PURPOSE: The purpose of this narrative review is to provide a comparison of several countries with different legislation and approaches to pharmacovigilance and to point out how these impact the number of adverse drug reactions (ADRs) that are reported to national competent authorities. METHODS: Legislative and statistical data regarding ADR reporting from various national competent authorities' websites, databases, and pharmacovigilance centers were used. In combination with the WHO pharmacovigilance quantitative indicator that was applied to evaluate the effectiveness of particular national pharmacovigilance systems in our scope. RESULTS: The study compared pharmacovigilance systems in six countries, focusing on ADR reporting from 2010 onwards. All countries required MAHs to report ADRs, while healthcare professionals' obligations varied. Per-capita ADR reports increased in all countries with available data, with the United States having a significantly higher reporting rate, possibly due to FDA campaigns. Despite starting later, China's per-capita reporting rate surpassed that of the Czech Republic and Japan. The study highlighted various measures taken by countries to enhance ADR reporting systems since the inception of their programs, contributing to the overall increase in reporting rates. CONCLUSIONS: ADR reporting is a global priority, with efforts made by different countries to strengthen their pharmacovigilance systems. Some success can be seen in gradually improving per-capita ADR reporting rates. The varying reporting rates and measures taken by each country may serve as a basis for further research and exchange of best practices to improve drug safety monitoring worldwide.
PURPOSE: Data on the anti-Xa efficacy of fondaparinux in dialysis-dependent chronic kidney disease (DD-CKD) patients are scarce. This study characterizes the pharmacokinetics (PK) and pharmacodynamics (PD) of fondaparinux in DD-CKD patients undergoing renal replacement therapy (RRT), to assess dosing strategies. METHODS: A retrospective, observational study was conducted using data on anti-Xa activity (112 samples) from 12 (3 male and 9 female) DD-CKD patients (median (IQR) age 71 years (63-88), weight 73 kg (59-98.5)). Eleven patients underwent high-flux or low-flux hemodialysis (HD) and one patient underwent peritoneal dialysis. Three patients were also treated with therapeutic plasma exchange (TPE). A non-linear mixed effects analysis was performed using NONMEM 7.3.0. RESULTS: The lab-specific slope of the relationship between fondaparinux concentration and anti-Xa levels was 1.18 IU/μg. In a one-compartment model, clearance (CL) and volume of distribution (Vd) were 0.05289 L/h and 5.55 L, respectively. High-flux HD was found to increase the CL of fondaparinux 2.26 times. TPE also considerably increased CL, but the fold-change could not be accurately estimated. Low-flux HD and peritoneal dialysis did not impact PK parameters. CONCLUSIONS: Model-based simulations showed that standard dosing (2.5 mg three times weekly before HD) results in a median anti-Xa activity of 0.55 IU/mL and 0.98 IU/mL, pre- and post-low-flux HD, respectively. In patients undergoing high-flux HD, these values are approximately 27% lower. Additional caution is warranted with TPE, as this treatment can reduce anti-Xa activity even further.
