Evaluation of the Safety Profile of Direct-Acting Antivirals on Patients with Hepatitis C Virus: A Pharmacovigilance Study

• Published in: Therapeutic innovation & regulatory science 2023-09, Vol.57 (5), p.997-1007
• Main Authors: El-Marakby, Mai G., Solayman, Mohamed H., Sabri, Nagwa A.
• Format: Article
• Language: English
• Subjects: Anemia; Anilides - therapeutic use; Antiviral agents; Antiviral Agents - adverse effects; Antiviral drugs; Cirrhosis; Cross-Sectional Studies; Drug Safety and Pharmacovigilance; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Hepacivirus; Hepatitis; Hepatitis C; Hepatitis C - drug therapy; Hepatitis C, Chronic - drug therapy; Humans; Impairment; Liver diseases; Medicine; Original Research; Patients; Pharmacotherapy; Pharmacovigilance; Pharmacy; Population studies; Population-based studies; Recurrence; Regression analysis; Renal function; Ribavirin; Ribavirin - adverse effects; Ritonavir; Ritonavir - therapeutic use; Safety; Side effects; Sofosbuvir - adverse effects; Sustained Virologic Response; Viruses
• ISSN: 2168-4790; 2168-4804
• DOI: 10.1007/s43441-023-00537-x

Background Hepatitis C virus (HCV) is the primary contributor to chronic hepatic diseases. A rapid change in the situation took place with the advent of oral direct-acting antivirals (DAAs). However, a comprehensive review of the adverse event (AE) profile of the DAAs is lacking. This cross-sectional study aimed to analyze the reported Adverse Drug Reactions (ADRs) with DAA treatment using data from VigiBase, the WHO Individual Case Safety Report (ICSR) database. Methods All ICSRs reported to VigiBase with sofosbuvir (SOF), daclatasvir (DCV), sofosbuvir /ledipasvir (SOF/LDV) and ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) in Egypt were extracted. Descriptive analysis was performed to summarize patients’ and reactions’ characteristics. Information components (ICs) and proportional reporting ratios (PRRs) for all reported ADRs were calculated to identify signals of disproportionate reporting. Logistic regression analysis was performed to identify the DAAs association with serious events of concern while adjusting for age, gender, pre-existing cirrhosis, and ribavirin use. Results Out of 2925 reports, 1131 (38.6%) were serious. The most commonly reported reactions; anaemia (21.3%), HCV relapse (14.5%) and headache (14%). For the disproportionality signals; HCV relapse was reported with SOF/DCV (IC 3.65, 95% CrI 3.47–3.79) and SOF/RBV (IC 3.69, 95% CrI 3.37–3.92), while anaemia (IC 2.85, 95% CrI 2.26–3.27) and renal impairment (IC 2.12, 95% CrI 0.7–3.03) were reported with OBV/PTV/r. Conclusion The highest severity index and seriousness were reported with SOF/RBV regimen. A significant association was found for OBV/PTV/r with renal impairment and anaemia although being the superior regimen in terms of efficacy. The study findings call for further population-based studies for clinical validation.