Names and pronunciation
(flure-oh-yoor′a-sil) Carac, Efudex, Fluoroplex, Tolak
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Drug reference
(flure-oh-yoor′a-sil) Carac, Efudex, Fluoroplex, Tolak
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Func. class.: Antineoplastic, antime- tabolite
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Chem. class.: Pyrimidine analog F
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ACTION: Inhibits DNA, RNA synthe- sis; interferes with cell replication by competitively inhibiting thymidylate production, specific for S phase of cell cycle
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USES: Systemic: cancer of breast, colon, rectum, stomach, pancreas; topi- cal: multiple actinic keratoses, superfi- cial basal cell carcinomas
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Unlabeled uses: Anal carcinoma, blad- der cancer, cervical cancer, esophageal cancer, glaucoma surgery (adjunctive therapy), head and neck cancer, hepato- biliary cancers, pancreatic tumors, penile cancer, unknown primary cancer, vulvar cancer
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CONTRAINDICATIONS: Preg- nancy, breastfeeding, hypersensitivity, poor nutritional status, serious infec- tions, dihydropyrimidine dehydroge- nase deficiency , bone marrow suppression Precautions: Children, renal/hepatic disease, angina, stomatitis, diarrhea, sunlight exposure, vaccination, occlusive dressing, GI bleeding
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Black Box Warning: Requires an expe- rienced clinician and a specialized care setting Black Box Warning: Use only with an ex- perienced clinician in a specialized care setting, for cancer chemotherapy • Palmar-plantar erythrodysesthesia: hand/foot tingling changing to pain, redness • Infiltration: monitor frequently for pain, redness, inflammation at site; if present, stop infusion and start at new site, may use ice at site • 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; avoid IM injections, rectal temperatures • Inflammation of mucosa, breaks in skin; buccal cavity q8hr for dryness, sores or ulceration, white patches, oral pain, bleeding, dysphagia • Infection: fever, chills, cough, sore throat; those with current infections should be treated before receiving 5-FU, the dose reduced or discontinued if infection occurs • Toxicity: hemorrhage, severe vomiting, severe diarrhea, stomatitis, WBC <3500/ mm3, platelets <100,000/mm3, notify prescriber • Acute cerebellar dysfunction: dizzi- ness, weakness • Pregnancy: identify pregnancy before starting therapy; do not use in pregnancy or breastfeeding; drug may cause fetal harm
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SIDE EFFECTS Systemic use CNS: Malaise, acute cerebellar dys- function EENT: Light intolerance, lacrimation GI: Anorexia, stomatitis, diarrhea, nausea, vomiting, hemorrhage, enteri- F tis, glossitis HEMA: Thrombocytopenia, leukopenia, myelosuppression, anemia, agranulocytosis INTEG: Rash, fever, photosensitivity, anaphylaxis, alopecia, hand-foot syndrome
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INTERACTIONS Increase: bleeding—anticoagulants, NSAIDs, platelet inhibitors, thrombolytics Increase: toxicity—metroNIDAZOLE, irinotecan Increase: toxicity, bone marrow depres- sion—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, HB, WBC, platelets, 5-HIAA Decrease: albumin
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DOSAGE AND ROUTES Doses vary widely, based on actual body weight unless obese, then based on lean body weight Colorectal cancer • Adult: IV Bolus 400 mg/m2 bolus on day 1, then continuous IV infusion 2400-3000 mg/m2 over 46 hr q2 wk (with leucovorin ± either oxaliplatin or irinotecan) or IV Bolus 500 mg/m2 on days 1, 8, 15, 22, 29, and 36 (1 hr after the start of leucovorin) q8 wk (with leucovorin) for 4 cycles Gastric cancer • Adult: IV Continuous Infusion 200- 1000 mg/m2/day over 24 hr (as part of a platinum-containing regimen); the duration and frequency of each cycle vary based on the dose and regimen Pancreatic cancer • Adult: IV Continuous Infusion 2400 mg/m2 over 46 hr q14 days (with leucovorin, irinotecan, and oxaliplatin) for 24 wk Breast