Doxepin is a tricyclic antidepressant that is metabolized by cytochrome P450 2D6 (CYP2D6). A hypofunctioning CYP2D6 genotype can result in decreased metabolism with drug accumulation, which can result in toxicity.
Patient selection: receiving doxepin
Primary metabolite: N-desmethyldoxepin
Doxepin is formulated as a mixture of 2 stereo-isomers:
(1) trans, designated the E-isomer, comprising 85%
(2) cis, designated the Z-isomer, comprising 15%
The E-isomer is metabolized faster, while the Z-isomer may be more therapeutically active.
A CYP2D6 genotype that is nonfunctioning or that shows greatly reduced activity, resulting in a poor metabolizer phenotype and drug accumulation, especially after high doses.
Differential diagnosis:
(1) drug or food interaction that inhibits CYP2D6
(2) overdosage
