Women who don't have BRCA mutations could have other high-risk genes that affect treatment choices
by NashDad on Mon Feb 18, 2008 12:00 AM
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.
The second sentence above should read "Some believe that this makes Efudex 10 times stronger than Carac."
by TruthsKeeper on Wed Feb 20, 2008 12:00 AM
Your information is great. Future members will benefit a lot from this. I was also fortunate that I was given Carac. There are many people posting what they've learned, tricks of the trade, so here's mine. I'm on application 22 for Facial area.
Plan ahead - Carac being used only once a day is usually at bedtime. I apply it about 7 p.m. so if the need comes for another cream (for me it hasn't) then the alloted time would pass before my usual 10 p.m. bedtime.
Daily prep - I wash and air dry (no towel) for 20 minutes before applying Carac. Don't scrub the area with a cloth, use your hands, or you'll get RAW fast.
Drink plenty of water along with juices, to stay hydrated, heated/conditioned air in buildings dry your skin out.
Applying to sore spots - use your ring finger. It has the least strength so you won't rub it in too hard and cause more pain. Tapping it on lightly at extra senitive areas. Wash hands and under nails thoroughly when done.
Itching - use your fingernail and lightly poke the area and the itch goes away.
by NashDad on Wed Feb 20, 2008 12:00 AM
I agree with your tip regarding timing of application. To me one of the major benefits of the once per day application of Carac was the ability to put it on in the evening allowing sufficient time prior to going to bed in the event you wanted to use vaseline, aquaphor, etc. after 2 or 3 hours. Also, since there was no application in the morning, you could apply these or sunscreen without having to wait.
For washing my face, I also found a very good product that was quite gentle and did not cause irritation. It is a Nivea for Men product called "Sensitive Face Wash". It contains no alcohol, soap or fragrance and did a good job of cleansing without contributing greatly to the overall dryness of the skin. I used it prior to applying Carac (waiting the indicated 20 minutes) and again in the morning. Although it is a product targeted at men, I think it would be fine for women given how gentle it is.
by kelmar on Wed Feb 20, 2008 12:00 AM
On 2/20/2008 NashDad wrote:Truths-- I agree with your tip regarding timing of application. To me one of the major benefits of the once per day application of Carac was the ability to put it on in the evening allowing sufficient time prior to going to bed in the event you wanted to use vaseline, aquaphor, etc. after 2 or 3 hours. Also, since there was no application in the morning, you could apply these or sunscreen without having to wait.For washing my face, I also found a very good product that was quite gentle and did not cause irritation. It is a Nivea for Men product called "Sensitive Face Wash". It contains no alcohol, soap or fragrance and did a good job of cleansing without contributing greatly to the overall dryness of the skin. I used it prior to applying Carac (waiting the indicated 20 minutes) and again in the morning. Although it is a product targeted at men, I think it would be fine for women given how gentle it is.
I am glad I found this site as i am terribly confused about my use of Carac. My Derm just game me the prescription and told me to use it once a day (did not specify how many days). I used for 21 days, once a day on my face and continued use on those areas that 'highlighted'. On the 21 day, I went to my Derm. he took one look at my face and told me to discontinue the Carac, prescribed antibodics and healing cream. I asked him about the erosion stage and he told me we must heal the redness, not seeming to know too much about the erosion stage (that I have been reading so much about). My face is terribly red and raw and I am wondering if I use 'healing' cream, am I defeating the purpose of the treatment by healing rather than eroding. Am I going backward??
by bfoley on Wed Feb 20, 2008 12:00 AM
I don't want to sound dumb, but is the erosion stage when your skin starts to peel ? I'm on day 12 of 14 days, and when I wash my face at night, I peel alot of skin off the treated areas.
by TruthsKeeper on Thu Feb 21, 2008 12:00 AM
Yes, the peeling actually is the erosion stage. Use caution that you don't rub the skin or force peel it off as it can and will get extremely sore. You can also end up removing too much, too soon making it more prone to cracking/splitting/bleeding. Ever had chapped lips that split? Imagine other areas of your face with that same sensation. Ouch. The more cracking and rawness you create, the more open you are to bacterial infections.
My advice: Don't rub, don't pick, don't scratch.
by luvlivin on Thu Feb 21, 2008 12:00 AM
by gary_o on Thu Feb 21, 2008 12:00 AM
On 2/21/2008 luvlivin wrote:Hey Brian-I am on day 21 out of 28? I just keep on keepin' on. Something odd- My forehead which I thought would react first is only reacting now! I am so frustrated about this- I have stopped total application and began only spot treating on certain areas of my face-some areas are turning brownish grey and then peel off-minimal cracking-mostly on jawline but am Pi352% off about this forehead-I wanted to stop asap but looks like I have to keep going on the lesions until they turn brownish gray and fall off-UUUUUGGGGGHHH. When do you go and see your derm AND why do you only have a 14 day script for carac? How old are you? (if you don't mind)-Best to you Heather
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