Current Drug Safety[JOURNAL]
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200 papers
Linezolid-Induced Pancytopenia with Hyponatremia: A Case Report.
Anwar MD, Kapur A, Hazarika K … +2 more , Ghadlinge M, Lote VBS
Curr Drug Saf · 2026 Mar · PMID 41879437 · Publisher ↗
BACKGROUND: Linezolid is an oxazolidinone antibiotic widely prescribed for actinomycetoma. Haematological adverse reactions, such as thrombocytopenia, have been widely reported due to linezolid. We report an unusual case...
BACKGROUND: Linezolid is an oxazolidinone antibiotic widely prescribed for actinomycetoma. Haematological adverse reactions, such as thrombocytopenia, have been widely reported due to linezolid. We report an unusual case of pancytopenia and hyponatremia secondary to injectable linezolid treatment for actinomycetoma. This case is peculiar as previous long-term exposure to oral linezolid one year back was uneventful. CASE REPORT: A 31-year-old male patient, a known case of actinomycetoma, presented to the dermatology outpatient department (OPD) with progressively worsening lesions for which injectable linezolid, meropenem, and sulfamethoxazole-trimethoprim combination were given. Patient developed pancytopenia with hyponatremia within 10 days of therapy initiation. Linezolid was stopped and replaced with doxycycline, whereas other drugs were continued. The test results were normalized within a week. Previous long-term exposure to similar oral therapy one year back did not cause any haematological or electrolyte abnormalities. CONCLUSION: Based on the World Health Organization-Uppsala Monitoring Centre (WHOUMC) causality assessment scale, the association between linezolid and pancytopenia with hyponatremia is considered probable in this case. This case report emphasizes that clinicians should be cautious, as these serious adverse effects can occur on re-exposure to linezolid, even if absent during previous use.
Is "More" Always Better than "Less"? Deprescribing to Improve Patients' Clinical Outcomes: A Case Series.
Gareri P, Marcianò G, Siniscalchi A … +5 more , Rania V, Gareri I, Vocca C, Palleria C, Gallelli L
Curr Drug Saf · 2026 Mar · PMID 41863119 · Publisher ↗
INTRODUCTION: Polypharmacy represents a significant clinical concern, particularly among elderly patients, due to the increased risk of adverse drug reactions (ADRs). This population is often affected by multiple comorbi...
INTRODUCTION: Polypharmacy represents a significant clinical concern, particularly among elderly patients, due to the increased risk of adverse drug reactions (ADRs). This population is often affected by multiple comorbidities and is typically followed by various specialists, which can lead to the concurrent use of multiple medications, commonly defined as polypharmacy when five or more drugs are prescribed. The use of numerous medications heightens the potential for drug-drug interactions (DDIs), thereby increasing the likelihood of ADRs. Deprescribing has emerged as a potential strategy to mitigate pharmacological risk. While the theoretical benefits of deprescribing are well recognized, real-world clinical data are essential to substantiate its efficacy and safety. Discontinuing certain medications may prove beneficial in some cases, yet potentially harmful in others. This study aimed to present a case series that highlights the positive clinical impact of deprescribing in elderly patients undergoing polypharmacy. CASE PRESENTATION: The first case involves an 86-year-old male with Alzheimer's disease, presenting with delusions, cognitive decline, and behavioral disturbances. The second case concerns an 88-year-old bedridden female with vascular dementia, characterized by hallucinations and delusions. The third case concerns an 82-year-old female with major depressive disorder, Parkinsonism, and vascular cerebropathy, who was experiencing drowsiness and confusion. In all three cases, deprescribing led to a marked improvement or complete resolution of clinical symptoms. Patients were selected based on the onset of ADRs and the presence of concerning clinical symptoms. Medication regimens were thoroughly reviewed by a multidisciplinary team comprising clinical pharmacologists and geriatricians, utilizing tools, such as Intercheck and DrugPin, to identify potential drug interactions. Clinical improvement and symptom resolution were used as outcome measures to evaluate the effectiveness of deprescribing. CONCLUSION: This case series illustrates how careful and evidence-informed deprescribing in elderly patients with polypharmacy can significantly reduce the incidence of ADRs, thereby improving clinical outcomes and enhancing therapeutic adherence. These findings underscore the importance of integrating deprescribing into routine geriatric care as a personalized and patientcentered approach. </p>.
Magnitude and Predictors of Antimicrobial Use-Related Drug Problems in Geriatric Inpatients: Evaluation of Pharmacist Interventions.
Hussain MW, Lucca JM, Gulam SM … +1 more , Menon V
Curr Drug Saf · 2026 Mar · PMID 41863118 · Publisher ↗
INTRODUCTION: Infections remain a major cause of illness and death in older adults. Physiological changes, polypharmacy, and chronic conditions complicate antimicrobial therapy and increase the risk of drug problems. Pha...
