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Therapeutic Drug Monitoring and Adverse Drug Reactions: 2nd Edition
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Therapeutic Drug Monitoring and Adverse Drug Reactions: 2nd Edition

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: 25 August 2025 | Viewed by 9776

Special Issue Editors

Dr. Engi Abd El Hady Algharably

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Guest Editor
Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Clinical Pharmacology and Toxicology, Charitéplatz 1, 10117 Berlin, Germany
Interests: clinical pharmacokinetics; pharmacogenetics; risk assessment; pbpk modeling; hypertension
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Ursula Gundert-Remy

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Guest Editor
Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Institute of Clinical Pharmacology and Toxicology, Charitéplatz 1, 10117 Berlin, Germany
Interests: toxicokinetics; toxicity; pharmacokinetics; bioavailability; clinical pharmacokinetics pharmacokinetic modeling; pkpd modeling; pharmacovigilance; risk assessment; toxicology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Therapeutic drug monitoring (TDM) and the prevention of adverse drug reactions (ADRs) are of utmost importance in optimizing patient care and medication safety. To explore the latest advancements and insights in this field, Pharmaceuticals is pleased to continue the journey with the second volume of the Special Issue “. In this Special Issue, we aim to provide a platform for researchers, clinicians, and pharmacologists to present their original research, reviews, and case studies related to TDM and ADRs which have translational impact on drug users.

The Special Issue seeks contributions covering various topics related to medication safety in the context of TDM methodologies or studies focusing on the subtopic of ADRs. Relevant research work focusing on novel methodologies for TDM, individualized dosing strategies, biomarkers for predicting drug response and ADRs, strategies for minimizing ADRs and enhancing medication safety, pharmacokinetic modeling, as well as pharmacogenomics.

By exploring these themes, this Special Issue aims to enhance our understanding of drug efficacy, toxicity, and personalized treatment strategies. It seeks to highlight the importance of TDM and its implementation in clinical practice in order to minimize ADRs and improve patient outcomes using all available research disciplines. We welcome and encourage researchers and clinicians to submit their high-quality manuscripts to contribute to the advancements in therapeutic drug monitoring and adverse drug reactions.

Dr. Engi Abd El Hady Algharably
Prof. Dr. Ursula Gundert-Remy
Guest Editors

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • therapeutic drug monitoring
  • adverse drug reactions
  • pharmacokinetics
  • personalized medicine
  • medication safety
  • pharmacogenomics
  • medication review
  • pharmacokinetic modelling

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15 pages, 664 KiB  
Article
Real-World Safety of Vedolizumab in Inflammatory Bowel Disease: A Retrospective Cohort Study Supported by FAERS Signal Analysis
by Bojana Milašinović, Sandra Vezmar Kovačević, Srđan Marković, Marija Jovanović, Tamara Knežević Ivanovski, Đorđe Kralj, Petar Svorcan, Branislava Miljković and Katarina Vučićević
Pharmaceuticals 2025, 18(8), 1127; https://doi.org/10.3390/ph18081127 - 28 Jul 2025
Abstract
Background/Objectives: Vedolizumab is a gut-selective anti-integrin monoclonal antibody approved for the treatment of inflammatory bowel disease (IBD). While clinical trials have demonstrated a favorable safety profile, real-world studies are essential for identifying rare adverse events (AEs) and evaluating post-marketing safety. This study [...] Read more.
