The burden and management of cytochrome P450 2D6 (CYP2D6)-mediated drug-drug interaction (DDI): co-medication of metoprolol and paroxetine or fluoxetine in the elderly

作者：Bahar Muh Akbar; Hak Eelko; Bos Jens H J; Borgsteede Sander D; Wilffert Bob

来源：Pharmacoepidemiology and Drug Safety, 2017, 26(7): 752-765.

DOI：10.1002/pds.4200

• cytochrome P450 (CYP)-based drug-drug interactions (DDI)
• CYP2D6
• paroxetine
• fluoxetine
• metoprolol
• beta-blockers
• antidepressants
• pharmacoepidemiology

PurposeMetoprolol and paroxetine/fluoxetine are inevitably co-prescribed because cardiovascular disorders and depression often coexist in the elderly. This leads to CYP2D6-mediated drug-drug interactions (DDI). Because systematic evaluations are lacking, we assessed the burden of metoprolol-paroxetine/fluoxetine interaction in the elderly and how these interactions are managed in Dutch community pharmacies.
MethodDispensing data were collected from the University of Groningen pharmacy database (IADB.nl, 1999-2014) for elderly patients (60years) starting beta-blockers and/or antidepressants. Based on the two main DDI alert systems (G-Standard and Pharmabase), incidences were divided between signalled (metoprolol-fluoxetine/paroxetine) and not-signalled (metoprolol-alternative antidepressants and alternative beta-blockers-paroxetine/fluoxetine) combinations. Incident users were defined as patients starting at least one signalled or a non-signalled combination. G-Standard signalled throughout the study period, whereas Pharmabase stopped after 2005.
ResultsA total of 1763 patients had 2039 metoprolol-paroxetine/fluoxetine co-prescriptions, despite DDI alert systems, and about 57.3% were signalled. The number of metoprolol-alternative antidepressant combinations (incidences=3150) was higher than alternative beta-blocker-paroxetine/fluoxetine combinations (incidences=1872). Metoprolol users are more likely to be co-medicated with an alternative antidepressant (incidences=2320) than paroxetine/fluoxetine users (incidences=1232) are. The number of paroxetine/fluoxetine users co-prescribed with alternative beta-blockers was comparable to those co-medicated with metoprolol (about 50%). Less than 5% of patients received a substitute therapy after using metoprolol-paroxetine/fluoxetine. Most of the metoprolol users (90%) received a low dose (mean DDD=0.47) regardless whether they were prescribed paroxetine/fluoxetine.
ConclusionDespite the signalling software, metoprolol-paroxetine/fluoxetine combinations are still observed in the elderly population. The clinical impact of these interactions needs further investigation.

• 出版日期2017-7