Drugs List

Therapeutic Indications

Uses

Topical treatment of slightly palpable and/or moderately thick hyperkeratotic actinic keratosis (grade I/II) in immunocompetent adults.

Grade I/II intensity is based on the 4-point scale of Olsen et al.

Administration

For topical application.

The solution should not be used if crystals occur.

Handling

Fluorouracil is cytostatic.

Contraindications

Pregnancy - see Pregnancy section
Breastfeeding - see Lactation section
Renal impairment
Dihydropyrimidine dehydrogenase deficiency
Children under 18 years of age

Precautions and Warnings

Dihydropyrimidine dehydrogenase (DPD) enzyme plays an important role in breaking down fluorouracil. Inhibition, deficiency or decreased activity of this enzyme can result in the accumulation of fluorouracil.
If applicable, DPD enzyme activity should be indicated before treatment with fluorouracil or other fluoropyrimidines.

Close monitoring of the affected area is required in patients with sensory disturbances e.g. diabetes mellitus.

The solution should be applied less frequently to areas of skin with thin epidermis, and treatment should be monitored more often.

There has been clinical experience with the use of fluorouracil and salicylic acid on the face, forehead and bald scalp. The thickness of the epidermis on other parts of the body such as the upper trunk, arms or legs should be taken into consideration when deciding on treatment.

Fluorouracil and salicylic acid should not come into contact with eyes or mucous membranes.

Avoid contact with textiles or acrylics (e.g. acrylic bathtubs) as fluorouracil and salicylic acid may cause permanent stains.

Patients should be counseled to protect the skin against further excessive or cumulative exposure to UV/sunlight, especially in the area being actively treated.

Pregnancy and Lactation

Pregnancy

Fluorouracil with salicylic acid cutaneous solution is contraindicated in pregnancy.

There are no data from the use of topical fluorouracil in pregnant women. The amount of fluorouracil absorbed systemically when applied topically in patients with actinic keratoses is approximately 6%.

Animal studies have not been conducted with topical fluorouracil. However, fluorouracil was embryotoxic and teratogenic in mice, rats, and hamsters given parenteral doses equivalent to the human dose.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Fluorouracil with salicylic acid cutaneous solution is contraindicated in breastfeeding.

It is not known if fluorouracil is excreted in breast milk after topical application. The low molecular weight (about 130) probably indicates that the drug is excreted into milk.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Erythema
Inflammation (application site)
Irritation (application site)
Burning (application site)
Pain
Pruritus
Bleeding
Erosion
Dermatitis
Oedema
Ulceration (application site)
Skin exfoliation
Headache
Dry eyes
Eye pruritus
Increased lacrimation

Presentation

Cutaneous solution containing fluorouracil 5mg/g and salicylic acid 100mg/g.

Drugs List

Therapeutic Indications

Uses

Topical treatment of slightly palpable and/or moderately thick hyperkeratotic actinic keratosis (grade I/II) in immunocompetent adults.

Grade I/II intensity is based on the 4-point scale of Olsen et al.

Dosage

Adults

Elderly

Children

Patients with Renal Impairment

Administration

For topical application.

The solution should not be used if crystals occur.

Handling

Fluorouracil is cytostatic.

Contraindications

Pregnancy - see Pregnancy section
Breastfeeding - see Lactation section
Renal impairment
Dihydropyrimidine dehydrogenase deficiency
Children under 18 years of age

Precautions and Warnings

Dihydropyrimidine dehydrogenase (DPD) enzyme plays an important role in breaking down fluorouracil. Inhibition, deficiency or decreased activity of this enzyme can result in the accumulation of fluorouracil.
If applicable, DPD enzyme activity should be indicated before treatment with fluorouracil or other fluoropyrimidines.

Close monitoring of the affected area is required in patients with sensory disturbances e.g. diabetes mellitus.

The solution should be applied less frequently to areas of skin with thin epidermis, and treatment should be monitored more often.

There has been clinical experience with the use of fluorouracil and salicylic acid on the face, forehead and bald scalp. The thickness of the epidermis on other parts of the body such as the upper trunk, arms or legs should be taken into consideration when deciding on treatment.

Fluorouracil and salicylic acid should not come into contact with eyes or mucous membranes.

Avoid contact with textiles or acrylics (e.g. acrylic bathtubs) as fluorouracil and salicylic acid may cause permanent stains.

Patients should be counseled to protect the skin against further excessive or cumulative exposure to UV/sunlight, especially in the area being actively treated.

Pregnancy and Lactation

Pregnancy

Fluorouracil with salicylic acid cutaneous solution is contraindicated in pregnancy.

There are no data from the use of topical fluorouracil in pregnant women. The amount of fluorouracil absorbed systemically when applied topically in patients with actinic keratoses is approximately 6%.

Animal studies have not been conducted with topical fluorouracil. However, fluorouracil was embryotoxic and teratogenic in mice, rats, and hamsters given parenteral doses equivalent to the human dose.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14-17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Fluorouracil with salicylic acid cutaneous solution is contraindicated in breastfeeding.

It is not known if fluorouracil is excreted in breast milk after topical application. The low molecular weight (about 130) probably indicates that the drug is excreted into milk.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Effects on Ability to Drive and Operate Machinery

No influence on the ability to drive or operate machinery.

Side Effects

Erythema
Inflammation (application site)
Irritation (application site)
Burning (application site)
Pain
Pruritus
Bleeding
Erosion
Dermatitis
Oedema
Ulceration (application site)
Skin exfoliation
Headache
Dry eyes
Eye pruritus
Increased lacrimation

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Shelf Life and Storage

Store below 25 degrees C
Do not freeze or refrigerate
Keep the bottle tightly closed
Caution flammable: keep away from fire or flames

Further Information

Last Full Review Date: June 2011

Reference Sources

British National Formulary, 61st Edition (2011) Pharmaceutical Press, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 8th edition (2008) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Summary of Product Characteristics: Actikerall 5mg/g + 100mg/g Cutaneous Solution. Almirall Ltd. Revised May 2014.