Introduction
Pharmacogenomics has been described as the study of differential
responses to pharmacological treatment due to heredity, which has drawn
attention to personalized medicine [1-5]. The genetically determined
inter-individual variability in enzyme activity, receptors,
transporters, and various other drug targets has been associated with
the efficacy and toxicity of pharmaceutical treatment [6-9].
Polymorphisms, mutations, gene expression differences, and chromosomal
abnormalities that cause changes in these targets may be the main reason
for variations in the body’s reaction to drug exposure. Variability in
drug efficacy and safety is explained by pharmacogenomics besides
factors such as age, sex, body mass index, renal and liver functions,
other diseases, and lifestyle differences [10-14].
Inter-individual variations in drug responses not only affect drug
efficacy but also can lead to adverse drug reactions (ADRs) in patients.
ADRs are associated with morbidity and mortality and are a burden to the
healthcare system, accounting for a cost of almost 100 billion USD
[7]. According to a prospective analysis, up to 6.5% of acute
hospital admissions in the United Kingdom are still related to ADRs
[16].
ADRs can be minimized by rational prescription and personalization of
medicine for each patient, the precision of which can be increased by
considering the pharmacogenomic information (PGx) during these
processes. The European Commission published a guideline on the summary
of product characteristics (SmPCs) in 2009, which emphasized that all
available relevant PGx should be included in the SmPCs [17]. In
2015, a review of 517 pharmaceutical products approved for use by the
European Medicines Agency (EMA) from 1995 to 2014 showed that the SmPCs
of approximately 15% of medications consisted of PGx that directly
impacted treatment [18]. Similarly, Frueh et al. performed a review
of the labels of the drugs approved by the United States Food and Drug
Administration (FDA) and estimated that almost one-fourth of patients in
2006 (approximately 8.8 million) were prescribed one or more drugs for
which the label included PGx in the US [19]. We estimate that this
number has increased considerably over time.
Providing adequate PGx of the drugs to patients has some ethical
implications in terms of providing benefits, avoiding harm, mitigating
risks, strengthening the trust in healthcare providers, and empowering
patients, as the new-found scientific information in pharmacogenomics
increases the moral responsibility to effectively transfer this
information to patients. Therefore, the aim of this study was to
determine if there are discrepancies among various agency-approved
labels for the same active ingredient and where the labels approved by
the Turkish Medicines and Medical Devices Agency (TMMDA) stand regarding
the inclusion of PGx and discuss the ethical implications of SmPCs with
inadequate and outdated information in the context of the principles of
medical ethics.