Common Adverse Drug Reactions Research Articles

Usefulness of Mirogabalin in Central Neuropathic Pain After Stroke: Post Hoc Analysis of a Phase3 Study by Stroke Type and Location.

Central post-stroke pain (CPSP) is a common type of central neuropathic pain (CNeP) that can occur following the onset of stroke. The oral gabapentinoid mirogabalin besylate (mirogabalin) is a selective α2δ ligand that is effective for the treatment of CNeP, including CPSP. However, it is unknown whether the analgesic effect of mirogabalin on CPSP varies in patients with different background factors. This was a post hoc subgroup analysis of a multinational, open-label, long-term phase3 study of mirogabalin for the treatment of CNeP conducted between March 2019 and December 2020. Data from patients with CPSP were stratified by type of stroke (ischemic or hemorrhagic), stroke location (thalamus, putamen, brainstem, or other), presence/absence of motor weakness, median time since stroke (≥ 59 or < 59months), and median duration of CPSP (≥ 55.5 or < 55.5months). Efficacy was assessed with the short-form McGill Pain Questionnaire (SF-MPQ), and treatment-emergent adverse events (TEAEs) and adverse drug reactions (ADRs) were recorded. This subanalysis included all 94 patients with CPSP from the phase3 study; all were Japanese, and the mean age was 65.3years. The least squares mean change [95% confidence interval] in SF-MPQ visual analog scale (VAS) score from baseline at week52 (last observation carried forward) was - 17.0 [- 22.1, - 11.9] mm. Among the subgroups, least squares mean changes in SF-MPQ VAS scores were not different. Most TEAEs were mild or moderate; severe TEAEs occurred in six patients (6.4%). Somnolence (25.5%), peripheral edema (13.8%), dizziness (11.7%), and weight gain (6.4%) were the most common ADRs, and the types and frequencies of ADRs were similar among subgroups. Mirogabalin was generally effective and well tolerated in patients with CPSP, regardless of background factors such as stroke type or location, presence/absence of motor weakness, time since stroke, and duration of CPSP. Trial registration number NCT03901352.

Mechanisms Underlying the Protective Effects of Obeticholic Acid-Activated FXR in Valproic Acid-Induced Hepatotoxicity via Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulations.

Valproic acid (VPA)-induced hepatotoxicity is among the most common and severe adverse drug reactions, limiting its clinical application. Recent studies have suggested that activating the farnesoid X receptor (FXR) could be a promising therapeutic approach to alleviate VPA-induced hepatotoxicity; however, related research remains limited. This study aims to comprehensively investigate the mechanisms underlying FXR activation by obeticholic acid (OCA) for the treatment of VPA-induced hepatotoxicity. Network pharmacology was performed to identify potential targets and pathways underlying the amelioration of VPA-induced hepatotoxicity by OCA. The identified pathways were validated through GEO data analysis, and the affinities between OCA and potential key targets were predicted using molecular docking as well as molecular dynamics simulations. A total of 462 targets associated with VPA-induced hepatotoxicity and 288 targets of OCA were identified, with 81 shared targets. KEGG pathway and GO enrichment analysis indicated that the effect of OCA on VPA-induced hepatotoxicity primarily involved lipid metabolism, as well as oxidative stress and inflammation. The results from GEO data analysis, molecular docking, and molecular dynamics simulations revealed a close association between bile secretion, the PPAR signaling pathway, and the treatment of VPA-induced hepatotoxicity by OCA. Our findings suggest that OCA exhibits potential therapeutic efficacy against VPAinduced hepatotoxicity through multiple targets and pathways, thereby highlighting the therapeutic potential of FXR as a target for treating VPA-induced hepatotoxicity.

Clinical guidance for cannabidiol-associated hepatotoxicity: A narrative review.

There is increasing evidence that cannabidiol (CBD) use is associated with clinically significant liver enzyme (LE) elevations and drug-induced liver injury (DILI). The proportion of LE elevations and DILI events reported in the literature meet the Council for International Organizations of Medical Sciences' (CIOMS) classification of a common adverse drug reaction. However, these potential adverse events are unknown to many clinicians and may be overlooked. The increasing use of CBD for both medical and non-medical use necessitates clear direction in the diagnosis and management of CBD-associated hepatotoxicity. To our knowledge, no such clinical guidance currently exists. For people presenting with elevated LEs, CBD use should be screened for and be considered in the differential diagnosis. This narrative review will provide clinicians with guidance in the prevention, detection, and management of CBD-related hepatotoxicity.