Background/Objectives: Vedolizumab is a gut-selective anti-integrin monoclonal antibody approved for the treatment of inflammatory bowel disease (IBD). While clinical trials have demonstrated a favorable safety profile, real-world studies are essential for identifying rare adverse events (AEs) and evaluating post-marketing safety. This study assessed vedolizumab’s safety in a real-world cohort and supported the detection of potential safety signals. Methods: A retrospective chart review was conducted on adult IBD patients treated with vedolizumab at a tertiary center in the Republic of Serbia between October 2021 and August 2022. Data included demographics, AEs, and newly reported extraintestinal manifestations (EIMs). Exposure-adjusted incidence rates were calculated per 100 patient-years (PYs). Disproportionality analysis using the FDA Adverse Event Reporting System (FAERS) was performed to identify safety signals, employing reporting odds ratios (RORs) and proportional reporting ratios (PRRs) for AEs also observed in the cohort. Prior IBD therapies and reasons for discontinuation were evaluated. Results: A total of 107 patients (42.1% Crohn’s disease, 57.9% ulcerative colitis) were included, with a median vedolizumab exposure of 605 days. There were 92 AEs (56.51/100 PYs), most frequently infections (23.95/100 PYs), gastrointestinal disorders (4.30/100 PYs), and skin disorders (4.30/100 PYs). The most frequently reported preferred terms (PTs) included COVID-19, COVID-19 pneumonia, nephrolithiasis, and nasopharyngitis. Arthralgia (12.90/100 PYs) was the most frequent newly reported EIM. No discontinuations due to vedolizumab AEs occurred. FAERS analysis revealed potential signals for events not listed in prescribing information but observed in the cohort: nephrolithiasis, abdominal pain, diarrhea, malaise, cholangitis, gastrointestinal infection, blood pressure decreased, weight decreased, female genital tract fistula, respiratory symptom, and appendicectomy. Most patients had received three prior therapies, often stopping one due to AEs. Conclusions: Vedolizumab demonstrated a favorable safety profile in the IBD cohort. However, FAERS-identified signals, such as nephrolithiasis, gastrointestinal infections, and decreased blood pressure, warrant further investigation in larger, more diverse populations. Full article
(This article belongs to the Special Issue Therapeutic Drug Monitoring and Adverse Drug Reactions: 2nd Edition)
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27 pages, 17405 KiB  
Article
Population Pharmacokinetic Modeling of Piperacillin/Tazobactam in Healthy Adults and Exploration of Optimal Dosing Strategies
by Yun Jung Lee, Gaeun Kang, Dae Young Zang and Dong Hwan Lee
Pharmaceuticals 2025, 18(8), 1124; https://doi.org/10.3390/ph18081124 - 27 Jul 2025
Abstract
Background/Objectives: Current dosing recommendations for piperacillin/tazobactam suggest adjustments only for patients with creatinine clearance (CrCl) below 40 mL/min, potentially neglecting the variability in drug exposure among patients with a CrCl greater than 40 mL/min. This study aimed to develop a population pharmacokinetic (PK) [...] Read more.
Background/Objectives: Current dosing recommendations for piperacillin/tazobactam suggest adjustments only for patients with creatinine clearance (CrCl) below 40 mL/min, potentially neglecting the variability in drug exposure among patients with a CrCl greater than 40 mL/min. This study aimed to develop a population pharmacokinetic (PK) model for piperacillin/tazobactam and explore optimal dosage regimens tailored by renal function and pathogen susceptibility. Methods: Twelve healthy adults received a single intravenous dose of piperacillin/tazobactam (4 g/0.5 g). Population PK models were developed using nonlinear mixed-effects modeling. Monte Carlo simulations were conducted to identify optimal dosing regimens across various renal functions and MIC levels, guided by pharmacodynamic targets defined as the percentage of time that free drug concentrations exceed the minimum inhibitory concentration (fT>MIC). Results: PK profiles of both drugs were best described by two-compartment models. Estimated glomerular filtration rate (eGFR) adjusted by body surface area and body weight were identified as significant covariates influencing drug clearance and peripheral volume of distribution. Simulations showed that the standard dosing regimen (4/0.5 g q6h with 30 min infusion) achieved a 90% probability of target attainment (PTA) for 50%fT>MIC at MIC values up to 4 mg/L in patients with normal renal function. However, this regimen often did not achieve a 90% PTA for stringent targets (100%fT>MIC, 100%fT>4MIC) or higher MICs, particularly in patients with eGFR ≥ 130 mL/min. Conclusions: These findings suggest current dosing regimens may be inadequate and highlight the potential of alternative strategies, such as extended or continuous infusion, which warrant further investigation in clinical populations to optimize therapeutic outcomes. Full article
(This article belongs to the Special Issue Therapeutic Drug Monitoring and Adverse Drug Reactions: 2nd Edition)
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14 pages, 929 KiB  
Article
Possible Association Between Concomitant Use of SSRIs with NSAIDs and an Increased Risk of Adverse Events Among People with Depressive Disorders: Data Mining of FDA Adverse Event Reporting System
by Yi Zhang, Xiaoyu Liu, Jianru Wu, Xuening Zhang, Fenfang Wei, Limin Li, Hongqiao Li, Xinru Wang, Bei Wang, Wenyu Wu and Xiang Hong
Pharmaceuticals 2025, 18(7), 1062; https://doi.org/10.3390/ph18071062 - 18 Jul 2025
Viewed by 269
Abstract
Background: Depression, a major global health issue, is commonly treated with selective serotonin reuptake inhibitors (SSRIs). Given the link between depression and inflammation, nonsteroidal anti-inflammatory drugs (NSAIDs) may have adjunctive benefits. Clinically, SSRIs and NSAIDs are often co-prescribed for comorbid pain or [...] Read more.
