Medication guide for dose adjustment and management of cardiotoxicity and lipid metabolic adverse events of oral antineoplastic therapy.

Objective: The management of cardiotoxicity concerning the use of oral antineoplastic agents (OAAs) is a challenge for healthcare professionals. Our objective was to create a comprehensive medication management guide with dose adjustment recommendations on OAAs concerning cardiotoxic and lipid metabolic adverse events (AEs) to assist healthcare professionals when prescribing OAAs. Materials and methods: A review of the available information on all dose adjustments necessary to safely prescribe and dispense OAAs concerning cardiotoxicity was conducted. In January 2023, we identified all OAAs authorized by the European Medicines Agency (EMA). For each drug, the latest summary of product characteristics (SPC) approved by the EMA and the tertiary data source Lexicomp® were reviewed. Cardiotoxic AEs were recorded, namely, QT interval prolongation, decrease in left ventricular ejection fraction (LVEF), imbalances in blood pressure (hypertension and hypotension), alterations in heart rate (tachycardia and bradycardia), and thrombosis. Any available dose adjustment recommendations in case of an occurrence of these adverse events were collected. Results: In all, 93 different OAAs had been approved by the EMA and were reviewed. Among them, 51.6% have recognized cardiotoxic AEs and 10.8% can cause alterations in lipid metabolism. A total of 27 (29.0%) OAAs had specific recommendations regarding QT prolongation; 88.9% were listed in the SPC and 59.3% in Lexicomp®. Eight OAAs (9.68%) have reported a decrease in LVEF, and four of these drugs, namely, encorafenib, lorlatinib, ripretinib, and sunitinib, have specific management recommendations. Almost half (49.5%) of currently approved OAAs can potentially alter blood pressure; 34 (36.6%) of them have been reported to cause hypertension and 12 (12.9%) are related to hypotension. Tachycardia and/or bradycardia are associated with 22.6% and 8.6% of the evaluated drugs, respectively. Regarding thrombosis, 30 (32.3%) of the drugs analyzed included the appearance of a thrombus as a possible AE. Conclusions: More than half of the OAAs can produce cardiotoxic effects, with the most frequent being blood pressure alteration and QT interval prolongation with a non-depreciable incidence of LV dysfunction or thrombosis. Before starting the treatment, it is necessary to stratify baseline cardiovascular risk, plan a surveillance schedule, and consider referral to cardio-oncology units.

Possible heart failure caused by osimertinib in a lung cancer patient.

INTRODUCTION: Osimertinib is a third-generation tyrosine kinase inhibitor (TKI) indicated for the treatment of epidermal growth factor receptor mutated non-small cell lung cancer (NSCLC). It has demonstrated better results concerning effectiveness than other TKIs for the same indication. However, despite a good safety profile, it could produce some cardiotoxicity that does not occur with other drugs of the same group. CASE REPORT: We report the evolution and management of a female patient diagnosed with NSCLC who developed a grade 3 cardiotoxicity due to treatment with osimertinib. This patient suffered from a left bundle branch block, dyslipidemia, and hypertension as cardiovascular risk factors. After a long period of treatment with osimertinib, she developed a severe heart failure (HF) with an important decrease in left ventricular ejection fraction (LVEF), which triggered an admission to the oncology unit for eight days. MANAGEMENT AND OUTCOMES: Treatment with osimertinib was first suspended and then resumed after stabilization of the HF. She also developed atrial fibrillation during admission and has required narrow cardiac monitoring and management since the debut of the HF. After evaluating the benefit-risk balance, osimertinib was reintroduced and the patient continues in treatment at the moment, although the baseline LVEF is not recovered. DISCUSSION: There is scarce evidence in the literature concerning HF and important LVEF decrease due to osimertinib. However, its severity and repercussion for the patient justify the thorough screening of cardiovascular risk factors before starting the therapy.

Design and implementation of a mobile app for the pharmacotherapeutic follow-up of patients diagnosed with immune-mediated inflammatory diseases: eMidCare.

