Sunday, May 31, 2009
BLOG HAS MOVED! See new link >>
I've moved my blog after realizing Blogger doesn't get picked up in the search engines much. You can now see my Efudex pictures and photos at www.hybriddesign.net/efudex
Monday, May 25, 2009
WARNING! READ THIS!
To anyone contemplating purchasing Efudex from Canada
I purchased the generic form of Efudex, Fluorouracil, from an online Canadian pharmacy. What many people don't know is that the majority of these pharmacies receive their medications from other countries. They will tell you this if you ask, so PLEASE ASK! I thought I was getting a real deal by purchasing a 40 gram tube for $33, which would be $250 in the U.S. (and that's generic!)
My order of 40 grams came in 3 tubes of 15 grams each. When I opened the first tube, it was very runny, with some small clumps of white cream. With each application as I got further down the tube, the cream got drier and drier. Eventually it was too dry to spread, and just ended up in clumps on my face. The cream also appeared curdled, kind of like cottage cheese only smaller curds. The expiration date wasn't until 2010, but I read the box that it came in and it stated it was manufactured in India. It also, like many meds, states that it must be kept in certain temperatures. I went through all three tubes, and they were all the same.
I had an uneasy feeling about this and spoke to a few people who have used Efudex in the past. They all said it should be smooth and creamy throughout. At this point I was already 10 days in, and not wanting to have gone through this for no reason, I decided to bite the bullet and purchase the generic form from my local Walgreens pharmacy (yes, it was actually cheaper there than Wal-Mart!). This cream was totally different than the cream I received from Canada.
Would my reaction had been any different if I never used the generic cream that I got from the Canadian pharmacy? Who knows. But the cream itself definitely wasn't right, and even the Canadian pharmacy offered to send me another tube if I sent this one back. With me in the middle of the treatment, it wasn't an option.
"Drugs from Canada don't always come from Canada. According to President of CanaRX, a Canadian Web site that sells online, 70 percent of drugs sold to Americans from Canada are made elsewhere, so the drug you think you're importing from Canada probably comes from a third world country with less stringent protections than either the US or Canada." READ MORE
"Customs-FDA operation in August 2005 at New York, Miami and Los Angeles airports, showing that a large percentage of drugs purportedly coming from Canadian pharmacies actually originated in India, Israel, Costa Rica and other countries, and many were counterfeit.
...Canadian Internet pharmacies may be run by shady dealers in countries such as India, China and North Korea." READ MORE
I purchased the generic form of Efudex, Fluorouracil, from an online Canadian pharmacy. What many people don't know is that the majority of these pharmacies receive their medications from other countries. They will tell you this if you ask, so PLEASE ASK! I thought I was getting a real deal by purchasing a 40 gram tube for $33, which would be $250 in the U.S. (and that's generic!)
My order of 40 grams came in 3 tubes of 15 grams each. When I opened the first tube, it was very runny, with some small clumps of white cream. With each application as I got further down the tube, the cream got drier and drier. Eventually it was too dry to spread, and just ended up in clumps on my face. The cream also appeared curdled, kind of like cottage cheese only smaller curds. The expiration date wasn't until 2010, but I read the box that it came in and it stated it was manufactured in India. It also, like many meds, states that it must be kept in certain temperatures. I went through all three tubes, and they were all the same.
I had an uneasy feeling about this and spoke to a few people who have used Efudex in the past. They all said it should be smooth and creamy throughout. At this point I was already 10 days in, and not wanting to have gone through this for no reason, I decided to bite the bullet and purchase the generic form from my local Walgreens pharmacy (yes, it was actually cheaper there than Wal-Mart!). This cream was totally different than the cream I received from Canada.
Would my reaction had been any different if I never used the generic cream that I got from the Canadian pharmacy? Who knows. But the cream itself definitely wasn't right, and even the Canadian pharmacy offered to send me another tube if I sent this one back. With me in the middle of the treatment, it wasn't an option.
"Drugs from Canada don't always come from Canada. According to President of CanaRX, a Canadian Web site that sells online, 70 percent of drugs sold to Americans from Canada are made elsewhere, so the drug you think you're importing from Canada probably comes from a third world country with less stringent protections than either the US or Canada." READ MORE
"Customs-FDA operation in August 2005 at New York, Miami and Los Angeles airports, showing that a large percentage of drugs purportedly coming from Canadian pharmacies actually originated in India, Israel, Costa Rica and other countries, and many were counterfeit.
...Canadian Internet pharmacies may be run by shady dealers in countries such as India, China and North Korea." READ MORE
Sunday, May 24, 2009
Before pic
Found lots of pics online of those going through the Efudex treatment, but none of females, unless you count the lady on the Efudex manufacturer's website. So, I've decided to post mine here, but due to reasons of vanity, I have to post a before pic :)
Living in FL, I spent a lot of days in the sun. When I was younger it was bike riding and as soon as I was able to drive, it was going to the beach. For a few years, I practically lived at the beach. Sunscreen?? Who needs it? By the time any sun damage catches up with me, I'll be old, so who cares anyway? haha The thoughts of a 19-year-old, like many, who think being in your 30's is old. My mother had melanoma, which thankfully did not metastasize. My sisters have both had skin cancer (squamous & basal). This time I'm doing my face, but next time around I am going to do my chest. Enjoy these beautiful pics, and once in a while, please scroll up and remind yourself that I did look normal at one time!
Day 5
Day 5 - Spots are getting darker and skin is tender to the touch. With the flash from the camera it doesn't appear as dark or as red as it really was.
Day 7
This will be the last day I'll apply make up. It's too tender and having to wash it off isn't pleasant. Skin tender. Started applying aloe, and then aloe & lidocaine spray. My face got very red very fast by this evening. See next pic.
Day 7 - Evening
Full blown red. It actually looks like my face got dragged over concrete. Kind of like scrapes. No more make-up. No more leaving the house. Had some neighbors ask me, "what happened to your face???" The shine is from the Aquaphor I applied to help ease the burn.
