Mariaconcetta Currò

Background/Objectives: L-carnitine and Coenzyme Q₁₀ (CoQ₁₀) are widely used in health and sports supplementation settings to improve energy metabolism, reduce fatigue, and support recovery. Although generally perceived as safe, their safety profiles are mainly based on pre-marketing studies and selected clinical populations, while real-world pharmacovigilance evidence remains limited. This study aimed to evaluate and compare the adverse drug reaction (ADR) reporting patterns associated with L-carnitine and CoQ10 using the EudraVigilance database. Methods: A retrospective pharmacovigilance analysis was conducted using spontaneous individual case safety reports (ICSRs) retrieved from the EudraVigilance database. ADRs associated with L-carnitine and CoQ₁₀ were analyzed and compared at the System Organ Class (SOC) level. Disproportionality analyses were performed using the reporting odds ratio (ROR) and proportional reporting ratio (PRR). Results: A total of 257 ICSRs for L-carnitine and 271 for CoQ10 were identified. Serious cases accounted for 34.2% of L-carnitine reports and 74.5% of CoQ₁₀ reports. For L-carnitine, the most frequently reported SOC categories were gastrointestinal disorders, skin and subcutaneous tissue disorders, general disorders and administration site conditions, and nervous system disorders. For CoQ₁₀, the most commonly reported SOC categories were general disorders and administration site conditions, nervous system disorders, investigations, and gastrointestinal disorders. Comparative disproportionality analysis showed higher reporting frequencies for CoQ₁₀ in blood and lymphatic system disorders (ROR 3.04; PRR 2.99), musculoskeletal and connective tissue disorders (ROR 2.63; PRR 2.52). Conclusions: Real-world pharmacovigilance data suggest partially different ADR reporting patterns for L-carnitine and CoQ₁₀ compared with those described in pre-marketing studies. CoQ₁₀ was associated with a higher proportion of serious reports and greater disproportionality signals for selected SOC categories; however, these findings should be interpreted cautiously, as reporting patterns may be influenced by reporting bias, comorbidities, concomitant therapies, and differences in the populations using these compounds. Continuous pharmacovigilance monitoring and periodic reassessment of their benefit–risk profile remain essential given their widespread use in health and sports supplementation settings.

Background/Objectives: L-carnitine is a naturally occurring compound involved in energy metabolism, while Coenzyme Q10 (CoQ10) is primarily indicated for CoQ10 deficiency and as adjuvant therapy in chronic heart failure. Both are widely used off-label in sports to enhance performance, reduce fatigue, and improve recovery. Despite their popularity, their safety profiles are mainly derived from pre-marketing studies conducted in deficient or clinical populations, not in athletes. Given this limitation, the present study aimed to evaluate and compare the real-world safety profiles of L-carnitine and CoQ10 using spontaneous reports of adverse drug reactions (ADRs) from the EudraVigilance database. Methods: EudraVigilance, managed by the European Medicines Agency (EMA), collects spontaneous reports of suspected ADRs related to authorized medicines. ADRs associated with L-carnitine and CoQ10 were analyzed and compared at the System Organ Class (SOC) level using reporting odds ratio (ROR) and proportional reporting ratio (PRR). Results: For L-carnitine, the most frequently reported ADRs were gastrointestinal disorders, followed by skin and subcutaneous tissue disorders, general disorders, and nervous system disorders. For CoQ10, the most common ADRs were general disorders and administration site conditions, followed by nervous system disorders, investigations, and gastrointestinal disorders. Comparative analysis (ROR and PRR) showed that CoQ10 was associated with a higher probability of reporting certain ADR categories, particularly blood and lymphatic disorders, musculoskeletal and connective tissue disorders, and nervous system disorders. Conclusions: Although L-carnitine and CoQ10 are widely perceived as safe and commonly used by athletes, real-world data highlight the need for increased awareness of potential risks. Continuous monitoring and periodic reassessment of their benefit–risk profile are essential, especially considering their widespread off-label use.

Background: The tyrosine kinase inhibitors (TKIs) asciminib, bosutinib, dasatinib, imatinib, nilotinib, and ponatinib have been approved for chronic myelogenous leukemia (CML) therapy. However, pharmacovigilance reports associated with these drugs are neither consistent nor homogenous, with reports of pulmonary toxicity, which could limit their utilization. To better clarify TKIs’ pulmonary risk, we used the European database EudraVigilance to conduct a study on adverse events suspected to be caused by the TKIs asciminib, bosutinib, dasatinib, imatinib, nilotinib, and ponatinib when used for CML therapy. Methods: Suspected adverse reactions to TKIs in the EudraVigilance database (2020–2024) coming from European countries and the United Kingdom were analyzed and compared through a disproportionality analysis. Results: The most frequent alerts concerned the respiratory disorders “pleural effusion” (PE) and “pulmonary arterial hypertension” (PAH) in relation to dasatinib and bosutinib use. Among the TKIs, the prescription of dasatinib is associated with a higher occurrence of PE and PAH, while the prescription of bosutinib induces PE at a minor frequency that nonetheless carries a significant risk for PAH, occurring more often in women. Conclusions: The results indicate that respiratory disorders induced by the TKIs dasatinib and bosutinib need to be diagnosed in a timely manner, and suggest that caution should be taken when prescribing these TKIs to patients affected by CML and pulmonary comorbidities.

