Fluorouracil Cream (Efudex) inhibits the synthesis of DNA of rapidly dividing cells. It is used in the treatment of superficial basal cell carcinoma where surgical resection is not possible.

Fluorouracil Cream Uses:

• Actinic or solar keratosis:

  • It is indicated for the treatment of multiple actinic or solar keratoses

• Basal cell carcinoma (5%):

  • It is indicated for the treatment of superficial basal cell carcinomas when conventional methods of treatment are not possible such as in patients with multiple lesions or those with difficult-to-treat sites.
• Limitations of use:
  • The diagnosis of superficial basal cell carcinoma should be established before treatment initiation. It has not been proven to be effective in other types of basal cell carcinomas.
  • The success rate of topical fluorouracil is close to 93% in the treatment of superficial basal cell carcinoma while the success rate of surgery in lesions that can be easily accessed is 100%. Surgical resection is therefore preferred where possible.

Fluorouracil Cream Dose in Adults

Fluorouracil Cream Dose in the treatment of Actinic or solar keratosis: 

• Cream (0.5%):
  • Apply a thin film to the affected area once a day for up to four weeks, as tolerated
• Cream (1%):
  • Apply to the lesions two times a day for 2 to 6 weeks
• Cream (4%):
  • Apply topically to the lesions once a day for four weeks as tolerated
• Cream (5%) or solution (2% and 5%):
  • Apply topically to the lesions two times a day for 2 to 4 weeks;
  • It may take 1 to 2 months after treatment initiation for healing to be noted.

Fluorouracil Cream Dose in the treatment of Superficial basal cell carcinoma:

• Topical: Cream (5%) or solution (5%):
  • Apply the solution or the cream to the affected area two times a day for 3 to 6 weeks;
  • The treatment may be continued for up to 10 to 12 weeks

Fluorouracil Cream Use in Children:

Not indicated.

Pregnancy Risk Factor X

• Although Topical Fluorouracil was not studied during pregnancy, it has been shown to have serious teratogenic effects with the parenteral fluorouracil.
• Reports of adverse reactions to topical fluorouracil events have been made.
• Pregnancy should be avoided and women with reproductive potential should be advised to use effective contraception during treatment.
• This should also be done for at least one year after the last topical fluorouracil dose.

Use fluorouracil while breastfeeding

• It is unknown whether the drug will be excreted into breastmilk after topical fluorouracil use.
• Due to the potential for serious adverse drug reactions in the infant's feeding, treatment in the mother and breastfeeding should be stopped.
• This is taking into consideration the importance of maternal diseases and the benefits of drug therapy in mother.

Dose in Kidney disease:

There are no dosage adjustments provided in the manufacturer’s labeling.

Dose in Liver disease:

There are no dosage adjustments provided in the manufacturer’s labeling.

Common Side Effects of Fluorouracil Cream:

• Dermatologic:

  • Application Site Scaling
  • Application Site Dryness
  • Stinging Of The Skin
  • Skin Erosion

• Local:

  • Application Site Erythema
  • Application Site Reaction
  • Application Site Burning
  • Application Site Pruritus
  • Application Site Edema
  • Application Site Pain

Less Common Side Effects of Fluorouracil Cream:

• Central nervous system:

  • Headache

• Dermatologic:

  • Skin irritation

• Infection:

  • Common cold

• Ophthalmic:

  • Eye irritation
    • Burning
    • Watering
    • Sensitivity
    • Stinging
    • Itching

• Respiratory:

  • Sinusitis

Contraindications to Fluorouracil Cream (Efudex):

• Allergy reactions to fluorouracil and any component of the formulation
• Patients suffering from dihydropyrimidine-dehydrogenase enzyme deficiency (DPD); Women who may be pregnant or are currently pregnant with a baby

Warnings and precautions

• Hypersensitivity

  • Topical fluorouracil use is linked to delayed-type hypersensitivity reactions, primarily manifested as contact allergic dermatitis.
  • It may indicate drug hypersensitivity if the patient experiences severe pruritus or eczema.
  • Hypersensitivity reactions in patients must be stopped immediately.
  • For the evaluation of hypersensitivity reactions, patch testing is not recommended.

• Local skin reactions

  • When the drug is applied topically to the skin, local reactions such as vesicles and erosion, desquamation or re-epithelization can occur.
  • After treatment is over, skin reactions and changes may continue for several weeks.
  • The most common skin reactions are stinging, burning and crusting, dryness. edema, pain. itching. scaling. soreness, scarring.
  • Applying the drug to inflamed skin or areas with ulcers can increase the risk of it being absorbed.

• Photosensitivity

  • Use of topical fluorouracil can cause severe sunburns or photosensitivity in patients.
  • Patients should be warned to avoid prolonged exposure of sunlight and ultraviolet radiations.

• Deficiency of dihydropyrimidine hydrogenase enzyme:

  • Topical fluorouracil may cause severe toxicities in people who are deficient of the enzyme dihydropyrimidine deshydrogenase.
  • Patients with toxicities may experience bloody diarrhea, stomatitis, or inflammation of the gastrointestinal tract, including the stomach and intestine. 
  • Patients can also experience severe abdominal pain, fever, skin rash and thrombocytopenia.
  • If signs of toxicemia are detected, treatment must be stopped immediately. 
  • Patients who become toxic should not be given lower doses. This has been a problem that has not been investigated.

Fluorouracil (topical): Drug Interaction

How to administer Fluorouracil Cream?

Topical:

• After washing the skin, rinse it, and dry the area, apply the cream for 10 minutes.
• You should apply enough to cover all lesions using a non-metal applicator and suitable gloves.

Crème (4%)

• After washing the area, rinse it, and dry it, apply the cream to the affected areas.
• Apply enough cream to cover the ears, face, and scalp. Massage the skin with your fingertips and gently using your fingertips.
• Wash your hands immediately after applying the cream using your fingertips. You should not apply any occlusive treatment to this area.
• You should not apply the cream to mucous membranes, intravaginal, or oral cavity.

Mechanism of action of Fluorouracil Cream:

• It is a pyrimidine-antimetabolite. It prevents cell proliferation in rapidly dividing cells, and causes cell death through interfering DNA synthesis.
• It prevents the methylation from deoxyuridylic to thymidylic acids, thereby preventing DNA synthesis.

Absorption:

• About 6% of a topical dose is absorbed systemically (5% cream)

Time to Peak:

• About one hour following application (4% cream)

International Brand Names of Fluorouracil:

• Carac
• Efudex
• Fluoroplex
• Tolak
• Acler
• Efurix
• Neoflur

Fluorouracil Brand Names in Pakistan: