Acta Pharm. 2025 Jan 9;74(4):693-708. doi: 10.2478/acph-2024-0038. Print 2024 Dec 1.

ABSTRACT

Cardiovascular diseases (CVDs) are the leading cause of mortality and morbidity globally. It is estimated that 17.9 million people died from CVDs in 2019, which represents 32 % of all deaths worldwide. Cardiovascular drugs are the most common medical intervention for the prevention of cardiovascular events. CV medications have many benefits however their application is often complicated by multimorbidity and polypharmacy. Drug-drug interactions (DDIs) can lead to adverse drug events, hospitalizations, prolonged hospital stays, increased healthcare costs, and increased risk of mortality. Hospital admission provides an opportunity for pharmacotherapy analysis and for identifying DDIs which can jeopardize medication safety. The aim of this study is to determine the type and prevalence of potential clinically significant DDIs in patients with CVD and to examine factors associated with exposure to DDIs. A prospective study was conducted at the Dubrava University Hospital at the Clinic of Cardiology during a 6-month period (September 2023 - February 2024). Demographic, clinical and pharmacotherapy data were collected for each patient. The first prescribed pharmacotherapy was analyzed. The research was approved by the Hospital's Ethics Committee and each patient involved in the study signed an informed consent. Lexicomp® Lexi-InteractTM Online (Lexi-Comp, Inc., USA) was used for DDI analysis. Poisson regression was used for regression analysis for determining risk factors associated with exposure to DDIs. Total of 151 patients admitted to Cardiology ward were included in the research, and the average age was 67 years. Patients had an average of 9 medications in their therapy and 8 diagnoses. Overall, 1268 potential clinically significant DDIs were determined, of which the most frequently determined interactions were grade C (90.9 %), then grade D (8.6 %) and grade X (0.6 %). CV medications were involved in 88 % DDIs. The most common interventions regarding identified DDIs included exclusion one of the drugs, dose adjustment, increased monitoring of signs of bleeding, cardiac disorders, hypoglycemia, CNS depression and rhabdomyolysis, blood pressure, markers of renal function and electrolyte status. Factors associated with the prevalence of potential clinically significant DDIs were decreased renal function, recent hospitalization, total number of comorbidities and polypharmacy. Specific comorbidities associated with DDIs were arrhythmia, heart failure, diabetes mellitus and disease of the respiratory system. A high prevalence of DDIs of CV medications in all categories of clinical significance was determined. Managing medication safety in specific patient groups with CVDs can represent a greater challenge regarding DDIs. Certain medical conditions, such as arrhythmia, heart failure, diabetes, and diseases of the respiratory system, multimorbidity, polypharmacy, impaired renal function and recent hospitalization are identified in this research as additional factors associated with DDIs occurrence in patients with CVDs at hospital admission. Hospital admission is one of the crucial points for managing medication safety. Clinical pharmacists should regularly analyze DDIs in prescribed pharmaco-therapy which enhances medication safety and also contributes to the quality of provided health care.

PMID:39787625 | DOI:10.2478/acph-2024-0038

Alzheimers Dement. 2024 Dec;20 Suppl 5:e086936. doi: 10.1002/alz.086936.

ABSTRACT

BACKGROUND: The use of potentially inappropriate medications (PIMs) in older adults with dementia and/or Mild Cognitive Impairment (MCI) has been associated with increased adverse events, drug-related problems (DRPs), prolonged hospitalization, risk of falls, and increased length of stay. This study aimed to identify which explicit tool, Beers criteria 2023 or Screening Tool of Older Persons Potentially Inappropriate Prescriptions (STOPP) 2023, identifies more PIM use among older adults with MCI or dementia.

METHODS: A cross-sectional study was conducted at a Multispecialty Interprofessional Team-based (MINT) memory clinic. Patients with MCI or dementia were recruited between Jan and August 2023. Patient medical records were reviewed for PIMs using Beers Criteria 2023 and STOPP criteria 2023. Bivariate logistic regression analysis was employed to identify potential factors associated with the use of PIMs.

RESULTS: Overall, 44 participants were enrolled in the study, with a mean age of 80.2± 6.2 years. Among 44 patients, 36.4% (n = 16) patients had MCI, followed by one-fifth of patients (n = 9) who had mixed dementia and 11.4% (n = 5) with vascular cognitive impairment. At least one PIM was identified in 47.7% (n = 21) and 27.2% (n = 12) of the study participants based on Beers' and STOPP's criteria, respectively. Using the Beers criteria, 50 PIMs were found, with an average of 0.9 PIMs for each patient, while a total of 31 PIMs were identified using the STOPP criteria, with an average of 0.6 PIMs per patient. There was a significant association between ≥ 9 number of comorbidities and PIMs as per Beers criteria (OR = 8.4, 95% Confidence interval: 1.27- 55.39, P = 0.027). However, no statistically significant association was observed with PIMs as per STOPP criteria.

CONCLUSION: The frequency of PIMs identified using Beers and STOPP criteria highlights the importance of identifying and addressing PIMs in this population. This study adds valuable insights to the progressing comprehension of medication-related complexities in older adults living with MCI or dementia.

PMID:39781973 | DOI:10.1002/alz.086936

Alzheimers Dement. 2024 Dec;20 Suppl 5:e086917. doi: 10.1002/alz.086917.

ABSTRACT

BACKGROUND: Up to 30% of hospitalizations in older adults living with Mild Cognitive Impairment (MCI) and dementia are attributed to drug-related problems (DRPs), including adverse drug reactions, drug interactions, potentially inappropriate medication (PIM) use, and medication non-adherence. This study categorizes the identified DRPs according to the Pharmaceutical Care Network Europe (PCNE) Classification for DRPs version 9.1.

METHODS: A cross-sectional study was carried out with older adults receiving care for MCI or dementia at an Interdisciplinary memory clinic over eight months. The study employed four tools: the Medication Appropriateness Index (MAI), and the Medication Review in Cognitive Impairment and Dementia (MedRevCiD) checklist, Beers Criteria 2023, and Screening Tool of Older Persons Potentially Inappropriate Prescription (STOPP) 2023 to conduct a medication review. Identified DRPs were categorized according to their types and root causes with the PCNE classification system, version 9.1.

RESULTS: Forty-four participants (45.5% female, n = 20) were enrolled. The average age of the study participants was 80.2 years (standard deviation (SD) 6.2). Most of the participants (61.4%, n = 28) had six or more comorbidities ((mean ± SD) 6.7 ± 3.4). A total of 375 medications were prescribed to the 44 study participants. The median number of medications per day was 7.5 (interquartile range (IQR): 6 per day). A total of 119 DRPs were detected in 36 patients, with an average of 2.7 DRPs per patient. The most common type of DRP was within the classification of treatment safety, accounting for 63% of the reported DRPs (n = 75), followed by treatment effectiveness (15.9%, n = 19). The most common cause of DRPs noted was inappropriate drugs according to guidelines/formulary (43.6%, n = 52), followed by an inappropriate combination of drugs, or drugs and herbal or drug-drug interaction (21%, n = 25) from the drug selection category. A total of 53 recommendations were made by the pharmacist in the medical records for the study participants.

CONCLUSION: The high prevalence of DRPs, notably those involving treatment safety and inappropriate drug selection, emphasizes the importance of medication reviews and tailored interventions to improve medication management and safety in this at-risk population.

PMID:39781930 | DOI:10.1002/alz.086917

Alzheimers Res Ther. 2025 Jan 8;17(1):15. doi: 10.1186/s13195-024-01669-4.

ABSTRACT

BACKGROUND: The safety data of lecanemab in the post-marketing period has yet to be fully investigated in the current literature. We aimed to identify and characterise the safety profile of lecanemab in the post-marketing period.

METHODS: We searched and reviewed the reports submitted to the FDA's Adverse Event Reporting System (FAERS). We used a case/non-case approach to estimate the reporting odds ratio (ROR) and information component (IC) with 95% confidence intervals (CI) for lecanemab-related adverse events (AEs) reported at least four counts. We compared the difference between serious and non-serious reports using non-parametric tests.

RESULTS: The FAERS recorded 1,986 lecanemab-related AEs affecting 868 patients. Two hundred and three patients experienced serious AEs, including 22 deaths. The most frequently reported AEs were headache (n = 193), chills (n = 100), fatigue (n = 93), and amyloid-related imaging abnormality-oedema/effusion (ARIA-E) (n = 91). Safety signals were detected, such as headache (ROR: 10.4, 95%CI: 8.97, 12.07; IC: 3.25, 95%CI: 2.97, 3.40), ARIA-E (ROR: 18,299.69, 95%CI: 14,001.27, 23,917.73; IC: 13.37, 95%CI: 6.15, 6.87), and infusion-related reaction (ROR: 35.25, 95CI 27.58, 45.07; IC: 5.09, 95CI 4.15, 4.87). We also identified several new AEs, such as migraine and pancreatic carcinoma. Patients with serious AEs were more likely to be on polypharmacy for Alzheimer's disease and use aspirin, acid-suppressing medications, statins, antidepressants, or benzodiazepines compared to those with non-serious AEs.

