Is bufexamac worth the risk?

Bufexamac, a nonsteroidal anti-inflammatory drug agent used cutaneously and rectally, is well known globally as an initiator of allergic contact dermatitis. In fact, it has been removed from the European market (except Switzerland) for inducing allergic reactions, and is also banned in Japan, New Zealand, and the United States (where it was never approved).¹ This column will primarily discuss recent findings in human trials and weigh in on the issue.

Dr. Leslie S. Baumann

Antioxidant activity

In addition to its known anti-inflammatory activity, bufexamac has been found to exert antioxidant effects. In 2003, Trommer and Neubert demonstrated that bufexamac displayed antioxidant activity in lipid models and HaCaT keratinocytes, as measured through mass spectrometry.² In a 2005 in vitro study of the impact of 47 drugs, plant extracts and ingredients, and polysaccharides on lipid peroxidation engendered by UV irradiation, Trommer and Neubert found that bufexamac was among the drugs shown to exhibit antioxidant activity.³

Minor allergen? Worth using?

In a 2009 study on the prevalence and risk factors for allergic contact dermatitis to topical atopic dermatitis (AD) treatments, Mailhol et al. patch tested 641 children with AD using seven then-common ingredients (chlorhexidine, hexamidine, budesonide, tixocortol pivalate, bufexamac, sodium fusidate and with the current emollient used by the child). Bufexamac was identified as an allergen in only 2.5% of the 41 positive patch tests.⁴

To ban or not to ban

In 2012, the European Medicines Agency’s Committee for Medicinal Products for Human Use recommended that the marketing of formulations containing bufexamac be disallowed throughout the European Union because of a tendency toward inducing severe allergic contact dermatitis.⁵

Given its continuing use in Australia for the local treatment of several dermatoses, Pan and Nixon, in 2012, retrospectively reviewed patch-test data at the Skin and Cancer Foundation Inc. and found 19 cases of positive reactions to bufexamac (5% petrolatum) from 451 people patch tested. In 13 of 19 patients (68%), the reaction to bufexamac was considered to be associated with the identified dermatitis. The authors concluded that allergic contact dermatitis from bufexamac exposure is underreported in the English-language literature and cautioned that physicians should consider bufexamac allergy in patients who have a history of exposure.⁵

Bufexamac remained available over the counter in topical formulations in Australia as of early 2019. In response, Harris et al. presented several cases of patients who experienced severe skin eruptions after using such preparations in support of their advocacy to the Therapeutic Goods Administration in Australia to ban its use.⁶

In the middle of that year, Wong et al. reported on the hospitalization of a 41-year-old administrative worker who applied a first aid cream containing bufexamac (5%), lignocaine (1%), and chlorhexidine (0.1%) to a superficial right foot abrasion and who developed facial edema and widespread polymorphic eruptions 2 hours later. The authors suggested that this case reinforced the need to remove bufexamac from the markets where it remains because of the tendency to provoke severe allergic contact dermatoses and lack of efficacy.¹

Conclusion

Bufexamac offers the somewhat rare opportunity for advocacy. That is to say, I think there is sufficient evidence to justify the removal of this potent allergen from the market in Australia, Switzerland, and other countries where it may be available.

Dr. Baumann is a private practice dermatologist, researcher, author, and entrepreneur who practices in Miami. She founded the Cosmetic Dermatology Center at the University of Miami in 1997. Dr. Baumann has written two textbooks and a New York Times Best Sellers book for consumers. Dr. Baumann has received funding for advisory boards and/or clinical research trials from Allergan, Evolus, Galderma, and Revance. She is the founder and CEO of Skin Type Solutions Franchise Systems LLC. She had no relevant disclosures. Write to her at dermnews@mdedge.com.

References

1. Wong GN et al. Contact Dermatitis. 2019 Jun;80(6):395-7.

2. Trommer H et al. J Pharm Pharmacol. 2003 Oct;55(10):1379-88.

3. Trommer H, Neubert RH. J Pharm Pharm Sci. 2005 Sep 15;8(3):494-506.

4. Mailhol C et al. Allergy. 2009 May;64(5):801-6.

5. Pan Y, Nixon R. Australas J Dermatol. 2012 Aug;53(3):207-10.

6. Harris AG et al. Australas J Dermatol. 2019 Feb;60(1):53-6.