Pharmazie. 2023 May 1;78(5):63-66. doi: 10.1691/ph.2023.3521.

ABSTRACT

There are case reports of mouth ulcers caused by the coronavirus disease 2019 (COVID-19) messenger ribonucleic acid (mRNA) vaccine; however, the actual number and characteristics of cases are unknown. Therefore, we examined this issue using the Japanese Adverse Drug Event Report (JADER), a large Japanese database. We calculated the reported odds ratio (ROR) of drugs that may be specifically associated with mouth ulcers and assumed that a signal was present if the lower limit of the calculated ROR's 95% confidence interval (CI) was > 1. In addition, the time to symptom onset after administration of the COVID-19 mRNA and influenza HA vaccines was investigated. We found that the JADER database contained 4,661 mouth ulcer cases between April 2004 and March 2022. The COVID-19 mRNA vaccine was the eighth most common causative drug for mouth ulcers, with 204 reported cases. The ROR was 1.6 (95% CI, 1.4-1.9) and a signal was detected. There were 172 mouthulcer cases associated with the Pfizer-BioNTech's COVID-19 mRNA vaccine, 76.2% of which were female. The outcome was no unrecovered cases with the influenza HA vaccine, whereas the COVID-19 mRNA vaccine showed unrecovered cases (Pfizer-BioNTech: 12.2%, Moderna: 11.1%). The median time-to-onset of the mouth ulcers was two days for the COVID-19 mRNA vaccine and one day for the influenza HA vaccine, indicating that mouth ulcers caused by the COVID-19 mRNA vaccine were delayed adverse events. In this study, the COVID-19 mRNA vaccine was shown to cause mouth ulcers in a Japanese population.

PMID:37189267 | DOI:10.1691/ph.2023.3521

Pharmazie. 2023 May 1;78(5):42-46. doi: 10.1691/ph.2023.2584.

ABSTRACT

Adverse drug events (ADEs) rates associated with anti-dementia acetylcholinesterase inhibitors are estimated to be 5%-20% and show a wide range of symptoms. No report has examined whether there is a difference in the anti-dementia drugs' ADEs profile. This study aimed to establish whether anti-dementia drugs' ADEs profile differed. Data was based on the Japanese Adverse Drug Event Report (JADER) database. The reporting odds ratios (RORs) was used to analyze data for ADEs from April 2004-October 2021. The target drugs were donepezil, rivastigmine, galantamine, and memantine. The top ten most frequently occurring adverse events were selected. The association between the RORs and antidementia drug ADEs was evaluated, and compared the distribution rate of expression age related to ADEs and each ADEs' timing of onset due to anti-dementia drugs. The primary outcome was RORs. Secondary outcome were expression age and time-to-onset of ADE associated with anti-dementia drugs. A total of 705,294 reports were analyzed. The adverse events incidence differed. Bradycardia, loss of consciousness, falls, and syncope incidence were significantly diverse. The Kaplan-Meier curve results for the cumulative ADEs incidence showed that donepezil had the slowest onset, while galantamine, rivastigmine, and memantine had approximately the same timing of onset.

PMID:37189266 | DOI:10.1691/ph.2023.2584

Pharmazie. 2023 May 1;78(5):56-62. doi: 10.1691/ph.2023.3509.

ABSTRACT

Overactive bladder (OAB) is a frequent chronic disorder which impairs quality of life by frequent, uncontrollable urination. Newly developed selectiveβ 3-adrenoceptor agonists (sβ 3-agonists) have the same efficacy in treating OAB but significantly fewer side effects than the traditionally used anti-muscarinics. However, safety data on these compounds are scarce. In this study, we analysed the occurrence of adverse effects in patients taking sβ 3-agonists and their characteristics using the JADER database. The most frequently reported adverse effect associated with the use of sβ 3-agonists was urinary retention [mirabegron; crude reporting odds ratios (ROR): 62.1, 95% confidence interval (CI): 52.0-73.6, P<0.001, vibegron; crude ROR: 250, 95% CI : 134-483, P<0.001]. Data from patients with urinary retention were stratified by sex. In both men and women, the rate of urinary retention was higher when using the mirabegron/anti-muscarinic drug when compared to mirabegron monotherapy; its occurrence was higher in men with a history of benign prostatic hypertrophy than in those without. Weibull analysis showed that approximately 50% of sβ 3 agonist-induced urinary retention occurred within 15 days after initiation of treatment, and then gradually decreased. Although sβ 3-agonists are useful against OAB, they may induce several side effects, especially urinary retention, which can further evolve into more severe conditions. Urinary retention occurs more frequently in patients concomitantly taking medication that either increases urethral resistance or has organic factors that block the urethra. When using sβ 3-agonists, the concomitantly used medications and underlying diseases should be thoroughly reviewed, and safety monitoring should be instituted early during the treatment.

