Discontinuation and dose adjustment of metoprolol after metoprolol‐paroxetine/fluoxetine co‐prescription in Dutch elderly

Abstract

PurposeCo‐prescription of paroxetine/fluoxetine (a strong CYP2D6 inhibitor) in metoprolol (a CYP2D6 substrate) users is common, but data on the clinical consequences of this drug‐drug interaction are limited and inconclusive. Therefore, we assessed the effect of paroxetine/fluoxetine initiation on the existing treatment with metoprolol on the discontinuation and dose adjustment of metoprolol among elderly.MethodsWe performed a cohort study using the University of Groningen IADB.nl prescription database (www.IADB.nl). We selected all elderly (≥60 years) who had ever been prescribed metoprolol and had a first co‐prescription of paroxetine/fluoxetine, citalopram (weak CYP2D6 inhibitor), or mirtazapine (negative control) from 1994 to 2015. The exposure group was metoprolol and paroxetine/fluoxetine co‐prescription, and the other groups acted as controls. The outcomes were early discontinuation and dose adjustment of metoprolol. Logistic regression was applied to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI).ResultsCombinations of metoprolol‐paroxetine/fluoxetine, metoprolol‐citalopram, and metoprolol‐mirtazapine were started in 528, 673, and 625 patients, respectively. Compared with metoprolol‐citalopram, metoprolol‐paroxetine/fluoxetine was not significantly associated with the early discontinuation and dose adjustment of metoprolol (OR = 1.07, 95% CI:0.77‐1.48; OR = 0.87, 95% CI:0.57‐1.33, respectively). In comparison with metoprolol‐mirtazapine, metoprolol‐paroxetine/fluoxetine was associated with a significant 43% relative increase in early discontinuation of metoprolol (OR = 1.43, 95% CI:1.01‐2.02) but no difference in the risk of dose adjustment. Stratified analysis by gender showed that women have a significantly high risk of metoprolol early discontinuation (OR = 1.62, 95% CI:1.03‐2.53).ConclusionParoxetine/fluoxetine initiation in metoprolol prescriptions, especially for female older patients, is associated with the risk of early discontinuation of metoprolol.

The impact of CYP2D6 mediated drug–drug interaction: a systematic review on a combination of metoprolol and paroxetine/fluoxetine

“…Meanwhile, the control group consisted of metoprolol users without hospitalization and who were newly treated with the studied drugs (394 patients). The second study is a retrospective cohort study by Bahar et al using a prescription database (IADB.nl) among Dutch elderly (≥60 years) patients with metoprolol prescription (64 578 patients) who were co‐prescribed with paroxetine/fluoxetine (528 patients), with citalopram (673 patients), and with mirtazapine (625 patients) . No PK data were presented in these studies.…”

“…The authors explained that it might be caused by differences in the body mass index and the rate of CYP2D6 metabolic activity between men and women. However, the data regarding the latter is not clear [32].…”

Patterns and Characteristics of Polypharmacy Among Elderly Residents in Danish Nursing Homes

“…However, it has been observed that coadministration of Metoprolol and Mirtazapine is safe with no clinically significant DDIs [ 83 ]. In fact, this lack of clinical adverse effects has been documented to such a degree that Mirtazapine has been used as the negative control in a case–control study of interactions between Metoprolol and selective serotonin reuptake inhibitors [ 84 ].…”

Influence of age on real-life effects of doxycycline for acute exacerbations among COPD outpatients: a population-based cohort study

“…We applied a retrospective inception cohort study (figure 1) using the University of Groningen’s prescription database IADB.nl that contains over 1.2 million dispensings from about 600 000 patients in 60 community pharmacies in the Netherlands since 1994 25 26. IADB.nl provided complete information including date of birth, gender, prescribed drug name, anatomical therapeutic chemical (ATC) codes, dispensing date, quantity dispensed and dose regimen 27.…”