Etoricoxib and its hidden risks: a case-based review of dermatological, hematological, and cardiovascular complications

Abstract

This review analyzes case reports of adverse drug reactions (ADRs) attributed to etoricoxib, with particular emphasis on Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), fixed drug eruptions (FDE), atrial fibrillation, hypertension, thrombocytopenia (TP), immune hemolytic anemia (IHA), acute generalized exanthematous pustulosis (AGEP), maculopapular rash, pretibial erythema with edema, and reversible cerebral vasoconstriction syndrome (RCVS). Although infrequent, these severe hypersensitivity and cardiovascular events pose significant clinical risks due to their association with substantial morbidity and, in some cases, mortality. The primary aim of this review is to consolidate available clinical evidence to evaluate the causality, characteristic clinical presentations, and broader safety implications of etoricoxib in relation to these adverse outcomes. While SJS/TEN are marked by widespread epidermal necrosis and detachment, FDE typically recurs at fixed sites with residual pigmentation. Hematological complications such as drug-induced (TP) and Drug-induced IHA have also been reported, presenting as sudden platelet decline or severe hemolysis, respectively. These adverse effects often appear within hours to weeks of initiating therapy. Cutaneous manifestations, including exanthematous pustulosis and maculopapular rashes, further complicate the drug's safety profile. Etoricoxib's pro-thrombotic potential, possibly linked to COX-2 selectivity, remains a cardiovascular concern. Causality assessments via the Naranjo Scale and WHO-UMC often support a probable link. These findings underscore the necessity for careful evaluation of patient history, immediate drug discontinuation upon clinical suspicion, and strengthened pharmacovigilance systems to better capture and characterize the full range of these rare yet serious reactions. See also the graphical abstract(Fig. 1).

Keywords: Stevens-Johnson syndrome; atrial fibrillation; etoricoxib; fixed drug eruptions; hypertension; toxic epidermal necrolysis.

Table 1. Dosage and indication of etoricoxib

Table 2. Cases reported on Etoricoxib induced TEN and SJS-TEN Overlap

Table 3. Cases reported of Etoricoxib induced SJS

Table 4. Cases reported on Etoricoxib induced FDE

Table 5. Cases reported on Etoricoxib induced AF and hypertension

Table 6. Cases reported on Etoricoxib induced Thrombocytopenia

Table 7. Cases reported on Etoricoxib induced Immune Hemolytic Anemia

Table 8. Cases reported on Etoricoxib induced AGEP, maculopapular rash, pretibial erythema and RCVS with ischemic stroke

Figure 1. Graphical abstract

Figure 2. Physiological roles of COX-1 and COX-2

Figure 3. Pathway mediated by COX-1, COX-2 and inhibition by NSAIDs

Figure 4. Cardio and nephrotoxicity pathway of etoricoxib