Aims
Adverse drug reactions (ADRs) are important causes of death. However, the main involved drugs are relatively unknown. The present study was performed to characterise death‐related drugs recorded ...in a large pharmacovigilance database during the last 10 years.
Methods
A retrospective analysis of VigiBase, the World Health Organization pharmacovigilance database, was performed investigating fatal ADRs registered between 1 January 2010 and 31 December 2019 in male and female patients aged ≥18 years and reported by physicians. Analyses were descriptive investigating age, sex and suspected drugs. Differences in reporting according to sex, age and continents were investigated using disproportionality analysis with calculation of reporting odds ratio and its 95% confidence interval.
Results
Among the 23 millions ADRs recorded in VigiBase, 3 250 967 were included with 43 685 fatal. They were reported mainly in patients older than 75 years. The 3 most frequently involved drug classes were antineoplastic/immunomodulating drugs followed by nervous system and cardiac drugs. The top 3 individual drugs were denosumab, lenalidomide and thalidomide with marked differences according to age, sex, continents and countries. The risk of reporting fatal ADRs was higher in males, in the Americas and in patients ≥65 years.
Conclusion
Fatal ADRs registered in a large pharmacovigilance database during the last 10 years correspond to just over 1% of the total number of ADRs. They occurred more in males, after 65 years and with antineoplastic/immunomodulating drugs in general. Our study also highlighted, for the first time, important differences in fatal ADRs between continents and countries.
Rhabdomyolysis is a serious adverse drug reaction of statins. There are few studies comparing the risk of rhabdomyolysis between the different statins. Using the WHO pharmacovigilance database, ...VigiBase®, we compared the risk of rhabdomyolysis reporting of seven statins (atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin and simvastatin, with cerivastatin excluded). All reports of rhabdomyolysis in VigiBase® in adults with statins until 31 December 2022 were included. Results are expressed as reporting odds ratio (ROR, 95% CI). Among 10 657 reports with rhabdomyolysis with statins, simvastatin was the highest risk statin in comparison with others: ROR = 2.20 (2.11–2.29). The risk was higher in men, older than 74 years and in cases of drug interactions.
Thirst is a complex physiological compensatory mechanism but could also be associated with drugs. This association was poorly investigated previously. Using the WHO global pharmacovigilance database, ...Vigibase®, disproportionality analyses potential associations between exposure to drugs and thirst reports were performed. All reports of thirst in adults between 01/01/2000 and 31/12/2023 were included. Results are expressed as reporting odds ratio (ROR). Analysis of the 3186 reports of thirst (978 ‘serious’) allowed, first, to confirm the association between thirst and exposure to vasopressin antagonists (tolvaptan), lithium, gliflozins (dapagliflozin, empagliflozin), pregabalin and antimuscarinic drugs (glycopyronium, oxybutynin, tiotropium). Second, new safety signals were described with monoamine reuptake inhibitors (antidepressants: duloxetine, venlafaxine; anti‐obesity agent: sibutramine), antipsychotic (olanzapine), glucocorticoid (prednisolone), diuretic (furosemide) drugs as well with ribavirin or sodium oxybate. This study is the first to offer a list of drugs associated with thirst in humans.
Bruxism is a movement disorder of uncertain aetiology. Beside local peripheral and central psychological factors, drugs were suspected. Using the World Health Organization (WHO) global ...pharmacovigilance database, Vigibase®, we investigated through disproportionality analyses potential associations between exposure to drugs and bruxism reports. All reports of bruxism in adults between 01/01/2000 and 31/12/2022 were included. Results are expressed as reporting odds ratio (ROR). Among the 564 reports of bruxism, an association was found with eight antidepressants (first sertraline followed by escitalopram, venlafaxine, vortioxetine, citalopram, paroxetine, fluoxetine, duloxetine) and four antipsychotics (first ziprasidone followed by aripiprazole, olanzapine, risperidone). A signal was also described for oxybate sodium and metoclopramide. For antidepressants, a negative association was found between ROR values and NET (norepinephrine transporter) but not SERT (serotonin transporter) pKi values, suggesting this ADR is more closely linked to norepinephrine than serotonin reuptake inhibition.
Aims
Adverse drug reactions (ADRs) represent a significant public health burden. There are few data on fatal ADRs in children. This population is particularly at risk due to metabolic and ...physiological immaturity, frequent off‐label drug use and limited paediatric clinical pharmacology studies. The study investigated the main characteristics of drug‐related deaths registered in World Health Organization pharmacovigilance database, during the past decade.
Methods
Fatal outcomes registered between 2010 and 2019 in children (<18 y) and reported by physicians were investigated. Age, sex and suspected drugs were described and disproportionality analyses investigated differences according to sex, age and continents with calculation of reporting odds ratio and its 95% confidence interval.
Results
Among the 1 198 560 reports registered in children, 1585 (0.13%) were fatal. They occurred mainly in boys, aged 28 days–23 months. Reports mostly came from the Americas and Europe and involved, besides anti‐infectious drugs (mainly vaccines), central nervous system (vigabatrin, paracetamol, methylphenidate…) and antineoplastic/immunomodulating (mainly thalidomide) and cardiovascular (mainly bosentan) drugs without major differences between boys and girls. Large differences were found according to continents and age. The risk of reporting was higher in boys, in children aged <23 months, in the Americas and Africa.
Conclusion
Fatal ADRs represented a small part (around 1/1000) of total registered ADRs, occurred more frequently in boys and during the first 2 years of life. Beside anti‐infectious drugs (vaccines), neuropsychiatric drugs were the most frequently involved, with large differences according to continents and classes of age.
