Efudix Cream (Efudex – the American spelling, 5-Flurouracil)
It stops an enzyme called thymidylate synthetase from working. This basically stops DNA from being made. This kills cells which are dividing (because dividing cells need to make another copy of their DNA). Because cancerous and precancerous cells divide more often than regular skin cells, we preferentially can kill cancerous or precancerous cells by stopping DNA production.
Your individual course depends on your doctor’s instructions – usually 3-4 weeks for Actinic Keratosis, and 6 weeks for Squamous Cell Carcinoma in situ.
You apply it to the lesion and usually an extra 5 millimetres around the lesion. Care must be taken to protect your finger that you apply the cream with – I recommend wearing disposable nitrile gloves when applying, and then wash hands afterwards. You also have to be very careful not to get efudix too close to the eyes or other sensitive body parts. Discuss this with your doctor.
How useful is efudix?
It is one of the most effective treatments we have for actinic keratosis. It has around a 75% chance of removing at least 75% of actinic keratosis from treated areas for one year.
It can be an effective treatment for Squamous Cell Carcinoma in situ (Bowen’s disease). The studies vary widely in cure rate – from 50-85% depending on multiple factors including treatment length.
Doctors may occasionally use efudix for other lesions. You should talk with your treating doctor.
How much efudix should I use?
This depends on your treatment area. Discuss with your doctor. In general, I recommend pouring a pea sized blob of efudix onto your finger, and applying 4-5 pea sized blobs if you are treating your entire face (e.g. 1.5-2 for forehead and nose, 1 for each cheek, 1 for the chin area). Advice may differ, and you should discuss exact details of dose with your treating doctor.
How bad is being on efudix?
It is pretty uncomfortable. I tell patients to imagine the worst sunburn of their life, multiply the pain a few times, and imagine being like that for 4-6 weeks. It is easier to deal with if you only have small areas you are treating, and especially if those areas are not on the face or not in areas of facial expression. Moving the facial muscles or laughing can be quite painful.
It is usually not too bad for the first 5-7 days. Then it gets very red and sore. The skin can become cracked and often there can be ooze. If you are concerned about the possibility of infection, you should talk to your doctor (see below). Many people who use it on the face will take 2-4 weeks off work.
If you are in a lot of pain, talk to your doctor about options. We can decrease the pain, but doing this may decrease how effective the treatment is.
After you stop treatment, it generally takes a few weeks for the skin to settle down to normal.
How to use Efudix
Wash the skin with warm water. Do not use soap.
Pat the area dry, and then wait 10-15 minutes.
Apply the efudix to the lesion and the extra margin recommended by your doctor (usually 5 mm). Use a glove. You can use a cotton bud or Q-Tip, but I find you tend to waste more of the cream this way.
Avoid contact with mucous membranes – eyes, nostrils and lips. Talk to your doctor if the treatment area involves these.
Wash your hands thoroughly after application.
Do not cover the treatment area (e.g. with a dressing) unless your doctor has told you to. Covering the area with an occlusive dressing will increase the strength of the reaction and may increase the risk of side effects or toxicity. You may choose to cover the area (for cosmetic reasons) with a non-occlusive porous gauze dressing, which is unlikely to increase the reaction. You should discuss with your doctor.
After 20 minutes, you can apply moisturisers, sunscreen and/or make-up as part of your usual skin care routine.
Efudix can take up to 2 hours to completely absorb into the skin – it is a good idea to apply your evening efudix at least 2-3 hours before bedtime, so it doesn’t get rubbed off onto your pillow.
Do not treat an area larger than 23x23cm. Treating the whole face for actinic keratosis in one go is usually fine, but you should clarify with your doctor for your individual needs.
Side effects / Toxicity:
Efudix is usually a well tolerated medicine with minimal risks when used correctly.
Efudix should not be used in pregnancy or if you are trying for pregnancy or breastfeeding.
Temporary or Permanent Hyper or Hypopigmentation
Whenever the skin is inflamed (for whatever reason) there is always a chance of irritating the pigment cells – potentially causing permanent light or dark blotches. In my experience, permanent pigmentation change is very rare, but you should be aware of this risk and discuss with your doctor. If you already have facial pigmentation problems (e.g. Chloasma, Melasma) you may be at increased risk and should talk to your doctor.
Any treatment that causes a lot of inflammation in the skin has a risk of scarring. Efudix is no exception to this. The risks of scarring with Efudix are low, but not zero. In my experience, only a few patients have had scarring afterwards, and they have still preferred the small scar to a (much more obvious) surgical scar. Scars can also be treated with laser or other cosmetic treatments if needed. Discuss this with your doctor prior to starting if you have any concerns.
Worsening of rosacea or new telangiectasia
Sometimes the inflammation of the efudix can increase the size of blood vessels in the skin, which can give facial skin a mottled or blushed appearance. We can use creams or laser to help this, but uncommonly this can be permanent and distressing for patients. If you already have rosacea or red blotchiness of your facial skin, you should talk to your doctor about this and potentially consider other treatments if you are concerned about this risk.
This is mainly a problem with the lower leg. Because the blood supply isn’t very good on the lower leg, sometimes the wound caused by efudix has trouble healing after the efudix has finished.
In my experience as a skin doctor, it is very unusual for areas treated with efudix to be truly infected by bacteria. It is much more common for patients or doctors without much experience to think the skin is infected because it looks horrible, particularly near the end of treatment – it is often a red, sore, oozing mess. I have never needed to use antibiotics for an infection after efudix. Sometimes, if there is any doubt, consideration can be given to topical antiseptics. If you have any concerns, you should see a doctor familiar with efudix straight away.
Life-threatening toxic reaction
This is extremely rare with topical efudix use. It is important to be aware of the symptoms. If you have any concerns, you should immediately attend your doctor or emergency department.
The symptoms include:
- Abdominal problems – pain, cramps, (usually bloody) diarrhoea and vomiting
- Swelling and soreness of the mouth or tongue
- Fevers and Chills – feeling like you have the flu
Blood tests may show pancytopaenia – neutropaenia, thrombocytopaenia.
Dihydropyrimidine dehydrogenase deficiency (DPD)
A very small amount of people have a condition known as DPD. These people cannot break down efudix properly. This increases the amount of efudix in their body, as they can’t get rid of it as well. It may increase their risk of developing toxic reactions. If you or a family member have this condition, you should inform your treating doctor. In general in Australia we do not test people for this condition before starting efudix.