INTRODUCTION: Infections remain a major cause of illness and death in older adults. Physiological changes, polypharmacy, and chronic conditions complicate antimicrobial therapy and increase the risk of drug problems. Pharmacist-led interventions improve prescribing, but evidence from the United Arab Emirates is limited. This study evaluated the magnitude and determinants of antimicrobial use-related drug problems and assessed clinical pharmacist interventions in hospitalized older adults with infections. METHODS: A retrospective observational study was conducted from February to July 2022 at a 350-bed tertiary care academic hospital in the United Arab Emirates. Medical records of patients aged 60 years and older admitted with infections and treated with systemic antimicrobials were reviewed. Drug-related problems were classified using the Hepler and Strand framework. RESULTS: Among 102 patients, 85 antimicrobial-related drug problems were identified, with half experiencing at least one. Common categories were drug-drug interactions (29%), unnecessary use (18%), and overdosing (14%). Cephalosporins (21%), penicillins (12%), and fluoroquinolones (12%) were the most frequently implicated classes. Clinical pharmacists made 79 recommendations; 95% were accepted, and 91% were implemented. Main interventions were drug omission (28%), substitution (25%), and dose modification (23%). Prior antimicrobial use, polypharmacy, and longer hospital stay predicted drug problems. DISCUSSION: The high prevalence of antimicrobial use-related drug problems highlights the challenges of polypharmacy and prolonged hospitalization. Findings reinforce the feasibility and acceptance of pharmacist-led interventions, supporting their role in antimicrobial stewardship. CONCLUSION: Clinical pharmacists are integral to optimizing antimicrobial therapy and improving medication safety in older adults.
Buccal Transmucosal Controlled Drug Delivery System: Emerging Strategy For Oral Antidiabetic Therapy - A Review.
Kumar P, Tomar AS, Gupta A … +2 more , Sachan N, Wal P
Curr Drug Saf · 2026 Mar · PMID 41863117 · Publisher ↗
Diabetes mellitus is a common long-term illness that requires steady medical treatment. Standard oral medicines for diabetes often have problems like low absorption, being broken down by the liver before they work, and p...
Diabetes mellitus is a common long-term illness that requires steady medical treatment. Standard oral medicines for diabetes often have problems like low absorption, being broken down by the liver before they work, and patients forgetting to take their doses. Buccal drug delivery, which means giving medicine through the inside lining of the mouth, is a promising alternative. It helps control how fast the drug is released and avoids breakdown by the liver. This review examines the structure and function of the buccal mucosa, its drug-absorption capacity, and its utility for drug delivery. Different systems, such as tablets, patches, films, gels, and sticky polymers, are discussed, along with methods to help drugs pass through the mouth lining more easily. The article also explains how buccal drug delivery affects the behavior of medicines in the body, especially for diabetes drugs like Metformin and Glibenclamide. Clinical benefits, recent research, and future opportunities with new technologies are highlighted. Buccal drug delivery is convenient and can improve absorption, but it has limitations, such as poor absorption, mouth irritation, a small absorption area, salivary washout, low permeability, and commercial unavailability for some drugs. Similarly, many oral diabetes medicines, like metformin and alpha-glucosidase inhibitors, can irritate the stomach and intestines, making it harder for patients to continue treatment. These irritations can occur due to changes in pH, changes in gut motility and bile salts, fermentation of food, causing extra fluid in the intestines, or infections such as fungal overgrowth with SGLT2 inhibitors. This review aims to give a clear overview of buccal drug delivery for diabetes and its potential to improve treatment.
Extended Pharmacy Services in Pakistani Community Pharmacies: A Cross-Sectional Assessment of Implementation Status, Barriers, and Practitioner Perspectives.
Kamal A, Muhammad IN, Wei CR … +1 more , Osama M
Curr Drug Saf · 2026 Mar · PMID 41830573 · Publisher ↗
INTRODUCTION: Extended pharmacy services (EPS) encompass comprehensive healthcare interventions beyond traditional medication dispensing, representing a paradigmatic shift toward patient-centered pharmaceutical care. Whi...
INTRODUCTION: Extended pharmacy services (EPS) encompass comprehensive healthcare interventions beyond traditional medication dispensing, representing a paradigmatic shift toward patient-centered pharmaceutical care. While well-established internationally, EPS implementation remains limited in Pakistan due to regulatory gaps and insufficient public awareness. This study evaluated current EPS provision in Pakistani community pharmacies and identified key implementation barriers. METHOD: A cross-sectional mixed-methods survey was conducted between July toOctober 2024 in Karachi, Pakistan. Data collection utilized online and in-person questionnaires comprising 12 structured items addressing EPS knowledge, perceptions, and demographic characteristics among 220 community pharmacy professionals. The Questionnaire's reliability was validated using Cronbach's alpha coefficient (α = 0.705). RESULTS: Among 220 respondents (127 pharmacists, 93 pharmacy technicians), Medication Therapy Management emerged as the most frequently offered extended service (45.5%). Primary implementation barriers included workload and time constraints (56.4%), insufficient staffing (44.1%), and medication shortages (47.3%). While 43.6% demonstrated EPS familiarity, 49.5% reported no specialized training. Most respondents perceived EPS as valuable healthcare additions (65.5%) and anticipated significant future expansion (58%). DISCUSSION: Study findings reveal Pakistan's community pharmacy practice remains predominantly dispensing-focused despite growing recognition of expanded pharmacist roles nationwide. Barriers reflect significant systemic challenges requiring coordinated multisectoral interventions across regulatory, educational, and infrastructure domains to enable sustainable EPS implementation. CONCLUSION: Extended pharmacy services present significant opportunities for Pakistani healthcare advancement but require comprehensive paradigmatic shifts through legal frameworks, enhanced professional training, and increased stakeholder awareness to successfully transform community pharmacists into fully recognized clinical healthcare providers nationwide.
Equity in Pharmacovigilance: The Role of Health Literacy in Centering Marginalized Patient Voices.