Adverse Drug Reactions in Children with Congenital Heart Disease: A Scoping Review.

Congenital heart disease (CHD) is one of the leading causes of death. Safe and timely medical interventions, especially in children, can prolong their survival. The drugs prescribed for children with CHD are mainly based on the outcomes of drug therapy in adults with cardiovascular diseases, and their adverse drug reactions (ADRs) might be different. Therefore, the aim of this study was to investigate ADRs in children with CHD. This was a scoping review conducted in 2023. PubMed, Web of Science, Scopus, the Cochrane Library, Ovid, ProQuest, and Google Scholar databases were searched. All studies that reported ADRs for children with CHD and were published in English by 1 November 2023 were included in this study. Finally, the results were reported using a content analysis method. A total of 87 articles were included in the study. The results showed that symptoms/signs/clinical findings, and cardiovascular disorders were the most common ADRs reported in children with CHD. The results also showed that most of the ADRs were reported for prostaglandin E1, amiodarone, prostaglandin E2, dexmedetomidine, and captopril, respectively. The review underscores the wide array of ADRs in children with CHD, particularly in antiarrhythmics, diuretics, beta-blockers, anticoagulants, and vasodilators, which affected cardiovascular, respiratory, endocrine, metabolic, genitourinary, gastrointestinal, and musculoskeletal systems. Tailored treatment is imperative, considering individual patient characteristics, especially in the vulnerable groups. Further research is essential for optimizing dosing, pharmacogenetics, and alternative therapies to enhance patient outcomes in CHD management.

Safety and effectiveness of tofogliflozin in Japanese people with type 2 diabetes: A multicenter prospective observational study in routine clinical practice.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors effectively and safely reduce fasting and postprandial hyperglycemia while promoting weight loss. However, their unique mechanism of action contributes to concerns regarding their safety. We therefore carried out a large-scale, non-commercial, investigator-initiated study on the safety and effectiveness of the SGLT2 inhibitor tofogliflozin. This multicenter, open-label, uncontrolled, prospective observational study was carried out at hospitals and clinics across Japan in participants aged ≥20 years who were SGLT2 inhibitor-naïve and had an established diagnosis of type 2 diabetes. The primary endpoint was adverse drug reactions (ADRs) of special interest. Secondary endpoints included all other ADRs and adverse events, glycated hemoglobin (HbA1c), and weight loss. The study, carried out from June 2014 through February 2020, enrolled 11,480 participants from 1,103 medical institutions; 6,967 participants completed the 104-week follow up. The most common ADRs of special interest were urinary and genital tract infections (1.53%), followed by volume depletion (1.25%). Hypoglycemia occurred in 27 participants (0.24%), adverse events in 1,054 (9.18%) and ADRs in 645 (5.62%). HbA1c decreased by 0.85% (95% confidence interval 0.82%-0.88%) and bodyweight decreased by 3.05 kg (95% confidence interval 2.94-3.17 kg). The HbA1c target was achieved by 51.70% of participants for target HbA1c <7.0%, 85.3% for <8.0% and 5.4% for <6.0% at week 104. Tofogliflozin was associated with only mild or moderate ADRs characteristic of SGLT2 inhibitors, with no unpredictable, new, serious, or high-incidence adverse events or ADRs. This independent study confirmed the safety and effectiveness of tofogliflozin in adult type 2 diabetes patients.

Efficacy and safety of levetiracetam for migraine prophylaxis in children: a systematic review and meta-analysis.

