Current Drug Safety - Online First

Thalidomide has emerged as a novel antitumor drug with antiangiogenic and immunomodulatory properties. It was taken off the market in the early 1960s due to its infamous connection with congenital defects. Recently, the FDA approved thalidomide for treating erythema nodosum leprosum, adhering to strict guidelines and safety measures. Sensory peripheral neuropathy and teratogenicity, fatigue, vertigo, headache, gastrointestinal issues, skin eruptions, dizziness, galactorrhoea, decreased libido, and constitutional symptoms like fever, weakness, headaches, and weight loss are the main adverse effects of thalidomide.

We report a case of a 46-year-old female diagnosed with lepromatous leprosy on multibacillary multidrug therapy presenting with unusual adverse reactions, such as generalized burning sensation, breathlessness, and low backache after the intake of thalidomide.

We describe an unusual adverse reaction to thalidomide that has not previously been reported in the literature and aim to alert clinicians about the unusual, adverse reaction as an uncommon side effect of thalidomide and to always keep in mind if the patient develops any of these symptoms.

Capecitabine is known to be associated with many Adverse Drug Reactions (ADRs). Due to a lack of prospective studies, we aimed to determine the frequency and pattern of the ADR profile associated with the Capecitabine-based Chemotherapy Regimen (CBCR).

A prospective observational study was carried out at a tertiary care hospital in South India. ADRs in patients on CBCR were evaluated throughout the complete course of chemotherapy. They were graded for severity as per CTCAE criteria (v4.03) and assessed for causality and preventability. The Chi-squared test was used to analyze differences in the frequency of ADRs among cancer types, gender, and chemotherapy regimens.

Most ADRs (96.6%) reported were related to the gastrointestinal system, followed by neurological events (93.3%) among 120 cancer patients on CBCR. Among the detected ADRs, skin/nail discoloration and fatigue/weakness were the most frequently reported. The majority of ADRs were classified as “possible” (50.5% by WHO and 50.9% by the Naranjo scale). Most ADRs were of grade I severity (54.5%) and were deemed “probably preventable.”

The observed frequency of ADRs was similar to a few reported studies, but differed on the basis of the type of ADR. There is a lack of literature on the causality and preventability of ADRs with CBCR.

CBCR was associated with several ADRs, although most were of grade I severity and involved the gastrointestinal system. The majority of ADRs were classified as “possible” based on causality analysis, and most were deemed “probably preventable.” Future research should focus on mitigating these ADRs to avoid dose adjustments or discontinuation of chemotherapy.

DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms) is a rare adverse drug reaction characterized by cutaneous and systemic manifestations, with a mortality rate of up to 10%. In this study, we describe the case of a 77-year-old man who developed DRESS syndrome with cold agglutination.

A 77-year-old man prescribed phenytoin and carbamazepine for suspected cranial neuralgia after a tooth extraction developed high-grade fever and hemorrhagic crusting on the upper and lower lips and oral mucosa, morbilliform rashes over the chest, abdomen, and back along with facial edema, all occurring over 2 weeks. Clinically significant right-sided submandibular, cervical, and axillary lymphadenopathy was observed. Additional findings, including peripheral blood eosinophilia, hepatitis, and coagulopathy, helped us make a provisional diagnosis of DRESS syndrome. The peripheral blood smear showed an incidental finding of cold agglutination phenomenon at room temperature (16 °C; winter months in North India), which disappeared under warmer conditions. However, gross hemolysis was not confirmed. The patient showed significant response in both clinical and hematological parameters within 24 hours of initiating intravenous dexamethasone, which was continued and gradually tapered over 14 days. Follow-up at one month showed the disappearance of the cold agglutination phenomenon.

Cold agglutination in DRESS syndrome has not been documented in detail in the past. One hypothesis is the agglutination of red blood cells (RBCs) due to the effect of the pathogenetic antibodies in DRESS syndrome directed against RBC antigens. Further molecular research may elucidate the pathways of this rare clinical finding.

Biosimilars, a class of biologic medications that are highly similar to reference biologics, have emerged as cost-effective alternatives to their expensive originator counterparts. Due to their complex nature and manufacturing processes, biosimilars differ significantly from small molecule generics and must undergo a rigorous assessment to ensure safety, efficacy, and accessibility. This review explores the regulatory landscape surrounding biosimilars across key markets such as the United States, Europe, and India, with a focus on approval processes and post-marketing pharmacovigilance for patient safety.

The study conducted a detailed review of regulatory guidelines, approval frameworks, and post-marketing requirements for biosimilars across various countries. Data was collected from official sources such as the European Medicines Agency (EMA), the United States Food and Drug Administration (FDA), and relevant Indian regulatory bodies. The research also analysed guidelines focusing on pharmacovigilance practices, particularly for vulnerable populations like paediatric and geriatric patients.

The analysis found that while regulatory agencies such as the EMA and FDA have established stringent biosimilar approval pathways, India's regulatory framework, though promising, still lacks comprehensive pharmacovigilance guidelines. The harmonization of global biosimilar guidelines has contributed to their widespread adoption in new therapeutic areas and emerging markets, driving market expansion. The study highlights the importance of post-marketing monitoring to ensure continued safety, with particular emphasis on vulnerable populations.

The regulatory landscape for biosimilars is evolving, with increasing global collaboration fostering the harmonization of guidelines. Regulatory agencies such as the European Medicines Agency (EMA) and the United States Food and Drug Administration (FDA) have established rigorous approval frameworks, ensuring biosimilars meet the necessary standards for safety and efficacy. In emerging markets like India, the biosimilar sector is poised for significant growth, though the regulatory framework is still maturing. Strengthening regulatory infrastructure, particularly in areas such as approval processes and quality control, will be crucial in supporting this expansion. The review emphasizes the importance of robust and clear regulations to facilitate the safe and effective integration of biosimilars into global healthcare systems, ensuring greater accessibility for patients without compromising on quality.

