Recommended Topic Related To:

Asacol

"The U.S. Food and Drug Administration today approved a new use for Simponi (golimumab) injection to treat adults with moderate to severe ulcerative colitis.

Simponi works by blocking tumor necrosis factor (TNF), which plays an important"...

Asacol

WARNINGS

No information provided.

PRECAUTIONS

General

Patients with pyloric stenosis may have prolonged gastric retention of Asacol tablets which could delay release of mesalamine in the colon.

Exacerbation of the symptoms of colitis has been reported in 3% of Asacol (mesalamine delayed-release tablets) -treated patients in controlled clinical trials. This acute reaction, characterized by cramping, abdominal pain, bloody diarrhea, and occasionally by fever, headache, malaise, pruritus, rash, and conjunctivitis, has been reported after the initiation of Asacol tablets as well as other mesalamine products. Symptoms usually abate when Asacol (mesalamine delayed-release tablets) tablets are discontinued.

Some patients who have experienced a hypersensitivity reaction to sulfasalazine may have a similar reaction to Asacol tablets or to other compounds which contain or are converted to mesalamine.

Renal

Renal impairment, including minimal change nephropathy, acute and chronic interstitial nephritis, and, rarely, renal failure has been reported in patients taking Asacol tablets as well as other compounds which contain or are converted to mesalamine. In animal studies (rats, dogs), the kidney is the principal target organ for toxicity. At doses of approximately 750 mg/kg to 1000 mg/kg [15 to 20 times the administered recommended human dose (based on a 50 kg person) on a mg/kg basis and 3 to 4 times on a mg/m² basis], mesalamine causes renal papillary necrosis. Therefore, caution should be exercised when using Asacol (or other compounds which contain or are converted to mesalamine or its metabolites) in patients with known renal dysfunction or history of renal disease. It is recommended that all patients have an evaluation of renal function prior to initiation of Asacol (mesalamine delayed-release tablets) tablets and periodically while on Asacol (mesalamine delayed-release tablets) therapy.

Use in Hepatic Impairment

There have been reports of hepatic failure in patients with preexisting liver disease who have been administered mesalamine. Caution should be exercised when administering Asacol (mesalamine delayed-release tablets) to patients with liver disease.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Dietary mesalamine was not carcinogenic in rats at doses as high as 480 mg/kg/day, or in mice at 2000 mg/kg/day. These doses are 2.4 and 5.1 times the maximum recommended human maintenance dose of Asacol (mesalamine delayed-release tablets) of 1.6 g/day (32 mg/kg/day if 50 kg body weight assumed or 1184 mg/m²), respectively, based on body surface area. Mesalamine was negative in the Ames assay for mutagenesis, negative for induction of sister chromatid exchanges (SCE) and chromosomal aberrations in Chinese hamster ovary cells in vitro , and negative for induction of micronuclei (MN) in mouse bone marrow polychromatic erythrocytes. Mesalamine, at oral doses up to 480 mg/kg/day (about 1.6 times the recommended human treatment dose on a body surface area basis), was found to have no effect on fertility or reproductive performance of male and female rats.

Pregnancy

Pregnancy Category C

There are no adequate and well controlled studies of Asacol use in pregnant women. Limited published human data on mesalamine show no increase in the overall rate of congenital malformations. Some data show an increased rate of preterm birth, stillbirth, and low birth weight; however, these adverse pregnancy outcomes are also associated with active inflammatory bowel disease. Animal reproduction studies of mesalamine found no evidence of fetal harm. However, dibutyl phthalate (DBP) is an inactive ingredient in Asacol (mesalamine delayed-release tablets) 's enteric coating, and in animal studies at doses > 190 times the human dose based on body surface area, maternal DBP was associated with external and skeletal malformations and adverse effects on the male reproductive system. Asacol (mesalamine delayed-release tablets) should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Mesalamine crosses the placenta. In prospective and retrospective studies of over 600 women exposed to mesalamine during pregnancy, the observed rate of congenital malformations was not increased above the background rate in the general population. Some data show an increased rate of preterm birth, stillbirth, and low birth weight, but it is unclear whether this was due to underlying maternal disease, drug exposure, or both, as active inflammatory bowel disease is also associated with adverse pregnancy outcomes.

