Acta Endocrinol (Buchar). 2024 Apr-Jun;20(2):249-255. doi: 10.4183/aeb.2024.249. Epub 2025 Jan 18.

ABSTRACT

INTRODUCTION: Diabetes mellitus, a chronic metabolic disorder stemming from pancreatic dysfunction, is surging in India, notably among those aged 60 and above. The escalating disease prevalence in this demographic necessitates heightened medication use, escalating the risk of Adverse Drug Reactions (ADRs). This underscores the vital role of ADR monitoring to curtail potential harm.

METHOD: A 12-month cross-sectional, prospective, observational study engaged 200 participants from the geriatric Outpatient Department (OPD). Diabetic patients in the geriatric OPD, willing to participate, underwent face-to-face evaluations using a structured questionnaire focused on adverse reactions to anti-diabetic medications. The study also included a Knowledge, Attitude, and Practice (KAP) assessment.

RESULTS: Of the 200 patients, 57% were male, 43% female. Thirteen participants (7 male, 6 female) reported ADR encounters during therapy, predominantly categorized as mild in causality and severity. KAP assessments unveiled a robust understanding of ADRs, primarily shaped by physicians and reinforced by pharmacists. Anticipation of ADR occurrence was noted in 70% of respondents, linked to non-compliance and lifestyle factors.

CONCLUSION: Educating caregivers about the critical importance of monitoring medication adherence among the elderly is imperative. Cultivating an attitude of reporting even minor ADRs to appropriate authorities is essential for harm prevention.

PMID:39845748 | PMC:PMC11750232 | DOI:10.4183/aeb.2024.249

Clin Transl Sci. 2025 Jan;18(1):e70134. doi: 10.1111/cts.70134.

ABSTRACT

The Timor-Leste Pharmacovigilance (PV) became an associate member of the WHO Programme for International Drug Monitoring in 2019; however, the adverse drug reaction (ADR) reporting rate remains low, with only nine reports per 1342 million inhabitants over 5 years. This study aimed to evaluate the knowledge, attitude, practice, and barriers related to ADRs, pharmacovigilance, and ADR reporting among healthcare professionals (HCPs) in Timor-Leste. A cross-sectional survey with a validated, self-administered questionnaire was conducted among 600 HCPs, including clinical doctors, nurses, and pharmacy employees from one national referral and five referral hospitals. Of the 461 HCPs who responded (76.8% response rate), 98 were clinical doctors (21.3%), 311 nurses (67.4%), and 52 pharmacy employees (11.3%). The knowledge score on ADRs was 3.81 ± 0.36 out of 8, with clinical doctors, nurses, and pharmacy employees scoring 4.49 ± 0.51, 3.47 ± 0.24, and 4.56 ± 0.26, respectively. On pharmacovigilance and ADR reporting, the score was 3.00 ± 0.16 out of 8, with clinical doctors, nurses, and pharmacy employees scoring 3.36 ± 0.26, 2.81 ± 0.08, and 3.50 ± 0.24, respectively. All scores referred to the number of correctly answered questions. Positive attitudes were observed, with 53.4% agreeing that ADR reporting is crucial for drug safety, although only 22.0% reported observed ADRs. Key barriers included unavailability of reporting forms (81.0%), insufficient financial support (71.9%), and lack of reporting by colleagues (71.4%). These findings highlight the need for increased awareness, training, and resources to improve ADR reporting in Timor-Leste.

PMID:39844473 | DOI:10.1111/cts.70134

BMC Immunol. 2025 Jan 23;26(1):4. doi: 10.1186/s12865-025-00682-y.

