Side Effects of Bladder Cancer Drug Padcev Linked To Stevens-Johnson Syndrome, TENS Risk: Study

The findings of a new study suggest the side effects of the new bladder medication Padcev may increase the risk of severe and fatal skin reactions, known as Stevens-Johnson Syndrome (SJS) and Toxic Epidermal necrolysis (TEN).

Padcev (enfortumab vedotin-ejfv) was granted accelerated approval by the FDA in December 2019, as a treatment for bladder cancer. It is manufactured and marketed by Astellas Pharma US, Inc. and distributed and marketed by Seagen, Inc. However, in July, the FDA required a black box warning be added to the label and prescribing information, warning about the risk of the severe and debilitating skin reactions.

Stevens-Johnson Syndrome has been linked to a number of prescription medications, resulting in burning of the skin from the inside out, producing blisters, severe rash and often causing the skin to separate from the body. It also often results in vision loss or blindness. When the skin lesions affect more than 30% of the body, the condition is typically referred to as toxic epidermal necrolysis (TEN), usually resulting in the need for treatment in a hospital Intensive Care Unit (ICU) or Burn Unit, and the conditions can be fatal in many cases.

In a research letter, published in JAMA Dermatology on September 8, FDA researchers presented the findings that led to the new black box warning; the most serious warning the agency can require a drug to carry.

The researchers reviewed the side effects of Padcev submitted to the FDA Adverse Event Reporting System (FAERS), as well as literature published in PubMed and Embase from December 18, 2019, when the drug was first approved, until October 7, 2020. They found eight cases of SJS or TEN during that time period. In five of those cases, the diagnosis was confirmed by dermatologists or through biopsies. Four of those cases resulted in death, and four cases resulted in admission to hospital burn units.

The study found that the median onset time of SJS/TEN was 11 days, ranging from nine to 21 days, following the start of treatment.

The Boxed Warning advises health care professionals to immediately withhold Padcev for patients suffering severe skin reactions and indicates they should consider referring patients for specialized care in those cases, or in cases where SJS or TEN is suspected. The warning also recommends Padcev be discontinued in patients with confirmed cases of SJS or TEN, or in the event of Grade 4 or recurrent Grade 3 skin reactions.