Table 4. [2016 CPIC Dosing recommendations for amitriptyline based on CYP2C19 phenotype]. - Medical Genetics Summaries

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Table 4.

2016 CPIC Dosing recommendations for amitriptyline based on CYP2C19 phenotype

Phenotype	Implication	Therapeutic recommendation
CYP2C19 ultrarapid metabolizer and CYP2C19 rapid metabolizer	Increased metabolism of tertiary amines as compared to normal metabolizers Greater conversion of tertiary amines to secondary amines may affect response or side effects	Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine.
		If a tertiary amine is warranted, utilize therapeutic drug monitoring to guide dose adjustments^a.
CYP2C19 normal metabolizer	Normal metabolism of tertiary amines	Initiate therapy with recommended starting dose^b.
CYP2C19 intermediate metabolizer	Reduced metabolism of tertiary amines compared to normal metabolizers	Initiate therapy with recommended starting dose^b.
CYP2C19 poor metabolizer	Greatly reduced metabolism of tertiary amines compared to normal metabolizers	Avoid tertiary amine use due to potential for sub-optimal response. Consider alternative drug not metabolized by CYP2C19. TCAs without major CYP2C19 metabolism include the secondary amines nortriptyline and desipramine. For tertiary amines, consider a 50% reduction of recommended starting dose^b. Utilize therapeutic drug monitoring to guide dose adjustments^a.
CYP2C19 poor metabolizer	Decreased conversion of tertiary amines to secondary amines may affect response or side effects

: Dosing recommendations apply only to higher initial doses of amitriptyline for treatment of conditions such as depression. The therapeutic recommendations for amitriptyline are classified as “strong” for normal and intermediate CYP2C19 metabolizers, “moderate” for poor metabolizers, and “optional” for ultrarapid metabolizers.
^a: Titrate dose to observed clinical response with symptom improvement and minimal (if any) side effects).
^b: Patients may receive an initial low dose of tricyclic, which is then increased over several days to the recommended steady-state dose. The starting dose in this guideline refers to the recommended steady-state dose.
: Table has been adapted from Hicks J.K., Sangkuhl K., Swen J.J., Ellingrod V.L., Müller D.J., Shimoda K., Bishop J.R., Kharasch E.D., Skaar T.C., Gaedigk A., Dunnenberger H.M., Klein T.E., Caudle K.E. Clinical Pharmacogenetics Implementation Consortium Guideline (CPIC®) for CYP2D6 and CYP2C19 Genotypes and Dosing of Tricyclic Antidepressants: 2016 Update. Clinical pharmacology and therapeutics. 2016 Dec 20 [Epub ahead of print] (2).

From: Amitriptyline Therapy and CYP2D6 and CYP2C19 Genotype

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Pratt VM, Scott SA, Pirmohamed M, et al., editors.

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