Levetiracetam (LEV), an antiepileptic drug, has been effective in adult migraine prevention but lacks extensive research in children. This study evaluates LEV's efficacy and safety for pediatric migraine prophylaxis. We reviewed randomized controlled trials (RCTs) and non-RCTs in major databases through 8 January 2024, focusing on four efficacy endpoints and adverse drug reactions (ADRs). Data synthesis involved pooled relative risks or odds ratios for dichotomous outcomes and mean differences for continuous outcomes, using fixed- or random-effects models as appropriate. Eight studies with 190 participants showed that after taking LEV, the mean headache frequency decreased 5.19 per month (MD: -5.19, 95% CI: -7.11 to -3.27, p < 0.00001) and improved headache-free rates to 28% (95% CI: 0.17-0.41). More than 83% experienced a >50% reduction in monthly headache frequency. The migraine disability score decreased by 33.51 points (MD: -33.51, 95% CI: -38.46 to -28.55, p < 0.00001). ADR incidence did not significantly differ between LEV and control groups (RR: 1.06, 95% CI: 0.39 to 2.85, p = 0.91), with an overall ADR rate of 18% (95% CI: 0.13-0.24). The most common ADR was irritability (12%), leading to treatment discontinuation in 13% of cases (95% CI: 0.05-0.30). LEV has shown good efficacy in preventing pediatric migraines. However, its safety requires further confirmation through more extensive and well-designed RCTs. Identifier PROSPERO CRD42024497643.

A multicenter, prospective, non-interventional real-world study to assess the effectiveness of mecapegfilgrastim in preventing neutropenia in patients with gastrointestinal cancer.

Mecapegfilgrastim, a long-actinggranulocyte-colony stimulating factor has been approved for reducing the incidence of infection, particularly febrile neutropenia (FN), in China. We conducted a multicenter prospective observational study to examine the safety and effectiveness of mecapegfilgrastim in preventing neutropenia in gastrointestinal patients receiving the chemotherapy, including S-1/capecitabine-based regimens or thefluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI)/fluorouracil, leucovorin, and oxaliplatin (FOLFOX)/fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFIRINOX) regimens. Five hundred and sixty-one gastrointestinal patients from 40 sites across China, between May 2019 and November 2021, were included. The administration of mecapegfilgrastim was prescribed at the discretion of local physicians. The most common adverse drug reactions (ADRs) of any grade for all patients was increased white blood cells (2.9%). Grade 3/4 ADRs were observed for anemia (0.2%), decreased white blood cells (0.2%), and decreased neutrophil count (0.2%). Among the 116 patients who received S-1/capecitabine-based chemotherapy throughout all cycles, ADRs of any grade included anemia (1.7%), myalgia (0.9%), and increased alanine aminotransferase (0.9%). No grade 3/4 ADRs were observed. In 414 cycles of patients who underwent S-1/capecitabine-based regimens, only one (0.2%) cycle experienced grade 4 neutropenia. In the FOLFIRINOX, FOLFOXIRI, and FOLFOX chemotherapy regimens, grade 4 neutropenia occurred in one (2.7%) of 37 cycles, four (4.7%) of 85 cycles, and two (1.2%) of 167 cycles, respectively. In a real-world setting, mecapegfilgrastim has proven effective in preventing severe neutropenia in gastrointestinal patients following chemotherapy. This includes commonly used moderate or high-risk FN regimens or regimens containing S1/capecitabine, all of which have demonstrated favorable efficacy and safety profiles.

A real-world data analysis of ocular adverse events linked to anti-VEGF drugs: a WHO-VigiAccess study.

Vascular endothelial growth factor (VEGF) is key to wet age-related macular degeneration (wAMD). Anti-VEGF drugs are the main treatment in clinics. This study assessed ocular adverse events (AE) from anti-VEGF drugs in VigiAccess, WHO's database, and compared adverse drug reaction (ADR) profiles of four drugs to aid personalized treatment choices for optimal benefit and safety. The design was a descriptive retrospective study. We observed four anti-VEGF drugs commonly used in the clinical treatment of wAMD, and their ADR reports came from WHO-VigiAccess. The collected data included the age group, gender, and regional data, as well as the data of disease systems and symptoms caused by ADR recorded in the annual ADR reports and reports received by the WHO. We observed the overall characteristics of the ADR reports of these drugs, then explored the distribution of 27 SOCs of these drugs. Subsequently, we compared the most common ocular ADRs of the drugs. Finally, we compared the commonalities and differences of ocular ADRs related to the drugs. Overall, 57,779 AE associated with the four anti-VEGF drugs were reported. The results showed that the number of females experiencing ADRs (67.83%) was significantly higher than males (32.17%), the age group with the highest reported incidence was over 75years old. More than half of the ADR reports came from the Americas (50.86%). The five most common types of AE were: eye disorders (43.56%), general disorders and administration site conditions (34.47%), injury poisoning and procedural complications (13.36%), infections and infestations (11.61%), nervous system disorders (9.99%). Compared with the other three inhibitors, brolucizumab had a significantly higher rate of ocular ADR reports. The most common ocular ADRs of these four anti-VEGF drugs were mostly related to visual impairment, vision blurred, and blindness. However, there is still a disparity of ADRs between different drugs. The presence of ocular AEs when using anti-VEGF drugs to treat wAMD in clinical practice should attract clinical attention. Clinicians should use these expensive drugs more rationally based on the characteristics of ADRs and develop personalized treatment plans for patients.

