Fluorouracil (Topical) (Monograph)
Brand names: Carac, Efudex, Fluoroplex
Drug class: Antiproliferants
Introduction
Pyrimidine antagonist; antimetabolite; antineoplastic agent.
Uses for Fluorouracil (Topical)
Actinic Keratoses
Used topically for the treatment of multiple actinic (solar) keratoses.
Curettage or cryotherapy are preferred treatment options for isolated lesions.
Basal Cell Carcinoma
Used topically for the treatment of superficial basal cell carcinoma when conventional methods are impractical (e.g., in patients with multiple lesions or difficult treatment sites). Efficacy not established for treatment of other basal cell carcinomas; establish diagnosis before initiating treatment.
When lesions are isolated and easily accessible, conventional techniques (e.g., surgery, curettage and dessication, cryotherapy) are preferred because they have a higher response rate.
Fluorouracil (Topical) Dosage and Administration
General
-
Following topical application, response is manifested by erythema, followed by scaling, tenderness, vesiculation, erosion, ulceration, necrosis, and reepithelialization.
-
Complete healing of actinic keratoses lesions may not occur until 1–2 months after cessation of therapy.
-
Evaluate patients treated for superficial basal cell carcinoma for a reasonable period of time to determine if a cure has been obtained.
Administration
Topical Administration
Apply cream or solution topically with a nonmetallic applicator, clean fingertips, or gloved fingers in an amount sufficient to cover lesions. If the fingers are used to apply the drug, wash hands immediately afterward.
For external use only; notfor ophthalmic, oral, or intravaginal use. Avoid contact with eyes, nose, mouth, or other mucous membranes. (See Local Inflammatory Reactions under Cautions.)
Actinic Keratoses
Apply topically to lesions as a 0.5, 1, or 5% cream or as a 2 or 5% solution. Apply 0.5% cream to lesions on the face and anterior scalp.
Apply a sufficient amount of 1–5% cream or 2–5% solution to cover lesions twice daily.
Apply a thin film of 0.5% cream to lesions on face and anterior scalp once daily.
Wash skin and wait 10 minutes before applying 0.5% cream to affected area(s) of face and anterior scalp.
Basal Cell Carcinoma
Apply topically as a 5% cream or solution; apply a sufficient amount to cover lesions twice daily.
Dosage
At equivalent concentrations, solutions are considered more effective than creams.
Adults
Actinic Keratoses
For multiple actinic (solar) keratoses, increased frequency of application, longer duration of treatment, or temporary, initial combination therapy with topical tretinoin may be necessary on areas other than the head and neck (e.g., hands, arms).
Topical
Apply 1–5% cream or 2–5% solution twice daily. Continue therapy until erosion, necrosis, and ulceration stage is reached, usually 2–4 weeks (for 5% cream or 2–5% solution) or 2–6 weeks (for 1% cream) after initiation of treatment, then discontinue the drug.
Apply 0.5% cream once daily to face and anterior scalp for up to 4 weeks as tolerated. Generally, local irritation resolves within 2 weeks of cessation of drug.
Basal Cell Carcinoma
Confirmed Superficial Basal Cell Carcinoma
TopicalApply 5% cream or solution twice daily for at least 3–6 weeks; may require up to 10–12 weeks before the lesions are obliterated.
Prescribing Limits
Adults
Actinic Keratoses
Topical
0.5% cream: Maximum 4 weeks of therapy recommended.
Special Populations
No special population dosage recommendations at this time.
Cautions for Fluorouracil (Topical)
Contraindications
-
Known hypersensitivity to fluorouracil or any ingredient in the formulation.
-
Dihydropyrimidine dehydrogenase activity deficiency. (See Dihydropyrimidine Dehydrogenase Activity Deficiency under Cautions.)
-
Known or suspected pregnancy. (See Fetal/Neonatal Morbidity and Mortality under Cautions.)
Warnings/Precautions
Warnings
Fetal/Neonatal Morbidity and Mortality
May cause fetal harm. Birth defects (i.e., cleft lip and palate, ventricular septal defect) and miscarriages reported.
Advise women to avoid becoming pregnant during therapy. If used during pregnancy, or if patient becomes pregnant, apprise of potential fetal hazard.
Dihydropyrimidine Dehydrogenase Activity Deficiency
Deficiency of dihydropyrimidine dehydrogenase activity may cause prolonged fluorouracil clearance and toxicity.
Risk of severe, unexpected toxic reactions including stomatitis, diarrhea, neutropenia, and neurotoxicity; life-threatening symptoms including severe abdominal pain, bloody diarrhea, vomiting, fever, and chills reported following topical application of 5% fluorouracil. Discontinue therapy if symptoms of toxicity occur.
Local Inflammatory Reactions
Local inflammatory reactions (e.g., swelling, scaling, pain, pruritus, burning, soreness, tenderness, suppuration, scarring, hyperpigmentation) occur in most patients.
Avoid application to mucous membranes due to the possibility of local inflammation and ulceration.
Occlusive Dressings
Occlusive dressings may increase percutaneous penetration of drug.
Increased incidence and severity of inflammatory reactions in adjacent normal skin with use of occlusive dressings. If required, apply a porous gauze dressing.
