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

Pharmacogenomics of CNS Disorder Treatments
203
TABLE 8.1
FDA Product Labeling for CNS Medications
Drug Name
Pharmacogenetic
Biomarker
Label Information
Amitriptyline CYP2D6 • PM: May have higher than expected plasma concentrations
of TCAs when given usual doses, and the increase in
plasma concentration range can be large.
Aripiprazole CYP2D6 • PMs: Initial dose should be reduced to ½ of the usual dose.
• PMs: 80% increase in aripiprazole exposure and about a
30% decrease in exposure to the active metabolite
compared to EMs.
• Mean elimination half-lives are 75 h for EMs and 146 h
for PMs.
Aripiprazole
(Abilify
Maintena)
CYP2D6
• PMs and taking a CYP3A4 inhibitor for greater than
14 days: adjusted dose of 200 mg.
• PMs: Adjusted dose of 300 mg.
Atomoxetine CYP2D6 • PMs: 10-fold higher AUC and a 5-fold higher C max to a
given dose of atomoxetine compared with EMs; higher
rates of some adverse effects.
• Children/adolescents up to 70 kg body weight: Initiation
dose should be 0.5 mg/kg/day and only increased to the
usual start dose of 1.2 mg/kg/day if symptoms fail to be
improved after 4 weeks and the initial dose is well
tolerated.
• Children/adolescents >70 kg body weight: Initial dose
should be 40 mg/day and only increased to the usual target
dose of 80 mg/day if symptoms fail to be improved after
4 weeks and the initial dose is well tolerated.
Carbamazepine HLA-B*1502 • Chinese ancestry: Strong association between risk of
developing SJS/TEN and the presence of HLA-B*1502
• Patients with ancestry in genetically at-risk populations
should be screened for the presence of HLA-B*1502 prior
to initiating treatment with carbamazepine.
• Patients testing positive should not be treated with
carbamazepine unless the benefit clearly outweighs
the risk.
Citalopram CYP2C19 • Maximum dose should be limited to 20 mg/day in patients
who are CYP2C19 PMs due to risk of QT prolongation.
Clomipramine 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).
Clozapine CYP2D6 • PMs: May develop higher than expected plasma
concentrations of clozapine when given usual doses.
(Continued)