Pronunciation:

(flure oh YOOR a sil)

U.S. Brand Names:

Synonyms:

Generic Available:

Canadian Brand Names:

Use:

Pregnancy Risk Factor:

Pregnancy Implications:

Lactation:

Contraindications:

Warnings/Precautions:

Adverse Reactions:

I.V.:

Cardiovascular: Angina, myocardial ischemia, nail changes

Central nervous system: Acute cerebellar syndrome, confusion, disorientation, euphoria, headache, nystagmus

Dermatologic: Alopecia, dermatitis, dry skin, fissuring, palmar-plantar erythrodysesthesia syndrome, pruritic maculopapular rash, photosensitivity, vein pigmentations

Gastrointestinal: Anorexia, bleeding, diarrhea, esophagopharyngitis, nausea, sloughing, stomatitis, ulceration, vomiting

Hematologic: Agranulocytosis, anemia, leukopenia, pancytopenia, thrombocytopenia

Myelosuppression:

Onset: 7-10 days

Nadir: 9-14 days

Recovery: 21-28 days

Local: Thrombophlebitis

Ocular: Lacrimation, lacrimal duct stenosis, photophobia, visual changes

Respiratory: Epistaxis

Miscellaneous: Anaphylaxis, generalized allergic reactions, loss of nails

Topical: Note: Systemic toxicity normally associated with parenteral administration (including neutropenia, neurotoxicity, and gastrointestinal toxicity) has been associated with topical use particularly in patients with a genetic deficiency of dihydropyrimidine dehydrogenase (DPD).

Central nervous system: Headache, telangiectasia

Dermatologic: Photosensitivity, pruritus, rash, scarring

Hematologic: Leukocytosis

Local: Allergic contact dermatitis, burning, crusting, dryness, edema, erosion, erythema, hyperpigmentation, irritation, pain, soreness, ulceration

Ocular: Eye irritation (burning, watering, sensitivity, stinging, itching)

Miscellaneous: Birth defects, miscarriage

Overdosage/Toxicology:

Drug Interactions:

Ethanol/Nutrition/Herb Interactions:

Ethanol: Avoid ethanol (due to GI irritation).

Herb/Nutraceutical: Avoid black cohosh, dong quai in estrogen-dependent tumors.

Stability:

Injection: Store intact vials at room temperature and protect from light; slight discoloration does not usually denote decomposition. If exposed to cold, a precipitate may form; gentle heating to 60°C will dissolve the precipitate without impairing the potency; solutions in 50-1000 mL NS or D5W, or undiluted solutions in syringes are stable for 72 hours at room temperature.

Topical: Store at controlled room temperature.

Compatibility:

Y-site administration: Compatible: Allopurinol, amifostine, aztreonam, bleomycin, cefepime, cisplatin, cyclophosphamide, doxorubicin, doxorubicin liposome, etoposide phosphate, fludarabine, furosemide, gatifloxacin, gemcitabine, granisetron, heparin, hydrocortisone sodium succinate, leucovorin, linezolid, mannitol, melphalan, methotrexate, metoclopramide, mitomycin, paclitaxel, piperacillin/tazobactam, potassium chloride, propofol, sargramostim, teniposide, thiotepa, vinblastine, vincristine, vitamin B complex with C. Incompatible: Amphotericin B cholesteryl sulfate complex, droperidol, filgrastim, ondansetron, topotecan, vinorelbine

Compatibility in syringe: Compatible: Bleomycin, cisplatin, cyclophosphamide, furosemide, heparin, leucovorin, methotrexate, metoclopramide, mitomycin, vinblastine, vincristine. Incompatible: Droperidol, epirubicin. Variable (consult detailed reference): Doxorubicin

Compatibility when admixed: Compatible: Bleomycin, cyclophosphamide, cyclophosphamide with methotrexate, etoposide, floxuridine, hydromorphone, ifosfamide, methotrexate, mitoxantrone, vincristine. Incompatible: Carboplatin, cisplatin, cytarabine, diazepam, doxorubicin, fentanyl, leucovorin, metoclopramide, morphine

