fluorouracil

ROUTE	ONSET	PEAK	DURATION
IV	1–9 days	9–21 days (nadir)	30 days
Top	2–3 days	2–6 wk	1–2 mo

More likely to occur with systemic use than with topical use

Derm: alopecia, maculopapular rash, local inflammatory reactions (topical only), melanosis of nails, nail loss, palmar-plantar erythrodysesthesia, phototoxicity

Endo: sterility

GI: diarrhea, nausea, stomatitis, vomiting

Hemat: anemia, leukopenia, thrombocytopenia

Local: thrombophlebitis

Neuro: acute cerebellar dysfunction

Misc: fever

Interactions ⬆ ⬇

Drug-drug:

Combination chemotherapy with irinotecan may produce unacceptable toxicity (dehydration, neutropenia, sepsis).
Additive bone marrow depression with other bone marrow depressants, including other antineoplastics and radiation therapy.
May ↓ antibody response to live-virus vaccines and ↑ risk of adverse reactions.

Route/Dosage ⬆ ⬇

Advanced Colorectal Cancer

IV (Adults ): In combination with leucovorin alone or leucovorin + oxaliplatin or irinotecan: 400 mg/m² as IV bolus on Day 1, then 2400–3000 mg/m² continuous infusion every 2 wk; In combination with leucovorin: 500 mg/m² as IV bolus 1 hr after leucovorin on Days 1, 8, 15, 22, 29, and 36 every 8 wk.

Breast Cancer

IV (Adults ): In combination with cyclophosphamide + epirubicin or cyclophosphamide + methotrexate: 500 mg/m² or 600 mg/m² on Days 1 and 28 every 28 days for 6 cycles.

Gastric Adenocarcinoma

IV (Adults ): As part of platinum-containing regimen: 200–1000 mg/m² as IV infusion (frequency of administration and number of cycles depends on specific regimen used).

Pancreatic Adenocarcinoma

IV (Adults ): In combination with leucovorin or as part of multidrug regimen: 400 mg/m² as IV bolus on Day 1, then 2400 mg/m² continuous infusion every 2 wk.

Actinic (Solar) Keratoses

(Adults ): Carac: Apply 0.5% cream to lesions once daily for up to 4 wk; Efudex: Apply 2% or 5% solution or cream to lesions twice daily for 2–4 wk.

Superficial Basal Cell Carcinomas

(Adults ): Efudex: Apply 5% solution or cream to lesions twice daily for 3–6 wk (up to 12 wk).

Availability ⬆ ⬇

(Generic available)

Solution for injection: 50 mg/mL
Topical cream: 0.5%; 4%; 5%
Topical solution: 2%; 5%

Assessment ⬆ ⬇

Monitor vital signs before and frequently during therapy.
- Assess mucous membranes, number and consistency of stools, and frequency of vomiting. Assess for signs of infection (fever, chills, sore throat, cough, hoarseness, pain in lower back or side, difficult or painful urination). Assess for bleeding (bleeding gums; bruising; petechiae; and guaiac test stools, urine, and emesis). Avoid IM injections and taking rectal temperatures. Apply pressure to venipuncture sites for 10 min. Notify health care provider if Grade 3 or 4 toxicity (stomatitis or esophagopharyngitis, uncontrollable vomiting, diarrhea, GI bleeding, myocardial ischemia, leukocyte count <3500/mm³, platelet count <100,000/mm³, or hemorrhage from any site) occurs; hold fluorouracil until resolution to Grade ≤1. May be reinitiated at a lower dose when side effects have subsided.
Assess skin for palmar-plantar erythrodysesthesia (tingling of hands and feet followed by pain, erythema, swelling, desquamation) throughout therapy. Occurs more frequently with continuous infusion. Usually occurs after 8–9 wk of therapy, but may occur earlier. Hold fluorouracil for Grades 2 or 3 and resume at lower dose when resolved or Grade 1.
- Monitor intake and output, appetite, and nutritional intake. GI effects usually occur on 4th day of therapy. Adjusting diet as tolerated and administering antidiarrheal agents may help maintain fluid and electrolyte balance and nutritional status. May cause severe diarrhea. Withhold therapy if Grade 3 or 4 diarrhea occurs and until resolved or decreased to Grade 1; then resume at reduced dose.
- Monitor for cerebellar dysfunction (ataxia, confusion, disorientation, visual disturbances). This may persist after discontinuation of therapy.
- Monitor for angina, myocardial infarction/ischemia, arrhythmia, and HF in patients with no history of coronary artery disease or cardiac dysfunction. Discontinue therapy if symptoms occur.
- Monitor for signs and symptoms of hyperammonemic encephalopathy (altered mental status, confusion, disorientation, coma, ataxia) with ↑ serum ammonia level within 72 hr of start of infusion. Discontinue fluorouracil and initiate ammonia-lowering therapy.
- Assess for mucositis, stomatitis, and esophagopharyngitis during therapy. May lead to mucosal sloughing or ulceration. Occurs more frequently with IV bolus doses. If Grade 3 or 4 mucositis occurs, withhold dose and resume at reduced dose when resolved or reduced to Grade 1.
Topical Inspect involved skin before and throughout therapy.

