Clinical Information
Gen. Code and Des.
7502 fluorouracil TOPICAL CREAM (G) 5 %
GCN and Des.
30781 fluorouracil TOPICAL CREAM (G) 5 %
Strength
5%
Dose Form
CREAM (GRAM)
Product Category
RX Pharmaceuticals
Fine Line Class
850085008510 All Rx Products
DEA Class
NC
OMP Family
AHFS Class
10000000 ANTINEOPLASTIC AGENTS
84920000 SKIN AND MUCOUS MEMBRANE AGENTS, MISC.
Active Ingredients
2646 fluorouracil 51218
Inactive Ingredients
2468 propylene glycol 57556
3203 paraben 99967
EFUDEX- fluorouracil solution
EFUDEX- fluorouracil cream
Valeant Pharmaceuticals North America LLC
FOR TOPICAL USE ONLY
NOT FOR OPHTHALMIC, ORAL,
OR INTRAVAGINAL USE
DESCRIPTION:
Efudex Solutions and Cream are topical preparations containing the fluorinated pyrimidine 5-fluorouracil, an antineoplastic antimetabolite.
Efudex Solution consists of 2% or 5% fluorouracil on a weight/weight basis, compounded with disodium edetate, hydroxypropyl cellulose, methylparaben, propylene glycol, propylparaben, and tris (hydroxymethyl) aminomethane.
Efudex Cream contains 5% fluorouracil in a vanishing cream base consisting of methylparaben, polysorbate 60, propylene glycol, propylparaben, purified water, stearyl alcohol, and white petrolatum.
Chemically, fluorouracil is a 5-fluoro-2,4(1H ,3H)-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 StructureChemical Structure
CLINICAL PHARMACOLOGY:
There is evidence that the metabolism of fluorouracil in the anabolic pathway blocks the methylation reaction of deoxyuridylic acid to thymidylic acid. In this manner, fluorouracil interferes with the synthesis of deoxyribonucleic acid (DNA) and to a lesser extent inhibits the formation of ribonucleic acid (RNA). Since DNA and RNA are essential for cell division and growth, the effect of fluorouracil may be to create a thymine deficiency which provokes unbalanced growth and death of the cell. The effects of DNA and RNA deprivation are most marked on those cells which grow more rapidly and take up fluorouracil at a more rapid rate. The catabolic metabolism of fluorouracil results in degradation products (e.g., CO2 , urea, ?-fluoro-?-alanine) which are inactive.
Systemic absorption studies of topically applied fluorouracil have been performed on patients with actinic keratoses using tracer amounts of 14 C-labeled fluorouracil added to a 5% preparation. All patients had been receiving nonlabeled fluorouracil until the peak of the inflammatory reaction occurred (2 to 3 weeks), ensuring that the time of maximum absorption was used for measurement. One gram of labeled preparation was applied to the entire face and neck and left in place for 12 hours. Urine samples were collected. At the end of 3 days, the total recovery ranged between 0.48% and 0.94% with an average of 0.76%, indicating that approximately 5.98% of the topical dose was absorbed systemically. If applied twice daily, this would indicate systemic absorption of topical fluorouracil to be in the range of 5 to 6 mg per daily dose of 100 mg. In an additional study, negligible amounts of labeled material were found in plasma, urine, and expired CO2 after 3 days of treatment with topically applied 14 C-labeled fluorouracil.
INDICATIONS AND USAGE:
Efudex 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 Efudex Cream and Solution is approximately 93%, based on 113 lesions in 54 patients. Twenty-five lesions treated with the solution produced 1 failure and 88 lesions treated with the cream produced 7 failures.
