Epidemiology of Drug-Drug Interactions as a Cause of Hospital Admissions

Abstract

The purpose of this review was to focus on hospital admissions caused by a specific type of adverse drug reaction (ADR) that can be assumed to be avoidable in almost all cases: the drug-drug interaction (D-DI). To determine the epidemiology of D-DIs in hospital admissions, a review of the adverse drug reaction literature was undertaken to answer several questions: (a) what is the incidence of hospital admissions attributable to D-DIs?; (b) what percentage of drug-related hospital admissions are attributable to D-DIs?; (c) are there any patterns to the above findings, i.e. are some D-DIs or specific drugs more likely to have been associated with hospital admissions?; and (d) are there certain patient risk factors (e.g. age) that are associated with D-DIs that led to a hospital admission? Nine ADR studies were found that either included a D-DI category as a cause for hospital admissions, or provided sufficient information so that a causal relationship could be inferred. The incidence of hospital admissions due to D-DIs ranged from 0 to 2.8%. The data found in the studies we reviewed, however, were insufficient to allow meaningful quantification of specific drugs as usual causes for D-DI-related admissions, and because of the very small numbers of patients for which a D-DI was believed to be the cause it is not possible to provide a meaningful summary of risk factors specific for D-DI admissions. We cannot conclude that D-DIs are a significant problem. There is a need to view the quantification of D-DIs in relation to the number of medications prescribed by physicians, dispensed by pharmacists and taken by patients.

A Pharmacoepidemiologic Study of Drug Interactions in a Brazilian Teaching Hospital

“…There is only a partial agreement among DDI compendia. 7,17 In this study, a compendium that lists most of the known interactions was used. This may have resulted in an overestimation of DDI in the whole sample.…”

Prediction of the Effect of Erythromycin, Diltiazem, and Their Metabolites, Alone and in Combination, on CYP3A4 Inhibition

“…In conclusion, the additive model predicted the combined effect of multiple inhibitors on CYP3A inhibition in vitro. However, simultaneous reversible and irreversible inhibition effects should be taken into account in a reaction mixture of substrate and multiple inhibitors of CYP3A4.Concomitant medications causing drug-drug interactions (DDIs) have led to serious adverse drug events during treatment and resulted in restrictions in prescribing drugs and withdrawal of drugs from the market (Jankel and Fitterman, 1993;Yuan et al, 1999). The incidence and extent of DDIs would be expected to increase when multiple inhibitors of a specific drug-metabolizing enzyme are administered simultaneously compared with administration of a single inhibitor alone.…”

“…Concomitant medications causing drug-drug interactions (DDIs) have led to serious adverse drug events during treatment and resulted in restrictions in prescribing drugs and withdrawal of drugs from the market (Jankel and Fitterman, 1993;Yuan et al, 1999). The incidence and extent of DDIs would be expected to increase when multiple inhibitors of a specific drug-metabolizing enzyme are administered simultaneously compared with administration of a single inhibitor alone.…”

Evaluation of Time-Dependent Cytochrome P450 Inhibition Using Cultured Human Hepatocytes

“…Inhibition of cytochrome P450 (P450)-dependent metabolism is a prevalent source of drug-drug interactions (DDIs) and may result in serious clinical consequences (Jankel and Fitterman, 1993;Bertz and Granneman, 1997) via either reversible or irreversible means. An assessment of the potential of a new chemical entity to cause DDIs via inhibition of P450 metabolism is important early in the drug discovery process.…”