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Purpose: Recent studies suggest that women are more susceptible to diuretic-induced hyponatremia resulting in hospital admission than men. The aim of this study was to confirm whether these sex differences in hyponatremia-related hospital admissions in diuretic users remain after adjusting for several confounding variables such as age, dose, and concurrent medication., Methods: In a case-control design nested in diuretic users, cases of hyponatremia associated hospital admissions between 2005 and 2017 were identified from the PHARMO Data Network. Cases were 1:10 matched to diuretic users as controls. Odds ratios (OR) with 95%CIs were calculated for women versus men and adjusted for potential confounders (age, number of diuretics, other hyponatremia-inducing drugs, chronic disease score) using unconditional logistic regression analysis. A subgroup analysis was performed for specific diuretic groups (thiazides, loop diuretics and aldosterone antagonists)., Results: Women had a statistically significantly higher risk of a hospital admission associated with hyponatremia than men while using diuretics (OR 1.86, 95%CI 1.64-2.11). Adjusting for the potential confounders resulted in an increased risk for women compared to men (ORadj 2.65, 95% CI 2.31-3.04). This higher risk in women was also seen in the three subgroup analyses after adjustment., Conclusion: Our findings show a higher risk of hyponatremia-related hospital admission in women than men while using diuretics. Further research is needed to understand the underlying mechanism of this sex difference to be able to provide sex-specific recommendations., (© 2023 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)

Purpose: Current guidelines have no sex-specific dosage advice for metoprolol. To evaluate whether women and men are prescribed the same dose a cohort analysis was performed in the population-based Rotterdam Study (RS). Results were replicated in the Integrated Primary Care Information (IPCI) database of automated general practice data., Methods: The mean daily starting doses of metoprolol in both sexes were compared with independent-samples t-tests and a linear regression analysis was used to adjust in the RS for co-variables, notably, cardiovascular comorbidity, migraine, age, SBP, DBP, BMI, socioeconomic status, use of other antihypertensive drugs, smoking, and alcohol. In the IPCI-database, adjustment was for age only., Results: The mean daily starting dose was statistically significantly lower in women than in men in both the RS and IPCI database, with a mean difference of 4.8 mg (95%CI -7.8, -1.8) and 4.6 mg (95%CI -5.3,-4.0), respectively. Statistical significance remained after adjustment in both databases., Conclusions: Women received lower starting doses of metoprolol than men in two independent data collections despite non-sex specific cardiovascular guideline recommendations. This example of real-life pharmacotherapy can lead to a form of confounding by contraindication in pharmacoepidemiology., (© 2021 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)

Purpose: Several studies have been conducted to assess determinants affecting the performance or accuracy of self-reports. These studies are often not focused on pregnant women, or medical records were used as a data source where it is unclear if medications have been dispensed. Therefore, our objective was to evaluate the concordance between self-reported medication data and pharmacy records among pregnant women and its determinants., Methods: We conducted a population-based cohort study within the Generation R study, in 2637 pregnant women. The concordance between self-reported medication data and pharmacy records was calculated for different therapeutic classes using Yule's Y. We evaluated a number of variables as determinant of discordance between both sources through univariate and multivariate logistic regression analysis., Results: The concordance between self-reports and pharmacy records was moderate to good for medications used for chronic conditions, such as selective serotonin reuptake inhibitors or anti-asthmatic medications (0.88 and 0.68, respectively). Medications that are used occasionally, such as antibiotics, had a lower concordance (0.51). Women with a Turkish or other non-Western background were more likely to demonstrate discordance between pharmacy records and self-reported data compared with women with a Dutch background (Turkish: odds ratio, 1.63; 95% confidence interval, 1.16-2.29; other non-Western: odds ratio, 1.33; 95% confidence interval, 1.03-1.71)., Conclusions: Further research is needed to assess how the cultural or ethnic differences may affect the concordance or discordance between both medication sources. The results of this study showed that the use of multiple sources is needed to have a good estimation of the medication use during pregnancy., (Copyright © 2017 John Wiley & Sons, Ltd.)

Purpose: Simvastatin and atorvastatin are metabolized by the CYP3A4 enzyme and transported by the ABCB1 transporter. We studied whether the polymorphism CYP3A4*1B and the polymorphisms C1236T, G2677A/T and C3435T in the ABCB1 gene were associated with a decrease of the prescribed dose or a switch to another cholesterol lowering drug during simvastatin and atorvastatin therapy. These events may indicate that statin plasma levels were too high and resulted in an adverse drug reaction or a too strong reduction in cholesterol level., Methods: We identified 1239 incident simvastatin and atorvastatin users in the Rotterdam Study, a population-based cohort study. Associations between the polymorphisms in the CYP3A4 and ABCB1 gene and the time to a decrease in dose or a switch to another cholesterol lowering drug were studied using Cox proportional hazards., Results: Simvastatin and atorvastatin users with the CYP3A4*1B variant G allele had a lower risk (HR 0.46; 95%CI 0.24-0.90) for these events than users with the wild-type AA genotype. No significant associations were found for the ABCB1 polymorphisms. The association with the CYP3A4*1B polymorphism was found in women (HR 0.33; 95%CI 0.12-0.89) and was non-significant in men (HR 0.69 95%CI 0.28-1.70). This association was stronger in patients with the ABCB1 3435T variant allele versus the G allele., Conclusion: In simvastatin and atorvastatin users, the CYP3A4*1B G allele is associated with a lower risk of elevated statin plasma levels, particularly in women and in users with the ABCB1 3435T variant allele.

Purpose: Our objective was to evaluate the incidence of adverse patient outcomes due to drug-drug interactions (D-DIs), the type of drugs involved and the underlying reason. As a proxy for adverse patient outcomes, emergency department (ED) visits, hospital admissions and re-hospitalisations were assessed., Methods: A literature search in the Medline and Embase database (1990-2006) was performed and references were tracked. An overall cumulative incidence was estimated by dividing the sum of the cases by the sum of the study populations., Results: Twenty-three studies were found assessing the relationship between D-DIs and ED-visits, hospitalisations or re-hospitalisations. The studies with a large study size showed low incidences and vice versa. D-DIs were held responsible for 0.054% of the ED-visits, 0.57% of the hospital admissions and 0.12% of the re-hospitalisations. In the elderly population, D-DIs were held responsible for 4.8% of the admissions. Drugs most often involved were NSAIDs and cardiovascular drugs. The reasons for admissions or ED-visits, which were most often found were GI-tract bleeding, hyper- or hypotension and cardiac rhythm disturbances., Conclusion: This review provides information on the overall incidence of D-DIs as a cause of adverse patient outcomes, although there is still uncertainty about the impact of D-DIs on adverse patient outcomes. Our results suggest that a limited number of drugs are involved in the majority of cases and that the number of reasons for admission as a consequence of D-DIs seems to be modest., (Copyright (c) 2006 John Wiley & Sons, Ltd.)