Drug Safety最新文献

Introduction: Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome is gaining attention in pharmacovigilance, but its association with antipsychotics, other than clozapine, is still unclear.

Methods: We conducted a case/non-case study with disproportionality analysis based on the World Health Organization (WHO) global spontaneous reporting database, VigiBase®. We analyzed individual case safety reports of DRESS syndrome related to antipsychotics compared to (1) all other medications in VigiBase®, (2) carbamazepine (a known positive control), and (3) within classes (typical/atypical) of antipsychotics. We calculated reporting odds ratio (ROR) and Bayesian information component (IC), with 95% confidence intervals (CIs). Disproportionate reporting was prioritized based on clinical importance, according to predefined criteria. Additionally, we compared characteristics of patients reporting with serious/non-serious reactions.

Results: A total of 1534 reports describing DRESS syndrome for 19 antipsychotics were identified. The ROR for antipsychotics as a class as compared to all other medications was 1.0 (95% CI 0.9-1.1). We found disproportionate reporting for clozapine (ROR 2.3, 95% CI 2.1-2.5; IC 1.2, 95% CI 1.1-1.3), cyamemazine (ROR 2.3, 95% CI 1.5-3.5; IC 1.2, 95% CI 0.5-1.7), and chlorpromazine (ROR 1.5, 95% CI 1.1-2.1; IC 0.6, 95% CI 0.1-1.0). We found 35.7% of cases with co-reported anticonvulsants, and 25% with multiple concurrent antipsychotics in serious compared to 8.6% in non-serious cases (p = 0.03). Fatal cases were 164 (10.7%).

Conclusions: Apart from the expected association with clozapine, chlorpromazine and cyamemazine (sharing an aromatic heteropolycyclic molecular structure) emerged with a higher-than-expected reporting of DRESS. Better knowledge of the antipsychotic-related DRESS syndrome should increase clinicians' awareness leading to safer prescribing of antipsychotics.

Introduction: Adverse drug reactions (ADRs) are common among people with dementia; however, little is known about the magnitude and predictors associated with ADR-related hospitalisation among these individuals. This study aimed to determine the magnitude, types, drugs implicated and predictors of ADRs associated with hospitalisation among people with dementia.

Methods: This retrospective case-control study analysed medical records of individuals aged ≥ 65 years with dementia admitted to major public hospitals in Tasmania, Australia, from July 2010 to July 2021. Adverse drug reactions and implicated drugs were identified using administrative data and cross-checked with hospital medical records, with consensus reached among the research team.

Results: Of the 7928 people admitted to hospital at least once within the study period, 1876 (23.7%) experienced at least one ADR-related hospitalisation. Of these, 300 case patients with 311 ADRs and 300 control patients were randomly selected. The most common types of ADRs were renal (acute kidney injury; AKI) (36.0%), followed by neuropsychiatric (17.6%), cardiovascular (16.0%) and haematological (13.1%). Diuretics, renin-angiotensin system (RAS) inhibitors and anti-thrombotics constituted the main implicated drug classes. The ADR-related hospitalisation was associated with: chronic kidney disease (CKD) (OR 8.00, 95% CI 2.63-24.28, p < 0.001), Australian-born (OR 1.62, 95% CI 1.08-2.43, p = 0.019), hypertension (OR 1.48, 95% CI 1.01-2.17, p = 0.044) and the number of medicines (OR 1.06, 95% CI 1.00-1.12, p = 0.022). Potentially inappropriate medication use and anticholinergic burden did not predict ADR-related hospitalisation.

Conclusions: These predictors could help identify the individuals at the highest risk and enable targeted interventions to be designed.

Background and objective: It is unclear which comparator is the most appropriate for bias reduction in disproportionality analyses based on spontaneous reports. We conducted a quasi-quantitative bias analysis using two well-studied drug-event combinations to assess how different comparators influence the directionality of bias in pharmacovigilance.

Methods: We used the US Food and Drug Administration Adverse Event Reporting System focusing on two drug-event combinations with a propensity for stimulated reporting: rivaroxaban and hepatotoxicity, and canagliflozin and acute kidney injury. We assessed the directionality of three disproportionality analysis estimates (reporting odds ratio, proportional reporting ratio, information component) using one unrestricted comparator (full data) and two restricted comparators (active comparator, active comparator with class exclusion). Analyses were conducted within two calendar time periods, defined based on external events (approval of direct oral anticoagulants, Food and Drug Administration safety warning on acute kidney injury with sodium-glucose cotransporter 2 inhibitors) hypothesized to alter reporting rates.

Results: There were no false-positive signals for rivaroxaban and hepatotoxicity irrespective of the comparator. Restricting to the initial post-approval period led to false-positive signals, with restricted comparators performing worse. There were false-positive signals for canagliflozin and acute kidney injury, with restricted comparators performing better. Restricting to the period before the Food and Drug Administration warning weakened the false-positive signal for canagliflozin and acute kidney injury across comparators.

Conclusions: We could not identify a consistent and predictable pattern to the directionality of disproportionality analysis estimates with specific comparators. Calendar time-based restrictions anchored on relevant external events had a considerable impact.

Introduction and objective: As the population ages, understanding the potential risks associated with inappropriate medication use becomes increasingly important. Given the lack of studies in this area, our objective was to study the risk of mortality associated with potentially inappropriate medication use involving opioids in community-dwelling older adults.

