Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2019 Publisher: Mylan Products Ltd., Station Close, Potters Bar, Herts, EN6 1TL, United Kingdom
Efudix is contraindicated in patients with known hypersensitivity to fluorouracil or any of the excipients listed in section 6.1. Coadministration of Efudix with antiviral nucleoside drugs (e.g. brivudine and analogues) may lead to a substantial increase in plasma levels of fluorouracil and associated toxicity and is contraindicated. Brivudine and analogues are potent inhibitors of DPD, a fluorouracil metabolising enzyme (see section 4.4 and 4.5)
Use of Efudix during pregnancy and in breast-feeding mothers is contraindicated.
The normal pattern of response includes: early and severe inflammatory phases (typically characterised by erythema, which may become intense and blotchy), a necrotic phase (characterised by skin erosion) and finally healing (when epithelialisation occurs). The clinical manifestation of response usually occurs in the second week of Efudix treatment. However these treatment effects sometimes be more severe and include pain, blistering and ulceration (see section 4.8). Occlusive dressing may increase inflammatory reactions of the skin.
Instruct patients not to smoke or go near naked flames – risk of severe burns. Fabric (clothing, bedding, dressings etc) that has been in contact with this product burns more easily and is a serious fire hazard. Washing clothing and bedding may reduce product build-up but not totally remove it.
Exposure to UV-radiation (e.g natural sunlight, tanning salon) should be avoided.
Pre-existing subclinical lesions may become apparent following Efudix use.
Any severe skin discomfort during treatment with Efudix may be alleviated by the use of an appropriate topical steroid cream.
When used according to the approved prescribing information Efudix should have minimal effect on healthy skin.
Significant systemic drug toxicity is unlikely via percutaneous absorption of fluorouracil when Efudix is administered as per the approved prescribing information. However the likelihood of this is increased if the product is used excessively, especially on skin areas in which the barrier function is impaired (e.g. cuts) and/or in individuals with deficiency in dihydropyrimidine dehydrogenase (DPD), see section 4.8. DPD is a key enzyme involved in metabolising and eliminating fluorouracil. Determination of DPD activity may be considered where systemic drug toxicity is confirmed or suspected. There have been reports of increased toxicity in patients who have reduced activity/deficiency of the enzyme dihydropyrimidine dehydrogenase. In the event of suspected systemic drug toxicity, consideration should be given to stopping Efudix treatment.
An interval of at least four weeks should elapse between treatment with brivudine, sorivudine or analogues and subsequent administration of Efudix.
The excipients stearyl alcohol and propylene glycol may cause local skin irritations (e.g. contact dermatitis); the excipients methyl parahydroxybenzoate and propyl parahydroxybenzoate may cause allergic reactions (possibly delayed).
Although no significant drug interactions with Efudix have been reported, potential drug interactions are possible as indicated below.
Brivudine, sorivudine and analogues are potent inhibitors of DPD, a fluorouracil metabolising enzyme (see section 4.4). For this reason concomitant administration of these drugs with Efudix is contraindicated (See section 4.3).
There are no adequate data from the use of topical fluorouracil in pregnant women.
Studies in animals have shown that fluorouracil is teratogenic (see section 5.3). The potential risk for humans is unknown, hence Efudix should not be used during pregnancy (see section 4.3).
Women of childbearing potential should not become pregnant during topical fluorouracil therapy and should use effective method of contraception during treatment with fluorouracil therapy. If a pregnancy occurs during treatment the patient should be advised about the risk for the child of adverse effects associated with the treatment and genetic counselling is recommended.
No information is available on the excretion of fluorouracil into breast milk. Studies in animals have shown the fluorouracil is teratogenic (see section 5.3). A risk to the suckling g child cannot be excluded, so Efudix should not be used in nursing mothers (see section 4.3). If use during breastfeeding is absolutely necessary, breastfeeding must be discontinued.
No clinical data in humans are available on the effects of topical fluorouracil on fertility.
Experiments in various species revealed an impairment of the fertility and reproductive performance of systemic 5-fluorouracil. The reduced systemic exposure to 5-FU following its topical administration will reduce the potential toxicity. The use of topical 5-fluorouracil may impair female and male fertility. Topical fluorouracil is not recommended in men attempting to father a child.
It is unlikely that treatment will have any effect on the ability to drive and use machines when used according to the dosage instructions.
Within the system organ classes, adverse reactions are listed under headings of frequency (number of patients expected to experience the reaction), using the following categories: Very common (>1/10), Common (>1/100 to <1/10), Uncommon (>1/1,000 to <1/100), Rare (>1/10,000 to <1/1,000), Very rare (<1/10,000), Frequency not known (cannot be estimated from the available data).
Adverse reactions associated with exacerbations of normal pattern of response (see section 4.4) which are related to pharmacological activity of fluorouracil on the skin are the most frequently reported reactions. Allergic type skin reactions and reactions related to systemic drug toxicity are very rarely reported.
Very rare: Haematological disorders, associated with systemic drug toxicity, e.g. pancytopenia, neutropenia, thrombocytopenia.
Very rare: Allergic conditions (e.g. hypersensitivity and allergic reactions).
Frequency not known: Dysgeusia, headache, dizziness.
Frequency not known: Conjunctival irritation, keratitis, increased lacrimation.
Very rare: Diarrhoea haemorrhagic, diarrhoea, vomiting, abdominal pain, stomatitis, associated with systemic drug toxicity.
Frequency not known: Nausea.
Very rare: Pruritus, urticaria, rash (usually local but also generalised if associated with systemic drug toxicity); erythemas including erythema multiforme; dermal and epidermal conditions (such as skin burning sensation, skin exfoliation, skin swelling); skin and subcutaneous skin ulcerations; dermatitis and eczema conditions (such as contact dermatitis, skin irritation); blisters, and alopecia.
Exposure to sunlight may increase the intensity of the reaction.
See also normal pattern of response in section 4.4
Very rare: Pyrexia, chills and mucosal inflammation, associated with systemic drug toxicity.
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at: www.mhra.gov.uk/yellowcard.
None known.
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