CONCLUSIONS: Lecanemab may have a significant potential for AEs. Our results provide evidence for healthcare professionals and patients to weigh the risks and benefits of lecanemab treatment. Further prospective studies are needed to explore rare and unexpected AEs.

PMID:39780222 | DOI:10.1186/s13195-024-01669-4

BMJ Case Rep. 2025 Jan 8;18(1):e263129. doi: 10.1136/bcr-2024-263129.

ABSTRACT

Denosumab, an anti-RANKL antibody, induces bone metabolism to a low-turnover bone status by arresting osteoclast activity. Frequent adverse events include infusion reactions, fever and hypocalcaemia but not hypophosphataemia. We report a case of severe hypophosphataemia associated with secondary hyperparathyroidism following denosumab administration in a young boy with recurrent osteosarcoma who was successfully treated with evocalcet. He developed hypocalcaemia and severe refractory hypophosphataemia after receiving denosumab for bone metastases despite calcium, cholecalciferol and phosphorus supplementation. Laboratory data revealed secondary hyperparathyroidism due to denosumab-induced hypocalcaemia as the cause of hypophosphataemia. Evocalcet contributed to the normalised parathyroid hormone and phosphorus levels, allowing the discontinuation of phosphorus supplementation. This case highlights the complexity of managing electrolyte imbalances induced by bone-modifying agents, such as denosumab, underscoring the importance of monitoring bone metabolism markers and the potential effectiveness of evocalcet in managing drug-induced secondary hyperparathyroidism and hypophosphataemia.

PMID:39778963 | DOI:10.1136/bcr-2024-263129

Adv Clin Exp Med. 2025 Jan 8. doi: 10.17219/acem/193023. Online ahead of print.

ABSTRACT

BACKGROUND: Turmeric and boswellia supplements have gained popularity for their anti-inflammatory and antioxidant properties. It is important to critically assess the safety of such supplements for prolonged use.

OBJECTIVES: To assess the safety and tolerability of turmeric-boswellia-sesame oil formulation (TBSF) in healthy human volunteers.

MATERIAL AND METHODS: Forty participants were supplemented with TBSF at a dose of 2,000 mg daily for 90 days. Safety assessments were performed at baseline, as well as on day 30, 60 and 90. Adverse events were monitored throughout the study period. Any evidence of hepatotoxicity injury or drug induced liver injury (DILI) was assessed using R value (R ratio/R factor), which is a relative pattern of liver enzymes. Additionally, Hy's law criteria, based on liver enzymes and bilirubin levels, were employed, along with an evaluation of drug-induced serious hepatotoxicity (eDISH) plot. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were calculated, as these values are relevant to the safety of the intervention.

RESULTS: The study found that TBSF supplementation did not cause any adverse effects or clinically significant variations in vital signs, hematological parameters, lipid profile, liver function enzymes, and renal function markers, and all were within the normal range after 90 days of TBSF supplementation. Platelet-to-lymphocyte ratio and NLR did not change significantly and were within the normal range. All the participants when plotted were in the normal range quadrant of the eDISH plot throughout the study period. No abnormal findings were observed in R value and Hy's law criteria, indicating that TBSF does not induce any hepatotoxicity. The present study showed a normal estimated glomerular filtration rate (eGFR), blood urea nitrogen (BUN), creatinine (Cr), Cr clearance, and BUN/Cr ratio throughout the study period. There was no significant change between these values at 4 abovementioned time points.

CONCLUSIONS: The study findings suggest that TBSF is a safe supplement for regular and long-term consumption.

PMID:39778015 | DOI:10.17219/acem/193023

Aust Prescr. 2024 Dec;47(6):186-191. doi: 10.18773/austprescr.2024.056.

ABSTRACT

Reporting adverse events (adverse drug reactions) associated with medicines and vaccines assists with identifying previously unrecognised side effects and other safety concerns. Reporting adverse events to the Therapeutic Goods Administration is mandatory for sponsors (pharmaceutical companies), and strongly encouraged but voluntary for healthcare professionals and consumers. Adverse events should be reported even when causality is uncertain, as reports may contribute to identification of a safety signal for new or uncommon events. Suspected adverse events associated with new medicines and vaccines (registered in the last 5 years), and medicines included in the Black Triangle Scheme, should be prioritised for reporting. For other medicines, serious adverse events and unexpected adverse events should be prioritised. The Therapeutic Goods Administration analyses adverse event reporting data and uses signal detection methods to identify and evaluate emerging safety signals, which may lead to regulatory actions and communication to address safety issues.

