What is fluorouracil cream?
Topical fluorouracil 5% cream is often abbreviated to 5-FU. The trade name in New Zealand is Efudix™ and it is a prescription medicine. It is a cytotoxic agent or antimetabolite and it is toxic to living cells, especially to certain cancer or precancerous cells. It destroys sun-damaged skin cells, so the skin appears smoother and more youthful.
In many countries, 0.5% fluorouracil cream combined with 10% salicylic acid is also available (Actikerall®).
Reaction to fluorouracil cream after 2 weeks' use on actinic keratoses
How does fluorouracil work?
Fluorouracil is a pyrimidine analogue that irreversibly binds within a cell to thymidylate synthetase. This prevents the incorporation uracil into nuclear RNA, which destroys abnormal cancer cells.
What is fluorouracil used for?
Fluorouracil cream is most often prescribed to clear up actinic keratoses and intraepidermal carcinoma (in situ squamous cell carcinoma). A full-face course has been shown to substantially reduce the risk of cutaneous squamous cell carcinoma (SCC) developing in the treated site during the following year.
Fluorouracil is also occasionally used to treat the following skin conditions:
- Superficial basal cell carcinoma
- Viral warts
- Genital warts
- Disseminated superficial porokeratosis and linear porokeratosis.
It works best on face and scalp and is less effective on other body sites.
How should fluorouracil cream be used?
Fluorouracil cream is a powerful, destructive medication and must be used exactly as directed. Keep it locked up so other people cannot mistakenly use it to treat a rash.
Pretreatment with cryotherapy or keratolytics, such as urea cream or glycolic acid lotion, is useful to minimise scaling and permit optimum absorption of the active ingredient, 5-FU.
Fluorouracil cream is applied once or twice a day after washing with plain water. A tiny amount of the cream should be gently rubbed into all of the treatment areas with a fingertip. It is important to apply it to all the skin and not just visible lesions. Afterwards, rinse the finger thoroughly with water (or use a glove or cotton bud to apply the cream). Treatment for actinic keratoses is continued for 2 to 4 weeks. Longer may be necessary for the treatment of squamous cell carcinoma in situ.
The manufacturer's guidelines indicate that the maximum area to be treated at one time is 500 cm2.
Combination treatments with fluorouracil cream
Sometimes fluorouracil cream is prescribed in combination with another topical agent.
- The combination of 5% fluorouracil cream with tretinoin cream works best if the tretinoin has been used for at least two weeks prior to starting fluorouracil. Tretinoin cream enhances the effect of fluorouracil by peeling off the top layer of skin. It reduces the time required for the course of fluorouracil treatment. Tretinoin cream can be continued afterwards long term to reduce the signs of skin ageing and prevent deterioration, using very careful sun protection.
- Combining low-potency 0.5% fluorouracil cream with 10% salicylic acid> (Actikerall™) has also been shown to be effective for actinic keratoses on the face and hands and forearms over a 12-week course. It is especially useful for hyperkeratotic (horny) lesions.
- 5% fluorouracil cream with 0.005% calcipotriol ointment has been reported to improve efficacy and reduce the number of days required for treatment of actinic keratoses compared to 5% fluorouracil cream alone.
Fluorouracil wraps, also known as chemowraps, are an in-office occlusive treatment for extensive field treatment for actinic keratoses and intraepidermal carcinomas. They are most often used to treat severely sun damaged lower legs. After cleansing the area to be treated, a thick coat of fluorouracil cream is applied to scaly lesions and surrounding skin, often circumferentially around the limb. About 10 to 20 g of 5-FU is used for each limb. Paraffin gauze is applied over the fluorouracil cream to areas of movement (eg ankle) as protection. The limb is then carefully bandaged using loose layers of zinc oxide (to improve healing and reduce pain), cotton conforming bandage and crepe or self-adherent roll for compression.
The chemowrap is left in place for 7 days, then removed. The treated skin is washed and gently scrubbed to remove loose skin and scabs. Fluorouracil treatment is repeated once weekly for 4 to 12 weeks. If treated areas become eroded, treatment is stopped and petroleum jelly is applied to the affected area. It can be recommenced if necessary.
