ADVERSE REACTIONS
In combined domestic and foreign clinical trials, more than 2100 patients with ulcerative colitis or Crohn's disease received PENTASA therapy. Generally, PENTASA therapy was well tolerated. The most common events (ie, greater than or equal to 1%) were diarrhea (3.4%), headache (2.0%), nausea (1.8%), abdominal pain (1.7%), dyspepsia (1.6%), vomiting (1.5%), and rash (1.0%).
In two domestic placebo-controlled trials involving over 600 ulcerative colitis patients, adverse events were fewer in PENTASA-treated patients than in the placebo group (PENTASA 14% vs placebo 18%) and were not dose-related. Events occurring at 1% or more are shown in the table below. Of these, only nausea and vomiting were more frequent in the PENTASA group. Withdrawal from therapy due to adverse events was more common on placebo than PENTASA (7% vs 4%)
Table 1. Adverse Events Occurring in More Than 1% of Either Placebo or PENTASA Patients in Domestic Placebo-controlled Ulcerative Colitis Trials. (PENTASA Comparison to Placebo) | Event | PENTASA
n=451 | Placebo
n=173 |
|---|
| Diarrhea | 16 (3.5%) | 13 (7.5%) |
| Headache | 10 (2.2%) | 6 (3.5%) |
| Nausea | 14 (3.1%) | --- |
| Abdominal Pain | 5 (1.1%) | 7 (4.0%) |
| Melena (Bloody Diarrhea) | 4 (0.9%) | 6 (3.5%) |
| Rash | 6 (1.3%) | 2 (1.2%) |
| Anorexia | 5 (1.1%) | 2 (1.2%) |
| Fever | 4 (0.9%) | 2 (1.2%) |
| Rectal Urgency | 1 (0.2%) | 4 (2.3%) |
| Nausea and Vomiting | 5 (1.1%) | --- |
| Worsening of Ulcerative Colitis | 2 (0.4%) | 2 (1.2%) |
| Acne | 1 (0.2%) | 2 (1.2%) |
Clinical laboratory measurements showed no significant abnormal trends for any test, including measurement of hematologic, liver, and kidney function.
The following adverse events, presented by body system, were reported infrequently (ie, less than 1%) during domestic ulcerative colitis and Crohn's disease trials. In many cases, the relationship to PENTASA has not been established.
Gastrointestinal: abdominal distention, anorexia, constipation, duodenal ulcer, dysphagia, eructation, esophageal ulcer, fecal incontinence, GGTP increase, GI bleeding, increased alkaline phosphatase, LDH increase, mouth ulcer, oral moniliases, pancreatitis, rectal bleeding, SGOT increase, SGPT increase, stool abnormalities (color or texture change), thirst
Dermatological: acne, alopecia, dry skin, eczema, erythema nodosum, nail disorder, photosensitivity, pruritus, sweating, urticaria
Nervous System: depression, dizziness, insomnia, somnolence, paresthesia
Cardiovascular: palpitations, pericarditis, vasodilation
Other: albuminuria, amenorrhea, amylase increase, arthralgia, asthenia, breast pain, conjunctivitis, ecchymosis, edema, fever, hematuria, hypomenorrhea, Kawasaki-like syndrome, leg cramps, lichen planus, lipase increase, malaise, menorrhagia, metrorrhagia, myalgia, pulmonary infiltrates, thrombocythemia, thrombocytopenia, urinary frequency
One week after completion of an 8-week ulcerative colitis study, a 72-year-old male, with no previous history of pulmonary problems, developed dyspnea. The patient was subsequently diagnosed with interstitial pulmonary fibrosis without eosinophilia by one physician and bronchiolitis obliterans with organizing pneumonitis by a second physician. A causal relationship between this event and mesalamine therapy has not been established. Published case reports and/or spontaneous postmarketing surveillance have described infrequent instances of pericarditis, fatal myocarditis, chest pain and T-wave abnormalities, hypersensitivity pneumonitis, pancreatitis, nephrotic syndrome, interstitial nephritis, hepatitis, aplastic anemia, pancytopenia, leukopenia, agranulocytosis, or anemia while receiving mesalamine therapy. Anemia can be a part of the clinical presentation of inflammatory bowel disease. Allergic reactions, which could involve eosinophilia, can be seen in connection with PENTASA therapy.
Postmarketing Reports
The following events have been identified during post-approval use of products which contain (or are metabolized to) mesalamine in clinical practice. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These events have been chosen for inclusion due to a combination of seriousness, frequency of reporting, or potential causal connection to mesalamine:
Gastrointestinal: Reports of hepatotoxicity, including elevated liver function tests (SGOT/AST, SGPT/ALT, GGT, LDH, alkaline phosphatase, bilirubin), jaundice, cholestatic jaundice, cirrhosis, and possible hepatocellular damage including liver necrosis and liver failure. Some of these cases were fatal. One case of Kawasaki-like syndrome which included hepatic function changes was also reported.
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