Fluorouracil
Fluorouracil Prescribing Information
Warnings and Precautions, Serious
Adverse Reactions from Dihydropyrimidine
Dehydrogenase (DPD) Deficiency (5.1) 01/2024
[Enter Indications here]
• Fluorouracil is recommended for administration either as an intravenous bolus or as an intravenous infusion. (
Fluorouracil is recommended for administration either as an intravenous bolus or as anintravenous infusion. Do not inject the entire contents of the vial directly into patients. Individualize the dose and dosing schedule of fluorouracil based on tumor type, the specific regimen administered, disease state, response to treatment, and patient risk factors.
• See Full Prescribing Information for dose individualization (
Fluorouracil is recommended for administration either as an intravenous bolus or as anintravenous infusion. Do not inject the entire contents of the vial directly into patients. Individualize the dose and dosing schedule of fluorouracil based on tumor type, the specific regimen administered, disease state, response to treatment, and patient risk factors.
Withhold fluorouracil for any of the following:
• Development of angina, myocardial infarction/ischemia, arrhythmia, or heart failure in patients with no history of coronary artery disease or myocardial dysfunction [see Warnings and Precautions ]
• Hyperammonemic encephalopathy [see Warnings and Precautions ]
• Acute cerebellar syndrome, confusion, disorientation, ataxia, or visual disturbances [see Warnings and Precautions ]
• Grade 3 or 4 diarrhea [see Warnings and Precautions ]
• Grade 2 or 3 palmar-plantar erythrodysesthesia (hand-foot syndrome) [see Warnings and Precautions ]
• Grade 3 or 4 mucositis [see Warnings and Precautions ]
• Grade 4 myelosuppression [see Warnings and Precautions ]
Upon resolution or improvement to Grade 1 diarrhea, mucositis, myelosuppression, or palmarplantar erythrodysesthesia, resume fluorouracil administration at a reduced dose.
There is no recommended dose for resumption of fluorouracil administration following development of any of the following adverse reactions:
• Cardiac toxicity
• Hyperammonemic encephalopathy
• Acute cerebellar syndrome, confusion, disorientation, ataxia, or visual disturbances
• See Full Prescribing Information for recommended doses of fluorouracil for adenocarcinoma of the colon and rectum (
- The recommended dose of fluorouracil, administered in an infusional regimen in combination with leucovorin alone, or in combination with leucovorin and oxaliplatin or irinotecan, is 400 mg/m2 by intravenous bolus on Day 1, followed by 2400 mg/m2 to 3000 mg/m2 intravenously as a continuous infusion over 46 hours every two weeks.
- The recommended dose of fluorouracil, if administered in a bolus dosing regimen in combination with leucovorin, is 500 mg/m2 by intravenous bolus on Days 1, 8, 15, 22, 29, and 36 in 8-week cycles.
• The recommended dose of fluorouracil, administered as a component of a cyclophosphamide based multidrug regimen, is 500 mg/m2 or 600 mg/m2 intravenously on Days 1 and 8 every 28 days for 6 cycles.
- The recommended dose of fluorouracil, administered as a component of a platinum-containing multidrug chemotherapy regimen, is 200 mg/m2 to 1000 mg/m2 intravenously as a continuous infusion over 24 hours. The frequency of dosing in each cycle and the length of each cycle will depend on the dose of fluorouracil and the specific regimen administered.
- The recommended dose of fluorouracil, administered as an infusional regimen in combination with leucovorin or as a component of a multidrug chemotherapy regimen that includes leucovorin, is 400 mg/m2 intravenous bolus on Day 1, followed by 2400 mg/m2 intravenously as a continuous infusion over 46 hours every two weeks.
• Pharmacy Bulk Package: Prepare doses for more than one patient in a Pharmacy Admixture Service under appropriate conditions for cytotoxic drugs. Do not inject entire contents of vial directly into patients. Use within 4 hours of puncture (
Fluorouracil is supplied in a pharmacy bulk package consisting of a vial. The pharmacy bulk package can be used to prepare doses for more than one patient. It is not supplied with a sterile transfer device, which is required for dispensing when multiple doses will be prepared from the single vial. The 50 mL/100 mL vial is only intended for preparation in a Pharmacy Admixture Service under appropriate conditions for cytotoxic drugs [see References ]. Store vial at room temperature.
