Snapshot A 54-year-old man presents to his primary care physician with fatigue and issues with sleep. His symptoms are associated with nausea and abdominal discomfort. A few days ago, he noted dark urine but denies any dysuria. He said that in the past he experienced severe right upper quadrant pain and jaundice approximately 8 years ago, requiring treatment which he does not remember the specifics. Social history is remarkable for intravenous drug use and had required a transfusion over a decade ago. Laboratory testing is remarkable for slightly elevated alanine aminotransferase (ALT) and aspartate aminotransferase (AST) level. He has a reactive HCV antibody and positive HCV RNA test. He is started on sofosbuvir-ledipasvir for chronic HCV infection. Introduction Note that none of these medications are used as monotherapy Hepatitis C Drugs Medications Comments Ledipasvir Mechanism of action hepatitis C virus (HCV) NS5A protein inhibitorNS5A is an HCV viral phosphoprotein that is necessary for viral replication Clinical use HCV chronic infection Adverse effects headache weakness fatigue Ribavirin Mechanism of action inosine monophosphate dehydrogenase competitive inhibitor impairs viral DNA and RNA replication Clinical use HCV chronic infection Adverse effects hemolytic anemia severe teratogen Simeprevir Mechanism of action HCV protease (NS3/4A) inhibitor NS3/4A is also essential for viral replication this is a specifically targeted antiviral therapy for HCV Clinical use HCV chronic infection Adverse effects photosensitivity reactions rash Sofosbuvir Mechanism of action inhibits HCV RNA-dependent RNA polymerase (NS5B), which is also essential for viral replication Clinical use HCV chronic infection Adverse effects headache fatigue nausea Mechanism of action inosine monophosphate dehydrogenase competitive inhibitor impairs viral DNA and RNA replication Clinical use HCV chronic infection Adverse effects hemolytic anemia severe teratogen Mechanism of action HCV protease (NS3/4A) inhibitor NS3/4A is also essential for viral replication this is a specifically targeted antiviral therapy for HCV Clinical use HCV chronic infection Adverse effects photosensitivity reactions rash Mechanism of action inhibits HCV RNA-dependent RNA polymerase (NS5B), which is also essential for viral replication Clinical use HCV chronic infection Adverse effects headache fatigue nausea