Kazuyo Shimada1, Shiori Hasegawa1,2, Satoshi Nakao1, Ririka Mukai1, Kiyoka Matsumoto1, Mizuki Tanaka1, Hiroaki Uranishi1,3, Mayuko Masuta1,4, Shohei Nishida5, Shinya Shimizu5, Yuichi Hayashi6, Akio Suzuki5, Mitsuhiro Nakamura7. 1. Laboratory of Drug Informatics, Gifu Pharmaceutical University, 1-25-4, Daigaku-nishi, Gifu, 501-1196, Japan. 2. Department of Pharmacy, Kobe City Medical Center General Hospital, 2-1-1, Minatojima minamimachi, Chuo-ku, Kobe-city, Hyogo, 650-0047, Japan. 3. Division of Pharmacy, Nara Medical University Hospital, 840, Shijo-cho, Kashihara-shi, Nara, 634-8522, Japan. 4. Division of Pharmacy, Kyoto City Hospital, 1-2, Mibu Higashitakadacho, Nakagyo-ku Kyoto-shi, Kyoto, 604-8845, Japan. 5. Department of Pharmacy, Gifu University Hospital, 1-1 Yanagido, Gifu, 501-1194, Japan. 6. Department of Neurology, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu, 501-1194, Japan. 7. Laboratory of Drug Informatics, Gifu Pharmaceutical University, 1-25-4, Daigaku-nishi, Gifu, 501-1196, Japan. mnakamura@gifu-pu.ac.jp.
Abstract
PURPOSE: Ifosfamide is extensively used to treat several malignant conditions. Administration of ifosfamide can cause encephalopathy and other neurotoxic effects. The aim of this study was to obtain novel information on the onset profiles of ifosfamide-induced encephalopathy (IIE) considering other associated clinical factors using the US Food and Drug Administration Adverse Event Reporting System (FAERS) and the Japanese Adverse Drug Event Report (JADER) databases. METHODS: We analyzed the reports of encephalopathy between 2004 and 2018 from the FAERS and JADER databases. To define IIE, we used the Medical Dictionary for Regulatory Activities (MedDRA) preferred terms and standardized queries. The reporting odds ratios (ROR) at 95% confidence interval (CI) was used to detect the signal for IIE and adjusted for covariates using a multivariate logistic regression technique. We evaluated the time-to-onset profile of IIE and used the association rule mining technique to discover undetected associations, such as potential risk factors. RESULTS: In the FAERS database, the ROR (CI) for encephalopathy (preferred term, PT) and encephalopathy (standardized MedDRA queries, SMQ) was 56.58 (51.69-61.93) and 1.57 (1.48-1.67), respectively. In the JADER database, the ROR (95% CI) for encephalopathy (PT) and encephalopathy (SMQ) was 13.54 (9.91-18.50) and 1.24 (1.01-1.53), respectively. The multivariate logistic regression analysis showed a significant contribution in IIE signal in the ≥ 60 year group (p = 0.00094; vs. < 60 year group) and ≥ 2000 mg/m2 dosage group (p = 0.00045; vs. < 2000 mg/m2 dosage group). The association rules of {ifosfamide, aprepitant} → {encephalopathy (SMQ)} demonstrated high lift values. The average dose of ifosfamide in patients with encephalopathy (PT) and without encephalopathy (PT) was 2022.8 ± 592.8 (mean ± standard deviation) and 1568.5 ± 703.2 mg/m2, respectively (p < 0.05). Encephalopathy within the first 7 days of ifosfamide administration was 94.1% for encephalopathy (PT) and 87.7% for encephalopathy (SMQ), respectively. CONCLUSIONS: The present analysis demonstrated that the incidence of encephalopathy with ifosfamide should be closely monitored for a short onset (within 7 days). The patients who are administered a high dose of ifosfamide or co-administrated aprepitant should be carefully monitored for the development of encephalopathy.
PURPOSE:Ifosfamide is extensively used to treat several malignant conditions. Administration of ifosfamide can cause encephalopathy and other neurotoxic effects. The aim of this study was to obtain novel information on the onset profiles of ifosfamide-induced encephalopathy (IIE) considering other associated clinical factors using the US Food and Drug Administration Adverse Event Reporting System (FAERS) and the Japanese Adverse Drug Event Report (JADER) databases. METHODS: We analyzed the reports of encephalopathy between 2004 and 2018 from the FAERS and JADER databases. To define IIE, we used the Medical Dictionary for Regulatory Activities (MedDRA) preferred terms and standardized queries. The reporting odds ratios (ROR) at 95% confidence interval (CI) was used to detect the signal for IIE and adjusted for covariates using a multivariate logistic regression technique. We evaluated the time-to-onset profile of IIE and used the association rule mining technique to discover undetected associations, such as potential risk factors. RESULTS: In the FAERS database, the ROR (CI) for encephalopathy (preferred term, PT) and encephalopathy (standardized MedDRA queries, SMQ) was 56.58 (51.69-61.93) and 1.57 (1.48-1.67), respectively. In the JADER database, the ROR (95% CI) for encephalopathy (PT) and encephalopathy (SMQ) was 13.54 (9.91-18.50) and 1.24 (1.01-1.53), respectively. The multivariate logistic regression analysis showed a significant contribution in IIE signal in the ≥ 60 year group (p = 0.00094; vs. < 60 year group) and ≥ 2000 mg/m2 dosage group (p = 0.00045; vs. < 2000 mg/m2 dosage group). The association rules of {ifosfamide, aprepitant} → {encephalopathy (SMQ)} demonstrated high lift values. The average dose of ifosfamide in patients with encephalopathy (PT) and without encephalopathy (PT) was 2022.8 ± 592.8 (mean ± standard deviation) and 1568.5 ± 703.2 mg/m2, respectively (p < 0.05). Encephalopathy within the first 7 days of ifosfamide administration was 94.1% for encephalopathy (PT) and 87.7% for encephalopathy (SMQ), respectively. CONCLUSIONS: The present analysis demonstrated that the incidence of encephalopathy with ifosfamide should be closely monitored for a short onset (within 7 days). The patients who are administered a high dose of ifosfamide or co-administrated aprepitant should be carefully monitored for the development of encephalopathy.
Entities:
Keywords:
Encephalopathy; FAERS; FDA Adverse Event Reporting System; Ifosfamide; JADER; Japanese Adverse Drug Event Report
Authors: Daoud Ali Mohamed; Arthur Semedo; Boris Adeyemi; Leila Hessissen; Maria El Kababri; Nazik Allali; Latifa Chat; Siham El Haddad Journal: Glob Pediatr Health Date: 2021-07-14