Any
CYP2C9 phenotype and HLA-B*15:02 positive# | Increased risk of
phenytoin-induced SJS/ TEN | If the individual is
phenytoin-naïve, do not use phenytoin/fosphenytoin. Avoid carbamazepine
and oxcarbazepine.a If the individual has previously
used phenytoin continuously for longer than 3 months without incidence
of cutaneous adverse reactions, cautiously consider use of phenytoin in
the future. The latency period for drug-induced SJS/TEN is short with
continuous dosing and adherence to therapy (428 days), and cases usually
occur within 3 months of dosing.b |
CYP2C9 normal metabolizer and HLA-B*15:02 negative | Normal phenytoin
metabolism | No adjustments needed
from typical dosing strategies. Subsequent doses should be adjusted
according to therapeutic drug monitoring, response, and side effects. An
HLA-B*15:02 negative test does not
eliminate the risk of phenytoin-induced SJS/TEN, and individuals should
be carefully monitored according to standard
practice.a |
CYP2C9 intermediate metabolizer (activity
score 1.5) and HLA-B*15:02 negative | Slightly reduced
phenytoin metabolism: however, this does not appear to translate into
increased side effects. | No adjustments needed
from typical dosing strategies. Subsequent doses should be adjusted
according to therapeutic drug monitoring, response, and side effects. An
HLA-B*15:02 negative test does not
eliminate the risk of phenytoin-induced SJS/TEN, and individuals should
be carefully monitored according to standard practice.c |
CYP2C9 intermediate metabolizer (Activity
score 1.0) and HLA-B*15:02 negative | Reduced phenytoin
metabolism: Higher plasma concentrations will increase probability of
toxicities. | For first dose, use
typical initial or loading dose. For subsequent doses, use approximately
25% less than typical maintenance dose. Subsequent doses should be
adjusted according to therapeutic drug monitoring, response, and side
effects. An HLA-B*15:02 negative test does
not eliminate the risk of phenytoin-induced SJS/TEN, and individuals
should be carefully monitored according to standard
practice.c |
CYP2C9 poor metabolizer and HLA-B*15:02 negative | Reduced phenytoin
metabolism: Higher plasma concentrations will increase probability of
toxicities. | For first dose, use
typical initial or loading dose. For subsequent doses use approximately
50% less than typical maintenance dose. Subsequent doses should be
adjusted according to therapeutic drug monitoring, response, and side
effects. An HLA-B*15:02 negative test does
not eliminate the risk of phenytoin-induced SJS/TEN, and individuals
should be carefully monitored according to standard
practice.a |