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Previous Volume 361:1317-1318 September 24, 2009 Number 13

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To the Editor: The use of generic drugs has increased in the European Union in recent years. The main regulatory requirement for these products is that they be bioequivalent to the branded drug. However excipients such as soybean oil can be a cause of hypersensitivity reactions^1,2; the protein content of fully refined seed oils should be suspected in the case of allergic reactions.³

We report on two women (58 and 81 years of age) who presented with anaphylaxis a few minutes after ingesting a generic omeprazole capsule.^4,5 In both women the systolic blood pressure fell to less than 90, and both had sudden onset of difficulty breathing. Both women had previously taken nongeneric omeprazole and had not had a reaction. The generic drug that each of the women took contained approved soybean oil as an excipient. After the women provided written informed consent, skin-prick tests and soybean-specific IgE assays (ImmunoCAP assay, Phadia) were performed. Patient 1 had a wheal diameter of 20 mm after the injection of soybean extract (ALK-Abelló) and a wheal diameter of 14 mm after the injection of the powder contained in a capsule of generic omeprazole diluted 1:10 in 0.9% saline solution; her soybean-specific IgE level was 9.01 kU per liter. Patient 2 had a wheal diameter of 14 mm after the injection of soybean extract and of 12 mm after the injection of the powder contained in generic omeprazole; her soybean-specific IgE level was 23 kU per liter.

The skin-prick tests for nongeneric omeprazole were negative in the 2 patients and in 10 controls without atopy. The skin-prick tests for generic omeprazole extract were positive in five patients who were sensitized to soybean (wheal diameter, 10 mm).

An IgE dot blot (Bio-Rad) was performed on the powder contained in generic omeprazole capsules from two manufacturers, on the powder in nongeneric omeprazole capsules reconstituted in 20% ethanol and 80% water, on soybean extract, and on soybean oil. The serum from the two patients showed a positive response to the generic omeprazole produced by each of the two manufacturers, to soybean oil, and to soybean extract but a negative reaction to diluent control wells and to nongeneric omeprazole. The serum from nonatopic controls did not react to any of the products tested (Figure 1).

View larger version (25K): [in this window] [in a new window]   Figure 1. Results of IgE Dot Blot Assay. Responses of serum from Patients 1 and 2 and from a nonatopic patient to generic omeprazole from two different manufacturers, to nongeneric omeprazole, to soybean oil, to soybean extract, and to diluents are shown. The response to Dermatophagoides pteronyssinus of serum from a patient who was sensitized to D. pteronyssinus extract, which was used as a positive control of the assay, is also shown.

 
Whereas active ingredients are clearly identified in the labels of generic drugs, excipients and additives are frequently defined as "excip. c.s." A diagnosis of soy allergy should not be overlooked in cases of drug hypersensitivity. We suggest testing for soy in all patients who have hypersensitivity reactions to any drug that may contain soy.

Antonio Dueñas-Laita, M.D., Ph.D.
Rio Hortega University Hospital
Valladolid, Spain

Fernando Pineda, D.Pharm., Ph.D.
Diater Laboratories
Madrid, Spain

Alicia Armentia, M.D., Ph.D.
Rio Hortega University Hospital
Valladolid, Spain
aliciaarmentia{at}gmail.com

Dr. Pineda reports being an employee of Diater Laboratories, which specializes in the manufacture of specific immunotherapy with allergens. No other potential conflict of interest relevant to this letter was reported.

References

1. Moneret-Vautrin DA, Morisset M, Flabbee J, Kanny G, Kirch F, Parisot L. Unusual soy oil allergy. Allergy 2002;57:266-267. [Web of Science][Medline]
2. Hofer KN, McCarthy MW, Buck ML, Hendrick AE. Possible anaphylaxis after propofol in a child with food allergy. Ann Pharmacother 2003;37:398-401. [Free Full Text]
3. Ramazzotti M, Mulinacci N, Pazzagli L, et al. Analytic investigations on protein content in refined seed oils: implications in food allergy. Food Chem Toxicol 2008;46:3383-3388. [CrossRef][Web of Science][Medline]
4. Stefanaki EC, Vovolis V, Letsa I, Koutsostathis N. Anaphylactic reaction to omeprazole. Am J Gastroenterol 2008;103:1581-1583. [CrossRef][Web of Science][Medline]
5. Confino-Cohen R, Goldberg A. Anaphylaxis to omeprazole: diagnosis and desensitization protocol. Ann Allergy Asthma Immunol 2006;96:33-36. [Web of Science][Medline]

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