[Is therapeutic drug monitoring (TDM) in paediatric patients necessary?]

Abstract

There is increasing discussion about the clinical usefulness of routine TDM of selected drugs in paediatrics. Routine TDM is performed as a way to individualize dosing requirements so as to achieve "therapeutic" concentrations in all patients, independently of age and individual drug response. The therapeutic ranges established for most drugs are based upon studies performed in adults. Extrapolation of these ranges to paediatric patients, especially to neonates, is questionable because drugs disposition and pharmacodynamics differ in this population compared to adults. The scepticism of the value of routine TDM in paediatric patients concerns antiepileptic drugs and digoxin. Recently also the value of vancomycin TDM in neonates has been the subject of discussion, resulting in new recommendation for dosing schedule in this age group. Therapeutic monitoring of methotrexate, especially administered in high doses in anticancer therapy is not questioned. Aminoglycosides have an extremely important role in paediatric antimicrobial therapy. They are still frequently used in the neonatal period. The rationale for monitoring of aminoglycosides is a narrow therapeutic range resulting in risk of oto- and nephrotoxicity, and large inter- and intra-subject variation in pharmacokinetics. Routine TDM is not recommended for paediatric patients (other than neonates) with normal renal function and without chronic illnesses associated with changes in pharmacokinetics of aminoglycosides. In these patients the peak and trough concentrations are within the therapeutic range using standard dosing regimes. Therapeutic monitoring of aminoglycosides is still obligatory in neonates, especially in premature and low birthweight neonates because of particularly wide inter-patient and intra-patient pharmacokinetic variability and risk of oto- and nephrotoxicity.