PMID:37189265 | DOI:10.1691/ph.2023.3509

Drug Ther Bull. 2023 May 16:dtb-2022-000050. doi: 10.1136/dtb.2022.000050. Online ahead of print.

ABSTRACT

Living with multiple long-term health conditions (multimorbidity) is increasingly common in older age. The more long-term conditions that an individual has, the more medicines they are likely to take. Hospitalisation as a consequence of medication-related harm is increasing and a concerted effort is needed to reduce the burden of harm caused by medication. However, making decisions about the balance between benefit and harm for an older person with multimorbidity and polypharmacy is very complex. There are various clinical tools that can help to identify patients at higher risk of harm and numerous strategies, including medicines optimisation reviews that incorporate personalised health information, to try to reduce risk. Further education and training of the healthcare professionals is needed to equip the multidisciplinary workforce with the skills and knowledge to address these challenges. This article discusses some of the changes that can be implemented now and highlights areas that will require more research before they can be introduced, in order to help patients to get the best out of their medicines.

PMID:37193588 | DOI:10.1136/dtb.2022.000050

Curr Oncol. 2023 Apr 11;30(4):4139-4152. doi: 10.3390/curroncol30040315.

ABSTRACT

Adverse drug reactions (ADRs) are responsible for almost 5% of hospital admissions, making it necessary to implement different pharmacovigilance strategies. The additional monitoring (AM) concept has been highlighted and intended to increase the number of suspected ADRs reported, namely in medicines with limited safety data. A prospective, descriptive study of active pharmacovigilance (AP) was conducted between 2019 and 2021 in the Local Health Unit of Matosinhos (LHUM) (Porto, Portugal). A model of AP for medicines under AM, namely oral antineoplastic agents, was designed. Follow-up consultations were performed, and adverse events (AEs) data were collected. The overall response to the treatment was evaluated through the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. A total of 52 patients were included in the study, and 14 antineoplastic drugs under AM were analyzed. Of the total number of patients included, only 29 developed at least one type of toxicity. Hematological disorders were the most reported suspected ADR. However, only four patients interrupted their treatment due to toxicity. After 12 months of treatment, most patients had disease progression, which was the main reason for therapy discontinuation. This AP model played an important role in the early detection of AEs and, consequently, contributed to better management of them. Increasing the number of suspected ADR reports is crucial for drugs with limited safety data.

PMID:37185428 | PMC:PMC10137106 | DOI:10.3390/curroncol30040315

Sr Care Pharm. 2023 May 1;38(5):179-184. doi: 10.4140/TCP.n.2023.179.

ABSTRACT

Older patients are often prescribed many medications and are at higher risk for medication-related problems. Pharmacists can help to identify potentially inappropriate medication use that may precipitate adverse drug events resulting in mental status changes, falls, and hospitalization. A Pharmacist-Driven Geriatric Medication Assessment program was established by clinical pharmacists to evaluate medication use in older patients admitted to a pilot unit of an acute care hospital as part of an Age-Friendly Care initiative. This article describes the implementation of this program and the types of medication interventions pursued by the pharmacists. Pharmacist recommendation acceptance rate by the health care team was greater than 90% overall for medication reconciliation, potentially inappropriate medications, and other medication interventions.

PMID:37185144 | DOI:10.4140/TCP.n.2023.179

Zhongguo Fei Ai Za Zhi. 2023 Apr 20;26(4):257-264. doi: 10.3779/j.issn.1009-3419.2023.101.08.

ABSTRACT

BACKGROUND: Immune-related adverse events (irAEs) are commonly occurred in patients treated with immune checkpoint inhibitors. However, evidence of irAEs derived from the Chinese population is relatively lacking. The aim of this study was to investigate the incidence and outcomes of irAEs in Chinese patients with lung cancer after receiving immune checkpoint inhibitors (ICIs).