Efficacy and Safety of Lurasidone vs. Quetiapine XR in Acutely Psychotic Patients With Schizophrenia in Korea: A Randomized, Double-Blind, Active-Controlled Trial.

This study was performed to evaluate the efficacy and safety of lurasidone (160 mg/day) compared to quetiapine XR (QXR; 600 mg/day) in the treatment of acutely psychotic patients with schizophrenia. Patients were randomly assigned to 6 weeks of double-blind treatment with lurasidone 160 mg/day (n=105) or QXR 600 mg/day (n=105). Primary efficacy measure was the change from baseline to week 6 in Positive and Negative Syndrome Scale (PANSS) total score and Clinical Global Impressions severity (CGI-S) score. Adverse events, body measurements, and laboratory parameters were assessed. Lurasidone demonstrated non-inferiority to QXR on the PANSS total score. Adjusted mean±standard error change at week 6 on the PANSS total score was -26.42±2.02 and -27.33±2.01 in the lurasidone and QXR group, respectively. The mean difference score was -0.91 (95% confidence interval -6.35-4.53). The lurasidone group showed a greater reduction in PANSS total and negative subscale on week 1 and a greater reduction in end-point CGI-S score compared to the QXR group. Body weight, body mass index, and waist circumference in the lurasidone group were reduced, with significantly lower mean change compared to QXR. Endpoint changes in glucose, cholesterol, triglycerides, and low-density lipoprotein levels were also significantly lower. The most common adverse drug reactions with lurasidone were akathisia and nausea. Lurasidone 160 mg/day was found to be non-inferior to QXR 600 mg/day in the treatment of schizophrenia with comparable efficacy and tolerability. Adverse effects of lurasidone were generally tolerable, and beneficial effects on metabolic parameters can be expected.

Use of an estradiol transdermal spray in women with menopausal symptoms: a non-interventional study

Objective This study aimed to investigate the effectiveness, tolerability and application of estradiol metered-dose transdermal spray (EMDTS) in postmenopausal women during real-world use. Methods This was a prospective, non-interventional, multicenter, observational phase IV cohort study. The Menopause Rating Scale II (MRS II) was used to assess symptoms and clinical response. Safety was assessed by the occurrence of adverse events and adverse drug reactions (ADRs). Results A total of 451 postmenopausal women were enrolled at 52 gynecological practices across Germany; 383 patients were evaluated for effectiveness and 430 patients for safety. Mean age was 54.3 ± 7.4 years. In total, 228 patients (59.5%) received EMDTS monotherapy and 155 patients (40.5%) received EMDTS plus progestogens. Significant improvements (p < 0.0001) from baseline in symptom severity were recorded for all 11 items of the MRS II at 3, 6 and 12 months of treatment. At 12 months, 81.4% of patients reported improvement in hot flushes/sweating. At final visit, 73% of patients and 77% of physicians were ‘satisfied/very pleased’ with EMDTS. Most common ADRs were headache (n = 6), nausea (n = 4), dizziness (n = 4) and pruritus (n = 3). Conclusions EMDTS is an effective, well tolerated and easily applied hormone replacement therapy for women experiencing postmenopausal symptoms.

