Association of CYP2C9*3 with phenytoin ‐induced Stevens‐Johnson syndrome and toxic epidermal necrolysis: A systematic review and meta‐analysis

Summary What is known and objectiveStevens‐Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe cutaneous adverse reactions that can be induced by phenytoin (PHT). CYP2C9*3 is the key enzyme in PHT metabolism. The aim of this meta‐analysis was to evaluate the association between CYP2C9*3 and PHT‐induced SJS/TEN. MethodsAn extensive search was performed in multiple databases, including the Cochrane Library, EMBASE, PubMed, OVID and EBSCO. Studies exploring the relationship between CYP2C9*3 and PHT‐induced SJS and TEN were included. Odds ratios (ORs) with corresponding 95% confidence intervals (CI) were calculated for dichotomous data. Data analysis was performed using Review Manager (version 5.3). Results and discussionFour studies, with 117 PHT‐induced SJS/TEN cases and 338 matched controls (PHT‐tolerant patients) or 4231 population controls (general population), were identified. SJS and TEN were found to be significantly associated with the CYP2C9*3 allele, comparing both matched controls (OR, 8.93; 95% CI, 2.63‐30.36; P = .0005) with substantial heterogeneity (I2 = 46%) and population controls (OR, 8.88; 95% CI, 5.01‐15.74; P < .00001). What is new and conclusionA significant association between CYP2C9*3 and PHT‐induced SJS/TEN was identified, especially in a Thai population. CYP2C9*3 is thus a credible predictive genetic marker of PHT‐induced SJS/TEN. Further multicenter studies and large prospective observational studies are,...
Source: Journal of Clinical Pharmacy and Therapeutics - Category: Drugs & Pharmacology Authors: Tags: ORIGINAL ARTICLE Source Type: research