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).
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 Recommendation||Level of Evidence||Clinical 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 endpoints||Clinical 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 endpoints||Minor 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)||None||no data was retrieved with the literature search||no data was retrieved with the literature search|