Background
Current guidelines recommend the treatment of hormone receptor–positive breast cancer with aromatase inhibitors (AIs) and tamoxifen in the adjuvant setting. Some observational studies have ...raised concerns that tamoxifen may be associated with an increased risk of Parkinson disease (PD). However, no studies have directly compared the risk of PD between AIs and tamoxifen in women diagnosed with breast cancer.
Methods
Using the UK Clinical Practice Research Datalink, the authors assembled a cohort of women newly diagnosed with breast cancer and newly treated with either AIs or tamoxifen between January 1, 1995, and December 31, 2017. Patients were followed 1 year after treatment initiation (ie, a 1‐year lag) until an incident diagnosis of PD or were censored at death from any cause, the date of transfer out of the practice, or the end of the study period (December 31, 2018). Cox proportional hazards models with inverse probability of treatment weights were used to estimate weighted hazard ratios (HRs) and 95% confidence intervals (CIs) for PD comparing AIs with tamoxifen and accounting for more than 30 confounders.
Results
In all, 30,140 women with nonmetastatic breast cancer were identified: 13,838 initiated AIs, and 16,302 initiated tamoxifen. Compared with tamoxifen, AIs were not associated with an increased risk of PD (HR, 0.94; 95% CI, 0.60‐1.47). Consistent results were observed across all secondary and sensitivity analyses.
Conclusions
In this large observational study, the use of AIs, in comparison with tamoxifen, was not associated with an increased risk of PD in women diagnosed with nonmetastatic breast cancer in a real‐world setting.
Lay Summary
Previous studies have indicated that tamoxifen may increase the risk of Parkinson disease in the treatment of breast cancer.
However, no studies have directly compared the risk of Parkinson disease between aromatase inhibitors and tamoxifen.
This study included 30,140 women diagnosed with breast cancer and treated with aromatase inhibitors or tamoxifen.
Overall, compared with tamoxifen, aromatase inhibitors were not associated with an increased risk of Parkinson disease in women diagnosed with breast cancer.
This study provides an important addition to the comparative safety profile of aromatase inhibitors and tamoxifen in the treatment of breast cancer.
In this study, which included 30,140 women with breast cancer, aromatase inhibitors were not associated with an increased risk of Parkinson disease in comparison with tamoxifen. This study provides an important addition to the comparative safety profile of aromatase inhibitors and tamoxifen in the treatment of breast cancer.
Several vaccines are being developed as part of the COVID‐19 pandemic. The results of clinical trials for these vaccines were published with efficacy values of more than 90%, using mainly relative ...risk (RR). In this paper, we decided to reanalyse the data using the different validated methods of risk expression. Using main publications, absolute risks (AR), AR reduction (ARR), number needed to treat (NNT) were calculated for five COVID‐19 vaccines (tozinameran Comirnaty®, Moderna, Vaxzevria®, Janssen, and Sputnik V vaccines). AR, ARR, NNT, and RR values varied according to COVID‐19 vaccines. The order of the different vaccines was not the same according to the chosen efficacy parameters. This is a further example of the need to express results of clinical trials, using not only RR, but also AR, ARR, and NNT in order to clearly present the clinical interest of drugs.
A fifth vaccine against Covid‐19, NVX‐CoV2373 Nuvavoxid® (Novavax), a protein‐based adjuvanted vaccine, was recently marketed in Europe. The main clinical trial before marketing concluded to a ...‘vaccine efficacy’ of 89.7% without talking about other validated efficacy parameters. We further analysed the data of this clinical trial using the different validated methods of risk expression: absolute risks (AR), AR reduction (ARR) and number needed to treat (NNT). ARR and NNT values were 1.22% and 82, respectively, for an RR value of 0.10. Description of these parameters allowed defining some interesting characteristics of NVX‐CoV2373 efficacy according to age, race, variant and coexisting illness. Finally, we ask that the results of clinical trials be systematically presented, using not only RR but also including AR, ARR and NNT.
The epidemiology of immune thrombocytopenia (ITP) is not well known. The purpose of this study was to assess ITP incidence at a nationwide level (France) with recent data (mid-2009 to mid-2011; 129 ...248 543 person-years). The data source is the French health insurance database. We selected cases with diagnosis codes for in-hospital stays and long-term disease attributions, thus restricting our search to ITPs necessitating health care. We studied incidence by age, gender, calendar month, regions, and proportion of secondary ITPs, of ITPs becoming persistent or chronic, and of severe bleeding at disease onset. We identified 3771 incident ITP patients. Incidence was 2.9/100 000 person-years, with peaks among children and in those >60 years of age. ITP was more frequent among males in these subgroups. The incidence was lower in overseas Caribbean French departments, suggesting a lower incidence among Afro-American people. There was a north-south gradient in mainland France and seasonal variations (peak in winter and nadir in summer). Persistence or chronicity occurred in 36% of children compared with 67% of adults. Among adults, 18% of ITPs were secondary. Malignancy was the main cause (10.9%). Myelodysplastic syndromes were not rare (2.3%). Severe gastrointestinal or central nervous system bleeding at ITP onset was rare (<1%).
•Incidence of ITP was 2.9/100 000 person-years with age, seasonal, and regional variations; in adults, 18% were secondary.•Severe (gastrointestinal or central nervous system) bleeding at ITP onset was rare (<1%); the risk increased with age.
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