Day 10
DAY 10 - Aloe burned now. Stopped using it. The Aquaphor was a bitch to wash off, and the water felt like needles so I stopped using that as well. Now I'm using a refrigerated ice pack (the soft gel kind) to help the burning and itching.
My sister got an infection while using Efudex, so just as a precaution I use rubber gloves (the thin latex kind). It also, for some reason, seems to not hurt as bad than when I used my fingers. I took some advice from my dr and applied the Efudex in a dimly lit room, just enough to see my face (so I'd know where I'm applying it), but not enough to see the details. Apparently studies have shown that one's perception of pain is increased when they can actually see the severity of the injury (or wound, or whatever...)
Day 11
DAY 11 - Not looking so good. Face burned like hell when rinsing off the Aquaphor. Don't think I'll be using that anymore for a while.
Day 12
DAY 12 - Using cold compresses and as little Aquaphor as possible. The cold feels good when it's on, but once you take it off, it stings a lot. A lot of stinging in the apples of my cheeks.
Day 14 - last day of Efudex (except for forehead)
DAY 14 - THE LAST DAY - Skin still smooth but very tender and red. Lots of tightness and itching. Some burning. This is the last day of Efudex, except for my forehead, which I will continue applying for a few more days. That's where I had the most sun damage.
2 days post treatment (except for forehead)
2 DAYS POST TREATMENT
DAY 16 FOREHEAD ONLY
I've finished applying the Efudex everywhere but on my forehead. May be just me, but it seems a little less red today. Tried rinsing chin with water, but felt like hot needles! Then it got very tight. I'm using Aristocort steroid cream as needed. I apply a light coat of Aquaphor twice a day.
3 days post treatment (except for forehead)
3 DAYS POST TREATMENT
DAY 17 (FOREHEAD ONLY)
Some peeling on forehead today.
Last day of forehead application
No big changes today. More peeling, mainly on chin and forehead. Yesterday was the last day of my forehead application.
5th day post-treatment (2nd day for forehead)
No more burning, just itching and more peeling. I washed my face this morning to try and get off some of the loose skin. It's tempting to pick at it but the skin underneath looks & feels so delicate at this point. The places where there were dark spots are peeling off. Forehead very stiff. A lot of tenderness around the temples. After I washed with Cetaphil, I applied the triamcinolone (steroid cream) and after about 20 minutes applied the Aquaphor. My face is so dry at this point that when I apply it at night, by the morning it's already absorbed so there really isn't any greasy feeling to wash off like there was in the beginning.
Haven't had any trouble sleeping. I attribute this to using the steroid cream and Aquaphor. I'll post a pic later.
Haven't had any trouble sleeping. I attribute this to using the steroid cream and Aquaphor. I'll post a pic later.
6th day post treatment (3rd day for forehead)
More peeling this morning. Applied steroid cream and then once absorbed applied Aquaphor. Took some lovely close up shots. It's been 6 days post treatment for everything except my forehead, which has been 3 days post treatment. I've read this happening to others, and yes, it's true, it can leave little divets in your skin. I have one in the place where I had an early stage basal cell carcinoma. I was washing my face this morning and when the skin came off of it, it left a nice little divet. I've read that these go away though. My skin is so dry and stiff that when I wash it, the little loose pieces end up causing little pin pricks of blood to appear when they rub over the tender, new red skin. They feel like tiny shards of glass.
It's a brighter shade of red today. A lot of the brown spots are sloughing off exposing tender red skin underneath.
Close up shots
6th day post treatment page close up pics:
http://efudex-photos.blogspot.com/2009/05/6-days-post-treatment-4-days-for.html
7th day post treatment:
http://efudex-photos.blogspot.com/2009/05/7th-day-post-treatment-4th-day-for.html
http://efudex-photos.blogspot.com/2009/05/6-days-post-treatment-4-days-for.html
7th day post treatment:
http://efudex-photos.blogspot.com/2009/05/7th-day-post-treatment-4th-day-for.html
7th day post treatment (4th day for forehead)
Most of the peeling is finished, now it's pretty much just dry and flaky, and tender where the new red skin is. When I touch it to wash it or put on the steroid cream, it usually bleeds a little in some spots. The tiny rough pieces of skin still feel like miniature shards of glass that pierce my skin and leave tiny pin pricks of blood.
8th day post treatment (5th day for forehead)
Forehead still tender. Some bleeding on forehead and the known bcc has scabbed over. Some crusting over my eyebrow.
9th day post treatment (6th day for forehead)
Not itching too bad today. Haven't applied the steroid cream, only using Aquaphor. A lot of bleeding on the forehead.
Friday, May 1, 2009
Efudex
Actinic Keratoses (AKs)
A skin disease also known as solar keratoses. These lesions are the result of years of unprotected exposure to the sun's ultraviolet (UV) rays. Although you may have been extra careful about sun protection in the recent past, if you spend time in the sun when you were younger, you have put yourself at risk for developing AKs. Many adults have AKs, so rest assured that you are not alone.
AKs actually represent the earliest stages of squamous cell carcinoma (SCC). Since the 1960s the incidence of the SCC has been increasing 4%-8% per year. SCC affects about 100,000 Americans each year and 2,000 to 2,500 Americans die each year due to SCC of the skin.
Superficial Basal Cell Carcinoma (sBCC)
sBCC is among the most common types of skin cancer, that traditionally does NOT spread to other parts of the body. sBCC has become more common in younger patients, probably due to increased sun exposure.3 The lifetime risk of developing some type of nonmelanoma skin cancer is 33%-39%.4 sBCC is another condition that is commonly treated with EFUDEX® 5% Solution or Cream when conventional methods such as surgery are impractical.
A skin disease also known as solar keratoses. These lesions are the result of years of unprotected exposure to the sun's ultraviolet (UV) rays. Although you may have been extra careful about sun protection in the recent past, if you spend time in the sun when you were younger, you have put yourself at risk for developing AKs. Many adults have AKs, so rest assured that you are not alone.
AKs actually represent the earliest stages of squamous cell carcinoma (SCC). Since the 1960s the incidence of the SCC has been increasing 4%-8% per year. SCC affects about 100,000 Americans each year and 2,000 to 2,500 Americans die each year due to SCC of the skin.
