Fluoroplex


fluorouracil (5-fluorouracil, 5-FU)

Adrucil, Efudex, Fluoroplex

Pharmacologic class: Antimetabolite

Therapeutic class: Antineoplastic

Pregnancy risk category D

Action

Inhibits DNA and RNA synthesis, leading to death of rapid-growing neoplastic cells. Cell-cycle-S-phase specific.

Availability

Cream: 1%, 5%

Injection: 50 mg/ml in 10-ml ampules and 10-, 20-, and 100-ml vials

Solution: 1%, 2%, 5%

Indications and dosages

➣ Advanced colorectal cancer

Adults: 370 mg/m2 I.V. for 5 days, preceded by leucovorin 200 mg/m2 daily for 5 days; may be repeated q 4 to 5 weeks. No single daily dose should exceed 800 mg.

➣ Colon, rectal, breast, gastric, and pancreatic cancer

Adults: Initially, 12 mg/kg/day I.V. for 4 days; then 6 mg/kg I.V. on days 6, 8, 10, and 12. Maximum dosage is 800 mg/day. For maintenance, start 30 days after last dose. If no toxicity, use dosage from first course. If toxicity occurs, give 10 to 15 mg/kg/week as single dose after toxicity subsides. Don't exceed 1 g/week.

➣ Actinic (solar) keratoses

Adults: 1% solution or cream applied once or twice daily to lesions on head, neck, or chest; 2% to 5% solution or cream may be needed for other areas.

➣ Superficial basal cell carcinoma

Adults: 5% solution or cream applied b.i.d. for 3 to 6 weeks (up to 12 weeks)

Contraindications

• Hypersensitivity to drug or its components

• Bone marrow depression

• Dihydropyrimidine dehydrogenase enzyme deficiency (with topical route)

• Poor nutritional status

• Serious infection

• Pregnancy or breastfeeding

Precautions

Use cautiously in:

• renal or hepatic impairment, infections, edema, ascites

• obese patients.

Administration

See Consult facility's cancer protocols to ensure correct dosage, administration technique, and cycle length.

• Give antiemetic before fluorouracil, as ordered, to reduce GI upset.

• Know that drug may be given without dilution by direct I.V. injection over 1 to 3 minutes.

• For I.V. infusion, dilute with dextrose 5% in water, sterile water, or normal saline solution in plastic bag (not glass bottle). Infusion may be given over a period of 24 hours or more.

See Be aware of the importance of leucovorin rescue with fluorouracil therapy, if prescribed.

• Check infusion site frequently to detect extravasation.

• Use nonmetal applicator or appropriate gloves to apply topical form.

• Avoid applying topical form to mucous membranes or irritated skin.

• Don't use occlusive dressings over topical form.

• Know that pyridoxine may be given with fluorouracil to reduce risk of palmar-plantar erythrodysesthesia (hand-foot syndrome).

Adverse reactions

CNS: confusion, disorientation, euphoria, ataxia, headache, weakness, malaise, acute cerebellar syndrome or dysfunction

CV: angina, myocardial ischemia, thrombophlebitis

EENT: vision changes, photophobia, lacrimation, lacrimal duct stenosis, nystagmus, epistaxis

GI: nausea, vomiting, diarrhea, stomatitis, anorexia, GI ulcer, GI bleeding

Hematologic: anemia, leukopenia, thrombocytopenia

Skin: alopecia, maculopapular rash, melanosis of nails, nail loss, palmar-plantar erythrodysesthesia, photosensitivity, local inflammation reaction (with cream), dermatitis

Other: fever, anaphylaxis

Interactions

Drug-drug. Bone marrow depressants (including other antineoplastics): additive bone marrow depression

Irinotecan: dehydration, neutropenia, sepsis

Leucovorin calcium: increased risk of fluorouracil toxicity

Live-virus vaccines: decreased antibody response to vaccine, increased risk of adverse reactions

Drug-diagnostic tests. Alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, bilirubin, lactate dehydrogenase, urinary 5-hydroxyindoleacetic acid: increased levels

Albumin, granulocytes, platelets, red blood cells, white blood cells (WBCs): decreased levels

Drug-behaviors. Sun exposure: increased risk of phototoxicity

Patient monitoring

See Watch for signs and symptoms of toxicity, especially stomatitis and diarrhea. If these occur, stop drug and notify prescriber. Note that toxicity may take 1 to 3 weeks to develop.

• Monitor CBC, WBC and platelet counts, and kidney and liver function test results.

• Assess fluid intake and output.

• With long-term use, watch for serious rash on hands and feet. If it occurs, consult prescriber regarding need for pyridoxine.

• Assess for bleeding tendency.

