Table 3.
Summary of the consensus guidelines for dose recommendation based on CYP450 pharmacogenetic testing
| Drug/therapeutic class | CYP | Dose recommendation |
|---|---|---|
| Codeine | CYP2D6 | EM: standard starting dose of codeinea |
| PM: avoid codeine, choose alternative analgesics (morphine or a non-opioid), avoid tramadola | ||
|
Analgesia: select alternative drug *or be alert to symptoms of insufficient pain reliefb Cough: nob | ||
| IM: monitored closely for less than optimal response, alternative analgesic if required. Begin with 15–60 mg every 4 h as needed for pain. If no response, consider alternative analgesics such as morphine or a non-opioid. Monitor tramadol use for responsea | ||
|
Analgesia: select alternative drug* or be alert to symptoms of insufficient pain reliefb Cough: nob | ||
| UM: avoid codeine (toxicity). Alternative analgesics (morphine or a non-opioid). Avoid tramadola | ||
|
Analgesia: select alternative drug *or be alert to ADEsb Cough: be extra alert to ADEs due to increased morphine plasma concentrationb | ||
| *(e.g. acetaminophen, NSAID, morphine—not tramadol or oxycodone) | ||
| Oxycodone | CYP2D6 | PM: alternative drug (not tramadol or codeine) or be alert to symptoms of insufficient pain reliefb |
| UM: be alert to ADEsb | ||
| Tramadol | CYP2D6 | PM and IM: alternative drug (not oxycodone or codeine) and/or be extra alert to insufficient pain reliefb |
| UM: dose reduction by 30 %, be alert for ADEs, or alternative drug (not oxycodone or codeine)b | ||
| Antiarrythmics | CYP2D6 | Metoprolol and propafenoneb |
| PM: dose reduction by 70–75 % or alternative drug, record ECG, monitor plasma concentration | ||
| IM: dose reduction by 50 % or alternative drug | ||
| UM: alternative drug or titration to a maximum of 250 % of the normal metoprolol dose; insufficient data to allow propafenone dose adjustment calculation but adjust to plasma concentration, record ECG or select alternative drug | ||
| Flecainideb | ||
| PM: dose reduction by 50 %, record ECG, monitor plasma concentration | ||
| IM: dose reduction by 25 %, record ECG, monitor plasma concentration | ||
| UM: dose reduction and monitor plasma concentration or select alternative drug (e.g. sotalol, disopyramide, quinidine, amiodarone) | ||
|
Carvedilol No recommendation at this timeb | ||
| Antidepressants | CYP2D6 |
Clomipramine and imipramine Dose should be reduced by 50 to 70 % in PMs and plasma concentrations should be monitored; in UM an alternative drug (*e.g. citalopram, sertraline) may be considered, plasma concentrations monitored or increase imipramine dose by 70 %b |
|
Amitriptyline PM and UM: select alternative drug* or monitor plasma concentration IM: dose reduction by 25 % and monitor plasma concentration or select alternative drug*b | ||
|
Nortriptyline PM (IM): reduce dose by 60 (40) % and monitor plasma concentrations UM: select alternative drug *or increase dose by 60 % and monitor plasma concentrationsb | ||
|
Venlafaxine PM, IM: insufficient data to allow calculation of dose adjustment, select an alternative drug or adjust dose to clinical response and monitor plasma concentration UM: titrate dose to a maximum of 150 % of the normal dose or select an alternative drug*b | ||
|
Doxepine PM (IM): reduce dose by 60 (20) %. Monitor plasma concentration UM: select alternative drug* or increase dose by 100 %b | ||
|
Paroxetine PM, IM: no dose adjustment UM: select alternative drug*b | ||
|
Duloxetine, mirtazapine No dose adjustment recommendationsb | ||
| Antipsychotics | CYP2D6 |
Risperidone All genotypes: select alternative (e.g. quetiapine, olanzapine, clozapine) or be extra alert to ADE and adjust dose to clinical responseb |
|
Aripriprazole PM: reduce maximum dose to 10 mg/day IM, UM: no recommendationb | ||
