PMID- 35046808 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220121 IS - 1663-9812 (Print) IS - 1663-9812 (Electronic) IS - 1663-9812 (Linking) VI - 12 DP - 2021 TI - Adverse Events During Pregnancy Associated With Entecavir and Adefovir: New Insights From a Real-World Analysis of Cases Reported to FDA Adverse Event Reporting System. PG - 772768 LID - 10.3389/fphar.2021.772768 [doi] LID - 772768 AB - Background: Due to the embryotoxicity found in animal studies and scarce clinical data in pregnant women, it is still controversial whether entecavir (ETV) and adefovir dipivoxil (ADV) are safe during human pregnancy. This is of paramount importance when counseling pregnant women with hepatitis B virus (HBV) on risks and benefits to their offspring. Objective: To quantify the association between administration of ETV and ADV in pregnant women and occurrence of adverse events (AEs) during pregnancy (AEDP). Methods: Pregnancy reports from the FDA Adverse Event Reporting System (FAERS) were used to perform a retrospective analysis of AEDP associated with ETV or ADV. Disproportionality analysis estimating the reporting odds ratio (ROR) was conducted to identify the risk signals. A signal was defined as ROR value >2, and lower limit of 95% confidence interval (CI)> 1. Results: A total of 1,286,367 reports involving AEDP were submitted to FAERS by healthcare professionals. Of these, there were 547 cases reporting ETV and 242 cases reporting ADV as primary suspected drugs. We found a moderate or strong signal for increased risk of spontaneous abortion when comparing ETV with tenofovir disoproxil fumarate (TDF) and telbivudine (LdT), with RORs equal to 1.58 (95% CI, 1.09-2.30) and 2.13 (95% CI, 1.04-4.36), respectively. However, when the included reports were limited to indication containing HBV infection, no signals for increased AEDP were detected. Futhermore, a strong signal for increased risk of spontaneous abortion was identified in patients with HBV infection when comparing ETV or ADV with lamivudine (LAM), with RORs of 3.55 (95% CI, 1.54-8.18) and 2.85 (95% CI, 1.15-7.08), respectively. Conclusion: We found a strong signal for increased risk of spontaneous abortion in patients with HBV infection taking ETV or ADV, in comparison with those prescribed with LAM. Moreover, no obvious signal association of human teratogenicity with exposure to ETV or ADV was identified in fetuses during pregnancy. Nevertheless, owing to the limitations of a spontaneous reporting database, which inevitably contains potential biases, there is a pressing need for well-designed comparative safety studies to validate these results in clinical practice. CI - Copyright (c) 2022 Yang, Yin, Zhao, Li, Zhang, Li, Zhang and Faiola. FAU - Yang, Renjun AU - Yang R AD - State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, China. AD - College of Resources and Environment, University of Chinese Academy of Sciences, Beijing, China. FAU - Yin, Nuoya AU - Yin N AD - State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, China. AD - College of Resources and Environment, University of Chinese Academy of Sciences, Beijing, China. FAU - Zhao, Ying AU - Zhao Y AD - Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, China. FAU - Li, Dandan AU - Li D AD - Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, China. FAU - Zhang, Xuanling AU - Zhang X AD - Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, China. FAU - Li, Xingang AU - Li X AD - Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, China. FAU - Zhang, Yang AU - Zhang Y AD - Department of Pharmacy, Beijing Friendship Hospital, Capital Medical University, Beijing, China. AD - Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, China. FAU - Faiola, Francesco AU - Faiola F AD - State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, China. AD - College of Resources and Environment, University of Chinese Academy of Sciences, Beijing, China. LA - eng PT - Journal Article DEP - 20220103 PL - Switzerland TA - Front Pharmacol JT - Frontiers in pharmacology JID - 101548923 PMC - PMC8762051 OTO - NOTNLM OT - FAERS OT - adefovir OT - disproportionality analysis OT - entecavir OT - pregnancy OT - reporting odds ratio COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/01/21 06:00 MHDA- 2022/01/21 06:01 PMCR- 2022/01/03 CRDT- 2022/01/20 06:01 PHST- 2021/09/09 00:00 [received] PHST- 2021/11/30 00:00 [accepted] PHST- 2022/01/20 06:01 [entrez] PHST- 2022/01/21 06:00 [pubmed] PHST- 2022/01/21 06:01 [medline] PHST- 2022/01/03 00:00 [pmc-release] AID - 772768 [pii] AID - 10.3389/fphar.2021.772768 [doi] PST - epublish SO - Front Pharmacol. 2022 Jan 3;12:772768. doi: 10.3389/fphar.2021.772768. eCollection 2021.