Clinical medicine profile
Fluorouracil
Nucleoside Metabolic Inhibitor [EPC]
- Route
- See product SmPC
- Schedule
- POM
- ATC
- Not assigned
- PPB status
- registered
Safety essentials
The information most likely to change a prescribing or dispensing decision.
Contraindications
- CONTRAINDICATIONS Fluorouracil Cream may cause fetal harm when administered to a pregnant woman.
- There are no adequate and well-controlled studies in pregnant women with either the topical or the parenteral forms of fluorouracil.
- One birth defect (cleft lip and palate) has been reported in the newborn of a patient using Fluorouracil Cream as recommended.
- One birth defect (ventricular septal defect) and cases of miscarriage have been reported when Fluorouracil Cream was applied to mucous membrane areas.
- Multiple birth defects have been reported in a fetus of a patient treated with intravenous fluorouracil.
- Animal reproduction studies have not been conducted with Fluorouracil Cream.
- Fluorouracil administered parenterally has been shown to be teratogenic in mice, rats, and hamsters when given at doses equivalent to the usual human intravenous dose
- however, the amount of fluorouracil absorbed systemically after topical administration to actinic keratoses is minimal (see CLINICAL PHARMACOLOGY ).
- Fluorouracil exhibited maximum teratogenicity when given to mice as single intraperitoneal injections of 10 to 40 mg/kg on Day 10 or 12 of gestation.
- Similarly, intraperitoneal doses of 12 to 37 mg/kg given to rats between Days 9 and 12 of gestation and intramuscular doses of 3 to 9 mg/kg given to hamsters between Days 8 and 11 of gestation were teratogenic and/or embryotoxic (i.e., resulted in increased resorptions or embryolethality).
- In monkeys, divided doses of 40 mg/kg given between Days 20 and 24 of gestation were not teratogenic.
- Doses higher than 40 mg/kg resulted in abortion.
Precautions
- WARNINGS Application to mucous membranes should be avoided due to the possibility of local inflammation and ulceration.
- Additionally, cases of miscarriage and a birth defect (ventricular septal defect) have been reported when Fluorouracil Cream was applied to mucous membrane areas during pregnancy.
- Occlusion of the skin with resultant hydration has been shown to increase percutaneous penetration of several topical preparations.
- If any occlusive dressing is used in treatment of basal cell carcinoma, there may be an increase in the severity of inflammatory reactions in the adjacent normal skin.
- A porous gauze dressing may be applied for cosmetic reasons without increase in reaction.
- Exposure to ultraviolet rays should be minimized during and immediately following treatment with Fluorouracil Cream because the intensity of the reaction may be increased.
- Patients should discontinue therapy with Fluorouracil Cream if symptoms of DPD enzyme deficiency develop (see CONTRAINDICATIONS ).
- Rarely, life-threatening toxicities such as stomatitis, diarrhea, neutropenia, and neurotoxicity have been reported with intravenous administration of fluorouracil in patients with DPD enzyme deficiency.
- One case of life-threatening systemic toxicity has been reported with the topical use of Fluorouracil Cream in a patient with DPD enzyme deficiency.
- Symptoms included severe abdominal pain, bloody diarrhea, vomiting, fever, and chills.
- Physical examination revealed stomatitis, erythematous skin rash, neutropenia, thrombocytopenia, inflammation of the esophagus, stomach, and small bowel.
- Although this case was observed with 5% fluorouracil cream, it is unknown whether patients with profound DPD enzyme deficiency would develop systemic toxicity with lower concentrations of topically applied fluorouracil.
Dosing matrix
Population and organ-function guidance, shown together for faster comparison.
DOSAGE AND ADMINISTRATION When Fluorouracil Cream is applied to a lesion, a response occurs with the following sequence: erythema, usually followed by vesiculation, desquamation, erosion, and re-epithelialization. Fluorouracil Cream should be applied preferably with a nonmetal applicator or suitable glove. If Fluorouracil Cream is applied with the fingers, the hands should be washed immediately afterward. Actinic or Solar Keratosis Apply cream twice daily in an amount sufficient to cover the lesions. Medication should be continued until the inflammatory response reaches the erosion stage, at which time use of the drug should be terminated. The usual duration of therapy is from 2 to 4 weeks. Complete healing of the lesions may not be evident for 1 to 2 months following cessation of Fluorouracil Cream therapy. Superficial Basal Cell Carcinomas Only the 5% strength is recommended. Apply cream twice daily in an amount sufficient to cover the lesions. Treatment should be continued for at least 3 to 6 weeks. Therapy may be required for as long as 10 to 12 weeks before the lesions are obliterated. As in any neoplastic condition, the patient should be followed for a reasonable period of time to determine if a cure has been obtained.