PMID:39777041 | PMC:PMC11703569 | DOI:10.18773/austprescr.2024.056

Front Immunol. 2024 Dec 24;15:1503316. doi: 10.3389/fimmu.2024.1503316. eCollection 2024.

ABSTRACT

BACKGROUND: The occurrence of immune-related adverse events (irAEs) seemed to be associated with better outcomes in advanced gastric cancer (AGC) patients. However, research focusing on the impact of the single-organ irAE (uni-irAE) or multi-organ irAEs (multi-irAEs) on the AGC outcome is relatively limited. In this study, we investigated individually the impact of the different irAEs on AGC survival as well as the co-occurrence patterns of multi-irAEs.

METHODS: The uni-irAE, multi-irAEs, and non-irAE were identified based on National Comprehensive Cancer Network (NCCN) guidelines. ICI efficacy for the disease control rate (DCR) and the objective response rate (ORR) was assessed based on the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1. The association for the irAEs with progression-free survival (PFS) or overall survival (OS) was analyzed using the Kaplan-Meier method and Cox regression model. We also performed pairwise correlation analysis to identify co-occurrence patterns of multi-organ irAEs.

RESULTS: A total of 288 patients including 175 non-irAE, 73 uni-irAE, and 40 multi-irAE patients were evaluated for their association with AGC outcome. The irAEs patients displayed higher DCR (78.8% vs. 67.4%, p=0.037) when compared with those of non-irAE patients, and both uni-irAE patients (82.2% vs. 67.4%, p=0.019) and multi-irAE patients (72.5% vs. 67.4%, p=0.534) showed higher DCR than that of non-irAE patients. The multivariate analyses revealed that multi-irAEs was an independent risk factor for PFS (hazard ratio [HR] of 0.63, 95% confidence interval [CI] 0.41~0.96, p=0.031) and OS (HR 0.47, 95% CI 0.29~0.76, p=0.002), whereas the survival association for uni-irAE was not obtained. The analysis of the co-occurrence patterns for multi-irAEs revealed that the thyroid, adrenal gland, heart, skin, and lung irAEs exhibited a high risk of co-occurrence of multi-irAEs. The multivariate Cox regression analysis for organ-specific irAEs revealed that patients experiencing thyroid, adrenal gland, and skin irAEs had favorable survival outcomes compared with those without these irAEs.

CONCLUSION: Multi-irAEs and some organ-specific irAEs can be used as predictive indicators for ICI treatment efficacy in AGC patients. The thyroid, adrenal gland, heart, skin, and lung irAEs are often accompanied by multi-irAE occurrence.

PMID:39776906 | PMC:PMC11703953 | DOI:10.3389/fimmu.2024.1503316

Pharmacoepidemiol Drug Saf. 2025 Jan;34(1):e70084. doi: 10.1002/pds.70084.

ABSTRACT

BACKGROUND AND OBJECTIVES: Based on the Adverse Event Reporting System (FAERS) data from the US FDA, this study mined the adverse drug reactions of obeticholic acid (OCA) in the real world and provided reference for clinical safe drug use.

METHODS: Adverse event reports for OCA from the second quarter of 2016 to the third quarter of 2023 were extracted. The analysis for adverse reaction signal detection was conducted using reporting odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker methods.

RESULTS: A total of 5661 OCA-related adverse event reports were collected, and 105 OCA-related adverse reaction signals were obtained, involving 14 systems, among which 46 new signals were not previously mentioned in the product labeling. Severe adverse event of OCA accounted for a relatively high proportion (1445 cases, 25.53%), among which the number of hospitalization reports was the largest (1042 cases, 18.41%). The top five adverse events were pruritus, fatigue, constipation, elevated blood alkaline phosphatase, and abdominal distention. The top five adverse reaction signals intensity were abnormal blood alkaline phosphatase, abnormal ratio of albumin globulin, spider nevus, combined with abnormal bilirubin, and γ-abnormal glutamyl transferase.

DISCUSSION: Based on the pharmacovigilance study of the FAERS database, it is necessary to strengthen the clinical medication monitoring of OCA, so as to provide reference for effective pharmaceutical monitoring and rational clinical medication.

PMID:39776053 | DOI:10.1002/pds.70084

Age Ageing. 2025 Jan 6;54(1):afae276. doi: 10.1093/ageing/afae276.

ABSTRACT

INTRODUCTION: Drug-related hospital admissions (DRAs) can account for 5%-40% of total hospital admissions in older adults, with a significant proportion deemed preventable. To increase the detection of DRAs, in 2021, a revised trigger tool listing 21 frequent causes of admissions and medications at risk was proposed. This study aimed to describe DRAs using this trigger tool in a French acute geriatric ward and to assess the performance of the tool.