ABSTRACT

Vanishing bile duct syndrome (VBDS) is a serious drug induced liver injury characterized by chronic cholestasis and loss of intrahepatic bile ducts. VBDS has been reported also following checkpoint inhibitor treatment. We compared CD3 + , CD4 + , CD8 + , CD20 + , CD57 + , PD-1 + and PD-L1 + lymphocyte infiltrates in liver biopsies of patients that encountered VBDS (n = 2) or hepatotoxicity (n = 3) after pembrolizumab (n = 4) or nivolumab (n = 1) treatment with samples from normal liver (n = 10), non-alcohol steatohepatitis (NASH, n = 10), primary biliary cholangitis (PBC, n = 10) or pembrolizumab-treated patients without adverse events (n = 2). Notably, none of the cancer patients had primary nor metastatic liver tumors. We also studied direct growth effects of pembrolizumab on primary human intrahepatic biliary epithelial cells (HIBEpiC) in vitro. Liver sections of all checkpoint inhibitor- treated patients exhibited significantly higher CD3 + infiltration than normal livers, and significantly higher PD-L1 + , CD4 + and CD8 + infiltration, than other groups. PD-1 + infiltration was significantly increased in livers of patients with severe hepatic adverse event. CD57 + infiltration was similar in normal livers, NASH- and PBC groups, but highly increased in the checkpoint inhibitor-treated patients. Immune cell infiltrates were similar between NASH and normal livers. PBC samples had significantly higher CD3 + , CD4 + , CD8 + and CD20 + infiltrates than normal livers. HIBEpiC express PD-L1 but pembrolizumab did not affect their viability in vitro. Our findings suggest that VBDS is not due to direct cytotoxicity of checkpoint inhibitors and that the immunological attack against livers induced by these drugs is different from other cholestatic liver conditions.Biological insight: Checkpoint inhibitors upregulate PD-1 and PD-L1, as well as cytotoxic CD57 + cells in the non-cancerous liver tissues and this may be associated with checkpoint inhibitor-induced hepatotoxicity.

PMID:39844069 | DOI:10.1186/s12865-025-00682-y

Pharmacoepidemiol Drug Saf. 2025 Feb;34(2):e70104. doi: 10.1002/pds.70104.

ABSTRACT

PURPOSE: The p.G12C mutation in KRAS is commonly found in many cancers and was previously untreatable until drugs like sotorasib were developed. However, up to 15% of patients treated with sotorasib have experienced hepatobiliary adverse events. To investigate whether these side effects are more common among sotorasib users, a pharmacovigilance study is necessary.

METHODS: This study used the FDA adverse event reporting system (FAERS) database, a publicly available repository of reported drug adverse events, and AERSMine, an open-access pharmacovigilance tool, to investigate these adverse events.

RESULTS: A total of 428 hepatobiliary adverse events were linked to sotorasib. Hepatic cytolysis had the highest reported relative risk at 26.541 and a safety signal of 4.726. Elevated liver and biliary enzymes such as AST, ALT, ALP, and GGT were commonly observed, but with lower reported relative risk and safety signal values, which supports previous real-world reports.

CONCLUSIONS: These findings highlight the hepatobiliary risks associated with sotorasib and underscore the importance of closely monitoring liver function in patients who are using the medication. This is particularly crucial for patients with hepatobiliary cancers, as disease progression and adverse events could be misinterpreted.

PMID:39842846 | DOI:10.1002/pds.70104

Am J Med. 2025 Jan 20:S0002-9343(25)00042-7. doi: 10.1016/j.amjmed.2025.01.011. Online ahead of print.

ABSTRACT

BACKGROUND: Amiodarone is a widely used antiarrhythmic agent with significant toxicities and drug interactions more likely to affect older adults. Nevertheless, data regarding amiodarone safety in this population are limited.

METHODS: We conducted a retrospective analysis of FDA Adverse Event Reporting System (FAERS) data from 2003 to 2024 . Reports with amiodarone as the primary suspect were compared to other antiarrhythmics (sotalol, dronedarone, flecainide, propafenone, dofetilide). Disproportionality analysis assessed reporting odds ratios (RORs) for predefined adverse events in adults (<75 years) and older adults (≥75 years). Interaction analysis evaluated differences between age groups.

RESULTS: Among 9,196 amiodarone FAERS reports, 4,129 (44.9%) involved older adults. Hyperthyroidism (ROR 39.1, 95% CI [25-61] and ROR of 23.4 [11-49.8]) and hypothyroidism (ROR 36.9 [15.2-89.8] and ROR 24.5 [11.5-52.1]) were substantially over-reported in amiodarone users among both adults and older adults, respectively. Drug-induced liver injury and peripheral neuropathy were also over-reported without a significant age interaction. Interstitial lung disease was reported more frequently in amiodarone users overall, with significantly higher reporting in older adults (ROR 11.4 [6.9-18.6] vs. 4.9 [3.4-7.0], Pinteraction=0.007). Bradycardia was also over-reported in older adults compared to adults (ROR 1.6 [1.3-2] vs. 1.0 [0.8-1.3], Pinteraction=0.003). Torsades de Pointes/QT prolongation were less frequently reported in both age groups.

CONCLUSIONS: In this global postmarketing study, interstitial lung disease and bradycardia were more frequently reported in older adults treated with amiodarone. These findings support vigilant monitoring for these adverse events, particularly in older patients.

