Correspondence

Hypersensitivity to Generic Drugs with Soybean Oil

N Engl J Med 2009; 361:1317-1318September 24, 2009

Article

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 reactions1,2; 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 1Figure 1Results of IgE Dot Blot Assay.).

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@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.

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Citing Articles (2)

Citing Articles

1. 1

   Maria Grazia Ursino, Elisabetta Poluzzi, Carla Caramella, Fabrizio De Ponti. (2011) Excipients in medicinal products used in gastroenterology as a possible cause of side effects. Regulatory Toxicology and Pharmacology 60:1, 93-105
   CrossRef

2. 2

   Joel Shuster. (2009) ISMP Adverse Drug Reactions - Interferon Beta–Induced Panniculitis Mimicking Acute Appendicitis; Acute Methotrexate NeurotoxicityWith Associated Choreiform Movements; Chorea Associated With Gabapentin Use; Acute Interstitial Nephritis Associated With Linezolid; Atypical Neuroleptic Malignant Syndrome With Quetiapine; Hypersensitivity Reactions to Generic Drugs With Soybean Oil. Hospital Pharmacy 44:12, 1066-1071
   CrossRef