Table 1.
Proposed dose adjustment of clopidogrel based on a patient whose CYP2C19 genotype is known and a drug metabolized by CYP2C19 and interacting with clopidogrel is added
| Interacting drug | Different CYP2C19 genotypes
|
|||||
|---|---|---|---|---|---|---|
| *17*17 | *1*17 | *1*1 | *2-3*17 | *1*2-3 | *2-3*2-3 | |
| Amiodarone 1,200 mg/d | 45 (0.6) | 54 (0.72) | 75 (1) | 86 (1.15) | 137 (1.83) | 212 (2.83) |
| Azithromycin 250–500 mg/d | 45 (0.6) | 54 (0.72) | 75 (1) | 86 (1.15) | 137 (1.83) | 212 (2.83) |
| Benzbromarone 100 mg/d | 45 (0.6) | 54 (0.72) | 75 (1) | 86 (1.15) | 137 (1.83) | 212 (2.83) |
| Boceprevir 800–2400 mg/d | 45 (0.6) | 54 (0.72) | 75 (1) | 86 (1.15) | 137 (1.83) | 212 (2.83) |
| Bosentan 500–1,000 mg/d | 25 (0.33) | 30 (0.4) | 44 (0.59) | 52 (0.7) | 100 (1.33) | 210 (2.8) |
| Bupropion 300 mg | 45 (0.6) | 54 (0.72) | 75 (1) | 86 (1.15) | 137 (1.83) | 212 (2.83) |
| Carbamazepine 200–600 mg/d | 45 (0.6) | 54 (0.72) | 75 (1) | 86 (1.15) | 137 (1.83) | 212 (2.83) |
| Cilcosporin 2.5–5 g/d | 45 (0.6) | 54 (0.72) | 75 (1) | 86 (1.15) | 137 (1.83) | 212 (2.83) |
| Cimetidine 800–1,200 mg/d | 45 (0.6) | 54 (0.72) | 75 (1) | 86 (1.15) | 137 (1.83) | 212 (2.83) |
| Clarithromycin 500–1,000 mg/d | 75 (0.99) | 86 (1.15) | 111 (1.48) | 123 (1.64) | 167 (2.23) | 213 (2.84) |
| Diltiazem 90–270 mg/d | 45 (0.6) | 54 (0.72) | 75 (1) | 86 (1.15) | 137 (1.83) | 212 (2.83) |
| Diphenhydramine 150 mg/d | 45 (0.6) | 54 (0.72) | 75 (1) | 86 (1.15) | 137 (1.83) | 212 (2.83) |
| Dronedarone 800 mg/d | 45 (0.6) | 54 (0.72) | 75 (1) | 86 (1.15) | 137 (1.83) | 212 (2.83) |
| Duloxetine 120 mg/d | 45 (0.6) | 54 (0.72) | 75 (1) | 86 (1.15) | 137 (1.83) | 212 (2.83) |
| Efavirenz 600 mg/d | 45 (0.6) | 54 (0.72) | 75 (1) | 86 (1.15) | 137 (1.83) | 212 (2.83) |
| Erythromycin 1,000–2,000 mg/d | 45 (0.6) | 54 (0.72) | 75 (1) | 86 (1.15) | 137 (1.83) | 212 (2.83) |
| Fluconazole 100–400 mg/d | 117 (1.56) | 130 (1.73) | 152 (2.03) | 161 (2.15) | 191 (2.55) | 214 (2.85) |
| Fluoxetine 20–60 mg/d | 69 (0.92) | 81 (1.08) | 105 (1.4) | 117 (1.56) | 164 (2.18) | 213 (2.84) |
| Fluvoxamine 50–200 mg/d | 200 (2.66) | 203 (2.7) | 206 (2.75) | 208 (2.77) | 212 (2.83) | 215 (2.86) |
| Gatifloxacin 400 mg/d | 45 (0.6) | 54 (0.72) | 75 (1) | 86 (1.15) | 137 (1.83) | 212 (2.83) |
| Itraconazole 100–200 mg/d | 45 (0.6) | 54 (0.72) | 75 (1) | 86 (1.15) | 137 (1.83) | 212 (2.83) |
| Ketoconazole 200–400 mg/d | 45 (0.6) | 54 (0.72) | 75 (1) | 86 (1.15) | 137 (1.83) | 212 (2.83) |
| Levomepromazine 10 mg/d | 45 (0.6) | 54 (0.72) | 75 (1) | 86 (1.15) | 137 (1.83) | 212 (2.83) |
| Miconazole 125 mg/d | 45 (0.6) | 54 (0.72) | 75 (1) | 86 (1.15) | 137 (1.83) | 212 (2.83) |
| Nefazodone 400 mg/d | 45 (0.6) | 54 (0.72) | 75 (1) | 86 (1.15) | 137 (1.83) | 212 (2.83) |
| Noscapine 150 mg/d | 45 (0.6) | 54 (0.72) | 75 (1) | 86 (1.15) | 137 (1.83) | 212 (2.83) |
| Omeprazole 40–80 mg/d | 68 (0.91) | 80 (1.06) | 104 (1.39) | 116 (1.55) | 163 (2.17) | 213 (2.84) |
| Pantoprazole 80 mg/d | 56 (0.75) | 68 (0.9) | 90 (1.2) | 102 (1.36) | 152 (2.02) | 213 (2.84) |
| Paroxetine 20 mg/d | 45 (0.6) | 54 (0.72) | 75 (1) | 86 (1.15) | 137 (1.83) | 212 (2.83) |
