capsules.

5.3 Hypersensitivity 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.

5.4 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 extended-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 [see Adverse Reactions (6.2)]. Discontinue mesalamine extended-release capsules 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 extended-release capsules.

5.8 Risks in Patients with Phenylketonuria

Phenylalanine can be harmful to patients with phenylketonuria (PKU). Mesalamine extended-release capsules contain phenylalanine, a component of aspartame. Each mesalamine extended-release 0.375 g capsule contains 0.56 mg of phenylalanine. Before prescribing mesalamine extended-release capsules to a patient with PKU, consider the combined daily amount of phenylalanine from all sources, including mesalamine extended-release capsules.

5.9 Interference with Laboratory Tests

Use of mesalamine extended-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.

6 ADVERSE REACTIONS

The following clinically significant adverse reactions are described elsewhere in labeling:

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Renal Impairment [see Warnings and Precautions (5.1)]

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Mesalamine-Induced Acute Intolerance Syndrome [see Warnings and Precautions (5.2)]

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Hypersensitivity Reactions [see Warnings and Precautions (5.3)]

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Hepatic Failure [see Warnings and Precautions (5.4)]

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Severe Cutaneous Adverse Reactions [see Warnings and Precautions (5.5)]

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Photosensitivity [see Warnings and Precautions (5.6)]

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Nephrolithiasis [see Warnings and Precautions (5.7)]

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Risks in Patients with Phenylketonuria [see Warnings and Precautions (5.8)]