How do genetics affect tramadol?

Pain-relieving and side effects of tramadol are greatly affected by a person’s genetics, particularly their capacity for tramadol metabolism through a liver enzyme system called cytochrome P450 2D6.

20% of African Americans, 10% of Caucasians, and 2% of Asians have genetic polymorphisms that reduce the activity of this enzyme, which decreases how much tramadol is metabolized. People who are poor metabolizers at CYP 2D6 may find tramadol ineffective.

Individuals who are CYP2D6 ultra-rapid metabolizers (about 3% of the population) are at risk of life-threatening or fatal breathing side effects from tramadol (respiratory depression) even at regular dosages because they convert tramadol into its active metabolite more rapidly than other people. They are also at an increased risk for overdosing or misusing tramadol. Rapid CYP2D6 metabolizers should not use tramadol.

Genetic testing is available through hospitals, specialized clinics, and doctor's clinics. Blood is the preferred specimen type. About 21% of currently approved drugs are processed through CYP 2D6 including opioids, antidepressants, antipsychotics, β-blockers, antiemetics, and tamoxifen, and it is helpful for you and your healthcare provider to know if you are a:

• Poor metabolizer: Process drugs slowly; may need lower dosages to avoid side effects
• Intermediate metabolizer: Process drugs less efficiently; might not be as effective as normal metabolizers
• Normal metabolizer: Process drugs efficiently; likely to benefit from treatment with fewer side effects
• Ultrarapid metabolizer: Process drugs too quickly. Some drugs may not be suitable for these people, because the rapid metabolism puts them at a much higher risk of side effects.