Generic Name

Fluorouracil

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Classification

FDA Approved Indications

• Treatment of actinic keratosis, superficial basal cell carcinoma, and certain types of colorectal and breast cancers

Mechanism of Action

Fluorouracil inhibits thymidylate synthase, leading to decreased DNA synthesis and cell death, particularly in rapidly dividing cancer cells.

Dosage and Administration

Adult: Varies based on condition; for topical use, apply thin layer to affected area as directed, typically twice daily.

Pediatric: Use is off-label; dosing depends on condition and site of application.

Geriatric: Adjust doses based on renal and hepatic function, with close monitoring.

Renal Impairment: Use with caution; dosage adjustments may be necessary.

Hepatic Impairment: Use with caution; monitor hepatic function and adjust dose accordingly.

Pharmacokinetics

Absorption: Poorly absorbed through intact skin; systemic absorption can occur after topical application, especially in damaged skin.

Distribution: Widely distributed; crosses the placental barrier.

Metabolism: Primarily hepatic via dihydropyrimidine dehydrogenase (DPD); variability in DPD activity affects toxicity.

Excretion: Renal excretion of metabolites.

Half Life: Approximately 10-20 minutes systemically, but half-life can vary with formulation and route.

Contraindications

• Known hypersensitivity to fluorouracil or other pyrimidines.
• Bone marrow depression.
• Pregnancy and breastfeeding—use only if potential benefit justifies potential risk.

Precautions

• Monitor blood counts during systemic therapy.
• Use cautiously in patients with hepatic or renal impairment.
• Avoid topical application on large or open wounds, or compromised skin.

Adverse Reactions - Common

• Mild local skin reactions (erythema, burning, itching) (Common)
• Mucositis or stomatitis (Common)

Adverse Reactions - Serious

• Bone marrow suppression, including leukopenia, neutropenia, anemia, thrombocytopenia (Serious; monitoring required)
• Hand-foot syndrome (palmar-plantar erythrodysesthesia) (Serious; more common with topical formulations in prolonged use)
• Allergic contact dermatitis (Serious; rare)

Drug-Drug Interactions

• Warfarin (may increase bleeding risk)
• Other myelosuppressive agents

Drug-Food Interactions

N/A

Drug-Herb Interactions

N/A

Nursing Implications

Patient/Family Teaching

• Apply medication exactly as prescribed.
• Report signs of skin irritation, skin breakdown, bleeding, or infection.
• Avoid unnecessary sun exposure or skin trauma during topical therapy.

Special Considerations

Black Box Warnings:

• Use with extreme caution in pregnant women due to potential fetal harm.
• Potential for severe toxicity if DPD deficiency is present.

Genetic Factors: Dihydropyrimidine dehydrogenase (DPD) deficiency increases risk of severe toxicity.

Lab Test Interference: Can cause false elevations in certain lab tests due to tissue necrosis.

Overdose Management

Signs/Symptoms: Severe myelosuppression, neurotoxicity, mucositis, skin reactions.

Treatment: Supportive care; leucovorin rescue may be considered; dialysis is not effective for removal.

Storage and Handling

Storage: Store at room temperature, protected from light.

Stability: Stable for specified period as per manufacturer instructions.