INTRODUCTION
New medications are continuously being developed for the treatment of various disorders. The US Food and Drug Administration (FDA) is the regulatory body responsible for protecting public and individual health, overseeing drug approvals, and ensuring food safety and vaccine oversight. Thus, the FDA certifies the safety, efficacy, and proper management of medications that are used in clinical care throughout the United States.
The FDA also oversees safety interventions, which include approving and revising package inserts (PIs). The PI includes information on indications, dosing, adverse effects, interactions, and safety warnings. This ensures that patients are protected by warning them of the potential adverse effects of medications when they are approved for use. However, FDA warnings can occasionally negatively impact patient care by making providers, patients, or both, hesitant to prescribe and use efficacious medications that may ultimately lead to undertreatment or a complete avoidance of a particular therapy. Frequently, FDA warnings, including the most serious boxed warnings, are not supported by clinical evidence. Making matters worse, the FDA is currently not obligated to reveal the fact that such warnings are not evidence-based. This controversial practice of issuing the most serious boxed warnings without clearly referencing the clinical or scientific evidence supporting them is relatively unique to the US FDA; the European Union (EU) and Japan do not follow this practice of issuing non-evidence-based warnings.
The following brief communication reveals this current reality in detail and communicates the authors' recommendations encouraging the FDA to be truthful and transparent about warnings that are not supported by clinical evidence.
Tacrolimus and Pimecrolimus
Boxed warnings are the most serious warnings the FDA can issue regarding a medication. However, within dermatology, there have been examples of the FDA issuing warnings with questionable scientific support, ultimately discouraging the use of many safe medications. One example is topical tacrolimus and pimecrolimus, which are FDA approved for the treatment of atopic dermatitis. Notoriously, the PIs of these medications contain boxed warnings about malignancy despite there being no human studies that support this risk being elevated with topical use. This has likely led to an increase in provider and patient hesitation and a resulting decrease in the use of these medications. Overall, this impacts clinical practices and likely contributes to the undertreatment of patients, especially amongst parents who are deciding on topical therapies for their children. After over twenty years of these medications being on the market, there remains no evidence that either contributes to an increased risk of cancer.2 Nevertheless, the FDA has yet to retract the boxed warning about malignancy that continues to persist in PIs for these medications.
