Hypersensitivity reactions to anthranilic acid derivatives

Abstract

Anthranilic acid derivatives are a group of nonsteroidal antiinflammatory drugs that include glafenine and fenamates. We report a woman who had immediate adverse reactions to glafenine and meclofenamate sodium. Skin prick and intradermal tests were performed with solutions of glafenine and meclofenamate in phosphate-buffered saline (PBS) and with the drugs bound to human serum albumin (HSA). Prick and intradermal tests with PBS solutions were negative for both drugs as were prick tests with HSA solutions. Intradermal tests with HSA-glafenine, however, were positive at 20 minutes, and at 6 and 24 hours. Intradermal tests with HSA-meclofenamate elicited a positive response at 6 and 24 hours. These tests were negative when performed in control subjects. A leukocyte histamine release test and a RAST assay were negative for both drugs. The patient was challenged following a double-blind placebo-controlled oral procedure and tolerated therapeutic doses of aspirin, indomethacin, ibuprofen, dipyrone, diclofenac, piroxicam, and acetaminophen. The oral challenge with glafenine and meclofenamate reproduced the reactions (eliciting doses: 50 mg and 15 mg, respectively), and the patient also reacted to 30 mg of mefenamic acid, an anthranilic acid derivative she had never previously received. This is an exceptional case of selective adverse reactions to glafenine and fenamates, anthranilic acid derivatives, in a patient tolerating aspirin and other cyclooxygenase inhibitors. Our study implicates an immunologic mechanism, and the existence of cross-reactivity between the drugs (or some active metabolite generated in vivo).