METHODS: Clinical and follow-up data from lung cancer patients who received at least one time of ICIs from January 2018 to September 2021 at Huadong Hospital, Fudan University were included. Statistical descriptions and Kaplan-Meier method were used to analyze the overall incidence of irAEs, as well as the incidence and outcomes of each type of irAEs.

RESULTS: 135 patients were included in the study. 106 patients (78.5%) presented at least one type of irAEs, and the median time to first irAEs onset was 28 d. Most irAEs occurred at early time after treatment, and most irAEs were mild-moderate and reversible. 57 patients (42.2%) died at the study cutoff. The mortality rate of severe irAEs was 12.6% (n=17), and among them 7 patients (41.2%) died of pneumonitis. The median progression-free survival (PFS) and overall survival (OS) time of the total population was 505 d (95%CI: 352-658) and 625 d (95%CI: 491-759), respectively. Patients who presented any irAEs achieved a longer PFS than those who did not (median PFS: 533 d vs 179 d, P=0.037, HR=0.57), while patients who presented skin toxicities achieved a longer OS than patients who did not (median OS: 797 d vs 469 d, P=0.006, HR=0.70).

CONCLUSIONS: In real-world settings, irAEs in lung cancer patients were commonly observed, with pneumonitis as the most common fatal irAEs. In addition, patients who presented any irAEs may tend to achieve a longer PFS.

PMID:37183640 | DOI:10.3779/j.issn.1009-3419.2023.101.08

Drug Ther Bull. 2023 May 15:dtb-2023-000025. doi: 10.1136/dtb.2023.000025. Online ahead of print.

NO ABSTRACT

PMID:37188499 | DOI:10.1136/dtb.2023.000025

Neurooncol Pract. 2023 Feb 11;10(3):291-300. doi: 10.1093/nop/npad008. eCollection 2023 Jun.

ABSTRACT

BACKGROUND: High-dose methotrexate (HDMTX) is a mainstay of primary central nervous system lymphoma (PCNSL) treatment. Transient hepatotoxicity from HDMTX has been characterized in pediatric patients but not in adults. We sought to characterize hepatotoxicity in adult PCNSL patients undergoing HDMTX treatment.

METHODS: Retrospective study of 65 PCNSL patients treated at the University of Virginia from 02/01/2002 to 04/01/2020 was performed. Hepatotoxicity was defined using National Cancer Institute Common Toxicity Criteria (CTC) for adverse events, fifth version. High-grade hepatotoxicity was defined as a bilirubin or aminotransferase CTC grade of 3 or 4. Relationships between clinical factors and hepatotoxicity were assessed with logistic regression.

RESULTS: Most patients (90.8%) had a rise of at least one aminotransferase CTC grade during HDMTX treatment. 46.2% had high-grade hepatotoxicity based on aminotransferase CTC grade. No patients developed high-grade bilirubin CTC grades during chemotherapy. Liver enzyme test values decreased to low CTC grade or normal in 93.8% of patients after the conclusion of HDMTX treatment without treatment regimen changes. Prior ALT elevation (P = .0120) was a statistically significant predictor of high-grade hepatotoxicity during treatment. Prior history of hypertension was associated with increased risk of toxic serum methotrexate levels during any cycle (P = .0036).

CONCLUSIONS: Hepatotoxicity develops in the majority of HDMTX-treated PCNSL patients. Transaminase values decreased to low or normal CTC grades in almost all patients after treatment, without modification of MTX dosage. Prior ALT elevation may predict patients' increased hepatotoxicity risk, and hypertension history may be a risk factor for delayed MTX excretion.

PMID:37188158 | PMC:PMC10180358 | DOI:10.1093/nop/npad008

Infect Dis Ther. 2023 Apr 25. doi: 10.1007/s40121-023-00794-1. Online ahead of print.

ABSTRACT

INTRODUCTION: Adintrevimab is a fully human immunoglobulin G1 extended half-life monoclonal antibody that was developed to have broad neutralization against SARS-CoV, SARS-CoV-2, and other SARS-like CoVs with pandemic potential. Here we report the safety, pharmacokinetics (PK), serum viral neutralizing antibody (sVNA) titers, and immunogenicity results of the first three cohorts evaluated in the first-in-human study of adintrevimab in healthy adults.