METHODS: This was a retrospective cohort study in a 20-bed geriatric unit including all patients hospitalised in 2023. During the first quarter of 2024, each patient's chart was adjudicated by using a two-step standardised review procedure to assess whether the admission was a DRA. The potentially at cause medications and reasons for admission were also assessed.

RESULTS: During the study period, 483 patients were hospitalised in the acute-care geriatric ward (mean age 86.7 ± 6.15 years). After adjudication, 207 admissions (43%) were identified as DRAs; 70% were considered preventable. The main causes of DRAs were falls/fractures (33%), bleeding (23%) and delirium (14%). The drugs most frequently responsible were diuretics (21%), renin-angiotensin system inhibitors (20%) and direct oral anticoagulants (15%). The overall sensitivity and specificity of the tool for detecting DRAs was 90% (95% CI 88-93) and 72% (68-76), respectively. After adjudication, the trigger tool helped detect 83% more DRAs as compared with the attending geriatrician.

CONCLUSION: DRAs are frequent in a geriatric population and often preventable. Their detection may be improved by the use of a trigger tool.

PMID:39775781 | DOI:10.1093/ageing/afae276

Theranostics. 2025 Jan 1;15(3):1122-1134. doi: 10.7150/thno.101358. eCollection 2025.

ABSTRACT

Rationale: Acute liver failure (ALF) is characterized by rapid hepatic dysfunction, primarily caused by drug-induced hepatotoxicity. Due to the lack of satisfactory treatment options, ALF remains a fatal clinical disease, representing a grand challenge in global health. Methods: For the drug repositioning to ALF of mesalamine, which is clinically approved for the treatment of inflammatory bowel disease (IBD), we propose a supramolecular prodrug nanoassembly (SPNs). Mesalamine is modified with a functional peptide of the FRRG sequence. The resulting mesalamine prodrugs form nanoassemblies solely through intermolecular interactions, ensuring high drug loading capacity and reducing the potential toxicity associated with the carrier materials of conventional nanoparticle systems. Results: In acetaminophen (APAP)-induced ALF mouse models, the SPNs predominantly accumulate in injured target tissues owing to the nanoparticles' propensity to target the liver. Subsequently, cathepsin B overexpressed in hepatocytes by drug-induced inflammation triggers the release of mesalamine from the nanoassemblies via enzymatic cleavage, resulting in remarkable therapeutic efficacy. Meanwhile, nonspecific drug release in healthy cells is inhibited due to their relatively lower cathepsin B expression, which helps prevent the exacerbation of the ALF by minimizing adverse events related to drug exposure. Conclusions: This study provides valuable insights into designing rational nanomedicine for repurposing mesalamine in ALF treatment, potentially inspiring further research to discover effective and safe therapeutic options for patients.

PMID:39776792 | PMC:PMC11700871 | DOI:10.7150/thno.101358

Sci Rep. 2025 Jan 7;15(1):1141. doi: 10.1038/s41598-024-79723-2.

ABSTRACT

Sodium aescinate (SA), a natural plant extract with various bioactivities, is widely used to treat oedema and inflammation in clinics. However, adverse events, including liver injury, kidney injury, and phlebitis, have been reported in patients with SA in recent years. In this study, we used BALB/c mice and L02 cells to evaluate the role of ferroptosis in SA-induced liver injury. SA significantly increased AST, ALT, MDA and Fe2+, decreased GSH levels, and induced pathological changes in the liver in vivo. SA also reduced the viability of L02 cells and induced LDH release, intracellular cysteine reduction, GSH depletion, iron accumulation, ROS production, and lipid peroxidation, indicating that SA causes ferroptosis. In addition, SA inhibited transcriptional activity of activating transcription factor 4 (ATF4) and subsequently reduced the expression of the downstream genes xCT (solute carrier family 7a member 11, SLC7A11) and Cystathionine gamma-lyase (CTH) which play vital roles in GSH biosynthesis. Interestingly, the cytotoxic effects of SA were effectively attenuated by ATF4 overexpression, while they were significantly aggravated by ATF4 silencing. These results revealed that SA triggers hepatocyte ferroptosis by inhibiting the activity of ATF4, which causes an oxidative imbalance.

PMID:39774712 | DOI:10.1038/s41598-024-79723-2

PLoS One. 2025 Jan 8;20(1):e0313338. doi: 10.1371/journal.pone.0313338. eCollection 2025.