Lab Test Considerations:

May cause ↓ in plasma albumin.
- Consider testing for genetic variants of the DPYD gene prior to initiating fluorouracil to reduce the risk of serious adverse reactions. Patients with certain variants in this gene may have dihydropyrimidine dehydrogenase deficiency, which can result in serious adverse reactions including mucositis, diarrhea, neutropenia, and neurotoxicity.
- Monitor hepatic (AST, ALT, LDH, and serum bilirubin), renal, and hematologic (hematocrit, hemoglobin, leukocyte, platelet count) functions before each treatment and periodically during therapy.
- Monitor CBC daily during IV therapy. Report WBC of <3500/mm³ or platelets <100,000/mm³ immediately; they are criteria for discontinuation. Nadir of leukopenia usually occurs in 9–14 days, with recovery by day 30. May also cause thrombocytopenia. Hold doses if Grade 4 myelosuppression occurs. Resume at ↓ dose when resolved or improved to Grade 1.
- May cause ↑ in urine excretion of 5-hydroxyindoleacetic acid.

Implementation ⬆ ⬇

High Alert: Fatalities have occurred with incorrect administration of chemotherapeutic agents. Before administering, clarify all ambiguous orders; double-check single, daily, and course-of-therapy dose limits; have second practitioner independently double-check original order, calculations, and infusion pump settings.
When administering fluorouracil via IV push, 30 min of cryotherapy is recommended to prevent oral mucositis.
Topical Consult health care provider before administering topical preparations to determine which skin preparation regimen should be followed. Avoid tight occlusive dressings because of irritation to surrounding healthy tissue. A loose gauze dressing for cosmetic purposes is usually preferred. Wear gloves when applying medication. Do not use metallic applicator.

IV Administration:

Fluorouracil is an irritant. If extravasation occurs, immediately stop infusion. Leave needle/cannula in place temporarily but do not flush the line. Gently aspirate extravasated solution; then remove needle/cannula. Elevate patient's extremity and apply dry cold compresses for 20 min 4 times day for 1–2 days.
IV Push: Diluent: May be administered undiluted.Concentration: 50 mg/mL.
Rate: Rapid IV push administration (over 1–2 min) is most effective, but there is a more rapid onset of toxicity.
Intermittent Infusion: Diluent: May be diluted with D5W or 0.9% NaCl.
- Use plastic IV tubing and IV bags to maintain greater stability of medication. Solution is stable for 24 hr at room temperature; do not refrigerate. Solution is colorless to faint yellow. Discard highly discolored or cloudy solution. If crystals form, dissolve by warming solution to 140°F, shaking vigorously, and cooling to body temperature.Concentration: Up to 50 mg/mL.
Rate: Onset of toxicity is greatly delayed by administering an infusion over 2–8 hr.
Y-Site Compatibility:
- acyclovir
- allopurinol
- amikacin
- aminophylline
- amphotericin B liposomal
- ampicillin
- ampicillin/sulbactam
- anidulafungin
- argatroban
- atracurium
- azithromycin
- aztreonam
- bivalirudin
- bleomycin
- bumetanide
- butorphanol
- calcium gluconate
- carboplatin
- carmustine
- cefazolin
- cefepime
- cefotaxime
- cefotetan
- cefoxitin
- ceftazidime
- ceftriaxone
- cefuroxime
- cisatracurium
- cisplatin
- clindamycin
- cyclophosphamide
- cyclosporine
- dacarbazine
- daptomycin
- dexamethasone
- dexmedetomidine
- dexrazoxane
- digoxin
- docetaxel
- dopamine
- doxorubicin liposomal
- enalaprilat
- ephedrine
- ertapenem
- erythromycin
- esmolol
- etoposide phosphate
- famotidine
- fentanyl
- fluconazole
- fludarabine
- foscarnet
- fosphenytoin
- furosemide
- ganciclovir
- gemcitabine
- gentamicin
- granisetron
- heparin
- hetastarch
- hydrocortisone
- hydromorphone
- ifosfamide
- imipenem/cilastatin
- isoproterenol
- ketorolac
- labetalol
- leucovorin
- lidocaine
- linezolid
- magnesium sulfate
- mannitol
- melphalan
- meperidine
- meropenem
- mesna
- methohexital
- methotrexate
- methylprednisolone
- metoprolol
- metronidazole
- milrinone
- mitomycin
- mitoxantrone
- morphine
- nalbuphine
- naloxone
- nitroglycerin
- nitroprusside
- octreotide
- paclitaxel
- palonosetron
- pamidronate
- pantoprazole
- pemetrexed
- pentobarbital
- phenobarbital
- phenylephrine
- piperacillin/tazobactam
- potassium acetate
- potassium chloride
- potassium phosphates
- procainamide
- propofol
- propranolol
- remifentanil
- rituximab
- sargramostim
- sodium acetate
- sodium bicarbonate
- sodium phosphates
- succinylcholine
- sufentanil
- tenoposide
- theophylline
- thiotepa
- tigecycline
- tirofiban
- tobramycin
- trastuzumab
- trimethoprim/sulfamethoxazole
- vasopressin
- vecuronium
- vinblastine
- vincristine
- voriconazole
- zidovudine
- zoledronic acid
Y-Site Incompatibility:
- aldesleukin
- amiodarone
- amphotericin B deoxycholate
- buprenorphine
- calcium chloride
- caspofungin
- chlorpromazine
- ciprofloxacin
- diazepam
- diltiazem
- diphenhydramine
- dobutamine
- doxycycline
- droperidol
- epinephrine
- epirubicin
- filgrastim
- haloperidol
- idarubicin
- irinotecan
- levofloxacin
- lorazepam
- methadone
- midazolam
- minocycline
- moxifloxacin
- nicardipine
- pentamidine
- phenytoin
- prochlorperazine
- promethazine
- topotecan
- vancomycin
- verapamil
- vinorelbine