Background: Depression, a major global health issue, is commonly treated with selective serotonin reuptake inhibitors (SSRIs). Given the link between depression and inflammation, nonsteroidal anti-inflammatory drugs (NSAIDs) may have adjunctive benefits. Clinically, SSRIs and NSAIDs are often co-prescribed for comorbid pain or inflammatory conditions. However, both drug classes pose risks of adverse effects, and their interaction may lead to clinically significant drug–drug interactions. Objectives: This study analyzed FDA Adverse Event Reporting System (FAERS) data (2004–2024) to assess gastrointestinal bleeding, thrombocytopenia, and acute kidney injury (AKI) potential risks linked to SSRIs (citalopram, escitalopram, fluoxetine, paroxetine, fluvoxamine, and sertraline) and NSAIDs (propionic/acetic/enolic acid derivatives, COX-2 inhibitors) in depression patients, alone and combined. Methods: Disproportionality analysis (crude reporting odds ratios, cROR) identified possible associations; drug interactions were evaluated using Ω shrinkage, additive, multiplicative, and combination risk ratio (CRR) models. Results: Gastrointestinal bleeding risk was potentially elevated with citalopram (cROR = 2.81), escitalopram (2.27), paroxetine (2.17), fluvoxamine (3.58), sertraline (1.69), and propionic acid NSAIDs (3.17). Thrombocytopenia showed a potential correlation with fluoxetine (2.11) and paroxetine (2.68). AKI risk may be increased with citalopram (1.39), escitalopram (1.36), fluvoxamine (3.24), and COX-2 inhibitors (2.24). DDI signal analysis suggested that citalopram in combination with propionic acid derivatives (additive model = 0.01, multiplicative model = 1.14, and CRR = 3.13) might increase the risk of bleeding. Paroxetine combined with NSAIDs (additive model = 0.014, multiplicative model = 2.65, and CRR = 2.99) could potentially increase the risk of thrombocytopenia. Sertraline combined with NSAIDs (Ω025 = 0.94, multiplicative model = 2.14) might be associated with an increasing risk of AKI. Citalopram combined with propionic acid derivatives (Ω025 = 1.08, multiplicative model = 2.17, and CRR = 2.42) could be associated with an increased risk of acute kidney injury. Conclusions: Certain combinations of SSRIs and NSAIDs might further elevate these risks of gastrointestinal bleeding, thrombocytopenia, and acute kidney injury in patients with depression. Given the potential drug–drug interactions, heightened clinical vigilance is advised when prescribing SSRIs and NSAIDs in combination to patients with depression. Full article
(This article belongs to the Special Issue Therapeutic Drug Monitoring and Adverse Drug Reactions: 2nd Edition)
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16 pages, 679 KiB  
Article
Pharmacogenetic Biomarkers of Ibrutinib Response and Toxicity in Chronic Lymphocytic Leukemia: Insights from an Observational Study
by Noelia Pérez-Gómez, Antonio Sanz-Solas, Beatriz Cuevas, María Victoria Cuevas, Cristina Alonso-Madrigal, Javier Loscertales, Rodolfo Álvarez-Nuño, Covadonga García, Pablo Zubiaur, Gonzalo Villapalos-García, Raúl Miguel Parra-Garcés, Gina Mejía-Abril, Raquel Alcaraz, Raquel Vinuesa, Francisco Javier Díaz-Gálvez, María González-Oter, Natalia García-Sancha, Raúl Azibeiro-Melchor, Tomás José González-López, Francisco Abad-Santos, Jorge Labrador and Miriam Saiz-Rodríguezadd Show full author list remove Hide full author list
Pharmaceuticals 2025, 18(7), 996; https://doi.org/10.3390/ph18070996 - 2 Jul 2025
Viewed by 349
Abstract
Background/Objectives: Ibrutinib is a selective Bruton’s tyrosine kinase inhibitor approved for the treatment of chronic lymphocytic leukemia (CLL). This drug exhibits significant variability in response and toxicity profile, possibly due to genetic polymorphisms in drug-metabolizing enzymes and transporters. The aim of this observational [...] Read more.