Gastroparesis treatment options metoclopramide and prucalopride: analysis of the FDA Adverse Event Reporting System (FAERS) database

ABSTRACT Background We aimed to examine the common adverse drug reactions (ADRs) of metoclopramide, FDA-approved for treating many gastrointestinal conditions including gastroparesis, and prucalopride, FDA-approved for treating chronic idiopathic constipation but used off-label for other gastrointestinal conditions including gastroparesis. Research design and methods The FDA Adverse Event Reporting System (FAERS) was analyzed from January 2013 to December 2023. ADR reports regarding use of only metoclopramide or prucalopride were analyzed following exclusion of reports indicating use for treatment of non-gastrointestinal conditions. Results Analysis of 1,085 reports on metoclopramide revealed tardive dyskinesia (n = 393, 36.2%) and dystonia (n = 170, 15.7%) among the most reported ADRs in addition to QTc prolongation (n = 16, 1.5%) with progression to Torsade de pointes (n = 5, 0.5%) and triggering of pheochromocytoma crisis (n = 24, 2.2%). Analysis of 865 reports on prucalopride revealed headache (n = 120, 13.9%), diarrhea (n = 116, 13.4%), and abdominal pain (n = 100, 11.6%) as the most common ADRs with 22 reports (2.5%) of dystonia with the use of prucalopride. Conclusions This FAERS database analysis shows post-marketing reports of ADRs from metoclopramide most frequently include tardive dyskinesia, dystonia, and tremor in addition to potentially fatal arrhythmias such as Torsade de pointes. Consumers of prucalopride may also be at risk of dystonia and other ADRs.

Rash caused by lurasidone in old chinese patient with bipolar disorder: case-based review

BackgroundRash is one of common adverse drug reaction and which have been reported in typical and atypical antipsychotics. Reports of lurasidone induced skin reactions are sparse. In this study, we report a case of rash caused by lurasidone.Case presentationA 63-year-old man with bipolar disorder (BD) who is treated by lurasidone. However, the patient presents a rash all over after lurasidone dose increasing from 40 mg/day to 60 mg/day. With the diagnosis of drug induced rash, lurasidone was discontinued, and the rash complete disappears within 2 weeks. In addition, all case reports about antipsychotics associated rash were reviewed by searching English and Chinese database including Pubmed, Embase, Cochrane Library, CNKI and Wanfang database. A total of 139 articles contained 172 patients were included in our study. The literature review and our case suggest that the cutaneous adverse events caused by antipsychotic drugs should not be ignored, particularly for the patient who was first use or at dose increasing of antipsychotic.ConclusionsIn conclusion, we report a case of lurasidone related rash and review rash caused by antipsychotics. Psychiatrists should be alert to the possibility of the rash caused by antipsychotics, especially the patient was first use of antipsychotics or the antipsychotic dose was increasing.

A Real-World Safety Profile in Neurological, Skin, and Sexual Disorders of Anti-Seizure Medications Using the Pharmacovigilance Database of the Korea Adverse Event Reporting System (KAERS).

(1) Background: The utilization of high-quality evidence regarding the safety of anti-seizure medications (ASMs) is constrained by the absence of standardized reporting. This study aims to examine the safety profile of ASMs using real-world data. (2) Methods: The data were collected from the Korea Adverse Event Reporting System Database (KAERS-DB) between 2012 and 2021. In total, 46,963 adverse drug reaction (ADR)-drug pairs were analyzed. (3) Results: At the system organ class level, the most frequently reported classes for sodium channel blockers (SCBs) were skin (37.9%), neurological (16.7%), and psychiatric disorders (9.7%). For non-SCBs, these were neurological (31.2%), gastrointestinal (22.0%), and psychiatric disorders (18.2%). The most common ADRs induced by SCBs were rash (17.8%), pruritus (8.2%), and dizziness (6.7%). Non-SCBs were associated with dizziness (23.7%), somnolence (13.0%), and nausea (6.3%). Rash, pruritus, and urticaria occurred, on average, two days later with SCBs compared to non-SCBs. Sexual/reproductive disorders were reported at a frequency of 0.23%. SCBs were reported as the cause more frequently than non-SCBs (59.8% vs. 40.2%, Fisher's exact test, p < 0.0001). (4) Conclusions: Based on real-world data, the safety profiles of ASMs were identified. The ADRs induced by SCBs exhibited different patterns when compared to those induced by non-SCBs.

