FLUOROURACIL [5-FLUOROURACIL (5-FU)]

(flure-oh-yoor'a-sil)

Carac, Efudex, Fluoroplex
Classifications: antineoplastic agent; antimetabolite, pyrimidine;
Therapeutic: antineoplastic
Pregnancy Category: D

Availability

50 mg/mL injection; 1%, 2%, 5% topical solution; 0.5%, 1%, 5% topical cream

Action

Pyrimidine antagonist and cell-cycle specific. Blocks action of enzymes essential to normal DNA and RNA synthesis and may become incorporated in RNA to form a fraudulent molecule; unbalanced growth and death of cell follow. Exhibits higher affinity for tumor tissue than healthy tissue.

Therapeutic Effect

Highly toxic, especially to proliferative cells in neoplasms, bone marrow, and intestinal mucosa. Low therapeutic index with high potential for severe hematologic toxicity.

Uses

Systemically as single agent or in combination with other antineoplastics for treatment of patients with inoperable neoplasms of breast, colon or rectum, stomach, pancreas, urinary bladder, ovary, cervix, liver. Also topically for solar or actinic keratoses and superficial basal cell carcinoma.

Unlabeled Uses

To induce repigmentation in vitiligo; actinic cheilitis; malignant effusions; mucosal leukoplakia.

Contraindications

Poor nutritional status; myelosuppression; pregnancy (category D), lactation.

Cautious Use

Major surgery during previous month; history of high-dose pelvic irradiation, metastatic cell infiltration of bone marrow, previous use of alkylating agents; cardiac disease, CAD, angina; men and women in childbearing ages; hepatic or renal impairment.

Route & Dosage

Carcinoma
Adult: IV 12 mg/kg/d for 4 consecutive days up to 800 mg or until toxicity develops or 12 d therapy, may repeat at 1 mo intervals; if toxicity occurs, 15 mg/kg once weekly can be given until toxicity subsides

Actinic and Solar Keratosis
Adult: Topical Apply cream or solution b.i.d. for 2–4 wk; apply Carac once daily

Superficial Basal Cell Carcinoma
Adult: Topical Apply 5% cream b.i.d. for 3–6 wk

Administration

Topical

Use gloved fingers to apply topical drug.
Do not use occlusive dressings with topical drug. Use a porous gauze dressing for cosmetic purposes; does not cause inflammation.
Note: Second-degree burns resulting from contact between plastic eyeglass frames and treated skin have been reported. Reduce risk of burns or irritation by treating skin that contacts frames only at night when glasses are not worn, and using the lowest effective strength of topical preparation.
Store at 15°–30° C (59°–86° F) unless otherwise directed. Protect from light and freezing.

Intravenous

Note: Parenteral dose is determined by actual weight unless patient is obese, in which case ideal weight is used.
Safe handling: Double-glove with latex gloves, and change the double set after every 30 min of exposure. If a drug spill occurs, change gloves immediately after it is cleaned up.

PREPARE: Direct: This drug may be given without dilution.

ADMINISTER: Direct: Give by direct IV injection over 1–2 min. Inspect injection site frequently; avoid extravasation. If it occurs, stop infusion and restart in another vein. Ice compresses may reduce danger of local tissue damage from infiltrated solution.

INCOMPATIBILITIES Solution/additive: Carboplatin, chlorpromazine, cisplatin, cytarabine, diazepam, doxorubicin, epirubicin, fentanyl, leucovorin calcium, metoclopramide, morphine. Y-site: Aldesleukin, amphotericin B cholesteryl, droperidol, filgrastim, gallium, lansoprazole, ondansetron, TPN, topotecan, vinorelbine.

Fluorouracil solution is normally colorless to faint yellow. Slight discoloration during storage does not appear to affect potency or safety. Discard dark yellow solution. If a precipitate forms, redissolve drug by heating to 60° C (140° F) and shake vigorously. Allow to cool to body temperature before administration.

Adverse Effects (≥1%)

CNS: Euphoria, acute cerebellar syndrome (dysmetria, nystagmus, ataxia, severe mental deterioration); pustular contact hypersensitivity. CV: Cardiotoxicity (rare), angina. GI: Anorexia, nausea, vomiting, stomatitis, esophagopharyngitis, medicinal taste, diarrhea, proctitis. Hematologic: Anemia, leukopenia, thrombocytopenia, eosinophilia. Body as a Whole: Hypersensitivity: Pustular contact eruption, edema of face, eyes, tongue, legs. Skin: SLE-like dermatitis, alopecia, photosensitivity, erythema, increased pigmentation, skin dryness and fissuring, pruritic maculopapular rash. [Topical] Local pain, pruritus, hyperpigmentation, burning at site of application, dermatitis, suppuration, swelling, scarring, toxic granulation.

Diagnostic Test Interference

Fluorouracil may increase excretion of 5-hydroxyindoleacetic acid (5-HIAA) and decrease plasma albumin (because of drug-induced protein malabsorption).

Interactions

Drug: Metronidazole may increase general floxuridine toxicity; may increase or decrease serum levels of phenytoin, fosphenytoin; hydroxyurea can decrease conversion to active metabolite.

Pharmacokinetics

Distribution: Distributed to tumor, intestinal mucosa, bone marrow, liver, and CSF; probably crosses placenta. Metabolism: In liver. Elimination: 15% in urine, 60–80% through lungs as carbon dioxide. Half-Life: 16 min.

Nursing Implications

Assessment & Drug Effects

Lab tests: Obtain total and differential leukocyte counts before each dose is administered. Discontinue drug if leukopenia occurs (WBC <3500/mm³) or if patient develops thrombocytopenia (platelet count <100,000/mm³). Baseline and periodic checks of Hct and liver and kidney function are also advised.
Use protective isolation of patient during leukopenic period (WBC <3500/mm³).
Watch for and report signs of abnormal bleeding from any source during thrombocytopenic period (day 7–17); inspect skin for ecchymotic and petechial areas. Protect patient from trauma.
Report disorientation or confusion; drug should be withdrawn immediately.
Establish a reference data base for body weight, I&O ratio and pattern, food preferences and dietary habits, bowel habits, and condition of mouth.
Report intractable vomiting to physician.
Indications to discontinue drug: Severe stomatitis, leukopenia (WBC <3500/mm³ or rapidly decreasing count), intractable vomiting, diarrhea, thrombocytopenia (platelets <100,000/mm³), and hemorrhage from any site.
Inspect patient's mouth daily. Promptly report cracked lips, xerostomia, white patches, and erythema of buccal membranes.
Report development of maculopapular rash; it usually responds to symptomatic treatment and is reversible.
Be aware of expected response of lesion to topical 5-FU: Erythema followed in sequence by vesiculation, erosion, ulceration, necrosis, epithelialization. Applications of drug are continued until ulcerative stage is reached (2–6 wk after initial applications) and then discontinued.
Note: Systemic toxicity may follow use of topical drug on large ulcerated area. Report symptoms promptly.

Patient & Family Education

Understand that it is very important to report the first signs of toxicity: Anorexia, vomiting, nausea, stomatitis, diarrhea, GI bleeding.
Schedule and make sure to complete periodic checks on liver and kidney function.
Do not change dosage regimen (i.e., do not increase or omit doses or change dosage intervals).
Avoid exposure to sunlight or ultraviolet lamp treatments. Protect exposed skin. Photosensitivity usually subsides 2–3 mo after last dose.
Report promptly to physician any difficulty in maintaining balance while ambulating.
Be aware that your hair may fall out; new hair growth usually begins within 6–8 wk.
Use contraception during 5-FU treatment. If you suspect you are pregnant, tell your physician.

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug

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