fluorouracil (5-FU)
Adrucil, Carac, Efudex, Fluoroplex

Pharmacologic classification: antimetabolite (specific to S phase of cell cycle)
Therapeutic classification: antineoplastic
Pregnancy risk category D (injection), X (topical)

Available forms
Available by prescription only
Cream: 0.5 %, 1%, 5%
Injection: 50 mg/ml in 10-ml, 20-ml, 50-ml, 100-ml vials
Topical solution: 1%, 2%, 5%

Indications and dosages
Dosage and indications may vary. Check current literature for recommended protocol.
 Palliative management of colon, rectal, breast, gastric, pancreatic, ovarian ◇, cervical ◇, bladder ◇, and liver ◇ cancers. Adults and children: 12 mg/kg I.V. for 4 days. Then, if no toxicity occurs, give 6 mg/kg I.V. on days 6, 8, 10, and 12. Maintenance therapy is a repeated course q 30 days. Don’t exceed 800 mg daily (400 mg daily in severely ill patients).
 Actinic or solar keratoses. Adults: Sufficient cream or lotion to cover lesions b.i.d. for 2 to 4 weeks. Usually, 1% preparations are used on head, neck, and chest, 2% and 5% on hands.
 Topical treatment of multiple actinic or solar keratosis of the face and anterior scalp (Carac). Adults age 18 and older: Wash and dry area; wait 10 minutes. Apply a thin layer of medication to skin where lesions appear, daily, for up to 4 weeks.
 Superficial basal cell carcinomas. Adults: 5% solution or cream in a sufficient amount to cover lesion b.i.d. for 3 to 6 weeks, up to 12 weeks.

Antineoplastic action: Fluorouracil exerts cytotoxic activity by acting as an antimetabolite, competing for the enzyme that’s important in the synthesis of thymidine, an essential substrate for DNA synthesis. Therefore, DNA synthesis is inhibited. Drug also inhibits RNA synthesis to a lesser extent.

Absorption: Topical absorption unknown.
Distribution: Widely into all areas of body water and tissues, including tumors, bone marrow, liver, and intestinal mucosa. Fluorouracil crosses the blood-brain barrier to a significant extent.
Metabolism: A small amount is converted in the tissues to the active metabolite, with most of drug degraded in the liver.
Excretion: Metabolites are primarily excreted through the lungs as carbon dioxide. A small portion of a dose is excreted in urine as unchanged drug.

Route Onset Peak Duration
I.V., topical Unknown Unknown Unknown

Contraindications and precautions
Contraindicated in patients hypersensitive to drug, patients who are in a poor nutritional state, patients with bone marrow suppression (WBC counts of 5,000/mm3 or less or platelet counts of 100,000/mm3 or less), patients with potentially serious infections, and patients who have had major surgery within the previous month. Topical 5-FU should be avoided during pregnancy.
  Use cautiously in patients who have had high-dose pelvic radiation therapy or have received alkylating agents. Also use cautiously in patients with widespread neoplastic infiltration of bone marrow and impaired renal or hepatic function.

Drug-drug. Leucovorin calcium, previous treatment with alkylating drugs: May enhance toxicity. Use extremely cautiously.
Drug-lifestyle. Sun exposure: May cause photosensitivity reactions. Advise patient to take precautions.

Adverse reactions
CNS: acute cerebellar syndrome, confusion, disorientation, euphoria, ataxia, headache, weakness, malaise, pain.
CV: myocardial ischemia, angina, thrombophlebitis.
EENT: nystagmus.
GI: stomatitis, GI ulcer (may precede leukopenia), nausea, vomiting, diarrhea, anorexia, GI bleeding.
Hematologic: leukopenia, thrombocytopenia, agranulocytosis, anemia.
Metabolic: hypoalbuminemia because of drug-induced protein malabsorption.
Skin: reversible alopecia, dermatitis, erythema, scaling, pruritus, nail changes, pigmented palmar creases, erythematous contact dermatitis, desquamative rash of hands and feet with long-term use ("hand-foot syndrome").
Other: burning, soreness, suppuration, swelling (with topical use), anaphylaxis.

Effects on lab test results
• May increase alkaline phosphatase, AST, ALT, bilirubin, and LDH levels. May decrease albumin level.
• May increase 5-hydroxyindoleacetic acid in urine. May decrease hemoglobin and WBC, RBC, platelet, and granulocyte counts.

Overdose and treatment
Signs and symptoms of overdose include myelosuppression, diarrhea, alopecia, dermatitis, hyperpigmentation, nausea, and vomiting.
 Treatment is usually supportive and includes transfusion of blood components, antiemetics, and antidiarrheals.
 If Carac is accidentally ingested, induce emesis and perform gastric lavage. Treatment is usually symptomatic and supportive.

Special considerations
• Drug may be administered I.V. push over 1 to 2 minutes.
• Drug may be further diluted in D5W or normal saline solution for infusions up to 24 hours in duration.
• Solution is more stable in plastic I.V. bags than in glass bottles.
• Don’t refrigerate fluorouracil.
• Drug can be diluted in 120 ml of water and administered orally; however, this isn’t an FDA-approved method of administration, and absorption is erratic.
• Topical application to larger ulcerated areas may cause systemic toxicity.
• Do not occlude area.
• Local irritation isn’t markedly increased by extending treatment from 2 to 4 weeks and is generally resolved within 2 weeks of cessation of treatment.
• WBC count nadir occurs 9 to 14 days after first dose; platelet count nadir occurs in 7 to 14 days.
• General photosensitivity occurs for 2 to 3 months after a dose.
• Monitor intake and output, CBC, and renal and hepatic function.
Pregnant patients
• During pregnancy, use drug only for life-threatening or serious situations when no other safe alternatives are available.
Breast-feeding patients
• It isn’t known whether drug appears in breast milk. However, because of potential for serious adverse reactions, mutagenicity, and carcinogenicity in the infant, breast-feeding isn’t recommended.
Pediatric patients
• Safety and efficacy in children haven’t been established.

Patient education
• Warn patient to avoid strong sunlight or ultraviolet light because it will intensify the skin reaction. Encourage use of sunscreens. Advise patient that he may apply sunscreen and moisturizer 2 hours after Carac application.
• Tell patient to avoid exposure to people with infections. Advise patient to promptly report signs of infection or unusual bleeding.
• Reassure patient that hair should grow back after treatment is discontinued.
• Advise patient to apply topical fluorouracil with gloves and wash hands thoroughly after application.
• Warn patient that treated area may be unsightly during therapy and for several weeks after therapy is stopped. Complete healing may not occur until 1 or 2 months after treatment is stopped.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use