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Pharmacoepidemiological assessment of drug interactions with vitamin K antagonists
Author(s) -
Pottegård Anton,
Christensen Rene,
Wang Shirley V.,
Gagne Joshua J.,
Larsen Torben B.,
Hallas Jesper
Publication year - 2014
Publication title -
pharmacoepidemiology and drug safety
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.023
H-Index - 96
eISSN - 1099-1557
pISSN - 1053-8569
DOI - 10.1002/pds.3714
Subject(s) - medicine , tramadol , concomitant , warfarin , vitamin k antagonist , rate ratio , confidence interval , pharmacoepidemiology , drug , pharmacology , medical prescription , anesthesia , atrial fibrillation , analgesic
Abstract Purpose We present a database of prescription drugs and international normalized ratio (INR) data and the applied methodology for its use to assess drug–drug interactions with vitamin K antagonists (VKAs). We use the putative interaction between VKAs and tramadol as a case study. Methods We used a self‐controlled case series to estimate the incidence rate ratio (IRR) comparing the rate of INR measurements of ≥4.0 in concomitant tramadol and VKA‐exposed periods to VKA‐only‐exposed periods. Secondary analyses considered specific subgroups, alternative exposure criteria, alternative outcome definitions, and other drugs. Results We identified 513 VKA users with at least 1 INR measurement ≥4.0 and concomitant tramadol and VKA exposure during the observation period. The overall IRR was 1.80 (95% confidence interval [CI], 1.53–2.10), with a stronger association among users of phenprocoumon compared to warfarin (IRR, 3.37; 95%CI, 2.50–4.53 and IRR, 1.46; 95%CI, 1.20–1.76, respectively). We observed larger IRRs with stricter outcome definitions. Concomitant tramadol and VKA exposure was also associated with an increased rate of low INR measurements (i.e., <1.5; IRR, 1.70; 95%CI, 1.37–2.13). Morphine and, to some extent, oxycodone, penicillin, beta‐blockers, and inhaled beta‐agonists were associated with high INR. Conclusions The approach successfully identified an interaction between tramadol and VKA. However, associations observed for other drugs with no known VKA interaction suggest that the current approach may have too low specificity to be useful as a screening tool, at least for drugs for which time‐varying confounding may be present. Copyright © 2014 John Wiley & Sons, Ltd.