Background/Objectives: Ibrutinib is a selective Bruton’s tyrosine kinase inhibitor approved for the treatment of chronic lymphocytic leukemia (CLL). This drug exhibits significant variability in response and toxicity profile, possibly due to genetic polymorphisms in drug-metabolizing enzymes and transporters. The aim of this observational study is to address interindividual variability in the efficacy and safety of ibrutinib treatment in 49 CLL patients. Methods: Genotyping of nine polymorphisms was performed by quantitative polymerase chain reaction (qPCR) using a ViiA7® PCR Instrument and TaqMan assays, and ibrutinib plasma concentrations were determined using high-performance liquid chromatography coupled to a tandem mass spectrometry detector (HPLC-MS/MS). Results: Our study confirmed a high response rate, with 62% of patients achieving complete remission (CR), 9% CR with incomplete hematologic recovery (CRi), and 24% partial remission (PR). The impact of genetic polymorphisms on the CR rate was evaluated, revealing no statistically significant associations for CYP3A4, CYP3A5, ABCB1, ABCG2, and SLCO1B1 variants. However, a tendency was observed for patients carrying ABCB1 rs1128503, rs1045642 T/T, or rs2032582 A/A genotypes to achieve a higher CR rate. Adverse drug reactions (ADRs) were frequent, with vascular disorders (39%) and infections (27%) being the most common. Genetic polymorphisms influenced ibrutinib toxicity, with CYP3A4 *1/*22 appearing to be protective against overall ADRs. Conclusions: The unexpected association between CYP3A4 *1/*22 genotype and lower ADR incidence, as well as the trend toward improved treatment response in patients carrying ABCB1 genotypes, suggests compensatory metabolic mechanisms. However, given the small sample size, larger studies are needed to confirm these findings and their clinical implications, while also aiming to uncover other non-genetic factors that may contribute to a better understanding of the variability in treatment response and toxicity. Full article
(This article belongs to the Special Issue Therapeutic Drug Monitoring and Adverse Drug Reactions: 2nd Edition)
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16 pages, 1090 KiB  
Article
Suicidality Risks Associated with Finasteride, a 5-Alpha Reductase Inhibitor: An Evaluation of Real-World Data from the FDA Adverse Event Reports
by Hilal A. Thaibah, Otilia J. F. Banji, David Banji, Hadi A. Almansour and Thamir M. Alshammari
Pharmaceuticals 2025, 18(7), 957; https://doi.org/10.3390/ph18070957 - 25 Jun 2025
Viewed by 1099
Abstract
Background: Finasteride, a 5α-reductase inhibitor, is used for androgenetic alopecia and benign prostatic hyperplasia. However, concerns have emerged about its psychiatric side effects, including suicidality. This study analyzed finasteride-related reports from the FDA Adverse Event Reporting System (FAERS) to identify potential safety [...] Read more.