Adverse Drug Reactions: A Retrospective Analysis from the ADR Monitoring Centre at a Tertiary Care Hospital

Background: Adverse Drug Reactions (ADRs) present significant challenges in healthcare, necessitating vigilant monitoring and analysis to enhance medication safety protocols. This retrospective study aimed to analyse ADRs reported at an Adverse Drug Reactions Monitoring Centre (AMC) to understand prevalence, patterns, and characteristics of ADRs. Methods: Retrospective data from January to December 2023 were collected from the AMC at Vaishampayan Memorial Medical College, Solapur. A total of 282 ADR reports were analysed for frequency, severity, implicated medications, patient demographics, and associated clinical factors. Causality assessment was performed using the WHO- Uppsala Monitoring Centre scale. Results: The majority of ADRs were associated with the oral route of drug administration (79.43%), and most were categorized as minor severity (68.44%) and probable causality (91.84%). Common ADR symptoms included vomiting (9.55%) and rash (9.22%). Antimicrobial agents were the most suspected drugs causing ADRs (17.38%). The study revealed discrepancies in ADR reporting patterns and highlighted the importance of pharmacovigilance in capturing and addressing ADR occurrences. Conclusion: Our study provides valuable insights into the prevalence, patterns, and characteristics of ADRs, emphasizing the need for continued surveillance and reporting to promote patient safety and improve healthcare outcomes. Strategies to improve ADR reporting and enhance medication safety protocols are warranted to optimize patient care.

Cutaneous Adverse Drug Reactions to Antidiabetic Medications and Medical Devices Used in Management of Diabetes Mellitus

Context: Approximately 537 million adults (20 - 79 years) worldwide suffer from diabetes, a number that is estimated to reach 643 million by 2030. With the rising prevalence of diabetes, pharmacological therapy has become a cornerstone for its management. The advent of newer devices and drug categories has led to a multitude of adverse drug reactions, with a significant portion being cutaneous side effects. Given that the majority of patients are on multiple other medications, such as oral hypoglycemic agents, antihypertensives, and drugs for coronary artery disease and dyslipidemia, establishing the specific cause of adverse reactions can be challenging. Since the major step in management depends on avoiding or regulating the dose of the culprit drug, it is crucial for the treating clinician to be aware of the common adverse drug reactions associated with these medications. Objective: The article aims to review the reported cutaneous adverse events of oral hypoglycemic agents, insulin, and newer devices in the management of diabetes mellitus. Evidence Acquisition: A PubMed search was conducted using the keywords 'diabetes,' 'cutaneous side effects,' 'insulin,' 'OHA,' 'sulfonylureas,' 'metformin,' and 'antidiabetic drugs.' Results: New adverse events for each category of drugs are continually being identified and reported. These adverse events range from mild rash/pruritus to severe, life-threatening allergies. Conclusions: The management of any adverse reaction includes identifying and avoiding the causative agent. However, with limited literature on the cutaneous side effects of antidiabetic therapeutics, and many being case reports, it can be difficult for clinicians to diagnose these reactions. Our article provides a concise review of the vast spectrum of cutaneous side effects that these drugs and devices can cause, along with diagnostic tests and management strategies.

CYP2C19 polymorphisms on escitalopram treatment outcome in South Indian population with major depressive disorder

Various CYP2C19-mediated metabolizer groups may arise as a result of inter-individual variability, which potentially influences the efficacy and safety of escitalopram. Hence, it is crucial to establish a comprehensive collection of information relevant to each phenotype regarding the efficacy and tolerability of therapy. This will enable psychiatrists to make optimal decisions for individual patients. The aim of the study: The aim of this study is to classify MDD patients into various CYP2C19 metabolizer groups and to determine the association between phenotype and treatment outcome. Materials and Methods: The study enrolled 119 escitalopram monotherapy-treated MDD patients aged 18–58. MADRS, HDRS-17, and CGI were used to measure efficacy at baseline, weeks 4, 8, and 12. Safety and tolerability outcomes were examined from occurring ADRs. Clinical outcomes were compared among phenotypes based on changes in HDRS-17 and CGI scores from week 4 to week 12. Results: Subjects were categorized by CYP2C19 genotype: 20 poor (PM), 64 intermediate (IM), 24 extensive (EM), and 11 ultra-rapid (UM) metabolizers. Response and remission occurred in 67.2 % and 26.8 % of the 119 subjects at the end of the 12th week of the study. The response rate in PM was much lower (21.6 %) compared to EM. There were 312 adverse drug reactions (ADRs), and 88 (73.94 %) individuals had at least one. In safety data, nervousness was the most common ADR among the four groups 66 (55.4 %), followed by decreased appetite 48 (40.3 %). There were no severe ADRs. Men had more ADRs than women. Conclusion: CYP2C19 genotyping may help personalize escitalopram medication. The study found that the reduced ability of PM to metabolize escitalopram is probably associated with the decreased efficacy and tolerance shown in PM compared to EM and IM. The relationship between metabolizer status and treatment response followed the anticipated direction. Our findings should guide future clinical studies that include pharmacokinetic assessments

Real-World Safety and Effectiveness of Letermovir in Patients Undergoing Allogenic Hematopoietic Stem Cell Transplantation: Final Results of Post-Marketing Surveillance in Japan.