Reproduction studies with mesalamine were performed during organogenesis in rats and rabbits at oral doses up to 480 mg/kg/day. There was no evidence of impaired fertility or harm to the fetus. These mesalamine doses were about 1.6 times (rat) and 3.2 times (rabbit) the recommended human dose, based on body surface area.

Dibutyl phthalate (DBP) is an inactive ingredient in Asacol (mesalamine delayed-release tablets) 's enteric coating. The human daily intake of DBP from the maximum recommended dose of Asacol (mesalamine delayed-release tablets) tablets is about 21 mg. Published reports in rats show that male rat offspring exposed in utero to DBP ( ≥ 100 mg/kg/day, approximately 39 times the human dose based on body surface area), display reproductive system aberrations compatible with disruption of androgenic dependent development. The clinical significance of this finding in rats is unknown. At higher dosages ( ≥ 500 mg/kg/day, approximately 194 times the human dose based on body surface area), additional effects, including cryptorchidism, hypospadias, atrophy or agenesis of sex accessory organs, testicular injury, reduced daily sperm production, permanent retention of nipples, and decreased anogenital distance are noted. Female offspring are unaffected. High doses of DBP, administered to pregnant rats was associated with increased incidences of developmental abnormalities, such as cleft palate ( ≥ 630 mg/kg/day, about 244 times the human dose, based on body surface area) and skeletal abnormalities ( ≥ 750 mg/kg/day, about 290 times the human dose based on body surface area) in the offspring.

Nursing Mothers

Mesalamine and its N-acetyl metabolite are excreted into human milk. In published lactation studies, maternal mesalamine doses from various oral and rectal formulations and products ranged from 500 mg to 3 g daily. The concentration of mesalamine in milk ranged from non-detectable to 0.11 mg/L. The concentration of the N-acetyl-5aminosalicylic acid metabolite ranged from 5 to 18.1 mg/L. Based on these concentrations, estimated infant daily doses for an exclusively breastfed infant are 0 - 0.017 mg/kg/day of mesalamine and 0.75-2.72 mg/kg/day of N-acetyl-5-aminosalicylic acid. Caution should be exercised when Asacol (mesalamine delayed-release tablets) is administered to a nursing woman.

Dibutyl phthalate (DBP), an inactive ingredient in the enteric coating of Asacol (mesalamine delayed-release tablets) tablets, and its primary metabolite mono-butyl phthalate (MBP) are excreted into human milk. In pregnant rats, DBP causes fetal reproductive system aberrations/malformations in male offspring [see PRECAUTIONS, Pregnancy]. The clinical significance of this is has not been determined.

Pediatric Use

Safety and effectiveness of Asacol (mesalamine delayed-release tablets) tablets in pediatric patients have not been established.

Geriatric Use

Clinical studies of Asacol (mesalamine delayed-release tablets) did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy in elderly patients should be considered when prescribing Asacol (mesalamine delayed-release tablets) . Reports from uncontrolled clinical studies and post-marketing reporting systems suggest a higher incidence of blood dyscrasias, i.e., agranulocytosis, neutropenia, pancytopenia, in subjects receiving Asacol (mesalamine delayed-release tablets) who are 65 years or older. Caution should be taken to closely monitor blood cell counts during drug therapy.

This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken when prescribing this drug therapy. As stated in the PRECAUTIONS section, it is recommended that all patients have an evaluation of renal function prior to initiation of Asacol (mesalamine delayed-release tablets) tablets and periodically while on Asacol (mesalamine delayed-release tablets) therapy.

Last reviewed on RxList: 6/17/2010
This monograph has been modified to include the generic and brand name in many instances.

A A A

Report Problems to the Food and Drug Administration

 

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.


Women's Health

Find out what women really need.