Fluorouracil (Rx)
(flure-oh-yoor′a-sil)
Adrucil, Carac, Efudex, 5-FU
Func. class.: Antineoplastic, antimetabolite
Chem. class.: Pyrimidine analog
Do not confuse:
fluorouracil/flucytosine
Action:
Inhibits DNA, RNA synthesis; interferes with cell replication by competitively inhibiting thymidylate
production, specific for S phase of cell cycle
Uses:
Systemic: cancer of breast, colon, rectum, stomach, pancreas; topical: multiple actinic keratoses,
superficial basal cell carcinomas
Unlabeled uses:
Anal, biliary tract, cervical, head and neck, hepatocellular, ovarian cancer
Contraindications:
Pregnancy (X), breastfeeding, hypersensitivity, poor nutritional status, serious infections
Black Box Warning:
Bone marrow suppression
Precautions:
Children, renal/hepatic disease, angina
Black Box Warning:
GI bleeding
Dosage and routes
Doses vary widely, based on actual body weight unless obese, then based on lean body weight
Advanced colorectal cancer
• Adult:
IV bolus 300-500 mg/m2/day × 4-5 days q28days or 600-1500 mg/m2 weekly or every other wk;
continuous IV inf: 300-1000 mg/m2/day × 4-5 days q4wk or 300 mg/m2/day indefinitely, high dose
3000-3400 mg/m2 over 24-72 hr
Breast cancer
• Adult:
IV bolus 400-600 mg/m2 on days 1 and 8 of every cycle with cyclophosphamide and methotrexate or
600 mg/m2 day 1 with cyclophosphamide and methotrexate q21-28days
Pancreatic cancer
• Adult:
IV bolus 600 mg/m2 on days 1, 8, 29, 36 with DOXOrubicin and mitoMYcin q8wk
Actinic/solar keratoses
• Adult:
TOP 1% cream/sol 1-2×/day or 2-5% sol for hands
Superficial basal cell carcinoma
• Adult:
TOP 5% sol or cream 2×/day × 3-12 wk
Available forms:
Inj 50 mg/ml; cream 0.5%, 1%, 5%; sol 1%, 2%, 5%
Administer:
• Antiemetic 30-60 min before product to prevent vomiting, for several days thereafter
Topical route
• The 1% strength is used on face; higher strengths are used on other parts of the body
• Wear gloves when applying; may use with a loose dressing; use plastic or wooden applicator
IV route
• Prepared in biologic cabinet using gloves, gown, mask; use cytotoxic handling procedures
• Undiluted; may inject through Y-tube or 3-way stopcock; give over 1-3 min; may be diluted in NS,
D5W; given as a continuous inf in plastic containers; do not refrigerate/freeze; protect from light;
discard unused portion
Y-site compatibilities:
Acyclovir, alatrofloxacin, alfentanil, allopurinol, amifostine, amikacin, amphotericin B lipid complex,
amphotericin B liposome, ampicillin, ampicillin-sulbactam, anidulafungin, argatroban, atenolol,
atracurium, azithromycin, aztreonam, bivalirudin, bleomycin, bumetanide, butorphanol, calcium
gluconate, CARBOplatin, ceFAZolin, cefepime, cefoperazone, cefotaxime, cefoTEtan, cefOXitin,
cefTAZidime, ceftizoxime, cefTRIAXone, cefuroxime, cimetidine, cisatracurium, CISplatin, clindamycin,
codeine, cyclophosphamide, cycloSPORINE, DAPTOmycin, dexamethasone, digoxin, DOCEtaxel,
DOPamine, doripenem, DOXOrubicin liposomal, enalaprilat, ePHEDrine, ertapenem, erythromycin,
esmolol, etoposide phosphate, famotidine, fenoldopam, fentaNYL, fluconazole, fludarabine, foscarnet,
fosphenytoin, furosemide, ganciclovir, gatifloxacin, gemcitabine, gentamicin, granisetron, heparin,
hydrocortisone, HYDROmorphone, ifosfamide, imipenem-cilastatin, inamrinone, isoproterenol,
ketorolac, labetalol, leucovorin, levorphanol, lidocaine, linezolid, magnesium sulfate, mannitol,
melphalan, meperidine, meropenem, mesna, methohexital, methotrexate, methylPREDNISolone,
metoprolol, metroNIDAZOLE, milrinone, mitoMYcin, mitoXANtrone, morphine sulfate, nalbuphine,
naloxone, nesiritide, nitroglycerin, nitroprusside, octreotide, ofloxacin, PACLitaxel, palonosetron,
pamidronate, pancuronium, pantoprazole, PEMEtrexed, PENTobarbital, PHENobarbital, phenylephrine,
