Drug Plasma Levels and ADRs: Usefulness of the TDM Plus Algorithm

Abstract

onigsfelden, Brugg, Switzerland More than 80% of all Adverse Drug Reactions (ADR) are Type A reactions and dependent on drug concentrations. Therapeutic Drug Monitoring (TDM), Drug Interactions checking programs and pharmacogenetic tests are valuable instruments in elucidating or preventing Type A ADR, and stand for Quality Assurance in clinical practice. Based on many years work experience in pharmacovigilance in psychiatry we developed an algorithm[1] which prevents unnecessary testing. This decision tree leads in several “stop/go” steps from the clinical situation of inefficacy or adverse reaction to measuring and interpreting plasma levels, checking for pharmacokinetic interactions and finally, if indicated, to pharmacogenetic tests with genotyping and/or phenotyping. Genetic results should be noted for future treatments, a “pharmacogenetic card” is proposed. Clinical cases, mainly from the pharmacovigilance program AMSP (Arzneimittelsicherheit in der Psychiatrie = Drug Safety in Psychiatry), are used to illustrate its practical use: interpretation of plasma levels and metabolic ratios, benefit and limitations of drug interaction programs, indication for pharmacogenetic testing, and examples of other factors influencing drug response. The interplay of genetics, drug interactions, lifestyle and other personal vulnerabilities like comorbidity make prediction of drug response very complex. The use of TDM plus has proven useful guiding the clinicians in difficult clinical situations and helping elucidating the causality of adverse drug reactions.