• Monitor blood glucose level in patients at risk for hyperglycemia.

Patient teaching

See Emphasize importance of taking leucovorin as prescribed with high-dose therapy.

See Instruct patient to report signs and symptoms of toxicity, particularly stomatitis and diarrhea. Tell him that these may not occur for 1 to 3 weeks.

• Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration and alertness.

• Tell patient to avoid activities that can cause injury. Instruct him to use soft toothbrush and electric razor to avoid gum and skin injury.

• Advise patient to minimize GI upset by eating frequent, small servings of food and drinking adequate fluids.

• Tell patient that drug may cause reversible hair loss.

• Inform patient that he'll undergo regular blood testing during therapy.

See Advise female to inform prescriber immediately if she is pregnant. Caution her not to breastfeed.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, and behaviors mentioned above.

fluorouracil

(flure-oh-yoor-a-sill) fluorouracil,

Carac

(trade name),

Efudex

(trade name),

Fluoroplex

(trade name),

5-FU

(trade name)

Classification

Therapeutic: antineoplastics
Pharmacologic: antimetabolites
Pregnancy Category: D

Indications

Intravenous: Used alone and in combination with other modalities (surgery, radiation therapy, other antineoplastics) in the treatment of:
  • Colon cancer,
  • Breast cancer,
  • Rectal cancer,
  • Gastric cancer,
  • Pancreatic carcinoma.
Topical: Management of multiple actinic (solar) keratoses and superficial basal cell carcinomas.

Action

Inhibits DNA and RNA synthesis by preventing thymidine production (cell-cycle S-phase–specific).

Therapeutic effects

Death of rapidly replicating cells, particularly malignant ones.

Pharmacokinetics

Absorption: Minimal absorption (5–10%) after topical application.Distribution: Widely distributed; concentrates and persists in tumors.Metabolism and Excretion: Metabolized by dihydropyrimidine dehydrogenase to a less toxic compound; inactive metabolites are excreted primarily in urine.Half-life: 20 hr.

Time/action profile (IV = effects on blood counts, Top = dermatologic effects)

ROUTEONSETPEAKDURATION
IV1–9 days9–21 days (nadir)30 days
Top2–3 days2–6 wk1–2 mo

Contraindications/Precautions

Contraindicated in: Hypersensitivity;genetic implication Dihydropyrimidine dehydrogenase deficiency (patients at ↑ risk of 5-FU toxicity); Obstetric / Lactation: Pregnancy or lactation.Use Cautiously in: Infections;Depressed bone marrow reserve;Other chronic debilitating illnesses;Obese patients, patients with edema or ascites (dose should be based on ideal body weight).

Adverse Reactions/Side Effects

More likely to occur with systemic use than with topical use

Central nervous system

  • acute cerebellar dysfunction

Gastrointestinal

  • diarrhea (most frequent)
  • nausea (most frequent)
  • stomatitis (most frequent)
  • vomiting (most frequent)

Dermatologic

  • alopecia (most frequent)
  • maculopapular rash (most frequent)
  • local inflammatory reactions (topical only)
  • melanosis of nails
  • nail loss
  • palmar-plantar erythrodysesthesia
  • phototoxicity

Endocrinologic

  • sterility

Hematologic

  • anemia (most frequent)
  • leukopenia (most frequent)
  • thrombocytopenia (most frequent)

Local

  • thrombophlebitis

Miscellaneous

  • fever

Interactions

Drug-Drug interaction

Combination chemotherapy with irinotecan may produce unacceptable toxicity (dehydration, neutropenia, sepsis).Additive bone marrow depression with other bone marrow depressants, including other antineoplastics and radiation therapy.May ↓ antibody response to live-virus vaccines and ↑ risk of adverse reactions.

Route/Dosage

Doses may vary greatly, depending on tumor, patient condition, and protocol usedAdvanced Colorectal CancerIntravenous (Adults) 370 mg/m2 preceded by leucovorin or 425 mg/m2 preceded by leucovorin daily for 5 days. May be repeated q 4–5 wk.Other TumorsIntravenous (Adults) Initial dose—12 mg/kg/day for 4 days, then 1 day of rest, then 6 mg/kg every other day for 4–5 doses or 7–12 mg/kg/day for 4 days followed by 3-day rest, then 7–10 mg/kg q 3–4 days for 3 doses. Maintenance—7–12 mg/kg q 7–10 days or 300–500 mg/m2/day for 4–5 days, repeated monthly (no single daily dose should exceed 800 mg). Poor-Risk Patients: 3–6 mg/kg/day on days 1–3, 3 mg/kg/day on days 5, 7, 9 (not to exceed 400 mg/dose). Doses of 370–425 mg/m2/day for 5 days have been used in combination with leucovorin.Actinic (Solar) KeratosesTopical (Adults) Carac—Apply 0.5% cream to lesions once daily for up to 4 wk; Efudex—Apply 2% or 5% solution or cream to lesions twice daily for 2–4 wk; Fluoroplex—Apply 1% cream to lesions twice daily for 2–6 wk.Superficial Basal Cell CarcinomasTopical (Adults) Efudex—Apply 5% solution or cream to lesions twice daily for 3–6 wk (up to 12 wk).