ABSTRACT

BICSTaR (BICtegravir Single Tablet Regimen) is an ongoing, observational cohort study assessing the virologic effectiveness and safety of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in treatment-experienced (TE) and treatment-naïve (TN) people with HIV across 14 countries over 24 months. We present 12-month outcomes from participants in the BICSTaR Japan cohort. Retrospective and prospective data were pooled from people with HIV aged ≥20 years receiving B/F/TAF within routine clinical care in Japan. Outcomes included virologic effectiveness (primary endpoint; HIV-1 RNA <50 copies/mL), CD4 count, CD4/CD8 ratio, drug-related adverse events (DRAEs), persistence, and patient-reported outcomes (prospective TN cohort only). Overall, 200 participants were enrolled and included in the 12-month analysis population (150 retrospective, 50 prospective; 116 TN and 84 TE). Most participants were male at birth (99%); median age was 34 years in TN and 45 years in TE participants. At 12 months, virologic effectiveness was high: 92% (90/98) of TN and 95% (72/76) of TE participants had HIV-1 RNA <50 copies/mL (missing = excluded analysis). Median (quartile [Q]1, Q3) CD4 cell count increased by +202.0 (126.0, 311.0) cells/μL in TN (p<0.001) and +11.0 (-60.0, 87.0) cells/μL in TE (p = 0.380) participants. Through 12 months, DRAEs were reported by 13% (25/200) of all participants (16% [18/116] TN, 8% [7/84] TE); diarrhea, weight gain, and headache were the most common. Most DRAEs were mild in severity and no severe DRAEs were reported. One TN participant (<1%; 1/116) and two TE participants (2%; 2/84) discontinued B/F/TAF due to DRAEs (macrocytic anemia, vertigo, diarrhea, and headache). Treatment persistence at 12 months exceeded 98% in both TN and TE participants. In prospective TN participants, improvements in bothersome symptom count and quality-of-life measures were observed. B/F/TAF demonstrated high levels of virologic effectiveness and tolerability in people with HIV treated as part of routine clinical care in Japan.

PMID:39774438 | DOI:10.1371/journal.pone.0313338

Sci Rep. 2025 Jan 7;15(1):1220. doi: 10.1038/s41598-024-84679-4.

ABSTRACT

Macular degeneration is a leading cause of irreversible vision loss, significantly impacting quality of life. To enhance clinical practice and reduce the risk of drug-related macular degeneration, we analyzed drug-related trends using real-world data. Disproportionality analysis of adverse event reports from the FDA Adverse Event Reporting System (FAERS, 2004-2023) identified 67,683 cases involving 1402 drugs. Among these, 42 drugs were linked to significant risks, including treatments for breast cancer (tamoxifen, raloxifene, anastrozole, letrozole) and diabetes (insulin lispro, insulin human). The BCPNN algorithm revealed that 45.2% (19/42) of these drugs had the strongest associations with macular degeneration, with pentosan polysulfate sodium, travoprost, and tolterodine being the highest-risk drugs. Lifitegrast, nicotine, and travoprost were associated with the shortest onset times for ocular adverse events. Among drug classes, glucocorticosteroids were linked to the most rapid onset of ocular side effects (P < 0.001), typically occurring within two months compared to other drugs. Drug-related macular degeneration was more common in women (70.4%) and predominantly affected those aged 60-80. The incidence of drug-related macular degeneration has steadily increased in recent years. This study offers valuable pharmacovigilance insights, highlighting drugs and demographic factors linked to macular degeneration.

PMID:39774257 | DOI:10.1038/s41598-024-84679-4

Int J STD AIDS. 2025 Jan 8:9564624241308372. doi: 10.1177/09564624241308372. Online ahead of print.

ABSTRACT

BACKGROUND: BICSTaR is a multi-national, observational cohort evaluating the effectiveness, safety, and patient-reported outcomes (PROs) in treatment-naïve (TN) and -experienced (TE) people with HIV-1 receiving bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in routine clinical care. We present the 12-month (M12) outcomes of the Italian BICSTaR cohort.

METHODS: Participants initiating B/F/TAF in routine care were prospectively followed. Outcomes included virological and immunologic effectiveness, drug-related adverse events (DRAEs), treatment persistence, and PROs using the HIV Symptom Index (HIV-SI) and the HIV Treatment Satisfaction Questionnaires (HIVTSQ).

