INDICATIONS AND USAGE
LIALDA tablets are indicated for the induction of remission in patients with active, mild to moderate ulcerative colitis. Safety and effectiveness of LIALDA beyond 8 weeks has not been established.
LIALDA is contraindicated in patients with hypersensitivity to salicylates (including mesalamine) or to any of the components of LIALDA.
General: Patients with pyloric stenosis may have prolonged gastric retention of LIALDA, which could delay mesalamine release in the colon.
The majority of patients who are intolerant or hypersensitive to sulfasalazine can take mesalamine medications without risk of similar reactions. However, caution should be exercised when treating patients allergic to sulfasalazine.
Mesalamine has been associated with an acute intolerance syndrome that may be difficult to distinguish from a flare of inflammatory bowel disease. 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. If acute intolerance syndrome is suspected, prompt withdrawal is required. Mesalamine-induced cardiac hypersensitivity reactions (myocarditis and pericarditis) have been reported with other mesalamine medications. Caution should be taken in prescribing this medication to patients with conditions predisposing to the development of myocarditis or pericarditis.
Renal: Reports of renal impairment, including minimal change nephropathy, and acute or chronic interstitial nephritis have been associated with mesalamine medications and pro-drugs of mesalamine. Forany patient with known renal dysfunction, caution should be exercised and LIALDA should be used only if the benefits outweigh the risks. It is recommended that all patients have an evaluation of renal function prior to initiation of therapy and periodically while on treatment. In animal studies with mesalamine, a 13-week oral toxicity study in mice and 13-week and 52-week oral toxicity studies in rats and cynomolgus monkeys have shown the kidney to be the major target organ of mesalamine toxicity. Oral daily doses of 2400 mg/kg in mice and 1150 mg/kg in rats produced renal lesions including granular and hyaline casts, tubular degeneration, tubular dilation, renal infarct, papillary necrosis, tubular necrosis, and interstitial nephritis. In cynomolgus monkeys, oral daily doses of 250 mg/kg or higher produced nephrosis, papillary edema, and interstitial fibrosis.
Hepatic Impairment: No information is available on patients with hepatic impairment, and therefore, caution is recommended in these patients.
Information for Patients: Patients should be instructed to swallow LIALDA tablets whole, taking care not to break the outer coating. The outer coating is designed to remain intact to protect the active ingredient, mesalamine, and ensure its availability throughout the colon. Drug Interaction: No investigations have been performed between LIALDA and otherdrugs. However, the following are reports of interactions between mesalamine medications and other drugs. The concurrent use of mesalamine with known nephrotoxic agents, including non-steroidal anti-inflammatory drugs (NSAIDs) may increase the risk of renal reactions. In patients receiving azathioprine or 6-mercaptopurine, concurrent use of mesalamine can increase the potential for blood disorders.
Carcinogenesis, Mutagenesis, Impairment of Fertility: In a 104-week dietary carcinogenicity study in CD-1 mice, mesalamine at doses up to 2500 mg/kg/day was not tumorigenic. This dose is 2.2 times the maximum recommended human dose (based on a body surface area comparison) of LIALDA. Furthermore, in a 104-week dietary carcinogenicity study in Wistar rats, mesalamine up to a dose of 800 mg/kg/day was not tumorigenic. This dose is 1.4 times the recommended human dose (based on a body surface area comparison) of LIALDA.
No evidence of mutagenicity was observed in an in vitro Ames test or an in vivo mouse micronucleustest.
No effects on fertility or reproductive performance were observed in male or female rats at oral doses of mesalamine up to 400 mg/kg/day (0.7 times the maximum recommended human dose based on a body surface area comparison). Semen abnormalities and infertility in men, which have been reported in association with sulfasalazine, have not been seen with other mesalamine products during controlled clinical trials.
Teratogenic Effects: Pregnancy Category B
Reproduction studies with mesalamine have been performed in rats at doses up to 1000 mg/kg/day (1.8 times the maximum recommended human dose based on a body surface area comparison) and rabbits at doses up to 800 mg/kg/day (2.9 times the maximum recommended human dose based on a body surface area comparison) and have revealed no evidence of impaired fertility or harm to the fetus due to mesalamine. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Mesalamine is known to cross the placental barrier. Nursing Mothers: Low concentrations of mesalamine and higher concentrations of its N-acetyl metabolite have been detected in human breast milk. While there is limited experience of lactating women using mesalamine, caution should be exercised if LIALDA is administered to a nursing mother, and used only if the benefits outweigh the risks. Pediatric Use: Safety and effectiveness of LIALDA tablets in pediatric patients who are less than 18 years of age have not been studied.
Geriatric Use: Clinical trials of LIALDA did not include sufficient numbers of patients aged 65 and over to determine whether they respond differently from younger patients.
Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concurrent disease or other drug therapy.