Methods: Data came from a longitudinal study on older adults aged ≥ 65 years recruited in primary care clinics between 2011 and 2013 with an average follow-up of 4.25 years. Older adults were excluded if they used an opioid or had a malignant tumor diagnosis in the year before the study survey. A nested case-control within a cohort of older adults with at least one opioid claim during follow-up was used to evaluate the risk of all-cause mortality. Four controls per case were matched on follow-up time using risk-set sampling, i.e., while still at risk of death when their matched case died. The risk of mortality was estimated using conditional logistic regression analyses. Exposure to potentially inappropriate medication use involving opioids, defined using the Beers 2019 criteria, was assessed from provincial drug claims data in the 0-90 days before death.

Results: In a cohort of 472 community-dwelling older adults with an incident episode of opioid use, there were 40 cases matched to 160 controls. Exposure to inappropriate medication use involving opioids in the 90 days before death was associated with an increased risk of mortality (odds ratio 6.81, 95% confidence interval 1.69-27.47), after adjusting for potential confounders.

Conclusions: Exposure to inappropriate medication use involving opioids in the 90 days before death is associated with an increased risk of mortality in older adults. These findings can be used to encourage safer pain management strategies in older adults.

Introduction: Angiotensin receptor blockers are widely used antihypertensive drugs in South Korea. In 2021, the Korea Ministry of Food and Drug Safety acknowledged the need for national compensation for a drug-induced liver injury (DILI) after azilsartan use. However, little is known regarding the association between angiotensin receptor blockers and DILI.

Objective: We conducted a retrospective cohort study in incident users of angiotensin receptor blockers from a common data model database (1 January, 2017-31 December, 2021) to compare the risk of DILI among specific angiotensin receptor blockers against valsartan.

Methods: Patients were assigned to treatment groups at cohort entry based on prescribed angiotensin receptor blockers. Drug-induced liver injury was operationally defined using the International DILI Expert Working Group criteria. Cox regression analyses were conducted to derive hazard ratios and the inverse probability of treatment weighting method was applied. All analyses were performed using R.

Results: In total, 229,881 angiotensin receptor blocker users from 20 university hospitals were included. Crude DILI incidence ranged from 15.6 to 82.8 per 1000 person-years in treatment groups, most were cholestatic and of mild severity. Overall, the risk of DILI was significantly lower in olmesartan users than in valsartan users (hazard ratio: 0.73 [95% confidence interval 0.55-0.96]). In monotherapy patients, the risk was significantly higher in azilsartan users than in valsartan users (hazard ratio: 6.55 [95% confidence interval 5.28-8.12]).

Conclusions: We found a significantly higher risk of suspected DILI in patients receiving azilsartan monotherapy compared with valsartan monotherapy. Our findings emphasize the utility of real-world evidence in advancing our understanding of adverse drug reactions in clinical practice.

Introduction: Zopiclone, a controlled substance prescribed for insomnia, has become a common toxicological finding in forensic autopsy cases. This study investigated the role and extent of zopiclone use in fatal intoxications in Sweden.

Methods: All forensic autopsy cases positive for zopiclone in femoral blood during 2012-2020 were selected. Among these cases, fatalities caused by intoxication according to the cause of death certificates issued by the forensic pathologist were identified. Intoxications where zopiclone contributed to the cause of death were included in the study. The Swedish Prescribed Drug Register was utilized to examine whether the included cases were prescribed zopiclone or not.

Results: In total 7320 fatal intoxications underwent a forensic autopsy during the study period, 573 of them were caused by zopiclone. Among the zopiclone fatalities, 87% (n = 494) had a prescription for zopiclone, and 8% (n = 43) were monointoxications. Most fatalities, 62% (n = 354) were suicides, and zopiclone was involved in about 17% (n = 354) of all intoxication suicides in Sweden. Women were significantly (p < 0.01) overrepresented in suicides with zopiclone, comprising 56% (n = 291) of fatalities. The median age was 55 years among zopiclone intoxications compared with 44 years amongst all fatal intoxications.

Conclusion: This study demonstrates that the toxicity of zopiclone can be lethal both in combination with other substances and on its own. Most individuals dying in fatal zopiclone intoxications were prescribed zopiclone, which potentially indicates that a more restrictive prescribing rate could prevent future intoxication deaths, especially when caring for patients with an increased suicide risk.

Statins represent the primary therapy for combatting hypercholesterolemia and reducing mortality from cardiovascular events. Despite their pleiotropic effects in lowering cholesterol synthesis, circulating cholesterol, as well as reducing the risk of other systemic diseases, statins have adverse events in a small, but significant, population of treated patients. The most prominent of these adverse effects is statin-induced myopathy, which lacks precise definition but is characterised by elevations in the muscle enzyme creatine kinase alongside musculoskeletal complaints, including pain, weakness and fatigue. The exact aetiology of statin-induced myopathy remains to be elucidated, although impaired mitochondrial function is thought to be an important underlying cause. This may result from or be the consequence of several factors including statin-induced inhibition of coenzyme Q₁₀ (CoQ₁₀) biosynthesis, impaired Ca²⁺ signalling and modified reactive oxygen species (ROS) generation. The purpose of this review article is to provide an update on the information available linking statin therapy with mitochondrial dysfunction and to outline any mechanistic insights, which may be beneficial in the future treatment of myopathic adverse events.