METHODS: This is a phase 1, randomized, placebo-controlled, single ascending-dose study of adintrevimab administered intramuscularly (IM) or intravenously (IV) to healthy adults aged ≥ 18-55 years with no current or prior SARS-CoV-2 infection. Participants were randomized 8:2 to adintrevimab or placebo in each of three dose cohorts: adintrevimab 300 mg IM (cohort 1), 500 mg IV (cohort 2), and 600 mg IM (cohort 3). Follow-up was 12 months. Blood samples were taken predose and at multiple time points postdose up to month 12 to assess sVNA, PK, and antidrug antibodies (ADAs).

RESULTS: Thirty participants received a single dose of adintrevimab (n = 24; 8 per cohort) or placebo (n = 6). All except one adintrevimab participant in cohort 1 completed the study. No participants in any treatment arm experienced a study drug-related adverse event. Across adintrevimab-treated participants, 11 (45.8%) experienced at least one TEAE. All but one TEAE were mild in severity, and all were either viral infection or respiratory symptoms. There were no serious adverse events, discontinuations due to adverse events, or deaths. Adintrevimab exhibited a linear and dose-proportional PK profile and extended serum half-life (mean 96, 89, and 100 days in cohorts 1, 2, and 3, respectively). Participants receiving adintrevimab demonstrated dose-dependent increased sVNA titers and breadth across multiple variants.

CONCLUSION: Adintrevimab at doses of 300 mg IM, 500 mg IV, and 600 mg IM was well tolerated in healthy adults. Adintrevimab demonstrated dose-proportional exposure, rapid development of neutralizing antibody titers, and an extended half-life.

PMID:37185797 | DOI:10.1007/s40121-023-00794-1

Nanomedicine (Lond). 2023 May 15. doi: 10.2217/nnm-2023-0021. Online ahead of print.

ABSTRACT

Background: The subcellular organelle-targeting strategy has attracted wide attention for a variety of reasons, including strong specificity, high accuracy, low dose administration and few side effects. It is an important and challenging task to explore the multisubcellular organelle-targeting strategy to achieve effective tumor treatment. Materials & methods: Using bovine serum albumin as a nanoreactor, BSA/Cu/NQ/IR780/DOX nanoparticles (NPs) were constructed via drug-induced protein self-assembly. Folic acid was then coupled to the surface of NPs to prepare folate receptor-targeted FA-BSA/Cu/NQ/IR780/DOX NPs. Results & conclusion: The FA-BSA/Cu/NQ/IR780/DOX NPs exhibit multifunctional properties, including multisubcellular organelle-targeting, induction of response release in the tumor microenvironment, fluorescence imaging capabilities and potential for synergistic chemotherapy and photodynamic/photothermal tumor therapy.

PMID:37183879 | DOI:10.2217/nnm-2023-0021

Br J Clin Pharmacol. 2023 May 15. doi: 10.1111/bcp.15786. Online ahead of print.

ABSTRACT

AIMS: Brepocitinib is a tyrosine kinase 2/Janus kinase 1 inhibitor being investigated for the treatment of several autoimmune diseases. This study assessed the absorption, distribution, metabolism and excretion of oral brepocitinib, and the absolute oral bioavailability (F) and fraction absorbed (Fa ) using a 14 C microtracer approach.

METHODS: This was a phase 1 open-label, non-randomised, fixed sequence, two-period, single-dose study of brepocitinib in healthy male participants. Participants received a single oral 60 mg dose of 14 C brepocitinib (~300 nCi) in Period A, then an unlabelled oral 60 mg dose followed by an intravenous (IV) 30 μg dose of 14 C labelled brepocitinib (~300 nCi) in Period B. Mass balance, pharmacokinetic parameters and safety were assessed.

RESULTS: Six participants were enrolled. Brepocitinib was absorbed rapidly following oral administration. In Period A, total recovery of the oral dose was 96.7 ± 6.3% (88.0 ± 8.0% in urine; 8.7 ± 2.1% in faeces). In Period B, a small fraction (6.0% of the oral dose) was recovered unchanged in urine. F and Fa were 74.6% (90% confidence interval: 67.3, 82.8%) and 106.9%, respectively. Brepocitinib demonstrated an acceptable safety profile and was well tolerated following oral or oral then IV administrations. No deaths, serious adverse events or discontinuations were reported.

