Fluorouracil

A to Z Drug Facts

Actions 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. Following IV injection, fluorouracil distributes into tumors, intestinal mucosa, bone marrow, liver, and other body tissues. In spite of its limited lipid solubility, fluorouracil diffuses readily across the blood-brain barier and distributes into CSF and brain tissue. The parent drug is excreted unchanged (7% to 20%) in the urine in 6 hr; of this, > 90% is excreted in the first hour. The remaining percentage is metabolized, primarily in the liver. The mean half-life of elimination from plasma is » 16 min and is dose-dependent.

 Indications Colorectal carcinoma, breast carcinoma, gastric carcinoma, pancreatic carcinoma, actinic keratoses (topical), superficial basal cell carcinoma (topical).

Ovarian, cervical, bladder, hepatic, islet cell, prostate, endometrial, esophageal, and head and neck carcinoma.

 Contraindications Poor nutritional status; depressed bone marrow function; potentially serious infections; hypersensitivity to fluorouracil or product components; pregnancy (topical).

 Route/Dosage

Colorectal, Breast, Gastric, and Pancreatic Carcinomas

ADULTS: IV bolus Initial dose: 12 mg/kg/day for 4 days, then 6 mg/kg on days 6, 8, 10, and 12. Giving daily doses > 800 mg is not recommended by the manufacturer. In poor risk patients and those with inadequate nutritional status: 6 mg/kg for 3 days, then 3 mg/kg on days 5, 7, and 9. 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. Weekly maintenance dosage should not exceed 1000 mg. Poor risk patients may require a reduced maintenance dose.

ADULTS: Continuous IV infusion 750 to 1000 mg/m²/day for 4 to 5 days, in combination with other chemotherapy agents. Repeat every 21 to 28 days.

Actinic Keratosis

ADULTS: Topical Apply enough medication to cover affected areas twice daily for 2 to 6 wk. Complete healing may not occur until 1 to 2 mo after therapy is stopped.

Superficial Basal Cell Carcinoma

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. Use only 5% fluorouracil.

Hepatic Insufficiency Adjustment

ADULTS: Some clinicians recommend not giving fluorouracil to patients with a bilirubin > 5 mg/dL.

Interactions

Cimetidine, metronidazole

May increase serum concentrations of fluorouracil and potentially increase toxicity.

Leucovorin

Leucovorin may enhance GI toxicity of fluorouracil. Fatalities have occurred because of severe toxic enterocolitis.

Levamisole

Risk of hepatotoxicity may be increased.

Lab Test Interferences None well documented.

 Adverse Reactions

CARDIOVASCULAR: Coronary vasospasm, which may cause angina, especially in patients with established coronary artery disease. CNS: Disorientation; confusion; cerebellar syndrome. DERMATOLOGIC: Alopecia; pruritic maculopapular rash; palmar-plantar erythrodysesthesia; hyperpigmentation; photosensitivity; pain, pruritus, hyperpigmentation and burning at application site (topical). GI: Nausea and vomiting; mucositis; esophagopharyngitis; diarrhea, watery stools; anorexia; GI ulceration; loss of appetite. HEMATOLOGIC: Bone marrow suppression, neutrophil nadir at 9 to 14 days, platelet nadir at 7 to 17 days. HYPERSENSITIVITY: Angioedema. SPECIALSENSES: Conjunctivitis; tear duct fibrosis.

 Precautions

Pregnancy: Category D (injection); Category X (topical). Lactation: Undetermined. Children: Safety and efficacy not established. Extravasation: Can cause local irritation or phlebitis. Refer to your institution-specific protocol. Special risk patients: Use with extreme caution in poor-risk patients who have had high-dose pelvic irradiation or previous use of alkylating agents, who have wide-spread involvement of bone marrow by metastatic tumors, or impaired hepatic or renal function. Obese/Edematous patients: Base dose on body surface area in obese or edematous patients. Discontinue use: Discontinue if signs of toxicity occur: stomatitis or esophagopharyngitis (at first visible sign); rapidly falling WBC count; leukopenia (WBC < 3500/mm³; intractable vomiting; diarrhea or frequent bowel movements; GI ulceration and bleeding; thrombocytopenia (platelets < 100,000/mm³); hemorrhage. Angina: Coronary vasospasm with episodes of angina may occur. Topical use: Avoid application to mucous membrances because of possibility of local inflammation and ulceration. Occlusive dressing may increase the incidence of inflammatory reactions. Photosensitivity: Avoid exposure to UV rays because the intensity of the reaction may be increased.

 Administration/Storage

• Store all dosage forms at room temperature. Protect from light and freezing. Fluorouracil solutions diluted in 5% Dextrose or 0.9% Sodium Chloride are chemically stable for up to 5 days at room temperature, unprotected from light. However, because fluorouracil injection is preservative-free, use solution within 24 hr of preparation.
• Fluorouracil solution for injection may be given undiluted or mixed with 5% Dextrose or 0.9% Sodium Chloride prior to IV administration.
• Adminster IV or topically.
• Give by IV push as undiluted product or infuse over 2 to 24 hr to decrease toxicity.
• Health care workers should use gloves when applying fluorouracil topically.
• Area may be covered with a porous gauze dressing if necessary. Avoid occlusive dressings.

 Assessment/Interventions

• Measure WBC count with differential before each dose

 Patient/Family Education

• Avoid exposure to the sun after topical application.
• Wash hands immediately after topical application.
• Do not apply to eye, eyelids, nose, or mouth.
• Transient alopecia may occur with fluorouracil; alert patient to this possibility.
• Contraceptive measures are recommended for men and women during therapy.
• Notify health care provider if chills, nausea, vomiting, unusual bleeding or bruising, yellowing of skin or eyes, abdominal pain, flank or joint pain, or swelling of feet or legs occurs.
• Notify health care provider if the following become pronounced: diarrhea, fever, weakness.
• Drink plenty of liquids while taking this drug.

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Copyright © 2003 Facts and Comparisons
David S. Tatro
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