- MeSH
- chronická renální insuficience metabolismus terapie MeSH
- fondaparinux farmakokinetika farmakologie MeSH
- inhibitory faktoru Xa farmakokinetika farmakologie MeSH
- lidé středního věku MeSH
- lidé MeSH
- náhrada funkce ledvin * MeSH
- retrospektivní studie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- tělesná hmotnost MeSH
- věkové faktory MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
- MeSH
- hepatocelulární karcinom * epidemiologie MeSH
- inhibitory zpětného vychytávání serotoninu a noradrenalinu * MeSH
- kohortové studie MeSH
- lidé MeSH
- nádory jater * chemicky indukované epidemiologie MeSH
- selektivní inhibitory zpětného vychytávání serotoninu škodlivé účinky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- dopisy MeSH
- komentáře MeSH
- systematický přehled MeSH
PURPOSE: Recent studies have suggested a lower risk of hepatocellular carcinoma (HCC) in patients receiving selective serotonin reuptake inhibitors (SSRIs). The current study aimed to provide an updated and comprehensive assessment of the association between SSRI use and development of HCC. METHODS: This is a systematic review and meta-analysis of all observational studies published until June 2021. We comprehensively searched PubMed/Medline, Web of Science, and Embase to identify studies comparing SSRIs use with control in relation to the risk of HCC. We calculated pooled relative risks (RRs) and 95% confidence intervals (CIs) for the association between SSRI use and incident HCC risk using random-effects meta-analysis. A dose-response analysis was conducted to evaluate the HCC risk according to the defined daily dose (DDD) of SSRI use. RESULTS: Eight observational studies, comprising 1,051,096 participants and 22,316 incidences of HCC, examining the association between SSRIs use and HCC risk, were included in the systematic review (adjusted RR: 0.66; 95% CI: 0.56-0.79; P ≤ 0.001). In subgroup analysis, the magnitude of benefit associated with SSRIs was significantly higher in patients with hepatitis infection (RR: 0.70, 95% CI: 0.51-0.95) than the general population (Pheterogeneity = 0.700). The dose-response analysis indicated strong inverse association between cumulative DDD of SSRI and risk of HCC (coefficient: - 0.0030; P = 0.002; R2 = 0.78). CONCLUSIONS: The results of this review show that SSRI use was associated with a 34% lower risk of HCC, which tend to be dose dependent. Further prospective studies are warranted to confirm these observations across the spectrum of chronic liver disease and hepatitis infection.
- MeSH
- hepatocelulární karcinom * epidemiologie MeSH
- kohortové studie MeSH
- lidé MeSH
- nádory jater * chemicky indukované epidemiologie MeSH
- pozorovací studie jako téma MeSH
- riziko MeSH
- selektivní inhibitory zpětného vychytávání serotoninu škodlivé účinky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- přehledy MeSH
- systematický přehled MeSH
PURPOSE: The aim of this study was to explore patterns and long-term development in prescribing potentially inappropriate medication (PIM) according to the EU(7)-PIM list to elderly patients in Germany. METHODS: We analysed anonymized German claims data. The study population comprised 6.0 million insured individuals at least 65 years old, including all their prescriptions reimbursed in 2019. For the analysis of long-term development, we used data for the years 2009-2019. Factors associated with PIM prescribing were considered from two perspectives: patient-oriented analysis was performed with logistic regression and prescriber-oriented analysis was performed with multiple linear regression. RESULTS: EU(7)-PIM prevalence was reduced from 56.9% in 2009 to 45.1% in 2019. Average annual volume (DDDs/insured) decreased from 145 in 2009 to 121 in 2019. These figures are substantially greater than those for the older PRISCUS list. The majority of investigated ATC level 2 groups with the highest EU(7)-PIM DDD volume exhibited substantial decreases; moderate increases were found for antihypertensive and urological drugs. Antithrombotics increased strongly with the introduction of direct oral anticoagulants. The most prevalent EU(7)-PIM medication was diclofenac; however, in the age group 85+ years, apixaban was twice as prevalent as diclofenac. Polypharmacy, female sex, age < 90 years, need for nursing care and living in Eastern regions were identified as risk factors. Prescriber specialty was the most marked factor in the prescriber-oriented analysis. CONCLUSION: Although the use of EU(7)-PIMs has been declining, regional differences indicate considerable room for improvement. The comparison with PRISCUS highlights the necessity of regular updates of PIM lists.