Mukherjee S
Curr Drug Saf · 2026 Mar · PMID 41830572 · Publisher ↗
Health literacy is a critical yet often overlooked determinant in pharmacovigilance, particularly in the context of socioeconomically disadvantaged populations. This article explores how low health literacy impedes the r...
Health literacy is a critical yet often overlooked determinant in pharmacovigilance, particularly in the context of socioeconomically disadvantaged populations. This article explores how low health literacy impedes the recognition and reporting of adverse drug reactions (ADRs), contributing to systemic underreporting and inequity in drug safety monitoring. Despite global advances in pharmacovigilance infrastructure, marginalized groups, such as rural communities, indigenous populations, and low-income patients, remain underrepresented in safety databases due to barriers in accessing, understanding, and acting upon medication-related information. Cultural misconceptions, linguistic challenges, limited digital access, and distrust in health systems further exacerbate this exclusion. The article advocates for an equity-based approach to pharmacovigilance that prioritizes tailored communication strategies, community engagement, and participatory design of ADR tools. It highlights the role of community health workers, culturally appropriate education, and inclusive digital platforms in bridging the literacy gap. Policymakers are urged to integrate health literacy and equity into pharmacovigilance frameworks, invest in localized interventions, and support research that measures the impact of such efforts. Ultimately, enhancing health literacy is not merely a public health goal but a moral imperative, necessary to empower patient voices, improve drug safety outcomes, and build a truly inclusive pharmacovigilance ecosystem that leaves no one behind.
Enhancing Type 2 Diabetes Treatment Through C-Peptide Assessment.
Al Rashid S, Ke B, Balasubramanian R … +1 more , Pakkir Maideen NM
Curr Drug Saf · 2026 Mar · PMID 41830571 · Publisher ↗
Abstract loading — click title to view on PubMed.
Preface.
Siniscalchi A
Curr Drug Saf · 2026 Mar · PMID 41830570 · Publisher ↗
Abstract loading — click title to view on PubMed.
Effectiveness and Safety of Roflumilast in the Treatment of Psoriasis: A Systematic Review and Meta-Analysis..
Aleid AM, Mohammed Alshreef S, Tariq Alrubaiaan M … +7 more , Hamoud Alrowais S, Khalid Alghamdi M, Saleh AlGhamdi S, Mohammed Alali L, Yasir Nukaly H, A Alghamdi M, Al Dhafiri M
Curr Drug Saf · 2026 Feb · PMID 41691689 · Publisher ↗
BACKGROUND: Psoriasis, a chronic autoimmune condition, can severely impact patients' well-being. It is characterized by erythema, thickening, and scaling of the skin. Plaque psoriasis, the most prevalent type, affects 80...
BACKGROUND: Psoriasis, a chronic autoimmune condition, can severely impact patients' well-being. It is characterized by erythema, thickening, and scaling of the skin. Plaque psoriasis, the most prevalent type, affects 80%-90% of psoriasis patients, ranging from localized to severe cases. Although corticosteroids are commonly used to treat psoriasis, prolonged use poses risks. Therefore, alternative therapies are needed. Roflumilast, a potent phosphodiesterase 4 inhibitor, is currently being considered as a treatment for plaque psoriasis. METHODS: We searched four electronic databases (Cochrane Central Register of Controlled Trials, PubMed, Scopus, and Web of Science) up to March 2024 for relevant articles evaluating the efficacy and tolerability of roflumilast in the management of psoriasis. The quality of evidence from trials was assessed using the Cochrane Risk of Bias tool (RoB1). Data from the included studies were extracted into a standardized online sheet and analyzed using RevMan 5.4. RESULTS: Roflumilast significantly increased the proportion of patients achieving an Investigator's Global Assessment score of 0 or 1 and a 2-point improvement score at both weeks 4 and 8 compared to placebo (RR = 3.48, 95% CI [2.04 to 5.92], P < 0.00001, and RR = 4.02, 95% CI [3.17 to 5.11], P < 0.00001, respectively). The pooled studies demonstrated homogeneity at both weeks 4 (P = 0.17, I² = 38%) and 8 (P = 0.38, I² = 5%). Regarding the results of the Psoriasis Area and Severity Index, 75% favored roflumilast over placebo (RR = 2.72, 95% CI [1.18 to 6.28], P < 0.00001, and RR = 3.41, 95% CI [2.19 to 5.32], P < 0.00001, at weeks 4 and 8, respectively). Subgroup analysis addressed the observed heterogeneity in the results. CONCLUSION: This meta-analysis represents the first investigation into the efficacy and safety of roflumilast for treating psoriasis. Results suggest that roflumilast is both effective and well-tolerated in managing psoriasis. However, additional robust clinical trials are needed to validate these observations..
In vivo Tissue Reaction Assessment of a Novel Polycaprolacton-based Endodontic Sealer in Rat Model.
Attari K, Janani M, Shahi S … +3 more , Aghbali A, Mesgari-Abbasi M, Dizaj SM
Curr Drug Saf · 2026 Jan · PMID 41582377 · Publisher ↗
INTRODUCTION: One of the most important materials needed for root canal therapy is a sealer. The aim of this study was to assess the tissue reaction of a new polycaprolactone-based root canal sealer in a rat model. METHO...
