Mesalamine
MESALAMINE- mesalamine tablet, delayed release
Major Pharmaceuticals
1. INDICATIONS AND USAGE
Mesalamine delayed-release tablets are indicated for the:
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- induction and maintenance of remission in adult patients with mildly to moderately active ulcerative colitis.
Pediatric use information is approved for Takeda Pharmaceuticals U.S.A., Inc.’s LIALDA (mesalamine) delayed-release tablets. However, due to Takeda Pharmaceuticals U.S.A., Inc.’s marketing exclusivity rights, this drug product is not labeled with that information.
2. DOSAGE AND ADMINISTRATION
Administration Instructions
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- Evaluate renal function prior to initiation of mesalamine and periodically while on therapy.
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- Swallow mesalamine delayed-release tablets whole; do not split or crush.
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- Administer mesalamine delayed-release tablets with food [see Clinical Pharmacology (12.3)].
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- Drink an adequate amount of fluids [see Warnings and Precautions (5.8)].
Adults
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- The recommended dosage for the induction of remission in adult patients with mildly to moderately active ulcerative colitis is 2.4 g to 4.8 g (two to four 1.2-g tablets) taken once daily.
- •
- The recommended dosage for the maintenance of remission is 2.4 g (two 1.2-g tablets) taken once daily.
Pediatric use information is approved for Takeda Pharmaceuticals U.S.A., Inc.’s LIALDA (mesalamine) delayed-release tablets. However, due to Takeda Pharmaceuticals U.S.A., Inc.’s marketing exclusivity rights, this drug product is not labeled with that information.
3. DOSAGE FORMS AND STRENGTHS
Mesalamine Delayed-release Tablets USP, 1.2 g are pale red-brown, oval-shaped, biconvex, bevel film-coated tablets debossed with the ‘711’ on one side and plain on other side.
4. CONTRAINDICATIONS
Mesalamine delayed-release tablets are contraindicated in patients with known or suspected hypersensitivity to salicylates, aminosalicylates, or to any of the ingredients of mesalamine delayed-release tablets [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, rarely, renal failure, has been reported in patients given products such as mesalamine delayed-release tablets 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, history of renal disease, or taking concomitant nephrotoxic drugs [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, 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 tablets.
5.3 Hypersensitivity Reactions
Hypersensitivity reactions have been reported in patients taking sulfasalazine. Some of these 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 in patients with known liver impairment.
5.5 Severe Cutaneous Adverse Reactions
Severe cutaneous adverse reactions, such as 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 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 Upper Gastrointestinal Tract Obstruction
Pyloric stenosis or other organic or functional obstruction in the upper gastrointestinal tract may cause prolonged gastric retention of mesalamine delayed-release tablets, which would delay mesalamine release in the colon. Avoid mesalamine in patients at risk of upper gastrointestinal tract obstruction.
5.7 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.
5.8 Nephrolithiasis
Cases of nephrolithiasis have been reported with the use of mesalamine, including stones with a 100% mesalamine content. Mesalamine-containing stones are radiotransparent and undetectable by standard radiography or computed tomography (CT). Ensure adequate hydration during treatment with mesalamine delayed-release tablets.
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.
6. ADVERSE REACTIONS
The following clinically significant adverse reactions are described elsewhere in labeling:
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- Renal impairment, including renal failure [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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- Upper gastrointestinal tract obstruction [see Warnings and Precautions (5.6)]
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- Photosensitivity [see Warnings and Precautions (5.7)]
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- Nephrolithiasis [see Warnings and Precautions (5.8)]
6.1 Clinical Trials Experience
Because clinical trials 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.
Adults
Induction
The most common adverse reactions occurring in at least 1% of mesalamine- or placebo-treated adult patients with mildly to moderately active ulcerative colitis in two eight-week, randomized, double-blind, placebo-controlled trials (Study 1 and Study 2) [see Clinical Studies (14.1)] are listed in Table 2.
*Reported in at least 1% of patients in at least one mesalamine group and greater than placebo | |||
Adverse Reaction | Mesalamine Delayed-Release Tablets 2.4 g once daily (n = 177) | Mesalamine Delayed-Release Tablets 4.8 g once daily (n = 179) | Placebo (n = 179) |
Headache | 6% | 3% | <1% |
Flatulence | 4% | 3% | 3% |
Liver Function Test Abnormal | <1% | 2% | 1% |
Alopecia | 0 | 1% | 0 |
Pruritus | <1% | 1% | 1% |
Pancreatitis occurred in less than 1% of patients during induction in clinical trials and resulted in discontinuation of therapy with mesalamine in patients experiencing this event.
Maintenance of Remission
A mesalamine dosage of 2.4 g/day, administered as either 1.2 g twice daily or 2.4 g once daily, was evaluated for safety in three maintenance trials in patients with mildly to moderately active ulcerative colitis: a 6-month double-blind, active-controlled study (Study 3) [see Clinical Studies (14.1)] and two 12 to 14 month open-label studies. The most common adverse reactions with mesalamine in these maintenance trials are listed in Table 3.
* Reported in at least 1% of patients | |||||
† Administered either as 1.2 g twice daily or 2.4 g once daily | |||||
Mesalamine Delayed-Release Tablets 2.4 g/day† (n=1082) | |||||
Adverse Reaction | % | ||||
Headache | 3% | ||||
Liver function test abnormal | 2% | ||||
Abdominal pain | 2% | ||||
Diarrhea | 2% | ||||
Abdominal distension | 1% | ||||
Abdominal pain upper | 1% | ||||
Dyspepsia | 1% | ||||
Back pain | 1% | ||||
Rash | 1% | ||||
Arthralgia | 1% | ||||
Fatigue | 1% | ||||
Hypertension | 1% |
The following adverse reactions, presented by body system, were reported in less than 1% of mesalamine delayed-release tablets-treated patients with ulcerative colitis in either induction or maintenance trials:
Cardiac Disorder
Tachycardia
Ear and Labyrinth Disorders
Ear pain
Gastrointestinal Disorders
Abdominal distention, colitis, diarrhea, flatulence, nausea, pancreatitis, rectal polyp, vomiting
General Disorders and Administrative Site Disorders
Asthenia, face edema, fatigue, pyrexia
Investigations
Decreased platelet count
Musculoskeletal and Connective Tissue Disorders
Arthralgia, back pain
Nervous System Disorders
Dizziness, somnolence, tremor
Respiratory, Thoracic and Mediastinal Disorders
Pharyngolaryngeal pain
Skin and Subcutaneous Tissue Disorders
Acne, prurigo, rash, alopecia, pruritus, urticaria
Vascular Disorders
Hypertension, hypotension
Pediatric use information is approved for Takeda Pharmaceuticals U.S.A., Inc.’s LIALDA (mesalamine) delayed-release tablets. However, due to Takeda Pharmaceuticals U.S.A., Inc.’s marketing exclusivity rights, this drug product is not labeled with that information.
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