Antibiotic resistance poses a significant challenge in healthcare, requiring effective management of antibiotic use. This study examines systemic antibiotic consumption at ASST Bergamo Ovest, a northern Italian hospital, from January 2022 to June 2023, with a focus on Healthcare-Associated Infections (HAIs) and prescription appropriateness. This retrospective observational study aims to analyze antibiotic usage trends and to evaluate prescribing practices against national guidelines.

Data on systemic antibiotic consumption were reviewed, categorized by the AWaRe classification system (Access, Watch, Reserve), and analyzed using the Defined Daily Dose per 100 patient-days metric.

The study observed a 7% overall reduction in antibiotic use, including a 5% decrease in the AWaRe Watch category. Despite this progress, the appropriateness of prescribing remained consistently low. These findings suggest partial alignment with the Italian Plan against Antibiotic Resistance but highlight the need for improvement in prescribing practices.

While ASST Bergamo Ovest has reduced antibiotic consumption and the use of higher-risk antibiotics, low prescribing appropriateness underscores the need for enhanced real-time monitoring and more effective stewardship programs.

Targeted interventions are essential to improve prescribing practices, combat multidrug-resistant infections, and meet European antibiotic stewardship standards.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely accepted for managing Type 2 Diabetes Mellitus. However, numerous drug-related problems (DRPs) have recently been reported about GLP-1 RAs. The present descriptive study aims to compile and report the DRPs of various GLP-1 RAs.

The DRPs reported for all the GLP-1 RAs, including exenatide, lixisenatide, liraglutide, dulaglutide, semaglutide, and trazeptide, were extracted from the category of injury, poisoning, and procedural complications of VigiAccess. The Pharmaceutical Care Network Europe Association (PCNE) classification for drug-related problems (version 9.1) was used to categorize the DRPs into patient-related, healthcare practice-related, and patient- or healthcare practice-related.

Overall, 315952 potential side effects (PSEs) were reported regarding GLP-1 RAs in VigiAccess under injury, poisoning, and procedural complications. Out of 315952 PSE reports, 84187 were DRPs of GLP-1 RAs. Among the patient-related DRPs, the administered incorrect dose (17797; 48.37%) was predominant, and most of the reports were documented for tirzepatide (9993; 23.82%). Off-label use (13600; 48.37%) was a predominant healthcare practice-related DRP, most of which were from Tirzepatide (4945; 17.59%).

The alarming DRP reports in this descriptive analysis regarding the dosing and off-label use of GLP-1 Ras need further investigation to establish the contribution of underlying factors.

Qualified healthcare practitioners must educate the patients administering the GLP-1 RAs to minimize preventable DRPs. Also, careful and frequent monitoring of GLP-1 RAs improves therapeutic outcomes by ruling out DRPs. Healthcare practitioners should comply with approved therapeutic guidelines to enhance the treatment quality of GLP-1 RAs.

The use of complementary and alternative medicine (CAM) in cancer patients is increasing. However, some patients are reluctant to disclose their use to their oncology treatment team. Often, the consumption of these products is not well studied, and little is known about their potential interactions with chemotherapy, radiation therapy, or biological methods, and their relationship to treatment outcomes.

In the present study, we examined the rate of supplement use in cancer patients treated with chemotherapy.

Patients who came to the University Cancer and Chemotherapy Center for treatment were asked to complete an anonymous questionnaire to assess their use of CAM.

Among 395 patients, of the questionnaire respondents, 62.5% reported using at least 1 type of CAM after their cancer diagnosis. Management of anticancer drug potential toxicities, anxiolysis, and sedation were the major reasons for using CAM by the study population. Vitamin and mineral use was reported by 72.4% of respondents, with vitamin D being the most popular (47.3% of respondents reporting use).

The use of CAM is common among many cancer patients. CAM products may interact with chemotherapy drugs, potentially affecting treatment outcomes. Therefore, it is very important to take an accurate history of these products in every chemotherapy session in order to assess the safety of CAM consumption. Further research is required to evaluate the impact of CAM use on the efficacy and safety of cancer treatments.

The new European Union clinical trials regulation (EU CTR 536/2014) introduced the novel concept of Auxiliary Medicinal Products (AxMPs) to be implemented in clinical trials in Europe. This study aimed to understand the changes introduced under EU CTR 536/2014 with respect to AxMP requirements, implement the new regulatory mandates for AxMPs, and raise awareness among the sponsors on the collection, analysis, and reporting obligation of adverse events (AEs) to AxMPs.

Using the cross-functional approach to incorporate new methods for collecting, reporting, and assessing AEs with AxMPs, the commonly prescribed AxMPs used to treat the target indication were identified. The pharmacovigilance (PV) system [safety database] was also updated to ensure appropriate AxMP-related case processing and reporting.

Based on impact assessment, PV processes related to safety data collection and submissions were updated to reflect EU CTR requirements for AxMPs. The study documents were updated to comply with AxMP-related regulatory obligations. World Health Organization (WHO) Anatomical Therapeutic Chemical (ATC) code level 3 was used to classify relevant AxMPs. Study drug configurations and user-defined field customizations were made to the safety database.

Otsuka submitted a Clinical Trial Application (CTA) under EU CTR for one of the ongoing clinical trials. This manuscript discusses an approach to meet the regulatory mandates for safety reporting requirements of AxMPs and provides an opportunity to implement learnings from the extensive gap analysis to internal systems and processes.

From the gap analysis and impact assessment of EU CTR, appropriate changes were made to the existing PV processes, study-specific documents, and the safety database to ensure compliance with the EU CTR.