INTRODUCTION: One of the most important materials needed for root canal therapy is a sealer. The aim of this study was to assess the tissue reaction of a new polycaprolactone-based root canal sealer in a rat model. METHODS: Eighty adult male rats were randomly divided into 5 groups (n=16, for assessment at 3, 7, 15, 30, and 60 days' intervals). The rats were anesthetized with Ketamine and Xylazine. Surgical anesthesia lasted thirty minutes. After shaving their back hair and cleaning the spot with 5% iodine, two grooves with a length of 1 cm were created with a scalpel no. 15 Thus, one of the tested materials was randomly inserted into each of the incisions, and an empty polyethylene angioket tube with a length of 8 mm and an internal diameter of 1.1 mm was inserted into one of the incision sites as a control. After the 3, 7, 15, 30, and 60 day intervals, the rats were anesthetized again. The rats were sacrificed by overdosing on an anesthetic drug injection (barbiturate or ether). The samples were kept in 10% formalin and then sent for slide preparation. After preparing the paraffin blocks, longitudinal sections were prepared along the axis of the tubes with a thickness of 6 μm, passing through the studied material. Four sections were prepared from each block, passing longitudinally through the largest diameter of the tube. RESULTS: The results showed that there was no significant difference between the case and control groups in the degree of inflammation and the cell count (lymphocytes, macrophages, mast cells, plasma cells, neutrophils, eosinophils) in the study groups during the two-month evaluation period (P-value < 0.05). DISCUSSION: These results support its potential for clinical application, although further studies are needed to confirm safety and efficacy in human treatments. CONCLUSION: The studied new sealer was biocompatible in the animal rat model.
Fatigue Associated with Trastuzumab Deruxtecan in Solid Tumors: A Meta-Analysis and Pharmacovigilance Signal Detection Study.
Ye Y, Tang Y, Li Y … +4 more , Zhang C, Tao X, Ma Q, Zhao J
Curr Drug Saf · 2026 Jan · PMID 41503896 · Publisher ↗
INTRODUCTION: With the increasing use of trastuzumab deruxtecan (T-DXd) in the treatment of solid tumors, fatigue has emerged as a clinically significant toxicity. We aimed to quantify the risk and incidence of T-DXd-ass...
INTRODUCTION: With the increasing use of trastuzumab deruxtecan (T-DXd) in the treatment of solid tumors, fatigue has emerged as a clinically significant toxicity. We aimed to quantify the risk and incidence of T-DXd-associated fatigue using randomized evidence and single-arm data, and to corroborate these findings with the evidence from pharmacovigilance databases. METHODS: We searched major databases and oncology meetings up to January 29th, 2025, for randomized controlled trials (RCTs) and single-arm studies in adults receiving T-DXd. Odds ratios, incidences, and 95% confidence intervals (CIs) were synthesized using Peto fixed- or random- effects models, according to the level of heterogeneity. Disproportionality was assessed using reporting odds ratios (RORs) from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) and the Japanese Adverse Drug Event Report (JADER). Additionally, time-to-onset data were analyzed using Weibull modeling. RESULTS: Five RCTs (2,713 patients) and nine single-arm studies (1,096 patients) met the inclusion criteria. T-DXd increased fatigue risk (OR 1.51; 95% CI 1.28-1.78; I²=12%) as compared to the control. Pooled fatigue incidence in single-arm studies was 49% (95% CI 33%-65%; I²=94.9%). Fatigue was more frequent in breast cancer than in gastrointestinal tumors. Disproportionality signals were consistent (FAERS ROR 2.15, 95% CI 1.97-2.35; JADER ROR 3.33, 95% CI 1.38-8.03). The median onset was 33.5 days, with an early-failure pattern. DISCUSSION: Fatigue associated with T-DXd is common, appears early, and is clinically significant. Heterogeneity and limitations of spontaneous reports (e.g., under-reporting and confounding) reduce the certainty of findings and underscore the need for standardized assessment and mitigation strategies. CONCLUSION: T-DXd is associated with substantially increased fatigue risk and high incidence across solid tumors. Early detection, proactive management, and routine monitoring of patientreported outcomes are recommended to support treatment adherence and quality of life.
Myocardial Infarction, Pulmonary Embolism, and Deep Vein Thrombosis Following Testosterone Cypionate Use: A Pharmacovigilance Study.
Kandukuru A, Gupta D, Sharma P … +4 more , Kandukuru A, Nkembo A, Sutariya V, Gupta SV
Curr Drug Saf · 2026 Jan · PMID 41503895 · Publisher ↗
INTRODUCTION: Testosterone Cypionate (TC) is a widely prescribed anabolic steroid for male hypogonadism and gender-affirming hormone therapy. While therapeutically beneficial, concerns have emerged regarding its potentia...
