What Is the Risk of Harm Associated With Topical Calcineurin Inhibitors?

Abstract

The topical calcineurin inhibitors (TCIs), tacrolimus (Protopic) and pimecrolimus (Elidel), were approved in the early 2000s and were widely used as a nonsteroid treatment for atopic dermatitis (AD) in adult and pediatric populations. In 2005, the addition of a boxed warning was mandated for TCIs based on a potential risk of malignancy, and there was subsequently a substantial decline in their use. Since then, evidence has mounted to support the safety of this class of medications and suggests that the increased risk of malignancy remains theoretical. This review aims to dispel some of the common myths surrounding the safety of TCIs by evaluating the key evidence regarding their safety and tolerability in adult and pediatric populations. Four major themes are addressed in a practical question-and-answer format: the risk of harm associated with TCIs including common and serious adverse events; warnings and precautions for their use including the risk of systemic absorption, immunosuppression, and malignancy; the comparative safety of TCIs; and suggestions for counselling patients about the risk of harm with TCIs. Based on the available evidence, international professional dermatological organizations and regulatory authorities have concluded that the benefits of TCIs outweigh their potential risks when used in the appropriate patient populations for the recommended duration of time.