Availability (generic available)

Injection: 50 mg/mL Cream: 0.5%, 1%, 5% Solution: 2%, 5%

Nursing implications

Nursing assessment

  • Monitor vital signs before and frequently during therapy.
    • Assess mucous membranes, number and consistency of stools, and frequency of vomiting. Assess for signs of infection (fever, chills, sore throat, cough, hoarseness, pain in lower back or side, difficult or painful urination). Assess for bleeding (bleeding gums; bruising; petechiae; and guaiac test stools, urine, and emesis). Avoid IM injections and taking rectal temperatures. Apply pressure to venipuncture sites for 10 min. Notify health care professional if symptoms of toxicity (stomatitis or esophagopharyngitis, uncontrollable vomiting, diarrhea, GI bleeding, myocardial ischemia, leukocyte count <3500/mm3, platelet count <100,000/mm3, or hemorrhage from any site) occur; drug will need to be discontinued. May be reinitiated at a lower dose when side effects have subsided.
    • Assess IV site frequently for inflammation or infiltration. Patient should notify nurse if pain or irritation at injection site occurs. May cause thrombophlebitis. If extravasation occurs, infusion must be stopped and restarted in another vein to avoid damage to subcut tissue. Report immediately. Standard treatment includes application of ice compresses.
  • Assess skin for palmar-plantar erythrodysesthesia (tingling of hands and feet followed by pain, erythema, and swelling) throughout therapy.
    • Monitor intake and output, appetite, and nutritional intake. GI effects usually occur on 4th day of therapy. Adjusting diet as tolerated may help maintain fluid and electrolyte balance and nutritional status.
    • Monitor patient for cerebellar dysfunction (weakness, ataxia, dizziness). This may persist after discontinuation of therapy.
  • Topical: Inspect involved skin before and throughout therapy.
  • Lab Test Considerations: May cause ↓ in plasma albumin.
    • Monitor hepatic (AST, ALT, LDH, and serum bilirubin), renal, and hematologic (hematocrit, hemoglobin, leukocyte, platelet count) functions before and periodically during therapy. Monitor CBC daily during IV therapy. Report WBC of <3500/mm3 or platelets <100,000/mm3 immediately; they are criteria for discontinuation. Nadir of leukopenia usually occurs in 9–14 days, with recovery by day 30. May also cause thrombocytopenia.
    • May cause ↑ in urine excretion of 5-hydroxyindoleacetic acid (5-HIAA).

Potential Nursing Diagnoses

Risk for infection (Side Effects)
Imbalanced nutrition: less than body requirements (Side Effects)

