Fluorouracil is a nucleoside metabolic inhibitor indicated for the treatment of patients with

• Adenocarcinoma of the Colon and Rectum 
• Adenocarcinoma of the Breast
• Gastric Adenocarcinoma
• Pancreatic Adenocarcinoma

Colorectal Cancer

Breast Cancer

Stomach Cancer

Pancreatic Cancer

Recommended Dosage for Adenocarcinoma of the Colon and Rectum:

• In combination with leucovorin alone, or with leucovorin and oxaliplatin or irinotecan, fluorouracil is recommended at a dose of 400 mg/m2 via intravenous bolus on Day 1. This is followed by 2400 mg/m2 to 3000 mg/m2 administered intravenously as a continuous infusion over 46 hours every two weeks.
• For bolus dosing in combination with leucovorin, the recommended dose is 500 mg/m2 via intravenous bolus on Days 1, 8, 15, 22, 29, and 36 in 8-week cycles.

Recommended Dosage for Adenocarcinoma of the Breast:

• Fluorouracil, as part of a cyclophosphamide-based multidrug regimen, is recommended at a dose of 500 mg/m2 or 600 mg/m2 administered intravenously on Days 1 and 8 every 28 days for 6 cycles.

Recommended Dosage for Gastric Adenocarcinoma:

• In a platinum-containing multidrug chemotherapy regimen, the recommended dose of fluorouracil is 200 mg/m2 to 1000 mg/m2 administered intravenously as a continuous infusion over 24 hours. The dosing frequency and cycle length depend on the specific regimen and fluorouracil dose.

Recommended Dosage for Pancreatic Adenocarcinoma:

• Administered as an infusional regimen with leucovorin or as part of a multidrug chemotherapy regimen with leucovorin, the recommended dose of fluorouracil is 400 mg/m2 via intravenous bolus on Day 1. This is followed by 2400 mg/m2 administered intravenously as a continuous infusion over 46 hours every two weeks.

Adverse reactions associated with fluorouracil include-

• Myelosuppression (leukopenia, thrombocytopenia, anemia)
• Gastrointestinal disturbances (nausea, vomiting, diarrhea)
• Mucositis
• Hand-foot syndrome
• Dermatological reactions (rash, photosensitivity)
• Neurological effects (neuropathy, cerebellar dysfunction)
• Cardiotoxicity (chest pain, arrhythmias)

Myelosuppression

Diarrhea

Rash

Neuropathy

Increased Risk of Serious or Fatal Adverse Reactions in Patients with Low or Absent Dipyrimidine Dehydrogenase Activity:

• Consider withholding or permanently discontinuing fluorouracil in patients demonstrating acute early-onset or unusually severe toxicity, indicating potential near complete or total absence of dipyrimidine dehydrogenase (DPD) activity. No fluorouracil dose has been proven safe in patients lacking DPD activity.

Cardiotoxicity:

• Fluorouracil may lead to cardiotoxicity, including angina, myocardial infarction/ischemia, arrhythmia, and heart failure. In case of cardiac toxicity, withhold fluorouracil.

Hyperammonemic Encephalopathy:

• Within 72 hours of starting fluorouracil, patients may experience altered mental status, confusion, disorientation, coma, or ataxia with elevated serum ammonia levels. In such cases, withhold fluorouracil and initiate ammonia-lowering therapy.

Neurologic Toxicity:

• Fluorouracil may induce acute cerebellar syndrome, confusion, disorientation, ataxia, or visual disturbances. Withhold fluorouracil in the presence of neurologic toxicity.

Diarrhea:

• Severe diarrhea can occur with fluorouracil use. Withhold the medication until severe diarrhea resolves.

Palmar-Plantar Erythrodysesthesia (Hand-Foot Syndrome):

• Fluorouracil may cause hand-foot syndrome. If severe, discontinue fluorouracil until resolved or reduced to Grade 1, then resume at a reduced dose.

Myelosuppression:

• Severe and fatal myelosuppression may result from fluorouracil use. Withhold fluorouracil until severe myelosuppression resolves, then resume at a reduced dose.

Mucositis:

• Fluorouracil can induce severe mucositis. Discontinue fluorouracil until resolved or reduced to Grade 1, then resume at a reduced dose.

Increased Risk of Elevated INR with Warfarin:

• Concurrent use with warfarin may lead to clinically significant increases in coagulation parameters. Monitor INR and prothrombin time closely.

Embryofetal Toxicity:

• Fluorouracil has the potential to cause fetal harm. Inform females and males of reproductive potential about the potential risk to a fetus.