Background: Finasteride, a 5α-reductase inhibitor, is used for androgenetic alopecia and benign prostatic hyperplasia. However, concerns have emerged about its psychiatric side effects, including suicidality. This study analyzed finasteride-related reports from the FDA Adverse Event Reporting System (FAERS) to identify potential safety signals. Methods: Adverse events reported from 2015 to 2024 were extracted using preferred terms, quantified using Bayesian analysis and disproportionality metrics, including empirical Bayesian geometric mean (EBGM), information component (IC), reporting odds ratio (ROR), and proportional reporting ratio (PRR). Results: Most were male (87%), with 43% aged 18–40 years, primarily using finasteride for hair loss. Disproportionality metrics for suicidality-related events fluctuated between 2019 and 2024. In 2019, the ROR was 27.51 (95% CI: 23.22–32.58), the PRR was 21.96 (95% CI: 18.54–26.01), the EBGM was 20.50, and the IC was 4.36. A slight decline was observed in 2020, a surge in 2021, and a peak in 2022 (ROR 34.64 (95% CI: 28.36–41.88), PRR 27.82 (95% CI: 22.30–34.61), EBGM 24.96, IC 4.64). Although a sharp rise in suicidality reports was noted in 2024, the rates of ROR and PRR dropped to 19.04 (95% CI: 17.02–21.30) and 16.53 (95% CI: 14.78–18.50), respectively. Serious outcomes such as disability (18.7%), life-threatening events (12.9%), and death (7.5%) were also noted. Conclusions: The upward trend in suicidality-related safety signals among young male users since 2019, which peaked in 2024, reflects emerging safety concerns among finasteride users, reinforcing the need for pharmacovigilance. Collaborative action among healthcare professionals, regulatory authorities, and pharmaceutical companies, along with clear warnings and mental health assessments before and throughout finasteride therapy, can mitigate potential psychiatric risks and enhance patient safety. Full article
(This article belongs to the Special Issue Therapeutic Drug Monitoring and Adverse Drug Reactions: 2nd Edition)
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16 pages, 604 KiB  
Article
The Role of GST Gene Polymorphic Variants in Antipsychotic-Induced Metabolic Disorders in Schizophrenia: A Pilot Study
by Irina A. Mednova, Ekaterina V. Mikhalitskaya, Natalia M. Vyalova, Diana Z. Paderina, Dmitry A. Petkun, Vladimir V. Tiguntsev, Elena G. Kornetova, Nikolay A. Bokhan and Svetlana A. Ivanova
Pharmaceuticals 2025, 18(7), 941; https://doi.org/10.3390/ph18070941 - 21 Jun 2025
Viewed by 427
Abstract
The life expectancy of patients with psychotic disorders is significantly shorter than that of the general population; antipsychotic-induced metabolic disorders play a significant role in reducing life expectancy. Both metabolic syndrome (MetS) and schizophrenia are multifactorial conditions. One area where the two conditions [...] Read more.
The life expectancy of patients with psychotic disorders is significantly shorter than that of the general population; antipsychotic-induced metabolic disorders play a significant role in reducing life expectancy. Both metabolic syndrome (MetS) and schizophrenia are multifactorial conditions. One area where the two conditions overlap is oxidative stress, which is present in both diseases. The glutathione-S-transferase (GST) system is a major line of defense against exogenous toxicants and oxidative damage to cells. The aim of our study was to perform an association analysis of gene polymorphisms with metabolic disorders in patients with schizophrenia treated with antipsychotic therapy. Methods: A total of 639 white patients with schizophrenia (ICD-10) from Siberia (Russia) were included in the study. Genotyping was carried out using real-time polymerase chain reaction for two single-nucleotide polymorphisms (SNPs) in the GSTP1 (rs614080 and rs1695) and one SNP in the GSTO1 (rs49252). Results: We found that rs1695*GG genotype of GSTP1 is a risk factor for the development of overweight (OR 2.36; 95% CI: 1.3–4.29; p = 0.0054). In the subgroup of patients receiving first-generation antipsychotics as basic therapy, the risk of overweight was associated with carriage of the rs1695*GG (OR 5.43; 95% CI: 2.24–13.16; p < 0.001) genotype of GSTP1 in a recessive model of inheritance. In contrast, an association of rs1695*G GSTP1 with obesity (OR: 0.42; 95% CI: 0.20–0.87; p = 0.018) was shown in the dominant model of inheritance in patients receiving second-generation antipsychotics. Conclusions: The pilot results obtained confirm the hypothesis of a violation of the antioxidant status, in particular the involvement of GSTP1, in the development of antipsychotic-induced metabolic disorders in schizophrenia. Further studies with larger samples and different ethnic groups are needed to confirm the obtained results. Full article
(This article belongs to the Special Issue Therapeutic Drug Monitoring and Adverse Drug Reactions: 2nd Edition)
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15 pages, 2870 KiB  
Article
5-Fluorouracil Toxicity: Revisiting the Relevance of Pharmacokinetic Parameters
by Hans Mielke, Engi Abd Elhady Algharably and Ursula Gundert-Remy
Pharmaceuticals 2025, 18(5), 653; https://doi.org/10.3390/ph18050653 - 29 Apr 2025
Viewed by 954
Abstract
Background/Objectives: 5-fluorouracil (5-FU) is used in the treatment of solid cancer types. Because of its narrow therapeutic window, drug monitoring is recommended. We were confronted to answer a question on the relevance of concentration as opposed to the area under the plasma [...] Read more.