What are the results of treatment with fluorouracil cream?
Fluorouracil cream frequently results in a mild to a severe stinging or burning sensation, depending on the sensitivity of the skin, the severity of the sun damage and how long it has been used for. After five to ten days of treatment, the sun-damaged parts of treated skin become red, scaly and tender. As treatment is continued, sores and crusts may appear. These raw areas result from the destruction of defective skin cells. They are a necessary part of treatment and are expected to heal, once the treatment is stopped.
Treated areas can be covered with a light dressing or left open. An occlusive dressing will increase penetration of 5-FU and enhance the effect and adverse reactions. Make-up can be worn if the reaction is mild, but should be avoided in the case of erosions and ulceration.
Arrange for your dermatologist, family doctor, or skin cancer nurse to review you during treatment to check on progress and to determine how long to continue using fluorouracil cream. If any unusual or severe reaction occurs, stop applying it and contact your health professional.
Effect of fluorouracil cream
Precautions when using fluorouracil cream
Fluorouracil cream must not be used during pregnancy because it has been shown to cause birth deformities. It is classified as Category D. It should also be avoided during breastfeeding, to minimise the chance of excretion in breast milk and subsequent risk to the nursing infant.
Avoid putting fluorouracil cream in the eyes; it is not normally used on eyelids. Keep it off the lips, unless specifically instructed to use it on this site. Use it with care in skin folds (such as those around the nose and lips), since it may irritate more severely in these areas.
Due to interaction with sunlight, it is best to use fluorouracil cream during the winter months. Treated skin should normally be very carefully protected from the sun; stay indoors during the middle part of the day. If the treated area is inadvertently exposed to the sun, the reaction to fluorouracil is more vigorous than normal.
Follow up after fluorouracil treatment
After you have been instructed to stop using the fluorouracil cream, you may be prescribed a specific moisturiser or mild topical steroid< to help to heal the treated area. If you have been given no specific instructions, apply plain white petrolatum thinly to raw and crusted areas at bedtime. Stop the petrolatum when the crusts and scabs have healed.
When treatment is stopped the skin heals rapidly. It takes two to four weeks for healthy new skin to replace the sun-damaged skin destroyed by the fluorouracil cream. After healing, the treated areas are often redder than normal and may feel more sensitive; this redness and sensitivity will gradually fade over a few weeks. Occasionally it persists for several months.
Persistent or recurrent actinic keratoses can be treated with a further course of fluorouracil cream, imiquimod cream or by cryotherapy. However, it is important to ask your dermatologist if this is appropriate because skin cancers can look very similar and may need surgery or other procedures.
Complications of treatment with fluorouracil cream
The action of fluorouracil cream means that some degree of itch, pain, erosions, crusting, dermatitis and other inflammatory reactions are expected during treatment.
The following complications may occasionally occur during fluorouracil cream treatment.
- Excessive local inflammatory reaction may cause ulceration, blistering and local swelling.
- Phototoxic reactions develop on treated areas exposed to sunlight or another source of ultraviolet radiation.
- Hypersensitivity reactions are a particular risk for patients with dihydropyrimidine dehydrogenase enzyme deficiency, who may also develop systemic toxicity.
- Systemic symptoms may include fever, nausea, diarrhoea, headache and mouth ulcers (stomatitis).
- Blood tests may show leukocytosis (raised white cell count) or leukopenia (reduced white cell count).
- Irritant contact dermatitis or allergic contact dermatitis may affect some or all treated areas, including skin that is not sun damaged. The cause can be the 5-FU itself, a preservative (eg parabens) or an excipient in the cream (stearyl alcohol, propylene glycol).
- Secondary infection (impetiginisation) can occur due to bacteria penetrating eroded skin.
The following complications may follow fluorouracil cream treatment:
- Persistent white marks or scarring
- Undiagnosed skin cancers; these may appear to heal with fluorouracil cream but recur later.
Excessive inflammatory reactions to fluorouracil cream