A closer look at immune-mediated myocarditis in the era of combined checkpoint blockade and targeted therapies.

Immune checkpoint inhibitors (ICI) and tyrosine kinase inhibitors (TKI) have transformed the management of many malignancies. Although rare, immune-mediated myocarditis presents unique clinical challenges due to heterogenous presentation, potential life-threatening consequences, and the time-critical need to differentiate it from other causes of cardiac dysfunction. Increasingly, TKI are being combined with ICI to promote immune modulation and improve efficacy. However, these combinations are associated with more toxicities. This series describes six patients with advanced melanoma who developed immune-mediated myocarditis while receiving an anti-PD-1 antibody or an anti-PD-L1 antibody plus a mitogen-activated protein kinase inhibitor. It provides a review of their heterogenous clinical presentations, investigational findings and treatment outcomes. Presentations ranged from asymptomatic cardiac enzyme elevation to death due to heart failure. We highlight the role of cardiac MRI (CMRI), a sensitive and non-invasive tool for the early detection and subsequent monitoring of myocardial inflammation. Five of the six patients exhibited CMRI changes characteristic of myocarditis, including mid-wall myocardial oedema and late gadolinium enhancement in a non-coronary distribution. Critically, two of these patients had normal findings on echocardiogram. Of the five patients who received immunosuppression, four recovered from myocarditis and one died of cardiac failure. The sixth patient improved with cardiac failure management alone. Three of the four patients responding to ICI derived long-term benefit. Clinical vigilance, prompt multimodal diagnosis and multidisciplinary management are paramount for the treatment of immune-mediated myocarditis.

Critical appraisal of commercially available suspending vehicles for extemporaneous compounding of cardiovascular medicines: physical and chemical stability mini review.

Oral liquid formulations are compounded by pharmacists to meet the needs of patients when a suitable commercially available product is not available. To minimize the errors associated with measuring multiple excipients and to enhance the shelf-life of the medicines, commercially available suspending bases are commonly used. This review aims to compare the stability and shelf life of commercially available extemporaneous formulation to traditional formulation methods. Five (5) databases were searched (Pubmed, SCOPUS, Science direct, Embase, and EBSCOhost). Twelve articles, comprising of seven cardiovascular medications (amiodarone, captopril, carvedilol, furosemide, nifedipine, sotalol, and valsartan), met the study inclusion criteria and were reviewed. Chemical stability of the drugs was comparable between the two formulation methods except for furosemide, captopril, and valsartan. The traditional compounding method provided superior stability for furosemide (90 vs. 14 days) and captopril (50 vs. 14 days), while the commercial vehicles provided superior stability for valsartan (90 vs. 14 days). Physical stability tests indicated that sedimentation does occur with both formulation methods. Microbial studies within the data were lacking and further research can be undertaken in this area. This review highlights the importance of assessing the suitability of compounding ingredients prior to preparation of the formulation.