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fluorouracil (5-fluorouracil, 5-FU)
Pharmacologic class: Antimetabolite
Therapeutic class: Antineoplastic
Pregnancy risk category D
Inhibits DNA and RNA synthesis, leading to death of rapid-growing neoplastic cells. Cell-cycle-S-phase specific.
Cream: 1%, 5%
Injection: 50 mg/ml in 10-ml ampules and 10-, 20-, and 100-ml vials
Solution: 1%, 2%, 5%
Indications and dosages
➣ Advanced colorectal cancer
Adults: 370 mg/m2 I.V. for 5 days, preceded by leucovorin 200 mg/m2 daily for 5 days; may be repeated q 4 to 5 weeks. No single daily dose should exceed 800 mg.
➣ Colon, rectal, breast, gastric, and pancreatic cancer
Adults: Initially, 12 mg/kg/day I.V. for 4 days; then 6 mg/kg I.V. on days 6, 8, 10, and 12. Maximum dosage is 800 mg/day. For maintenance, start 30 days after last dose. If no toxicity, use dosage from first course. If toxicity occurs, give 10 to 15 mg/kg/week as single dose after toxicity subsides. Don't exceed 1 g/week.
➣ Actinic (solar) keratoses
Adults: 1% solution or cream applied once or twice daily to lesions on head, neck, or chest; 2% to 5% solution or cream may be needed for other areas.
➣ Superficial basal cell carcinoma
Adults: 5% solution or cream applied b.i.d. for 3 to 6 weeks (up to 12 weeks)
• Hypersensitivity to drug or its components
• Bone marrow depression
• Dihydropyrimidine dehydrogenase enzyme deficiency (with topical route)
• Poor nutritional status
• Serious infection
• Pregnancy or breastfeeding
Use cautiously in:
• renal or hepatic impairment, infections, edema, ascites
• obese patients.
☞ Consult facility's cancer protocols to ensure correct dosage, administration technique, and cycle length.
• Give antiemetic before fluorouracil, as ordered, to reduce GI upset.
• Know that drug may be given without dilution by direct I.V. injection over 1 to 3 minutes.
• For I.V. infusion, dilute with dextrose 5% in water, sterile water, or normal saline solution in plastic bag (not glass bottle). Infusion may be given over a period of 24 hours or more.
☞ Be aware of the importance of leucovorin rescue with fluorouracil therapy, if prescribed.
• Check infusion site frequently to detect extravasation.
• Use nonmetal applicator or appropriate gloves to apply topical form.
• Avoid applying topical form to mucous membranes or irritated skin.
• Don't use occlusive dressings over topical form.
• Know that pyridoxine may be given with fluorouracil to reduce risk of palmar-plantar erythrodysesthesia (hand-foot syndrome).
CNS: confusion, disorientation, euphoria, ataxia, headache, weakness, malaise, acute cerebellar syndrome or dysfunction
CV: angina, myocardial ischemia, thrombophlebitis
EENT: vision changes, photophobia, lacrimation, lacrimal duct stenosis, nystagmus, epistaxis
GI: nausea, vomiting, diarrhea, stomatitis, anorexia, GI ulcer, GI bleeding
Hematologic: anemia, leukopenia, thrombocytopenia
Skin: alopecia, maculopapular rash, melanosis of nails, nail loss, palmar-plantar erythrodysesthesia, photosensitivity, local inflammation reaction (with cream), dermatitis
Other: fever, anaphylaxis
Drug-drug. Bone marrow depressants (including other antineoplastics): additive bone marrow depression
Irinotecan: dehydration, neutropenia, sepsis
Leucovorin calcium: increased risk of fluorouracil toxicity
Live-virus vaccines: decreased antibody response to vaccine, increased risk of adverse reactions
Drug-diagnostic tests. Alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, bilirubin, lactate dehydrogenase, urinary 5-hydroxyindoleacetic acid: increased levels
Albumin, granulocytes, platelets, red blood cells, white blood cells (WBCs): decreased levels
Drug-behaviors. Sun exposure: increased risk of phototoxicity
☞ Watch for signs and symptoms of toxicity, especially stomatitis and diarrhea. If these occur, stop drug and notify prescriber. Note that toxicity may take 1 to 3 weeks to develop.
• Monitor CBC, WBC and platelet counts, and kidney and liver function test results.
• Assess fluid intake and output.
• With long-term use, watch for serious rash on hands and feet. If it occurs, consult prescriber regarding need for pyridoxine.
• Assess for bleeding tendency.
• Monitor blood glucose level in patients at risk for hyperglycemia.
☞ Emphasize importance of taking leucovorin as prescribed with high-dose therapy.
☞ Instruct patient to report signs and symptoms of toxicity, particularly stomatitis and diarrhea. Tell him that these may not occur for 1 to 3 weeks.
• Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration and alertness.
• Tell patient to avoid activities that can cause injury. Instruct him to use soft toothbrush and electric razor to avoid gum and skin injury.
• Advise patient to minimize GI upset by eating frequent, small servings of food and drinking adequate fluids.
• Tell patient that drug may cause reversible hair loss.
• Inform patient that he'll undergo regular blood testing during therapy.
☞ Advise female to inform prescriber immediately if she is pregnant. Caution her not to breastfeed.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, and behaviors mentioned above.