CONCLUSION: Intestinal absorption of brepocitinib was essentially complete after oral administration, with F ~75%. Drug-related material recovery was high, with the majority excreted in urine. The major route of elimination of brepocitinib was renal excretion as metabolites, whereas urinary elimination of unchanged brepocitinib was minor. NCT: NCT03770039.

PMID:37183779 | DOI:10.1111/bcp.15786

Front Pharmacol. 2023 Apr 26;14:1158421. doi: 10.3389/fphar.2023.1158421. eCollection 2023.

ABSTRACT

Purpose: Older cancer patients are more likely to develop and die from chemotherapy-related toxicity. However, evidence on drug safety and optimal effective doses is relatively limited in this group. The aim of this study was to develop a tool to identify elderly patients vulnerable to chemotherapy toxicity. Patients and methods: Elderly cancer patients ≥60 years old who visited the oncology department of Peking Union Medical College Hospital between 2008 and 2012 were included. Each round of chemotherapy was regarded as a separate case. Clinical factors included age, gender, physical status, chemotherapy regimen and laboratory tests results were recorded. Severe (grade ≥3) chemotherapy-related toxicity of each case was captured according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. Univariate analysis was performed by chi-square statistics to determine which factors were significantly associated with severe chemotherapy toxicity. Logistic regression was used to build the predictive model. The prediction model was validated by calculating the area under the curve of receiver operating characteristic (ROC). Results: A total of 253 patients and 1,770 cases were included. The average age of the patients was 68.9 years. The incidence of grade 3-5 adverse events was 24.17%. Cancer type (non-GI cancers), BMI<20 kg/m2, KPS<90%, severe comorbidity, polychemotherapy, standard dose chemotherapy, low white blood cells count, anemia, low platelet cells count, low creatine level and hypoalbuminemia were associated with severe chemotherapy-related toxicity. We used these factors to construct a chemotherapy toxicity prediction model and the area under the ROC curve was 0.723 (95% CI, 0.687-0.759). Risk of toxicity increased with higher risk score (11.98% low, 31.51% medium, 70.83% high risk; p < 0.001). Conclusion: We constructed a predictive model of chemotherapy toxicity in elderly cancer patients based on a Chinese population. The model can be used to guide clinicians to identify vulnerable population and adjust treatment regimens accordingly.

PMID:37180715 | PMC:PMC10169599 | DOI:10.3389/fphar.2023.1158421

Ann Surg Treat Res. 2023 May;104(5):288-295. doi: 10.4174/astr.2023.104.5.288. Epub 2023 Apr 28.

ABSTRACT

PURPOSE: Venoactive drugs are widely used to improve the symptoms and signs of chronic venous disease. This study aimed to analyze the rate of adverse events after venoactive drug prescription and subsequent compliance and switching rates.

METHODS: Using the National Health Insurance Service database, individuals with at least one chronic venous disease code between January 2009 and December 2019 were identified, and 30% (2,216,780 individuals) of these were sampled. Finally, 1,551,212 patients were included, and we analyzed adverse events, compliance, and switching rates with 8 venoactive drugs, including Vitis vinifera extract, naftazone, micronized purified flavonoid fraction, Vitis vinifera leaf extract, diosmin, diobsilate calcium, bilberry fruit dried extract, and sulodexide.

RESULTS: The most commonly prescribed venoactive drug was Vitis vinifera extract (72.2%), followed by sulodexide (9.3%), and Vitis vinifera leaf dry extract (8.2%). Adverse event rates were significantly lower in the naftazone and diosmin groups (P = 0.001 and P = 0.002, respectively) and significantly higher in the Vitis vinifera leaf dry extract group (P = 0.009). Drug adherence to sulodexide was the highest throughout the study period, followed by billberry extract and dobesilate (all P < 0.001). For most drugs, the drug switching rate was low (<5.0%).

CONCLUSION: Vitis vinifera extract was the most commonly prescribed venoactive drug in Korea, and drug adherence to sulodexide was the highest among all venoactive drugs. The adverse event rates were significantly lower in the naftazone and diosmin groups.

PMID:37179697 | PMC:PMC10172027 | DOI:10.4174/astr.2023.104.5.288

Int J Mol Sci. 2023 May 3;24(9):8194. doi: 10.3390/ijms24098194.

ABSTRACT

The use of large sized materials in drug delivery raises several challenges, including in vivo stability, poor bioavailability/solubility/absorption, and issues with target-specific delivery, in addition to the side effects of the delivered drugs [...].