INTRODUCTION: Testosterone Cypionate (TC) is a widely prescribed anabolic steroid for male hypogonadism and gender-affirming hormone therapy. While therapeutically beneficial, concerns have emerged regarding its potential to increase the risk of serious cardiovascular adverse events, including Pulmonary Embolism (PE), Deep Vein Thrombosis (DVT), and Myocardial Infarction (MI). This study investigates the disproportionality, severity, and stratified risk of TC-related cardiovascular events using real-world pharmacovigilance data. MATERIAL AND METHODS: A retrospective analysis was conducted using the FDA Adverse Event Reporting System (FAERS). Disproportionality was evaluated using Reporting Odds Ratios (ROR) and 95% Confidence Intervals (CI) for PE, DVT, and MI associated with TC. Event severity, temporal trends, polypharmacy levels, and demographic characteristics were also assessed. Stratified analyses and comparison with alternative testosterone formulations (e.g., AndroGel) were included. RESULTS: The RORs for PE (0.039; 95% CI: 0.036-0.043) and DVT (0.133; 95% CI: 0.122- 0.145) were below 1, indicating no disproportionality. Myocardial infarction had an ROR of 0.83 (95% CI: 0.71-0.97), also below the disproportional threshold. While patients with five or more concomitant medications (polypharmacy) showed numerically higher rates of hospitalization and death, chi-square tests revealed no statistically significant associations between polypharmacy and severity for MI (p = 0.627), PE (p = 0.773), or DVT (p = 0.763). Older age groups and common co-reported cardiovascular medications (e.g., aspirin, lisinopril) were prominent across serious cases. Compared to AndroGel, TC was associated with more frequent and severe MI outcomes. DISCUSSION: Although no disproportionality signal was detected for PE, DVT, or MI, the severity of outcomes in older individuals and those with multiple medications warrants vigilant prescribing practices. Though polypharmacy was associated with higher raw frequencies of adverse outcomes, statistical testing did not confirm a significant relationship. These findings emphasize the importance of individualized cardiovascular risk assessment in TC users, particularly in older and complex patients receiving testosterone therapy. CONCLUSIONS: Based on the current FAERS data, testosterone cypionate does not appear to increase the risk of major cardiovascular events more than expected. Still, serious outcomes can and do happen, especially in patients with more complex medical histories. These results highlight the importance of evaluating each patient's individual risk and show why post-marketing surveillance remains such an important tool for tracking drug safety in real-world clinical settings.
Severe Orolingual and Laryngeal Angioedema after Thrombolysis with Alteplase: Angiotensin II Receptor Blockers Should Not Be Underestimated.
González-Bravo L, Barbarroja-Escudero J, Laiseca-Antón A … +4 more , Álvarez-Mon M, Matas-Domínguez T, Monjo-Paz J, Sánchez-González MJ
Curr Drug Saf · 2026 Jan · PMID 41487006 · Publisher ↗
INTRODUCTION: Alteplase is a recombinant tissue plasminogen activator (rt-PA), used for intravenous thrombolysis in ischaemic strokes. Orolingual angioedema is a rare but potentially lifethreatening complication of altep...
INTRODUCTION: Alteplase is a recombinant tissue plasminogen activator (rt-PA), used for intravenous thrombolysis in ischaemic strokes. Orolingual angioedema is a rare but potentially lifethreatening complication of alteplase. Concomitant treatment with angiotensin-converting enzyme (ACE) inhibitors has been identified as a primary risk factor. Angiotensin II receptor blockers (ARBs) have been rarely related to angioedema. CASE PRESENTATION: A 72-year-old woman with a personal history of type 1 diabetes mellitus, dyslipidemia, stage 3 CKD, and arterial hypertension, in treatment with valsartan/amlodipine, atorvastatin, acetylsalicylic acid, and metformin, visited the emergency room with a diagnosis of an ischemic stroke, affecting the right middle cerebral artery territory. Intravenous alteplase (Actilyse™) was administered for thrombolysis. Twenty minutes later, the patient developed progressive lingual angioedema. She was initially treated with methylprednisolone, hydrocortisone, and intramuscular adrenaline. Her angioedema worsened, leading to an acute hypoxemic respiratory failure. A C1 esterase inhibitor (Berinert™) was administered with no improvement. Sedation and orotracheal intubation were finally necessary. No other symptoms were associated. Due to the suspicion of an interaction between alteplase and valsartan, the ARB was discontinued. No history of previous episodes of angioedema was mentioned. After 3 days, extubation failed due to respiratory distress and severe stridor, probably secondary to laryngeal edema. Successful extubation was achieved 7 days later, and the patient was discharged from the ICU after 9 days of admission. She was later referred, and an allergy workup was carried out. A blood analysis with a basal tryptase, an ACE, a total immunoglobulin E (IgE) profile, and complement proteins (C3, C4, C1q, C1 inhibitor) showed normal serum levels. Skin prick and intradermal tests with alteplase were performed, which showed negative results. The increased production of bradykinin due to alteplase and the decreased degradation of bradykinin due to ACE inhibition explained the development of angioedema. ARBs, such as valsartan, have a different pathway. They directly block the angiotensin II receptors (AT1 receptors), preventing angiotensin II (ATII) from exerting its vasoconstrictive effect. By blocking the effect of ATII, the negative feedback that normally regulates bradykinin is deactivated, potentially leading to higher concentrations of bradykinin. The main suspicion in our patient was a solitary rt-PA-induced bradykininmediated angioedema, secondary to an increase of bradykinin promoted by alteplase and likely amplified by valsartan. CONCLUSION: We have presented the case of a patient with severe and life-threatening nonimmunologic angioedema secondary to a combination of IV alteplase and valsartan. We emphasize the importance of being aware of this potentially severe complication in patients with ischaemic stroke treated with an rt-PA and in patients on treatment with ACEi and ARB. Alteplase and tenecteplase are recombinant tPA, with a potential risk of producing angioedema. There are no solid treatment recommendations for angioedema caused by rt-PA. Still, an early treatment with icatibant seems to be a consistent option in a bradykinin-mediated angioedema independent of the pathway responsible for bradykinin formation. Specific and revised protocols to manage this solitary angioedema based on severity are crucial and urgent. Finding an alternative IV thrombolytic treatment to improve the patients' safety should become an objective of research.
A Meta-Analysis of Efficacy and Safety of Penehyclidine for Postoperative Nausea and Vomiting.
