Hepatotoxicity induced by coxibs: How concerned should we be?

HERNÁNDEZ N.; MENDIZÁBAL M.; LUCENA M.I.; ROMA M.G.; MEDINA CÁLIZ I.; ANDRADE R.J.; BESSONE F.; RIDRUEJO E.; ROBLES-DÍAS M.

EXPERT OPINION ON DRUG SAFETY

INFORMA HEALTHCARE

Lugar: London; Año: 2016 vol. 15 p. 1463 - 1475

1474-0338

Introduction: The selective inhibitors of COX-2, coxibs, arenonsteroidal anti-inflammatory drugs (NSAIDs) that have much bettergastrointestinal safety profile as compared with non-selective NSAIDs. In thisreview, we analyze both the epidemiological featuresof coxib-induced hepatotoxicity and the clinical impact of coxib-associatedliver damage, based on literature data.Areas covered: We carried out a systematic search of thedatabases MEDLINE (PubMed), LILACS and SCIELO, from December 1999 to January2016, to retrieve studies exploring both the real impact of coxibs in livertoxicity and its incidence compared with non-selective COX-2 inhibitors NSAIDs.Expert opinion: Although reliable data on the incidence ofcelecoxib- and etoricoxib-induced hepatotoxicity are lacking because of cohortstudies have been generally underpowered to detect hepatic events, coxibs havebeen scarcely related to hepatotoxicity. Hence, coxib-induced liver injuryseems to be an uncommon event, presenting with a wide spectrum of damage.Increasing COX-2 drug selectivity, as for rofecoxib, valdecoxib, parecoxib, andlumiracoxib, has been associated with higher cardiovascular risk, as well as dermatologicaland serious hepatic reactions. The actual risk of livertoxicity from the currently approved coxibs compared with non-selective NSAIDswill be discussed. Finally, classical and novel molecular mechanisms of coxib-inducedhepatotoxicity are also described.