oh YOOR a
|Adrucil® Injection; Efudex®
Antineoplastic Agent, Antimetabolite
Treatment of carcinoma of stomach, colon, rectum, breast, and pancreas; also
used topically for management of multiple actinic keratoses and superficial
basal cell carcinomas
D (injection); X (topical)
Hypersensitivity to fluorouracil or any component, poor nutritional status,
bone marrow depression, or potentially serious infections; pregnancy with
The U.S. Food and Drug Administration (FDA) currently recommends that
procedures for proper handling and disposal of antineoplastic agents be
considered. Use with caution in patients with impaired kidney or liver function.
The drug should be discontinued if intractable vomiting or diarrhea, precipitous
falls in leukocyte or platelet counts, stomatitis, hemorrhage, or myocardial
ischemia occurs. Use with caution in patients who have had high-dose pelvic
radiation or previous use of alkylating agents. Patient should be hospitalized
during initial course of therapy.
Toxicity depends on route and duration of infusion
Dermatologic: Dermatitis, pruritic maculopapular rash, alopecia
Gastrointestinal (route and schedule dependent): Heartburn, nausea, vomiting,
anorexia, stomatitis, esophagitis, anorexia, stomatitis, and diarrhea; bolus
dosing produces milder GI problems, while continuous infusion tends to produce
severe mucositis and diarrhea; vomiting is moderate, occurring in 30% to 60% of
patients, and responds well to phenothiazines and dexamethasone
<1000 mg: Moderately low (10% to 30%)
greater than or equal to 1000 mg: Moderate (30% to 60%)
Hematologic: Myelosuppressive: Granulocytopenia occurs around 9-14 days after
5-FU and thrombocytopenia around 7-17 days. The marrow recovers after 22 days.
Myelosuppression tends to be more pronounced in patients receiving bolus dosing
Platelets: Mild to moderate
Onset (days): 7-10
Nadir (days): 14
Recovery (days): 21
1% to 10%:
Dermatologic: Dry skin
Gastrointestinal: GI ulceration
<1%: Hypotension, chest pain, EKG changes similar to ischemic changes, and
possibly cardiac enzyme abnormalities. Usually occurs within the first two days
of therapy, and may resolve with nitroglycerin and calcium channel blockers. May
be due to coronary vessel vasospasm induced by 5-FU.
Cerebellar ataxia, headache, somnolence, ataxia are seen primarily in
intracarotid arterial infusions for head and neck tumors. This is believed to be
caused by fluorocitrate, a neurotoxic metabolite of the parent compound.
Pruritic maculopapular rash, alopecia, hyperpigmentation of nailbeds, face,
hands, and veins used in infusion; photosensitization with UV light;
palmar-plantar syndrome (hand-foot syndrome); coagulopathy, hepatotoxicity,
conjunctivitis, tear duct stenosis, excessive lacrimation, visual disturbances,
shortness of breath
Symptoms of overdose include myelosuppression, nausea, vomiting, diarrhea,
No specific antidote exists; monitor hematologically for at least 4 weeks;
Methotrexate: This interaction is schedule dependent; 5-FU should be
given following MTX, not prior to
If MTX is given first: The cells exposed to MTX before 5-FU have a depleted
reduced folate pool which inhibits the binding of the 5dUMP to TS. However, it
does not interfere with FUTP incorporation into RNA. Polyglutamines, which
accumulate in the presence of MTX may be substituted for the folates and allow
binding of FdUMP to TS. MTX given prior to 5-FU may actually activate 5-FU due
to MTX inhibition of purine synthesis.
If 5-FU is given first: 5-FU inhibits the TS binding and thus the reduced
folate pool is not depleted, thereby negating the effect of MTX
Increased effect: Leucovorin:
the folate pool and
in certain tumors, may promote TS inhibition and
activity. Must be given before or with the 5-FU to prime the cells; it is not
used as a rescue agent in this case.
Allopurinol: Inhibits thymidine phosphorylase (an enzyme that activates
5-FU). The antitumor effect of 5-FU appears to be unaltered, but decreases
Cimetidine: Results in increased plasma levels of 5-FU due to drug metabolism
inhibition and reduction of liver blood flow induced by cimetidine
Store intact vials at room temperature and protect from light; slight
discoloration does not usually denote decomposition
Further dilution in D5W or NS at concentrations of 0.5-10 mg/mL
are stable for 72 hours at 4°C to
Incompatible with cytarabine, diazepam, doxorubicin, methotrexate;
concentrations of >25 mg/mL of fluorouracil and >2 mg/mL of leucovorin are
incompatible (precipitation occurs)
Compatible with vincristine, methotrexate, potassium chloride,
Standard I.V. dilution: I.V. push: Dose/syringe (concentration: 50
Maximum syringe size for IVP is a 30 mL syringe and syringe should be <75%
CIV/IVPB: Dose/50-1000 mL D5W or NS
Syringe and solution are stable for 72 hours at 4°C to
A pyrimidine antimetabolite that interferes with DNA synthesis by blocking
the methylation of deoxyuridylic acid; 5-FU rapidly enters the cell and is
activated to the nucleotide level; there it inhibits thymidylate synthetase
(TS), or is incorporated into RNA (most evident during the GI phase of the cell
cycle). The reduced folate cofactor is required for tight binding to occur
between the 5-FdUMP and TS.