Aleid AM, Almulhim MY, Al Sahlawi M … +3 more , Al Hussaini HA, Binkhunaysir RT, A Albekery M
Curr Drug Saf · 2025 Nov · PMID 41235572 · Publisher ↗
<p>Introduction: Postoperative nausea and vomiting (PONV) remain among the most frequent and distressing complications following surgery, often hindering patient recovery and comfort. Penehyclidine, an anticholinergic ag...
<p>Introduction: Postoperative nausea and vomiting (PONV) remain among the most frequent and distressing complications following surgery, often hindering patient recovery and comfort. Penehyclidine, an anticholinergic agent, has been explored as a potential treatment for PONV, yet its safety and efficacy are still under investigation. This systematic review and metaanalysis aim to synthesize current evidence on the effectiveness and safety of penehyclidine in preventing and managing PONV. </p><p> Methods: A comprehensive search was performed across several major databases, including PubMed, Scopus, Web of Science, and the Cochrane Library, to identify randomized controlled trials evaluating penehyclidine's efficacy in PONV management. Relevant data were extracted from eligible studies, and outcomes of interest were analyzed. A meta-analysis using a randomeffects model was conducted with RevMan software.</p><p> Results: Meta-analysis revealed that penehyclidine significantly reduced the incidence of PONV at both 24 hours (RR = 0.61, 95% CI [0.48-0.82]; p = 0.001) and 48 hours postoperatively (RR = 0.69, 95% CI [0.55-0.86]; p = 0.0009). It also significantly lowered the requirement for rescue antiemetics (RR = 0.34, 95% CI [0.19-0.61]; p = 0.0003). Additionally, patients receiving penehyclidine experienced a greater likelihood of complete symptom relief (RR = 1.37, 95% CI [1.10-1.72]; p = 0.005) and a reduced incidence of severe PONV (RR = 0.36, 95% CI [0.22- 0.60]; p < 0.0001). However, there were no significant differences observed in postoperative analgesic use (RR = 0.99, 95% CI [0.71-1.36]; p = 0.93) or length of stay in the post-anesthesia care unit (PACU) (MD = 0.14 minutes, 95% CI [-0.95, 1.23]; p = 0.81). Notably, penehyclidine was associated with an increased risk of dry mouth (RR = 2.68, 95% CI [2.10-3.43]; p < 0.00001), although other adverse effects-including headache, dizziness, fever, and urinary retention- showed no significant differences between groups.</p><p> Conclusion: Penehyclidine demonstrates significant benefits in reducing both the incidence and severity of PONV, along with minimizing the need for additional antiemetic therapy. Its antiemetic effect extends up to 48 hours postoperatively, although this benefit is tempered by a higher likelihood of dry mouth. Importantly, its use does not influence postoperative analgesic consumption or PACU stay duration, supporting its specific utility in PONV management with a manageable safety profile.</p>.
Possible Liposomal Amphotericin B-Triggered Intracerebral Hemorrhage in Kala-Azar with Hemophagocytic Lymphohistiocytosis: A Case Study.
Sahu SN, Gupta AK, Panda PK … +1 more , Singh S
Curr Drug Saf · 2025 Oct · PMID 41116270 · Publisher ↗
<p> Introduction: Liposomal amphotericin B is the treatment of choice for visceral leishmaniasis (VL), but its potential adverse effects, including hematologic and neurologic complications, remain a subject of concern. H...
<p> Introduction: Liposomal amphotericin B is the treatment of choice for visceral leishmaniasis (VL), but its potential adverse effects, including hematologic and neurologic complications, remain a subject of concern. Hemophagocytic lymphohistiocytosis (HLH) is a rare but severe hyperinflammatory syndrome that can occur in VL, and the development of intracerebral hemorrhage (ICH) during treatment adds a critical dimension to patient management. While ICH is an uncommon complication, its possible association with liposomal amphotericin B warrants further exploration. </p><p> Case Study: This report discusses a middle-aged man who presented with a 4-month history of recurrent fever. He also reported progressive breathlessness, a sensation of heaviness in the left abdomen, and pedal edema over the past 4 weeks. Additionally, he experienced black discoloration of urine and stool for 2 weeks. Physical examination revealed massive splenomegaly, melena, hematuria, and pancytopenia. Bone marrow aspiration confirmed hemophagocytosis, and the recombinant kinesin antigen-39 (rk39) test for VL was positive. An H-score of 234 indicated a 98-99% probability of HLH. The patient was initiated on treatment with a single dose of liposomal amphotericin B. However, on the fourth day of therapy, he developed a sudden onset of headache followed by altered sensorium. Neuroimaging revealed ICH with surrounding edema and intraventricular extension, causing a significant mass effect. Given the temporal association with treatment initiation, liposomal amphotericin B-induced ICH was considered a potential etiology. He was managed conservatively with three units of single-donor platelets and showed gradual neurological improvement without further invasive intervention. He was eventually discharged in a hemodynamically stable condition. </p><p> Conclusion: This case describes the potential risk of ICH as an adverse or trigger effect of liposomal amphotericin B in the setting of VL and HLH. Clinicians should remain vigilant for neurological complications during treatment, emphasizing the importance of close monitoring and individualized therapeutic decisions to optimize patient outcomes.
Ecchymosis Induced by Sertraline: A Case Report of a Rare Adverse Reaction.
