Photosensitivity From Avapritinib: Pharamacovigilance Analysis

Abstract

Certain protein kinase inhibitors have been reported to cause photosensitivity. Avapritinib is a tyrosine kinase inhibitor that was approved in January 2020. The aim of this analysis was to determine if a statistically significant signal exists between Avapritinib and photosensitivity in the real-world population. A disproportionality analysis was conducted using the Food and Drug Administration Adverse Event Reporting System (FAERS) from January 1, 2020, to December 31, 2021. A literature review was also performed to identify case reports of Avapritinib-induced photosensitivity. A total of 13 adverse event reports with Avapritinib as the drug and photosensitivity as the reaction were identified in FAERS. Avapritinib was the suspect drug in all 13 reports, and in 12 of the 13 reports, Avapritinib was the only drug listed. Disproportionality analysis found a proportional reporting ratio of 11.0, χ21=107, reporting odds ratio of 11.0, and a lower limit of the 95% CI of the information component of 2.1. The literature review found 1 case report of Avapritinib-induced photosensitivity in a patient who had been taking Avapritinib 300 mg daily for 5 months. A statistically significant signal was found between Avapritinib use and photosensitivity. Clinicians should continue to balance the benefits and risks when prescribing Avapritinib to patients.

Neuropsychiatric Adverse Drug Reactions with Tyrosine Kinase Inhibitors in Gastrointestinal Stromal Tumors: An Analysis from the European Spontaneous Adverse Event Reporting System

“…In accordance with the disproportionality analyses, all ADRs with a higher frequency for AVA and SU have already been reported in their SmPC as very common [ 9 , 18 ]. In detail, the photosensitivity reactions with AVA may share a similar mechanism to the skin toxicities of other TKIs, such as IM, for the potent inhibition of the KIT gene [ 42 ]. Blood disorders, including neutropenia and thrombocytopenia, can be induced by SU through binding to Fms-like tyrosine kinase 3 (FLT-3) expressed on the surface of hematopoietic cells [ 43 ].…”

“…Despite its strengths, the SRS database has some intrinsic limitations, such as the underreporting phenomena, the absence of denominators (i.e., the total number of GIST patients who have undergone treatment with TKIs), and the poor quality of information listed in each ICSR (i.e., seriousness and outcome, previous/current medical conditions, additional suspected or concomitant drugs) that could potentially affect the occurrence of analyzed ADRs [ 65 ]. In contrast to other SRS database studies, the use of the EV database does not allow the detection of all ICSR information, making it impossible to compute disproportionality analyses for all ICSRs related to SOC Nervous system disorders and Psychiatric disorders [ 42 , 66 , 67 ]. Therefore, further ad hoc studies are essential to establish the real neuropsychiatric safety profile of TKIs used in GISTs.…”