Version November 2024
Note: Fluoroplex 1% has been discontinued in the United States for >1 year.
Actinic or solar keratosis: Topical:
Cream (0.5%): Apply thin film to lesions once daily for up to 4 weeks, as tolerated.
Cream (1%): Apply to lesions twice daily for 2 to 6 weeks.
Cream (4%): Apply to lesions once daily for 4 weeks as tolerated.
Cream (5%) or solution (2% and 5%): Apply to lesions twice daily for 2 to 4 weeks (apply until inflammatory response reaches erosion stage, then stop); complete healing may not be evident for 1 to 2 months following treatment.
Basal cell carcinoma, superficial: Topical: Cream (5%) or solution (5%): Apply to affected lesions twice daily for 3 to 6 weeks; treatment may be continued for up to 10 to 12 weeks.
Penile carcinoma (in situ) (off-label use; based on limited data): Topical: Cream (5%): Apply to lesion for 12 hours every 48 hours for 28 days (Ref).
Squamous cell carcinoma (in situ; Bowen disease) (off-label use; based on limited data): Topical: Cream (5%): Apply to lesion(s) twice daily for 9 weeks; a repeat course may be applied for recurrences (Ref).
There are no dosage adjustments provided in the manufacturer's labeling.
There are no dosage adjustments provided in the manufacturer's labeling.
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Dermatologic: Application site scaling (≤95%), application site dryness (70% to ≤95%), stinging of the skin (application site: ≤87%), skin erosion (application site: 25% to 68%)
Local: Application site erythema (90% to 99%), application site reaction (92% to 97%; crusting: 87%), application site burning (60% to ≤87%), application site pruritus (85%), application site edema (14% to 69%), application site pain (31% to 61%)
1% to 10%:
Central nervous system: Headache (4%)
Dermatologic: Skin irritation (1% to 2%)
Infection: Common cold (5%)
Ophthalmic: Eye irritation (3% to 7%; burning, watering, sensitivity, stinging, itching)
Respiratory: Sinusitis (5%)
<1%, postmarketing, and/or case reports: Allergic contact dermatitis, alopecia, anxiety, bullous pemphigoid, burning sensation of skin, conjunctival irritation, conjunctivitis, corneal disease, eosinophilia, eye irritation, herpes simplex infection, hyperpigmentation, ichthyosis, inflammation, insomnia, irritability, lacrimation, leukocytosis, lymphocytic leukemia, medicine-like taste, muscle tenderness, nasal discomfort, pain, pancytopenia, pruritus, scarring, skin blister, skin irritation, skin neoplasm (nonmelanoma), skin photosensitivity, skin rash, skin tenderness, stomatitis, suppuration, swelling, swelling of eye, telangiectasia, thrombocytopenia, toxic granulations, ulcer, urticaria
Hypersensitivity to fluorouracil or any component of the formulation; dihydropyrimidine dehydrogenase (DPD) enzyme deficiency; patients who are or may become pregnant.
Canadian labeling: Additional contraindications (not in US labeling): Concurrent use with brivudine, sorivudine, and analogues; breastfeeding.
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Concerns related to adverse effects:
• Hypersensitivity: Delayed-type hypersensitivity reactions, including allergic contact dermatitis, have been reported. Severe pruritus or eczema (at the application site or at a distant site) may be indicative of hypersensitivity. Patch testing may not be useful in the evaluation of these reactions. Discontinue immediately for signs of hypersensitivity.
• Local skin reactions: When applied to a lesion, erythema followed by vesiculation, desquamation, erosion and reepithelialization occurs. Local reactions and alterations in skin appearance may persist for several weeks after discontinuation. Bruising, burning, crusting, dryness, edema, irritation, pain, pruritus, scaling, scarring, soreness, stinging, and ulceration may commonly result from topical therapy. Increased absorption through ulcerated or inflamed skin is possible.
• Ocular adverse reactions: Corneal and conjunctival disorders have occurred with topical fluorouracil; avoid application to the periocular area.
• Photosensitivity: Topical fluorouracil is associated with photosensitivity, including severe sunburn. Avoid prolonged exposure to sunlight or UV irradiation during treatment; reaction intensity may be increased.
Disease-related concerns:
• Dihydropyrimidine dehydrogenase enzyme deficiency: Dihydropyrimidine dehydrogenase (DPD) enzyme deficiency may result in increased cytotoxic activity and severe toxicity with topical fluorouracil. Life-threatening systemic toxicity has been reported with topical fluorouracil in a patient with DPD enzyme deficiency; signs/symptoms included bloody diarrhea, stomatitis, esophagus, stomach, and small bowel inflammation, severe abdominal pain, vomiting, chills, fever, erythematous skin rash, neutropenia, and thrombocytopenia. Discontinue if signs of DPD deficiency develop.
Dosage form specific issues:
• Benzyl alcohol and derivatives: Some dosage forms may contain benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity ("gasping syndrome") in neonates; the "gasping syndrome" consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension and cardiovascular collapse (AAP 1997; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacturer's labeling.
• Peanut oil: Some dosage forms contain peanut oil.
• Polysorbate 80: Some dosage forms may contain polysorbate 80 (also known as Tweens). Hypersensitivity reactions, usually a delayed reaction, have been reported following exposure to pharmaceutical products containing polysorbate 80 in certain individuals (Isaksson 2002; Lucente 2000; Shelley 1995). Thrombocytopenia, ascites, pulmonary deterioration, and renal and hepatic failure have been reported in premature neonates after receiving parenteral products containing polysorbate 80 (Alade 1986; CDC 1984). See manufacturer's labeling.
