Natural rubber pharmaceutical vial closures release latex allergens that produce skin reactions

Background: The release of allergenic proteins from natural rubber vial clo sures (stoppers) into aqueous pharmaceuticals may induce allergic reactions In individuals with latex allergy (LA) receiving medications from such via ls. Objective: The goal of this study was to determine whether solutions stored in vials containing natural rubber closures release allergenic proteins de tectable by skin testing of subjects with LA. Methods: Five pharmaceutical vial closures (2 natural rubber and 3 syntheti c) were coded, inserted onto vials containing phenol-saline-human serum alb umin, and stored in an inverted position before use. Twelve volunteers with and 11 volunteers without LA underwent skin testing with solutions from ea ch of the 5 vials, either those not punctured (OP) or those punctured 40 ti mes with a 21-gauge needle 12 to ZA hours before testing (40P), Results: Al l intradermal skin test responses in the group without LA were negative. Tw o and 5 of the 12 subjects with LA had positive intradermal skin reactions to OP and 40P solutions, respectively, from vials containing rubber closure s. Two subjects with LA had inexplicable, positive, nonreproducible intrade rmal skin test reactions to solutions from vials containing bromobutyl but not vials with isoprene synthetic closures. In vitro inhibition analysis de tected 6 to 7 AU/g latex allergen in extracts of cut natural rubber contain ing closures but not in extracts of synthetic closures. Conclusion: Natural rubber vial closures released allergenic latex proteins into the tested solutions in direct contact during storage in sufficient q uantities to elicit positive intradermal skin reactions in some individuals with LA. These data support a recommendation to eliminate natural rubber f rom closures of pharmaceutical vials.