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

Bahar, M. A., Wang, Y., Bos, J. H. J., Wilffert, B. & Hak, E., Jun-2018, In : Pharmacoepidemiology and Drug Safety. 27, 6, p. 621-629 9 p.

Research output: Contribution to journalArticleAcademicpeer-review

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 (60years) 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.

Original languageEnglish
Pages (from-to)621-629
Number of pages9
JournalPharmacoepidemiology and Drug Safety
Volume27
Issue number6
Publication statusPublished - Jun-2018

    Keywords

  • citalopram, CYP2D6, drug-drug interactions (DDI), metoprolol, mirtazapine, paroxetine, fluoxetine, pharmacoepidemiology, SEROTONIN REUPTAKE INHIBITORS, DRUG-DRUG INTERACTIONS, HUMAN LIVER-MICROSOMES, HEALTHY-VOLUNTEERS, INTRAINDIVIDUAL VARIABILITY, CLINICAL-PHARMACOLOGY, COMMUNITY PHARMACIES, TREATED PATIENTS, CYP2D6 GENOTYPE, PAROXETINE

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