A-Z Drug Facts > Fluorouracil

Fluorouracil

Pronouncation: (FLURE-oh-YOUR-uh-sill)
Class: Pyrimidine antimetabolite

Trade Names:
Adrucil
- Injection 50 mg/mL

Trade Names:
Carac
- Cream 0.5%

Trade Names:
Efudex
- Cream 5%
- Solution 2%
- Solution 5%

Trade Names:
Fluoroplex
- Cream 1%

Pharmacology

The metabolism of fluorouracil in the anabolic pathway blocks the methylation reaction of deoxyuridylic acid to thymidylic acid. In this manner, fluorouracil interferes with the synthesis of DNA and to a lesser extent inhibits the formation of RNA.

Pharmacokinetics

Distribution

Fluorouracil distributes into tumors, intestinal mucosa, bone marrow, liver, CSF, and brain tissue.

Metabolism

Metabolization takes place primarily in the liver; catabolic metabolism results in inactive degradation products.

Elimination

The parent drug is excreted unchanged (7% to 20%) in the urine in 6 h. The mean t _½ is about 16 min (range, 8 to 20 min) and is dose dependent.

Indications and Usage

Colon, rectum, breast, gastric, and pancreatic carcinoma (injection); multiple actinic or solar keratoses, superficial basal cell carcinoma (topical).

Unlabeled Uses

Ovarian, cervical, bladder, hepatic, islet cell, prostate, endometrial, esophageal, and head and neck carcinoma.

Contraindications

Poor nutritional status; depressed bone marrow function; potentially serious infections; hypersensitivity to fluorouracil or product components; pregnancy (topical); dihydropyrimidine dehydrogenase enzyme (DPD) deficiency ( Carac ).

Dosage and Administration

Colon, Rectum, Breast, Gastric, and Pancreatic Carcinomas
Adults

IV Individualize dosage based on actual body weight. Use lean body weight if patient is obese or has abnormal fluid retention.

Initial dose

12 mg/kg/day for 4 days. Do not exceed 800 mg/day. If no toxicity is observed, give 6 mg/kg on days 6, 8, 10, and 12. No therapy is given on days 5, 7, 9, or 11. Discontinue at end of day 12, even with no apparent toxicity.

In poor risk patients and those with inadequate nutritional status

6 mg/kg/day for 3 days. If no toxicity is observed, give 3 mg/kg on days 5, 7, and 9. Give no therapy on days 4, 6, or 8. Do not exceed 400 mg/day.

Maintenance therapy

Start maintenance therapy 30 days after the last dose. If no toxicity is observed with the first course of therapy, repeat that dose of fluorouracil at 30-day intervals. If toxicity is observed with the first course of therapy, after the patient has recovered from initial toxicity, use a single weekly dose of 10 to 15 mg/kg. Do not exceed a weekly maintenance dose of 1,000 mg. Poor risk patients may require a reduced maintenance dose.

Multiple Actinic or Solar Keratoses
Adults

Topical Apply enough medication to cover affected areas twice daily for 2 to 6 wk. Complete healing may not occur until 1 to 2 mo after therapy is stopped. Continue medication until the inflammatory response reaches the erosion stage.

Carac

The 0.5% cream is only indicated for the face and anterior scalp areas. Using fingertips, apply every day to cover lesions with a thin film. Do not apply near eyes, nostrils, or mouth. Apply 10 min after thoroughly washing, rinsing, and drying the entire area. After application, wash hands thoroughly. Continued treatment up to 4 wk results in greater lesion reduction.

Superficial Basal Cell Carcinoma (5% Strength Only)
Adults

Topical Apply a sufficient amount to cover the lesions twice daily for 3 to 6 wk. Treatment may be required for 10 to 12 wk.

Drug Interactions

Cimetidine

May increase serum concentrations of fluorouracil and potentially increase toxicity.

Leucovorin

Leucovorin may enhance GI toxicity of fluorouracil. Fatalities have occurred because of severe toxic enterocolitis.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Adrucil

Myocardial ischemia, angina.

CNS

Adrucil

Acute cerebellar syndrome (may persist following discontinuation treatment); nystagmus; headache; disorientation; confusion; euphoria.

Carac

Headache (3%).

Dermatologic

Adrucil

Alopecia; dermatitis (pruritic maculopapular rash usually appearing on extremities and less frequently on the trunk); dry skin; fissuring; photosensitivity (erythema or increased pigmentation of the skin); vein pigmentation; palmar-plantar erythrodysesthesia syndrome (tingling of the hands and feet followed by pain, erythema, and swelling).

Carac

Application-site reaction (95%); erythema (93%); dryness (83%); burning (75%); erosion, pain (44%); irritation (1%).

Efudex

Ulceration (most frequent); burning; crusting; allergic contact dermatitis; erosions; erythema; hyperpigmentation; irritation; pain; photosensitivity; pruritus; scarring; rash; soreness.

Fluoroplex

Pain; pruritus; burning; irritation; inflammation; allergic contact dermatitis; telangiectasia.