PMID:39842538 | DOI:10.1016/j.amjmed.2025.01.011

J Bone Joint Surg Am. 2025 Jan 22. doi: 10.2106/JBJS.24.00261. Online ahead of print.

ABSTRACT

BACKGROUND: Limb-salvage surgery for malignant bone tumors can be associated with considerable perioperative blood loss. The aim of this randomized controlled trial was to assess the safety and efficacy of the intraoperative infusion of tranexamic acid (TXA) in children and adolescents undergoing limb-salvage surgery.

METHODS: All participants were <18 years of age at the time of surgery and diagnosed with a malignant bone tumor of the femur that was treated with resection and reconstruction with a megaprosthesis. Exclusion criteria included anatomic locations other than the femur, reconstruction with a vascularized fibular graft, and a previous history of deep venous thrombosis, coagulopathy, or renal dysfunction. Participants were randomly allocated to either the TXA group (a preoperative loading dose infusion of 10 mg/kg of TXA followed by a continuous infusion of 5 mg/kg/hr until the end of surgery) or the placebo group (the same dosage but with TXA substituted with an infusion of normal saline solution). Intraoperative and perioperative blood loss were calculated with use of the hemoglobin balance method. Perioperative blood loss at postoperative day 1 and at discharge from the hospital were calculated. The total volumes of blood transfused intraoperatively and postoperatively were recorded. A statistical comparison between the groups was performed for blood loss and blood transfusion as well as for possible independent variables other than TXA, including age, body mass index, histopathologic diagnosis, tumor volume, preoperative hemoglobin level, type of resection, and the duration of surgery.

RESULTS: A total of 48 participants, with a mean age of 12.5 ± 3.44 years (range, 5 to 18 years) and a male-to-female ratio of 1.18, were included. All participants were Egyptians by race and ethnicity. There were no minor or major drug-related adverse events. There was no significant difference between the groups with respect to intraoperative blood loss (p = 0.0616) or transfusion requirements (p = 0.812), but there was a significant difference in perioperative blood loss at postoperative day 1 (p = 0.0144) and at discharge from the hospital (p = 0.0106) and in perioperative blood transfusion (p = 0.023).

CONCLUSIONS: TXA can be safely infused intraoperatively in children and adolescents undergoing limb-salvage surgery, and it contributes significantly to the reduction of perioperative blood loss and transfusion requirements.

LEVEL OF EVIDENCE: Therapeutic Level I. See Instructions for Authors for a complete description of levels of evidence.

PMID:39841811 | DOI:10.2106/JBJS.24.00261

Front Pharmacol. 2025 Jan 7;15:1502791. doi: 10.3389/fphar.2024.1502791. eCollection 2024.

ABSTRACT

BACKGROUND: Statins, as an important class of lipid-lowering drugs, play a key role in the prevention and treatment of cardiovascular diseases. However, with their widespread use in clinical practice, some adverse events have gradually emerged. In particular, the hepatotoxicity associated with statins use has become one of the clinical concerns that require sufficient attention.

METHODS: In this study, we conducted a comprehensive and detailed analysis of the hepatotoxicity of statins based on the data of the US Food and Drug Administration Adverse Event Reporting System database from the first quarter (Q1) of 2004 to the Q1 of 2024 and used Reporting Odds Ratios and Empirical Bayes Geometric Mean to mine the signal of adverse events.

RESULTS: In this study, hepatic disorder related seven statins all exhibited positive signals. Through signal mining, we identified a total of 14,511 cases of adverse events associated with hepatic disorder caused by these statin drugs, with atorvastatin, simvastatin, and rosuvastatin occurring at a higher rate. A total of 148 positive signals related to adverse events of hepatic disorder were captured. Autoimmune hepatitis and drug-induced liver injury both presented positive signals across multiple statin drugs. Notably, atorvastatin had the most significant signal strength in cholestatic pruritus and bilirubin conjugation abnormal. Fluvastatin also showed notable signal strength in autoimmune hepatitis, while simvastatin had a relatively weaker signal strength for hepatic enzyme increased.

CONCLUSION: This study discovered specific adverse event signal values, revealing potential hepatotoxic risks associated with the use of statin drugs. The results provide an important reference for the safe clinical use of drugs, help to improve the understanding of the safety of statins, and also provide a scientific basis for clinicians to make more accurate and safe decisions when making treatment plans.

