The safety of codeine in patients with non-steroidal anti-inflammatory drug hypersensitivity: a preliminary study.

BACKGROUND: Drug provocation testing should be performed before safely prescribing an analgesic for patients that are hypersensitive to non-steroidal anti-inflammatory drugs (NSAIDs). Whether or not the direct histamine releasing effect of codeine renders it useful in NSAID-hypersensitive patients is unknown. This study aimed to determine if codeine could be recommended as a safe treatment option for NSAID-hypersensitive patients without the need for oral drug provocation testing.

METHODS: The study included NSAID-hypersensitive patients with and without concurrent asthma, rhinitis, and chronic urticaria that presented to the allergy clinic between 1 January 1991 and 31 December 2010. Patient data were collected from the allergy clinic computer database. Patients challenged with codeine were included in the codeine group. The non-codeine group included those patients that were tested with analgesics other than codeine.

RESULTS: In total, data for 1071 patients, of whom 301 were in the codeine group, were analysed. The reaction rate to codeine was 7.3% and when compared in pairs, the rate was significantly lower than to meloxicam and nimesulide (odds ratios=0.26-0.31, respectively). The reaction rate to codeine did not differ from that to benzydamine, rofecoxib, and paracetamol. Symptomatic dermographism was associated (p=0.009) with test positivity to any drug.

CONCLUSIONS: Although, codeine was among the safest alternative drugs and none of the patients had an anaphylactic reaction to it, thus a challenge with codeine may be considered especially in patients with dermographism. The results of this preliminary study should be confirmed in a prospective study including a control group.