From the Guidelines
Patients with allergies to codeine and morphine can generally take tramadol, but caution is warranted due to the potential for cross-sensitivity and the need for careful assessment of the nature of the previous allergic reactions. Tramadol works differently than traditional opioids like morphine and codeine, as it is a synthetic opioid that acts as a weak mu-opioid receptor agonist and also inhibits serotonin and norepinephrine reuptake, as noted in the NCCN clinical practice guidelines in oncology 1. This different mechanism of action means that cross-reactivity between tramadol and natural opioids like morphine and codeine is relatively uncommon. However, some patients with true opioid allergies may still experience cross-sensitivity. Before taking tramadol, patients should inform their healthcare provider about their allergies to codeine and morphine so that the provider can assess the nature of the previous reactions. If the previous reactions were true allergic responses (like hives, swelling, or anaphylaxis) rather than side effects (like nausea or constipation), the provider might recommend starting with a low dose of tramadol under close supervision or might suggest alternative non-opioid pain medications altogether. Key considerations for tramadol use include:
- Maximum daily dose of 400 mg for IR formulations or 300 mg/day for ER formulations for adults with normal hepatic and renal function, as recommended by the NCCN panel 1
- Lower doses recommended for older adults and those with hepatic and/or renal dysfunction to reduce the risk of seizures
- Potential for adverse effects, including vomiting, dizziness, and weakness, as observed in a double-blind study of patients with cancer 1.
From the FDA Drug Label
Patients with a history of anaphylactoid reactions to codeine and other opioids may be at increased risk and therefore should not receive tramadol hydrochloride (see CONTRAINDICATIONS). Tramadol hydrochloride tablets, USP should not be administered to patients who have previously demonstrated hypersensitivity to tramadol, any other component of this product or opioids.
A patient with an allergy to codeine and morphine should not take tramadol due to the risk of anaphylactoid reactions. This is a contraindication as stated in the drug label 2 and 2.
From the Research
Allergy to Codeine and Morphine
- A patient with an allergy to codeine and morphine may be able to take tramadol, but with caution, as tramadol is structurally related to codeine and morphine 3.
- Tramadol has a different mechanism of action, with both opioid and aminergic effects, which may reduce the risk of cross-reactivity 3, 4.
Cross-Reactivity and Safety
- There is limited evidence on the safety of tramadol in patients with allergies to codeine and morphine, and more research is needed to fully understand the risks 5, 6.
- Tramadol can cause adverse effects, including respiratory depression, serotonin syndrome, and seizures, which may be more severe in patients with a history of opioid allergy 6.
Alternatives and Precautions
- If a patient with an allergy to codeine and morphine requires pain management, alternative options such as non-opioid analgesics or other opioids with a lower risk of cross-reactivity may be considered 7, 6.
- Patients should be closely monitored for signs of an allergic reaction or adverse effects when taking tramadol, and the dose should be adjusted accordingly 3, 4.