RESULTS: N = 201 were included (29 TN, 172 TE), 83% male, median age 38 years in TN, 48 years in TE. At baseline, 94% of TE had an HIV-1 RNA <50 cp/mL, 92% switched to B/F/TAF for simplification. Overall, 69% reported comorbidities (TN: 59%, TE: 70%). At M12, 88% (23/26) of TN and 96% (152/159) of TE had an HIV-1 RNA <50 cp/mL in the discontinuation = failure analysis (without emergence of resistance to B/F/TAF). Median CD4 count changes were +296 cells/µL (interquartile range [IQR], 118, 383) in TN, and +23 cells/µl (-137, 114) in TE. DRAEs were reported for 5% and led to discontinuation in 1%. M12 persistence on B/F/TAF was 97%. TN had a median HIV-SI bothersome symptom count decrease of -1.5 (IQR, -5.0, 0.0). Median treatment satisfaction change score was +29.0 (21, 30) in TE indicating an improvement.

CONCLUSIONS: In this real-world Italian cohort of mostly treatment-experienced people switching for simplification, B/F/TAF demonstrated high effectiveness and persistence over 12 months and confirmed the favourable safety profile shown in clinical trials.

TRIAL REGISTRATION: European cohort: EUPAS22185.

PMID:39772928 | DOI:10.1177/09564624241308372

Pharmaceuticals (Basel). 2024 Nov 26;17(12):1592. doi: 10.3390/ph17121592.

ABSTRACT

Background: Paracetamol and non-steroidal anti-inflammatory drugs (NSAIDs) are frequently used during pregnancy. Due to their fetotoxicity, NSAIDs are contraindicated during the third trimester. There is ongoing controversy about the extent to which NSAIDs may cause cardiovascular and renal impairment in the fetus earlier in the second trimester. Paracetamol, used as an effective treatment for closure of patent ductus arteriosus (PDA) after birth, is suspected to cause similar but unwanted effects during the third trimester of pregnancy. Methods: Three major pharmacovigilance databases (VigilanceCentral, EudraVigilance, and VigiBase) were searched for Individual Case Safety Reports (ICSRs; n = 1288) on fetotoxic effects that have been shown to result from NSAID exposure in late pregnancy. Results: In 219/1288 cases, an NSAID and/or paracetamol was taken after the first trimester, and the ICSR was not related to other reported risk factors. Out of these 219 ICSRs, 48 were exposed to NSAIDs in the second but not the third trimester or to paracetamol in the third trimester. Causality assessment was "probable or likely" in four NSAID reports and none of the paracetamol reports. Conclusions: The scarcity of adverse drug reactions (ADRs) in our study and in the literature, despite decades of pharmaceutical marketing and worldwide use of paracetamol as an analgesic of choice in the third trimester and the absence of formal contraindications against NSAIDs in the second trimester, speaks against a substantial cardiovascular and nephrotoxic risk of temporary use of NSAIDs in the second trimester or paracetamol in the third trimester. NSAIDs continue to be contraindicated in the third trimester.

PMID:39770434 | DOI:10.3390/ph17121592

Int J Surg. 2025 Jan 7. doi: 10.1097/JS9.0000000000002214. Online ahead of print.

ABSTRACT

BACKGROUND: Dural arteriovenous fistulas (DAVFs) pose a significant health threat owing to their high misdiagnosis rate. Case reports suggest that DAVFs or related acute events may follow medication use; however, drug-related risk factors remain unclear. In clinical practice, the concomitant use of multiple drugs for therapy is known as "polypharmacy situations," further increasing the risk of drug-induced DAVF. Real-world studies linking medications and DAVF can alert clinicians to their possibilities and contribute to clinical decision-making and patient education.

METHOD: This study investigated adverse events spanning a decade from the FAERS database, employing pharmacovigilance analysis to systematically assess the risk of drug-induced DAVF. Furthermore, the clinical characteristics of these drug-related DAVFs, such as demographic information, complications, and outcomes, were characterized.

RESULT: This study generated a broad spectrum of drugs associated with DAVFs. A total of 355 DAVF events, involving 161 drugs across 73 categories, were compiled from millions of records. We identified eight classes of drugs for thorough investigation. Pharmacovigilance analysis revealed that tamoxifen, methylprednisolone, betamethasone, prednisone, rebif, ustekinumab, natalizumab, baclofen, dabigatran etexilate, and bupivacaine have the potential to induce DAVFs. Cerebrovascular thrombotic and embolic events emerge as the most prominent co-adverse events of drug-induced DAVFs. Analyses based on drug-disease targets suggested that the regulation of angiogenesis could be a potential mechanism in tamoxifen-induced DAVFs. Apart from medications with gender-specific prescription patterns, most exhibit a high risk of DAVF in adult male cohorts. Five patients with drug-related DAVFs experienced severe (fatal) outcomes, with four reports attributed to tamoxifen.

CONCLUSION: These findings highlight the diverse range of drugs implicated in the occurrence or progression of DAVF. Drugs such as tamoxifen, corticosteroids, multiple sclerosis medications, and oral anticoagulants require particular attention. Future research should focus on elucidating the underlying mechanisms and risk factors, such as thrombosis, contributing to drug-induced DAVF to inform preventive strategies and optimize patient care.

