Is Fluorouracil (Carac, Efudex) Absorbed Through The Skin?

Fluorouracil (Carac, Efudex) has minimal absorption when applied topically to the skin.


I was using fluorouracil 5% on my entire face, once a day. I also take acyclovir 1 time per day. I stopped taking the acyclovir when I started the fluorouracil due to the pamphlet saying to be aware of possible interactions. When is it safe to start the acyclovir again?

Asked by dmania On Dec 11, 2018

Answered by
Medical Content Reviewed By PharmacistAnswers Staff

On Dec 12, 2018
Tube Of Cream Squeezed Out

There is very little data available unfortunately regarding whether or not topical fluorouracil could interact with other medications you may be taking.

The prescribing information for Efudex and Carac, two brand name topical products that contain fluorouracil as the active ingredient, don't list any potential interactions.

Nevertheless, fluorouracil, when given intravenously (for certain indications like breast cancer), does have several well-documented drug interactions.

One such drug interaction is with anticoagulant medications. Systemic fluorouracil can lower blood platelet counts, which help to clot blood. Taking any medication that thins the blood with fluorouracil increases the risk of bleeding.

Going back to topical fluorouracil, the important question regarding potential interactions is whether or not it gets absorbed in clinically significant amounts.

Studies suggest that overall absorption of topical fluorouracil is minimal, but is absorbed in measurable amounts in a small number of individuals. However, no drug interactions have been reported with it.

Along the same lines, there are no known interactions between topical fluorouracil and acyclovir. Therefore, there is no need to separate doses of each unless otherwise directed by your doctor. Your pamphlet may have been referring only to fluorouracil given intravenously.

In the next section, I discuss fluorouracil skin absorption in more detail.

Answer Summary

Topical fluorouracil has minimal systemic absorption. There have been no studies evaluating the risk of potential drug interactions, but it isn't thought that the small amount of fluorouracil that is absorbed is clinically significant.

Fluorouracil Absorption

There are several published studies that have evaluated the extent of absorption of topical fluorouracil products.

The prescribing information for Efudex states that systemic absorption of a 1 gram dose is around 6%. Other sources list systemic absorption around 10% of the applied dose.

Study One

In the study 'Total Body Topical 5-fluorouracil For Extensive Non-melanoma Skin Cancer', two cases are discussed in which 5 grams of 5-fluorouracil was applied to the entire body of 2 individuals.

The doses used were far greater than what most individuals use (13-20 grams in the case studies vs. the typical 1-2 grams for most indications).

The study reported the following:

"Analysis of blood samples showed, in our patients, that systemic absorption did not lead to detectable blood levels or systemic side effects. Pharmacokinetic evaluation by Levy et al. showed that topical application results in a minimal systemic absorption (10%), however, absorption can be up to 75 times greater in diseased skin."

The 'Levy et al' study the excerpt above is referring to it a study in which measurable concentrations of fluorouracil were seen in a small number of patients, but in amounts far below what are thought to have any clinically significant effect.

Study Two

The prescribing information for a brand of topical fluorouracil (Tolak) describes a study in which 21 patients were given the 4% topical cream. Concentrations of the drug were measured after 4 weeks of continuous use.

Eight of the 21 patients had undetectable plasma concentrations while the remaining having measurables levels, but at concentrations not thought to be clinically significant.

A one gram application of 4% Tolak contains 40 mg of fluorouracil (of which only 6-10% is absorbed systemically).

When we consider that intravenous doses of fluorouracil are typically 500 mg or higher, the level of exposure to topical fluorouracil is minimal and a tiny percentage of what you are exposed to when used systemically.


Studies show that topical fluorouracil has minimal systemic absorption, with many individuals not having measurable concentrations at all, even after long-term use.

Additional Information

It is extremely important to apply fluorouracil as directed.

As discussed above, fluorouracil is not well absorbed into the skin, but absorption can significantly increase if used on mucus membranes or broken skin. This could increase the risk of side effects.

Be sure to not apply to the eyelids, nose, mouth or any place other than where your doctor has prescribed.

About the Pharmacist

Dr. Brian Staiger Pharm.D

Dr. Brian Staiger is a licensed pharmacist in New York State and the founder of He graduated from the University At Buffalo with a Doctor of Pharmacy degree in 2010. He has been featured in numerous publications including the Huffington Post as well as a variety of health and pharmacy-related blogs. Please feel free to reach out to him directly if you have any inquiries or want to connect! He's answered thousands of medication and pharmacy-related questions and he's ready to answer yours! Office: 716-389-3076

Recent Questions