Mechanism of Action:

Pharmacodynamics/Kinetics:

Duration: ~3 weeks

Distribution: Vd: ~22% of total body water; penetrates extracellular fluid, CSF, and third space fluids (eg, pleural effusions and ascitic fluid)

Metabolism: Hepatic (90%); via a dehydrogenase enzyme; FU must be metabolized to be active

Bioavailability: <75%, erratic and undependable

Half-life elimination: Biphasic: Initial: 6-20 minutes; two metabolites, FdUMP and FUTP, have prolonged half-lives depending on the type of tissue

Excretion: Lung (large amounts as CO2); urine (5% as unchanged drug) in 6 hours

Dosage:

Refer to individual protocols:

I.V. bolus: 500-600 mg/m² every 3-4 weeks or 425 mg/m² on days 1-5 every 4 weeks

Continuous I.V. infusion: 1000 mg/m²/day for 4-5 days every 3-4 weeks or

2300-2600 mg/m² on day 1 every week or

300-400 mg/m²/day or

225 mg/m²/day for 5-8 weeks (with radiation therapy)

Actinic keratoses: Topical:

Carac™: Apply thin film to lesions once daily for up to 4 weeks, as tolerated

Efudex®: Apply to lesions twice daily for 2-4 weeks; complete healing may not be evident for 1-2 months following treatment

Fluoroplex®: Apply to lesions twice daily for 2-6 weeks

Basal cell carcinoma: Topical: Efudex®: Apply to affected lesions twice daily for 3-6 weeks; treatment may be continued for up to 10-12 weeks

Dosage adjustment for renal impairment: Hemodialysis: Administer dose following hemodialysis.

Dosage adjustment for hepatic impairment: Bilirubin >5 mg/dL: Omit use.

Administration:

I.V.: I.V. bolus as a slow push or short (5-15 minutes) bolus infusion, or as a continuous infusion. Warm to body temperature before using. I.V. formulation may be given orally mixed in water, grape juice, or carbonated beverage. It is generally best to drink undiluted solution, then rinse the mouth. CocaCola® has been recommended as the "best chaser" for oral fluorouracil.

Topical: Apply 10 minutes after washing, rinsing, and drying the affected area. Apply using fingertip (wash hands immediately after application) or nonmetal applicator. Avoid eyes, nostrils, and mouth. Do not cover area with an occlusive dressing.

Monitoring Parameters:

Dietary Considerations:

Patient Education:

Topical: Use as directed; do not overuse. Wash hands thoroughly before and after applying medication. Avoid contact with eyes, nostrils, and mouth. Avoid occlusive dressings; use a porous dressing. May cause local reaction (pain, burning, or swelling); if severe contact prescriber.

Pregnancy/breast-feeding precautions: Inform prescriber if you are pregnant. Do not get pregnant during or for 1 month following therapy. Male: Do not cause a pregnancy. Male/female: Consult prescriber for instruction on appropriate contraceptive measures. This drug may cause severe fetal defects. Breast-feeding is not recommended.

Dental Health: Effects on Dental Treatment:

Dental Health: Vasoconstrictor/Local Anesthetic Precautions:

Mental Health: Effects on Mental Status:

Mental Health: Effects on Psychiatric Treatment:

Oncology: Emetic Potential:

Oncology: Vesicant:

Dosage Forms:

Cream, topical:

Carac™: 0.5% (30 g)

Efudex®: 5% (25 g, 40 g)

Fluoroplex®: 1% (30 g) [contains benzyl alcohol]

Injection, solution: 50 mg/mL (10 mL, 20 mL, 50 mL, 100 mL)

Adrucil®: 50 mg/mL (10 mL, 50 mL, 100 mL)

Solution, topical (Efudex®): 2% (10 mL); 5% (10 mL)

International Brand Names: