Identification and weighting of the most critical "real-life" drug-drug interactions with acenocoumarol in a tertiary care hospital.
OBJECTIVE
The objective of this study was to identify the most clinically relevant drug-drug interactions (DDIs) at risk of affecting acenocoumarol safety in our tertiary care university hospital, a 2,000 bed institution.


METHODS
We identified DDIs occurring with acenocoumarol by combining two different sources of information: a 1-year retrospective analysis of acenocoumarol prescriptions and comedications from our Computerized Physician Order Entry (CPOE) system (n = 2,439 hospitalizations) and a retrospective study of clinical pharmacology consultations involving acenocoumarol over the past 14 years (1994-2007) (n = 407). We classified these DDIs using an original risk-analysis method. A criticality index was calculated for each associated drug by multiplying three scores based on mechanism of interaction, involvement in a supratherapeutic international normalized ratio (INR) (≥ 6) and involvement in a severe bleeding.


RESULTS
One hundred and twenty-six DDIs were identified and weighted. Twenty-eight drugs had a criticality index ≥ 20 and were therefore considered at high risk for interacting with acenocoumarol by increasing its effect: 75% of these drugs involved a pharmacokinetic mechanism and 14 % a pharmacodynamic mechanism. An unknown mechanism of interaction was involved in 11 % of drugs.


CONCLUSIONS
Twenty-eight specific drugs were identified as being at high risk for interacting with acenocoumarol in our hospital using an original risk-analysis method. Most analyzed drugs interact with acenocoumarol via a pharmacokinetic mechanism. Actions such as the implementation of alerts in our CPOE system should be specifically developed for these drugs.
Division of Clinical Pharmacology and Toxicology, University Hospitals of Geneva, Rue Gabrielle-Perret-Gentil 4, 1211 Geneva 14, Switzerland. liliane.gschwind@gmail.com
L
L
Gschwind
V
V
Rollason
C
C
Lovis
F
F
Boehlen
P
P
Bonnabry
P
P
Dayer
J A
JA
Desmeules
D000074:Acenocoumarol / Q000009:adverse effects* / Q000493:pharmacokinetics; D016907:Adverse Drug Reaction Reporting Systems; D000925:Anticoagulants / Q000009:adverse effects* / Q000493:pharmacokinetics; D001777:Blood Coagulation / Q000187:drug effects*; D004347:Drug Interactions; D011307:Drug Prescriptions; D006470:Hemorrhage / Q000139:chemically induced; D006742:Hospital Bed Capacity; D006785:Hospitals, University; D006801:Humans; D019934:International Normalized Ratio; D050316:Medical Order Entry Systems; D008508:Medication Errors / Q000517:prevention & control; D016017:Odds Ratio; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013557:Switzerland; D062606:Tertiary Care Centers; D013997:Time Factors
D000925:Anticoagulants; D000074:Acenocoumarol