"The US prescribing information for EV currently includes information warning of serious skin reactions in various sections of the prescribing information, including the boxed warning for the drug," FDA press officer Audra Harrison told Reuters Health by email.
"While data generated to date do not implicate specific risk factors for EV-associated serious skin reactions, data collection is ongoing both in clinical trials and post-marketing surveillance, which may better elucidate potential risk factors for these adverse drug reactions," she said. "Identification of risk factors for rare and idiosyncratic events, such as SJS and TEN, is challenging and may require more extensive safety data collection."
As reported in JAMA Dermatology, the FDA's division of pharmacovigilance reviewed FAERS, PubMed, and Embase from December 18, 2019, EV's FDA-approval date, through October 7, 2020, to identify EV-associated SJS/TEN cases.
Eight cases of serious skin reactions similar to SJS/TEN were identified from FAERS, and the diagnosis was confirmed in five of these cases. No additional cases were identified from PubMed or Embase at the time.
The median time to SJS/TEN onset was 11 days from the start of EV. All cases had serious outcomes, including four SJS/TEN-attributed deaths. Other serious outcomes included admission to a burn unit in four cases.
The rapid accumulation of cases over an approximate 12-month marketing period was concerning, and the FDA investigated further. They considered the annual incidence of locally advanced urothelial cancer in the US, which is the population likely to receive EV (12,494-40,000 patients), and calculated a reporting rate of 200 cases per 1,000,000 patients, which well exceeds the expected incidence rate of SJS/TEN (i.e., 1-7 cases per 1,000,000 patients).
Harrison said, "Clinicians who encounter patients with serious skin reactions should consider EV as a potential cause and consider the guidance provided in the US prescribing information, such as monitoring patients for skin reactions; immediately withholding EV for suspected SJS/TEN or other severe skin reactions and considering a referral for specialized care; and permanently discontinuing enfortumab EV in patients with confirmed SJS/TEN or other life-threatening or recurrent severe skin reaction."
Health care professionals are encouraged to report (https://bit.ly/2VQFngP) adverse drug reactions to the FDA for evaluation," she added.
Dr. Karl Saardi, Director of the Inpatient Dermatology Service in the George Washington University Hospital in Washington, DC, commented on the report in an email to Reuters Health. "I have not seen cases of SJS/TEN from this medication."
"The potential risk of SJS/TEN should not dissuade prescribers from using this medication if the patient is an appropriate candidate," he said. "There is a real risk of SJS/TEN with the PD-1 inhibitors, but these medications have shot to the forefront of oncology because of how useful they are."
"The two most commonly used medications in this category, pembrolizumab and nivolumab, do not carry boxed warnings, but the prescribing information does contain highlighted warnings that severe skin toxicities may occur," he noted. "Clinicians should also keep in mind that active cancer is a marker for poor outcomes in patients with SJS/TEN."
SOURCE: https://bit.ly/39ijutH JAMA Dermatology, online September 8, 2021.
By Marilynn Larkin
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