Adverse effects reported following topical application of fluorouracil have been minimal and were generally limited to local inflammatory reactions involving particularly the creases and folds of the skin; dermatitis; stomatitis; and photosensitivity. Local adverse effects have occurred more frequently when propylene glycol solutions of the drug were used than when the cream was applied, probably because of the greater tendency for the liquid to collect in creases and folds of the skin such as the circumoral and nasolabial areas and the chin. Other adverse effects associated with fluorouracil topical therapy include insomnia, irritability, medicinal taste, telangiectasia, and lacrimation.
The major adverse effects of fluorouracil topical therapy are local inflammatory reactions at the site of the actinic lesions which are necessary for the therapeutic response. These reactions include swelling, scaling, pain, pruritus, burning, soreness, tenderness, suppuration, scarring, and hyperpigmentation. Inflammatory responses may occur in sites of normal appearing subclinical actinic keratoses. Increased incidence of inflammatory reactions may occur in the normal skin near a lesion if an occlusive dressing is used; a porous gauze dressing may be used for cosmetic reasons without increasing inflammatory reactions.
Although reports of systemic toxicity related to topical application of fluorouracil have not appeared in the published literature, one manufacturer reports that leukocytosis, thrombocytopenia, toxic granulation, and eosinophilia have occurred. In one study, 5% fluorouracil in hydrophilic petrolatum and up to 5% fluorouracil in propylene glycol were concurrently applied to the face, neck, chest, arms, and legs in patients with multiple solar keratoses and no systemic toxicity such as bone marrow depression was reported. Systemic absorption of fluorouracil following accidental ingestion of fluorouracil topical preparations may be manifested by leukopenia, thrombocytopenia, stomatitis, diarrhea, GI ulceration and bleeding, and hemorrhage from any site. If leukocytosis and granulocytopenia occur, the patient should be isolated and given prophylaxis against infection.