Superficial Basal Cell Carcinoma (sBCC)
sBCC is among the most common types of skin cancer, that traditionally does NOT spread to other parts of the body. sBCC has become more common in younger patients, probably due to increased sun exposure.3 The lifetime risk of developing some type of nonmelanoma skin cancer is 33%-39%.4 sBCC is another condition that is commonly treated with EFUDEX® 5% Solution or Cream when conventional methods such as surgery are impractical.
Wednesday, April 1, 2009
Why Efudex?
Rapid Clearance of AKs
Efficacy is achieved in as little as 2 weeks1
* Cures up to 86% of visible AK lesions in just 2-4 weeks1
* Additional AK lesions were also detected and resolved during treatment6,7
Benefits of EFUDEX®
* Starts working within the first week of treatment8
* Provides rapid resolution of AK lesions6,7
* Offers excellent cosmetic outcome7
Solar of Actinic Keratoses (AK) may Develop into Squamous Cell Carcinoma2
* AKs represent the earliest stages of squamous cell carcinoma (SCC)2
* Since the 1960's, the incidence of SCC has been increasing 4% to 8% per year9
* Squamous cell skin cancer affects about 100,000 Americans each year9
* 2,000 to 2,500 Americans die each year due to SCC of the skin2
* Patients may have up to 10 times as many subclinical/undetected lesions for each visible AK10
* Younger patients are developing AKs3
Proven Efficacy in sBCC(5% Strength)1
The Cure Rate for EFUDEX® is consistently high
* 93% cure rate in sBCC1
* At least 3-6 weeks, and up to 10-12 weeks sBCC treatment duration
EFUDEX® offers benefits when conventional methods are impractical
* Minimizes the risk of hypopigmentation11
* Provides an effective option for large and difficult to treat areas11
* Treats surrounding AK lesions1
sBCC is among the most common types of skin cancer
* BCC makes up about 80% of all skin cancers9
* An increased incidence of sBCC in younger patients may be due to greater sun exposure3
* sBCCs represent approximately 15% of BCCs12
Trust the experience of EFUDEX® in both sBCCs and AKs
* Over 30 years of proven clinical experience8
* Over 14 million prescriptions since 19725
* EFUDEX® is the #1 prescribed topical 5-FU13
Important Safety Information
EFUDEX® is contraindicated in women who are, or may become, pregnant during therapy because of potential hazards to the fetus. Cases of miscarriage and birth defects have been reported in women who are pregnant. The most frequent adverse events occur locally and may include itching, burning, soreness, tenderness, rash, scaling, scarring, photosensitivity, and swelling. Application to mucous membranes should be avoided due to the possibility of local inflammation and ulceration.
* Over 14 million prescriptions have been written for Efudex over last 30 years5
* High success rates
IMPORTANT SAFETY INFORMATION
EFUDEX® (fluorouracil) Topical Solutions and Cream 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.
EFUDEX is contraindicated in women who are, or may become, pregnant during therapy because of potential hazards to the fetus. Cases of miscarriage and birth defects have been reported in women who are pregnant.
The most frequent adverse events occur locally and may include itching, burning, soreness, tenderness, scaling, and swelling. Application to mucous membranes should be avoided due to the possibility of local inflammation and ulceration.
Please see complete Prescribing Information for EFUDEX.
Efficacy is achieved in as little as 2 weeks1
* Cures up to 86% of visible AK lesions in just 2-4 weeks1
* Additional AK lesions were also detected and resolved during treatment6,7
Benefits of EFUDEX®
* Starts working within the first week of treatment8
* Provides rapid resolution of AK lesions6,7
* Offers excellent cosmetic outcome7
Solar of Actinic Keratoses (AK) may Develop into Squamous Cell Carcinoma2
* AKs represent the earliest stages of squamous cell carcinoma (SCC)2
* Since the 1960's, the incidence of SCC has been increasing 4% to 8% per year9
* Squamous cell skin cancer affects about 100,000 Americans each year9
* 2,000 to 2,500 Americans die each year due to SCC of the skin2
* Patients may have up to 10 times as many subclinical/undetected lesions for each visible AK10
* Younger patients are developing AKs3
Proven Efficacy in sBCC(5% Strength)1
The Cure Rate for EFUDEX® is consistently high
* 93% cure rate in sBCC1
* At least 3-6 weeks, and up to 10-12 weeks sBCC treatment duration
EFUDEX® offers benefits when conventional methods are impractical
* Minimizes the risk of hypopigmentation11
* Provides an effective option for large and difficult to treat areas11
* Treats surrounding AK lesions1
sBCC is among the most common types of skin cancer
* BCC makes up about 80% of all skin cancers9
* An increased incidence of sBCC in younger patients may be due to greater sun exposure3
* sBCCs represent approximately 15% of BCCs12
Trust the experience of EFUDEX® in both sBCCs and AKs
* Over 30 years of proven clinical experience8
* Over 14 million prescriptions since 19725
* EFUDEX® is the #1 prescribed topical 5-FU13
Important Safety Information
EFUDEX® is contraindicated in women who are, or may become, pregnant during therapy because of potential hazards to the fetus. Cases of miscarriage and birth defects have been reported in women who are pregnant. The most frequent adverse events occur locally and may include itching, burning, soreness, tenderness, rash, scaling, scarring, photosensitivity, and swelling. Application to mucous membranes should be avoided due to the possibility of local inflammation and ulceration.
* Over 14 million prescriptions have been written for Efudex over last 30 years5
* High success rates
IMPORTANT SAFETY INFORMATION
EFUDEX® (fluorouracil) Topical Solutions and Cream 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.
EFUDEX is contraindicated in women who are, or may become, pregnant during therapy because of potential hazards to the fetus. Cases of miscarriage and birth defects have been reported in women who are pregnant.
The most frequent adverse events occur locally and may include itching, burning, soreness, tenderness, scaling, and swelling. Application to mucous membranes should be avoided due to the possibility of local inflammation and ulceration.
Please see complete Prescribing Information for EFUDEX.
What can I expect during treatment?
Rapid Clearance of AKs
What Can I Expect During My AK Treatment?