cancer • Adult: IV 500 mg/m2 on days 1 and 8 every 28 days; CMF regimen: 600 mg/ m2 on days 1 and 8 every 28 days Anal carcinoma (unlabeled) • Adult: IV Continuous Infusion 1000 mg/m2/day days 1 to 4 and days 29 to 32 (with mitomycin and radiation therapy) Bladder cancer, muscle invasive (unlabeled) • Adult: IV Continuous Infusion 500 mg/m2/day during radiation therapy frac- tions 1 to 5 and 16 to 20 (with mitomycin and radiation therapy) Cervical cancer (unlabeled) • Adult: IV Continuous Infusion 1000 mg/m2/day days 1 to 4 (with cispla- tin and radiation therapy) q3 wk for 3 cycles Esophageal cancer (unlabeled) • Adult: IV Continous Infusion 1000 mg/m2/day days 1 to 4 and days 29 to 32 of a 35-day treatment cycle (preoperative chemoradiation; with cisplatin) Glaucoma surgery, adjunctive ther- apy (unlabeled) • Adult: Ophthalmic: Intraoperative topical application: Apply sponge soaked in fluorouracil 50 mg/mL for 5 min. Postoperative subconjunctival injection: 5 mg once daily for 10 days or 5 mg once daily for 1 wk, then every other day the next week for a total of 10 doses Head and neck cancer, squamous cell (unlabeled) • Adult: IV Continuous Infusion 1000 mg/m2/day days 1 to 4 q3 wk (in combination with cisplatin) for at least 6 cycles or 1000 mg/m2/day days 1 to 4 q4 wk (with carboplatin) or 600 mg/ m2/day days 1 to 4, 22 to 25, and 43 to 46 (with carboplatin and radiation)
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Available forms: Inj 50 mg/mL; cream 0.5%, 1%, 4%, 5%; sol 2%, 5%
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Administer: 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, do not use occlusive dressings, may use gauze dressing IV route • Prepared in biologic cabinet using gloves, gown, mask; use cytotoxic han- dling procedures • Double-check all dosage amounts, type of product to be used; fatalities have oc- curred • Antiemetic 30-60 min before product to prevent vomiting, for several days thereafter IV direct • Undiluted; may inject through Y-tube or 3-way stopcock; give over 1-3 min; may be diluted in NS, D5W and given as an intermittent infusion; use infu- sion in plastic containers; given over 2-8 hr; do not refrigerate/freeze; pro- tect from light, discard unused por- tion, stable for 24 hr at room tempera- ture, do not use discolored, cloudy solution; solution is pale yellow; for crystals, dissolve by warming slowly and shaking, let cool to body tempera- ture before use Y-site compatibilities: Acyclovir, al- atrofloxacin, alfentanil, allopurinol, amifostine, amikacin, amphotericin B lipid complex, amphotericin B lipo- some, ampicillin, ampicillin-sulbactam, anidulafungin, argatroban, atenolol, atracurium, azithromycin, aztreonam, bivalirudin, bleomycin, bumetanide, butorphanol, calcium gluconate, CAR- BOplatin, ceFAZolin, cefepime, cefotax- ime, cefoTEtan, cefOXitin, cefTAZidime, ceftizoxime, cefTRIAXone, cefuroxime, cimetidine, cisatracurium, CISplatin, clindamycin, codeine, cyclophospha- mide, cycloSPORINE, DAPTOmycin, dexamethasone, digoxin, DOCEtaxel, DOPamine, doripenem, DOXOrubicin liposomal, enalaprilat, ePHEDrine, er- tapenem, erythromycin, esmolol, etopo- side phosphate, famotidine, fenoldopam, fentaNYL, fluconazole, fludarabine, fos- carnet, fosphenytoin, furosemide, gan- ciclovir, gatifloxacin, gemcitabine, gentamicin, granisetron, heparin, hy- drocortisone, HYDROmorphone, ifos- famide, imipenem-cilastatin, inamrinone, isoproterenol, ketorolac, labetalol, leu- covorin, levorphanol, lidocaine, line- zolid, magnesium sulfate, mannitol, melphalan, meperidine, meropenem, mesna, methohexital, methotrexate, methylPREDNISolone, metoprolol, met- roNIDAZOLE, milrinone, mitoMYcin, mitoXANtrone, morphine sulfate, nal- buphine, naloxone, nesiritide, nitro- glycerin, nitroprusside, octreotide, ofloxacin, PACLitaxel, palonosetron, pamidronate, pancuronium, pantopra- zole, PEMEtrexed, PENTobarbital, PHE- Nobarbital, phenylephrine, piperacillin, piperacillin-tazobactam, potassium chloride/phosphates, procainamide, propofol, propranolol, ranitidine, remifentanil, riTUXimab, sargramostim, sodium acetate/bicarbonate/phosphates, succinylcholine, SUFentanil, sulfa- methoxazole-trimethoprim, teniposide, theophylline, thiopental, thiotepa, ticar- cillin, ticarcillin-clavulanate, tigecy- cline, tirofiban, tobramycin, trastuzumab, vasopressin, vecuronium, vinBLAStine, vinCRIStine, vitamin B complex/C, vori- conazole, zidovudine, zoledronic acid
