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5-fluorouracil [5-FU] (Fluoroplex, Efudex, Adrucel, Carac)

Topical: Tradenames: Fluoroplex, Efudex. Indications: 1) topical - multiple actinic keratosis - 1-2% 5-FU BID to lesions on head & neck - 5% 5-FU BID to other areas - superficial basal cell carcinoma - 5% 5-FU BID for 3-6 weeks - treatment for 10-12 weeks may be necessary - prevention of squamous cell carcinoma skin in high-risk patients [9] - condyloma accuminata - verruca plana - leukoplakia [7] - actinic cheilitis [7] - radiodermatitis [7] 2) systemic chemotherapy for malignancy (Adrucel) - gastrointestinal carcinoma - colorectal carcinoma - esophageal carcinoma - gastric carcinoma - breast cancer - pancreatic cancer - islet cell tumor - head & neck cancer - liver cancer - biliary carcinoma [7] - carcinoid syndrome - bladder cancer - cervical cancer [7] - penile cancer Dosage: Administration: - topical - Wash hands after use. - Do not use occlusive dressings - 5% BID for 2-4 weeks (prevention of SCCS) Cream: 1% (Fluoroplex), 5% (Efudex) Solution: 1% (Fluroplex), 2% (Efudex), 5% (Efudex), 10 mL. Pharmacokinetics: 1) widely distributed 2) penetrates into CSF 3) metabolized in liver 4) eliminated in urine 5) 1/2life is 10-15 minutes Typical response (topical) 1) erythema followed by scaling, tenderness, vesiculation, erosion, ulceration, necrosis, re-epithelialization 2) therapy is continued until the erosion, ulceration, necrosis phase is reached 3) normal skin should show little response to 5-FU 4) initial combination therapy with tretinoin may be indicated 5) complete healing may take 1-2 months & may be hastened by application of topical glucocorticoid after 5-FU has bee discontinued Adverse effects: 1) topical: 1) no systemic toxicity reported 2) one manufacturer lists leukopenia & thrombocytopenia 3) local pain 4) pruritus 5) irritation 6) photosensitivity 2) systemic a) common (> 10%) - diarrhea - heartburn - mucositis, stomatitis - nausea/vomiting - dermatitis - anorexia - alopecia - bone marrow suppression - vasospasm [6] b) not common (1-10%) - GI ulceration, dry skin c) uncommon (< 1%) - shortness of breath, ataxia, paresthesias, cardiac arrhythmias, heart failure, hypotension, headache, hyperpigmentation of the skin, pruritic maculopapular rash, partial loss of fingernails &/or toenails, hyperpigmentation of fingernail &/or toenail bed, myelosuppression, hepatotoxicity, visual disturbances, photosensitivity d) other [3] - severe reaction in patients with DPYD deficiency - stomatitis, leukopenia, thrombocytopenia, hair loss, diarrhea, fever, marked weight loss, cerebellar ataxia, neurologic symptoms, progressing to semicoma - heart failure (rare) from myocardial infarction during treatment [6] - pseudo-porphyria cutanea tarda [6] - cutaneous lupus erythematosus [6] - hand-&-foot syndrome - excessive lacrimation - hyperpigmentation of palms [10] (image) 3) topical 5FU may be lethal if consumed by dog [8] Drug interactions: 1) cimetidine 2) leucovorin Laboratory: - see ARUP consult [5] Mechanism of action: 1) antimetabolite; inhibits thymidylate synthase 2) interferes with DNA synthesis 3) S-phase specific Mechanism of drug resistance: 1) increased activity of target enzyme thymidylate synthase 2) alteration in target enzyme thymidylate synthase

Related

thymidylate synthase; TS; TSase (TYMS, TS, OK/SW-cl29)

General

antineoplastic agent (chemotherapeutic agent) fluoropyrimidine

Properties

MISC-INFO: elimination route LIVER 1/2life 10-15 MINUTES pregnancy-category X

Database Correlations

PUBCHEM correlations

References

  1. AHFS Drug Information, American Society of Health-System Pharmacists, Bethesda, 1998
  2. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  3. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998 Department of Veterans Affairs, VA National Formulary
  4. Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 529, 533
  5. ARUP Consult: 5-Fluorouracil Sensitivity deprecated reference
  6. Medical Knowledge Self Assessment Program (MKSAP) 16, 17, 18. American College of Physicians, Philadelphia 2012, 2015, 2018
  7. Deprecated Reference
  8. FDA Animal & Veterinary Update. Jan 18, 2017 FDA Warns of Illnesses and Deaths in Pets Exposed to Prescription topical (human) cancer treatment: Fluorouracil; http://www.fda.gov/animalveterinary/newsevents/cvmupdates/ucm537434.htm
  9. Harrison P 5-FU Cream Reduces Surgery in High-Risk SCC Patients Medscape - Jan 08, 2018. https://www.medscape.com/viewarticle/891047
  10. Schaefer JK, Ramnath N Fluorouracil-Induced Hyperpigmentation N Engl J Med 2020; 382:e6. Jan 23 PMID: 31971682 https://www.nejm.org/doi/full/10.1056/NEJMicm1909329

Component-of

5 fluorouracil/diclofenac 5 fluorouracil/salicylic acid 5-fluorouracil/irinotecan/leucovorin/oxaliplatin (FOLFIRINOX) 5-fluorouracil/oxaliplatin/leucovorin (FOLFOX) cyclophosphamide/doxorubicin (Adriamycin)/5-fluorouracil (CAF) cyclophosphamide/epirubicin/fluorouracil (CEF, FEC-100) cyclophosphamide/methotrexate/5-fluorouracil (CMF)