During the first 2 to 4 weeks of treatment, the areas of your skin affected by AK or sBCC lesions will probably turn red and look and feel irritated. This is typical and should not cause concern. The redness, crusting, and peeling are signs that EFUDEX® is working to eliminate the unhealthy cells. Even though this stage of treatment may be unattractive and somewhat uncomfortable, it is important that you do not stop the therapy.
Some patients may be concerned with the inflammation associated with EFUDEX® therapy. Talk to your doctor; he or she can best assess the situation and advise you.
Areas of your skin where there were no lesions may become red and inflamed. This is because abnormal cells can become inflamed even if the cells were not previously noticeable on the skin's surface.1, 18-20 The more AKs you have, the more redness and inflammation you can expect during treatment.
"Photographs reproduced courtesy of the Skin Cancer Foundation, New York, NY. For more information about skin cancer prevention, detection and treatment,visit their website at www.skincancer.org"
Demonstrated Tolerability and Confirmed Patient Satisfaction in sBCC
What Can I Expect During My sBCC Treatment?
Your sBCC treatment lasts for at least 3-6 weeks, and up to 10-12 weeks. Your area of treatment may experience mild pain.21
* Over 14 million prescriptions have been written for Efudex over last 30 years5
* High success rates
IMPORTANT SAFETY INFORMATION
EFUDEX® (fluorouracil) Topical Solutions and Cream 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.
EFUDEX is contraindicated in women who are, or may become, pregnant during therapy because of potential hazards to the fetus. Cases of miscarriage and birth defects have been reported in women who are pregnant.
The most frequent adverse events occur locally and may include itching, burning, soreness, tenderness, scaling, and swelling. Application to mucous membranes should be avoided due to the possibility of local inflammation and ulceration.
What Can I Expect During My AK Treatment?
During the first 2 to 4 weeks of treatment, the areas of your skin affected by AK or sBCC lesions will probably turn red and look and feel irritated. This is typical and should not cause concern. The redness, crusting, and peeling are signs that EFUDEX® is working to eliminate the unhealthy cells. Even though this stage of treatment may be unattractive and somewhat uncomfortable, it is important that you do not stop the therapy.
Some patients may be concerned with the inflammation associated with EFUDEX® therapy. Talk to your doctor; he or she can best assess the situation and advise you.
Areas of your skin where there were no lesions may become red and inflamed. This is because abnormal cells can become inflamed even if the cells were not previously noticeable on the skin's surface.1, 18-20 The more AKs you have, the more redness and inflammation you can expect during treatment.
"Photographs reproduced courtesy of the Skin Cancer Foundation, New York, NY. For more information about skin cancer prevention, detection and treatment,visit their website at www.skincancer.org"
Demonstrated Tolerability and Confirmed Patient Satisfaction in sBCC
What Can I Expect During My sBCC Treatment?
Your sBCC treatment lasts for at least 3-6 weeks, and up to 10-12 weeks. Your area of treatment may experience mild pain.21
* Over 14 million prescriptions have been written for Efudex over last 30 years5
* High success rates
IMPORTANT SAFETY INFORMATION
EFUDEX® (fluorouracil) Topical Solutions and Cream 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.
EFUDEX is contraindicated in women who are, or may become, pregnant during therapy because of potential hazards to the fetus. Cases of miscarriage and birth defects have been reported in women who are pregnant.
The most frequent adverse events occur locally and may include itching, burning, soreness, tenderness, scaling, and swelling. Application to mucous membranes should be avoided due to the possibility of local inflammation and ulceration.
Efudex prescribing info
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 propylene glycol, tris (hydroxymethyl) aminomethane,
hydroxypropyl cellulose, parabens (methyl and propyl) and
disodium edetate.
Efudex Cream contains 5% fluorouracil in a vanishing cream base consisting
of white petrolatum, stearyl alcohol, propylene glycol, polysorbate 60
and parabens (methyl and propyl).
Chemically, fluorouracil is 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:
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 (eg, CO2, urea, a-fluoro-b-alanine) which are inactive.
Systemic absorption studies of topically applied fluorouracil have been
performed on patients with actinic keratoses using tracer amounts of 14Clabeled
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
14C-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.
CONTRAINDICATIONS: Efudex may cause fetal harm when administered
to a pregnant woman.
There are no adequate and well-controlled studies in pregnant women
with either the topical or the parenteral forms of fluorouracil. One birth
defect (cleft lip and palate) has been reported in the newborn of a patient
using Efudex as recommended. One birth defect (ventricular septal defect)
and cases of miscarriage have been reported when Efudex was applied to
mucous membrane areas. Multiple birth defects have been reported in a
fetus of a patient treated with intravenous fluorouracil.
Animal reproduction studies have not been conducted with Efudex.
Fluorouracil administered parenterally has been shown to be teratogenic in
mice, rats, and hamsters when given at doses equivalent to the usual
human intravenous dose; however, the amount of fluorouracil absorbed
systemically after topical administration to actinic keratoses is minimal
(see CLINICAL PHARMACOLOGY). Fluorouracil exhibited maximum teratogenicity
when given to mice as single intraperitoneal injections of 10 to
40 mg/kg on Day 10 or 12 of gestation. Similarly, intraperitoneal doses of
12 to 37 mg/kg given to rats between Days 9 and 12 of gestation and intramuscular
doses of 3 to 9 mg/kg given to hamsters between Days 8 and 11
of gestation were teratogenic and/or embryotoxic (ie, resulted in increased
resorptions or embryolethality). In monkeys, divided doses of 40 mg/kg
given between Days 20 and 24 of gestation were not teratogenic. Doses
higher than 40 mg/kg resulted in abortion.
Efudex should not be used in patients with dihydropyrimidine dehydrogenase
(DPD) enzyme deficiency. A large percentage of fluorouracil is
catabolized by the DPD enzyme. DPD enzyme deficiency can result in
shunting of fluorouracil to the anabolic pathway, leading to cytotoxic activity
and potential toxicities.
Efudex is contraindicated in women who are or may become pregnant
during therapy. If this drug is used during pregnancy, or if the
patient becomes pregnant while using this drug, the patient should
be apprised of the potential hazard to the fetus.
