Trade Names:Adrucil- Injection, solution 50 mg/mL
Trade Names:Carac- Cream 0.5%
Trade Names:Efudex- Cream 5%- Solution 5%
Trade Names:Fluorouracil- Injection, solution 50 mg/mL- Cream 5%- Solution 2%- Solution 5%
Trade Names:Fluoroplex- Cream 1%
The metabolism of fluorouracil in the anabolic pathway blocks the methylation reaction of deoxyuridylic acid to thymidylic acid. In this manner, fluorouracil interferes with the synthesis of DNA and, to a lesser extent, inhibits the formation of RNA.
Fluorouracil distributes into tumors, intestinal mucosa, bone marrow, liver, CSF, and brain tissue.
Metabolization takes place primarily in the liver; catabolic metabolism results in inactive degradation products.
The parent drug is excreted unchanged (7% to 20%) in the urine in 6 h. The mean t ½ is about 16 min (range, 8 to 20 min) and is dose dependent.
Palliative management of colon, rectum, breast, gastric, and pancreatic carcinoma.Topical Carac , Efudex , Fluoroplex
Multiple actinic or solar keratoses. Carac is only indicated for the face and anterior scalp areas.Efudex 5%
Superficial basal cell carcinoma.
Condylomata acuminata (topical).
Hypersensitivity to any component of the product.Parenteral
Depressed bone marrow function; poor nutritional status; potentially serious infections.Topical
Pregnancy; dihydropyrimidine dehydrogenase enzyme deficiency (except for 1% cream).
IV Individualize dosage based on actual body weight. Use lean body weight if patient is obese or has abnormal fluid retention.Initial dose
12 mg/kg/day for 4 days. Do not exceed 800 mg/day. If no toxicity is observed, give 6 mg/kg on days 6, 8, 10, and 12. Give no therapy on days 5, 7, 9, or 11. Discontinue at end of day 12, even with no apparent toxicity.In poor-risk patients and those with inadequate nutritional status
6 mg/kg/day for 3 days. If no toxicity is observed, give 3 mg/kg on days 5, 7, and 9. Give no therapy on days 4, 6, or 8. Do not exceed 400 mg/day.Maintenance therapy
Start maintenance therapy 30 days after the last dose. If no toxicity is observed with the first course of therapy, repeat that dose of fluorouracil at 30-day intervals. If toxicity is observed with the first course of therapy, after the patient has recovered from initial toxicity, use a single weekly dose of 10 to 15 mg/kg. Do not exceed a weekly maintenance dose of 1,000 mg. Poor-risk patients may require a reduced maintenance dose.Multiple Actinic or Solar KeratosisAdults
Apply amount sufficient to cover the lesions once daily for up to 4 wk as tolerated. Healing generally occurs within 2 wk after therapy is stopped. The 0.5% cream is only indicated for the face and anterior scalp areas. Using fingertips, apply every day to cover lesions with a thin film. Do not apply near eyes, nostrils, or mouth. Apply 10 min after thoroughly washing, rinsing, and drying the entire area. After application, wash hands thoroughly. Continued treatment up to 4 wk results in greater lesion reduction.Efudex
Apply amount sufficient to cover the lesions twice daily for 2 to 4 wk. Complete healing may not occur until 1 to 2 mo after therapy is stopped.Fluoroplex
Apply amount sufficient to cover the entire face or other affected areas twice daily for 2 to 6 wk. When the inflammatory reaction reaches the erosion, ulceration, and necrosis stages, terminate use.Superficial Basal Cell Carcinoma (5% Strength Only)Adults
Topical Apply a sufficient amount to cover the lesions twice daily for 3 to 6 wk. Treatment may be required for 10 to 12 wk.
Store at 68° to 77°F.Carac
Store at 68° to 77°F.Efudex
Store at 59° to 86°F.Fluoroplex
Store at 59° to 86°F. Avoid freezing.