|
Zuclopenthixol PM: reduce dose by 50 % or select alternative drug IM: reduce dose by 25 % or select alternative UM: insufficient data to allow calculation of dose adjustment, be alert to low plasma concentrations or select alternativeb | ||
|
Haloperidol PM: reduce dose by 50 % or select alternative (e.g. pimozide, flupenthixol, fluphenazine, quetiapine, olanzapine, clozapine) IM: none UM : insufficient data to allow calculation of dose. Be alert to decreased haloperidol plasma concentration and adjust maintenance dose in response to haloperidol plasma concentration or select alternativeb | ||
|
Clozapine, flupentixol and olanzapine No dose adjustment neededb | ||
| Tamoxifen | CYP2D6 | PM, IM: consider using aromatase inhibitors for postmenopausal women (IM: avoid concomitant CYP2D6 inhibitor use)b |
| UM: no recommendationb | ||
| Anticoagulants | CYP2C9 | Warfarin: |
| Two algorithms estimating stable warfarin dose across different ethnic populations [Articles: 18305455, 19228618]a | ||
| Daily warfarin doses recommendations based on CYP2C9 and VKORC1 genotype (warfarin product insert approved by the FDA)a | ||
| Acenocoumarol | ||
| *1/*2: check INR more frequentlyb | ||
| *2/*2, *1/*3, *2/*3, *3/*3: check INR more frequently after initiating or discontinuing NSAIDsb | ||
| Phenprocoumon | ||
| *1/*2, *1/*3: noneb | ||
| *2/*2, *2/*3, *3/*3: check INR more frequentlyb | ||
| Phenytoin | CYP2C9 | *1/*2, *1/*3: maintenance dose reduction by 25 %b |
| *2/*2, *2/*3, *3/*3: maintenance dose reduction by 50 %b | ||
| Evaluate response and serum concentration after 7–10 days. Be alert to ADEs (e.g. ataxia, nystagmus, dysarthria, sedation)b | ||
| Sulfonylureas | CYP2C9 | Glibenclamide, glimepiride, gliclazide, tolbutamide |
| No adaptation of dosage is recommendedb | ||
| Clopidogrel | CYP2C19 | UM, EM: clopidogrel label-recommended dosage and administrationa,b |
|
IM, PM: prasugrel or other alternative therapy (if no contraindication)a Consider alternative drug. Prasugrel is not, or to a much smaller extent, metabolised by CYP2C19 but is associated with an increased bleeding risk compared to clopidogrelb | ||
| Proton pump inhibitors | CYP2C19 | Esomeprazole, lansoprazole, omeprazole, pantoprazole |
| UM: be extra alert to insufficient response, dose increase by 50–400 %b | ||
| PM, IM: no dose recommendationb | ||
|
Rabeprazole No dose recommendationb | ||
| Antidepressants | CYP2C19 | Citalopram, escitalopramb |
| UM: monitor plasma concentration and titrate dose to a maximum of 150 % in response to efficacy and adverse drug event or select alternative drug (e.g. fluoxetine, paroxetine) | ||
| PM and IM: none | ||
| Sertralineb | ||
| PM: reduce dose by 50 % | ||
| IM: insufficient data to allow calculation of dose adjustment. Be extra alert to adverse drug events (e.g. nausea, vomiting, diarrhoea) | ||
| UM: none (no data were retrieved) | ||
| Imipramineb | ||
| PM: reduce dose by 30 % and monitor plasma concentration of imipramine and desipramine or select alternative drug (e.g. fluvoxamine, mirtazapine) | ||
| IM: insufficient data to allow calculation of dose adjustment. Select alternative drug (e.g. fluvoxamine, mirtazapine) | ||
| UM: no data | ||
|
Moclobemideb No recommendations at this time | ||
| Voriconazole | CYP2C19 | PM or IM: monitor serum concentrationb |
| UM: noneb |
ADEs adverse drug events, CYP cytochrome P450, EM extensive metaboliser, UM ultrarapid metaboliser, IM intermediate metaboliser, PM poor metaboliser, INR international normalised ratio, FDA US Food and Drug Administration
aAccording to the Clinical Pharmacogenetics Implementation Consortium of the Pharmacogenomics Research Network (CPIC)
bAccording to the Pharmacogenetics Working Group of the Royal Dutch Pharmacists Association