The CYP2D6*2 allele is assigned as a normal function allele by CPIC. Patients carrying the *2 allele in combination with alleles that result in a normal metabolizer phenotype may have decreased risk of toxicity when treated with tramadol as compared to patients carrying two increased function alleles or an increased function allele in combination with a normal function allele or a decreased function allele with an activity value of 0.5. Patients carrying the *2 allele in combination with alleles that result in a normal metabolizer phenotype may also have decreased risk of toxicity when treated with tramadol as compared to patients carrying an increased function allele with an activity value of 3 or greater in combination with a no function allele or a decreased function allele with an activity value of 0.25 but a similar risk of toxicity when treated with tramadol as compared to patients with a no function allele in combination with a decreased or normal function allele or two decreased or no function alleles. Other genetic and clinical factors may also influence risk of tramadol toxicity.