- MeSH
- charakteristiky bydlení MeSH
- lidé MeSH
- pojistná škoda - přezkoumání statistika a číselné údaje MeSH
- polypharmacy MeSH
- průřezové studie MeSH
- retrospektivní studie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- sexuální faktory MeSH
- seznam potenciálně nevhodných léčiv statistika a číselné údaje trendy MeSH
- věkové faktory MeSH
- Check Tag
- lidé MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
- Geografické názvy
- Německo MeSH
PURPOSE: This review focuses on the most common drugs administered to surgical patients during the perioperative period that affect the risk of venous thromboembolism (VTE). RESULTS: Among analgesics, the risk of VTE is increased in patients treated with diclofenac, ibuprofen, and rofecoxib, but not naproxen, while metamizole can confer a protective effect. The relationship between sedatives and VTE has not been sufficiently studied. Tricyclic antidepressants, low-potency serotonin reuptake inhibitors, and antipsychotics have been associated with increased risk of VTE. The use of diuretics in the perioperative period is poorly researched; however, hyponatremia is considered a risk factor. Other factors that may influence the risk of VTE include bridging anticoagulation, allogeneic transfusion, and hemostatic management before surgery. Pharmacotherapy for HIV or cancer may also increase VTE risk. CONCLUSION: Increased monitoring for VTE is therefore advisable in surgical patients and those receiving antipsychotics, antidepressants, diuretics, or analgesics.
- MeSH
- analgetika terapeutické užití MeSH
- antidepresiva terapeutické užití MeSH
- antipsychotika terapeutické užití MeSH
- diuretika terapeutické užití MeSH
- hormonální substituční terapie MeSH
- hypnotika a sedativa terapeutické užití MeSH
- kontraceptiva orální hormonální terapeutické užití MeSH
- lidé MeSH
- perioperační péče * MeSH
- rizikové faktory MeSH
- žilní tromboembolie chemicky indukované MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
INTRODUCTION: The importance of rational drug therapy is increasing with the aging of the population. Since one of the main reasons for inappropriate drug prescribing is also the "age-blind" approach, which results in ageist practices, this narrative literature review focuses on the description of the main barriers related to insufficient individualization of drug regimens associated with such age-blind approaches. METHODOLOGY: A narrative literature review using the PubMed, WoS, Embase, and Scopus databases was conducted by the EU COST Action IS1402. Experts in different scientific fields from six countries (the Czech Republic, Spain, Portugal, Hungary, Serbia, and Turkey) worked in four specific areas: (1) underrepresentation of older adults in clinical trials and clinical and ethical consequences; (2) insufficient consideration of age-related changes and geriatric frailty in the evaluation of the therapeutic value of drugs; (3) frequent prescribing of potentially inappropriate medications (PIMs); and (4) frequent underuse of highly beneficial nonpharmacological strategies (e.g., exercise). RESULTS: Older patients are underrepresented in clinical trials. Therefore, rigorous observational geriatric research is needed in order to obtain evidence on the real efficacy and safety of frequently used drugs, and e.g. developed geriatric scales and frailty indexes for claims databases should help to stimulate such research. The use of PIMs, unfortunately, is still highly prevalent in Europe: 22.6% in community-dwelling older patients and 49.0% in institutionalized older adults. Specific tests to detect the majority of age-related pharmacological changes are usually not available in everyday clinical practice, which limits the estimation of drug risks and possibilities to individualize drug therapy in geriatric patients before drug prescription. Moreover, the role of some nonpharmacological strategies is highly underestimated in older adults in contrast to frequent use of polypharmacy. Among nonpharmacological strategies, particularly physical exercise was highly effective in reducing functional decline, frailty, and the risk of falls in the majority of clinical studies. CONCLUSION: Several regulatory and clinical barriers contribute to insufficient knowledge on the therapeutic value of drugs in older patients, age-blind approach, and inappropriate prescribing. New clinical and observational research is needed, including data on comprehensive geriatric assessment and frailty, to document the real efficacy and safety of frequently used medications.
