Inconsistent reporting of drug-drug interactions for hormonal contraception and antiepileptic drugs - Implications for reproductive health for women with epilepsy.

Drug compendia are the source of safety prescribing information. We assessed the reporting concordance of drug-drug interactions between hormonal contraception and antiepileptic drugs (AEDs) among eight leading international drug compendia. Antiepileptic drugs reported to interact with ≥1 form of hormonal contraception were reviewed. Scaled concordance was quantified using linearly weighted percent agreement (wPA). Differences in interaction severity rankings between hormonal contraception forms were evaluated using the Wilcoxon signed-rank test. There was high agreement among compendia for interactions of combined hormonal contraception interactions with AEDs (wPA = 0.82-0.84), especially potent enzyme-inducing AEDs (wPA = 0.89). However, concordance was reduced for AED interactions with progestin-only contraception (wPA = 0.69-0.81). Extreme interaction reporting discrepancies were found for less potent enzyme-inducing AEDs. The greatest variability in interaction reporting was observed for injectable and intrauterine contraception (wPA = 0.69 and 0.70, respectively), which are the only hormonal contraception options currently classified as not interacting with enzyme-inducing AEDs. Drug-drug interaction reporting variability can have major clinical implications and highlights critical knowledge gaps in the care of women with epilepsy of childbearing age. Further research on AED-contraceptive interactions is needed to standardize compendia reporting and enhance evidence-based clinical guidelines for women with epilepsy.

Poor concordance among drug compendia for proposed interactions between enzyme-inducing antiepileptic drugs and direct oral anticoagulants.

PURPOSE: To assess concordance regarding proposed interactions between enzyme-inducing antiepileptic drugs (EI-AEDs) and direct oral anticoagulants (DOACs) in leading, international drug compendia. METHODS: We measured consistency of interaction reporting for each DOAC with a group of potent EI-AEDs among eight provider and consumer-focused drug compendia. Discrepant severity ranking systems were consolidated on a 0 to 4 scale. Percent agreement (PA) and Scott/Fleiss' Kappa (к) were used to quantify inter-compendia agreement on interaction listings, with linear weighting when consolidated severity rankings were taken into account (wPA and wк, respectively). RESULTS: For dabigatran, rivaroxaban, apixaban, and edoxaban, poor inter-compendia concordance was observed for interaction listings with EI-AEDs, with and without accounting for severity rankings (wPA: 0.54-0.72/wк: -0.08-0.03, and PA 0.47-0.79/к: -0.09-0.09, respectively). Conversely, betrixaban was consistently listed as not interacting with EI-AEDs in almost all assessed compendia, despite overlap in P-glycoprotein-based transport with other DOACs. Only 6/20 (30%) EI-AED/DOAC interactions were listed in all eight databases, and even in these six cases, severity rankings were universally discordant. Extreme inconsistencies in interaction reporting (some compendia assigning the highest possible severity ranking, while others reported no interactions) were observed in half of the individually examined interactions (10/20). CONCLUSIONS: Drug compendia are highly inconsistent in the inclusion and reported severity of interactions between EI-AEDs and DOACs. Generation of high-quality, real-world evidence from large-scale outcome studies is imperative to resolve discordance and provide clarity for clinical guidelines.

Implementing a Process to Review Product-Specific Misinformation in Online Drug Information Compendia.

Health care professionals and consumers often use online drug information compendia, which are intended to be user-friendly, readily available, accurate, and up-to-date. While these resources can be valuable, it has been shown that some compendia contain inaccuracies and outdated information, motivating the Medical Services (medical information) Department at Purdue Pharma LP to implement a periodic, standardized review of select online drug information compendia. Monographs within compendia for up to 9 Purdue products were reviewed and compared to their current Full Prescribing Information, with a focus on identifying safety-related misinformation. Content correction requests for nearly 1000 errors were submitted to 7 compendia clinical editors. This surprisingly large number of errors highlights the need for compendia to better maintain accurate product monographs, as well as for pharmaceutical companies to proactively and periodically review them for misinformation. Based on these findings, an overview on how the pharmaceutical industry may implement a drug information compendia review process is provided.