Background/Objectives: 5-fluorouracil (5-FU) is used in the treatment of solid cancer types. Because of its narrow therapeutic window, drug monitoring is recommended. We were confronted to answer a question on the relevance of concentration as opposed to the area under the plasma concentration–time curve (AUC) to predict toxicity when we had to assess the case of a patient who died after an erroneously high infusion rate. Methods: We used physiologically-based pharmacokinetic modeling (PBPK) to simulate the concentration–time profile of 5-FU data on doses, dosing schedules and life-threatening toxicity for both the patient in question as well as data from the literature. Furthermore, steady-state 5-FU concentrations were calculated from an additional set of data found in the literature on AUCs and non-life-threatening toxicity. Results: The model predictions matched well with experimental data, confirming the suitability of the model. Life-threatening toxicity was related to a concentration above 6 mg/L, whereas non-life-threatening toxicity was low at concentrations less than 3 mg/L but steeply increased between 3 and 4 mg/L. Data analysis supported by a decision algorithm suggests that the 5-FU steady-state plasma concentration is a better toxicity predictor than the AUC. Conclusions: We recommend monitoring the concentration one hour after infusion starts when about 50% of the steady state is reached in patients for whom higher doses are clinically considered relevant. Monitoring the concentration one hour after starting the infusion has the advantage that dose correction could be made early before toxicity can be observed. Full article
(This article belongs to the Special Issue Therapeutic Drug Monitoring and Adverse Drug Reactions: 2nd Edition)
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16 pages, 1061 KiB  
Article
Post-Marketing Pharmacovigilance of Canakinumab from the FDA Adverse Event Reporting System (FAERS)
by Weidong Zhang, Yunzhou Chen, Zeyu Yao, Mengling Ouyang, Minghui Sun and Shupeng Zou
Pharmaceuticals 2025, 18(1), 114; https://doi.org/10.3390/ph18010114 - 16 Jan 2025
Viewed by 1335
Abstract
Background: Canakinumab, a humanized anti-IL-1β monoclonal antibody, is known for its ability to suppress IL-1β-mediated inflammation. However, continuous monitoring of its safety remains essential. Thus, we comprehensively evaluated the safety signals of canakinumab by data mining from FAERS. Methods: We used a disproportionate [...] Read more.
Background: Canakinumab, a humanized anti-IL-1β monoclonal antibody, is known for its ability to suppress IL-1β-mediated inflammation. However, continuous monitoring of its safety remains essential. Thus, we comprehensively evaluated the safety signals of canakinumab by data mining from FAERS. Methods: We used a disproportionate analysis to quantify canakinumab-related adverse events (AEs) using four algorithms. Clinical prioritization of the detected signals was assessed with a semiquantitative score method. Serious and non-serious outcomes were compared by statistical methods. Additionally, a stratification analysis of serious infections was conducted at the system organ class (SOC) level. Results: A total of 28,496 canakinumab-related AEs were collected, and 71 suspicious signals detected. Among these, 19 preferred terms (PTs) were identified as unexpected signals, including deafness, appendicitis, brain oedema, cushingoid, cellulitis, and papilledema. Of the AEs, 16 were more likely reported as serious outcomes, such as pneumonia, abdominal pain, deafness, and infection. Based on clinical priority score, 44 PTs were classified as weak, 27 as moderate, and none as strong. Furthermore, 30 PTs demonstrated a high level of evidence, primarily derived from FDA prescribing information, randomized controlled trials, and systematic reviews. Stratification analysis of infections and infestations (serious outcomes) revealed a stronger association of severe infections with canakinumab in older or heavier individuals. All positive signals followed an early failure pattern, with the incidence of canakinumab-associated AEs decreasing over time. Conclusions: We found that most of the suspicious signals were associated with infections. More attention should be paid to serious infections, particularly in males, individuals aged ≥60 years, or those weighing >100 kg, who demonstrated the highest risk of serious infections. Full article
(This article belongs to the Special Issue Therapeutic Drug Monitoring and Adverse Drug Reactions: 2nd Edition)
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15 pages, 304 KiB  
Review
Improving the Dosing Schedules of Targeted Anticancer Agents
by Dominique Levêque
Pharmaceuticals 2025, 18(6), 848; https://doi.org/10.3390/ph18060848 - 6 Jun 2025
Viewed by 693
Abstract
Beyond developing new agents, cancer treatment can also be optimized by modifying the dosing regimen of approved drugs. Academic teams have experimented with different ways of improving drug regimens, leading to off-label practices for therapeutic and/or economic purposes, and currently, drug regulatory agencies [...] Read more.