piperacillin, piperacillin-tazobactam, potassium chloride/phosphates, procainamide, propofol,
propranolol, ranitidine, remifentanil, riTUXimab, sargramostim, sodium
acetate/bicarbonate/phosphates, succinylcholine, SUFentanil, sulfamethoxazole-trimethoprim,
teniposide, theophylline, thiopental, thiotepa, ticarcillin, ticarcillin-clavulanate, tigecycline, tirofiban,
tobramycin, trastuzumab, vasopressin, vecuronium, vinBLAStine, vinCRIStine, vitamin B complex/C,
voriconazole, zidovudine, zoledronic acid
Side effects
Systemic use
CNS:
Lethargy, malaise, weakness, acute cerebellar dysfunction
CV:
Myocardial ischemia, angina
EENT:
Light intolerance, lacrimation
GI:
Anorexia, stomatitis, diarrhea, nausea, vomiting, hemorrhage, enteritis, glossitis
Hema:
Thrombocytopenia, leukopenia, myelosuppression, anemia, agranulocytosis
Integ:
Rash, fever, photosensitivity, anaphylaxis
Pharmacokinetics
Half-life 20 hr terminal; metabolized in liver; excreted in urine; crosses blood-brain barrier
Interactions
Increase:
bleeding—anticoagulants, NSAIDs, platelet inhibitors, thrombolytics
Increase:
toxicity—metroNIDAZOLE
Increase:
toxicity, bone marrow depression—radiation or other antineoplastics, leucovorin
Decrease:
antibody response—live virus vaccines
Decrease:
effect of phenytoin
Drug/lab test
Increase:
AST, ALT, LDH, serum bilirubin, Hct, Hgb, WBC, platelets, 5-HIAA
Decrease:
albumin
Nursing considerations
Assess:
Black Box Warning:
Bone marrow suppression: CBC, differential, platelet count daily (IV); withhold product if WBC is
<3500/mm3 or platelet count is <100,000/mm3; notify prescriber of results; product should be
discontinued; nadir of leukopenia within 2 wk, recovery 1 mo, if pretreatment of WBC <2,000/mm3 or
platelets <100,000/mm3, delay until recovery of counts above this level
• Renal studies: BUN, serum uric acid, urine CCr, electrolytes before, during therapy
• Hepatic studies before, during therapy: bilirubin, alk phos, AST, ALT, LDH before, during therapy
• Bleeding: hematuria, guaiac, bruising, petechiae, mucosa or orifices q8hr
• Inflammation of mucosa, breaks in skin; buccal cavity q8hr for dryness, sores or ulceration, white
patches, oral pain, bleeding, dysphagia
• GI symptoms: frequency of stools, cramping, intractable vomiting, stomatitis
• Infection: those with current infections should be treated before receiving 5-FU, the dose reduced
or discontinued if infection occurs
Evaluate:
• Therapeutic response: decreased tumor size, spread of malignancy
Teach patient/family:
• To avoid crowds, persons with known infection
• To avoid foods with citric acid, hot or rough texture if stomatitis is present; to drink adequate fluids
• To report stomatitis: any bleeding, white spots, ulcerations in mouth; that patient should examine
mouth daily, report symptoms; viscous lidocaine may be used; rinsing of mouth tid-qid with water, club
soda; brushing of teeth bid-tid with soft brush or cotton-tipped applicator for stomatitis; use unwaxed
dental floss, give ice chips for mucositis
• To report signs of infection: fever, sore throat, flulike symptoms
• To report signs of anemia: fatigue, headache, faintness, shortness of breath, irritability
• To report bleeding: to avoid razors, commercial mouthwash, IM inj if counts are low
• Not to use aspirin products or NSAIDs
• To use contraception during therapy (men and women), pregnancy (X); to avoid breastfeeding
(topical use)
• Not to receive vaccinations during therapy
• To use sunscreen or stay out of the sun to prevent photosensitivity
• About hair loss; to explore use of wigs or other products until hair regrowth occurs
• To apply topically only to affected areas, being careful around mouth, nose, eyes