PMID:39840096 | PMC:PMC11747658 | DOI:10.3389/fphar.2024.1502791

Clin Transl Gastroenterol. 2025 Jan 21. doi: 10.14309/ctg.0000000000000803. Online ahead of print.

ABSTRACT

INTRODUCTION: X842 is a new type of gastric acid-suppressing agent with a rapid onset of action and a long duration of effect. We aim to investigate the efficacy and safety of different doses of X842 versus lansoprazole in the treatment of patients with erosive esophagitis (EE).

METHODS: This phase 2 study included 90 patients with EE (Los Angeles grades A-D) who were randomized (1:1:1) to receive oral low-dose X842 (50 mg/day, n=31), high-dose X842 (100 mg/day, n=31), or lansoprazole (30 mg/day, n=30) for 4 weeks. The main efficacy endpoint was the EE healing rate, which was the proportion of patients who achieved endoscopic healing after 4 weeks of treatment.

RESULTS: For ITT analysis, the EE healing rates at 4 weeks were 93.6% (29/31), 79.3% (23/29), and 80.0% (24/30) for the X842 50 mg, the X842 100 mg and the lansoprazole 30 mg groups. For PP analysis, the EE healing rates at 4 weeks were 93.6% (29/31), 80.8% (21/26), and 82.1% (23/28) in the three groups, respectively. The EE healing rate did not significantly differ among the three groups in either the ITT (p = 0.2351) or PP (p = 0.3320) analysis. The incidence of drug-related treatment-emergent adverse events (TEAEs) did not differ among groups. No severe drug-related TEAEs occurred in the X842 group.

CONCLUSIONS: Our findings confirmed that X842 had efficacy and a favourable safety profile similar to those of lansoprazole. Therefore, X842, a novel P-CAB, is expected to become a promising therapeutic agent for EE.

PMID:39836012 | DOI:10.14309/ctg.0000000000000803

Infect Drug Resist. 2025 Jan 16;18:307-311. doi: 10.2147/IDR.S501604. eCollection 2025.

ABSTRACT

The Hepatorenal Syndrome-Acute Kidney Injury (HRS-AKI) patients infected with methicillin-resistant Staphylococcus aureus (MRSA) urgently require safe and effective treatment options due to their compromised hepatic and renal functions, as well as thrombocytopenia resulting from hypersplenism. In our case, an HRS-AKI patient who underwent continuous renal replacement therapy for fluid overload developed fever with chills. His blood tests indicated elevated C-reactive protein and neutrophils, low platelet count, and bilateral lung infiltrates. Subsequently, his blood culture and catheter culture confirmed a catheter-related MRSA bloodstream infection. To address this complex clinical challenge, a novel oxazolidinone antibiotic, contezolid (800mg orally every 12 hours), was introduced into the patient's anti-infection regimen. Notably, the patient exhibited remarkable improvements and responded favorably to this treatment. During subsequent follow-up, no recurrence of the infection or drug-related adverse events was observed. The successful utilization of contezolid in this case underscores its potential as a novel therapeutic option for treating MRSA infections in patients with HRS-AKI.

PMID:39835163 | PMC:PMC11745060 | DOI:10.2147/IDR.S501604

Cureus. 2024 Dec 19;16(12):e76007. doi: 10.7759/cureus.76007. eCollection 2024 Dec.

ABSTRACT

Glucagon-like peptide-1 (GLP-1) receptor agonists, including tirzepatide (Mounjaro), are widely used to manage type 2 diabetes mellitus (T2DM) and obesity. While gastrointestinal side effects are common, acute pancreatitis remains a rare but significant complication. Limited evidence exists on the risks associated with switching between GLP-1 agonists, emphasizing the need for clinical awareness. We present a 59-year-old male with T2DM, hyperlipidemia, and hypertension, who was recently transitioned from semaglutide (Ozempic) to tirzepatide (Mounjaro). He presented with acute epigastric pain, nausea, and vomiting two days after initiating tirzepatide. Laboratory findings revealed elevated lipase levels (847 U/L), leukocytosis, and diagnostic imaging confirming acute pancreatitis with other causes ruled out. Supportive care improved symptoms initially, but the clinical course was complicated by fevers prompting repeat imaging, revealing worsening pancreatitis with colonic involvement and pleural effusion. The patient was treated with empiric antibiotics and supportive measures, resulting in resolution of symptoms. Tirzepatide was discontinued, with a follow-up arranged for glycemic management. Acute pancreatitis is a rare but documented adverse effect of GLP-1 agonists, with limited cases reported in the literature. Switching between GLP-1 agonists may increase the risk of adverse effects, especially if appropriate dose titration protocols are not followed. This case highlights the recognition of acute pancreatitis as a potential adverse effect of GLP-1 agonists when initiating or transitioning GLP-1 therapies and following titration protocols to help avoid this complication. GLP-1 agonists, including tirzepatide, offer significant therapeutic benefits for T2DM and obesity but carry risks of rare adverse effects like acute pancreatitis. Greater awareness, careful dose adjustments, and vigilant monitoring are essential to optimizing patient safety. Further research is needed to elucidate the safety profile of switching between GLP-1 agonists to guide clinical practice and improve patient outcomes.