Using aseptic conditions, penetrate the container closure once with a suitable sterile transfer device or dispensing set that allows measured distribution of the contents. Record the date and time the vial was opened on the vial label. Discard the pharmacy bulk package 4 hours after penetration of the container closure.
Withdraw the calculated dose for an individual patient into a sterile syringe. Inspect the solution in syringe for particulate matter and discoloration prior to administration or further dilution. Discard syringe if the solution is discolored or contains particulate matter.
Do not administer in the same intravenous line concomitantly with other medicinal products. For bolus administration, store undiluted fluorouracil in the syringe for up to 4 hours at room temperature (25°C). Administer fluorouracil as an intravenous bolus through an established intravenous line.
Store diluted solutions of fluorouracil for up to 4 hours at room temperature (25°C) prior to administration to the patient. For intravenous infusion regimens, administer through a central venous line using an infusion pump.
Fluorouracil injection USP is supplied as a pharmacy bulk package as a vial containing
2.5 g/50 mL (50 mg/mL) and 5 g/100 mL (50 mg/mL) fluorouracil.
• Nursing Mothers: Discontinue drug or discontinue nursing. (8.3)
• Females and Males of Reproductive Potential: Provide pregnancy planning and prevention counseling. (
Based on its mechanism of action, fluorouracil can cause fetal harm when administered to a pregnant woman. In animal studies, administration of fluorouracil at doses lower than a human dose of 12 mg/kg caused teratogenicity. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during and for 3 months following cessation of therapy with fluorouracil [see Use in Specific Populations , Clinical Pharmacology , and Nonclinical Toxicology ].
There are no adequate and well-controlled studies with fluorouracil in pregnant women. Based on its mechanism of action, fluorouracil can cause fetal harm when administered to a pregnant woman. Administration of fluorouracil to rats and mice during selected periods of organogenesis, at doses lower than a human dose of 12 mg/kg, caused embryolethality and teratogenicity. Malformations included cleft palate and skeletal defects. In monkeys, maternal doses of fluorouracil higher than an approximate human dose of 12 mg/kg resulted in abortion. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, apprise the patient of the potential hazard to a fetus
Malformations including cleft palate, skeletal defects and deformed appendages (paws and tails) were observed when fluorouracil was administered by intraperitoneal injection to mice at doses at or above 10 mg/kg (approximately 0.06 times a human dose of 12 mg/kg on a mg/m2 basis) for 4 days during the period of organogenesis. Similar results were observed in hamsters administered fluorouracil intramuscularly at doses lower than those administered in commonly used clinical treatment regimens. In rats, administration of fluorouracil by intraperitoneal injection at doses greater than 15 mg/kg (approximately 0.2 times a human dose of 12 mg/kg on a mg/m2 basis) for a single day during organogenesis resulted in delays in growth and malformations including microanophthalmos. In monkeys, administration of fluorouracil during organogenesis at doses approximately equal to a human dose of 12 mg/kg on a mg/m2 basis resulted in abortion; at a 50% lower dose, resorptions and decreased fetal body weights were reported.
Contraception
Based on its mechanism of action, fluorouracil can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with fluorouracil and for up to 3 months following cessation of therapy [see Use in Specific Populations ].
Fluorouracil may damage spermatozoa. Advise males with female partners of reproductive potential to use effective contraception during and for 3 months following cessation of therapy with fluorouracil [see Nonclinical Toxicology ].
Infertility
Advise females of reproductive potential that, based on animal data, fertility may be impaired while receiving fluorouracil [see Nonclinical Toxicology ].
Advise males of reproductive potential that, based on animal data, fertility may be impaired while receiving fluorouracil [see Nonclinical Toxicology ].
None.