EENT

Adrucil

Lacrimal duct stenosis; visual changes; lacrimation; photophobia.

Carac

Eye irritation (5%); sinusitis (2%).

GI

Adrucil

Stomatitis; esophagopharyngitis (which may lead to sloughing and ulceration), diarrhea; anorexia; nausea; emesis (most common); GI ulceration; bleeding.

Hematologic

Adrucil

Leukopenia (lowest WBC counts most commonly seen between the 9th and 14th days after first course of treatment, maximal depression may be delayed for as long as 20 days, count usually returns to normal by the 30th day); pancytopenia; thrombocytopenia; agranulocytosis; anemia.

Efudex

Leukocytosis (frequent); eosinophilia; thrombocytopenia; toxic granulation (infrequent).

Hypersensitivity

Adrucil

Anaphylaxis; generalized allergic reactions.

Miscellaneous

Adrucil

Thrombophlebitis; epistaxis; mail changes (including loss of nails).

Carac

Edema (35%); common cold (2%); allergy (1%).

Efudex

Cases of miscarriage/birth defect (ventricular septal defect) when applied to mucous membranes.

Precautions

Warnings Hospitalization recommended for first course of injection therapy because of the possibility of severe toxic reactions.

Pregnancy

Category D (injection); Category X (topical).

Lactation

Undetermined.

Children

Safety and efficacy not established.

Hypersensitivity

The potential for delayed hypersensitivity exists (topical).

Special Risk Patients

Use with extreme caution in poor-risk patients who have had high-dose pelvic irradiation or previous use of alkylating agents, who have widespread involvement of bone marrow by metastatic tumors, or impaired hepatic or renal function.

Photosensitivity

Avoid exposure to ultraviolet (UV) rays because the intensity of the reaction may be increased.

Discontinue use

Discontinue if the following signs of toxicity occur: stomatitis or esophagopharyngitis (at first visible sign); rapidly falling WBC count; leukopenia (WBC less than 3,500/mm ³ ); intractable vomiting; diarrhea or frequent bowel movements; GI ulceration and bleeding; thrombocytopenia (platelets less than 100,000/mm ³ ); hemorrhage.

DPD deficiency ( Carac and Adrucil )

Rarely, severe toxicity (eg, stomatitis, diarrhea, neutropenia, neurotoxicity) has been attributed to DPD deficiency.

Extravasation

Can cause local irritation or phlebitis. Refer to your institution-specific protocol.

Hand-foot syndrome (injection)

May occur; characterized as a tingling sensation of hands and feet which progress over the next few days to pain when holding objects or walking. Interruption of therapy is followed by gradual resolution over 5 to 7 days.

Obese/Edematous patients

Base dose on body surface area in obese or edematous patients.

Topical use

Avoid application to mucous membranes because of possibility of local inflammation and ulceration. Occlusive dressing may increase the incidence of inflammatory reactions.

Toxicity

Severe toxicity, including hematologic, GI hemorrhage, and death, have occurred.

Overdosage

Symptoms

Nausea, vomiting, diarrhea, GI ulceration and bleeding, bone marrow depression (including thrombocytopenia, leukopenia, agranulocytosis).

Patient Information

• Caution women of childbearing potential to avoid becoming pregnant while being treated.

• Injection
• Advise patient that medication will usually be prepared and administered by a health care professional in a health care setting but that home administration may be possible in some situations.
• If administering at home, ensure that the patient or caregiver understands how to store, prepare, and administer the dose and dispose of used equipment and supplies.
• Advise patient to notify health care provider if any of the following occur: diarrhea with 4 to 6 stools per day or diarrhea at night; sores in the mouth; persistent vomiting; redness, swelling, and pain of the hands or feet; fever, chills, or other signs of infection.
• Advise patient that hair loss and skin reactions (dermatitis) occur frequently during treatment but that these effects are reversible once therapy has been discontinued.

• Topical Solution and Cream
• Teach patient or caregiver proper technique for applying solution or cream.
• Instruct patient, unless advised differently by health care provider, to apply twice daily until ulceration of application site occurs and then discontinue use of solution or cream.
• Advise patient or caregiver that response to therapy is slow and may take several weeks with complete healing taking up to 1 to 2 mo to occur following discontinuation of therapy.
• Advise patient or caregiver that most common adverse reactions are application-site reactions (eg, burning, swelling, irritation) and to inform health care provider if reaction occurs and is intolerable.
• Advise patient or caregiver that treated areas may be unsightly during therapy and for several weeks following therapy and that area may be covered with a gauze wrap for cosmetic reasons. Caution patient not to cover area with an occlusive wrap.
• Caution patient to avoid prolonged or unnecessary exposure to UV light (eg, sunlight, tanning booths) while under treatment with fluorouracil to prevent increasing intensity of skin reaction to medication.
• Instruct patient to avoid contact with eyes, nose, mouth, and mucous membranes, or inflamed skin.
• Instruct patient to wash hands immediately after applying topical medication.

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