Mahjoubi YS, Hamza I, Charfi O … +4 more , Zgolli F, Kastalli S, Aouinti I, El Aidli S
Curr Drug Saf · 2025 Oct · PMID 41114488 · Publisher ↗
INTRODUCTION: Sertraline, an SSRI, is widely prescribed for depression and other psychiatric disorders. Although generally well-tolerated, SSRIs can rarely cause bleeding complications due to their effect on platelet agg...
INTRODUCTION: Sertraline, an SSRI, is widely prescribed for depression and other psychiatric disorders. Although generally well-tolerated, SSRIs can rarely cause bleeding complications due to their effect on platelet aggregation. This case highlights a rare but clinically significant presentation of sertraline-induced ecchymosis in the absence of predisposing factors, contributing to the limited literature on SSRI-associated bleeding events. CASE PRESENTATION: A 34-year-old woman presented with large ecchymotic lesions on both arms three weeks after initiating sertraline therapy. She had no history of trauma, bleeding disorders, or concurrent medications. Laboratory evaluations, including coagulation studies and platelet count, were within normal limits. Symptoms resolved after discontinuing sertraline. Causality assessment using the Naranjo adverse drug reaction scale suggested a probable link between sertraline and ecchymosis. CONCLUSION: This case underscores the importance of recognizing sertraline as a potential cause of unexplained bruising. Clinicians should maintain a high index of suspicion for rare SSRIinduced bleeding events to ensure timely diagnosis and management.
Evaluation of Hospital Antibiotic Consumption during the COVID-19 Pandemic.
Lazarova B, Eftimova B, Crcarevska MS … +3 more , Tashkov T, Miceva D, Naumovska Z
Curr Drug Saf · 2025 Sep · PMID 41029017 · Publisher ↗
INTRODUCTION: Antimicrobial resistance (AMR) is a pressing global health issue exacerbated by the overuse of antibiotics during the COVID-19 pandemic. Despite WHO guidelines against antibiotics for mild-to-moderate COVID...
INTRODUCTION: Antimicrobial resistance (AMR) is a pressing global health issue exacerbated by the overuse of antibiotics during the COVID-19 pandemic. Despite WHO guidelines against antibiotics for mild-to-moderate COVID-19 cases without bacterial co-infection, significant misuse has been reported globally. This study aimed to evaluate antibiotic consumption during the COVID-19 pandemic at a hospital in North Macedonia and to analyze adherence to WHO guidelines, with a focus on antimicrobial stewardship, using the ATC and WHO AWaRe classification systems. OBJECTIVE: To analyze antibiotic utilization trends from January 2020 to December 2021 and assess adherence to WHO guidelines, focusing on the potential impact on AMR. METHOD: This retrospective observational study measured antibiotic consumption in defined daily doses (DDD) per 100 occupied bed-days (DDD/100 OBD) using ATC and WHO AWaRe classifications. Data were obtained only from ICU inpatients treated at the Clinical Hospital in Shtip, North Macedonia. Trends in annual consumption were analyzed, including rate-of-change calculations for individual antibiotics between 2020 and 2021. RESULT: Total antibiotic consumption decreased from 2902.6 DDD/100 OBD in 2020 to 2286.5 DDD/100 OBD in 2021. A third-generation cephalosporin, ceftriaxone, was the most consumed antibiotic, accounting for 57.62% of total consumption in 2020 and 48.55% in 2021. Tetracycline use slightly increased from 13.88% in 2020 to 15.83% in 2021. Fluoroquinolone use decreased significantly from 15.22% in 2020 to 6.5% in 2021. Carbapenem consumption rose sharply from 1.7% in 2020 to 14.37% in 2021, while azithromycin use declined threefold. Antibiotics in the Access group accounted for less than 20% of total usage, while those in the Watch group predominated. DISCUSSION: The study highlights a continued reliance on broad-spectrum antibiotics during the pandemic, diverging from WHO recommendations emphasizing Access to antibiotics. These trends suggest inadequate implementation of antimicrobial stewardship practices and raise concerns about their long-term impact on AMR. Limitations include the retrospective, single-center design, which may limit the generalizability of the findings. CONCLUSION: The findings underscore the high dependency on Watch category antibiotics and a limited focus on Access antibiotics, contrary to WHO recommendations. This highlights the urgent need for robust antimicrobial stewardship programs to control inappropriate antibiotic use and combat AMR.
Clopidogrel-Induced Liver Injury: Clinical Features, Diagnostic Challenges, and Recovery Time - A Systematic Review of Current Reported Cases.
Suenghataiphorn T, Tribuddharat N, Danpanichkul P … +1 more , Kulthamrongsri N
Curr Drug Saf · 2025 Sep · PMID 40947721 · Publisher ↗
INTRODUCTION: Clopidogrel is a widely used agent in the management of cardiovascular disease. However, there have been reports of liver injury associated with its use, some of which have resulted in death. The atypical p...
