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Table 1 Potential GI and liver adverse effects and drug interaction profile of COVID-19 investigational drugs

From: SARS-CoV-2-associated gastrointestinal and liver diseases: what is known and what is needed to explore

  Mechanism of action GI affection Liver affection Major drug-drug interactions
Chloroquine/hydroxychloroquine [80] Interferences with terminal glycosylation of ACE2 receptor
Blocks viral entry by increasing endosomal pH and inhibiting viral fusion to the cell membrane
Nausea, vomiting, weight loss, abdominal pain Rare elevations in aminotransferases. Most reactions are Idiosyncrasy or oxidative stress. A moderate inhibitor of CYP2D6 and P-gp
Significant particularly with anti-rejection immunosuppressants.
Weak interaction with tenofovir/entecavir
Hydroxychloroquine given to a patient taking hepatitis c treatment should monitor for cardiac arrhythmia
Ivermectin [81] Inhibition of viral IMPα/β1-mediated nuclear import, which reduces the replication of the virus and so the viral load Nausea, vomiting, diarrhea Very few reports on elevated liver enzymes or Jaundice Avoid concomitant use of ivermectin with other drugs that enhance GABA activity
Nitazoxanide [82] Antiparasitic drug has broad-spectrum anti-viral activity Abdominal pain (8%), diarrhea (2%), nausea (3%), vomiting (1%) Increased ALT: <1% Rapidly hydrolyzed to tizoxanide. which is highly protein-bound (>99%), so caution when giving with other highly protein-bound drugs with narrow therapeutic indices.
Atazanavir [83] Protease inhibitors Diarrhea, nausea, vomiting, abdominal pain Indirect hyperbilirubinemia with overt jaundice
Elevation of hepatic enzymes especially in patients with underlying HBV or HCV co-infection
Inhibitor of CYP3A4 and CYP2C9
PPI decreases its concentrations.
Tenofovir and efavirenz should not be co-administered with atazanavir
Favipiravir [84] RNA-dependent RNA polymerase inhibitor Nausea/vomiting (5–15%), diarrhea (5%) Liver enzyme abnormalities Inhibitor for: CYP2C8 and aldehyde oxidase
Interferon beta [85] Cytokines with anti-viral and immunomodulatory effects. Nausea, vomiting Elevated liver enzymes DDI potential not fully evaluated.
Possible inhibitor of CYP enzymes
Lopinavir/ritonavir [86] HIV protease inhibitor/CYP450inhibitor Nausea/vomiting (5–10%), abdominal pain (1–10%), diarrhea (10–30%), dysgeusia (< 2%), increased serum amylase/lipase. Hepatotoxicity ranges from mild elevations in aminotransferases to acute liver failure.
Recovery takes 1–2 mo.
Might include drug-cytochrome P-450 interaction
Substrate for: CYP3A4, CYP2D6, P-gp
Inducer for: CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, UGT1A1
Inhibitor for: CYP3A4
Increased levels of Immunosuppressive drugs (calcineurin and mTOR inhibitors).
Moderate interaction risk with tenofovir with renal functions monitoring.
Lopinavir/ ritonavir increase concentrations of hepatitis C treatment.
Remdesivir [87] RNA-dependent RNA polymerase inhibitor Nausea, vomiting Deranged liver enzymes Hepatotoxicity reported; frequency is not yet known. NA
Ribavirin [88] Inhibit capping of viral messenger RNA, and the viral RNA-dependent polymerase Nausea Hepatotoxicity NA
Anakinra [89] IL-1R inhibitor Rare abdominal pain, nausea, diarrhea Hepatobiliary disorders: Elevated transaminases, noninfectious hepatitis No effect on CYP450.
Baricitinib [90] JAK1 and JAK2 inhibitor
Inhibit viral endocytosis
Bowel perforation, nausea, vomiting Hepatitis B reactivation Partially metabolized by CYP3A4 and a substrate for OAT3 and P-gp
OAT3 inhibitors cause a significant effect on baricitinib exposure
Dexamethasone/ Hydrocortisone [59] Reduction of IL-8, monocyte chemo-attractant protein-1, and Th1 chemokine IFN-γ-inducible protein-10 Nausea, peptic ulcers NA Aspirin can increase the risk of bleeding when used with it
Ruxolitinib [91] Selective JAK inhibitors NA Increased ALT
Increased AST
Metabolized by CYP3A4 and CYP2C9. So, it is liable to DDIs with inhibitors or inducers of these enzymes.
Ruxolitinib may inhibit BCRP and P-gp, and caution is indicated with co-administering with substrates of these transporters with narrow therapeutic indices.
Sarilumab [92] IL-6R inhibitor Few cases of gastrointestinal perforation Increased ALT No effect on CYP450
Tocilizumab [93] IL-6R inhibitor (Curbs cytokine release syndrome) Bowel perforation, pancreatitis, abdominal pain Elevated liver enzymes, Reactivation of chronic hepatitis B No effect on CYP450
  1. ACE angiotensin-converting enzyme, ALT alanine aminotransferase, AST aspartate aminotransferase, BCRP breast cancer resistance protein, COVID-19 coronavirus disease-19, CYP cytochrome P450, DDI drug-drug interaction, GABA γ-aminobutyric acid, GI gastrointestinal, HIV human immunodeficiency virus, IFN interferon, IL interleukin, IMP α/β-mediated nuclear import, JAK Janus kinase, OAT organic anion transporter, P-gp P-glycoprotein, PPI proton pump inhibitor, Th t-helper, TOR target of rapamycin