CYP2D6 and metabolic disease: Dose-related: individuals with CYP2D6 metabolic disorders (activity score 0) should avoid using codeine and tramadol; intermediate metabolizers (activity score 0.25–1) should use the recommended dosage in the instruction manual. If ineffective, alternative analgesics should be used; recommended dosage in the user manual for CYP2D6 normal metabolizers (activity score 1.25–2.25) (Crews et al., 2021)