Pediatric Use Safety and effectiveness in children have not been established.
Review renal impairment dosing; many agents need CrCl/eGFR adjustment.
- CrCl 0–120: Confirm renal dosing in product SmPC / primary label.
Review hepatic impairment dosing; monitor LFTs if agent is hepatically cleared or hepatotoxic.
Use, effects & interactions
Indications
- INDICATIONS AND USAGE Fluorouracil Cream is recommended for the topical treatment of multiple actinic or solar keratoses.
- In the 5% strength, it is also useful in the treatment of superficial basal cell carcinomas when conventional methods are impractical, such as with multiple lesions or difficult treatment sites.
- Safety and efficacy in other indications have not been established.
- The diagnosis should be established prior to treatment, since this method has not been proven effective in other types of basal cell carcinomas.
- With isolated, easily accessible basal cell carcinomas, surgery is preferred since success with such lesions is almost 100%.
- The success rate with Fluorouracil Cream is approximately 93%, based on 113 lesions in 54 patients.
- Eighty-eight lesions treated with the cream produced 7 failures.
Adverse effects
- ADVERSE REACTIONS The most frequent adverse reactions to Fluorouracil Cream occur locally and are often related to an extension of the pharmacological activity of the drug.
- These include burning, crusting, allergic contact dermatitis, pruritus, scarring, rash, soreness, and ulceration.
- Ulcerations, other local reactions, cases of miscarriage, and a birth defect (ventricular septal defect) have been reported when Fluorouracil Cream was applied to mucous membrane areas.
- Leukocytosis is the most frequent hematological side effect.
- Although a causal relationship is remote, other adverse reactions which have been reported infrequently are: Central Nervous System: Emotional upset, insomnia, irritability.
- Gastrointestinal: Medicinal taste, stomatitis.
- Hematological: Eosinophilia, thrombocytopenia, toxic granulation.
- Integumentary: Alopecia, blistering, bullous pemphigoid, discomfort, ichthyosis, scaling, suppuration, swelling, telangiectasia, tenderness, urticaria, skin rash.
- Special Senses: Conjunctival reaction, corneal reaction, lacrimation, nasal irritation.
- Miscellaneous: Herpes simplex.
- To report SUSPECTED ADVERSE REACTIONS contact Mayne Pharma at 1-844-825-8500 or FDA at 1-800-FDA-1088 or www.FDA.gov/medwatch.
Drug interactions
Open multi-drug checker ↗- Professional use: confirm indication, dose, duration, monitoring and patient counselling points against current Kenya STG / EML and the product SmPC.
- Document allergy status and key interactions.
Mechanism & disposition
Its deoxyribonucleotide metabolite, 5-fluoro-2'-deoxyuridine-5'-phosphate, inhibits thymidylate synthetase.
Read complete mechanism
Its deoxyribonucleotide metabolite, 5-fluoro-2'-deoxyuridine-5'-phosphate, inhibits thymidylate synthetase. This leads to inhibition of methylation of deoxyuridylic acid to thymidylic acid hence interfering with the formation of DNA. Some fluorouracil molecules are also incorporated into RNA to form fraudulent RNA strands. Fluorouracil is also known to inhibit utilization of preformed uracil in RNA synthesis by blocking uracil phosphatase.
Product-specific
Product-specific
See product SmPC
studies of topically applied fluorouracil have been performed on patients with actinic keratoses using tracer amounts of 14 C-labeled fluorouracil added to a 5% preparation. All patients had been receiving nonlabeled fluorouracil until the peak of the inflammatory reaction occurr...
of fluorouracil in the anabolic pathway blocks the methylation reaction of deoxyuridylic acid to thymidylic acid. In this manner, fluorouracil interferes with the synthesis of deoxyribonucleic acid (DNA) and to a lesser extent inhibits the formation of ribonucleic acid (RNA). Sin...
Pregnancy, lactation & diet
Use only if potential benefit justifies potential risk; prefer agents with better reproductive data when alternatives exist.
Nursing Mothers It is not known whether Fluorouracil Cream is excreted in human milk. Because there is some systemic absorption of fluorouracil after topical administration (see CLINICAL PHARMACOLOGY ), because many drugs are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue use of the drug, taking into account the importance of the drug to the mother.
Brands & loaded prices
| Brand | Manufacturer | Pack | Observed price |
|---|---|---|---|
| Additional labeling: 8. | Afya Index product / manufacturer unverified | inj 250mg 5ml x 5's | Unavailable |
Sources & review state
Decision support only. Confirm patient-specific decisions against the current product SmPC, Kenya STG/EML, and professional judgement.