PMID:39834977 | PMC:PMC11743417 | DOI:10.7759/cureus.76007

Front Pharmacol. 2025 Jan 6;15:1466875. doi: 10.3389/fphar.2024.1466875. eCollection 2024.

ABSTRACT

BACKGROUND: Urinary retention (UR) is a clinical condition where patients cannot fully empty their bladder. Although numerous drugs are associated with UR, comprehensive and reliable studies identifying drugs that induce UR are scarce.

METHODS: This study leveraged data from the FDA Adverse Event Reporting System (FAERS) and the Canadian Vigilance Adverse Reaction (CVAR) database to explore adverse events (AEs) related to UR from 2004 to Q1 2024. The top 50 drugs were analyzed for annual reporting trends using linear regression. Disproportionality analysis using the reporting odds ratio (ROR) method, with P-values adjusted via Bonferroni correction, identified significant signals, which were then validated against drug labels and re-evaluated using the CVAR database. Time-to-onset analysis was also performed.

RESULTS: From 2004 to Q1 2024, FAERS recorded 17,785,793 AEs, with 16,183 (0.09%) identified as UR cases. The median age among these cases was 65 years, with males comprising 53.4%. There were significant annual increases in UR reports associated with antineoplastic agents (0.19% per year) and antidiabetic drugs (0.09% per year), while reports linked to bronchodilators decreased (-0.53% per year). Disproportionality analysis revealed significant signals for 34 drugs (68%), with the highest RORs observed in Fesoterodine, Mirabegron, and Solifenacin. Initial signal detection identified potential new UR signals for Abiraterone, Valacyclovir, Fluoxetine, Empagliflozin, Clopidogrel, and Amlodipine, with CVAR confirming signals for Abiraterone, Fluoxetine, and Empagliflozin. The median time to onset of UR was 29 days, with over half of the cases occurring within 30 days of initiating medication.

CONCLUSION: The study identifies a rising trend in drug-related UR reports over the past 2 decades. The validation of new signals for Abiraterone, Fluoxetine, and Empagliflozin underscores the critical need for continuous drug safety monitoring and targeted research to better understand the mechanisms behind drug-induced UR.

PMID:39834827 | PMC:PMC11744018 | DOI:10.3389/fphar.2024.1466875

Respir Med Case Rep. 2024 Dec 27;53:102160. doi: 10.1016/j.rmcr.2024.102160. eCollection 2025.

ABSTRACT

Anaplastic lymphoma kinase tyrosine kinase inhibitors (ALK TKIs) show robust efficacy and has revolutionized the treatment of NSCLC patients harboring an ALK-rearrangement. Side effects, sometimes even serious such as pneumonitis, can occur with ALK TKIs. We report a case of a patient with ALK positive advanced NSCLC who developed pneumonitis during treatment with first-line alectinib. With no alternative etiology of pneumonitis identified, the patient was treated with corticosteroids and discontinuation of alectinib. Following rapid clinical recovery and radiographic resolution of the opacities, the patient was started with brigatinib, with no recurrence of the clinical symptoms or radiographic findings of pneumonitis. While further descriptions are needed, our experience suggests that switching to a second ALK-TKI may be a safe therapeutic option in some patients who develop drug-induced pneumonitis on ALK TKIs.

PMID:39834688 | PMC:PMC11743586 | DOI:10.1016/j.rmcr.2024.102160

Heliyon. 2024 Dec 25;11(1):e41483. doi: 10.1016/j.heliyon.2024.e41483. eCollection 2025 Jan 15.

