Fluorouracil (fluorouracil)

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Last reviewed · Source: First Databank (FDB) drug data

Overview

Fluorouracil, a pyrimidine antagonist, is an antimetabolite antineoplastic agent.

Although the precise mechanisms of action of fluorouracil have not been fully elucidated, the main mechanism is thought to be the binding of the deoxyribonucleotide of the drug (FdUMP) and the folate cofactor, N5-10-methylenetetrahydrofolate, to thymidylate synthase (TS) to form a covalently bound ternary complex, which inhibits the formation of thymidylate from uracil, thereby interfering with DNA synthesis. In addition, 5-fluorouridine-5'triphosphate (FUTP) can be incorporated into RNA in place of uridine triphosphate (UTP), producing a fraudulent RNA and interfering with RNA processing and protein synthesis.

Fluorouracil is distributed throughout the body into intestinal mucosa, bone marrow, liver, CSF, and brain tissue.205, It is not known whether the medication or its metabolites are distributed into human milk. Following direct IV injection, the plasma elimination half-life ranges from 8-20 minutes. The major portion of the medication is degraded in the liver.

Following direct IV injection of fluorouracil, 5-20% of the dose is excreted in urine as intact drug within 6 hours. The metabolites (e.g., urea, alpha-fluoro-beta-alanine) are excreted in urine over 3-4 hours.

Fluorouracil is used for the treatment of adenocarcinoma of the colon, rectum, breast, stomach, and pancreas. Fluorouracil is used off-label for a variety of other oncologic indications; refer to current treatment guidelines for the most up-to-date recommendations for use in such indications.

Generic name: fluorouracil
Pronunciation: (flewr-oh-YOUR-uh-sill)

Reference product & biosimilars

No reference, biosimilar or interchangeable associated with this drug.

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Indications

The following indications are listed for Fluorouracil:

  • Adenocarcinoma Of Pancreas
  • Colorectal Cancer
  • Gastric Cancer
  • Metastatic Breast Carcinoma
  • Metastatic Colorectal Cancer

Also known as: Adenocarcinoma Of Colon And Rectum, Advanced Breast Carcinoma, Cancer Of The Colon And Rectum, Gastric Malignancy, Malignancy Of Colon And Rectum, Malignant Neoplasm Of Stomach, Malignant Tumor Of Colon And Rectum, Malignant Tumor Of Stomach, Metastatic Breast Cancer, Metastatic Malignancy Of Breast, Metastatic Malignant Neoplasm Of Breast, Metastatic Malignant Tumor Of Breast, Pancreatic Adenocarcinoma.

Dosing

Dosage and dosage schedules of fluorouracil should be individualized based on the tumor type, specific regimen, clinical response, and concomitant comorbidities. Clinicians should consult published protocols for the dosage of fluorouracil and other chemotherapeutic agents and the method and sequence of administration.

If grade 3 or 4 diarrhea or mucositis, grade 4 myelosuppression, or grade 2 or 3 palmar-plantar erythrodysesthesia (hand-foot syndrome) occurs, withhold fluorouracil. When the toxicity has resolved or improved to grade 1, resume fluorouracil at a reduced dosage.

Withhold fluorouracil if cardiotoxicity (i.e., angina, myocardial infarction or ischemia, arrhythmia, heart failure) develops in patients with no history of coronary artery disease or cardiac dysfunction. Therapy with the medication also should be withheld if hyperammonemic encephalopathy or neurologic effects (i.e., acute cerebellar syndrome, confusion, disorientation, ataxia, visual disturbance) develop. The manufacturers state there is no recommended dosage for resumption of fluorouracil following development of cardiotoxicity, hyperammonemic encephalopathy, or neurologic effects.

Drug interactions

There is no enhanced messaging for this drug.

Contraindications

*None.

Adverse reactions

Reported adverse effects for fluorouracil come from postmarketing reports and include pancytopenia, gastrointestinal ulceration, nausea, vomiting, anaphylaxis and generalized allergic reactions, nystagmus, headache, dry skin, fissuring, photosensitivity (manifested by erythema or increased skin pigmentation), vein pigmentation, lacrimal duct stenosis, visual changes, lacrimation, photophobia, euphoria, thrombophlebitis, epistaxis, and nail changes.

Precautions

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ICD codes

No ICD codes are available for this drug.

Formulary status

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Last reviewed · Source: First Databank (FDB) drug data