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

Abstract

Background: The release of allergenic proteins from natural rubber vial closures (stoppers) into aqueous pharmaceuticals may induce allergic reactions in individuals with latex allergy (LA) receiving medications from such vials. Objective: The goal of this study was to determine whether solutions stored in vials containing natural rubber closures release allergenic proteins detectable by skin testing of subjects with LA. Methods: Five pharmaceutical vial closures (2 natural rubber and 3 synthetic) were coded, inserted onto vials containing phenol-saline-human serum albumin, and stored in an inverted position before use. Twelve volunteers with and 11 volunteers without LA underwent skin testing with solutions from each of the 5 vials, either those not punctured (0P) or those punctured 40 times with a 21-gauge needle 12 to 24 hours before testing (40P). Results: All intradermal skin test responses in the group without LA were negative. Two and 5 of the 12 subjects with LA had positive intradermal skin reactions to 0P and 40P solutions, respectively, from vials containing rubber closures. Two subjects with LA had inexplicable, positive, nonreproducible intradermal skin test reactions to solutions from vials containing bromobutyl but not vials with isoprene synthetic closures. In vitro inhibition analysis detected 6 to 7 AU/g latex allergen in extracts of cut natural rubber containing 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 quantities to elicit positive intradermal skin reactions in some individuals with LA. These data support a recommendation to eliminate natural rubber from closures of pharmaceutical vials.