Concordance of Severity Ratings Provided in Four Drug Interaction Compendia

Abarca, Jacob; Malone, Daniel C.; Armstrong, Edward P.; Grizzle, Amy J.; Hansten, Philip D.; Bergen, Robin C. Van; Lipton, Richard B.

doi:10.1331/154434504773062582

Cited by 164 publications

(126 citation statements)

References 9 publications

(9 reference statements)

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“…These reference sources are based on DDI studies using multiple methodologies of variable quality in a range of experimental models. Studies may be conducted in silico, in vitro or in vivo, the latter comprising formal pharmacokinetic interaction studies in animals and humans, or as reports of clinical observations.The assessment of these studies is seldom explicit, and there is lack of consistency and considerable disparity between resources [2][3][4][5][6]. For example, in a recent study of four international drug interaction compendia, between 14% and 44% of the interactions classified as major in any one compendium were not listed in other compendia [4].Thus, interpreting the clinical relevance of a given perpetrator is often difficult, particularly for healthcare providers subject to 'information overload' and 'alert fatigue' [7,8].…”

Section: Introductionmentioning

confidence: 99%

Perpetrators of pharmacokinetic drug–drug interactions arising from altered cytochrome P450 activity: a criteria‐based assessment

Polasek

Lin

Miners

et al. 2011

Brit J Clinical Pharma

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WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Many drugs inhibit or induce cytochrome P450 enzymes (CYP) to cause clinically significant changes in the concentrations of other drugs, i.e.'perpetrate' pharmacokinetic drug-drug interactions (PK-DDIs).• Tables that list the substrates, inhibitors and inducers of CYP are common, but they lack consistency and are constructed from evidence of variable quality. WHAT THIS STUDY ADDS• This is the first study to catalogue important perpetrators of PK-DDIs using objective criteria and clinical pharmacokinetic drug interaction studies. This information is intended to inform clinical decisions on PK-DDIs.• Existing tables of CYP inhibitors and inducers have low sensitivity and low positive predictive value in identifying the major perpetrators of PK-DDIs. • Several drugs were identified which potentially perpetrate CYP-mediated PK-DDIs, but quality clinical pharmacokinetic interaction studies are lacking. This information may be used to inform future research. AIMSTo catalogue the perpetrators of CYP-mediated pharmacokinetic drug-drug interactions (PK-DDIs) using clinically relevant criteria, and to compare this with an analogous catalogue. METHODSCandidate inhibitors and inducers of CYP1A2, CYP2C9, CYP2C19, CYP2D6 and CYP3A ('perpetrators') were evaluated using published clinical pharmacokinetic interaction studies. Studies were selected on the basis of Նsix human subjects, use of a validated in vivo probe substrate for the CYP enzyme, and clinically relevant dosing. Inhibitors were described according to the FDA classifications of strong, moderate or weak, whereas inducers were classified as major (Նtwofold decrease in AUC) or weak (

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Section: Introductionmentioning

confidence: 99%

Perpetrators of pharmacokinetic drug–drug interactions arising from altered cytochrome P450 activity: a criteria‐based assessment

Polasek

Lin

Miners

et al. 2011

Brit J Clinical Pharma

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“…In a Danish study of 26 337 elderly patients, 4.4% received drug combinations carrying a risk of severe interactions [4]. In a recent prospective study in the United Kingdom, drug interactions accounted for 16.6% of adverse drug reactions causing hospitalization [5]. Wide implementation of computerized prescribing and dispensing with clinical decision support systems is recognized as a priority to reduce medication incidents [3,6].…”