Beyond developing new agents, cancer treatment can also be optimized by modifying the dosing regimen of approved drugs. Academic teams have experimented with different ways of improving drug regimens, leading to off-label practices for therapeutic and/or economic purposes, and currently, drug regulatory agencies have begun to reappraise this often-neglected topic. This concept also considers the patient’s perspective in terms of quality of life and convenience, including the concept of time toxicity. Overall, the optimization of drug dosing of anticancer agents may be viewed on three sides: the improvement of the benefits/risks balance (patient), the improvement of the convenience of the treatment (patient, healthcare professionals), and the mitigation of the financial impact (health insurance, patient). Examples of dose reassessments of targeted therapies (approved since 1997) are chosen to illustrate the context. Suboptimal/overdosed regimens are found for certain molecularly targeted agents, mostly based on the ancient concept of maximum tolerated dose in oncology. This underlines the lack of comparative effective dose trials before approval. Fortunately, dosing regimens of newly approved molecularly targeted agents is going to evolve with the hope of more convenient and better tolerated treatments. This optimization will bring greater benefit to patients and to healthcare professionals but without addressing the economic issue. Full article
(This article belongs to the Special Issue Therapeutic Drug Monitoring and Adverse Drug Reactions: 2nd Edition)
29 pages, 6612 KiB  
Review
Artificial Intelligence Models and Tools for the Assessment of Drug–Herb Interactions
by Marios Spanakis, Eleftheria Tzamali, Georgios Tzedakis, Chryssalenia Koumpouzi, Matthew Pediaditis, Aristides Tsatsakis and Vangelis Sakkalis
Pharmaceuticals 2025, 18(3), 282; https://doi.org/10.3390/ph18030282 - 20 Feb 2025
Cited by 5 | Viewed by 3622
Abstract
Artificial intelligence (AI) has emerged as a powerful tool in medical sciences that is revolutionizing various fields of drug research. AI algorithms can analyze large-scale biological data and identify molecular targets and pathways advancing pharmacological knowledge. An especially promising area is the assessment [...] Read more.
Artificial intelligence (AI) has emerged as a powerful tool in medical sciences that is revolutionizing various fields of drug research. AI algorithms can analyze large-scale biological data and identify molecular targets and pathways advancing pharmacological knowledge. An especially promising area is the assessment of drug interactions. The AI analysis of large datasets, such as drugs’ chemical structure, pharmacological properties, molecular pathways, and known interaction patterns, can provide mechanistic insights and identify potential associations by integrating all this complex information and returning potential risks associated with these interactions. In this context, an area where AI may prove valuable is in the assessment of the underlying mechanisms of drug interactions with natural products (i.e., herbs) that are used as dietary supplements. These products pose a challenging problem since they are complex mixtures of constituents with diverse and limited information regarding their pharmacological properties, especially their pharmacokinetic data. As the use of herbal products and supplements continues to grow, it becomes increasingly important to understand the potential interactions between them and conventional drugs and the associated adverse drug reactions. This review will discuss AI approaches and how they can be exploited in providing valuable mechanistic insights regarding the prediction of interactions between drugs and herbs, and their potential exploitation in experimental validation or clinical utilization. Full article
(This article belongs to the Special Issue Therapeutic Drug Monitoring and Adverse Drug Reactions: 2nd Edition)
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