PMID:37175903 | PMC:PMC10179724 | DOI:10.3390/ijms24098194

Int J Mol Sci. 2023 Apr 30;24(9):8099. doi: 10.3390/ijms24098099.

ABSTRACT

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) were initially developed for the treatment of diabetes due to their antihyperglycemic activity. However, in the light of the most recent clinical studies, they are revolutionizing the approach to cardiovascular disease in patients with and without diabetes. We aimed to generate real-world data about the use of SGLT2i in patients with T2DM and coronary artery disease (CAD), focusing on their effectiveness in glycemic control, adherence, long-term efficacy, and safety outcomes. On the basis of the inclusion and exclusion criteria, 143 patients were enrolled. Patients were treated with canagliflozin (n = 33 patients; 23%), dapagliflozin (n = 52 patients, 36.4%), empagliflozin (n = 48 patients; 33.6%), or ertugliflozin (n = 10 patients; 7%) as monotherapy or in combination with other antidiabetic drugs. All patients performed a clinical visit, and their medical history, blood sampling, and anthropometric parameters were measured at discharge and at 1-year follow-up. The reduction in HbA1c % value at 12 months was significant (8.2 vs. 7.4; p < 0.001). Trends in body weight and body mass index also confirmed the positive effect of the treatment (p < 0.0001), as did the reduction in abdominal adiposity (expressed via waist circumference). At 1-year follow-up, 74.1% of patients were adherent to the treatment, and 81.1% were persistent to the treatment. A total of 27 patients (18.8%) had to discontinue treatment early due to drug intolerance caused by genitourinary infections (11.9%), the drub being permanently ineffective (HbA1c not at target or decreasing: 4.9%), or because of expressing. a desire not to continue (2%). No major drug-related adverse events (diabetic ketoacidosis, Fournier's gangrene, lower-limb amputations) occurred at follow-up, while MACE events occurred in 14 patients (9.8%). In real-world patients with T2DM and CAD, SGLT2i have been effective in long-term glycemic control and the improvement in anthropometric indices with good tolerance, high adherence, persistence to treatment, and no major adverse events at 1-year follow-up.

PMID:37175805 | DOI:10.3390/ijms24098099

Int J Mol Sci. 2023 Apr 27;24(9):7938. doi: 10.3390/ijms24097938.

ABSTRACT

Antiviral protease inhibitors are peptidomimetic molecules that block the active catalytic center of viral proteases and, thereby, prevent the cleavage of viral polyprotein precursors into maturation. They continue to be a key class of antiviral drugs that can be used either as boosters for other classes of antivirals or as major components of current regimens in therapies for the treatment of infections with human immunodeficiency virus (HIV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, sustained/lifelong treatment with the drugs or drugs combined with other substance(s) often leads to severe hepatic side effects such as lipid abnormalities, insulin resistance, and hepatotoxicity. The underlying pathogenic mechanisms are not fully known and are under continuous investigation. This review focuses on the general as well as specific molecular mechanisms of the protease inhibitor-induced hepatotoxicity involving transporter proteins, apolipoprotein B, cytochrome P450 isozymes, insulin-receptor substrate 1, Akt/PKB signaling, lipogenic factors, UDP-glucuronosyltransferase, pregnane X receptor, hepatocyte nuclear factor 4α, reactive oxygen species, inflammatory cytokines, off-target proteases, and small GTPase Rab proteins related to ER-Golgi trafficking, organelle stress, and liver injury. Potential pharmaceutical/therapeutic solutions to antiviral drug-induced hepatic side effects are also discussed.

PMID:37175645 | DOI:10.3390/ijms24097938

Biol Sex Differ. 2023 May 12;14(1):28. doi: 10.1186/s13293-023-00511-0.

ABSTRACT

BACKGROUND: Evidence from clinical research indicates that men and women can differ in response to drug treatment. The knowledge database Janusmed Sex and Gender was developed to illuminate potential sex and gender differences in drug therapy and, therefore, achieve a better patient safety. The database contains non-commercial evidence-based information on drug substances regarding sex and gender aspects in patient treatment. Here, we describe our experiences and reflections from collecting, analyzing, and evaluating the evidence.

