Arsenic trioxide and olanzapine co-administration: Case analysis

Abstract

Introduction:

Maximization of response with minimization of adverse effects is central to successful oncology chemotherapy. Since psychiatric comorbidity is significant in cancer patients, psychotropic co-administration with chemotherapy requires assessment of drug-drug interactions and cumulative adverse effects. Arsenic trioxide (ATO), indicated for treatment of relapsed acute promyelocytic leukemia (APL), prolongs QTc and has “black-box” warning regarding co-administration with medications with potential QTc prolongation. ATO administration is to be held if QTc > 500 milliseconds. This case describes ATO and olanzapine co-administration.

Methods:

Case analysis with literature review.

Results:

43-year-old Caucasian male presented with relapsed APL characterized by non-traumatic bruising, anemia, and thrombocytopenia confirmed by bone marrow biopsy. Psychiatric comorbidity included Obsessive-Compulsive Disorder, Panic Disorder, and Bipolar NOS treated with fluvoxamine and benzodiazepines. Chemotherapy consisted of ATO, 0.15 mg/kg IV infusion over 2 hours. Fluvoxamine and fluconazole were discontinued early in treatment; olanzapine (2.5 mg bid) initiated thereafter effectively controlled obsessive-compulsive/affective features. Serial EKGs were performed; serum K and Mg were monitored daily and supplemented with intention of maintaining K>4.0 and Mg>1.8. EKG findings revealed: mean QTc on fluvoxamine and fluconazole, before ATO, 447 (431-464); mean QTc after ATO initiation, before discontinuation of fluvoxamine and fluconazole, 474 (445-500); mean QTc after discontinuation of fluvoxamine and fluconazole, while on ATO, 466 (441-496); mean QTc after olanzapine initiation, while on ATO, 479 (450-497). No adverse cardiovascular events occurred during treatment with ATO.

Conclusion:

This case suggests olanzapine can be safely co-administered with ATO. Further studies are indicated.