Expert Opinion on Drug Safety最新文献

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.

Background: Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) have recently been linked to be associated with acute pancreatitis (AP), but the clinical characteristics are unclear. This study investigated the clinical characteristics of SGLT-2i and AP and provided reference for the prevention and treatment of AP.

Research design and methods: Case reports, case series, and clinical studies of SGLT2i induced AP were collected by retrieving Chinese and English data from the database until 31 December 2023.

Results: Twenty-one patients were included, with a median age of 50.5 years (range 26,73). SGLT-2i were mainly involved in empagliflozin (13 cases, 61.9%), canagliflozin (4 cases, 19%) and dapagliflozin (4 cases, 19%). The median time from initial administration to the onset of AP was 21 days (range 1, 120). Abdominal pain (21 cases, 100%) was the most commonly complained symptom. The median lipase value was 388 U/L (range 36, 10000), and the median amylase value was 535 U/L (range 26, 3765). Twenty-one patients recovered completely after stopping the drug and receiving conservative treatment.

Conclusions: SGLT-2i are associated with AP. Given the rising prescription of SGLT-2i, physicians should consider these agents as a potential cause of pancreatitis after excluding other etiologies.

Background: The comprehensive quantitative and comparative risk data of drug-induced erectile dysfunction (ED) are still lacking, and this study aims to supplement this information.

Research design and methods: We reviewed all the ED reports in the FDA Adverse Event Reporting System (FAERS) database from 2004 to 2023 and summarized a potential ED culprit-drug list and its corresponding reporting frequency. The reporting odds ratio (ROR) method was used to conduct disproportionality analysis.

Results: A total of 20,098 ED reports were retrieved from the FAERS database, which recorded 734 different ED culprit-drugs, involving 74 drug classes. Finasteride was the drug with the highest reporting frequency, and urologicals was the drug class with the highest reporting frequency. In disproportionality analysis, 209 drugs with positive signals showed a close relationship with ED occurrence, among which finasteride was the drug with the highest signal strength. Among 209 drugs with positive signals, 27 were compound preparations, and the risk level of compound preparations was usually higher than their single active ingredient.

Conclusions: Our study integrated quantitative and comparative ED risk data of 734 drugs by using the FAERS database, which can provide reference information for regulators, medical personnel, and others involved in drug management and use.

Background: In the United States, clozapine was first approved for treatment-resistant schizophrenia and then for suicidality in schizophrenia psychoses. Systematic reviews support clozapine's anti-suicidal effect, but the forensic literature stresses its lethality during overdoses.

Research design and methods: Clozapine reports to the international pharmacovigilance database (VigiBase) were analyzed for suicidal ideation, suicide attempts, intentional overdose, and completed suicides from introduction to 1 January 2024. VigiBase uses the information component (IC) as a disproportionality analysis.

Results: The clozapine ICs (range: other antipsychotics) were: 1) suicidal ideation IC = 0.570 with IC₀₂₅ = 0.454 to IC₉₇₅ = 0.680 (IC = 3.568 for aripiprazole and 1.729 for risperidone), 2) suicide attempt IC = 1.428 with IC₀₂₅ = 1.323 to IC₉₇₅ = 1.529 (IC = 4.150 for quetiapine and 2.968 for risperidone), 3) intentional overdose: IC = 0.995 with IC₀₂₅ = 0.864 to IC₉₇₅ = 1.120 (IC = 4.080 for quetiapine and 1.957 for aripiprazole), and 4) completed suicide IC = 1.133 with IC₀₂₅ = 1.026 to IC₉₇₅ = 1.235 (IC = 4.648 for quetiapine and 2.160 for risperidone). In summary, all clozapine ICs were significantly lower. We found 2391 clozapine-treated patients on the suicidality spectrum (627 cases with suicidal ideation, 752 with suicide attempt, 488 with intentional overdose, and 731 with completed suicide) but many were taking other antipsychotics. The most frequent reporting countries were the United States, the United Kingdom, and Croatia.

Conclusion: This pharmacovigilance study, with all its inherent limitations, provides independent proof, not overlapping with prior literature, that clozapine may have specific strong anti-suicidal effects that do not appear to be present in other antipsychotics. Further VigiBase studies are needed to compare the lethality of an intentional overdose of clozapine (14.3%) with other antipsychotics.

Background: As synthesis technology advances, novel and efficient derivatives of tetracyclines are found. Three new antibiotics were approved within the past 18 years, and represent a new era in the use of tetracyclines. To gain further insight into adverse events linked to tetracyclines and better protect pediatric patients, ongoing monitoring of safety data is crucial.

Methods: The FAERS data from the first quarter of 2004 to the third quarter of 2023 in the AERSMine were extracted to conduct disproportionality analysis. The association between five tetracyclines and adverse events was evaluated using reporting odds ratio, and their risk factors were explored by multivariate logistic regression analysis.

Results: Our study showed that thyroid gland disorders had the strongest signal in children. Patients aged 12-18 and treatment with minocycline are risk factors for thyroid adverse events (12-18: OR = 10.727 [7.113-16.177], p < 0.0001; minocycline: OR = 17.025 [10.475-27.678], p < 0.0001). Second-generation tetracycline and third-generation tetracycline ADR patterns differed. Blood fibrinogen decreased and hypofibrinogenaemia was primarily reported with tigecycline and eravacycline.

Conclusion: This study provided basic evidence for further research on tetracyclines-related adverse events. However, the safety of third-generation tetracycline in children requires additional validation through a large-scale prospective study.