Entecavir administration to pregnant Japanese woman with chronic hepatitis B and hepatocellular carcinoma: A case report

Abstract

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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

“…However, species and dosage differences make it difficult to determine whether the toxicity observed in pregnant animals after exposure to ETV or ADV could be translated to humans administered with the drug’s therapeutic dosage. To date, there are only limited cases available in the scientific literature regarding the safety of ETV or ADV in unintended pregnant women ( Kakogawa et al, 2011 ; Gao et al, 2020 ; Kakiuchi et al, 2021 ). As far as we know, our study is the first disproportionality analysis utilizing real-world data from a large pharmacovigilance database to identify the association between the adiministration of ETV or ADV in pregnant women and the occurrence of AEDP.…”

“…The FDA previously rated ETV and ADV as pregnancy category C agents, although that category classification is no longer applied due to oversimplified risk-benefit profile of the mother and fetus. Partly as a result, very few cases of patients treated with ETV or ADV during pregnancy have been reported in the literature ( Kakogawa et al, 2011 ; Gao et al, 2020 ; Kakiuchi et al, 2021 ). Limited reported cases may indicate that some women chose to continue administration of ETV or ADV for HBV treatment during pregnancy, with no evidence of increased incidence of birth defects in infants or higher risk of AEs for mothers ( Kakogawa et al, 2011 ; Yu et al, 2011 ; Gao et al, 2020 ; Kakiuchi et al, 2021 ).…”

“…Partly as a result, very few cases of patients treated with ETV or ADV during pregnancy have been reported in the literature ( Kakogawa et al, 2011 ; Gao et al, 2020 ; Kakiuchi et al, 2021 ). Limited reported cases may indicate that some women chose to continue administration of ETV or ADV for HBV treatment during pregnancy, with no evidence of increased incidence of birth defects in infants or higher risk of AEs for mothers ( Kakogawa et al, 2011 ; Yu et al, 2011 ; Gao et al, 2020 ; Kakiuchi et al, 2021 ). Generally, small-scale clinical studies are not robust enough to address drug safety.…”

“…First, we provided a head-to-head assessment of pregnancy-related safety signals for NAs in one of the largest pharmacovigilance databases, considering it is almost impossible to conduct a prospective clinical study to evaluate the safety profile of NAs in the mother and fetus during pregnancy, due to ethical concerns. Second, unlike the previous case reports or small-scale retrospective studies mentioned above ( Kakogawa et al, 2011 ; Gao et al, 2020 ; Kakiuchi et al, 2021 ), in which the included pregnant women treated with ETV or ADV were no more than 20, this study examined 789 women taking ETV or ADV during pregnancy, with a long study period of over 17 years (from Q1/2004 to Q1/2021), providing more convincing and relatively more valuable evidence for post-market surveillances of drug safety. Third, the FAERS database has the capability to capture some safety events such as abortion in pregnancy, which are not reported in the APR or missed in prospective studies ( Antiretroviral Pregnancy Registry Steering Committee, 2021 ).…”

Effect of Entecavir Combined with Adefovir Dipivoxil on Clinical Efficacy and TNF-α and IL-6 Levels in Patients with Hepatitis B Cirrhosis

“…Clinical trials have found that patients with hepatitis B cirrhosis may show liver fibrosis and increased expression levels of serum inflammatory factors during treatment, leaving them in a microinflammatory state for a long time and thus affecting the therapeutic effect [ 5 ]. Entecavir, adefovir dipivoxil, and lamivudine, with antibacterial and antivirus effects, are common and effective clinical drugs to treat liver cirrhosis [ 6 ]. Although entecavir has a good antiviral effect for newly diagnosed patients with hepatitis, they are easily affected by high variability of the virus.…”