ABSTRACT
OBJECTIVE To provide references for the clinical safe use of axitinib. METHODS Adverse drug event （ADE） data for axitinib were collected from the US FDA Adverse Event Reporting System （FAERS） database from the first quarter of 2012 to the fourth quarter of 2022. The data were mined and analyzed by utilizing the ratio-of-reporting-ratio （ROR） method and comprehensive standard method of the United Kingdom’s Medicines and Healthcare Products Regulatory Agency （MHRA） of proportional imbalance measurement. RESULTS A total of 13 962 reports of axitinib-related ADEs were obtained， with patients’ age concentrated in 65-85 years （43.25%）， gender predominantly male （65.23%）， country of reporting predominantly US （60.01%）， and serious ADE outcomes mostly hospitalization or prolonged hospitalization （31.51%）. A total of 172 ADE risk signals were detected， involving 18 system and organ classifications （SOC）， mainly systemic diseases and various reactions at the site of administration （3 749 cases， 30.84%） and gastrointestinal system diseases （2 067 cases， 17.00%）. ADE risk signals that occurred more frequently were generally consistent with the drug instruction， such as diarrhea， fatigue， and hypertension； new ADE risk signals requiring clinical attention were death， immune-mediated nephritis， and PT signals contained in the SOC of various benign， malignant， and tumors of undetermined nature （including cysts and polyps）. CONCLUSIONS For ADEs that occur frequently with axitinib and are already contained in the drug instruction （e.g. hypertension， diarrhea）， they should be adequately evaluated before administration， especially for patients with combined use of immune checkpoint inhibitors and patients with underlying hypertension； for ADEs with stronger signals and newer ADEs （e. g. death， disease progression， tumor progression）， the patient’s disease progression should be closely monitored during the treatment period for potentially fatal ADEs； for its rare ADEs （e. g.immune-mediated nephritis， scrotal ulcer， non-infectious encephalitis）， clinical validation should be further strengthened.
ABSTRACT
OBJECTIVE To mine the safety signals of FOLFOX scheme and FOLFIRI scheme-induced hepatotoxicity， and to provide reference for the selection of clinical rational treatment plan and the prevention and treatment of drug adverse reaction （ADR）. METHODS Reporting odds ratio method and proportion report ratio method were used to analyze adverse drug event （ADE） reports of FOLFOX scheme and FOLFIRI scheme in FDA adverse event reporting system during January 1， 2004-June 30， 2022. The potential safety signals of FOLFOX scheme and FOLFIRI scheme-induced hepatotoxicity were mined. RESULTS The amounts of ADE reports related to FOLFOX scheme and FOLFIRI scheme were respectively 3 454 and 1 359； the proportions of male and female patients involved were 1.50∶1 and 1.67∶1 in these two schemes， respectively. The top five countries with the largest number of reports were the United States， Japan， France， Italy and the United Kingdom， respectively accounting for 58.48% and 53.79% of the total reported cases. More than 90% of patients took no more than 5 drugs in combination， the proportion of patients receiving FOLFOX scheme and FOLFIRI scheme combined with anti-angiogenic drugs or epidermal growth factor receptor inhibitors was 45.45% and 86.82%， respectively. Totally 443 ADE reports of FOLFOX scheme-induced hepatotoxicity were collected， and 22 ADR signals were generated， including hepatic sinusoidal obstruction syndrome， nodular regenerative hyperplasia， drug-induced liver injury， blood bilirubin increased， etc. Totally 128 ADE reports of FOLFIRI scheme- induced hepatotoxicity were reported， and 9 ADR signals were generated， including blood bilirubin increased， hepatotoxicity， steatohepatitis， hepatic steatosis， etc. CONCLUSIONS FOLFOX scheme and FOLFIRI scheme can cause different types of hepatotoxicity. Clinical drug monitoring should be strengthened to guarantee drug safety.
ABSTRACT
OBJECTIVE To provide reference for clinically safe application of avapritinib. METHODS The adverse drug event （ADE） reports of avapritinib from January 9th，2020，to September 30th，2022 were collected from FDA Adverse Event Reporting System （FAERS） database. For data mining and analysis，reporting odds ratio （ROR） method and proportional reporting ratio （PRR） method in the proportional imbalance method were utilized. RESULTS A total of 10 895 ADE reports with avapritinib as the main suspect drug were gathered，and 201 ADE signals involving 19 systematic organ classifications were found after eliminating invalid signals. The instruction of the drugs did not mention any of the ADE，including tinnitus，dementia，chilly limbs， the reduction of blood iron，the reduction of blood sugar，fever，the reduction of vitamin D and vitamin B12，as well as all ADE in the 2 SOCs of musculoskeletal and connective tissue illnesses，diseases of the reproductive system，and diseases of the breast. The majority of the ADE reports 670 cases with complete drug information were for the nervous system （230 cases，accounting for 34.33%） and ocular organ （277 cases，accounting for 41.34%）. Compared with other systems，daily dose and treatment course showed significant effects on ADE of neurological system and ocular organ （P＜0.05），and the patient’s age had a significant impact on the ADE of the nervous system （P＜0.05）. CONCLUSIONS A greater incidence of ADE after using avapritinib is present in patients older than 65 with a daily dose of 300 mg/d and a treatment period lasting between 31 and 90 days； patients receiving a daily dose of 300 mg/d and a treatment regimen lasting 31 to 90 days are more likely to experience ADE of the ocular organ. Attention should be given to the aberrant symptoms of the patient’s eyes and nervous system throughout clinical use of avapritinib，and prompt intervention should be given.