fluorouracil: prescribing and clinical use
Focused clinical detail for use alongside current product information, local policy and patient-specific assessment.
fluorouracil: clinical details
Prescribing considerations
- Confirm the formulation and licensed indication; systemic and topical products are not interchangeable.
- Test for DPD deficiency before systemic treatment. A negative result does not eliminate severe toxicity risk.
- Assess performance and nutritional status, recent surgery or radiotherapy, infection, marrow reserve, renal and hepatic function, and cardiovascular history.
- Review contraception and fertility-preservation needs.
- For topical treatment, avoid damaged skin, mucosa, periocular application and occlusion.
Contraindications and cautions
- Systemic products: complete DPD deficiency, serious infection, marked debility or poor nutritional state, significant marrow depression, breastfeeding, hypersensitivity, and recent or concurrent brivudine, sorivudine or related antiviral exposure.
- Tolak: pregnancy, breastfeeding, peanut or soya allergy, hypersensitivity to ingredients, and concurrent brivudine, sorivudine or related antivirals.
Monitoring
- Before systemic treatment: DPD status, full blood count, renal and liver function, clinical fitness and interacting medicines.
- During systemic treatment: blood counts, gastrointestinal and mucosal toxicity, infection, hydration, neurological effects, hand-foot reactions and cardiac symptoms.
- Monitor INR with warfarin and phenytoin concentrations when clinically indicated.
- For topical treatment, assess local reaction, eye exposure, infection and possible systemic toxicity. Routine pretreatment DPD testing is not required.
Clinical pharmacology
Fluorouracil is a pyrimidine analogue. Its metabolites inhibit thymidylate synthase, impair DNA synthesis and disrupt RNA function. DPD-mediated catabolism is rate-limiting; reduced activity can substantially increase toxicity.
Formulation and product differences
- Injection solutions are cytotoxic preparations for intravenous injection, intravenous infusion or intra-arterial infusion and require specialist handling.
- Tolak is a topical cream for defined actinic keratosis sites. It contains refined arachis oil and is unsuitable for people allergic to peanut or soya.
- Systemic exposure from correctly applied topical treatment is low, but absorption and toxicity risk can increase through damaged skin or under occlusion.
fluorouracil preparations and strengths
Cream
Route: Cutaneous
Strengths: 40 mg/g, 5%
Injection
Route: Parenteral
Strengths: 25 mg/mL, 50 mg/mL
fluorouracil interactions
The treatment team should review all prescribed, over-the-counter and complementary products.
Brivudine, sorivudine and related antivirals
They inhibit DPD and can cause potentially fatal toxicity. Concurrent use is contraindicated and separation is required.
Folinic acid or calcium folinate
May enhance fluorouracil activity but increase gastrointestinal and blood-related toxicity, requiring careful monitoring.
Sources
These sources were used to prepare and review this medicine page.
Prepared and reviewed by the iatroX editorial team.