Pharmacogenetic information in Swiss drug labels - a systematic analysis

Abstract

Implementation of pharmacogenetics (PGx) and individualization of drug therapy is supposed to obviate adverse drug reactions or therapy failure. Health care professionals (HCPs) use drug labels (DLs) as reliable information about drugs. We analyzed the Swiss DLs to give an overview on the currently available PGx instructions. We screened 4306 DLs applying natural language processing focusing on drug metabolism (pharmacokinetics) and we assigned PGx levels following the classification system of PharmGKB. From 5979 hits, 2564 were classified as PGx-relevant affecting 167 substances. 55% (n = 93) were classified as "actionable PGx". Frequently, PGx information appeared in the pharmacokinetics section and in DLs of the anatomic group "nervous system". Unstandardized wording, appearance of PGx information in different sections and unclear instructions challenge HCPs to identify and interpret PGx information and translate it into practice. HCPs need harmonization and standardization of PGx information in DLs to personalize drug therapies and tailor pharmaceutical care.

Fig. 1. Flow chart depicting the process of analysis.

The natural language processing was followed by evaluation of the PGx-relevance as well as the attribution of the PGx level, which was both conducted under consultation of the expert group.

Fig. 2. Analysis of the 2564 PGx-relevant sentences.

Appearance in the different drug label sections (A), in the anatomic groups (indicated by the ATC code) of the drug described by the drug label (B) and of the biomarker mentioned in the sentences (C). Data shown are total number of PGx-relevant sentences per category.

Fig. 3. Drug label (DL) sections with PGx information.

Ten examples of DLs indicating the different DL sections in which the information on PGx is given. The corresponding section is marked with black color. The last column shows the sum of sections that specify PGx information.

Fig. 4. Analysis of the reference drug labels (refDLs).

Number of reference drug labels per PGx level (A, B), per anatomic group and the assigned PGx levels (C), and per biomarker (D, E).

Fig. 5. Excerpt of the Drug Label Annotations on the PharmGKB website.

Since 08/07/2019 the Drug Label Annotations include excerpts of  the drug labels of the  Food and Drug Administration (FDA), the European Medicines Agency (EMA), the Swissmedic, the Health Care Service Cooperation (HSCS), and the Pharmaceutical and Medical Devices Agency (PMDA).

Fig. 6. Comparative analysis of the attributed PGx levels of the Swiss DLs with those of other regulatory authorities, namely the Food and Drug Administration (FDA), the European Medicines Agency (EMA), the Health Care Service Cooperation (HSCS), and the Pharmaceutical and Medical Devices Agency (PMDA).

Each drug was included in the schematic of A, C, E, and G linking its PGx level indicated by the respective DL of the publishing agency to visualize heterogeneity. In B, D, F and H the number of drugs in each category is indicated by the width of the violin.