PMID:39764589 | DOI:10.1097/JS9.0000000000002214

Hosp Pharm. 2025 Jan 4:00185787241311138. doi: 10.1177/00185787241311138. Online ahead of print.

ABSTRACT

Drug-induced hypertension, though rare, often presents diagnostic challenges, particularly when the causative drug is not typically associated with hypertension. We describe a case involving a 55-year-old woman who presented with anxiety, confusion, and significantly high blood pressure unresponsive to standard treatments. Despite increasing medication doses, her blood pressure remained poorly controlled, leading to an investigation for secondary causes. Elevated plasma and urinary catecholamines were found. It was determined that the recent initiation of buspirone for anxiety was the cause. Discontinuation of buspirone normalized her catecholamine levels and improved blood pressure control. This case underscores the importance of considering drug-induced hypertension, particularly in instances of abrupt and severe blood pressure elevation, where elevated catecholamine levels may suggest conditions such as pheochromocytoma. It highlights the necessity for healthcare practitioners to be vigilant regarding the uncommon side effects of commonly prescribed medications, thereby ensuring accurate diagnosis and appropriate management.

PMID:39763711 | PMC:PMC11700387 | DOI:10.1177/00185787241311138

Arch Esp Urol. 2024 Dec;77(10):1179-1186. doi: 10.56434/j.arch.esp.urol.20247710.164.

ABSTRACT

BACKGROUND: This study aimed to explore factors affecting adherence to targeted therapy in patients with renal cell carcinoma, focusing on the fear of adverse drug reactions.

METHODS: This retrospective case-control study selected patients with renal cancer who received targeted therapy at our hospital from June 2021 to April 2023, categorising them based on their adherence to oral targeted drugs.

RESULTS: Patients with good compliance reported significantly lower levels of fear related to disease progression and adverse drug reactions (p < 0.05). This group showed greater perceived necessity of medication, fewer concerns about medication, and higher trust in their prescribed treatments (p < 0.05). Furthermore, while these patients rated their relationships with doctors lower, their perceptions were more positive overall (p < 0.05). Moreover, they reported more robust social support networks (p < 0.05). The heightened impact of the disease on their lives led them to adopt more proactive coping strategies (p < 0.05). The incidence of drug-related events at 1, 3, 6, 9, and 12 months was significantly lower in the good compliance group than in the poor compliance group (p < 0.001). Fear of adverse drug reactions emerged as an independent predictor of compliance (p < 0.001).

CONCLUSIONS: Adherence to targeted cancer therapy is significantly influenced by fear of adverse drug reactions, with psychological factors, patient-provider relationships, and the personal impact of the disease playing crucial roles.

PMID:39763258 | DOI:10.56434/j.arch.esp.urol.20247710.164

Hum Vaccin Immunother. 2025 Dec;21(1):2424611. doi: 10.1080/21645515.2024.2424611. Epub 2025 Jan 6.

ABSTRACT

Programmed cell death-1 (PD-1) inhibitors and programmed cell death ligand 1 (PD-L1) inhibitors are considered effective alternatives for the primary treatment of recurrent metastatic cancers. However, they can induce various adverse events affecting multiple organ systems, potentially diminishing patients' quality of life, and even leading to treatment interruptions. Adverse events related to PD-1/PD-L1 inhibitors differ from those associated with CTLA-4 inhibitors and are more commonly observed in the treatment of solid tumors. This study aimed to address the knowledge gap regarding adverse events related to PD-1/PD-L1 inhibitors. A visual bibliometric network was constructed using VOSviewer, CiteSpace, R software, and the Web of Science Core Collection (WoSCC) to quantitatively analyze this research field. Future research directions were also explored. The USA ranked first in publication count and total citations. Over time, publication types transitioned from case reports to clinical trials. Research on for nivolumab was the most prevalent. The spectrum of cancers treated by PD-1/PD-L1 inhibitors expanded beyond melanoma and lung cancer to include renal cell carcinoma, esophageal cancer, and others. Common adverse events included pneumonitis, myasthenia gravis, and vitiligo. There was a significant increase in multi-phase clinical trials and studies related to biomarkers. This study offers valuable insights for potential collaborators and institutions, highlighting trends in the study of adverse events related to PD-1/PD-L1 inhibitors. The management of these adverse events has become more refined and standardized. Biomarker research and multi-phase clinical trials are likely to be key areas of focus in future studies.

PMID:39757956 | DOI:10.1080/21645515.2024.2424611