JANUSMED SEX AND GENDER: Substances have been systematically reviewed and classified in a standardized manner. The classification considers clinically relevant sex and gender differences based on available evidence. Mainly biological sex differences are assessed except for gender differences regarding adverse effects and compliance. Of the 400 substances included in the database, clinically relevant sex differences were found for 20%. Sex-divided data were missing for 22% and no clinically relevant differences were found for more than half of the substances (52%). We noted that pivotal clinical studies often lack sex analyses of efficacy and adverse effects, and post-hoc analyzes are performed instead. Furthermore, most pharmacokinetic analyses use weight correction, but medicines are often prescribed in standard doses. In addition, few studies have sex differences as a primary outcome and some pharmacokinetic analyses are unpublished, which may complicate the classification of evidence.

CONCLUSIONS: Our work underlines the need of sex and gender analyses, and sex-divided data in drug treatment, to increase the knowledge about these aspects in drug treatment and contribute to a more individualized patient treatment.

PMID:37173796 | PMC:PMC10182642 | DOI:10.1186/s13293-023-00511-0

Medicine (Baltimore). 2023 May 12;102(19):e33717. doi: 10.1097/MD.0000000000033717.

ABSTRACT

We aimed to report the incidence and severity of nonionic low-osmolar iodine contrast medium (ICM)-related adverse drug reactions (ADRs) in the Republic of Korea, by analyzing data from our single tertiary institution and published Korean reports, and to determine whether there is a difference in the incidence of ICM-related ADR by ICM generics. A total of 1,161,419 consecutive contrast-enhanced computed tomography (CT) examinations between January 2016 and December 2021 at Asan Medical Center were included. A systematic search of the literature investigating the incidence of ICM-related ADR in the Republic of Korea published up to December 31, 2021 was performed. We pooled these outcomes with those of our study using a binomial-normal model, and the pooled incidences of ADRs were compared among ICM generics using chi-square tests. Seven studies with a total of 2,570,986 contrast-enhanced CT examinations from 12 institutions were included. The pooled incidences of overall, mild, moderate, and severe ICM-related ADRs in the Republic of Korea were 0.82% (95% CI: 0.61%-1.10%), 0.72% (95% CI: 0.50%-1.04%), 0.11% (95% CI: 0.08%-0.15%), and 0.013% (95% CI: 0.010%-0.018%), respectively. In multiple pairwise comparisons, there were no significant differences in the overall incidence of ADRs between ICM generics, except iomeprol versus iobitridol and iomeprol versus iohexol. For moderate and severe ADRs, there were no significant differences in ADR incidence between ICM generics. The incidence of moderate and severe ICM-related ADRs did not differ among ICM generics. Our results suggest that no restriction is required for selection among nonionic low-osmolar ICMs.

PMID:37171360 | PMC:PMC10174392 | DOI:10.1097/MD.0000000000033717

Mol Psychiatry. 2023 May 12. doi: 10.1038/s41380-023-02082-3. Online ahead of print.

ABSTRACT

Patients suffering from mental disorders are at high risk of developing cardiovascular diseases, leading to a reduction in life expectancy. Genetic variants can display greater influence on cardiometabolic features in psychiatric cohorts compared to the general population. The difference is possibly due to an intricate interaction between the mental disorder or the medications used to treat it and metabolic regulations. Previous genome wide association studies (GWAS) on antipsychotic-induced weight gain included a low number of participants and/or were restricted to patients taking one specific antipsychotic. We conducted a GWAS of the evolution of body mass index (BMI) during early (i.e., ≤ 6) months of treatment with psychotropic medications inducing metabolic disturbances (i.e., antipsychotics, mood stabilizers and some antidepressants) in 1135 patients from the PsyMetab cohort. Six highly correlated BMI phenotypes (i.e., BMI change and BMI slope after distinct durations of psychotropic treatment) were considered in the analyses. Our results showed that four novel loci were associated with altered BMI upon treatment at genome-wide significance (p < 5 × 10-8): rs7736552 (near MAN2A1), rs11074029 (in SLCO3A1), rs117496040 (near DEFB1) and rs7647863 (in IQSEC1). Associations between the four loci and alternative BMI-change phenotypes showed consistent effects. Replication analyses in 1622 UK Biobank participants under psychotropic treatment showed a consistent association between rs7736552 and BMI slope (p = 0.017). These findings provide new insights into metabolic side effects induced by psychotropic drugs and underline the need for future studies to replicate these associations in larger cohorts.

PMID:37173452 | DOI:10.1038/s41380-023-02082-3