Clinical Relevance of Drug–Drug Interactions in Hemato-Oncology with Focus on Contrast Media ^†

Background. Drug–drug interactions (DDIs) are a critical factor for the safety and efficacy of treatments, especially in polymedicated hematology–oncology patients. They receive complex chemotherapy regimens to manage both tumor burden and for the management of therapy-related toxicity, alongside treatments for comorbidities and paraneoplastic syndromes. Clinically specific pharmacokinetic changes—such as reduced absorption due to mucositis, increased volume of distribution from edema and malnutrition, and altered excretion due to organ dysfunction—further amplify DDI risk [1]. Moreover, periodic imaging monitoring requires the administration of iodinated contrast agents, such as iodixanol, which comes with an additional level of risk and can trigger allergic reactions (immediate or delayed) or contrast-induced nephropathy (CIN) [2,3,4]. Objective. This study aims to evaluate the prevalence and severity of DDI in a cohort of 165 hemato-oncology inpatients, with a focus on interactions involving iodixanol. Methods. In this retrospective study, we reviewed clinical records and therapeutic regimens in compliance with the necessary ethical standards. DDIs were classified as major, moderate, or minor, according to DrugBank [5]. We calculated distributions by sex and age group, as well as overall DDI frequency and iodixanol-specific interaction frequency. We also checked Drugs.com for the cross-validation of moderate and minor interactions. Results and Discussions. The cohort consisted of 53.33% women and 46.67% men, with 52.73% of the participants aged 60–79. Among 14434 drug pair interactions, DrugBank classifies 7.75% as major, 14.90% as moderate, 17.98% as minor, and 59.37% as “No interaction found”. The proportions of patients with at least one major, moderate, or minor DDI were 76.4%, 83.6%, and 82.4%, respectively. The 60–79 age group was most vulnerable to DDI. Fifteen patients (9.1%) received iodixanol, generating 245 DDIs: 105 (42.9%) minor, most frequently with allopurinol (n = 11), acetaminophen (8), acyclovir (5), alprazolam (3), and bisoprolol (3), and 4 (1.6%) moderate, with gentamicin (2), amikacin (1), and carbamazepine (1). No major DDIs were reported, and 55.5% of iodixanol cases had no risk flagged by DrugBank. Comparative analysis revealed discrepancies with Drugs.com [6]: it classifies interactions with allopurinol and furosemide as moderate (versus minor in DrugBank) and with acyclovir and ketoprofen as major. In high-risk patients (e.g., diabetes, renal insufficiency), forced diuresis with furosemide during iodixanol administration increases the risk of contrast-induced nephropathy (CIN); therefore, it is safer to hold diuretics when feasible, use minimal iodixanol doses, and closely monitor renal function. Furthermore, in patients with diabetes and preexisting renal impairment, concomitant use of iodixanol with nephrotoxic drugs (e.g., aminoglycosides, NSAIDs) markedly raises the risk of CIN [7,8]. Conclusions. DDIs are common in hemato-oncology patients and increase with treatment complexity and age. While iodixanol is generally considered safe, it poses clinically relevant interactions—predominantly minor, with some moderate events. Divergent severity ratings across databases underscore the need for critical, multidisciplinary evaluation and individualized risk assessment [9]. To optimize safety, vigilant therapy monitoring, the cross-database validation of DDI severity, and tailored therapeutic adjustments are essential.