Efudex is also contraindicated in patients with known hypersensitivity
to any of its components.
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 Efudex 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 Efudex because the intensity of the reaction may
be increased.
Patients should discontinue therapy with Efudex if symptoms of DPD
enzyme deficiency develop (see CONTRAINDICATIONS section).
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 lifethreatening
systemic toxicity has been reported with the topical use of
Efudex 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
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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.
PRECAUTIONS: General: There is a possibility of increased absorption
through ulcerated or inflamed skin.
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 Efudex because the intensity of the reaction may be increased.
If Efudex is applied with the fingers, the hands should be washed immediately
afterward. Efudex should not be applied on the eyelids or directly into
the eyes, nose or mouth because irritation may occur.
Laboratory Tests: Solar keratoses which do not respond should be biopsied
to confirm the diagnosis. Follow-up biopsies should be performed as
indicated in the management of superficial basal cell carcinoma.
Carcinogenesis, Mutagenesis, Impairment of Fertility: Adequate longterm
studies in animals to evaluate carcinogenic potential have not been
conducted with fluorouracil. Studies with the active ingredient of Efudex, 5-
fluorouracil, have shown positive effects in in vitro tests for mutagenicity
and on impairment of fertility.
5-Fluorouracil was positive in three in vitro cell neoplastic transformation
assays. In the C3H/10T1⁄ 2 clone 8 mouse embryo cell system, the resulting
morphologically transformed cells formed tumors when inoculated into
immunosuppressed syngeneic mice.
While no evidence for mutagenic activity was observed in the Ames test (3
studies), fluorouracil has been shown to be mutagenic in the survival count
rec-assay with Bacillus subtilis and in the Drosophilia wing-hair spot test.
Fluorouracil produced petite mutations in Saccharomyces cerevisiae and
was positive in the micronucleus test (bone marrow cells of male mice).
Fluorouracil was clastogenic in vitro (ie, chromatid gaps, breaks and
exchanges) in Chinese hamster fibroblasts at concentrations of 1.0 and
2.0 mg/mL and has been shown to increase sister chromatid exchange in
vitro in human lymphocytes. In addition, 5-fluorouracil has been reported
to produce an increase in numerical and structural chromosome aberrations
in peripheral lymphocytes of patients treated with this product.
Doses of 125 to 250 mg/kg, administered intraperitoneally, have been
shown to induce chromosomal aberrations and changes in chromosome
organization of spermatogonia in rats. Spermatogonial differentiation was
also inhibited by fluorouracil, resulting in transient infertility. However, in
studies with a strain of mouse which is sensitive to the induction of sperm
head abnormalities after exposure to a range of chemical mutagens and
carcinogens, fluorouracil was inactive at oral doses of 5 to 80 mg/kg/day.
In female rats, fluorouracil administered intraperitoneally at doses of 25
and 50 mg/kg during the preovulatory phase of oogenesis significantly
reduced the incidence of fertile matings, delayed the development of
preimplantation and postimplantation embryos, increased the incidence of
preimplantation lethality and induced chromosomal anomalies in these
embryos. Single dose intravenous and intraperitoneal injections of 5-fluorouracil
have been reported to kill differentiated spermatogonia and spermatocytes
(at 500 mg/kg) and to produce abnormalities in spermatids (at
50 mg/kg) in mice.
Pregnancy: Teratogenic Effects: Pregnancy Category X: See CONTRAINDICATIONS
section.
Nursing Mothers: It is not known whether Efudex 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.
Pediatric Use: Safety and effectiveness in children have not been established.
ADVERSE REACTIONS: The most frequent adverse reactions to Efudex
occur locally and are often related to an extension of the pharmacological
activity of the drug. These include burning, crusting, allergic contact dermatitis,
erosions, erythema, hyperpigmentation, irritation, pain, photosensitivity,
pruritus, scarring, rash, soreness and ulceration. Ulcerations, other
local reactions, cases of miscarriage and a birth defect (ventricular septal
defect) have been reported when Efudex was applied to mucous membrane
areas. Leukocytosis is the most frequent hematological side effect.
Although a causal relationship is remote, other adverse reactions which
have been reported infrequently are:
Central Nervous System: Emotional upset, insomnia, irritability.
Gastrointestinal: Medicinal taste, stomatitis.
Hematological: Eosinophilia, thrombocytopenia, toxic granulation.
Integumentary: Alopecia, blistering, bullous pemphigoid, discomfort,
ichthyosis, scaling, suppuration, swelling, telangiectasia, tenderness,
urticaria, skin rash.
Special Senses: Conjunctival reaction, corneal reaction, lacrimation, nasal
irritation.
Miscellaneous: Herpes simplex.
OVERDOSAGE: There have been no reports of overdosage with Efudex.
The oral LD50 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
LD50 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 LD50 of greater than 500 mg/kg.
DOSAGE AND ADMINISTRATION: When Efudex is applied to a lesion, a
response occurs with the following sequence: erythema, usually followed
by vesiculation, desquamation, erosion and reepithelialization.
Efudex should be applied preferably with a nonmetal applicator or suitable
glove. If Efudex is applied with the fingers, the hands should be washed
immediately afterward.
Actinic or Solar Keratosis: Apply cream or 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 Efudex therapy.
Superficial Basal Cell Carcinomas: Only the 5% strength is recommended.
Apply cream or 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.
HOW SUPPLIED: Efudex Solution is available in 10-mL drop dispensers
containing either 2% (NDC 0187-3202-10) or 5% (NDC 0187-3203-10) fluorouracil
and 25-mL drop dispensers containing either 2% (NDC 0187-3202-
02) or 5% (NDC 0187-3203-02) fluorouracil on a weight/weight basis
compounded with propylene glycol, tris (hydroxymethyl) aminomethane,
hydroxypropyl cellulose, parabens (methyl and propyl) and disodium edetate.
Efudex Cream is available in 40-gm tubes (NDC 0187-3204-47) containing
5% fluorouracil in a vanishing cream base consisting of white petrolatum,
stearyl alcohol, propylene glycol, polysorbate 60 and parabens (methyl
and propyl).
