Tramadol and Acetaminophen

Pharmacogenomic Information in the Context of the FDA-Approved Drug Label*

Tramadol and Acetaminophen is a mixture of two analgesic drugs used to treat pain. Tramadol is an opioid and metabolized mainly via CYP2D6. Acetaminophen is mainly metabolized via glucuronidation.

The FDA recommends, but does not require, genetic testing prior to initiating or reinitiating treatment with Tramadol and Acetaminophen.

Excerpt from the Tramadol and Acetaminophen drug label:
"Approximately 7% of the population has reduced activity of the CYP2D6 isoenzyme of cytochrome P450. These individuals are "poor metabolizers" of debrisoquine, dextromethorphan, tricyclic antidepressants, among other drugs. Based on a population PK analysis of Phase 1 studies in healthy subjects, concentrations of tramadol were approximately 20% higher in "poor metabolizers" versus "extensive metabolizers", while M1 concentrations were 40% lower. In vitro drug interaction studies in human liver microsomes indicates that inhibitors of CYP2D6 such as fluoxetine and its metabolite norfluoxetine, amitriptyline and quinidine inhibit the metabolism of tramadol to various degrees. The full pharmacological impact of these alterations in terms of either efficacy or safety is unknown. Concomitant use of SEROTONIN re-uptake INHIBITORS and MAO INHIBITORS may enhance the risk of adverse events, including seizure (see WARNINGS) and serotonin syndrome."

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the Tramadol and Acetaminophen drug label PDF.