Romidepsin-associated cardiac toxicity and ECG changes: A case report and review of the literature.

Background Romidepsin is a novel histone deacetylase inhibitor that is approved for the treatment of cutaneous and peripheral T-cell lymphoma in patients who have had at least one prior therapy. Romidepsin is generally well tolerated, though it comes with a risk of cardiac toxicities. Objective We report a case of electrocardiogram changes in a 64-year-old male with enteropathy-associated T-cell lymphoma, type 2, treated with salvage romidepsin therapy who relapsed after non-myeloablative allogeneic sibling peripheral blood stem cell transplant. Discussion Although histone deacetylase inhibitors have been investigated for many years, they have only recently been translated to clinical use as a therapy for malignancies. Furthermore, given their approval for a rare disease, clinicians often have limited experience with the dosing and side effects of histone deacetylase inhibitors. Conclusion This case report and literature review investigates the cardiac side effects of histone deacetylase inhibitors and illustrates the importance of cardiac monitoring prior to and during treatment.

Rifampin-sirolimus-voriconazole interaction in a hematopoietic cell transplant recipient.

Purpose Patients undergoing hematopoietic cell transplantation are treated with multiple medications, potentially complicated by drug-drug interactions. Drug interactions with sirolimus, voriconazole, and rifampin are particularly difficult because of the complex and simultaneous enzyme inhibition and induction mechanisms. We report a hematopoietic cell transplantation patient receiving sirolimus and voriconazole who was given rifampin while being treated for presumed methicillin-resistant Staphylococcus aureus meningitis. Summary A 31 year-old female received a nonmyeloablative allogeneic umbilical cord hematopoietic cell transplantation for myelodysplastic syndrome transformed to acute myeloid leukemia (AML). Her graft versus host disease and antifungal prophylaxis included sirolimus and voriconazole, respectively. Therapeutic drug monitoring prior to admission revealed a stable outpatient sirolimus regimen of 0.4 mg orally daily (trough goal 3-12 mcg/L). She was admitted to the inpatient hematopoietic cell transplantation service and diagnosed with methicillin-resistant Staphylococcus aureus bacteremia and presumed bacterial meningitis 217 days after transplant. Intravenous rifampin and vancomycin were initiated and voriconazole was changed to micafungin. Sirolimus trough concentrations were undetectable two days after starting rifampin. Therapeutic sirolimus concentrations were achieved four days later, at a sirolimus dose of 16-18 mg orally daily. Rifampin was discontinued after nine days and the sirolimus dose was adjusted accordingly, maintaining therapeutic levels throughout follow-up. The patient suffered a flare of chronic skin graft versus host disease requiring etanercept, high-dose systemic steroids, and topical steroids. Conclusion To the best of our knowledge, this is the first report describing the management of sirolimus during the transition from voriconazole inhibition to rifampin induction. Clinicians should be aware of potential drug-drug interactions.