A Case of Codeine Induced Anaphylaxis via Oral Route

Abstract

Codeine is widely prescribed in clinical settings for the relief of pain and non-productive coughs. Common adverse drug reactions to codeine include constipation, euphoria, nausea, and drowsiness. However, there have been few reports of serious adverse reactions after codeine ingestion in adults. Here, we present a case of severe anaphylaxis after oral ingestion of a therapeutic dose of codeine. A 30-year-old Korean woman complained of the sudden onset of dyspnea, urticaria, chest tightness, and dizziness 10 minutes after taking a 10-mg dose of codeine to treat a chronic cough following a viral infection. She had previously experienced episodes of asthma exacerbation following upper respiratory infections, and had non-atopic rhinitis and a food allergy to seafood. A skin prick test showed a positive response to 1-10 mg/mL of codeine extract, with a mean wheal size of 3.5 mm, while negative results were obtained in 3 healthy adult controls. A basophil histamine release test showed a notable dose-dependent increase in histamine following serial incubations with codeine phosphate, while there were minimal changes in the healthy controls. Following a CYP2D6 genotype analysis, the patient was found to have the CYP2D6*1/*10 allele, indicating she was an intermediate metabolizer. An open label oral challenge test was positive. To the best of our knowledge, this is the first report of a patient presenting with severe anaphylaxis after the ingestion of a therapeutic dose of codeine, which may be mediated by the direct release of histamine by basophils following exposure to codeine.

Perioperative Anaphylaxis

“…A study evaluating the role of SPT in investigating morphine, meperidine, and papaveratum hypersensitivity showed that opiate-sensitive individuals responded similarly as the control study in the SPT, suggesting that this test should not be performed and that placebo-controlled challenge should be considered when possible [76]. Some anaphylactic reports involving opioids have been published, including a recent case of anaphylaxis with codeine, with a positive investigation that included SPT (with negative tests in three healthy controls), histamine-release test, and oral challenge test [77]. However, there is data supporting the safe use of codeine in patients presenting chronic urticaria [78].…”

Update of the Scientific Opinion on opium alkaloids in poppy seeds

“…Allergic reactions to codeine are known, as also shown by newly published case reports, but rarely in a severe form (Fathallah et al., ; Deverriere et al., ; Ariosto, ; Yoo et al., ; Erfan et al., ; Prescribing Information, ).…”

Drug-Induced Pseudoallergy: A Review of the Causes and Mechanisms

“…It has been found that codeine and morphine are more prone to inducing mast cell degranulation than other opioids [50]. Codeine induces pseudoallergy via a non-immunologic mechanism, which is independent of both IgE and the high-affinity IgE receptor FcεRI [51,52]. The activation of mast cell degranulation by codeine may, therefore, occur through its actions at the opioid receptor [51].…”