Patient/Family Teaching ⬆ ⬇

Explain purpose of fluorouracil to patient.
Instruct patient to notify health care provider if fever; chills; sore throat; signs of infection; yellowing of skin or eyes; abdominal pain; joint or flank pain; swelling of feet or legs; bleeding gums; bruising; petechiae; or blood in urine, stool, or emesis occurs. Caution patient to avoid crowds and persons with known infections. Instruct patient to use soft toothbrush and electric razor. Patients should be cautioned not to drink alcoholic beverages or take products containing aspirin or NSAIDs.
- Advise patient to rinse mouth with clear water after eating and drinking and to avoid flossing to minimize stomatitis. Viscous lidocaine may be used if mouth pain interferes with eating. Stomatitis pain may require treatment with opioid analgesics.
- Discuss with patient the possibility of hair loss. Explore methods of coping.
- Caution patient to use sunscreen and protective clothing to prevent phototoxicity reactions.
- Instruct patient not to receive any vaccinations without advice of health care provider.
- Instruct patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care provider before taking any new medications. ↑ dietary intake of thiamine may be recommended.
- May cause fetal harm. Advise women of reproductive potential and men with female partners of reproductive potential to use effective contraception during therapy and for at least 3 mo following completion of therapy and to avoid breastfeeding during therapy. Inform patients that fertility may be impaired during therapy.
- Emphasize the importance of routine follow-up lab tests to monitor progress and to check for side effects.
Topical Instruct patient in correct application of solution or cream. Emphasize importance of avoiding the eyes; caution should also be used when applying medication near mouth and nose. If patient uses clean finger to self-administer, emphasize importance of washing hands thoroughly after application. Explain that erythema, scaling, and blistering with pruritus and burning sensation are expected. Advise patient to avoid sunlight or ultraviolet light (tanning booths) as much as possible; may increase side effects. Therapy is discontinued when erosion, ulceration, and necrosis occur in 2–6 wk (10–12 wk for basal cell carcinomas). Skin heals 4–8 wk later.
- Fluorouracil may be fatal if ingested by pets. Do not allow pets to be in contact with the container or the skin where fluorouracil topical has been applied. Store out of reach of pets. Safely discard or clean any cloth or applicator that may retain fluorouracil and avoid leaving any residues on your hands, clothing, carpeting or furniture.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇

Contraind./Precautions ⬆ ⬇

Adv. Reactions/Side Effects ⬆ ⬇