(1) Background: Tyrosine kinase inhibitors (TKIs) asciminib, bosutinib, dasatinib, imatinib, nilotinib, ponatinib have been approved for the therapy of chron-ic myelogenous leukemia (CML). Pharmacovigilance reports associated with these drugs are not consistent and homogenous and have been associated with pulmonary toxicity that could limit their utilization. To give a contribution for a more clear definition of TKIs pulmonary risk, we conducted a research investigating on adverse events sus-pected to be caused by TKIs asciminib, bosutinib, dasatinib, imatinib, nilotinib, ponatinib used for CML, using the european database EudraVigilance. (2) Methods: Suspected adverse reactions to TKIs in the data system EudraVigilance (2020–2024) coming from European countries and United Kingdom were analyzed and compared through a di-sproportionality analysis. (3) Results: most frequent alerts concerned the respiratory di-sorders “Pleural effusion” (PE) and Pulmonary arterial hypertension” (PAH) related to dasatinib and bosutinib. Among the category of TKIs, prescription of dasatinib is asso-ciated with a higher occurrence of PE and PAH, while prescription of bosutinib induces with minor frequency PE but it exposes at a significant risk for PAH, occurring more often in women. (4) Conclusions: Results indicate that respiratory disorders induced by the TKIs dasatinib and bosutinib need to be punctually and rapidly diagnosed and suggest caution before prescription of these TKIs in patients affected by CML with pulmonary comorbidities.

Amoxicillin is widely prescribed, either as a monotherapy or in combination with clavulanic acid, with its therapeutic indications including a broad range of infections. Its combination with clavulanic acid maintains its known activity against strains producing β-lactamase. There are limited studies on adverse reactions and antibiotic resistance, with researchers relying primarily on databanks that report spontaneous events caused by amoxicillin or the combination of amoxicillin/clavulanic acid. Antimicrobial resistance is an overlooked adverse event, and pharmacovigilance databases could serve as a tool in tracking resistance. On this basis, a study to define the safety profile of amoxicillin and amoxicillin/clavulanic acid and to increase the knowledge necessary to support the battle against antimicrobial resistance was undertaken through the analysis of pharmacovigilance databases. Suspected adverse reactions to amoxicillin and to the combination of amoxicillin/clavulanic acid in the data system EudraVigilance (2020–2024) were analyzed. The most frequent alerts concerned “Skin and subcutaneous disorders” for both drugs. Disproportionate analysis of cases concerning “Hepatobiliary disorders” or “Drug inefficiency” indicates a significant increase in these alerts with the amoxicillin/clavulanic acid combination compared to amoxicillin. The amoxicillin/clavulanic acid combination has previously been associated with a higher risk of hepatotoxicity and antibiotic resistance to amoxicillin/clavulanic acid; however, this is the first time that a post-marketing surveillance study has shown that antimicrobial resistance is more likely to occur with the combination in comparison to amoxicillin alone.

Alone or combined with clavulanic acid, amoxicillin is widely prescribed. Therapeu-tic indications include a broad spectrum of infections. Combination with clavulanic acid kept the known activity of amoxicillin against strains producing β-lactamase. Only poor studies exist on adverse reactions and antibiotic resistance by using databanks reporting spontaneous signals caused by amoxicillin or the combination amoxicillin/clavulanic acid. Antimicrobial resistance is an overlooked adverse event and pharmacovigilance da-tabases could serve as a tool in tracking resistance. On this basis, a study to define the safety profile of amoxicillin and amoxicillin/clavulanic acid and to increase the knowledge necessary to support the battle against antimicrobial resistance was undertook through the analysis of pharmacovigilance databases. Signals of suspected adverse reac-tions to amoxicillin and to the combination amoxicillin/clavulanic acid of the data system EudraVigilance in the years 2020-2024, were analyzed. A disproportionality analysis for hepatotoxic reactions and for drug inefficiency was performed comparing data of the two medicinal products. Most frequent signals were about “Skin and subcutaneous disorders” for both the drugs. Disproportionate analysis of cases signaling “Hepatobiliary disor-ders” or “Drug inefficiency”, indicates significant increase of these signals with the com-bination amoxicillin/clavulanic acid compared to amoxicillin. The combination amoxicil-lin/clavulanic acid has previously been associated with higher risk of hepatotoxicity, however, it is the first time that a post-marketing surveillance shows that antimicrobial resistance has a greater probability to occur with the combination in comparison to amoxicillin.

