While tramadol is classified as an opioid, there are many practice pearls that make it unique from other traditional opioids. In this blog post, I’ll share my top 5 tramadol practice pearls.
Tramadol has weak mu-opioid receptor activity, but it also inhibits the reuptake of serotonin and norepinephrine. This makes its pharmacology somewhat unique compared with traditional opioids such as morphine or hydrocodone.
Tramadol can cause serotonin syndrome. Because it increases serotonergic activity, combining it with SSRIs, SNRIs, TCAs, MAO inhibitors, or other serotonergic medications can increase the risk of serotonin syndrome. Watch for agitation, sweating, tremor, hyperreflexia, clonus, and changes in mental status. This is an important reason to review the entire medication list before prescribing tramadol.
Seizures are another important concern. Tramadol can lower the seizure threshold, and seizures have been reported even at therapeutic doses. The risk can increase with higher doses and with other medications that lower the seizure threshold, including some antidepressants and antipsychotics. Patients with a history of seizures deserve particular caution when this medication is being considered.
CYP2D6 matters with tramadol. Tramadol is metabolized by CYP2D6 to an active metabolite that contributes substantially to its opioid effects. Drugs that inhibit CYP2D6, such as fluoxetine, paroxetine, and bupropion, can reduce formation of this metabolite and potentially decrease analgesic effectiveness while leaving serotonergic adverse effects intact. Genetic differences in CYP2D6 activity can also contribute to significant variability in how patients respond to tramadol.
Because of the SNRI-type activity, it is important to remember that tramadol has been associated with hyponatremia. In patients at risk for hyponatremia or who are displaying symptoms of hyponatremia, it is critical to make sure that labs are assessed. This is a classic medication pearl that I’ve seen show up on board exams.
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