Background: Pharmacotherapeutic management of immune-mediated inflammatory diseases (IMID) has become more complex due to the development of new treatments, such as biological therapies. Mobile health, especially apps, can provide IMID patients with greater autonomy and facilitate communication with healthcare professionals. Our objective was to design and implement an app for remote monitoring and communication with IMID patients. Methods: A multidisciplinary group was created to design and develop an app for IMID patients in a tertiary hospital. The app functionalities were identified through a focus group with IMID patients and through an observational, descriptive study of available apps for IMID patients at App Store and Play Store platforms. Once the app was designed and developed, we offered the app to IMID patients who initiated a new biological therapy. The inclusion period was from December 2020 to August 2021. We performed an observational, longitudinal study to assess the app's impact on medication safety, communication, satisfaction, and usability. Results: We designed an app (eMidCare®) with the following modules: My Medication, My Questionnaires, Adverse Events, Useful Information, Messages, and Patient Profile. A total of 85 patients were installed with the app. The median (range) follow-up time for app use was 123 (5-270) days. In the My Medication module, 100% of patients registered their biological therapy and 25.9% also used this module to record each dose of medication administered. A total of 82 adverse events (AEs) were registered. Thirty-two percent of the patients registered at least 1 AE. The most frequent AEs were fatigue, injection site reaction, headache, and nausea. Fifty-two percent of patients used the Messages module to communicate with healthcare professionals. The most frequent messages concerned doubts about managing AEs (26.2%) and drug interactions (18.9%). The satisfaction survey yielded a median (range) score of 9.1 (7-10) out of 10. Conclusions: We developed an app, eMidCare®, which reminds patients to take their medication, enables them to record AEs, and helps them communicate with healthcare professionals. Approximately one-third of the patients registered the administration of the biological therapies and registered at least 1 AE. The most used and most satisfactory functionality was communication with health professionals.

Potential negative pharmacodynamic interaction of spironolactone and abiraterone in two prostate cancer patients.

INTRODUCTION: Spironolactone when combined with abiraterone in metastatic castration-resistant prostate cancer (mCRPC) may theoretically exert androgenic properties, thereby compromising the therapeutic effectiveness of abiraterone. CASE REPORT: Two patients with a medical history of cardiovascular disease and mCRPC combined spironolactone within the course of abiraterone regimen. The abiraterone-spironolactone interaction was identified using the Lexicomp® interaction tool (classified as risk C). MANAGEMENT & OUTCOME: Spironolactone treatment was maintained as it was considered beneficial due to the cardiac condition. The prostate-specific antigen (PSA) levels started to rise when these two drugs were used together. Eventually, tumour progression was observed. DISCUSSION: There is increasing evidence that spironolactone behaves as a selective androgen receptor modulator. Strategies to overcome abiraterone-spironolactone interaction could involve the use of eplerenone, although this drug is also controversial. The best strategy should imply a multidisciplinary evaluation by cardiologists and oncologists.

Clinical course of severe patients with COVID-19 treated with tocilizumab: report from a cohort study in Spain.

Background: We report the long-term outcomes, changes in laboratory parameters, the incidence of secondary nosocomial infections and treatment cost of a Spanish cohort of patients with severe COVID-19 that received tocilizumab (TCZ).Methods: Retrospective cohort of PCR confirmed adult patients who received TCZ from March 1 to 24, 2020 in a tertiary hospital was analyzed. Patients were followed up until 10 May 2020.Results: We included 162 patients (median age 64 years; 70.4% male). At time of TCZ administration, 48.1% of patients were on invasive mechanical ventilation (IMV). Over a median follow-up of 53 days, 46.9% of patients were discharge in good conditions and 19.8% were still hospitalized. The overall mortality was 33.3%, being higher in patients on IMV than those who did not (46.2% vs 26.7%, P < 0.001). A significant improvement in the lymphocyte count, C-reactive protein, lactate dehydrogenase, and D-dimer was observed. Overall, 43.2% patients presented nosocomial infections, causing death in 8%. Infections were more prevalent in ICU units (63.0% vs 17.1%, P < 0.001). The total cost of TCZ was €371,784.Conclusions: Among the patients who used TCZ, one third died, regardless the improvement in some inflammatory biomarkers. The incidence of secondary nosocomial infections was high.