The following drug interactions pertain to the injection doseform.Cimetidine
May increase serum concentrations of fluorouracil and potentially increase toxicity.Hydantoins (eg, phenytoin)
Hydantoin plasma levels may be elevated, increasing the risk of toxicity.Leucovorin
Leucovorin may enhance GI toxicity of fluorouracil. Fatalities have occurred because of severe toxic enterocolitis.Thiazide diuretics (eg, chlorothiazide)
Fluorouracil-induced leukopenia may be prolonged.Warfarin
Anticoagulant effect of warfarin may be increased.
None well documented.
Angina, myocardial ischemia, thrombophlebitis.
Acute cerebellar syndrome, confusion, disorientation, euphoria, headache.Topical Carac
Emotional upset, insomnia, irritability.
Alopecia, dermatitis (often presenting as a pruritic, maculopapular rash), dry skin, fissuring, nail changes (including loss of nails), palmar-plantar erythrodysethesia syndrome, photosensitivity, vein pigmentation.Topical Carac
Application-site reaction (95%); erythema (93%); dryness (83%); burning (75%); erosion, pain (44%); irritation (1%).Efudex
Allergic contact dermatitis, alopecia, blistering, bullous pemphigoid, burning, crusting, discomfort, erosions, erythema, hyperpigmentation, ichthyosis, irritation, pain, photosensitivity, pruritus, rash, scaling, scarring, soreness, suppuration, swelling, telangiectasias, tenderness, ulceration, urticaria.Fluoroplex
Allergic contact dermatitis, burning, hyperpigmentation, inflammation, irritation, pain, pruritus, scarring, telangiectasias.
Epistaxis, lacrimal duct stenosis, lacrimation, nystagmus, photophobia, visual changes.Topical Carac
Eye irritation (5%); sinusitis (2%).Efudex
Conjunctival reaction, corneal reaction, lacrimation, nasal irritation.
Anorexia, diarrhea, emesis, esophagopharyngitis, nausea, stomatitis, ulceration and bleeding.Topical Efudex
Medicinal taste, stomatitis.
Agranulocytosis, anemia, leukopenia, pancytopenia, thrombocytopenia.Topical Efudex
Eosinophilia, thrombocytopenia, toxic granulation.
Anaphylaxis, generalized allergic reactions.
Edema (35%); common cold (5%); allergy (1%).
Hospitalize for first course of injection therapy because of the possibility of severe toxic reactions.
Before each injection dose, obtain WBC with differential. Biopsy solar keratosis, which do not respond, to confirm the diagnosis. Perform follow-up biopsies as indicated in the management of superficial basal cell carcinoma.
Category D (injection); Category X (topical).
Safety and efficacy not established.
The potential for delayed hypersensitivity exists (topical).
Use with extreme caution in poor-risk patients who have had high-dose pelvic irradiation or previous use of alkylating agents, have widespread involvement of bone marrow by metastatic tumors, or have hepatic or renal function impairment.
Avoid exposure to ultraviolet (UV) rays because the intensity of the reaction may be increased.
Discontinue if the following signs of toxicity occur: diarrhea or frequent bowel movements, GI ulceration and bleeding, hemorrhage, intractable vomiting, leukopenia (WBC less than 3,500/mm 3 ), rapidly falling WBC count, stomatitis or esophagopharyngitis (at first visible sign), or thrombocytopenia (platelets less than 100,000/mm 3 ).
Rarely, severe toxicity (eg, diarrhea, neurotoxicity, neutropenia, stomatitis) has been attributed to dihydropyrimidine dehydrogenase deficiency.
Can cause local irritation or phlebitis. Refer to institution-specific protocol.
May occur; characterized as a tingling sensation of hands and feet that progresses over the next few days to pain when holding objects or walking. Interruption of therapy is followed by gradual resolution over 5 to 7 days.
Base dose on lean body mass in obese or edematous patients.
Avoid application to mucous membranes because of the possibility of local inflammation and ulceration. Occlusive dressing may increase the incidence of inflammatory reactions.
Severe toxicity, including hematologic, GI hemorrhage, and death, has occurred.
Symptoms for the injection doseform may include agranulocytosis, bone marrow depression (including leukopenia, thrombocytopenia), diarrhea, GI ulceration and bleeding, nausea, vomiting.
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