Approximately 40% of patients treated withmore than one form of chemotherapy will have some form of peripheral neuropathy . The neuropathy can have long-term effects on QOL . The practice guideline by the American Society of Clinical Oncol- ogy (ASCO) for the management of chemotherapy-induced peripheral neuropathy suggests the use of duloxetine, tricyclic antidepressants (TCAs), or gabapentin . Gabapentin metabo- lism is not significantly affected by known pharmacogenetic var- iations. However, duloxetine is inactivated by two liver enzymes, CYP2D6 and CYP1A2, whereas the TCAs have more complex pharmacogenomic considerations with CYP2D6 and CYP2C19.
Amitriptyline is metabolized by CYP2C19 into nortriptyline, whereas both agents require CYP2D6 for metabolism into less active compounds . In a large study, CYP2D6 PMs given TCAs were substantially more likely than patients in the control group to stop the drug because of adverse effects such as dry mouth, dizziness, and cardiac concerns .