Bladder Cancer Drug Padcev is Linked to Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN) in 2021
Padcev (enfortumab vedotin-ejfv), an injection drug for intravenous use, was approved by the FDA in December 2019 for the treatment of certain adult patients with locally advanced or metastatic urothelial cancer (mUC). Urothelial carcinoma, also known as transitional cell carcinoma (TCC), is by far the most common type of bladder cancer. As such, if you have bladder cancer it is almost certain to be a urothelial carcinoma. It is important for bladder cancer patients and their families to know that the Padcev skin side effects Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are serious skin reactions that can be life-threatening and even fatal.
As background, from "Stevens-Johnson syndrome/toxic epidermal necrolysis", a MedlinePlus document provided by the U.S. National Library of Medicine, we get the following:
Although Stevens-Johnson syndrome and toxic epidermal necrolysis were once thought to be separate conditions, they are now considered part of a continuum. Stevens-Johnson syndrome represents the less severe end of the disease spectrum, and toxic epidermal necrolysis represents the more severe end.
In more detail, in people who have developed Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) is diagnosed when more than 30% of the skin surface is affected and the moist linings of the body (mucous membranes) have extensive damage. Put otherwise, toxic epidermal necrolysis (TEN) is a severe form of Stevens-Johnson syndrome (SJS). And, significantly, TEN is such a serious skin reaction that it can be fatal, causing patient deaths in some situations.
Now we will look at the timeline as to how the Padcev Prescribing Information, or drug label, went from having no warning about Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) when approved by the FDA in December 2019 to the Padcev drug label having a "Black-Box" warning about the SJS and TEN skin side effects, now, less than 2 years after Padcev came on the market.
In the initial Padcev drug label ("Revised: 12/2019") there was a warning about general, low-level Padcev skin side effects in the Warnings and Precautions section at 5.4 Skin Reactions.
The first label change to add warnings for the Padcev skin side effects Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) came in March 2021. From the "Revised: 3/2021" Padcev drug label at 5.1 Skin Reactions:
Severe cutaneous adverse reactions, including fatal cases of Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) occurred in patients treated with PADCEV. SJS and TEN occurred predominantly during the first cycle of treatment but may occur later.
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But only four months later, in July 2021, the FDA mandated increased warnings about the Padcev skin side effects Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), in the form of a so-called "Black Box" warning with the bolded title WARNING: SERIOUS SKIN REACTIONS. There was also this bulked-up 5.1 Skin Reactions warning in the "Revised: 7/2021" version of the Padcev drug label:
Severe cutaneous adverse reactions, including fatal cases of SJS or TEN occurred in patients treated with PADCEV. SJS and TEN occurred predominantly during the first cycle of treatment but may occur later.
Skin reactions occurred in 55% of the 680 patients treated with PADCEV in clinical trials. Twenty-three percent (23%) of patients had maculopapular rash and 33% had pruritus. Grade 3-4 skin reactions occurred in 13% of patients, including maculo-papular rash, rash erythematous, rash or drug eruption, symmetrical drugrelated intertriginous and flexural exanthema (SDRIFE), dermatitis bullous, dermatitis exfoliative, and palmarplantar erythrodysesthesia. In clinical trials, the median time to onset of severe skin reactions was 0.6 months (range: 0.1 to 6.4 months). Among patients experiencing a skin reaction leading to dose interruption who then restarted PADCEV (n=59), 24% of patients restarting at the same dose and 16% of patients restarting at a reduced dose experienced recurrent severe skin reactions. Skin reactions led to discontinuation of PADCEV in 2.6% of patients [see Adverse Reactions (6.1)].
For an overview of the data which led to these two Padcev label changes in 2021, we point out this article, "Postmarketing Cases of Enfortumab Vedotin–Associated Skin Reactions Reported as Stevens-Johnson Syndrome or Toxic Epidermal Necrolysis", published online by the JAMA Dermatology medical journal on September 8, 2021. Notably, this "Research Letter" was written by FDA staff in the Division of Pharmacovigilance, Office of Surveillance and Epidemiology. It begins with this introduction:
During routine surveillance, the US Food and Drug Administration (FDA) Division of Pharmacovigilance identified postmarketing cases of Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN) associated with [Padcev (enfortumab vedotin)] from the FDA Adverse Event Reporting System (FAERS). To investigate a potential association between [Padcev (enfortumab vedotin)] and SJS/TEN, we evaluated all sources for postmarketing cases of SJS/TEN and report our findings.
Our law firm is investigating cases for patients who have suffered the Padcev skin side effects Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) as possible drug injury lawsuits to be filed against Astellas Pharma US, Inc., the manufacturer of Padcev.
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