It’s rare to have a codeine allergy, but allergy-like symptoms are possible from taking codeine. Learn about the differences and how to manage symptoms. Objectives: The purpose of this study was to characterize the incidence of newly suspected IgE-mediated reactions (IMRs) based on clinical criteria among patients with a chart-documented opioid allergy and to assess clinician perceptions of opioid allergies. Very few people have true allergies to codeine. In fact, doctors say allergic reactions to opioids like codeine make up less than 2% of all hypersensitivity reactions in patients undergoing anesthesia. Group 1 (the naturally occurring agents –opiates) and group 2 (the semi-synthetic) are structurally very similar to each other and should be avoided if there is a true allergy to any of the group 1 and 2 members. The natural and semi-synthetics have cross-reactivity. Learn about what a codeine allergy is, and how to recognize true allergic reactions. Expert guidance on treatment options and safe alternatives. Codeine is used to manage mild to moderate pain, where treatment with an opioid is appropriate, and when other pain treatments such as non-opioid pain medicines do not treat your pain well enough or you cannot tolerate them. For patients allergic to codeine, NSAIDs (ibuprofen 400–600 mg or naproxen) should be the first-line therapy for mild-to-moderate pain, and when opioids are required, tramadol, oxycodone, hydrocodone, morphine, fentanyl, or hydromorphone are all safe alternatives that do not cross-react with codeine allergy. 1 For patients with a codeine allergy, non-steroidal anti-inflammatory drugs (NSAIDs) are recommended as first-line alternatives for mild to moderate pain, while hydromorphone, morphine, or fentanyl are recommended for moderate to severe pain. 1 Codeine allergies are extremely rare, but codeine can cause a histamine reaction with allergy-like symptoms. Pseudoallergies with codeine have symptoms like hives and itching, while true codeine allergies can cause life-threatening complications like anaphylaxis. Codeine is an opioid medication often prescribed for mild to moderate pain relief and cough suppression. It acts on the central nervous system to reduce discomfort. A true, immune-mediated allergy to codeine is possible, but it is exceedingly rare.