Implementation

  • high alert: Fatalities have occurred with incorrect administration of chemotherapeutic agents. Before administering, clarify all ambiguous orders; double-check single, daily, and course-of-therapy dose limits; have second practitioner independently double-check original order, calculations, and infusion pump settings. The number 5 in 5-fluorouracil is part of the drug name and does not refer to the dose.
  • Prepare solution in a biologic cabinet. Wear gloves, gown, and mask while handling IV medication. Discard IV equipment in specially designated containers.
  • Intravenous Administration
  • pH: 8.6–9.2.
  • Diluent: May be administered undiluted.Concentration: 50 mg/mL.
  • Rate: Rapid IV push administration (over 1–2 min) is most effective, but there is a more rapid onset of toxicity.
  • Intermittent Infusion: Diluent: May be diluted with D5W or 0.9% NaCl.
    • Use plastic IV tubing and IV bags to maintain greater stability of medication. Solution is stable for 24 hr at room temperature; do not refrigerate. Solution is colorless to faint yellow. Discard highly discolored or cloudy solution. If crystals form, dissolve by warming solution to 140°F, shaking vigorously, and cooling to body temperature.Concentration: Up to 50 mg/mL.
  • Rate: Onset of toxicity is greatly delayed by administering an infusion over 2–8 hr.
  • Y-Site Compatibility: acyclovir, alfentanil, allopurinol, amifostine, amikacin, aminophylline, amphotericin B lipid complex, amphotericin B liposome, ampicillin, ampicillin/sulbactam, anidulafungin, argatroban, azithromycin, aztreonam, bivalirudin, bleomycin, bumetanide, butorphanol, calcium gluconate, carboplatin, carmustine, cefazolin, cefepime, cefoperazone, cefotaxime, cefotetan, cefoxitin, ceftazidime, ceftriaxone, cefuroxime, cisatracurium, cisplatin, clindamycin, cyclophosphamide, cyclosporine, daptomycin, dexamethasone, dexmedetomidine, dexrazoxane, digoxin, docetaxel, dopamine, doripenem, doxorubicin liposome, enalaprilat, ephedrine, ertapenem, erythromycin, esmolol, etoposide phosphate, famotidine, fenoldopam, fentanyl, fluconazole, fludarabine, foscarnet, fosphenytoin, furosemide, ganciclovir, gemcitabine, gentamicin, granisetron, heparin, hetastarch, hydrocortisone, hydromorphone, ifosfamide, imipenem/cilastatin, isoproterenol, ketorolac, labetalol, leucovorin, levorphanol, lidocaine, linezolid, magnesium sulfate, mannitol, melphalan, meperidine, meropenem, mesna, methohexital, methotrexate, methylprednisolone, metoprolol, metronidazole, milrinone, mitomycin, mitoxantrone, morphine, nalbuphine, naloxone, nesiritide, nitroglycerin, nitroprusside, octreotide, paclitaxel, palonsetron, pamidronate, pancuronium, pantoprazole, pemetrexed, pentobarbital, phenobarbital, phenylephrine, piperacillin/tazobactam, potassium acetate, potassium chloride, potassium phosphates, procainamide, propofol, propranolol, ranitidine, remifentanil, rituximab, sargramostim, sodium acetate, sodium bicarbonate, sodium phosphates, succinylcholine, sufentanil, teniposide, theophylline, thiopental, thiotepa, ticarcillin/clavulanate, tigecycline, tirofiban, tobramycin, trastuzumab, vasopressin, vecuronium, vinblastine, vincristine, vitamin B complex with C, voriconazole, zidovudine, zoledronic acid
  • Y-Site Incompatibility: aldesleukin, amiodarone, amphotericin B cholesteryl, amphotericin B colloidal, buprenorphine, calcium chloride, caspofungin, chlorpromazine, ciprofloxacin, diazepam, diltiazem, diphenhydramine, dobutamine, doxycycline, droperidol, epinephrine, epirubicin, filgrastim, haloperidol, hydroxyzine, idarubicin, irinotecan, levofloxacin, lorazepam, midazolam, nicardipine, pentamidine, phenytoin, prochlorperazine, promethazine, quinapristin/dalfopristin, topotecan, vancomycin, verapamil, vinorelbine
  • Topical: Consult health care professional before administering topical preparations to determine which skin preparation regimen should be followed. Tight occlusive dressings are not advised because of irritation to surrounding healthy tissue. A loose gauze dressing for cosmetic purposes is usually preferred. Wear gloves when applying medication. Do not use metallic applicator.

Patient/Family Teaching

  • Instruct patient to notify health care professional if fever; chills; sore throat; signs of infection; yellowing of skin or eyes; abdominal pain; joint or flank pain; swelling of feet or legs; bleeding gums; bruising; petechiae; or blood in urine, stool, or emesis occurs. Caution patient to avoid crowds and persons with known infections. Instruct patient to use soft toothbrush and electric razor. Patients should be cautioned not to drink alcoholic beverages or take products containing aspirin or NSAIDs.
    • Advise patient to rinse mouth with clear water after eating and drinking and to avoid flossing to minimize stomatitis. Viscous lidocaine may be used if mouth pain interferes with eating. Stomatitis pain may require treatment with opioid analgesics.
    • Discuss with patient the possibility of hair loss. Explore methods of coping.
    • Review with patient the need for contraception during therapy.
    • Caution patient to use sunscreen and protective clothing to prevent phototoxicity reactions.
    • Instruct patient not to receive any vaccinations without advice of health care professional.
    • Emphasize the importance of routine follow-up lab tests to monitor progress and to check for side effects.
  • Topical: Instruct patient in correct application of solution or cream. Emphasize importance of avoiding the eyes; caution should also be used when applying medication near mouth and nose. If patient uses clean finger to self-administer, emphasize importance of washing hands thoroughly after application. Explain that erythema, scaling, and blistering with pruritus and burning sensation are expected. Advise patient to avoid sunlight or ultraviolet light (tanning booths) as much as possible; may increase side effects. Therapy is discontinued when erosion, ulceration, and necrosis occur in 2–6 wk (10–12 wk for basal cell carcinomas). Skin heals 4–8 wk later.

Evaluation/Desired Outcomes

  • Tumor regression.
  • Removal of solar keratoses or superficial basal cell skin cancers.