Common diplotypesb | Expected population frequency, %c | PK/PD phenotype | Clinical phenotype | FDA guidelines | ||
---|---|---|---|---|---|---|
Caucasian ancestry | African ancestry | East Asian ancestry | ||||
CYP2D6*1/*1, CYP2D6*1/*3, CYP2D6*1/*4, CYP2D6*1/*5, CYP2D6*1/*6, CYP2D6*1/*7, CYP2D6*1/*9, CYP2D6*1/*10, and other rare diplotypes (see Additional file 1: Table S21)d | 80 | 69 | 45 | EM: normal enzymatic function and normal conversion of codeine to morphine | Normal analgesic response to standard dose of codeine | – |
CYP2D6*4/*41, CYP2D6*4/*9, CYP2D6*4/*10, CYP2D6*41/*41, CYP2D6*5/*41, CYP2D6*9/*41, CYP2D6*10/*41, and other rare diplotypes (see Additional file 1: Table S21) | 12 | 26 | 26 | IM; reduced enzymatic function, leading to reduced conversion of codeine to morphine | Reduced analgesic response (pain relief). May require an increased dose to obtain an analgesic effect or should consider alternative pain medication | – |
CYP2D6*3/*4, CYP2D6*4/*4, CYP2D6*4/*5, CYP2D6*4/*7 and other rare diplotypes (see Additional file 1: Table S21) | 8 | 3 | 14 | PM: greatly reduced or abolished enzymatic function, leading to greatly reduced conversion of codeine to morphine | Little or no analgesic response (pain relief). Should consider alternative pain medication | – |
Rare in Caucasians. The following are common in East Asians: CYP2D6*1/*1 × N, CYP2D6*1 × N/*1 × N, CYP2D6*1 × N/*4, CYP2D6*1 × N/*5, CYP2D6*1 × N/*10, CYP2D6*1 × N/*10C(*36) | <0.1 | 2 | 15 | UM: enhanced enzymatic function, leading to greater conversion of codeine to morphine and higher drug exposure | Increased risk of drug toxicity and ADRs. Should consider alternative pain medication | CYP2D6 PMs and UMs may experience different efficacy. Even at labeled dosage regimens, UMs may experience overdose symptoms. Use of codeine by UM mothers can potentially lead to serious ADRs, including death, in nursing infants |