Store at 25°C (77°F); excursions permitted to 15°C-30°C (59°F-86°F).
EFUDEX® (fluorouracil) EFUDEX® (fluorouracil)
containing the fluorinated pyrimidine 5-fluorouracil, an antineoplastic
antimetabolite.
Efudex Solution consists of 2% or 5% fluorouracil on a weight/weight
basis, compounded with propylene glycol, tris (hydroxymethyl) aminomethane,
hydroxypropyl cellulose, parabens (methyl and propyl) and
disodium edetate.
Efudex Cream contains 5% fluorouracil in a vanishing cream base consisting
of white petrolatum, stearyl alcohol, propylene glycol, polysorbate 60
and parabens (methyl and propyl).
Chemically, fluorouracil is 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:
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 (eg, CO2, urea, a-fluoro-b-alanine) which are inactive.
Systemic absorption studies of topically applied fluorouracil have been
performed on patients with actinic keratoses using tracer amounts of 14Clabeled
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
14C-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.
CONTRAINDICATIONS: Efudex may cause fetal harm when administered
to a pregnant woman.
There are no adequate and well-controlled studies in pregnant women
with either the topical or the parenteral forms of fluorouracil. One birth
defect (cleft lip and palate) has been reported in the newborn of a patient
using Efudex as recommended. One birth defect (ventricular septal defect)
and cases of miscarriage have been reported when Efudex was applied to
mucous membrane areas. Multiple birth defects have been reported in a
fetus of a patient treated with intravenous fluorouracil.
Animal reproduction studies have not been conducted with Efudex.
Fluorouracil administered parenterally has been shown to be teratogenic in
mice, rats, and hamsters when given at doses equivalent to the usual
human intravenous dose; however, the amount of fluorouracil absorbed
systemically after topical administration to actinic keratoses is minimal
(see CLINICAL PHARMACOLOGY). Fluorouracil exhibited maximum teratogenicity
when given to mice as single intraperitoneal injections of 10 to
40 mg/kg on Day 10 or 12 of gestation. Similarly, intraperitoneal doses of
12 to 37 mg/kg given to rats between Days 9 and 12 of gestation and intramuscular
doses of 3 to 9 mg/kg given to hamsters between Days 8 and 11
of gestation were teratogenic and/or embryotoxic (ie, resulted in increased
resorptions or embryolethality). In monkeys, divided doses of 40 mg/kg
given between Days 20 and 24 of gestation were not teratogenic. Doses
higher than 40 mg/kg resulted in abortion.
Efudex should not be used in patients with dihydropyrimidine dehydrogenase
(DPD) enzyme deficiency. A large percentage of fluorouracil is
catabolized by the DPD enzyme. DPD enzyme deficiency can result in
shunting of fluorouracil to the anabolic pathway, leading to cytotoxic activity
and potential toxicities.
Efudex is contraindicated in women who are or may become pregnant
during therapy. If this drug is used during pregnancy, or if the
patient becomes pregnant while using this drug, the patient should
be apprised of the potential hazard to the fetus.
Efudex is also contraindicated in patients with known hypersensitivity
to any of its components.
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 Efudex 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 Efudex because the intensity of the reaction may
be increased.
Patients should discontinue therapy with Efudex if symptoms of DPD
enzyme deficiency develop (see CONTRAINDICATIONS section).
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 lifethreatening
systemic toxicity has been reported with the topical use of
Efudex 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
EFUDEX® (fluorouracil)
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=
N
H
NH
O
F
3360197EX03 FPO
back page of 3360197EX03
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.
PRECAUTIONS: General: There is a possibility of increased absorption
through ulcerated or inflamed skin.
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 Efudex because the intensity of the reaction may be increased.
If Efudex is applied with the fingers, the hands should be washed immediately
afterward. Efudex should not be applied on the eyelids or directly into
the eyes, nose or mouth because irritation may occur.
Laboratory Tests: Solar keratoses which do not respond should be biopsied
to confirm the diagnosis. Follow-up biopsies should be performed as
indicated in the management of superficial basal cell carcinoma.
Carcinogenesis, Mutagenesis, Impairment of Fertility: Adequate longterm
studies in animals to evaluate carcinogenic potential have not been
conducted with fluorouracil. Studies with the active ingredient of Efudex, 5-
fluorouracil, have shown positive effects in in vitro tests for mutagenicity
and on impairment of fertility.
5-Fluorouracil was positive in three in vitro cell neoplastic transformation
assays. In the C3H/10T1⁄ 2 clone 8 mouse embryo cell system, the resulting
morphologically transformed cells formed tumors when inoculated into
immunosuppressed syngeneic mice.
While no evidence for mutagenic activity was observed in the Ames test (3
studies), fluorouracil has been shown to be mutagenic in the survival count
rec-assay with Bacillus subtilis and in the Drosophilia wing-hair spot test.
Fluorouracil produced petite mutations in Saccharomyces cerevisiae and
was positive in the micronucleus test (bone marrow cells of male mice).
Fluorouracil was clastogenic in vitro (ie, chromatid gaps, breaks and
exchanges) in Chinese hamster fibroblasts at concentrations of 1.0 and
2.0 mg/mL and has been shown to increase sister chromatid exchange in
vitro in human lymphocytes. In addition, 5-fluorouracil has been reported
to produce an increase in numerical and structural chromosome aberrations
in peripheral lymphocytes of patients treated with this product.
Doses of 125 to 250 mg/kg, administered intraperitoneally, have been
shown to induce chromosomal aberrations and changes in chromosome
organization of spermatogonia in rats. Spermatogonial differentiation was
also inhibited by fluorouracil, resulting in transient infertility. However, in
studies with a strain of mouse which is sensitive to the induction of sperm
head abnormalities after exposure to a range of chemical mutagens and
carcinogens, fluorouracil was inactive at oral doses of 5 to 80 mg/kg/day.
