There seems to be a lot of confusion regarding the difference between Carac and Efudex, particularly since Carac contains 0.5% fluorouracil and Efudex as much as 5%. Some believe that this makes Efudex 10 times stronger than Efudex. I was prescribed Carac and became very curious about the differences. From what I have been able to research, Carac has a different delivery system to the skin using what is called a "solid phase porous microsphere" or SPPM, which the Carac product data calls a "micosponge". One report I found regarding the effectiveness and use of SPPM's indicates "Topical drugs use a variety of ingredients to control the properties of the final product. Solid phase porous microspheres (SPPM, Microsponge[R]) have been incorporated into several topical prescription products in an effort to improve performance or tolerability. SPPMs provide a reservoir effect allowing more prolonged skin exposure to the active ingredient. They are used in products for acne vulgaris, actinic keratoses, and pigmentary changes."
"SPPMs consist of porous microspheres of an inert polymer that can entrap active ingredients and control their delivery rate to the skin. The advantage of the microsphere is that it releases active drug primarily into the epidermis with minimal transdermal penetration and little systemic absorption. Furthermore, drugs delivered using SPPMs can show the same efficacy at a lower concentration resulting in lower manufacturing costs and reduced irritancy potential."
Regarding fluorouracil in particular, I found the following sections of the analysis to be most relevant:
"For many years, 5-fluorouracil (5-FU) represented the standard in topical therapy for patients with multiple AKs. The poor tolerability of the product has been well characterized and various alternate dosing schemes have been published in an attempt to improve tolerability. The side effects of treatment with 5-FU include severe erythema as well as erosions and burning. A new cream formulation of 5-FU was developed using acrylate polymer SPPMs. This medication, Carac contains 5-FU reduced 10-fold in concentration to 0.5% and, presumably because of the gradual release nature of formulations containing SPPMs, needs only one daily application in contrast to the initially marketed 5-FU-containing drug, Efudex, which requires twice daily application."
"During the development of this new 5-FU product, comparison studies were conducted between the new formulation and the 5% cream product, Efudex. These studies revealed that the formulation including the SPPMs allowed similar percentages of their total dose of active ingredient to be absorbed. Far more importantly, the percentage of the applied dose that remained in the skin was nearly double for the SPPM-containing formulation."
"In an open-label, parallel-group study in which patients with AKs were treated with either the SPPM-containing 0.5% fluorouracil cream once a day or the 5% fluorouracil cream twice daily, tolerability of the treatments was compared. The 0.5% fluorouracil SPPM preparation seemed to be better tolerated than the 5% fluorouracil cream. Furthermore, the fluorouracil SPPM cream resulted in substantially less systemic absorption than did the 5% fluorouracil cream. More recently, a paired comparison clinical trial of 0.5% fluorouracil SPPM cream applied once a day versus 5% fluorouracil cream used twice a day was conducted for the treatment of AKs. This study also showed that treatment with the 0.5% fluorouracil SPPM cream was more efficacious but only slightly better tolerated than treatment with the 5% fluorouracil cream."
"Thus, the incorporation of SPPMs into a new 5-FU formulation is associated with multiple advantages. The amount of active ingredient required is substantially reduced (thus reducing the overall patient exposure to the drug), the dosing frequency is reduced to just once a day application, and there is a modest benefit in tolerability with similar or better efficacy. That the SPPM-containing 5-FU product is not substantially less irritating is not surprising. 5-FU takes effect through inhibiting nucleic acid synthesis in rapidly dividing cells, eventuating in cell death. This desired effect comes with the price of significant erythema and erosions. Such inflammation is noted with systemic 5-FU therapy as well. Thus the inflammation seen with 5-FU therapy may be inexorably linked to efficacy. It should not be expected to significantly uncouple the effectiveness of 5-FU from its known tolerability challenges without sacrificing efficacy."
While I am not versed in medical research, it seems at least from this report that:
1. Although Efudex contains 10 times the fluorouracil as Carac, the use of the SPPM technology in Carac provides for pretty much the same absorption into the skin even at the lower dosage and once a day application vs. twice.
2. The Carac may be tolerated a bit better than Efudex and it seems that while the same effect is obtained, less is absorbed into the body's overall system, which may reduce the other nasty side effects (nausea, etc.).
3. Both will produce the same redness, irritation, erosion, etc. even at the vastly different levels of fluorouracil since this is the only way the AK's themselves will be destroyed.
I was prescribed 4 weeks of Carac once a day. I did not use it for the full 4 weeks but stopped at 23 days since in my own view (and having read about the effects and erosion, etc.) the medicine had done its job. As others have indicated, I looked like hell, particularly after the second week and was lucky enough to be able to work from home. While my skin reaction was severe (as per most) I did not experience any other nasty side-effects so felt pretty lucky about that. I would say I started looking normal again after 7 days and by 14 days looked very good. As others have indicated it leaves your skin very smooth and soft, feeling great (I am a 54 year old male, so I was not much interested in the cosmetic benefits, more for the health, however I must say the way your skin looks after the treatment is a major side-benefit). I did not return to the dermotologist until two weeks after treatment (as per her instruction) and she indicated that the treatment was successful and the AK's had all been eliminated.
Sorry for such a long post, but I would encourage anyone beginning treatment to expore with their dermotologist the differences between Carac and Efudex and reasons for prescribing one vs. the other. I was not aware of the differences before beginning treatment and quite frankly my dermotologist prescribed Carac as it was the latest to be developed. My own view is that I would much rather use a lower dosage product once a day, particularly if the results are essentially comparable.