INTRODUCTION: Clopidogrel is a widely used agent in the management of cardiovascular disease. However, there have been reports of liver injury associated with its use, some of which have resulted in death. The atypical presentation of this liver injury has often led to delayed diagnosis and inappropriate treatment. We conducted a systematic review of reported cases to summarize the clinical characteristics, diagnostic approaches, and recovery durations associated with clopidogrel-induced liver injury. METHOD: Electronic databases, including MEDLINE, OVID, and EMBASE, were used to identify eligible studies from inception to December 2024. Eligible cases were required to have a clear diagnosis of clopidogrel-induced liver injury. Descriptive analysis and Kaplan-Meier analysis were used to explore the clinical features and survival durations. RESULTS: Our systematic review included 29 eligible studies, comprising 29 cases of hepatic abscess with a mean age of 67 years (58% male). Patients presented with abdominal pain in only 24% of cases, fever in 17%, but jaundice in 55%. The median recovery time was 25 days after the final diagnosis. A hepatocellular pattern was reported in 37% of cases. Diagnostic criteria were proposed and summarized based on these findings. CONCLUSION: Clinicians should be aware of clopidogrel-induced liver injury, as patients can present with a wide range of symptoms. Implementing our proposed diagnostic criteria is recommended to facilitate prompt diagnosis and treatment of clopidogrel-induced liver injury.
Global Analysis of Regulatory Frameworks and Drug Safety Standards in the Drug Approval Process.
Gomase VS, Sharma R, Dhamane SP
Curr Drug Saf · 2025 Sep · PMID 40916422 · Publisher ↗
The drug approval and review process plays a crucial role in the pharmaceutical industry, aiming to ensure that newly marketed drugs are safe, effective, and of high quality. Regulatory authorities overseeing this proces...
The drug approval and review process plays a crucial role in the pharmaceutical industry, aiming to ensure that newly marketed drugs are safe, effective, and of high quality. Regulatory authorities overseeing this process, tailored to geographically distinct needs, include the U.S. FDA, EMA, Japan's Pharmaceuticals and Medical Devices Agency (PMDA), China's National Medical Products Administration (NMPA), and India's Central Drugs Standard Control Organization (CDSCO). This analysis offers insight into the various drug approval processes employed by these authorities and examines the International Council for Harmonisation's ongoing efforts to establish a global consensus on drug regulation standards. It also compares regulatory pathways and highlights current harmonization initiatives. The focus is on analyzing operational aspects of drug regulation and identifying challenges arising from these regulations. The ultimate goal is to present a clear understanding of the intricacies and dynamics of the global drug approval process. Regulating the drug approval process is essential to ensure that new drugs are safe for public consumption, as the introduction of a new drug often faces numerous hurdles beyond safety and efficacy. The challenges highlighted include variations in regulations between authorities, the complexity of modern therapeutics, and the balance between safety and speed. This paper provides an overview of innovations in drug development, their impact on regulatory pathways, ongoing harmonization efforts, and potential obstacles that may arise during the regulatory process.
Cisplatin-Based Combinations-Associated Vasculopathy - A Disproportionality Analysis of Real-World Pharmacovigilance Data.
Pandya KK, Mann C, Fang W … +1 more , Patel B
Curr Drug Saf · 2025 Aug · PMID 40798964 · Publisher ↗
INTRODUCTION: Cisplatin, a platinum-based antineoplastic agent belonging to the alkylating class, is one of the most widely used chemotherapeutic agents in the treatment of solid tumors and hematologic malignancies. Cisp...
INTRODUCTION: Cisplatin, a platinum-based antineoplastic agent belonging to the alkylating class, is one of the most widely used chemotherapeutic agents in the treatment of solid tumors and hematologic malignancies. Cisplatin works by forming covalent bonds in DNA, resulting in cell cycle arrest, inadequate repair, and ultimately, apoptotic or non-apoptotic cell death. Despite its efficacy, cisplatin is known to be highly toxic, showing nephrological, Gastrointestinal (GI), and hepatotoxicity, but there is limited data on its association with adverse vascular events. Hence, we aimed to investigate the potential risk of drug-related adverse vascular events associated with four cisplatin-based combination therapies using the FDA Adverse Events Reporting System (FAERS). METHODS: We used the FDA Adverse Events Reporting System (FAERS) database to look for reported Adverse Events (AEs) for cisplatin-based combinations. In the current study, a case/non-case disproportionality analysis has been performed using the Reporting Odds Ratio (ROR) to investigate whether there is a signal for a potentially increased risk of drug-related vascular AE using the 2016-2020 FAERS datasets. To look for all vascular AEs, we included peripheral vascular events, cerebrovascular events, coronary artery-related events, venothromboembolic events, and other arterial events. "Cases" were defined as patients treated with cisplatin and any one of etoposide, gemcitabine, paclitaxel or docetaxel, and 5-fluorouracil or capecitabine, and have reported a composite event. Hence, cases were divided into 4 groups. Reporting Odds Ratio (ROR) and Information Component (IC) were derived to look for signals for these AEs being significant when compared to non-cases. All data processing and statistical analyses were performed using R 4.2.1. RESULTS: Between 2016 and 2020, 23,513 AEs were reported for patients who used cisplatinbased combinations, and 6,952,691 AEs in patients who did not. Baseline characteristics, including age, sex, and geographic distribution, were also reported. Looking at ROR and IC, all 4 groups showed statistically significant vasculopathies reported for cisplatin-based combinations, except for cisplatin and paclitaxel/docetaxel where there was a trend in ROR, but it did not reach statistical significance. It also gave the least signal for associated vasculopathy, while cisplatin and gemcitabine gave the highest signal with both ROR and IC for associated vasculopathy. CONCLUSION: Overall, these increased vasculopathies related to the use of cisplatin-based combinations can be related to the increased pro-thrombotic state in these patients. The results of this study highlight the need for caution when using cisplatin-based chemotherapy and the importance of monitoring patients for thrombotic events and other vasculopathies. Patient-specific factors, such as the type and stage of cancer, should be considered when determining the best treatment option and managing the risk of vascular complications.
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