ABSTRACT

Cisplatin (CDDP) is one of the main chemotherapeutic drugs that is widely used in many cancers. However, CDDP resistance is a frequent therapeutic challenge that reduces prognosis in cancer patients. Since, CDDP has noticeable side effects in normal tissues and organs, it is necessary to assess the molecular mechanisms associated with CDDP resistance to improve the therapeutic methods in cancer patients. Drug efflux, detoxifying systems, DNA repair mechanisms, and drug-induced apoptosis are involved in multidrug resistance in CDDP-resistant tumor cells. Mammalian target of rapamycin (mTOR), as a serine/threonine kinase has a pivotal role in various cellular mechanisms such as autophagy, metabolism, drug efflux, and cell proliferation. Although, mTOR is mainly activated by PI3K/AKT pathway, it can also be regulated by many other signaling pathways. PI3K/Akt/mTOR axis functions as a key modulator of drug resistance and unfavorable prognosis in different cancers. Regarding, the pivotal role of mTOR in CDDP response, in the present review we discussed the molecular mechanisms that regulate mTOR mediated CDDP response in tumor cells.

PMID:39834411 | PMC:PMC11743095 | DOI:10.1016/j.heliyon.2024.e41483

Psychiatry Clin Neurosci. 2025 Jan 21. doi: 10.1111/pcn.13785. Online ahead of print.

ABSTRACT

AIM: This study aimed to explore the comparative risks for dystonia among different second-generation antipsychotics (SGAs), the influence of sex, and the relationship between the time-to-onset of dystonia and its outcomes.

METHODS: We analyzed data from the Japanese Adverse Drug Event Report database from April 2004 to November 2023. Cases involving oral SGAs, excluding clozapine, were extracted. We used the odds ratios to assess the reporting proportions among SGAs and sex, analyzed the median time-to-onset and interquartile ranges (IQRs), and conducted a receiver operating characteristic (ROC) curve analysis to investigate the time-to-onset of dystonia and its relationship to outcomes.

RESULTS: We extracted 9837 cases involving oral SGAs. Lurasidone was associated with a significantly higher proportion of dystonia reports than risperidone, aripiprazole, quetiapine, and olanzapine. The reporting proportion of dystonia associated with aripiprazole was lower than that of paliperidone and risperidone, but higher than that of quetiapine and olanzapine. Female sex was significantly associated with a higher reporting proportion of dystonia compared with males. Among the 148 cases of oral SGA-induced dystonia, the median time-to-onset was 125 days (IQR, 19.75-453.25 days). Divided into the three outcome groups (recovered, improved, and unrecovered/residual), those with better outcomes had a shorter time-to-onset than those with poorer outcomes. ROC curve analysis suggested a threshold of 91.5 days for discriminating outcomes, with a sensitivity of 71.7% and specificity of 69.9%.

CONCLUSIONS: The risks of dystonia may vary among SGAs and between sexes. SGA-induced dystonia often manifests in the tardive form.

PMID:39834274 | DOI:10.1111/pcn.13785

BMC Psychiatry. 2025 Jan 20;25(1):52. doi: 10.1186/s12888-025-06493-0.

ABSTRACT

OBJECTIVE: Paliperidone palmitate is a second-generation antipsychotic that has undergone extensive investigation in clinical trials. However, real-world studies assessing its safety in large populations are lacking. As such, this study aimed to comprehensively evaluate real-world adverse drug events (ADEs) linked to paliperidone palmitate by employing data mining techniques on the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database and the Japanese Adverse Drug Event Report (JADER) database.

METHODS: The study retrieved ADE reports from the FAERS database covering the period from 2009 through the third quarter of 2024, and from the JADER database covering the period from 2013 through the second quarter of 2024. Utilizing disproportionality analyses such as the reporting odds ratios (ROR), proportional reporting ratios (PRR), Bayesian confidence propagation neural network (BCPNN), and multi-item Poisson shrinkage (MGPS), significant associations between ADEs and paliperidone palmitate were evaluated.

RESULTS: A total of 27,672 ADE reports related to paliperidone palmitate were identified in FAERS, with 285 significantly disproportionate preferred terms (PTs) identified by all four algorithms. Paliperidone palmitate-associated ADEs encompassed 27 System Organ Classes (SOCs). The top three PTs with the highest reported cases were off-label use, drug ineffective, and hospitalization. Common ADEs included increased blood prolactin, galactorrhea, and schizophrenia, which was consistent with drug label. Noteworthy, unexpected signals not listed in the drug label were also identified, such as psychosexual disorders, prolactin-producing pituitary tumors, suicide attempt, and sudden death. The median onset time for all ADEs was 40 days. Furthermore, gender-based difference in risk signals was detected. Females are more likely to experience elevated blood prolactin and weight increase, whereas males are more prone to sexual dysfunction. Among the 1,065 ADE reports from the JADER database, we identified 51 positive signals, 35 of which overlapped with those found in FAERS, including schizophrenia, hyperprolactinemia, and erectile dysfunction.