Sensitivity Reactions
Photosensitivity Reactions
Exposure to ultraviolet (UV) light increases the intensity of the inflammatory reaction. (See Local Inflammatory Reactions under Cautions.) Minimize exposure to UV rays during and immediately following treatment.
Hypersensitivity Reactions
Hypersensitivity reactions, including allergic contact dermatitis, reported.
Potential delayed hypersensitivity reaction; however, patch testing may be inconclusive.
General Precautions
Precautions Related to Treatment of Actinic Keratosis
Treatment responses in areas that appear clinically normal may indicate sites of subclinical actinic keratoses.
Topical Administration Precautions
Possible increased absorption through ulcerated or inflamed skin. Possible systemic toxicity when applied to large ulcerated area(s).
Response in treated areas may be unsightly during therapy and, in some cases, for several weeks after therapy is discontinued.
Laboratory Monitoring
If an affected area does not respond to treatment or keratotic lesion recurs following therapy, perform a biopsy to confirm the diagnosis of solar keratoses or as indicated in the management of superficial basal cell carcinoma.
Specific Populations
Pregnancy
Category X. (See Fetal/Neonatal Morbidity and Mortality under Cautions.)
Lactation
Not known whether topical fluorouracil is distributed into milk. Discontinue nursing or the drug.
Pediatric Use
Safety and efficacy not established.
Geriatric Use
No substantial differences in safety and efficacy measures were demonstrated in patients 65 years of age compared with younger adults.
Common Adverse Effects
Local effects (e.g., burning, dryness, allergic contact dermatitis, erosions, erythema, hyperpigmentation, irritation, pain, photosensitivity, pruritus, scarring, rash, soreness, ulceration, edema, telangiectasia), eye irritation .
Fluorouracil (Topical) Pharmacokinetics
Absorption
Bioavailability
Following application of fluorouracil 5% cream, approximately 6% of the topical dose is absorbed systemically, with peak plasma concentrations attained in 1 hour.
Absorption of the drug into cells may be selectively greater in diseased skin than in normal skin.
Distribution
Extent
Not known whether fluorouracil is distributed into human milk.
Elimination
Metabolism
Anabolized to active metabolites (e.g., 5-fluoro-2′-deoxyuridine-5′-monophosphate); catabolized to inactive metabolites (e.g., CO2, urea, α-fluoro-β-alanine).
Stability
Storage
Topical
Creams and Solutions
Cream 0.5%: 20–25°C.
Cream 1%: Tight containers at 15–30°C; avoid freezing.
Cream and solutions 2 and 5%: 25°C (may be exposed to 15–30°C); avoid freezing.
Actions
-
Interferes with DNA synthesis and, to a lesser extent, the formation of RNA by inhibiting the methylation of deoxyuridylic acid to thymidylic acid, a DNA precursor.
-
Since DNA and RNA are essential for cell division and growth, may create a thymine deficiency, which provokes unbalanced growth and death of the cell.
-
Effects of DNA and RNA deprivation are most marked on cells that grow more rapidly.
Advice to Patients
-
Importance of clinicians instructing patients about proper use of the drug, including associated precautions. Importance of reading manufacturer’s patient information.
-
Keep out of reach of children.
-
Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed; necessity for clinicians to advise women to avoid becoming pregnant during therapy, and advise pregnant women of risk to the fetus.
-
Importance of not using the drug for any disorder other than that for which it was prescribed.
-
Risk of photosensitivity reaction; importance of using sunscreen products and wearing protective clothing over treated areas.
-
Importance of washing hands immediately after application, if the drug is applied with fingers.
-
Advise patients not to apply on the eyelids or directly into the eyes, nose, or mouth.
-
Advise patients being treated for superficial basal cell carcinoma to contact their clinician if any suspicious lesion arises in the treatment area.
-
Warn patients that the reaction in the treated areas may be unsightly during therapy and, in some cases, for several weeks after therapy is discontinued.
-
Advise patients to continue therapy until erosion, necrosis, and ulceration stage is reached, usually 2–6 weeks after initiation of treatment, then discontinue the drug.
-
Advise patients not to apply other topical medications, moisturizing creams, or cosmetics on the affected area, unless specifically directed otherwise by their clinician.
-
Inform patients that if abdominal pain, bloody diarrhea, vomiting, fever, or chills occur during therapy to discontinue the drug and contact their clinician.
-
Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.
-
Importance of informing patients of other important precautionary information. (See Cautions.)
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Routes |
Dosage Forms |
Strengths |
Brand Names |
Manufacturer |
---|---|---|---|---|
Topical |
Cream |
0.5% |
Carac |
Dermik |
1% |
Fluroplex |
Allergan |
||
5% |
Efudex |
Valeant |
||
Solution |
2%* |
Efudex |
Valeant |
|
Fluorouracil Topical Solution |
Taro |
|||
5%* |
Efudex |
Valeant |
||
Fluorouracil Topical Solution |
Taro |
AHFS DI Essentials™. © Copyright 2025, Selected Revisions May 10, 2024. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
Reload page with references included
More about fluorouracil topical
- Compare alternatives
- Pricing & coupons
- Reviews (305)
- Side effects
- Dosage information
- During pregnancy
- Drug class: topical antineoplastics
- Breastfeeding
- En español
Patient resources
Professional resources
Other brands
Efudex, Tolak, Carac, Fluoroplex