In female rats, fluorouracil administered intraperitoneally at doses of 25
and 50 mg/kg during the preovulatory phase of oogenesis significantly
reduced the incidence of fertile matings, delayed the development of
preimplantation and postimplantation embryos, increased the incidence of
preimplantation lethality and induced chromosomal anomalies in these
embryos. Single dose intravenous and intraperitoneal injections of 5-fluorouracil
have been reported to kill differentiated spermatogonia and spermatocytes
(at 500 mg/kg) and to produce abnormalities in spermatids (at
50 mg/kg) in mice.
Pregnancy: Teratogenic Effects: Pregnancy Category X: See CONTRAINDICATIONS
section.
Nursing Mothers: It is not known whether Efudex 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.
Pediatric Use: Safety and effectiveness in children have not been established.
ADVERSE REACTIONS: The most frequent adverse reactions to Efudex
occur locally and are often related to an extension of the pharmacological
activity of the drug. These include burning, crusting, allergic contact dermatitis,
erosions, erythema, hyperpigmentation, irritation, pain, photosensitivity,
pruritus, scarring, rash, soreness and ulceration. Ulcerations, other
local reactions, cases of miscarriage and a birth defect (ventricular septal
defect) have been reported when Efudex was applied to mucous membrane
areas. Leukocytosis is the most frequent hematological side effect.
Although a causal relationship is remote, other adverse reactions which
have been reported infrequently are:
Central Nervous System: Emotional upset, insomnia, irritability.
Gastrointestinal: Medicinal taste, stomatitis.
Hematological: Eosinophilia, thrombocytopenia, toxic granulation.
Integumentary: Alopecia, blistering, bullous pemphigoid, discomfort,
ichthyosis, scaling, suppuration, swelling, telangiectasia, tenderness,
urticaria, skin rash.
Special Senses: Conjunctival reaction, corneal reaction, lacrimation, nasal
irritation.
Miscellaneous: Herpes simplex.
OVERDOSAGE: There have been no reports of overdosage with Efudex.
The oral LD50 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
LD50 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 LD50 of greater than 500 mg/kg.
DOSAGE AND ADMINISTRATION: When Efudex is applied to a lesion, a
response occurs with the following sequence: erythema, usually followed
by vesiculation, desquamation, erosion and reepithelialization.
Efudex should be applied preferably with a nonmetal applicator or suitable
glove. If Efudex is applied with the fingers, the hands should be washed
immediately afterward.
Actinic or Solar Keratosis: Apply cream or 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 Efudex therapy.
Superficial Basal Cell Carcinomas: Only the 5% strength is recommended.
Apply cream or 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.
HOW SUPPLIED: Efudex Solution is available in 10-mL drop dispensers
containing either 2% (NDC 0187-3202-10) or 5% (NDC 0187-3203-10) fluorouracil
and 25-mL drop dispensers containing either 2% (NDC 0187-3202-
02) or 5% (NDC 0187-3203-02) fluorouracil on a weight/weight basis
compounded with propylene glycol, tris (hydroxymethyl) aminomethane,
hydroxypropyl cellulose, parabens (methyl and propyl) and disodium edetate.
Efudex Cream is available in 40-gm tubes (NDC 0187-3204-47) containing
5% fluorouracil in a vanishing cream base consisting of white petrolatum,
stearyl alcohol, propylene glycol, polysorbate 60 and parabens (methyl
and propyl).
Store at 25°C (77°F); excursions permitted to 15°C-30°C (59°F-86°F).
EFUDEX® (fluorouracil) EFUDEX® (fluorouracil)
Efudex indications
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.
DOSAGE AND ADMINISTRATION
When Efudex is applied to a lesion, a response occurs with the following sequence: erythema, usually followed by vesiculation, desquamation, erosion and reepithelialization.
Efudex should be applied preferably with a nonmetal applicator or suitable glove. If Efudex is applied with the fingers, the hands should be washed immediately afterward.
Actinic or Solar Keratosis: Apply cream or 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 Efudex therapy.
Superficial Basal Cell Carcinomas: Only the 5% strength is recommended. Apply cream or 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.
HOW SUPPLIED
Efudex Solution is available in 10-mLdrop dispensers containing either 2% (NDC 0187-3202-10) or 5% (NDC 0187-3203-10) fluorouracil and 25-mLdrop dispensers containing either 2% (NDC 0187-3202-02) or 5% (NDC 0187-3203-02) fluorouracil on a weight/weight basis compounded with propylene glycol, tris (hydroxymethyl) aminomethane, hydroxypropyl cellulose, parabens (methyl and propyl) and disodium edetate.
Efudex Cream is available in 40-gm tubes containing 5% fluorouracil (NDC 0187-3204-47) in a vanishing cream base consisting of white petrolatum, stearyl alcohol, propylene glycol, polysorbate 60 and parabens (methyl and propyl).
Store at 25°C (77°F); excursions permitted to 15°C - 30°C (59°F - 86°F).
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.
DOSAGE AND ADMINISTRATION
When Efudex is applied to a lesion, a response occurs with the following sequence: erythema, usually followed by vesiculation, desquamation, erosion and reepithelialization.
Efudex should be applied preferably with a nonmetal applicator or suitable glove. If Efudex is applied with the fingers, the hands should be washed immediately afterward.
Actinic or Solar Keratosis: Apply cream or 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 Efudex therapy.
Superficial Basal Cell Carcinomas: Only the 5% strength is recommended. Apply cream or 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.
HOW SUPPLIED
Efudex Solution is available in 10-mLdrop dispensers containing either 2% (NDC 0187-3202-10) or 5% (NDC 0187-3203-10) fluorouracil and 25-mLdrop dispensers containing either 2% (NDC 0187-3202-02) or 5% (NDC 0187-3203-02) fluorouracil on a weight/weight basis compounded with propylene glycol, tris (hydroxymethyl) aminomethane, hydroxypropyl cellulose, parabens (methyl and propyl) and disodium edetate.
Efudex Cream is available in 40-gm tubes containing 5% fluorouracil (NDC 0187-3204-47) in a vanishing cream base consisting of white petrolatum, stearyl alcohol, propylene glycol, polysorbate 60 and parabens (methyl and propyl).
