Source: FDA, National Drug Code (US) Revision Year: 2020
EFUDEX 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 EFUDEX as recommended. One birth defect (ventricular septal defect) and cases of miscarriage have been reported when EFUDEX 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 EFUDEX. 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 teratogenicity 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.
EFUDEX 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.
EFUDEX 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.
EFUDEX 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 EFUDEX 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 EFUDEX because the intensity of the reaction may be increased.
Patients should discontinue therapy with EFUDEX if symptoms of DPD enzyme deficiency develop (see CONTRAINDICATIONS).
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 EFUDEX 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.
The most frequent adverse reactions to EFUDEX occur locally and are often related to an extension of the pharmacological activity of the drug. These include burning, crusting, allergic contact dermatitis, pruritus, scarring, rash, soreness, and ulceration. Ulcerations, other local reactions, cases of miscarriage, and a birth defect (ventricular septal defect) have been reported when EFUDEX was applied to mucous membrane areas. Leukocytosis is the most frequent hematological side effect.
Although a causal relationship is remote, other adverse reactions which have been reported infrequently are:
Central Nervous System: Emotional upset, insomnia, irritability.
Gastrointestinal: Medicinal taste, stomatitis.
Hematological: Eosinophilia, thrombocytopenia, toxic granulation.
Integumentary: Alopecia, blistering, bullous pemphigoid, discomfort, ichthyosis, scaling, suppuration, swelling, telangiectasia, tenderness, urticaria, skin rash.
Special Senses: Conjunctival reaction, corneal reaction, lacrimation, nasal irritation.
Miscellaneous: Herpes simplex.
There is a possibility of increased absorption through ulcerated or inflamed skin.
Patients should be forewarned that the reaction in the treated areas may be unsightly during therapy and, usually, for several weeks following cessation of therapy. Patients should be instructed to avoid exposure to ultraviolet rays during and immediately following treatment with EFUDEX because the intensity of the reaction may be increased. If EFUDEX is applied with the fingers, the hands should be washed immediately afterward. EFUDEX should not be applied on the eyelids or directly into the eyes, nose, or mouth because irritation may occur.
Solar keratoses which do not respond should be biopsied to confirm the diagnosis. Follow-up biopsies should be performed as indicated in the management of superficial basal cell carcinoma.
See CONTRAINDICATIONS.
It is not known whether EFUDEX is excreted in human milk. Because there is some systemic absorption of fluorouracil after topical administration (see CLINICAL PHARMACOLOGY), because many drugs are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue use of the drug, taking into account the importance of the drug to the mother.
Safety and effectiveness in children have not been established.
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