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Assess: • Bone marrow suppression: moni- tor daily during IV treatment: CBC, dif- ferential, platelet count daily (IV); with- hold 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 pretreat- ment of WBC <2000/mm3 or platelets <100,000/mm3, delay until recovery of counts above this level; nadir usually 9-14 days, recovery 30 days
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Evaluate: • Therapeutic response: decreased tu- mor size, spread of malignancy
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CLINICAL CONSIDERATIONS
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Patient and caregiver information: • To avoid crowds, persons with known infection • To avoid foods with citric acid, hot temperature, or rough texture if stomati- tis 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); 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 • Topical: to apply only to affected areas, being careful around mouth, nose, eyes; to avoid occlusive dressings; to wash hands after application
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PHARMACOKINETICS Half-life 16 min (IV): metabolized in liver; excreted in lungs (60%-80%) urine; IV onset 1-9 days, peak 9-21 days (nadir), duration 30 days; top: onset 2-3 days, peak 2-6 wk, duration 1-2 mo; crosses blood-brain barrier (up to 15%)
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• Adult: IV Bolus 400 mg/m2 bolus on day 1, then continuous IV infusion 2400-3000 mg/m2 over 46 hr q2 wk (with leucovorin ± either oxaliplatin or irinotecan) or IV Bolus 500 mg/m2 on days 1, 8, 15, 22, 29, and 36 (1 hr after the start of leucovorin) q8 wk (with leucovorin) for 4 cycles Gastric cancer
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• Adult: IV Continuous Infusion 200- 1000 mg/m2/day over 24 hr (as part of a platinum-containing regimen); the duration and frequency of each cycle vary based on the dose and regimen Pancreatic cancer
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• Adult: IV Continuous Infusion 2400 mg/m2 over 46 hr q14 days (with leucovorin, irinotecan, and oxaliplatin) for 24 wk Breast cancer
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• Adult: IV 500 mg/m2 on days 1 and 8 every 28 days; CMF regimen: 600 mg/ m2 on days 1 and 8 every 28 days Anal carcinoma (unlabeled)
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• Adult: IV Continuous Infusion 1000 mg/m2/day days 1 to 4 and days 29 to 32 (with mitomycin and radiation therapy) Bladder cancer, muscle invasive (unlabeled)
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• Adult: IV Continuous Infusion 500 mg/m2/day during radiation therapy frac- tions 1 to 5 and 16 to 20 (with mitomycin and radiation therapy) Cervical cancer (unlabeled)
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• Adult: IV Continuous Infusion 1000 mg/m2/day days 1 to 4 (with cispla- tin and radiation therapy) q3 wk for 3 cycles Esophageal cancer (unlabeled)
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• Adult: IV Continous Infusion 1000 mg/m2/day days 1 to 4 and days 29 to 32 of a 35-day treatment cycle (preoperative chemoradiation; with cisplatin) Glaucoma surgery, adjunctive ther- apy (unlabeled)
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• Adult: Ophthalmic: Intraoperative topical application: Apply sponge soaked in fluorouracil 50 mg/mL for 5 min. Postoperative subconjunctival injection: 5 mg once daily for 10 days or 5 mg once daily for 1 wk, then every other day the next week for a total of 10 doses Head and neck cancer, squamous cell (unlabeled)
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• Adult: IV Continuous Infusion 1000 mg/m2/day days 1 to 4 q3 wk (in combination with cisplatin) for at least 6 cycles or 1000 mg/m2/day days 1 to 4 q4 wk (with carboplatin) or 600 mg/ m2/day days 1 to 4, 22 to 25, and 43 to 46 (with carboplatin and radiation)
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