CONCLUSION: The study findings from two independent databases serve as crucial references for ensuring the safe of paliperidone palmitate. Additionally, the gender-specific monitoring references provided can enhance clinical surveillance efforts and facilitate more effective risk identification.

PMID:39833706 | DOI:10.1186/s12888-025-06493-0

Psychopharmacology (Berl). 2025 Jan 20. doi: 10.1007/s00213-025-06743-9. Online ahead of print.

ABSTRACT

RATIONALE AND OBJECTIVES: In vivo receptor interactions vary as a function of behavioral endpoint, with key differences between reflexive and non-reflexive measures that assess the motivational aspects of pain and pain relief. There have been no assessments of D1 dopamine agonist / mu opioid receptor (MOR) agonist interactions in non-reflexive behavioral measures of pain. We examined the hypothesis that D1/MOR mixtures show enhanced effectiveness in blocking pain depressed behaviors while showing decreased side effects such as sedation and drug reward.

METHODS: SKF82958 and methadone were used as selective/high efficacy D1 and mu agonists, respectively. An FR10 operant schedule was utilized in the presence and absence of a lactic acid inflammatory pain-like manipulation, to measure antinociceptive and operant-rate-suppressing effects, respectively. Rewarding properties of the drug combinations were determined using a conditioned place preference procedure.

RESULTS: Methadone alone, but not SKF82958 alone, produced dose-dependent restoration of pain-depressed responding. Both SKF82958 and methadone produced dose-dependent response rate suppression. Three fixed proportion mixtures, based on the relative potencies of the drugs in the rate suppression assay, produced dose-dependent antinociception and sedation. Isobolographic analysis indicated that the 0.17:1 mixture produced supra-additive antinociception and additive sedation. The 0.055:1 mixture produced additive antinociception with sub-additive sedation, and the 0.018:1 mixture had the highest therapeutic index (TI) relative to other mixtures and drugs alone. The antinociceptive doses and component doses for the 0.018:1 mixture did not produce conditioned place preference.

CONCLUSIONS: These results suggest that D1-selective dopamine agonists may have utility as candidate opioid-sparing analgesics.

PMID:39832015 | DOI:10.1007/s00213-025-06743-9

Pharmacotherapy. 2025 Jan 20. doi: 10.1002/phar.4648. Online ahead of print.

ABSTRACT

INTRODUCTION: Heart failure (HF) affects more than 6 million adults in the United States, contributing to substantial morbidity, mortality, and health care costs. Despite advances in medical care, many medications can exacerbate HF, yet their prevalence of use remains unknown. This study examined the national use of prescription medications that could exacerbate HF in adults with self-reported HF.

METHODS: We analyzed data from US adults with self-reported HF in the National Health and Nutrition Examination Survey (NHANES) from 2011 to March 2020. Medications known to exacerbate HF, identified from HF guidelines, were documented through pill bottle reviews. Weighted estimates were used to calculate prevalence overall and by sex, race and ethnicity, and level of evidence for avoidance. Multivariable logistic regression models calculated adjusted odds ratios (aORs) and 95% confidence intervals (95% CIs) for the use of these high-risk medications by sex and race and ethnicity.

RESULTS: A total of 687 participants, representing 5.2 million U.S. adults with HF after applying sampling weights, were included (mean age, 66.1 [95% CI 64.9, 67.4] years; 50.4% female [95% CI 45.9%, 55.0%]). Overall, 14.5% (95% CI 10.4%, 19.5%; n = 92) of adults with HF were prescribed at least one medication known to exacerbate HF, with the most common being diltiazem, meloxicam, and ibuprofen. Use of these medications was not significantly different by sex nor by race and ethnicity. Of these medications, 21.7% (95% CI 10.7%, 38.8%) had level A evidence warning against use, and 78.3% (95% CI 61.2%, 89.3%) had B level evidence.

CONCLUSION: Over one-seventh of U.S. adults with HF were likely to have been prescribed medications that could exacerbate the condition, underscoring the need to optimize care. Reducing high-risk medication use may mitigate HF exacerbations and improve outcomes in this vulnerable population.