Duration: ~3 weeks
Absorption: Oral: Erratic and rarely used
Distribution: Vd: ~22% of total body water; penetrates the
extracellular fluid, CSF, and third space fluids (such as pleural effusions and
Metabolism: 5-FU must be metabolized to be active. 90% metabolized;
accomplished by a dehydrogenase enzyme primarily found in the liver; dose may
need to be omitted in patients with liver failure (bilirubin >5 mg/dL)
Bioavailability: <75%, erratic and undependable
Half-life (biphasic): Initial: 6-20 minutes; doses of 400-600
mg/m2 produce drug concentrations above the threshold for
cytotoxicity for normal tissue and remain there for 6 hours; 2 metabolites,
FdUMP and FUTP, have prolonged half-lives depending on the type of tissue; the
clinical effect of these metabolites has not been determined
Elimination: 5% of dose excreted as unchanged drug in the urine in 6 hours,
and a large amount excreted as CO2 from the lung
Refer to individual protocols
Children and Adults:
I.V.: Initial: 400-500 mg/m2/day (12 mg/kg/day; maximum: 800
mg/day) for 4-5 days either as a single daily I.V. push or 4-day CIV
I.V.: Maintenance dose regimens:
200-250 mg/m2 (6 mg/kg) every other day for 4 days repeated in 4
500-600 mg/m2 (15 mg/kg) weekly as a CIV or I.V. push
I.V.: Concomitant with leucovorin:
370 mg/m2/day x 5 days
500-1000 mg/m2 every 2 weeks
600 mg/m2 weekly for 6 weeks
Although the manufacturer recommends no daily dose >800 mg, higher doses
of up to 2 g/day are routinely administered by CIV; higher daily doses have been
Hemodialysis: Administer dose posthemodialysis
Dosing adjustment/comments in hepatic impairment: Bilirubin >5
mg/dL: Omit use
Actinic or solar keratosis: Apply twice daily for 2-6 weeks
Superficial basal cell carcinomas: Apply 5% twice daily for at least 3-6
weeks and up to 10-12 weeks
Use of acidic solutions such as orange juice or other fruit juices to dilute
5-FU for oral administration may result in precipitation of the drug and
decreased absorption; increase dietary intake of thiamine
CBC with differential and platelet count, renal function tests, liver
|Mental Health: Effects
on Mental Status|
May cause drowsiness
Effects on Psychiatric
Myelosuppression is common; use caution with clozapine and
|Dental Health: Local
No information available to require special precautions
Effects on Dental Treatment|
No effects or complications reported
Avoid alcohol and all OTC drugs unless approved by your oncologist. Maintain
adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid
intake) and nutrition (small frequent meals may help). You may experience
sensitivity to sunlight (use sunblock, wear protective clothing, or avoid direct
sunlight); susceptibility to infection (avoid crowds or infected persons or
persons with contagious diseases); nausea, vomiting, diarrhea, or loss of
appetite (frequent small meals may help - request medication); weakness,
lethargy, dizziness, decreased vision (use caution when driving or engaging in
tasks requiring alertness until response to drug is known); headache (request
medication). Report signs and symptoms of infection (eg, fever, chills, sore
throat, burning urination, vaginal itching or discharge, fatigue, mouth sores);
bleeding (eg, black or tarry stools, easy bruising, unusual bleeding); vision
changes; unremitting nausea, vomiting, or abdominal pain; CNS changes;
respiratory difficulty; chest pain or palpitations; severe skin reactions to
topical application; or any other adverse reactions.
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.
Cool to body temperature before using; after vial has been entered, any
unused portion should be discarded within 1 hour; wash hands immediately after
topical application of the 5% cream; I.V. formulation may be given orally mixed
in water, grape juice, or carbonated beverage
Efudex®: 5% (25 g)
Fluoroplex®: 1% (30 g)
Injection (Adrucil®): 50 mg/mL (10 mL, 20 mL, 50 mL,
Efudex®: 2% (10 mL); 5% (10 mL)
Fluoroplex®: 1% (30 mL)
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