- MeSH
- geriatrické hodnocení MeSH
- lékové předpisy normy statistika a číselné údaje MeSH
- lidé MeSH
- nevhodné předepisování statistika a číselné údaje MeSH
- polypharmacy * MeSH
- prevalence MeSH
- randomizované kontrolované studie jako téma statistika a číselné údaje MeSH
- rizikové faktory MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- seznam potenciálně nevhodných léčiv statistika a číselné údaje MeSH
- věkové faktory MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Geografické názvy
- Evropa MeSH
- Turecko MeSH
- MeSH
- antikonvulziva aplikace a dávkování škodlivé účinky MeSH
- hyperamonemie chemicky indukované MeSH
- kyselina valproová aplikace a dávkování škodlivé účinky MeSH
- lidé MeSH
- nemoci mozku chemicky indukované MeSH
- novorozenec MeSH
- záchvaty farmakoterapie MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- Publikační typ
- dopisy MeSH
- kazuistiky MeSH
- přehledy MeSH
PURPOSE: The aim of this prospective study was to compare in non-Asian subjects the pharmacokinetics (PK), pharmacodynamics (PD), safety, and tolerability of two short-acting cardioselective β1-adrenergic antagonists, landiolol and esmolol, after administration of three different bolus dosages. MATERIALS AND METHODS: We conducted a single-center, prospective, double-blinded, randomized study in three cross-over periods with 12 healthy subjects (7 women and 5 men, mean age of 24.5 ± 6.9 years) each receiving three doses of landiolol (0.1, 0.2, and 0.3 mg/kg BW) either in a newly developed concentrate i.v. formulation (Rapibloc® 20 mg/2 mL concentrate) or a lyophilized formulation, or three doses of esmolol (0.5, 1, and 1.5 mg/kg BW) in an i.v. formulation (Brevibloc® 100 mg/10 mL). PK and PD parameters, safety, and tolerability were assessed. FINDINGS: Results of the two landiolol formulations were reported previously and were similar. For the landiolol concentrate formulation and esmolol, maximum blood concentrations were rapidly reached (mean t max ranged between 1.8 and 3.0 min for landiolol and 1.8 to 2.4 min for esmolol). The parent drugs disappeared very fast from the blood stream, with a t 1/2 of 3.2 ± 1.2 (SD) minutes and 3.7 ± 2.1 (SD) minutes for the low doses of landiolol and esmolol, respectively. Despite comparable injection rates (0.1 or 0.5 mg/kg/15 s for landiolol and esmolol, respectively), the onset of significant heart rate reduction occurred earlier in response to landiolol (1 min) than in response to esmolol (2 min). In addition, significantly lower heart rate values were obtained at every dose level of landiolol, in comparison to esmolol (p < 0.05). Both compounds reduced the systolic blood pressure to a comparable degree. Especially at the highest dose, the duration of blood pressure reduction was longer under esmolol compared to landiolol. Seven mild to moderate adverse events occurred after administration of landiolol, and five occurred after administration of esmolol. No serious adverse events were reported in this study. IMPLICATIONS: Heart rate reduction induced by a new liquid formulation of landiolol occurred faster, was more pronounced, and lasted longer than the effects of corresponding standard esmolol doses. Both agents reduced systolic blood pressure to a comparable degree, but the blood pressure decrease lasted longer after esmolol infusion. The local tolerance and safety profiles of the two formulations were similar. In summary, compared to esmolol, landiolol shows a more prominent and pronounced bradycardic effect in relation to its blood pressure-lowering effect, an action profile that might be of specific advantage in the perioperative setting. TRIAL REGISTRATION: NCT01652898 and 2012-002127-14. https://clinicaltrials.gov/ct2/show/NCT01652898?term=landiolol&rank=7.
- MeSH
- běloši * MeSH
- beta blokátory aplikace a dávkování farmakokinetika farmakologie MeSH
- dospělí MeSH
- dvojitá slepá metoda MeSH
- lidé MeSH
- mladý dospělý MeSH
- močovina aplikace a dávkování analogy a deriváty farmakokinetika farmakologie MeSH
- morfoliny aplikace a dávkování farmakokinetika farmakologie MeSH
- propanolaminy aplikace a dávkování farmakokinetika farmakologie MeSH
- prospektivní studie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
- srovnávací studie MeSH
