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Expert Opin Drug Metab Toxicol. 2018 May;14(5):483-491. doi: 10.1080/17425255.2018.1472236. Epub 2018 May 7.

An update on the toxicological considerations for protease inhibitors used for hepatitis C infection.

Author information

1
a Department of Medicine, Queen Mary Hospital , The University of Hong Kong , Hong Kong , China.
2
b State Key Lab for Liver Research , The University of Hong Kong , Hong Kong , China.

Abstract

Hepatitis C virus protease inhibitors (PIs) are important components of many direct acting antiviral regimens. Many clinical trials and real-world studies have described the safety data for individual PIs. We aimed to review the safety of both the first and second generation PIs in patients with chronic hepatitis C (CHC). Areas covered: The unique pharmacokinetic properties of PIs partly explain their toxicities. Second generation PIs, when used without interferon and ribavirin, are well-tolerated. Use of PIs in renal impaired patients or those on dialysis appears to be safe. Decompensated cirrhosis is a contraindication for PIs use due to increased drug exposure and risk of liver decompensation. Drug-drug interactions are common and should be always monitored; some drugs should not be co-administered with PIs. In patients with co-infected hepatitis B virus, reactivation after DAA (whether PI-containing or not) is a concern. Expert opinion: Second generation PIs are key players in the current DAA era. Post-marketing surveillance is essential to monitor unknown adverse events and drug-drug interactions. Non-PI based DAA should be used in decompensated liver disease. The use of these drugs should also be explored in the paediatric population.

KEYWORDS:

Chronic kidney disease; cirrhosis; direct acting antiviral; drug interaction; hepatitis B virus; hepatitis C virus; protease inhibitor; safety

PMID:
29718748
DOI:
10.1080/17425255.2018.1472236
[Indexed for MEDLINE]

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