5 Fluorouracil

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Contents 1 Introduction 2 Indications 3 Dosage 4 Pharmacokinetics 5 Adverse-effects 6 Drug-interactions 7 Mechanism-of-action 8 More General Terms 9 Additional Terms 10 Internet Database 11 References

Introduction

• Topical: Tradenames: Fluoroplex, Efudex.

Indications

• 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

• condyloma accuminata
• verruca plana
• breast carcinoma
• gastrointestinal carcinoma

• colorectal carcinoma
• esophageal carcinoma
• gastric carcinoma

• Systemic therapy: (Adrucel)

• colorectal cancer
• breast cancer
• esophageal cancer
• gastric cancer
• pancreatic cancer
• head & neck cancer
• liver cancer

Dosage

• Administration:

• topical

• Wash hands after use.
• Do not use occlusive dressings
  

• Cream: 1% ( Fluoroplex), 5% ( Efudex)
• Solution: 1% (Fluroplex), 2% (Efudex), 5% (Efudex), 10 mL.

Pharmacokinetics

• widely distributed
• penetrates into CSF
• metabolized in liver
• eliminated in urine
• 1/2life is 10-15 minutes
  

• Typical response (topical)

• erythema followed by scaling, tenderness, vesiculation, erosion, ulceration, necrosis, re- epithelialization
• therapy is continued until the erosion, ulceration, necrosis phase is reached
• normal skin should show little response to 5- FU
• initial combination therapy with tretinoin may be indicated
• complete healing may take 1-2 months & may be hastened by application of topical glucocorticoid after 5- FU has bee discontinued
  

• elimination via liver
• 1/2life = 10-15 minutes

Adverse-effects

• topical:

• no systemic toxicity reported
• one manufacturer lists leukopenia & thrombocytopenia
• local pain
• pruritis
• irritation
• photosensitivity

• systemic

• common (> 10%)

• diarrhea
• heartburn
• stomatitis
• nausea/vomiting
• dermatitis
• anorexia
• alopecia
• bone marrow suppression

• not common (1-10%)

• GI ulceration, dry skin

• 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

• other [3]

• mucositis
• excessive lacrimation
• severe reaction in patients with DPYD deficiency
• stomatitis, leukopenia, thrombocytopenia, hair loss, diarrhea, fever, marked weight loss, cerebellar ataxia, neurologic symptoms, progressing to semicoma

Drug-interactions

• cimetidine
• leucovorin

Mechanism-of-action

• antimetabolite; inhibits thymidylate synthase
• interferes with DNA synthesis
• S-phase specific
  

• Mechanism of drug resistance:

• increased activity of target enzyme thymidylate synthase
• alteration in target enzyme thymidylate synthase

More General Terms

• uracil (U)
• antineoplastic agent (chemotherapeutic agent)
• pyrimidine analog

Additional Terms

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

Internet Database

PubChem: 5281053
PubChem: 3385

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