Feng, Xiaodong_ Xie, Hong-Guang - Applying pharmacogenomics in therapeutics-CRC Press (2016)

204 Applying Pharmacogenomics in Therapeutics
TABLE 8.1 (Continued)
FDA Product Labeling for CNS Medications
Drug Name
Pharmacogenetic
Biomarker
Label Information
Desipramine CYP2D6 • PMs: Higher than expected plasma concentrations of TCAs
when given usual doses, the increase in plasma
concentration may be small or quite large (eightfold
increase in plasma AUC of the TCAs).
Diazepam
(rectal gel
formulation
only, not the
oral tablet)
CYP2C19
• Marked interindividual variability in the clearance of
diazepam reported, likely attributable to variability of
CYP2C19.
Doxepin CYP2D6 • PMs: 2D6 may have higher plasma levels than normal
subjects.
Fluoxetine CYP2D6 • PMs: Metabolized S-fluoxetine at a slower rate and
achieved higher concentrations of S-fluoxetine. Compared
to normal metabolizers, the total sum at steady state of the
plasma concentrations of the 4 active enantiomers was not
significantly greater among poor metabolizers. The net
pharmacodynamic activities were essentially the same for
PMs and normal metabolizers.
Fluoxetine and CYP2D6 • Same as fluoxetine.
olanzapine
combination
Fluvoxamine CYP2D6 • In vivo study of fluvoxamine single-dose pharmacokinetics
in 13 PMs demonstrated altered pharmacokinetic properties
compared to 16 EMs: mean C max , AUC, and t ½ were
increased by 52%, 200%, and 62%, respectively
Iloperidone CYP2D6 • PMs: Dose should be reduced by ½.
• Observed mean elimination half-lives for iloperidone, P88,
and P95 in EMs are 18, 26, and 23 h, respectively; and in
PMs are 33, 37, and 31 h, respectively.
Imipramine CYP2D6 • PMs: Higher than expected plasma concentrations of TCAs
when given usual doses. Depending on the fraction of drug
metabolized by CYP2D6, the increase in plasma
concentration may be small, or quite large (eightfold
increase in plasma AUC of the TCAs).
Modafinil CYP2D6 • PMs: Levels of CYP2D6 substrates may be increased by
coadministration of modafinil.
• Dose adjustments may be necessary for patients being
treated with CYP2D6 substrates or inhibitors.
Nortriptyline CYP2D6 • PMs: Higher than expected plasma concentrations of TCAs
when given usual doses. Depending on the fraction of drug
metabolized by CYP2D6, the increase in plasma
concentration may be small or quite large (eightfold
increase in plasma AUC of the TCAs).
(Continued)