Sex-Based Difference in the Effect of Metoprolol on Heart Rate and Bradycardia in a Population-Based Setting

Hendriksen, Linda C.; Omes-Smit, Grace; Koch, Birgit C. P.; Ikram, M. Arfan; Stricker, Bruno H. Ch.; Visser, Loes E.

doi:10.3390/jpm12060870

Cited by 9 publications

(4 citation statements)

References 31 publications

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“…Although this has to be confirmed in future prospective research, the higher dose-and age-adjusted drug/metabolite concentrations we observed in females are likely to contribute to the higher risk of ADRs described for multiple drug classes, including beta-blockers metabolized by CYP2D6. 32,33 Data regarding the risk of ADRs in females treated with allopurinol are more scarce, but lean toward an increased risk in older females. 34 Interestingly, in our study, more than half of females also reported previous drug allergies and intolerances to medication, which was consistently more than what was reported in males.…”

Section: Discussionmentioning

confidence: 99%

Females present higher dose‐adjusted drug concentrations of metoprolol and allopurinol/oxypurinol than males

Hindi

Pilon

Meloche

et al. 2023

Clinical Translational Sci

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Females present a higher risk of adverse drug reactions. Sex‐related differences in drug concentrations may contribute to these observations but they remain understudied given the underrepresentation of females in clinical trials. The aim of this study was to investigate whether anthropometric and socioeconomic factors and comorbidities could explain sex‐related differences in concentrations and dosing for metoprolol and oxypurinol, the active metabolite of allopurinol. We conducted an analysis of two cross‐sectional studies. Participants were self‐described “White” adults taking metoprolol or allopurinol selected from the Montreal Heart Institute Hospital Cohort. A total of 1007 participants were included in the metoprolol subpopulation and 459 participants in the allopurinol subpopulation; 73% and 86% of the participants from the metoprolol and allopurinol subpopulations were males, respectively. Females presented higher age‐ and dose‐adjusted concentrations of both metoprolol and oxypurinol (both p < 0.03). Accordingly, females presented higher unadjusted and age‐adjusted concentration:dose ratio of both metoprolol and allopurinol/oxypurinol compared to males (all p < 3.0 × 10−4). Sex remained an independent predictor of metoprolol concentrations (p < 0.01), but not of oxypurinol concentrations, after adjusting for other predictors. In addition to sex, age, daily dose, use of moderate to strong CYP2D6 inhibitors, weight, and CYP2D6 genotype‐inferred phenotype were associated with concentrations of metoprolol (all p < 0.01). Daily dose, weight, estimated glomerular filtration rate (eGFR), and employment status were associated with oxypurinol concentrations (all p < 0.01). Females present higher dose‐adjusted concentrations of metoprolol and oxypurinol than males. This suggests the need for sex‐specific dosing requirements for these drugs, although this hypothesis should be validated in prospective studies.

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Section: Discussionmentioning

confidence: 99%

Females present higher dose‐adjusted drug concentrations of metoprolol and allopurinol/oxypurinol than males

Hindi

Pilon

Meloche

et al. 2023

Clinical Translational Sci

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“…60 This means that dose adjustments should not be neglected to avoid adverse events (AEs). 61 Women also have a higher incidence of druginduced liver toxicity, gastrointestinal AEs due to NSAIDs, allergic skin rashes (up to 2-fold), cough with ACE-I (2-fold), hemorrhagic complications with anticoagulants, platelet antiaggregants and thrombolytics, and myopathy with statins. 21 Studies found that 74% of cases of acute liver failure due to drug toxicity appear in women, over 50% of them occurring using therapeutic doses of medication.…”

Section: Adverse Drug Reactionsmentioning

confidence: 99%

Sex Differences in Cardiovascular Management: A Call for Better Acknowledgment—Part 1 Pharmacological Differences in Women and Men; How Relevant Are They?

Ivanescu,

Dan

2024

American Journal of Therapeutics

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Background: Sex differences (SDs) in pharmacology of cardiovascular (CV) drugs have been described previously; however, paradoxically, there are scarce recommendations in therapy based on these differences. It is of utmost importance to identify whether these SDs determine a modified clinical response and the potential practical implications for this, to provide a base for personalized medicine. Area of uncertainty: The aim of this article was to outline the most important pharmacological drivers of cardiovascular drugs that differ between women and men, along with their implications and challenges in clinical practice. Data sources: A detailed assessment of English-written resources reflecting SDs impact in CV drug pharmacology was performed using PubMed and Embase databases. Results: Despite large variations in CV drug pharmacokinetics and pharmacodynamics in individuals, correcting for height, weight, surface area, and body composition compensate for most “sex-dependent” differences. In addition, individual, cultural, and social factors significantly impact disease management in women versus men. Gender-biased prescribing patterns and gender-dependent adherence to therapy also influence outcomes. The development of sex-specific guidelines requires that they should reflect the SDs implications for the management of a disease and that the evidence should be carefully evaluated as to whether there is an adequate representation of both sexes and whether sex-disaggregated data are reported. Conclusions: Pharmacological drivers are under the influence of an impressive number of differences between women and men. However, to establish their significance in clinical practice, an adequate representation of women in studies and the reporting of distinct results is mandatory.

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“… 79 Thus, a greater reduction in heart rate and blood pressure and a significantly increased risk of bradycardia have been reported in women. 80 …”

Section: Pharmacodynamic and Pharmacokinetic Differences In The Elderlymentioning

confidence: 99%

Italian Association of Hospital Cardiologists Position Paper ‘Gender discrepancy: time to implement gender-based clinical management’

Lucà,

Pavan,

Gulizia

et al. 2024

European Heart Journal Supplements

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It has been well assessed that women have been widely under-represented in cardiovascular clinical trials. Moreover, a significant discrepancy in pharmacological and interventional strategies has been reported. Therefore, poor outcomes and more significant mortality have been shown in many diseases. Pharmacokinetic and pharmacodynamic differences in drug metabolism have also been described so that effectiveness could be different according to sex. However, awareness about the gender gap remains too scarce. Consequently, gender-specific guidelines are lacking, and the need for a sex-specific approach has become more evident in the last few years. This paper aims to evaluate different therapeutic approaches to managing the most common women’s diseases.

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Sex-Based Difference in the Effect of Metoprolol on Heart Rate and Bradycardia in a Population-Based Setting

Cited by 9 publications

References 31 publications

Females present higher dose‐adjusted drug concentrations of metoprolol and allopurinol/oxypurinol than males

Females present higher dose‐adjusted drug concentrations of metoprolol and allopurinol/oxypurinol than males

Sex Differences in Cardiovascular Management: A Call for Better Acknowledgment—Part 1 Pharmacological Differences in Women and Men; How Relevant Are They?

Italian Association of Hospital Cardiologists Position Paper ‘Gender discrepancy: time to implement gender-based clinical management’

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