No information provided.

General

Overall, approximately 17% of subjects receiving olsalazine in clinical studies reported diarrhea sometime during therapy. This diarrhea resulted in withdrawal of treatment in 6% of patients. This diarrhea appears to be dose related, although it may be difficult to distinguish from the underlying symptoms of the disease.

Exacerbation of the symptoms of colitis thought to have been caused by mesalamine or sulfasalazine has been noted.

Although renal abnormalities were not reported in clinical trials with olsalazine, there have been rare reports from post-marketing experience (see under ADVERSE REACTIONS). Therefore, the possibility of renal tubular damage due to absorbed mesalamine or its n-acetylated metabolite, as noted in the CLINICAL PHARMACOLOGY: ANIMAL TOXICOLOGY subsection must be kept in mind, particularly for patients with pre-existing renal disease. In these patients, monitoring with urinalysis, BUN and creatinine determinations is advised.

Information for Patients

Patients should be instructed to take olsalazine with food. The drug should be taken in evenly divided doses. Patients should be informed that about 17% of subjects receiving olsalazine during clinical studies reported diarrhea sometime during therapy. If diarrhea occurs, patients should contact their physician.

Drug Interaction

Increased prothrombin time in patients taking concomitant warfarin has been reported.

Drug/Laboratory Test Interactions

None known.

Carcinogenesis Mutagenesis, Impairment of Fertility

In a two year oral rat carcinogenicity study, olsalazine was tested in male and female Wistar rats at daily doses of 200, 400 and 800 mg/kg/day (approximately 10 to 40 times the human maintenance dose, based on a patient weight of 50 kg and a human dose of 1 g). Urinary bladder transitional cell carcinomas were found in three male rats (6%, p=0.022, exact trend test) receiving 40 times the human dose and were not found in untreated male controls. In the same study, urinary bladder transitional cell carcinoma and papilloma occurred in 2 untreated control female rats (2%). No such tumors were found in any of the female rats treated at doses up to 40 times the human dose.

In an eighteen month oral mouse carcinogenicity study, olsalazine was tested in male and female CD-1 mice at daily doses of 500, 1000 and 2000 mg/kg/day (approximately 25 to 100 times the human maintenance dose). Liver hemangiosarcomata were found in two male mice (4%) receiving olsalazine at 100 times the human dose, while no such tumor occurred in the other treated male mice groups or any of the treated female mice. The observed incidence of this tumor is within the 4% incidence in historical controls.

Olsalazine was not mutagenic in in vitro Ames tests, mouse lymphoma cell mutation assays, human lymphocyte chromosomal aberration tests and the in vivo rat bone marrow, cell chromosomal aberration test.

Olsalazine in a dose range of 100 to 400 mg/kg/day (approximately 5 to 20 times the human maintenance dose) did not influence the fertility of male or female rats. The oligospermia and infertility in men associated with sulfasalazine have not been reported with olsalazine.

Pregnancy

Teratogenic Effects: Pregnancy Category C. Olsalazine has been shown to produce fetal developmental toxicity as indicated by reduced fetal weights, retarded ossifications and immaturity of the fetal visceral organs when given during organogenesis to pregnant rats in doses 5 to 20 times the human dose (100 to 400 mg/kg). There are no adequate and well-controlled studies in pregnant women. Olsalazine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers

Oral administration of olsalazine to lactating rats in doses 5 to 20 times the human dose produced growth retardation in their pups. It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when olsalazine is administered to a nursing woman.

Pediatric Use

Safety and effectiveness in a pediatric population have not been established.

Geriatric Use

Clinical studies of DIPENTUM 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, elderly patients should be treated with caution due to the greater frequency of decreased hepatic, renal, or cardiac function, co-existence of other disease, as well as concomitant drug therapy.

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