| Phenytoin 300–400 mg/d | 25 (0.33) | 30 (0.4) | 44 (0.59) | 53 (0.7) | 100 (1.33) | 210 (2.8) |
| Pioglitazone 45 mg/d | 45 (0.6) | 54 (0.72) | 75 (1) | 86 (1.15) | 137 (1.83) | 212 (2.83) |
| Posacpnazole 200–600 mg/d | 45 (0.6) | 54 (0.72) | 75 (1) | 86 (1.15) | 137 (1.83) | 212 (2.83) |
| Propafenone 675 mg/d | 45 (0.6) | 54 (0.72) | 75 (1) | 86 (1.15) | 137 (1.83) | 212 (2.83) |
| Quinidine 50 mg | 45 (0.6) | 54 (0.72) | 75 (1) | 86 (1.15) | 137 (1.83) | 212 (2.83) |
| Ranitidine 300–600 mg/d | 45 (0.6) | 54 (0.72) | 75 (1) | 86 (1.15) | 137 (1.83) | 212 (2.83) |
| Rifampicin 450–600 mg/d | 11 (0.14) | 13 (0.17) | 20 (0.27) | 25 (0.33) | 55 (0.73) | 205 (2.73) |
| Ritonavir 800 mg/d >14 d | 6 (0.08) | 7.5 (0.1) | 12 (0.16) | 15 (0.2) | 35 (0.47) | 197 (2.63) |
| Roxithromycin 300 mg/d | 45 (0.6) | 54 (0.72) | 75 (1) | 86 (1.15) | 137 (1.83) | 212 (2.83) |
| Saquinavir 3,600 mg/d | 45 (0.6) | 54 (0.72) | 75 (1) | 86 (1.15) | 137 (1.83) | 212 (2.83) |
| Sertraline 150 mg/d | 45 (0.6) | 54 (0.72) | 75 (1) | 86 (1.15) | 137 (1.83) | 212 (2.83) |
| St John Wart 600 mg/d | 29 (0.38) | 35 (0.47) | 51 (0.68) | 86 (1.15) | 110 (1.46) | 210 (2.81) |
| Sulfamethizole 600 mg/d | 45 (0.6) | 54 (0.72) | 75 (1) | 86 (1.15) | 137 (1.83) | 212 (2.83) |
| Sulfaphenazole 1,000 mg/d | 45 (0.6) | 54 (0.72) | 75 (1) | 86 (1.15) | 137 (1.83) | 212 (2.83) |
| Telaprevir 2.25 mg/d | 45 (0.6) | 54 (0.72) | 75 (1) | 86 (1.15) | 137 (1.83) | 212 (2.83) |
| Telithromycin 800 mg/d | 45 (0.6) | 54 (0.72) | 75 (1) | 86 (1.15) | 137 (1.83) | 212 (2.83) |
| Terbinafine 250 mg/d | 45 (0.6) | 54 (0.72) | 75 (1) | 86 (1.15) | 137 (1.83) | 212 (2.83) |
| Thioridazine 50 mg/d | 45 (0.6) | 54 (0.72) | 75 (1) | 86 (1.15) | 137 (1.83) | 212 (2.83) |
| Ticagrelor 90–180 mg/d | 45 (0.6) | 54 (0.72) | 75 (1) | 86 (1.15) | 137 (1.83) | 212 (2.83) |
| Ticlopidine 300 mg/d | 75 (1) | 88 (1.17) | 113 (1.5) | 86 (1.15) | 168 (2.24) | 214 (2.84) |
| Valproate 400–800 mg/d | 45 (0.6) | 54 (0.72) | 75 (1) | 86 (1.15) | 137 (1.83) | 212 (2.83) |
| Verapamil 240–480 mg/d | 45 (0.6) | 54 (0.72) | 75 (1) | 86 (1.15) | 137 (1.83) | 212 (2.83) |
| Voriconazole 400–800 mg/d | 100 (1.21) | 104 (1.38) | 128 (1.71) | 140 (1.86) | 179 (2.38) | 214 (2.85) |
Notes: Clopidogrel adjusted dose in mg for clopidogrel dose of 75 mg = (interacting drug AUCXM*/AUCEM) ×75 mg. The values shown in bold refer to the dose, and the values in brackets refer to interacting AUC values. List of CYP2C19 inhibitors and inducers. AUC ratio calculation was adopted from Castellan et al.13 AUC consists of the area under the substrate concentration in blood or plasma over the dosing interval at steady state; AUCEM is the AUC of the substrate given alone in “extensive metabolizers”; AUCXM is the AUC of the substrate given alone in patients with any other phenotype (ultra-extensive metabolizer to poor metabolizer) as defined by the genotype of the major CYP2C19 involved in the substrate metabolism; AUCXM* is the AUC of the substrate given with an inhibitor or an inducer. Data from Castellan et al.13
Abbreviations: AUC, area under the curve; d, day.