Cytomegalovirus (CMV) is a common opportunistic infection after allogenic hematopoietic stem cell transplantation (allo-HSCT). Letermovir, an inhibitor of CMV DNA terminase, is approved for CMV prophylaxis in allo-HSCT patients. We report the final results of post-marketing surveillance of letermovir in Japan. The case report forms were drafted in part by the Japanese Data Center for Hematopoietic Cell Transplantation using data elements in the Transplant Registry Unified Management Program and sent to individual HSCT centers to decrease the burden of reporting. Hematopoietic stem cell transplantation patients who received letermovir between May 2018 and May 2022 were registered. Data collected included physician-assessed adverse events/adverse drug reactions and clinical effectiveness (development of CMV disease, CMV antigen status, and use of preemptive therapy). A total of 821 HSCT patients were included in the safety analyses. Adverse drug reactions occurred in 11.33% of patients, with serious adverse drug reactions in 3.05%. The five most common adverse drug reactions were nausea (1.58%), renal impairment (1.46%), and acute graft versus host disease, CMV test positive, and hepatic function abnormal (0.61% each). A total of 670 patients were eligible for effectiveness analyses. Among these patients, 16.57% and 28.66% required preemptive therapy through week 14 and week 48, respectively. In addition, relatively few patients developed CMV disease throughout the follow-up period (1.34% at week 14 and 3.85% at week 48). This final analysis of post-marketing surveillance with up to 48 weeks follow-up period in Japan provides further evidence supporting the safety profile and effectiveness of letermovir for CMV prophylaxis in patients undergoing allo-HSCT in real-world settings.

Efficacy and safety of combinations of H1 antihistamines in the treatment of urticaria: A scoping review.

The efficacy and safety of combining H1 antihistamines (AHs) for treating urticaria are currently unclear. This scoping review aims to provide a comprehensive overview of the evidence regarding the efficacy and safety of H1 AH combinations in the management of urticaria up to May 2023. The search encompassed databases such as PubMed, Web of Science, the Cochrane Central Register of Controlled Trials, and the China Biological Medicine Database. The inclusion criteria comprised randomised controlled trials (RCTs), non-randomised trials (NRTs), case reports, and case series focusing on urticaria treatment. Initially screening 12,887 studies, this review ultimately selected 109 studies involving 11,435 patients. These studies documented 43 different combination treatments across 11 types of urticaria. In comparison to monotherapy, combination therapy exhibited superior efficacy in 94 studies that reported treatment efficacy. Regarding adverse drug reactions (ADRs), 67 studies disclosed ADR incidences, with combination therapy showing lower ADR rates in 32 studies. Additionally, 7 studies reported similar ADR rates between combination therapy and monotherapy with AHs. Common ADRs included symptoms such as drowsiness, nausea, fatigue, dry mouth, dizziness, and headache, while less frequent side effects encompassed hypotension, otitis media, polyuria, rhinorrhoea, abnormal liver function, and rash. ADR rates ranged from 0% to 21% in the treatment group, and from 0.5% to 75% in the control group. Importantly, patients generally tolerated these ADRs well, with symptoms resolving upon discontinuation of treatment. The study's findings suggest that combining AHs leads to enhanced efficacy and reduced safety risks compared to monotherapy in the context of urticaria treatment. These results advocate for considering combination therapy as a viable option in clinical practice, especially for chronic urticaria cases. Nonetheless, caution is advised, and close monitoring for potential ADRs is crucial during treatment.

Why Pharmacovigilance of Non-steroidal Anti-inflammatory Drugs is Important in India?