Section: Introductionmentioning

confidence: 99%

Comparative assessment of four drug interaction compendia

Vitry

2006

Brit J Clinical Pharma

134

106

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AimsTo assess the consistency of inclusion and grading of major drug interactions for 50 drugs in four leading international drug interaction compendia. MethodsFour international drug interaction compendia were compared: the drug interactions appendix of the British National Formulary, the interaction supplement in the French drug compendium Vidal, and two US drug interaction compendia, Drug Interaction Facts and the Micromedex (Drug-Reax) program. Major interactions were defined as potentially hazardous in BNF or with the warning 'contraindication' or 'avoid' in Vidal or with the significance grading 1 or 2 in DIF. Major interactions for a list of 50 drugs were searched in all four compendia. ResultsA total of 1264 interactions meeting the inclusion criteria were identified for these 50 drugs. After deletion of 169 duplicates, 1095 interactions were included in the analysis. Of the drug interactions classified as major in any one compendium between 14% and 44% were not listed in the other compendia. The grading systems used for the severity and the quality of the supporting evidence in Micromedex and DIF were inconsistent. ConclusionsThere is a lack of consistency in the inclusion and grading of drug interactions of major significance for 50 drugs across the four drug compendia examined. This may reflect the lack of standardization of the terminology used to classify drug interactions and the lack of good epidemiological evidence on which to base the assessment of the clinical relevance of drug interactions.

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“…[23,24] Although minimizing the number of alerts is an approach to increase the specificity, DDI compendia show little consensus about the most severe DDIs. [25] However, an expert panel recently suggested a set of 15 important DDIs for which all CIS should display alerts. [11] Limitations of our study include lack of a sensitivity analysis of the knowledge base implemented to identify DDIs.…”

Section: Discussionmentioning

confidence: 99%

“…Categorizing DDIs by severity is necessary but not sufficient to solve the problem. [7,25,28] Drug combinations associated with DDIs considered severe are sometimes ordered by prescribers because of a well-known DDI and not despite. E.g.…”

Section: Discussionmentioning

confidence: 99%

Use of an On-demand Drug–Drug Interaction Checker by Prescribers and Consultants: A Retrospective Analysis in a Swiss Teaching Hospital

Beeler

Eschmann

Rosen³

et al. 2013

Drug Saf

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BACKGROUND: Offering a drug-drug interaction (DDI) checker on-demand instead of computertriggered alerts is a strategy to avoid alert fatigue. OBJECTIVE: The purpose was to determine the use of such an on-demand tool, implemented in the clinical information system for inpatients. METH-ODS: The study was conducted at the University Hospital Zurich, an 850-bed teaching hospital. The hospital-wide use of the on-demand DDI checker was measured for prescribers and consulting pharmacologists. The number of DDIs identified on-demand was compared to the number that would have resulted by computer-triggering and this was compared to patient-specific recommendations by a consulting pharmacist. RESULTS: The on-demand use was analyzed during treatment of 64,259 inpatients with 1,316,884 prescriptions. The DDI checker was popular with nine consulting pharmacologists (648 checks/consultant). A total of 644 prescribing physicians used it infrequently (eight checks/prescriber). Among prescribers, internists used the tool most frequently and obtained higher numbers of DDIs per check (1.7) compared to surgeons (0.4). A total of 16,553 DDIs were identified on-demand, i.e., <10 % of the number the computer would have triggered (169,192). A pharmacist visiting 922 patients on a medical ward recommended 128 adjustments to prevent DDIs (0.14 recommendations/patient), and 76 % of them were applied by prescribers. In contrast, computer-triggering the DDI checker would have resulted in 45 times more alerts on this ward (6.3 alerts/patient). CONCLUSIONS: The on-demand DDI checker was popular with the consultants only. However, prescribers accepted 76 % of patient-specific recommendations by a pharmacist. The prescribers' limited on-demand use indicates the necessity for developing improved safety concepts, tailored to suit these consumers. Thus, different approaches have to satisfy different target groups. Running TitleUse of an On-demand DDI Checker Keywords (MeSH terms)

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Concordance of Severity Ratings Provided in Four Drug Interaction Compendia

Cited by 164 publications

References 9 publications

Perpetrators of pharmacokinetic drug–drug interactions arising from altered cytochrome P450 activity: a criteria‐based assessment

Perpetrators of pharmacokinetic drug–drug interactions arising from altered cytochrome P450 activity: a criteria‐based assessment

Comparative assessment of four drug interaction compendia

Use of an On-demand Drug–Drug Interaction Checker by Prescribers and Consultants: A Retrospective Analysis in a Swiss Teaching Hospital

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