|Manufacturer:||Taro Pharmaceuticals U.S.A., Inc.|
by: Taro Pharmaceutical Industries Ltd., Haifa Bay, Israel 26110Dist.by: Taro Pharmaceuticals U.S.A., Inc., Hawthorne, NY 10532Revised: November, 200590105-0706-2 307
Fluorouracil is recommended for the topical treatment of multiple actinic or solar keratoses.
In the 5% strength it is also useful in the treatment of superficial basal cell carcinomas when conventional methods are impractical, such as with multiple lesions or difficult treatment sites.
Safety and efficacy in other indications have not been established.The diagnosis should be established prior to treatment, since this method has not been proven effective in other types of basal cell carcinomas.
With isolated, easily accessible basal cell carcinomas, surgery is preferred since success with such lesions is almost 100%.
The success rate with Fluorouracil Topical Solution is approximately 93%, based on 113 lesions in 54 patients.Twenty-five lesions treated with the solution produced 1 failure.
Fluorouracil may cause fetal harm when administered to a pregnant woman.There are no adequate and well-controlled studies in pregnant women with either the topical or the parenteral forms of fluorouracil.
One birth defect (cleft lip and palate) has been reported in the newborn of a patient using fluorouracil as recommended.
One birth defect (ventricular septal defect) and cases of miscarriage have been reported when fluorouracil was applied to mucous membrane areas.
Multiple birth defects have been reported in a fetus of a patient treated with intravenous fluorouracil.Animal reproduction studies have not been conducted with fluorouracil.
Fluorouracil administered parenterally has been shown to be teratogenic in mice, rats, and hamsters when given at doses equivalent to the usual human intravenous dose; however, the amount of fluorouracil absorbed systemically after topical administration to actinic keratoses is minimal (see CLINICAL PHARMACOLOGY).
Fluorouracil exhibited maximum teratogencity when given to mice as single intraperitoneal injections of 10 to 40 mg/kg on Day 10 or 12 of gestation.
Similarly, intraperitoneal doses of 12 to 37 mg/kg given to rats between Days 9 and 12 of gestation and intramuscular doses of 3 to 9 mg/kg given to hamsters between Days 8 and 11 of gestation were teratogenic and/or embryotoxic (i.e., resulted in increased resorptions or embryolethality).
In monkeys, divided doses of 40 mg/kg given between Days 20 and 24 of gestation were not teratogenic.
Doses higher than 40 mg/kg resulted in abortion.Fluorouracil should not be used in patients with dihydropyrimidine dehydrogenase (DPD) enzyme deficiency.
A large percentage of fluorouracil is catabolized by the DPD enzyme.
DPD enzyme deficiency can result in shunting of fluorouracil to the anabolic pathway, leading to cytotoxic activity and potential toxicities.Fluorouracil is contraindicated in women who are or may become pregnant during therapy.If this drug is used during pregnancy, or if the patient becomes pregnant while using this drug, the patient should be apprised of the potential hazard to the fetus.Fluorouracil is also contraindicated in patients with known hypersensitivity to any of its components.
Application to mucous membranes should be avoided due to the possibility of local inflammation and ulceration.
Additionally, cases of miscarriage and a birth defect (ventricular septal defect) have been reported when fluorouracil was applied to mucous membrane areas during pregnancy.Occlusion of the skin with resultant hydration has been shown to increase percutaneous penetration of several topical preparations.
If any occlusive dressing is used in treatment of basal cell carcinoma, there may be an increase in the severity of inflammatory reactions in the adjacent normal skin.
A porous gauze dressing may be applied for cosmetic reasons without increase in reaction.Exposure to ultraviolet rays should be minimized during and immediately following treatment with fluorouracil because the intensity of the reaction may be increased.Patients should discontinue therapy with fluorouracil if symptoms of DPD enzyme deficiency develop (see CONTRAINDICATIONS section).Rarely, life-threatening toxicities such as stomatitis, diarrhea, neutropenia, and neurotoxicity have been reported with intravenous administration of fluorouracil in patients with DPD enzyme deficiency.
One case of life-threatening systemic toxicity has been reported with the topical use of fluorouracil in a patient with DPD enzyme deficiency.
Symptoms included severe abdominal pain, bloody diarrhea, vomiting, fever, and chills.
Physical examination revealed stomatitis, erythematous skin rash, neutropenia, thrombocytopenia, inflammation of the esophagus, stomach, and small bowel.Although this case was observed with 5% fluorouracil cream, it is unknown whether patients with profound DPD enzyme deficiency would develop systemic toxicity with lower concentrations of topically applied fluorouracil.