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- Topical Fluorouracil
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Carac: 0.5% (30 g) [contains methylparaben, polysorbate 80, propylene glycol, propylparaben, trolamine (triethanolamine)]
Efudex: 5% (40 g)
Fluoroplex: 1% (30 g) [contains benzyl alcohol]
Tolak: 4% (40 g) [contains cetyl alcohol, methylparaben, peanut oil, propylparaben]
Generic: 0.5% (30 g); 5% (40 g)
Generic: 2% (10 mL); 5% (10 mL)
Brand Names: U.S.
- Antineoplastic Agent, Antimetabolite
- Antineoplastic Agent, Antimetabolite (Pyrimidine Analog)
- Topical Skin Product
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.
~6% of a topical dose is absorbed systemically (5% cream)
Time to Peak
~1 hour following application (4% cream)
Use: Labeled Indications
Actinic or solar keratosis: Management of multiple actinic or solar keratoses
Basal cell carcinoma (5%): Treatment of superficial basal cell carcinomas 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 (use 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%.
Hypersensitivity to fluorouracil or any component of the formulation; dihydropyrimidine dehydrogenase (DPD) enzyme deficiency; women who are or may become pregnant
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; complete healing may not be evident for 1 to 2 months following treatment
Superficial basal cell carcinoma: 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
Refer to adult dosing.
Dosing: Renal Impairment
There are no dosage adjustments provided in the manufacturer’s labeling.
Dosing: Hepatic Impairment
There are no dosage adjustments provided in the manufacturer’s labeling.
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.
Store at controlled room temperature of 15°C to 30°C (59°F to 86°F). Do not freeze.
Fosphenytoin: Fluorouracil (Topical) may increase the serum concentration of Fosphenytoin. Monitor therapy
Gemcitabine: May increase the serum concentration of Fluorouracil (Topical). Monitor therapy
Leucovorin Calcium-Levoleucovorin: May enhance the adverse/toxic effect of Fluorouracil (Topical). Monitor therapy
Phenytoin: Fluorouracil (Topical) may increase the serum concentration of Phenytoin. Monitor therapy
SORAfenib: May decrease the serum concentration of Fluorouracil (Topical). SORAfenib may increase the serum concentration of Fluorouracil (Topical). Monitor therapy
Vitamin K Antagonists (eg, warfarin): Fluorouracil (Topical) may increase the serum concentration of Vitamin K Antagonists. Monitor therapy
Dermatologic: Application site scaling (≤95%), application site dryness (70% to ≤95%), application site crusting (87%), application site skin erosion (25% to 68%)
Local: Application site erythema (90% to 99%), application site reaction (92% to 97%), application site stinging (≤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% (Limited to important or life-threatening): Allergic contact dermatitis, alopecia, anxiety, bullous pemphigoid, burning sensation of skin, chronic lympocytic leukemia, conjunctivitis, corneal disease, eosinophilia, eye irritation, herpes simplex infection, hyperpigmentation, ichthyosis, inflammation, insomnia, irritability, lacrimation, leukocytosis, medicine-like taste, muscle tenderness, nasal discomfort, pain, pancytopenia, 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
Concerns related to adverse effects:
• Hypersensitivity: May be associated with delayed-type hypersensitivity reactions, including allergic contact dermatitis. 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.
• 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.
• Dihydropyrimidine dehydrogenase enzyme deficiency: Individuals lacking dihydropyrimidine dehydrogenase (DPD) enzyme activity may exhibit severe toxicity with topical fluorouracil. Life-threatening systemic toxicity has been reported with the topical use of 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. It is unknown if patients with profound DPD enzyme deficiency would develop systemic toxicity with lower concentrations of topical fluorouracil. 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 ["Inactive"[, 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.
• Appropriate use: Avoid topical application to mucous membranes due to potential for local inflammation and ulceration; cases of miscarriage and a birth defect (ventricular septal defect) have been reported when fluorouracil was applied to mucous membrane areas during pregnancy. The use of occlusive dressings with topical preparations 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 (corneal and conjunctival disorders have occurred with topical fluorouracil). Wash hands well following application; if ocular exposure occurs, flush with large amounts of water.
Pregnancy Risk Factor
Animal reproduction studies have not been conducted with topical fluorouracil, although teratogenic effects have been observed in animal studies with parenteral administration. Adverse effects have been reported following use of topical fluorouracil products in humans. Use is contraindicated during pregnancy. Women of reproductive potential should use effective contraception during and for one month after the final application of topical fluorouracil.
• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience burning, dry skin, or redness. Have patient report immediately to prescriber signs of infection, severe abdominal pain, bloody diarrhea, vomiting, severe skin irritation, severe diarrhea, vision changes, eye pain, or severe eye irritation (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.