Annotation of Dutch Pharmacogenetics Working Group (DPWG) guideline information
for sertraline and CYP2C19

last updated 08/10/2011

Summary

Reduce sertraline dose by 50% for patients with CYP2C19 poor metabolizer genotypes (PM), and be extra alert to adverse drug events in patients with CYP2C19 intermediate metabolizer genotypes (IM).

Annotation

The Royal Dutch Pharmacists Association - Pharmacogenetics Working Group has evaluated therapeutic dose recommendations for sertraline based on CYP2C19 genotype [Article:21412232].

Phenotype (Genotype)Therapeutic Dose RecommendationLevel of EvidenceClinical Relevance
CYP2C19 PM (*2/*2, *2/*3, *3/*3)Reduce dose by 50%.Published controlled studies of moderate quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpointsClinical effect (statistically significant difference): long-standing discomfort (48-168 hr) without permanent injury e.g. failure of therapy with tricyclic antidepressants, atypical antipsychotic drugs; extrapyramidal side effects; parkinsonism; adverse drug events resulting from increased bioavailability of tricyclic antidepressants, metoprolol, propafenone (central effects e.g. dizziness); international normalized ratio 4.5-6.0; neutropenia 1.0-1.5x109/l; leucopenia 2.0-3.0x109/l; thrombocytopenia 50-75x109/l
CYP2C19 IM (*1/*2, *1/*3, *17/*2, *17/*3)Insufficient data to allow calculation of dose adjustment. Be extra alert to adverse drug events (e.g., nausea, vomiting, diarrhea).Published controlled studies of moderate quality* relating to phenotyped and/or genotyped patients or healthy volunteers, and having relevant pharmacokinetic or clinical endpointsMinor clinical effect (statistically significant difference): QTc prolongation (<450 ms female, <470 ms male); international normalized ratio increase < 4.5; Kinetic effect (statistically significant difference)
CYP2C19 UM (*17/*17)Noneno data was retrieved with the literature searchno data was retrieved with the literature search

DPWG Guideline publication

Total publications: 1

Reference
1. Pharmacogenetics: From Bench to Byte- An Update of Guidelines. Clinical pharmacology and therapeutics. 2011. Swen J J, Nijenhuis M, de Boer A, Grandia L, Maitland-van der Zee A H, Mulder H, Rongen G A P J M, van Schaik R H N, Schalekamp T, Touw D J, van der Weide J, Wilffert B, Deneer V H M, Guchelaar H-J. PubMed

Guideline History