Annotation of HCSC Label for amitriptyline and CYP2C19, CYP2D6
PharmGKB ID
Summary
The product monograph for amitriptyline states that CYP2D6 or CYP2C19 poor metabolizers may have higher plasma concentrations of amitriptyline, and that dosage adjustment should be considered..
Prescribing
Use in CYP2D6 or CYP2C19 poor metabolizers These patients may have higher plasma concentrations of amitriptyline [...]. Dosage adjustment should be considered.
Annotation
Excerpts from the amitriptyline product monograph:
Use in CYP2D6 or CYP2C19 poor metabolizers These patients may have higher plasma concentrations of amitriptyline (see 9.2 Drug Interactions Overview). Dosage adjustment should be considered.
Tricyclic antidepressants (TCA) including amitriptyline are primarily metabolized by the hepatic cytochrome P450 isozymes CYP2D6 and CYP2C19, which are polymorphic in the population.
The biochemical activity of the drug metabolizing isozyme CYP2D6 is reduced in a subset of the Caucasian population (about 7% to 10% of Caucasians are so called “poor metabolizers”); reliable estimates of the prevalence of reduced P450 2D6 isozyme activity among Asian, African, and other populations are not yet available. The biochemical activity of the drug metabolizing isozyme CYP2C19 is also reduced in a subset of the population (CYP2C19 poor metabolizers). Poor metabolizers have higher than expected plasma concentrations of tricyclic antidepressants (TCAs) when given usual doses. For instance, in CYP2D6 poor metabolizers the increase in plasma concentration may be small, or quite large (8-fold increase in plasma AUC of the TCA), depending on the fraction of the drug metabolized by CYP2D6.
Other isozymes involved in the metabolism of amitriptyline are CYP3A4, CYP1A2 and CYP2C9.
For the complete product monograph text with sections containing pharmacogenetic information highlighted, see the amitriptyline product monograph.
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Evidence for Clinical Annotations
This annotation has been used as evidence for the following clinical annotations.
History
No history available.