PMID:39831652 | DOI:10.1002/phar.4648

Br J Hosp Med (Lond). 2024 Dec 30;85(12):1-12. doi: 10.12968/hmed.2024.0380. Epub 2024 Jul 16.

ABSTRACT

Aims/Background Tinnitus is a very common condition, and is a side effect of many medications. The panorama of drug-induced tinnitus has widened in recent decades, and post-marketing data are needed to gain a better insight into adverse drug reactions related to tinnitus. However, there are currently few studies on drug-induced tinnitus. We aimed to explore the details of real-world drug-related tinnitus. Methods We collected data on adverse drug reactions related to tinnitus from the Food and Drug Administration Adverse Event Reporting System (FAERS) database for the fourth quarter of 2012 to the fourth quarter of 2023. The top 25 tinnitus-associated drugs and indications were analyzed, and reporting odds ratios (RORs) were used to assess the association between drugs and adverse events (AEs). Results A total of 29,460 patients were enrolled in our study, with a greater proportion of women (59.1%) than men (31.7%). Among all tinnitus-related drugs, duloxetine (n = 1510, ROR [95% confidence interval (CI)] = 11.99 [11.38-12.63]), ciprofloxacin (n = 938, ROR [95% CI] = 9.96 [9.33-10.63]), and adalimumab (n = 759, ROR [95% CI] = 0.68 [0.64-0.73]) displayed the strongest associations. Among all tinnitus-related indications, depression (n = 1172), rheumatoid arthritis (n = 947), and multiple sclerosis (n = 914) were the most relevant indications. Vertigo (n = 2443, ROR [95% CI] = 7.51 [7.21-7.82]), deafness (n = 1740, ROR [95% CI] = 13.50 [12.86-14.18]), and hypoacusis (n = 1550, ROR [95% CI] = 6.11 [5.81-6.43]) were the most common concomitant ototoxic AEs in patients reporting tinnitus. Conclusion Our study mined and analyzed the AEs signals of drug-induced tinnitus and provided a reference for the safe clinical application of the drugs.

PMID:39831503 | DOI:10.12968/hmed.2024.0380

Brain Behav. 2025 Jan;15(1):e70200. doi: 10.1002/brb3.70200.

ABSTRACT

INTRODUCTION: The cognitive side-effects of medication are common, but often overlooked in practice, and not routinely considered in interventional trials or post-market surveillance. The cognitive footprint of a medication seeks to quantify the impact of its cognitive effects based on magnitude, duration, and interaction with other factors, evaluated across the exposed population.

METHODS: Bayesian multivariable regression analysis of retrospective population-based cross-sectional cohorts.

RESULTS: We replicate positive and negative cognitive effects of commonly used medications in UK Biobank, and extend observed associations to two additional cohorts, the EPIC Norfolk, and the Caerphilly Prospective Cohort. We quantify the resultant cumulative impact at the population level given known patterns of prescribing and compare it with exemplar common diseases.

CONCLUSION: The cognitive side-effects of commonly used drugs may have significant impact at the population level. Consideration should be given to a routine structured assessment of cognition in interventional trials and post-market surveillance.

PMID:39829148 | DOI:10.1002/brb3.70200

Sci Rep. 2025 Jan 19;15(1):2452. doi: 10.1038/s41598-025-86422-z.

ABSTRACT

Misoprostol was originally used to treat gastric ulcers, and has been widely used in abortion, cervical maturation, induced labour and postpartum hemorrhage. But there are still many undetected adverse events (AEs). The purpose of this study was to provide a comprehensive overview of the safety of misoprostol. Adverse events related to misoprostol were collected from the FDA Adverse Event Reporting System (FAERS) database from the first quarter of 2004 to the second quarter of 2024. This study used proportional disequilibrium methods such as reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and empirical Bayes geometric mean (EBGM) to detect AEs. After analyzing 17,427,762 adverse event reports, a total of 2032 adverse events reports related to misoprostol were identified, involving 23 system organ classes and 30 preferred terms. The most common AEs were foetal exposure during delivery(n = 201), uterine tachysystole(n = 95), uterine rupture (n = 95), and heart rate decreased (n = 93). Although most AEs complied with the drug instruction, new AEs signals such as congenital aqueductal stenosis and congenital brain damage were also identified. Clinicians should make appropriate evaluation when using misoprostol, closely monitor the indicators of patients, and have appropriate countermeasures for possible adverse events.

PMID:39828758 | DOI:10.1038/s41598-025-86422-z