The CYP2D6*1xN alleles (*1x2 and *1x鈮?) are assigned as increased function alleles by CPIC. Patients carrying a *1xN allele with an activity value of 3 or greater in combination with a normal, increased, decreased or no function allele may have an increased risk of toxicity when treated with codeine as compared to patients with alleles that result in a normal metabolizer phenotype. Patients carrying a *1xN allele with an activity value of 2 in combination with an increased or normal function allele or a decreased function allele with an activity value of 0.5 may also have an increased risk of toxicity when treated with codeine as compared to patients with alleles that result in a normal metabolizer phenotype, while patients carrying a *1xN allele with an activity value of 2 in combination with a no function allele or a decreased function allele with an activity value of 0.25 may have a similar risk of toxicity when treated with codeine as compared to patients with alleles that result in a normal metabolizer phenotype. Other genetic and clinical factors may also influence risk of codeine toxicity.