Expert Opinion on Drug Safety最新文献

Introduction: Placental abruption is a significant cause of fetomaternal mortality/morbidity. Management requires a difficult balance between opposing advantages/disadvantages for the fetus and mother. Remote from term, prompt delivery is best for the mother, but delayed delivery better for the fetus.

Areas covered: Prevalence of fetomaternal morbidity/mortality; range of clinical situations: certainty of diagnosis, gestational age, labor status, fetal condition/viability, presence of maternal shock/consumption coagulopathy, feasibility of prompt delivery. Pathophysiology: maternal hypovolaemia; abruption size; impairment of placental oxygenation; intrauterine tone and pressure; safety, efficacy, and application of tocolytic therapy to abruption; potential role of atosiban with emphasis on safety.

Expert opinion: The fetomaternal morbidity/mortality of placental abruption deserves consideration of further interventions that may improve fetomaternal outcome. More information is now available about signs/symptoms that do not require invasive diagnostic procedures. The contribution of maternal uterine hypertonus/tachysystole and increased uterine tone/pressure that affects fetal hypoxia/acidosis and consumption coagulopathy, strengthens the case for the use of a tocolytic to relax the uterus and improve fetal oxygenation. Due to its safety and efficacy profile, we make the case for atosiban as an agent to reduce uterine contractile frequency, tone, and pressure to improve fetal oxygenation and improve fetomaternal outcome.

Introduction: The United States Food and Drug Administration (FDA) requires post-marketing surveillance of approved drugs, and pharmaceutical manufacturers maintain comprehensive programs that include adverse event monitoring, internal safety assessments, and reporting to the FDA Adverse Events Reporting System (FAERS).

Areas covered: This report provides an overview of FAERS within the broader framework of post-marketing surveillance by pharmaceutical manufacturers. It also identifies several limitations to FAERS public dashboard data for safety analyses. A PubMed search for published findings of FAERS safety analyses with vesicular monoamine transporter 2 (VMAT2) inhibitors provide a case study that illustrates the need for careful interpretation based on the limitations of the FAERS database.

Expert opinion: Using a case study of VMAT2 inhibitors, we identified factors in data quality and manufacturer pharmacovigilance programs that must be considered when interpreting published analyses of FAERS public safety data. The application of artificial intelligence methodologies may prove helpful in identifying novel safety signals more accurately and more rapidly. At the same time, as clinicians consider individual treatment choices with their patients, discussion of safety data from the FAERS public dashboard should be contextualized within each drug's known safety profile.

Introduction: In patients with acute coronary syndromes (ACSs) undergoing percutaneous coronary intervention, 12 months of dual antiplatelet therapy (DAPT) with aspirin plus a P2Y₁₂ inhibitor is the current standard. However, DAPT is associated with an increased risk of bleeding. DAPT duration and intensity should be modulated according to the patient's specific risk profile to optimize outcomes.

Areas covered: Different DAPT regimens varying in intensity and duration have been shown to improve outcomes in specific settings. In patients at increased ischemic risk, DAPT escalation or prolongation can be considered, while de-escalation by discontinuing one of the antiplatelet drugs, reduction in the dose of the P2Y₁₂ inhibitor, or switching to a less potent P2Y₁₂ inhibitor should be considered in patients at increased risk of bleeding. Platelet function and genetic testing may help guiding the decision making. Antiplatelet agents also have specific drug-related adverse effects that clinicians should be aware of.

Expert opinion: Management of ACS patients has largely shifted over time, in order to achieve a patient-oriented approach. Development of specific scores based on genetic and clinical characteristics to predict patient's responsiveness to clopidogrel may allow to further reduce ischemic events, while technological and pharmacological advances are paving the way for further reduction of bleeding risk while preserving efficacy.

Background: Tirzepatide has shown benefits in weight reduction and glycemic control in type 2 diabetes and obesity, but its relative efficacy and safety across doses remain unclear.

Methods: We conducted a PROSPERO-registered systematic review and network meta-analysis of randomized controlled trials up to July 2024. Trials comparing tirzepatide (5, 10, or 15 mg weekly) with placebo, insulin, or GLP-1 receptor agonists in adults with type 2 diabetes and/or obesity were included. Random-effects models estimated mean differences (MDs) or relative risks (RRs), with treatment ranking assessed by SUCRA and evidence certainty rated with CINeMA.

Results: Thirteen RCTs (14,007 participants) were included. Tirzepatide produced dose-dependent weight reductions versus insulin (MD -14.5 kg for 15 mg; -12.5 kg for 10 mg; -10.2 kg for 5 mg; all p < 0.0001). The likelihood of ≥15% weight loss (RR 4.83 for 15 mg), HbA1c reduction (MD -12.6 mmol/mol), and normoglycemia (RR 11.3) was significantly higher with tirzepatide. Safety analyses showed fewer serious adverse events (RR 0.71-0.77) and hypoglycemia (RR 0.44-0.50) than insulin, but more gastrointestinal events.

Conclusions: Tirzepatide provides superior weight loss, glycemic improvements, and favorable safety versus insulin and other comparators, supporting its role as a leading therapy for type 2 diabetes and obesity.

Introduction: The landscape of oral anticoagulant (OAC) treatment dramatically changed with the introduction into clinical practice of the direct oral anticoagulants (DOACs), which have been able to overcome major limitations of vitamin K antagonists.

Areas covered: This review summarizes the pharmacokinetic and pharmacodynamic profiles of commercially available DOACs (apixaban, rivaroxaban, dabigatran, and edoxaban), as well as their efficacy and safety in the settings of atrial fibrillation, venous thromboembolism, prevention of cancer-associated thrombotic events, and atherosclerotic disease. Limitations of commercially available DOACs are also reviewed.

Expert opinion: The introduction into clinical practice of DOACs has significantly changed the landscape of OAC, given their favorable safety and efficacy profiles. However, there are still several unmet needs for patients requiring treatment with OAC, underscoring the need for further research in the field to optimize the safety and efficacy of these agents across different clinical settings.