fluorouracil 5 % Topical Solution
Generic Name: FLUOROURACIL
Brand Name: Fluorouracil
- Substance Name(s):
- FLUOROURACIL
WARNINGS
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 ).
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.
OVERDOSAGE
There have been no reports of overdosage with fluorouracil.
The oral LD 50 for the 5% topical cream was 234 mg/kg in rats and 39 mg/kg in dogs.
These doses represented 11.7 and 1.95 mg/kg of fluorouracil, respectively.
Studies with a 5% topical solution yielded an oral LD 50 of 214 mg/kg in rats and 28.5 mg/kg in dogs, corresponding to 10.7 and 1.43 mg/kg of fluorouracil, respectively.
The topical application of the 5% cream to rats yielded an LD 50 of greater than 500 mg/kg.
DESCRIPTION
Fluorouracil Topical Solutions are topical preparations containing the fluorinated pyrimidine 5-fluorouracil, an antineoplastic antimetabolite.
Fluorouracil Topical Solution consists of 2% or 5% fluorouracil on a weight/weight basis, compounded with edetate disodium, hydroxypropyl cellulose, methylparaben, propylene glycol, propylparaben, purified water and tromethamine.
Chemically, fluorouracil is 5-fluoro-2,4(1 H , 3 H )-pyrimidinedione.
It is a white to practically white, crystalline powder which is sparingly soluble in water and slightly soluble in alcohol.
One gram of fluorouracil is soluble in 100 mL of propylene glycol.
The molecular weight of 5-fluorouracil is 130.08 and the structural formula is: Chemical Structure
HOW SUPPLIED
Fluorouracil Topical Solution, USP is available in 10-mL drop dispensers containing either 2% (NDC 51672-4062-1) or 5% (NDC 51672-4063-1) fluorouracil on a weight/weight basis compounded with edetate disodium, hydroxypropyl cellulose, methylparaben, propylene glycol, propylparaben, purified water and tromethamine.
Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].
INDICATIONS AND USAGE
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.
PEDIATRIC USE
Pediatric Use Safety and effectiveness in children have not been established.
PREGNANCY
Pregnancy See CONTRAINDICATIONS .
NUSRING MOTHERS
Nursing Mothers It is not known whether fluorouracil 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.
INFORMATION FOR PATIENTS
Information for Patients 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 fluorouracil because the intensity of the reaction may be increased.
If fluorouracil is applied with the fingers, the hands should be washed immediately afterward.
Fluorouracil should not be applied on the eyelids or directly into the eyes, nose, or mouth because irritation may occur.
Fluorouracil, including fluorouracil topical solution may be fatal if ingested by pets.
Avoid allowing pets to contact the fluorouracil topical solution container or the skin where fluorouracil topical solution has been applied.
Store fluorouracil topical solution out of reach of pets.
Safely discard or clean any cloth or applicator that may retain fluorouracil topical solution and avoid leaving any residues of fluorouracil topical solution on your hands, clothing, carpeting or furniture.
DOSAGE AND ADMINISTRATION
When fluorouracil is applied to a lesion, a response occurs with the following sequence: erythema, usually followed by vesiculation, desquamation, erosion, and re-epithelialization.
Fluorouracil should be applied preferably with a nonmetal applicator or suitable glove.
If fluorouracil is applied with the fingers, the hands should be washed immediately afterward.
Actinic or Solar Keratosis Apply solution twice daily in an amount sufficient to cover the lesions.
Medication should be continued until the inflammatory response reaches the erosion stage, at which time use of the drug should be terminated.
The usual duration of therapy is from 2 to 4 weeks.
Complete healing of the lesions may not be evident for 1 to 2 months following cessation of fluorouracil therapy.
Superficial Basal Cell Carcinomas Only the 5% strength is recommended.
Apply solution twice daily in an amount sufficient to cover the lesions.
Treatment should be continued for at least 3 to 6 weeks.
Therapy may be required for as long as 10 to 12 weeks before the lesions are obliterated.
As in any neoplastic condition, the patient should be followed for a reasonable period of time to determine if a cure has been obtained.