Fluorouracil – Use, Dosage, Side Effects, Interaction

Fluorouracil is an antineoplastic anti-metabolite. Anti-metabolites masquerade as purine or pyrimidine – which become the building blocks of DNA. They prevent these substances from becoming incorporated into DNA during the “S” phase (of the cell cycle), stopping normal development and division. Fluorouracil blocks an enzyme that converts the cytosine nucleotide into the deoxy derivative. In addition, DNA synthesis is further inhibited because Fluorouracil blocks the incorporation of the thymidine nucleotide into the DNA strand.

Use in Cancer

Fluorouracil injection is approved to treat:

• Breast cancer.
• Colorectal cancer.
• Gastric (stomach) cancer.
• Pancreatic cancer.

Fluorouracil is also called 5-FU. Fluorouracil is also being studied in the treatment of other conditions and types of cancer.

Fluorouracil is also available in a topical form. For more information, see the Drug Information Summary for Fluorouracil (Topical).

Contra-Indications

• Hypersensitivity to the active component or any of the ingredients
• Pregnancy
• In patients with dihydropyrimidine dehydrogenase (DPD) enzyme deficiency
• caloric undernutrition
• decreased function of bone marrow?
• decreased blood platelets
• a significant decrease in certain blood clotting cells called platelets
• low levels of white blood cells
• low levels of a type of white blood cell called neutrophils
• angina?, a type of chest pain?
• abnormal EKG with QT changes from birth
• bleeding
• throat? irritation
• stomatitis, a condition with painful swelling? and sores inside the mouth
• stomach or intestinal ulcer?
• liver problems
• bleeding of the stomach or intestines
• decreased kidney? function
• erythrodysesthesia or tingling?, pain?, redness, and edema? in the hands and feet
• excessive vomiting?
• diarrhea?
• pregnancy
• a patient who is producing milk and breastfeeding
• dihydropyrimidine dehydrogenase deficiency
• spread of malignant cancer to the bone marrow

Dosage?

Strengths: 5%; 2%; 1%; 0.5%; 4%

Keratosis

• 0.5% cream (microsphere formulation): Apply to the affected area once a day where actinic keratosis lesions appear, using enough to cover the entire area with a thin film
• Duration of therapy: Apply for up to 4 weeks as tolerated; continued treatment up to 4 weeks results in greater lesion? reduction; local irritation is not markedly increased by extending treatment from 2 to 4 weeks, and is generally resolved within 2 weeks of cessation of therapy 1%, 2%, 5% cream or 2%, 5% solution: Apply 2 times a day in an amount enough to cover the lesions; continue until the inflammatory response reaches the erosion stage, then discontinue use
• Duration of therapy: 2 to 4 weeks; complete healing of the lesions may not be evident for 1 to 2 months following cessation of therapy
• The response starts with erythema?, usually followed by vesiculation, desquamation, erosion and re-epithelialization.
• This drug should not be applied near the eyes, nostrils, or mouth.
• Apply 10 minutes after washing, rinsing, and drying the entire area.
• This drug may be applied using the fingertips.
• Immediately after application, the hands should be thoroughly washed.
• Solar keratoses which do not respond to treatment should be biopsied to confirm the diagnosis?.

Basal Cell Carcinoma

• 5% cream or solution:
• Apply 2 times a day in an amount sufficient to cover the lesions; continue until the inflammatory response reaches the erosion stage, then discontinue use
• Duration of therapy: 3 to 6 weeks; however, therapy may be required for as long as 10 to 12 weeks before lesions are obliterated
• Only a 5% cream or solution is recommended to treat superficial basal cell carcinoma.
• The response starts with erythema, usually followed by vesiculation, desquamation, erosion and re-epithelialization.

Administration advice:

• Apply with a nonmetal applicator or glove; if applied with the fingers, the hands should be washed immediately afterward.
• Avoid contact with mucous membranes, eyelids, eyes, nostrils, or mouth.
• Avoid prolonged exposure to ultraviolet light or sunlight.
• Avoid occlusive dressings unless clinically indicated.

General:

• Deep, penetrating, or nodular basal cell and squamous cell carcinomas do not usually respond to this drug; it should be used only as a palliative therapy in such cases where no other form of treatment is possible.
• The 0.5%, 1%, and 2% strengths should not be used in the treatment of basal cell carcinoma.
• When this drug is applied to a lesion, a response occurs with the following sequence: erythema, usually followed by vesiculation, desquamation, erosion, and reepithelialization

Side Effects

The Most Common

• burning, crusting, redness,
• discoloration, irritation, pain,
• itching?, rash, or
• soreness at the site of application
• severe stomach pain
• bloody diarrhea
• vomiting
• fever
• chills
• severe red skin rash
• Local pain
• Itchiness
• Burning
• Stinging
• Crusting
• Weeping
• Dermatitis
• Photosensitivity

More Common

Drug Interaction

Pregnancy and lactation

AU TGA pregnancy category: D
US FDA pregnancy category: Not assigned.

Pregnancy

This drug can harm a developing fetus when administered to a pregnant woman. No adequate and well-controlled studies have been conducted in pregnant women with either topical or parenteral forms. One birth defect (ventricular septal defect) and cases of miscarriage have been reported when this drug was applied to mucous membrane areas. Multiple birth defects have been reported in the fetus of a patient treated with the IV formulation.

Lactation

Most sources consider breastfeeding to be contraindicated during maternal antineoplastic drug therapy. It might be possible to breastfeed safely during intermittent therapy with an appropriate period of breastfeeding abstinence, but the duration of abstinence is not clear.

References