EFUDEX

Clinical safety rating: caution

Comprehensive clinical and safety monograph for EFUDEX (EFUDEX).

How it works

Fluorouracil (5-FU) is a pyrimidine analog that inhibits thymidylate synthase, leading to depletion of thymidine triphosphate and disruption of DNA synthesis. It is incorporated into RNA as a false metabolite, interfering with RNA processing and function.

What the body does with it

Metabolism	Metabolized via dihydropyrimidine dehydrogenase (DPD) to dihydrofluorouracil, then further catabolized to alpha-fluoro-beta-alanine (FBAL). Approximately 80% of the drug is eliminated via the liver and kidneys.
Excretion	Primarily hepatic metabolism to inactive metabolites; <15% excreted unchanged in urine; biliary/fecal excretion accounts for ~15%.
Half-life	Terminal half-life is approximately 16 minutes (range 8-20 min) for parent drug; clinical context: due to rapid metabolism, continuous infusion or frequent dosing is required for sustained antimetabolite effect.
Protein binding	Less than 10% bound to plasma proteins (primarily albumin).
Volume of Distribution	0.1-0.6 L/kg; small Vd indicates limited extravascular distribution, consistent with rapid metabolism.
Bioavailability	Topical: limited systemic absorption (<10% of topically applied dose); oral: not available; IV: 100%.
Onset of Action	Topical: clinical effect (e.g., erythema, erosion) typically seen within 2-4 weeks of daily application; IV: not applicable for systemic use in this formulation.
Duration of Action	Topical: therapeutic effect lasts 2-6 weeks; clinical notes: repeated courses may be needed; systemic: not applicable for IV due to rapid clearance.

Classification & Brands

Dosing & administration

For actinic keratosis: Apply topically to lesions twice daily for 2-4 weeks. For superficial basal cell carcinoma: Apply 5% cream twice daily for 3-6 weeks. Not for systemic use.

Dosage form	CREAM
Renal impairment	No specific guidelines. Use with caution in severe renal impairment due to potential for systemic absorption.
Liver impairment	No specific guidelines. Caution in severe hepatic impairment as fluorouracil is hepatically metabolized.
Pediatric use	Safety and efficacy not established; no standard pediatric dosing.
Geriatric use	No specific dose adjustment; use with caution due to potential for increased systemic absorption from thinner skin.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for EFUDEX (EFUDEX).

Breastfeeding	Contraindicated during breastfeeding. No data on excretion in human milk; potential for serious adverse reactions in nursing infants. M/P ratio unknown.
Teratogenic Risk	FDA Pregnancy Category X. First trimester: High risk of fetal malformations including neural tube defects, craniofacial abnormalities, and limb defects. Second and third trimesters: Continued risk of teratogenicity, including growth retardation and fetal death. Contraindicated in all trimesters.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

Boxed warning for hypersensitivity reactions, particularly in patients with dihydropyrimidine dehydrogenase (DPD) deficiency, which can lead to severe, life-threatening toxicity including myelosuppression, neurotoxicity, and gastrointestinal bleeding.

Side Effect Profile

Serious Effects

Absolute Contraindications

Absolute: Known DPD deficiency, severe hypersensitivity to fluorouracil or any component. Relative: Pregnancy, lactation, active infection, compromised bone marrow function.

Clinical Precautions

Precautions	Monitor for myelosuppression; discontinue if severe bone marrow suppression occurs. Use with caution in patients with impaired renal or hepatic function. Avoid use in pregnant women due to teratogenicity. May cause photosensitivity; avoid excessive UV exposure.
Food/Dietary	No significant food interactions known for topical EFUDEX. Avoid ingestion or contact with food.

Clinical Tips & Counseling

Drug interactions

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EFUDEX

Clinical safety rating: caution

Comprehensive clinical and safety monograph for EFUDEX (EFUDEX).

How it works

What the body does with it

Metabolism	Metabolized via dihydropyrimidine dehydrogenase (DPD) to dihydrofluorouracil, then further catabolized to alpha-fluoro-beta-alanine (FBAL). Approximately 80% of the drug is eliminated via the liver and kidneys.
Excretion	Primarily hepatic metabolism to inactive metabolites; <15% excreted unchanged in urine; biliary/fecal excretion accounts for ~15%.
Half-life	Terminal half-life is approximately 16 minutes (range 8-20 min) for parent drug; clinical context: due to rapid metabolism, continuous infusion or frequent dosing is required for sustained antimetabolite effect.
Protein binding	Less than 10% bound to plasma proteins (primarily albumin).
Volume of Distribution	0.1-0.6 L/kg; small Vd indicates limited extravascular distribution, consistent with rapid metabolism.
Bioavailability	Topical: limited systemic absorption (<10% of topically applied dose); oral: not available; IV: 100%.
Onset of Action	Topical: clinical effect (e.g., erythema, erosion) typically seen within 2-4 weeks of daily application; IV: not applicable for systemic use in this formulation.
Duration of Action	Topical: therapeutic effect lasts 2-6 weeks; clinical notes: repeated courses may be needed; systemic: not applicable for IV due to rapid clearance.

Classification & Brands

Dosing & administration

For actinic keratosis: Apply topically to lesions twice daily for 2-4 weeks. For superficial basal cell carcinoma: Apply 5% cream twice daily for 3-6 weeks. Not for systemic use.

Dosage form	CREAM
Renal impairment	No specific guidelines. Use with caution in severe renal impairment due to potential for systemic absorption.
Liver impairment	No specific guidelines. Caution in severe hepatic impairment as fluorouracil is hepatically metabolized.
Pediatric use	Safety and efficacy not established; no standard pediatric dosing.
Geriatric use	No specific dose adjustment; use with caution due to potential for increased systemic absorption from thinner skin.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for EFUDEX (EFUDEX).

Breastfeeding	Contraindicated during breastfeeding. No data on excretion in human milk; potential for serious adverse reactions in nursing infants. M/P ratio unknown.
Teratogenic Risk	FDA Pregnancy Category X. First trimester: High risk of fetal malformations including neural tube defects, craniofacial abnormalities, and limb defects. Second and third trimesters: Continued risk of teratogenicity, including growth retardation and fetal death. Contraindicated in all trimesters.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

Side Effect Profile

Serious Effects

Absolute Contraindications

Absolute: Known DPD deficiency, severe hypersensitivity to fluorouracil or any component. Relative: Pregnancy, lactation, active infection, compromised bone marrow function.

Clinical Precautions

Precautions	Monitor for myelosuppression; discontinue if severe bone marrow suppression occurs. Use with caution in patients with impaired renal or hepatic function. Avoid use in pregnant women due to teratogenicity. May cause photosensitivity; avoid excessive UV exposure.
Food/Dietary	No significant food interactions known for topical EFUDEX. Avoid ingestion or contact with food.

Clinical Tips & Counseling

Drug interactions

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Clinical Pearls	EFUDEX (fluorouracil) 5% cream is a topical antimetabolite used for actinic keratoses. Apply thin film to lesions; avoid healthy skin. Inflammatory reaction indicates therapeutic effect. Use occlusive dressing only if directed. Contraindicated in pregnant or nursing women.
Patient Advice	Wash hands before and after application. · Apply only to affected areas; avoid eyes, nostrils, and mouth. · Expect redness, crusting, peeling, or burning during treatment. · Use sun protection; avoid tanning beds. · Do not use in pregnancy or breastfeeding. · Complete full treatment course even if lesions appear worse.