• Propylene glycol: Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated with hyperosmolality, lactic acidosis, seizures and respiratory depression; use caution (AAP 1997; Zar 2007). See manufacturer's labeling.
Other warnings/precautions:
• Appropriate use: Avoid application to mucous membranes due to potential for local inflammation and ulceration. Occlusive dressings may increase the severity of inflammation in nearby skin areas (a porous gauze dressing may be applied for cosmetic reasons without increase in reaction). Avoid eyelids, eyes, and periocular area when applying. Wash hands well following application; if ocular exposure occurs, flush with large amounts of water.
• Household pet safety: Avoid allowing house pets to come into contact with human skin following topical fluorouracil application. Small amounts of fluorouracil ingested by cats or dogs may result in toxic hyperammonemia and high rates of mortality (ISMP [Smetzer 2020]).
Some dosage forms may contain propylene glycol; in neonates large amounts of propylene glycol delivered orally, intravenously (eg, >3,000 mg/day), or topically have been associated with potentially fatal toxicities which can include metabolic acidosis, seizures, renal failure, and CNS depression; toxicities have also been reported in children and adults including hyperosmolality, lactic acidosis, seizures, and respiratory depression; use caution (AAP, 1997; Shehab, 2009).
Fluoroplex 1% has been discontinued in the United States for >1 year.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Cream, External:
Carac: 0.5% (30 g) [contains methylparaben, polysorbate 80, propylene glycol, propylparaben, trolamine (triethanolamine)]
Efudex: 5% (40 g) [contains methylparaben, propylene glycol, propylparaben]
Fluoroplex: 1% (30 g [DSC]) [contains benzyl alcohol]
Tolak: 4% (40 g) [contains cetyl alcohol, methylparaben, peanut oil, propylparaben]
Generic: 0.5% (30 g); 5% (40 g)
Solution, External:
Generic: 2% (10 mL); 5% (10 mL)
Yes
Cream (Carac External)
0.5% (per gram): $99.91
Cream (Efudex External)
5% (per gram): $1.80
Cream (Fluorouracil External)
0.5% (per gram): $59.21
5% (per gram): $6.43 - $9.62
Cream (Tolak External)
4% (per gram): $1.20
Solution (Fluorouracil External)
2% (per mL): $7.56
5% (per mL): $11.13
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Cream, External:
Efudex: 5% (40 g) [contains methylparaben, propylene glycol, propylparaben]
Tolak: 4% (40 g) [contains cetyl alcohol, methylparaben, peanut oil, propylparaben]
Topical: Apply 10 minutes after washing, rinsing, and drying the affected area. Apply a sufficient amount to cover lesions, preferably using a nonmetal applicator or suitable glove.
Cream (4%): Apply after washing, rinsing, and drying the affected area. Apply a sufficient amount to cover lesions of the face, ears, and/or scalp with a thin film, using fingertips to gently massage uniformly into skin.
If applied with fingertip, wash hands immediately after application. Do not cover area with an occlusive dressing. Topical preparations are for external use only; not for ophthalmic, oral, mucous membrane, or intravaginal use.
Hazardous agent (NIOSH 2016 [group 1]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
Actinic or solar keratosis: Management of multiple actinic or solar keratoses
Basal cell carcinoma, superficial (5%): Treatment of superficial basal cell carcinoma when conventional methods are impractical (eg, due to multiple lesions or difficult treatment sites)
Limitations of use: Establish diagnosis of superficial basal cell carcinoma prior to treatment (has not been proven effective in other types of basal cell carcinomas); surgery is preferred with isolated, easily accessible basal cell carcinomas because success with such lesions is almost 100% and the success rate with fluorouracil cream and solution is ~93%.
Penile carcinoma (in situ); Squamous cell carcinoma (in situ; Bowen disease)
Fluorouracil may be confused with flucytosine
Curac may be confused with Kuric brand name for methyldopa (NG)
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Aminolevulinic Acid (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Systemic). Risk X: Avoid combination
Aminolevulinic Acid (Topical): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Topical). Risk C: Monitor therapy
Brivudine: May enhance the adverse/toxic effect of Fluorouracil (Topical). Risk X: Avoid combination
Methoxsalen (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Methoxsalen (Systemic). Risk C: Monitor therapy
Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Risk C: Monitor therapy
Verteporfin: Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin. Risk C: Monitor therapy
Use is contraindicated in patients who may become pregnant.
Females of reproductive potential should use effective contraception during treatment and for 1 month after the final application of topical fluorouracil.
Use is contraindicated in patients who are pregnant.
Adverse effects, including ventricular septal defect and miscarriage, have been reported following topical application of fluorouracil products to mucous membranes in pregnant patients.
It is not known if fluorouracil (topical) is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, a decision should be made to discontinue breastfeeding or the drug, considering the importance of treatment to the mother.
Fluorouracil is a pyrimidine antimetabolite that interferes with DNA synthesis by blocking the methylation of deoxyuridylic acid to thymidylic acid; blocks DNA synthesis to prevent cell proliferation of fast growing cells and cause cell death.
Absorption: ~6% of a topical dose is absorbed systemically (5% cream)
Time to Peak: ~1 hour following application (4% cream)
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