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The aging process is characterized by relevant changes in pharmacokinetics. Renal function is known to decline with aging. However, as a result of reduced muscle mass, older individuals frequently have a depressed glomerular filtration rate (GFR) despite normal serum creatinine, and such a concealed renal insufficiency may impact significantly on the clearance of hydrosoluble drugs, as well as the risk of adverse drug reactions (ADRs) from hydrosoluble drugs. The assessment of renal function should thus be a mandatory item in the global examination of patient characteristics. Equations for estimating GFR have become very popular in recent years. However, different equations may yield significantly different estimated glomerular filtration rate (eGFR) values, which have important implications in dosing drugs cleared by the kidney. Current knowledge suggests that eGFR based on the Chronic Kidney Disease-Epidemiological Collaboration (CKD-EPI) study equation outperformed eGFR based on the Modification of Diet in Renal Disease (MDRD) study equation and creatinine clearance estimate based on the Cockcroft-Gault formula as a predictor of ADRs from kidney cleared drugs. More recently, the combined creatinine-cystatin C equation was shown to perform better than equations based on either of these markers alone in diagnosing CKD, even in older patients. However, its accuracy in predicting ADRs and usefulness in drug dosing is still to be investigated.

While polypathology and polypharmacy are well known risk factors for adverse drug reactions (ADRs), the association between geriatric conditions (GCs), i.e. a set of clinical and functional problems partly constitutive of and partly related to frailty, and ADRs is suspected but has not been fully elucidated. Several studies have assessed the relationship between single GCs and ADRs, but only a few studies have systematically evaluated the relationship between the whole spectrum of GCs and ADRs. The mechanism by which select GCs increase the risk of developing ADRs during a hospital stay might simply reflect a sort of general predictability of physical disability with respect to adverse outcomes. However, GCs pertaining to the physical dimension of frailty are generally associated with relevant changes in pharmacokinetics and pharmacodynamics of select drugs. While current evidence could not be considered either unequivocal or conclusive, select GCs, e.g. a history of falls and loss of independence in the activities of daily living, seem to define a condition of particular vulnerability of elderly patients to ADRs.

Adverse drug events (ADEs) are an increasingly relevant issue for healthcare systems as they are associated with poorer health outcomes and avoidable misuse of resources. The rates of ADEs are higher in the elderly population, as many older patients have comorbidities, multiple drug prescriptions and deteriorated physical and cognitive functioning. The occurrence of ADEs can lead to a perceived lack of therapy efficacy and further underuse or suboptimal adherence in elderly people, with detrimental clinical outcomes. The present article systematically reviews the studies evaluating the economic impact of ADEs occurring as consequence of poor therapy adherence, inappropriate drug use, underuse of effective treatments and poor adherence, medication errors, drug-drug and drug-disease interactions.A Medline systematic literature review of studies evaluating the economic consequences of inappropriate drug prescribing, lack of adherence and compliance, ADEs in older people was performed. English-language articles were screened through a three-step approach (title review, abstract review, full article review) to select pertinent studies quantitatively evaluating costs. We systematically reviewed evidence from767 articles. After title, abstract and full text review, 21 articles were found to measure economic implications ofADEs, inappropriate drug prescribing and poor adherence in elderly patients. Studies suggested that the economic impact of these undesired effects is substantial: hospital costs were the main cost driver, with a relevant part of them being preventable (consequences of inappropriate prescribing). Healthcare costs for unused drug wastage and destruction were also surprisingly high.Although economic evidence in elderly patients is still limited, all studies seemed to confirm that the financial burden due to pharmacological treatment issues is relevant in elderly people. Including economic effects of adverse events in pharmacoeconomic analysis would be beneficial to improve the reliability of results. Preliminary evidence suggests that programmes aimed at comprehensively assessing geriatric conditions, detecting 'high-risk' prescriptions and training patients to comply with prescribed therapies could be costeffective measures to reduce the burden of ADEs.