Store at 25°C (77°F); excursions permitted to 15°C - 30°C (59°F - 86°F).
Efudex 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 Efudex 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 Efudex because the intensity of the reaction may be increased.
Patients should discontinue therapy with Efudex if symptoms of DPD enzyme deficiency develop (see CONTRAINDICATIONS section).
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 Efudex 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.
PRECAUTIONS
General: There is a possibility of increased absorption through ulcerated or inflamed skin.
Laboratory Tests: Solar keratoses which do not respond should be biopsied to confirm the diagnosis. Follow-up biopsies should be performed as indicated in the management of superficial basal cell carcinoma.
Carcinogenesis, Mutagenesis, Impairment of Fertility: Adequate long-term studies in animals to evaluate carcinogenic potential have not been conducted with fluorouracil. Studies with the active ingredient of Efudex, 5-fluorouracil, have shown positive effects in in vitro tests for mutagenicity and on impairment of fertility.
5-Fluorouracil was positive in three in vitro cell neoplastic transformation assays. In the C3H/10T12 clone 8 mouse embryo cell system, the resulting morphologically transformed cells formed tumors when inoculated into immunosuppressed syngeneic mice.
While no evidence for mutagenic activity was observed in the Ames test (3 studies), fluorouracil has been shown to be mutagenic in the survival count rec-assay with Bacillus subtilis and in the Drosophila wing-hair spot test. Fluorouracil produced petite mutations in Saccharomyces cerevisiae and was positive in the micronucleus test (bone marrow cells of male mice).
Fluorouracil was clastogenic in vitro (ie, chromatid gaps, breaks and exchanges) in Chinese hamster fibroblasts at concentrations of 1.0 and 2.0 ug/mL and has been shown to increase sister chromatid exchange in vitro in human lymphocytes. In addition, 5-fluorouracil has been reported to produce an increase in numerical and structural chromosome aberrations in peripheral lymphocytes of patients treated with this product.
Doses of 125 to 250 mg/kg, administered intraperitoneally have been shown to induce chromosomal aberrations and changes in chromosome organization of spermatogonia in rats. Spermatogonial differentiation was also inhibited by fluorouracil, resulting in transient infertility. However, in studies with a strain of mouse which is sensitive to the induction of sperm head abnormalities after exposure to a range of chemical mutagens and carcinogens, fluorouracil was inactive at oral doses of 5 to 80 mg/kg/day. In female rats, fluorouracil administered intraperitoneally at doses of 25 and 50 mg/kg during the preovulatory phase of oogenesis significantly reduced the incidence of fertile matings, delayed the development of preimplantation and postimplantation embryos, increased the incidence of preimplantation lethality and induced chromosomal anomalies in these embryos. Single dose intravenous and intraperitoneal injections of 5-fluorouracil have been reported to kill differentiated spermatogonia and spermatocytes (at 500 mg/kg) and to produce abnormalities in spermatids (at 50 mg/kg) in mice.
Pregnancy: Teratogenic Effects: Pregnancy Category X: See CONTRAINDICATIONS section
Nursing Mothers: It is not known whether Efudex 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.
Pediatric Use: Safety and effectiveness in children have not been established.
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 Efudex because the intensity of the reaction may be increased.
Patients should discontinue therapy with Efudex if symptoms of DPD enzyme deficiency develop (see CONTRAINDICATIONS section).
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 Efudex 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.
PRECAUTIONS
General: There is a possibility of increased absorption through ulcerated or inflamed skin.
Laboratory Tests: Solar keratoses which do not respond should be biopsied to confirm the diagnosis. Follow-up biopsies should be performed as indicated in the management of superficial basal cell carcinoma.
Carcinogenesis, Mutagenesis, Impairment of Fertility: Adequate long-term studies in animals to evaluate carcinogenic potential have not been conducted with fluorouracil. Studies with the active ingredient of Efudex, 5-fluorouracil, have shown positive effects in in vitro tests for mutagenicity and on impairment of fertility.
5-Fluorouracil was positive in three in vitro cell neoplastic transformation assays. In the C3H/10T12 clone 8 mouse embryo cell system, the resulting morphologically transformed cells formed tumors when inoculated into immunosuppressed syngeneic mice.
While no evidence for mutagenic activity was observed in the Ames test (3 studies), fluorouracil has been shown to be mutagenic in the survival count rec-assay with Bacillus subtilis and in the Drosophila wing-hair spot test. Fluorouracil produced petite mutations in Saccharomyces cerevisiae and was positive in the micronucleus test (bone marrow cells of male mice).
Fluorouracil was clastogenic in vitro (ie, chromatid gaps, breaks and exchanges) in Chinese hamster fibroblasts at concentrations of 1.0 and 2.0 ug/mL and has been shown to increase sister chromatid exchange in vitro in human lymphocytes. In addition, 5-fluorouracil has been reported to produce an increase in numerical and structural chromosome aberrations in peripheral lymphocytes of patients treated with this product.
Doses of 125 to 250 mg/kg, administered intraperitoneally have been shown to induce chromosomal aberrations and changes in chromosome organization of spermatogonia in rats. Spermatogonial differentiation was also inhibited by fluorouracil, resulting in transient infertility. However, in studies with a strain of mouse which is sensitive to the induction of sperm head abnormalities after exposure to a range of chemical mutagens and carcinogens, fluorouracil was inactive at oral doses of 5 to 80 mg/kg/day. In female rats, fluorouracil administered intraperitoneally at doses of 25 and 50 mg/kg during the preovulatory phase of oogenesis significantly reduced the incidence of fertile matings, delayed the development of preimplantation and postimplantation embryos, increased the incidence of preimplantation lethality and induced chromosomal anomalies in these embryos. Single dose intravenous and intraperitoneal injections of 5-fluorouracil have been reported to kill differentiated spermatogonia and spermatocytes (at 500 mg/kg) and to produce abnormalities in spermatids (at 50 mg/kg) in mice.
Pregnancy: Teratogenic Effects: Pregnancy Category X: See CONTRAINDICATIONS section
Nursing Mothers: It is not known whether Efudex 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.
Pediatric Use: Safety and effectiveness in children have not been established.
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