Background/Objective: Major depressive disorder (MDD) is a common mental disorder, with a significant portion of patients developing treatment-resistant depression (TRD). Esketamine is an antagonist of the N-methyl-D-aspartate receptor indicated as a nasal spray in combination with other antidepressants for adults with TRD. Signals of suspected adverse reactions (SARs) to esketamine from the EudraVigilance database in European countries were analyzed for a more defined safety profile of this drug in the real world. Methods: SARs to esketamine reported in the data system EudraVigilance were analyzed, and disproportionality analysis for adverse reactions indicating suicidality for esketamine, in comparison to the antidepressants fluoxetine and venlafaxine, was performed. Results: Increases in blood pressure (15.4%) and dissociation (15.0%) were the most frequently reported SARs. The sex distribution indicates the prevalence of women, except for increased blood pressure and completed suicide, which were signaled in men, while adults (18–64 years) and elders (65–85 years) were the ages with the largest number of reported adverse reactions to esketamine. The results indicate the existence of a potential increase in the risk of suicide in depressed patients taking esketamine when compared with fluoxetine and venlafaxine. Conclusions: Apart from carefulness due to the known limitations of pharmacovigilance research conducted by using data systems of spontaneous signals for SARs, the analysis of data points toward the need for greater attention being paid to the potential risk of suicide following the prescription of esketamine in depressed subjects. In this regard, as regulatory agencies also recommend, patients with a history of suicide-related events or those exhibiting a significant degree of suicidal ideation prior to beginning treatment should receive more careful monitoring during treatment.

Background/ Objective: Major depressive disorder (MDD) is a common mental disorder, with a significant part of patients developing treatment-resistant depression (TRD). Esketamine is an antagonist of the N-methyl-D-aspartate receptor indicated as a nasal spray in combination with other antidepressants for adults with TRD. Signals of suspected adverse reactions (SARs) to esketamine from the EudraVigilance database in European countries were analyzed for a more defined safety profile of this drug in the real-world. Methods: SARs to esketamine reported in the data system EudraVigilance were analyzed and disproportionality analysis for adverse reactions indicating sui-cidality for esketamine, in comparison to the antidepressants fluoxetine and ven-lafaxine, was performed. Results: “Blood pressure increased” (15.4%) and “Dissocia-tion” (15.0%), are the more frequently reported SARs. Sex distribution indicates prevalence of women, except for “Blood pressure increased” and “Completed suicide”, more signaled for men, while adults (18-64 years) and elders (65-85 years) are the ages with the largest number of reported adverse reactions to esketamine. Results show a significant increase of risk of suicide for esketamine, when compared with fluoxetine and venlafaxine. Conclusions: Apart of carefulness due to the known limitations of pharmacovigilance research conducted by using datasystem of spontaneous signals for SARs, analysis of data on points towards the need for greater attention for risk suicide following prescription of esketamine in depressed subjects. In this regard, as well as regulatory agencies recommend, patients with a history of suicide-related events or those exhibiting a significant degree of suicidal ideation prior to begin treatment, should receive a more careful monitoring during treatment.

Background/Objectives: Neuronal Ceroid Lipofuscinosis type 2 is a rare pathology affecting mainly the central nervous system (CNS) and retina, and is caused by variants in the gene encoding the lysosomal enzyme tripeptidyl peptidase 1. Therapy with enzyme replacement through the brain infusion of the orphan drug cerliponase alfa, a recombinant human tripeptidyl peptidase 1 enzyme replacement therapy delivered via intracerebroventricular infusion, has been approved for Neuronal Ceroid Lipofuscinosis type 2 disease. The safety profile of cerliponase alfa has been established based on pre-authorization studies; currently, no post-marketing investigation has been performed to confirm it. Here, a descriptive analysis of real-world spontaneous reporting data of suspected adverse reactions (SARs) to cerliponase alfa in the EudraVigilance database was performed to compile clear information on the safety profile. Methods: Suspected adverse reactions to cerliponase alfa reported in the data system EudraVigilance were analyzed for age, sex of the patient, adverse reactions, and the indication for use. Results: Cases with suspected adverse reactions to cerliponase alfa were found to be more frequent in female patients (58.1%) and in children aged 3–11 years. The most common adverse reactions were, in decreasing order, fever/pyrexia, device-related infection, vomiting, seizures/convulsions, pleocytosis, irritability, ventriculitis, and respiratory disorders. Conclusions: The results confirm the safety profile of cerliponase alfa established with pre-registration clinical studies but suggest the need for further studies to investigate the occurrence of adverse reactions, as possible predictive prognostic markers, in more depth.