PRECAUTIONS General: There is a possibility of increased absorption through ulcerated or inflamed skin. Information for the Patient: Patients using Carac should receive the following information and instructions: 1.This medication is to be used as directed. 2.This medication should not be used for any disorder other than that for which it was prescribed. 3.It is for topical use only. 4.Avoid contact with the eyes, eyelids, nostrils, and mouth. 5.Cleanse affected area and wait 10 minutes before applying Carac. 6.Wash hands immediately after applying Carac. 7.Avoid prolonged exposure to sunlight or other forms of ultraviolet irradiation during treatment, as the intensity of the reaction may be increased. 8.Most patients using Carac get skin reactions where the medicine is used. These reactions include redness, dryness, burning, pain, erosion (loss of the upper layer of skin), and swelling. Irritation at the application site may persist for two or more weeks after therapy is discontinued. Treated areas may be unsightly during and after therapy. 9.If you develop abdominal pain, bloody diarrhea, vomiting, fever, or chills while on Carac therapy, stop the medication and contact your physician and/or pharmacist. 10.Report any side effects to the physician and/or pharmacist. Laboratory Tests: To rule out the presence of a frank neoplasm, a biopsy may be considered for those areas failing to respond to treatment or recurring after treatment. Carcinogenesis, Mutagenesis, and Impairment of Fertility: Adequate long-term studies in animals to evaluate carcinogenic potential have not been conducted with fluorouracil. Studies with the active ingredient of Carac, fluorouracil, have shown positive effects in in vitro and in vivo tests for mutagenicity and on impairment of fertility in in vivo animal studies. Fluorouracil produced morphological transformation of cells in in vitro cell transformation assays. Morphological transformation was also produced in an in vitro assay by a metabolite of fluorouracil, and the transformed cells produced malignant tumors when injected into immunosuppressed syngeneic mice. Fluorouracil has been shown to exert mutagenic activity in yeast cells, Bacillus subtilis, and Drosophila assays. In addition, fluorouracil has produced chromosome damage at concentrations of 1.0 and 2.0 mcg/mL in an in vitro hamster fibroblast assay, was positive in a microwell mouse lymphoma assay, and was positive in in vivo micronucleus assays in rats and mice following intraperitoneal administration. Some patients receiving cumulative doses of 0.24 to 1.0 g of fluorouracil parenterally have shown an increase in numerical and structural chromosome aberrations in peripheral blood lymphocytes. Fluorouracil has been shown to impair fertility after parenteral administration in rats. Fluorouracil administered at intraperitoneal doses of 125 and 250 mg/kg has been shown to induce chromosomal aberrations and changes in chromosome organization of spermatogonia in rats. In mice, single-dose intravenous and intraperitoneal injections of fluorouracil have been reported to kill differentiated spermatogonia and spermatocytes at a dose of 500 mg/kg and produce abnormalities in spermatids at 50 mg/kg. Pediatric Use: Actinic keratosis is not a condition seen within the pediatric population, except in association with rare genetic diseases. Carac should not be used in children. The safety and effectiveness of Carac have not been established in patients less than 18 years old. Geriatric Use: No significant differences in safety and efficacy measures were demonstrated in patients age 65 and older compared to all other patients. Pregnancy: See CONTRAINDICATIONS. Nursing Women: It is not known whether fluorouracil is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from fluorouracil, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.