Non-steroidal Anti-Inflammatory Drugs (NSAIDs) are among the drugs that are most regularly administered to manage inflammation and pain. Over-the-Counter (OTC) NSAIDs are widely accessible, particularly in developing countries like India. This casual approach to using NSAIDs may operate as a magnet for NSAID-related adverse drug reactions (ADRs) among patients. As patients in India are less informed about the appropriate use of NSAIDs and consumption patttern, adverse drug reactions, and the importance of reporting ADRs, the current study's objective is to promote patient safety by using pharmacovigilance as a tool to educate patients. A targeted literature methodology was utilized to gather the data pertaining to NSAIDs, their ADRs and their pharmacovigilance. Different scientific databases, such as Science Direct, PubMed, Wiley Online Library, Springer, and Google Scholar, along with authentic textbooks, were explored as reference literature. In general, NSAIDs consumption pattern depends upon the different age groups. Around 1.6 billion tablets of NSAIDs are consumed in India for ailments, such as headaches, arthritis, menstrual cramps, osteoarthritis, back pain, rheumatoid arthritis, gout, osteoporosis, tendinitis, cancer pain and chronic pain. Common ADRs of NSAIDs include nausea, vomiting, headache, gastritis, abdominal pain, and diarrhoea. Also, they can cause renal damage and cardiovascular problems if not consumed in a dose-dependent manner. However, Diclofenac and Ibuprofen have both been linked to depression and dementia. There have been reports of aplastic anaemia, agranulocytosis linked to phenylbutazone, Stevens-Johnson, and Lyell's syndrome linked to isoxicam and piroxicam, as well as the vulnerability of new-borns to Reye's syndrome after aspirin use. Lack of awareness, time constraints and unpredictability, poor training in ADRs identification, etc., are some of the reasons for the under-reporting of ADR of NSAIDs in India. In order to rationally prescribe NSAIDs, it is essential to be aware of probable ADR's and establish prescription guidelines. Prescribers' behaviour can be changed toward excellent prescribing practices by conducting routine prescription assessments dealing with NSAIDs and providing feedback. In the near future, it will be critical to strengthen ADR data management and expand the reach of pharmacovigilance programs, ADR monitoring centers, and healthcare professionals' especially pharmacists' training in rural locations.

Systematic review of drug-drug interactions of delta-9-tetrahydrocannabinol, cannabidiol, and Cannabis.

The recent exponential increase in legalized medical and recreational cannabis, development of medical cannabis programs, and production of unregulated over-the-counter products (e.g., cannabidiol (CBD) oil, and delta-8-tetrahydrocannabinol (delta-8-THC)), has the potential to create unintended health consequences. The major cannabinoids (delta-9-tetrahydrocannabinol and cannabidiol) are metabolized by the same cytochrome P450 (CYP) enzymes that metabolize most prescription medications and xenobiotics (CYP3A4, CYP2C9, CYP2C19). As a result, we predict that there will be instances of drug-drug interactions and the potential for adverse outcomes, especially for prescription medications with a narrow therapeutic index. We conducted a systematic review of all years to 2023 to identify real world reports of documented cannabinoid interactions with prescription medications. We limited our search to a set list of medications with predicted narrow therapeutic indices that may produce unintended adverse drug reactions (ADRs). Our team screened 4,600 reports and selected 151 full-text articles to assess for inclusion and exclusion criteria. Our investigation revealed 31 reports for which cannabinoids altered pharmacokinetics and/or produced adverse events. These reports involved 16 different Narrow Therapeutic Index (NTI) medications, under six drug classes, 889 individual subjects and 603 cannabis/cannabinoid users. Interactions between cannabis/cannabinoids and warfarin, valproate, tacrolimus, and sirolimus were the most widely reported and may pose the greatest risk to patients. Common ADRs included bleeding risk, altered mental status, difficulty inducing anesthesia, and gastrointestinal distress. Additionally, we identified 18 instances (58%) in which clinicians uncovered an unexpected serum level of the prescribed drug. The quality of pharmacokinetic evidence for each report was assessed using an internally developed ten-point scale. Drug-drug interactions with cannabinoids are likely amongst prescription medications that use common CYP450 systems. Our findings highlight the need for healthcare providers and patients/care-givers to openly communicate about cannabis/cannabinoid use to prevent unintended adverse events. To that end, we have developed a free online tool (www.CANN-DIR.psu.edu) to help identify potential cannabinoid drug-drug interactions with prescription medications.